July 2012 Clinical Advisor
The Clinical Advisor is a monthly journal for nurse practitioners and physician assistants in primary care. Its mission is to keep practitioners up to date with the latest information about diagnosing, treating, managing, and preventing conditions seen in a typical office-based primary-care setting.
A FORUM FOR NURSE PRACTITIONERS | J U LY 2 01 2 | www.ClinicalAdvisor.com NEWSLINE Food and fitness studies Hormone therapy review Hep C in baby-boomers ADVISOR FORUM CE: MANAGING PEDIATRC FOOD ALLERGY Manifestations of food allergy include urticaria and angioedema (shown here). Childhood obesity Postmenopausal hair loss Getting the cervix in view LEGAL ADVISOR Treatment for pancreatitis ends in foot amputation FREE CE COURSES! Dermatology Clinic BLUE-BLACK PAPULE ON THE HAND PAGE 47 Dermatology Clinic ERYTHEMATOUS PALM LESIONS PAGE 53 Expanded job listings! www.ClinicalAdvisor.com/Jobs GET INVOLVED AT ClinicalAdvisor.com! Editor Joe Kopcha, firstname.lastname@example.org Managing editor Marina Galanakis Senior editor Delicia Yard Web editor Nicole Blazek Contributing editors Bruce D. Askey, MSN, CRNP; Rebecca H. Bryan, APRN, CNP; Eileen F. Campbell, MSN, CRNP; Philip R. Cohen, MD; Deborah L. Cross, MPH, CRNP, ANP-BC; Sharon Dudley-Brown, PhD, FNP-BC; Maria Kidner, DNP, FNP-C; Joan W. Kiely, MSN, CRNP; Debra August King, PhD, PA; Ann W. Latner, JD; Claire B. O'Connell, MPH, PA-C; Kathy Pereira, MSN, FNP-BC; Sherril Sego, FNP, DNP; Julee B. Waldrop, MS, PNP; Kim Zuber, PA-C Art director Andrew Bass Group art director, Haymarket Medical Jennifer Dvoretz Production director Leslie Carsman Circulation manager Paul Silver Audience development director John Crewe National accounts manager Alison McCauley, 646.638.6098 email@example.com Group publisher Thomas P. Hennessy, 646.638.6085 firstname.lastname@example.org Editorial director Jeff Forster Vice president, medical magazines and digital products Jim Burke CEO, Haymarket Media Inc. Lee Maniscalco All correspondence to: The Clinical Advisor 114 West 26th Street, 4th Floor, New York, NY 10001 For advertising sales, call 646.638.6075. For reprints, contact Wright's Reprints at 877.652.5295. Persons appearing in photographs in "Newsline," "The Legal Advisor," and "Clinical Challenge" are not the actual individuals mentioned in the articles.They appear for illustrative purposes only. The Clinical Advisor� (USPS 017-546, ISSN 1524-7317), Volume 15, Number 7, is published 12 times a year, monthly, for $75.00 per year in the United States; $85.00 in Canada; $110.00 for all other foreign, in U.S. dollars, by Haymarket Media, Inc., 114 West 26th Street, 4th Floor, New York, NY 10001. Single copy: $20 U.S.; $30 foreign. www.ClinicalAdvisor.com. To order or update your paid subscription, call 800.436.9269. Periodicals postage rate paid at New York, NY, and additional mailing offices. POSTMASTER: Send all address changes to:The Clinical Advisor, c/o DMDData Inc., 2340 River Road, Des Plaines, IL 60018. Call 800.430.5450 to change your address or make other subscription inquiries. Requests for subscriptions from outside the United States must be accompanied by payment. All rights reserved. Reproduction in whole or in part without permission is prohibited. Copyright � 2012. SUBMIT QUESTIONS & PEARLS Are you stumped? Have no fear -- our panel of expert clinicians is ready to help. Submit your questions to the Advisor Forum at ClinicalAdvisor.com/AdvisorForum Pass it on! Do you have a Clinical Pearl others might find useful? Don't keep it to yourself. Share it with your colleagues at ClinicalAdvisor.com/ClinicalPearls TAKE OUR POLLS Find out how your opinion compares with that of your peers on how to handle different clinical situations by visiting ClinicalAdvisor.com/polls SUBSCRIBE TO WEEKLY E-NEWSLETTERS To stay on top of the latest information on our website, sign up for our regular e-newsletters at ClinicalAdvisor.com/subscribe Inside This Month's Issue � Latest CME/CE � Informed Consent � Clinical Advisor Spotlight � Derm Dx � Online First EARN CREDIT WITH CME/CE COURSES Every month, earn up to 1.0 hours of CME/ CE credit by completing the activities found at ClinicalAdvisor.com/CME-CE WIND DOWN WITH A LAUGH Now you can see our cartoons online, too. Treat yourself to a smile or chuckle and view our cartoon slideshows at ClinicalAdvisor.com/ cartoons 4 THE CLINICAL ADVISOR � JULY 2012 � www.ClinicalAdvisor.com � Roy Delgado "The road I tried to cross was the freeway." CONTENTS J U LY 2 0 1 2 NEWS AND COMMENT 18 Newsline Studies look at food and physical fitness Probiotics ease antibiotic GI effect And more Commentary 57 51 Alternative Meds Update Acupuncture is thought to alter the body's energy flow into healthier patterns. CME/CE Dermatologic Look-Alikes Two cases of palmar lesions--one in an HIV-positive man, the other a woman with systemic lupus erythematosus. CME/CE Posttest 53 58 FEATURES 23 CME/CE Evaluating and managing pediatric food allergy A multidisciplinary approach involving primary-care clinicians and specialists is crucial. Reducing diarrhea with probiotics 20 ADVISOR FORUM 38 Consultations Breastfeeding with a positive 30 Mixing herbal and prescription medications Combining supplements with other drugs can be dangerous. thyroid peroxidase Reversing childhood obesity And more 40 Clinical Pearls Show--don't tell--when it comes to weight loss Getting the cervix in view Sources of comfort for those with dementia Your Comments School clinician should be thankful for jury's decision DEPARTMENTS 42 Derm Dx Read the clinical descriptions, view the images, and then make your diagnosis. Legal Advisor Side effects of an IV antiemetic lead to tragedy in a patient with pancreatitis. CME/CE Dermatology Clinic An Asian girl presents with a blue-black mole on the dorsal hand. A man suffers 10 years of pruritic hyperkeratotic papules on his legs. Decade-long itchy rash on both legs 47 40 44 47 Pain relief through acupuncture 51 www.ClinicalAdvisor.com MAKING CONTACT Follow us on Twitter @ClinicalAdvisor Like us on Facebook facebook.com/TheClinicalAdvisor Visit us on the web ClinicalAdvisor.com Go mobile with us mobile.ClinicalAdvisor.com EXCLUSIVE TO THE WEB AT ClinicalAdvisor.com/web-only Web Exclusives ClinicalAdvisor.com/WebExclusives Psoriasis independently linked to diabetes risk Researchers have discovered a dosedependent link between psoriasis and type 2 diabetes, with risk increasing with the severity of the skin disorder. Hypertension-related hospitalizations up in U.S. children Pediatric hospitalizations due to hypertension were associated with $3.1 billion in charges from 1997 to 2006. Risk for shingles recurrence low in elderly Immunocompetent older people who have had shingles recently have a relatively low short-term risk for developing the skin condition again, regardless of vaccination status, study data show. Slideshows ClinicalAdvisor.com/Slideshows When to screen for prostate cancer Screening for prostate cancer has long been part of the yearly checkup for many men. Although this procedure may reduce a patient's risk for dying from the disease, evidence is conflicting regarding how helpful it actually is in reducing mortality. The Waiting Room Official Blog of The Clinical Advisor ClinicalAdvisor.com/Blog Julee Waldrop, DNP, PNP, FNP Asking teens about uncertainties helps ID depression Assessing mental health in primary care can be daunting, especially if community resources are scarce and your patient has limited finances. Robyn Carlisle, MSN, CNM, WHNP Making medicine social When used properly, social-networking platforms have the potential to improve the way medical providers share information. Sharon M. O'Brien, MPAS, PA-C Managing sleep issues in patients with chronic pain A night with inadequate sleep may result in increased pain the next day, which may disrupt sleep even further. Learn how to help patients break this detrimental cycle. Leigh Montejo, MSN, FNP-BC Quantity, frequency important in sunscreen application Patients may already know they should use an SPF 30 sunscreen, but are they applying it properly? Cartoon Archive � The New Yorker Collection 2012 from cartoonbank.com. All Rights Reserved. The Clinical Advisor 's monthly cartoons are now available online as well. ClinicalAdvisor.com/cartoons "Have you always felt like a victim?" MAKING CONTACT Follow us on Twitter @ClinicalAdvisor Like us on Facebook facebook.com/TheClinicalAdvisor Visit us on the web ClinicalAdvisor.com Go mobile with us mobile.ClinicalAdvisor.com 14 THE CLINICAL ADVISOR � JULY 2012 � www.ClinicalAdvisor.com While there are many diabetes complications, PAINFUL DPN IS ONE THEY CAN'T IGNORE Help manage your patients' painful Diabetic Peripheral Neuropathy with LYRICA ONLY LYRICA IS RECOMMENDED AS LEVEL A by AAN evidence-based guideline for the treatment of painful diabetic neuropathy (PDN)1 "If clinically appropriate, pregabalin should be offered for the treatment of PDN (Level A)."1 The medical organizations that developed this guideline (the AAN, the American Association of Neuromuscular and Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation) recognize that specific care decisions are the prerogative of the patient and physician caring for the patient, based on all of the circumstances involved. For full guideline, visit www.aan.com/guidelines. Level A=Established as effective, based on at least 2 Class I studies. Class I level evidence includes a randomized, controlled clinical trial of the intervention of interest with masked or objective outcome assessment, in a representative population, and other specified criteria. AAN=American Academy of Neurology. LYRICA is indicated for the management of neuropathic pain associated with Diabetic Peripheral Neuropathy, management of Postherpetic Neuralgia, as adjunctive therapy for adult patients with Partial Onset Seizures, and management of Fibromyalgia. PBP01859A/291945-01 � 2011 Pfizer Inc. Selected safety information: LYRICA is contraindicated in patients with known hypersensitivity to pregabalin or any of its other components. There have been postmarketing reports of hypersensitivity in patients shortly after initiation of treatment with LYRICA. Adverse reactions included skin redness, blisters, hives, rash, dyspnea, and wheezing. Discontinue LYRICA immediately in patients with these symptoms. There have been postmarketing reports of angioedema in patients during initial and chronic treatment with LYRICA. Specific symptoms included swelling of the face, mouth (tongue, lips, and gums), and neck (throat and larynx). There were reports of lifethreatening angioedema with respiratory compromise requiring emergency treatment. Discontinue LYRICA immediately in patients with these symptoms. Antiepileptic drugs (AEDs) including LYRICA increase the risk of suicidal thoughts or behavior in patients taking AEDs for any indication. Monitor patients treated with any AED for any indication for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Pooled analyses showed clinical trial patients taking an AED had approximately twice the risk of suicidal thoughts or behavior than placebotreated patients, and estimated the incidence rate of suicidal behavior or ideation was approximately one patient for every 530 patients treated with an AED. The most common adverse reactions across all LYRICA All rights reserved. clinical trials are dizziness, somnolence, dry mouth, edema, blurred vision, weight gain, constipation, euphoric mood, balance disorder, increased appetite, and thinking abnormal (primarily difficulty with concentration/attention). Inform patients taking LYRICA that dizziness and somnolence may impair their ability to perform potentially hazardous tasks such as driving or operating complex machinery until they have sufficient experience with LYRICA to determine its effect on cognitive and motor function. Higher frequency of weight gain and edema was observed in patients taking both LYRICA and thiazolidinedione antidiabetic drugs. Exercise caution when coadministering these drugs. Patients who are taking other drugs associated with angioedema such as angiotensin-converting enzyme inhibitors (ACE inhibitors) may be at increased risk of developing angioedema. Exercise caution when using LYRICA in patients who have had a previous episode of angioedema. For Full Prescribing Information and Medication Guide, please visit www.LyricaHCP .com. Please see the Brief Summary of Prescribing Information on adjacent pages. Reference: 1. Bril V, England JD, Franklin GM, et al. Evidence-based guideline: treatment of painful diabetic neuropathy. Report of the American Academy of Neurology, the American Association of Neuromuscular and Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation. Neurology. 2011;76:1758-1765. September 2011 Table 3 Treatment-emergent adverse reaction incidence in controlled trials in Neuropathic Pain Associated with Diabetic Peripheral Neuropathy (Events in at least 1% of all LYRICA-treated patients and at least numerically more in all LYRICA than in the placebo group) 75 mg/d 150 mg/d 300 mg/d 600 mg/d All PGB* Placebo Body System [N=77] [N=212] [N=321] [N=369] [N=979] [N=459] - Preferred term % % % % % % Body as a whole Asthenia 4 2 4 7 5 2 Accidental injury 5 2 2 6 4 3 Back pain 0 2 1 2 2 0 Chest pain 4 1 1 2 2 1 Face edema 0 1 1 2 1 0 Digestive system Dry mouth 3 2 5 7 5 1 Constipation 0 2 4 6 4 2 Flatulence 3 0 2 3 2 1 Metabolic and nutritional disorders Peripheral edema 4 6 9 12 9 2 Weight gain 0 4 4 6 4 0 Edema 0 2 4 2 2 0 Hypoglycemia 1 3 2 1 2 1 Nervous system Dizziness 8 9 23 29 21 5 Somnolence 4 6 13 16 12 3 Neuropathy 9 2 2 5 4 3 Ataxia 6 1 2 4 3 1 Vertigo 1 2 2 4 3 1 Confusion 0 1 2 3 2 1 Euphoria 0 0 3 2 2 0 Incoordination 1 0 2 2 2 0 1 0 1 3 2 0 Thinking abnormal Tremor 1 1 1 2 1 0 Abnormal gait 1 0 1 3 1 0 Amnesia 3 1 0 2 1 0 Nervousness 0 1 1 1 1 0 Respiratory system Dyspnea 3 0 2 2 2 1 Special senses 3 1 3 6 4 2 Blurry vision Abnormal vision 1 0 1 1 1 0 *PGB: pregabalin Thinking abnormal primarily consists of events related to difficulty with concentration/attention but also includes events related to cognition and language problems and slowed thinking. Investigator term; summary level term is amblyopia. Other Adverse Reactions Observed During the Clinical Studies of LYRICA Following is a list of treatment-emergent adverse reactions reported by patients treated with LYRICA during all clinical trials. The listing does not include those events already listed in the previous tables or elsewhere in labeling, those events for which a drug cause was remote, those events which were so general as to be uninformative, and those events reported only once which did not have a substantial probability of being acutely life-threatening. Events are categorized by body system and listed in order of decreasing frequency according to the following definitions: frequent adverse reactions are those occurring on one or more occasions in at least 1/100 patients; infrequent adverse reactions are those occurring in 1/100 to 1/1000 patients; rare reactions are those occurring in fewer than 1/1000 patients. Events of major clinical importance are described in the Warnings and Precautions section. Body as a Whole � Frequent: Abdominal pain, Allergic reaction, Fever; Infrequent: Abscess, Cellulitis, Chills, Malaise, Neck rigidity, Overdose, Pelvic pain, Photosensitivity reaction; Rare: Anaphylactoid reaction, Ascites, Granuloma, Hangover effect, Intentional Injury, Retroperitoneal Fibrosis, Shock. Cardiovascular System � Infrequent: Deep thrombophlebitis, Heart failure, Hypotension, Postural hypotension, Retinal vascular disorder, Syncope; Rare: ST Depressed, Ventricular Fibrillation. Digestive System � Frequent: Gastroenteritis, Increased appetite; Infrequent: Cholecystitis, Cholelithiasis, Colitis, Dysphagia, Esophagitis, Gastritis, Gastrointestinal hemorrhage, Melena, Mouth ulceration, Pancreatitis, Rectal hemorrhage, Tongue edema; Rare: Aphthous stomatitis, Esophageal Ulcer, Periodontal abscess. Hemic and Lymphatic System � Frequent: Ecchymosis; Infrequent: Anemia, Eosinophilia, Hypochromic anemia, Leukocytosis, Leukopenia, Lymphadenopathy, Thrombocytopenia; Rare: Myelofibrosis, Polycythemia, Prothrombin decreased, Purpura, Thrombocythemia. Metabolic and Nutritional Disorders � Rare: Glucose Tolerance Decreased, Urate Crystalluria. Musculoskeletal System � Frequent: Arthralgia, Leg cramps, Myalgia, Myasthenia; Infrequent: Arthrosis; Rare: Chondrodystrophy, Generalized Spasm. Nervous System � Frequent: Anxiety, Depersonalization, Hypertonia, Hypesthesia, Libido decreased, Nystagmus, Paresthesia, Stupor, Twitching; Infrequent: Abnormal dreams, Agitation, Apathy, Aphasia, Circumoral paresthesia, Dysarthria, Hallucinations, Hostility, Hyperalgesia, Hyperesthesia, Hyperkinesia, Hypokinesia, Hypotonia, Libido increased, Myoclonus, Neuralgia; Rare: Addiction, Cerebellar syndrome, Cogwheel rigidity, Coma, Delirium, Delusions, Dysautonomia, Dyskinesia, Dystonia, Encephalopathy, Extrapyramidal syndrome, Guillain-Barr� syndrome, Hypalgesia, Intracranial hypertension, Manic reaction, Paranoid reaction, Peripheral neuritis, Personality disorder, Psychotic depression, Schizophrenic reaction, Sleep disorder, Torticollis, Trismus. Respiratory System � Rare: Apnea, Atelectasis, Bronchiolitis, Hiccup, Laryngismus, Lung edema, Lung fibrosis, Yawn. Skin and Appendages � Frequent: Pruritus; Infrequent: Alopecia, Dry skin, Eczema, Hirsutism, Skin ulcer, Urticaria, Vesiculobullous rash; Rare: Angioedema, Exfoliative dermatitis, Lichenoid dermatitis, Melanosis, Nail Disorder, Petechial rash, Purpuric rash, Pustular rash, Skin atrophy, Skin necrosis, Skin nodule, Stevens-Johnson syndrome, Subcutaneous nodule. Special senses � Frequent: Conjunctivitis, Diplopia, Otitis media, Tinnitus; Infrequent: Abnormality of accommodation, Blepharitis, Dry eyes, Eye hemorrhage, Hyperacusis, Photophobia, Retinal edema, Taste loss, Taste perversion; Rare: Anisocoria, Blindness, Corneal ulcer, Exophthalmos, Extraocular palsy, Iritis, Keratitis, Keratoconjunctivitis, Miosis, Mydriasis, Night blindness, Ophthalmoplegia, Optic atrophy, Papilledema, Parosmia, Ptosis, Uveitis. Urogenital System � Frequent: Anorgasmia, Impotence, Urinary frequency, Urinary incontinence; Infrequent: Abnormal ejaculation, Albuminuria, Amenorrhea, Dysmenorrhea, Dysuria, Hematuria, Kidney calculus, Leukorrhea, Menorrhagia, Metrorrhagia, Nephritis, Oliguria, Urinary retention, Urine abnormality; Rare: Acute kidney failure, Balanitis, Bladder Neoplasm, Cervicitis, Dyspareunia, Epididymitis, Female lactation, Glomerulitis, Ovarian disorder, Pyelonephritis. Comparison of Gender and Race The overall adverse event profile of pregabalin was similar between women and men. There are insufficient data to support a statement regarding the distribution of adverse experience reports by race. Post-marketing Experience The following adverse reactions have been identified during postapproval use of LYRICA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Nervous System Disorders � Headache. Gastrointestinal Disorders � Nausea, Diarrhea. Reproductive System and Breast Disorders � Gynecomastia, Breast Enlargement. DRUG INTERACTIONS Since LYRICA is predominantly excreted unchanged in the urine, undergoes negligible metabolism in humans (<2% of a dose recovered in urine as metabolites), and does not bind to plasma proteins, its pharmacokinetics are unlikely to be affected by other agents through metabolic interactions or protein binding displacement. In vitro and in vivo studies showed that LYRICA is unlikely to be involved in significant pharmacokinetic drug interactions. Specifically, there are no pharmacokinetic interactions between pregabalin and the following antiepileptic drugs: carbamazepine, valproic acid, lamotrigine, phenytoin, phenobarbital, and topiramate. Important pharmacokinetic interactions would also not be expected to occur between LYRICA and commonly used antiepileptic drugs. Pharmacodynamics Multiple oral doses of LYRICA were co-administered with oxycodone, lorazepam, or ethanol. Although no pharmacokinetic interactions were seen, additive effects on cognitive and gross motor functioning were seen when LYRICA was co-administered with these drugs. No clinically important effects on respiration were seen. USE IN SPECIFIC POPULATIONS Pregnancy Pregnancy Category C. Increased incidences of fetal structural abnormalities and other manifestations of developmental toxicity, including lethality, growth retardation, and nervous and reproductive system functional impairment, were observed in the offspring of rats and rabbits given pregabalin during pregnancy, at doses that produced plasma pregabalin exposures (AUC) 5 times human exposure at the maximum recommended dose (MRD) of 600 mg/day. When pregnant rats were given pregabalin (500, 1250, or 2500 mg/kg) orally throughout the period of organogenesis, incidences of specific skull alterations attributed to abnormally advanced ossification (premature fusion of the jugal and nasal sutures) were increased at 1250 mg/kg, and incidences of skeletal variations and retarded ossification were increased at all doses. Fetal body weights were decreased at the highest dose. The low dose in this study was associated with a plasma exposure (AUC) approximately 17 times human exposure at the MRD of 600 mg/day. A no-effect dose for rat embryo-fetal developmental toxicity was not established. When pregnant rabbits were given LYRICA (250, 500, or 1250 mg/kg) orally throughout the period of organogenesis, decreased fetal body weight and increased incidences of skeletal malformations, visceral variations, and retarded ossification were observed at the highest dose. The no-effect dose for developmental toxicity in rabbits (500 mg/kg) was associated with a plasma exposure approximately 16 times human exposure at the MRD. In a study in which female rats were dosed with LYRICA (50, 100, 250, 1250, or 2500 mg/kg) throughout gestation and lactation, offspring growth was reduced at 100 mg/kg and offspring survival was decreased at 250 mg/kg. The effect on offspring survival was pronounced at doses 1250 mg/kg, with 100% mortality in high-dose litters. When offspring were tested as adults, neurobehavioral abnormalities (decreased auditory startle responding) were observed at 250 mg/kg and reproductive impairment (decreased fertility and litter size) was seen at 1250 mg/kg. The no-effect dose for pre- and postnatal developmental toxicity in rats (50 mg/kg) produced a plasma exposure approximately 2 times human exposure at the MRD. There are no adequate and well-controlled studies in pregnant women. Use LYRICA during pregnancy only if the potential benefit justifies the potential risk to the fetus. To provide information regarding the effects of in utero exposure to LYRICA, physicians are advised to recommend that pregnant patients taking LYRICA enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry. This can be done by calling the toll free number 1-888-233-2334, and must be done by patients themselves. Information on the registry can also be found at the website http://www. aedpregnancyregistry.org/. Labor and Delivery The effects of LYRICA on labor and delivery in pregnant women are unknown. In the prenatal-postnatal study in rats, pregabalin prolonged gestation and induced dystocia at exposures 50 times the mean human exposure (AUC (0�24) of 123 �g�hr/mL) at the maximum recommended clinical dose of 600 mg/day. Nursing Mothers It is not known if pregabalin is excreted in human milk; it is, however, present in the milk of rats. Because many drugs are excreted in human milk, and because of the potential for tumorigenicity shown for pregabalin in animal studies, decide whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Pediatric Use The safety and efficacy of pregabalin in pediatric patients have not been established. In studies in which pregabalin (50 to 500 mg/kg) was orally administered to young rats from early in the postnatal period (Postnatal Day 7) through sexual maturity, neurobehavioral abnormalities (deficits in learning and memory, altered locomotor activity, decreased auditory startle responding and habituation) and reproductive impairment (delayed sexual maturation and decreased fertility in males and females) were observed at doses 50 mg/kg. The neurobehavioral changes of acoustic startle persisted at 250 mg/kg and locomotor activity and water maze performance at 500 mg/kg in animals tested after cessation of dosing and, thus, were considered to represent long-term effects. The low effect dose for developmental neurotoxicity and reproductive impairment in juvenile rats (50 mg/kg) was associated with a plasma pregabalin exposure (AUC) approximately equal to human exposure at the maximum recommended dose of 600 mg/day. A no-effect dose was not established. Geriatric Use In controlled clinical studies of LYRICA in neuropathic pain associated with diabetic peripheral neuropathy, 246 patients were 65 to 74 years of age, and 73 patients were 75 years of age or older. In controlled clinical studies of LYRICA in neuropathic pain associated with postherpetic neuralgia, 282 patients were 65 to 74 years of age, and 379 patients were 75 years of age or older. No overall differences in safety and efficacy were observed between these patients and younger patients. In controlled clinical studies of LYRICA in fibromyalgia, 106 patients were 65 years of age or older. Although the adverse reaction profile was similar between the two age groups, the following neurological adverse reactions were more frequent in patients 65 years of age or older: dizziness, vision blurred, balance disorder, tremor, confusional state, coordination abnormal, and lethargy. LYRICA is known to be substantially excreted by the kidney, and the risk of toxic reactions to LYRICA may be greater in patients with impaired renal function. Because LYRICA is eliminated primarily by renal excretion, adjust the dose for elderly patients with renal impairment. DRUG ABUSE AND DEPENDENCE Controlled Substance LYRICA is a Schedule V controlled substance. LYRICA is not known to be active at receptor sites associated with drugs of abuse. As with any CNS active drug, carefully evaluate patients for history of drug abuse and observe them for signs of LYRICA misuse or abuse (e.g., development of tolerance, dose escalation, drug-seeking behavior). Abuse In a study of recreational users (N=15) of sedative/hypnotic drugs, including alcohol, LYRICA (450 mg, single dose) received subjective ratings of "good drug effect," "high" and "liking" to a degree that was similar to diazepam (30 mg, single dose). In controlled clinical studies in over 5500 patients, 4% of LYRICA-treated patients and 1% of placebo-treated patients overall reported euphoria as an adverse reaction, though in some patient populations studied, this reporting rate was higher and ranged from 1 to 12%. Dependence In clinical studies, following abrupt or rapid discontinuation of LYRICA, some patients reported symptoms including insomnia, nausea, headache or diarrhea [see Warnings and Precautions, Abrupt or Rapid Discontinuation], suggestive of physical dependence. OVERDOSAGE Signs, Symptoms and Laboratory Findings of Acute Overdosage in Humans There is limited experience with overdose of LYRICA. The highest reported accidental overdose of LYRICA during the clinical development program was 8000 mg, and there were no notable clinical consequences. Treatment or Management of Overdose There is no specific antidote for overdose with LYRICA. If indicated, elimination of unabsorbed drug may be attempted by emesis or gastric lavage; observe usual precautions to maintain the airway. General supportive care of the patient is indicated including monitoring of vital signs and observation of the clinical status of the patient. Contact a Certified Poison Control Center for up-to-date information on the management of overdose with LYRICA. Although hemodialysis has not been performed in the few known cases of overdose, it may be indicated by the patient's clinical state or in patients with significant renal impairment. Standard hemodialysis procedures result in significant clearance of pregabalin (approximately 50% in 4 hours). NONCLINICAL TOXICOLOGY Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis A dose-dependent increase in the incidence of malignant vascular tumors (hemangiosarcomas) was observed in two strains of mice (B6C3F1 and CD-1) given pregabalin (200, 1000, or 5000 mg/kg) in the diet for two years. Plasma pregabalin exposure (AUC) in mice receiving the lowest dose that increased hemangiosarcomas was approximately equal to the human exposure at the maximum recommended dose (MRD) of 600 mg/day. A no-effect dose for induction of hemangiosarcomas in mice was not established. No evidence of carcinogenicity was seen in two studies in Wistar rats following dietary administration of pregabalin for two years at doses (50, 150, or 450 mg/kg in males and 100, 300, or 900 mg/kg in females) that were associated with plasma exposures in males and females up to approximately 14 and 24 times, respectively, human exposure at the MRD. Mutagenesis Pregabalin was not mutagenic in bacteria or in mammalian cells in vitro, was not clastogenic in mammalian systems in vitro and in vivo, and did not induce unscheduled DNA synthesis in mouse or rat hepatocytes. Impairment of Fertility In fertility studies in which male rats were orally administered pregabalin (50 to 2500 mg/kg) prior to and during mating with untreated females, a number of adverse reproductive and developmental effects were observed. These included decreased sperm counts and sperm motility, increased sperm abnormalities, reduced fertility, increased preimplantation embryo loss, decreased litter size, decreased fetal body weights, and an increased incidence of fetal abnormalities. Effects on sperm and fertility parameters were reversible in studies of this duration (3�4 months). The no-effect dose for male reproductive toxicity in these studies (100 mg/kg) was associated with a plasma pregabalin exposure (AUC) approximately 3 times human exposure at the maximum recommended dose (MRD) of 600 mg/day. In addition, adverse reactions on reproductive organ (testes, epididymides) histopathology were observed in male rats exposed to pregabalin (500 to 1250 mg/kg) in general toxicology studies of four weeks or greater duration. The no-effect dose for male reproductive organ histopathology in rats (250 mg/kg) was associated with a plasma exposure approximately 8 times human exposure at the MRD. In a fertility study in which female rats were given pregabalin (500, 1250, or 2500 mg/kg) orally prior to and during mating and early gestation, disrupted estrous cyclicity and an increased number of days to mating were seen at all doses, and embryolethality occurred at the highest dose. The low dose in this study produced a plasma exposure approximately 9 times that in humans receiving the MRD. A no-effect dose for female reproductive toxicity in rats was not established. Human Data In a double-blind, placebo-controlled clinical trial to assess the effect of pregabalin on sperm motility, 30 healthy male subjects were exposed to pregabalin at a dose of 600 mg/day. After 3 months of treatment (one complete sperm cycle), the difference between placebo- and pregabalintreated subjects in mean percent sperm with normal motility was <4% and neither group had a mean change from baseline of more than 2%. Effects on other male reproductive parameters in humans have not been adequately studied. Animal Toxicology and/or Pharmacology Dermatopathy Skin lesions ranging from erythema to necrosis were seen in repeated-dose toxicology studies in both rats and monkeys. The etiology of these skin lesions is unknown. At the maximum recommended human dose (MRD) of 600 mg/day, there is a 2-fold safety margin for the dermatological lesions. The more severe dermatopathies involving necrosis were associated with pregabalin exposures (as expressed by plasma AUCs) of approximately 3 to 8 times those achieved in humans given the MRD. No increase in incidence of skin lesions was observed in clinical studies. Ocular Lesions Ocular lesions (characterized by retinal atrophy [including loss of photoreceptor cells] and/or corneal inflammation/mineralization) were observed in two lifetime carcinogenicity studies in Wistar rats. These findings were observed at plasma pregabalin exposures (AUC) 2 times those achieved in humans given the maximum recommended dose of 600 mg/day. A no-effect dose for ocular lesions was not established. Similar lesions were not observed in lifetime carcinogenicity studies in two strains of mice or in monkeys treated for 1 year. LAB-0294-21.0 June 2011 PBP01873/291898-01 � 2011 Pfizer Inc. All rights reserved. LYRICA� (pregabalin) CAPSULES BRIEF SUMMARY: For full prescribing information, see package insert. INDICATION AND USAGE LYRICA is indicated for: � Management of neuropathic pain associated with diabetic peripheral neuropathy DOSAGE AND ADMINISTRATION LYRICA is given orally with or without food. When discontinuing LYRICA, taper gradually over a minimum of 1 week. Neuropathic pain associated with diabetic peripheral neuropathy: � Administer in 3 divided doses per day � Begin dosing at 150 mg/day � May be increased to a maximum of 300 mg/day within 1 week � Dose should be adjusted for patients with reduced renal function Patients with Renal Impairment In view of dose-dependent adverse reactions and since LYRICA is eliminated primarily by renal excretion, adjust the dose in patients with reduced renal function. Base the dose adjustment in patients with renal impairment on creatinine clearance (CLcr), as indicated in Table 1. To use this dosing table, an estimate of the patient's CLcr in mL/min is needed. CLcr in mL/min may be estimated from serum creatinine (mg/dL) determination using the Cockcroft and Gault equation: [140 - age (years)] x weight (kg) (x 0.85 for female patients) 72 x serum creatinine (mg/dL) Next, refer to the Dosage and Administration section to determine the recommended total daily dose based on indication, for a patient with normal renal function (CLcr 60 mL/min). Then refer to Table 1 to determine the corresponding renal adjusted dose. (For example: A patient initiating LYRICA therapy for postherpetic neuralgia with normal renal function (CLcr 60 mL/min), receives a total daily dose of 150 mg/day pregabalin. Therefore, a renal impaired patient with a CLcr of 50 mL/min would receive a total daily dose of 75 mg/day pregabalin administered in two or three divided doses.) For patients undergoing hemodialysis, adjust the pregabalin daily dose based on renal function. In addition to the daily dose adjustment, administer a supplemental dose immediately following every 4-hour hemodialysis treatment (see Table 1). CLCr = Table 1. Pregabalin Dosage Adjustment Based on Renal Function Creatinine Clearance Total Pregabalin Daily Dose (CLcr) (mL/min) (mg/day)* 60 150 300 450 600 30�60 15�30 <15 75 25�50 25 150 75 25�50 225 100�150 50�75 300 150 75 Dose Regimen BID or TID BID or TID QD or BID QD Supplementary dosage following hemodialysis (mg) Patients on the 25 mg QD regimen: take one supplemental dose of 25 mg or 50 mg Patients on the 25�50 mg QD regimen: take one supplemental dose of 50 mg or 75 mg Patients on the 50�75 mg QD regimen: take one supplemental dose of 75 mg or 100 mg Patients on the 75 mg QD regimen: take one supplemental dose of 100 mg or 150 mg TID = Three divided doses; BID = Two divided doses; QD = Single daily dose. *Total daily dose (mg/day) should be divided as indicated by dose regimen to provide mg/dose. Supplementary dose is a single additional dose. CONTRAINDICATIONS LYRICA is contraindicated in patients with known hypersensitivity to pregabalin or any of its components. Angioedema and hypersensitivity reactions have occurred in patients receiving pregabalin therapy. WARNINGS AND PRECAUTIONS Angioedema There have been postmarketing reports of angioedema in patients during initial and chronic treatment with LYRICA. Specific symptoms included swelling of the face, mouth (tongue, lips, and gums), and neck (throat and larynx). There were reports of life-threatening angioedema with respiratory compromise requiring emergency treatment. Discontinue LYRICA immediately in patients with these symptoms. Exercise caution when prescribing LYRICA to patients who have had a previous episode of angioedema. In addition, patients who are taking other drugs associated with angioedema (e.g., angiotensin converting enzyme inhibitors [ACE-inhibitors]) may be at increased risk of developing angioedema. Hypersensitivity There have been postmarketing reports of hypersensitivity in patients shortly after initiation of treatment with LYRICA. Adverse reactions included skin redness, blisters, hives, rash, dyspnea, and wheezing. Discontinue LYRICA immediately in patients with these symptoms. Withdrawal of Antiepileptic Drugs (AEDs) As with all AEDs, withdraw LYRICA gradually to minimize the potential of increased seizure frequency in patients with seizure disorders. If LYRICA is discontinued, taper the drug gradually over a minimum of 1 week. Suicidal Behavior and Ideation Antiepileptic drugs (AEDs), including LYRICA, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Monitor patients treated with any AED for any indication for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Pooled analyses of 199 placebo-controlled clinical trials (mono- and adjunctive therapy) of 11 different AEDs showed that patients randomized to one of the AEDs had approximately twice the risk (adjusted Relative Risk 1.8, 95% CI: 1.2, 2.7) of suicidal thinking or behavior compared to patients randomized to placebo. In these trials, which had a median treatment duration of 12 weeks, the estimated incidence rate of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43%, compared to 0.24% among 16,029 placebo-treated patients, representing an increase of approximately one case of suicidal thinking or behavior for every 530 patients treated. There were four suicides in drug-treated patients in the trials and none in placebo-treated patients, but the number is too small to allow any conclusion about drug effect on suicide. The increased risk of suicidal thoughts or behavior with AEDs was observed as early as one week after starting drug treatment with AEDs and persisted for the duration of treatment assessed. Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be assessed. The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed. The finding of increased risk with AEDs of varying mechanisms of action and across a range of indications suggests that the risk applies to all AEDs used for any indication. The risk did not vary substantially by age (5-100 years) in the clinical trials analyzed. Table 2 shows absolute and relative risk by indication for all evaluated AEDs. Table 2 Risk by indication for antiepileptic drugs in the pooled analysis Indication Placebo Patients Drug Patients Relative Risk: Risk Difference: with Events Per with Events Per Incidence of Events Additional Drug Patients 1000 Patients 1000 Patients in Drug Patients/Incidence with Events Per in Placebo Patients 1000 Patients Epilepsy 1.0 3.4 3.5 2.4 Psychiatric 5.7 8.5 1.5 2.9 Other 1.0 1.8 1.9 0.9 Total 2.4 4.3 1.8 1.9 The relative risk for suicidal thoughts or behavior was higher in clinical trials for epilepsy than in clinical trials for psychiatric or other conditions, but the absolute risk differences were similar for the epilepsy and psychiatric indications. Anyone considering prescribing LYRICA or any other AED must balance the risk of suicidal thoughts or behavior with the risk of untreated illness. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Should suicidal thoughts and behavior emerge during treatment, the prescriber needs to consider whether the emergence of these symptoms in any given patient may be related to the illness being treated. Inform patients, their caregivers, and families that LYRICA and other AEDs increase the risk of suicidal thoughts and behavior and advise them of the need to be alert for the emergence or worsening of the signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Report behaviors of concern immediately to healthcare providers. Peripheral Edema LYRICA treatment may cause peripheral edema. In short-term trials of patients without clinically significant heart or peripheral vascular disease, there was no apparent association between peripheral edema and cardiovascular complications such as hypertension or congestive heart failure. Peripheral edema was not associated with laboratory changes suggestive of deterioration in renal or hepatic function. In controlled clinical trials the incidence of peripheral edema was 6% in the LYRICA group compared with 2% in the placebo group. In controlled clinical trials, 0.5% of LYRICA patients and 0.2% placebo patients withdrew due to peripheral edema. Higher frequencies of weight gain and peripheral edema were observed in patients taking both LYRICA and a thiazolidinedione antidiabetic agent compared to patients taking either drug alone. The majority of patients using thiazolidinedione antidiabetic agents in the overall safety database were participants in studies of pain associated with diabetic peripheral neuropathy. In this population, peripheral edema was reported in 3% (2/60) of patients who were using thiazolidinedione antidiabetic agents only, 8% (69/859) of patients who were treated with LYRICA only, and 19% (23/120) of patients who were on both LYRICA and thiazolidinedione antidiabetic agents. Similarly, weight gain was reported in 0% (0/60) of patients on thiazolidinediones only; 4% (35/859) of patients on LYRICA only; and 7.5% (9/120) of patients on both drugs. As the thiazolidinedione class of antidiabetic drugs can cause weight gain and/or fluid retention, possibly exacerbating or leading to heart failure, exercise caution when co-administering LYRICA and these agents. Because there are limited data on congestive heart failure patients with New York Heart Association (NYHA) Class III or IV cardiac status, exercise caution when using LYRICA in these patients. Dizziness and Somnolence LYRICA may cause dizziness and somnolence. Inform patients that LYRICA-related dizziness and somnolence may impair their ability to perform tasks such as driving or operating machinery. In the LYRICA controlled trials, dizziness was experienced by 31% of LYRICAtreated patients compared to 9% of placebo-treated patients; somnolence was experienced by 22% of LYRICA-treated patients compared to 7% of placebo-treated patients. Dizziness and somnolence generally began shortly after the initiation of LYRICA therapy and occurred more frequently at higher doses. Dizziness and somnolence were the adverse reactions most frequently leading to withdrawal (4% each) from controlled studies. In LYRICA-treated patients reporting these adverse reactions in short-term, controlled studies, dizziness persisted until the last dose in 30% and somnolence persisted until the last dose in 42% of patients. Weight Gain LYRICA treatment may cause weight gain. In LYRICA controlled clinical trials of up to 14 weeks, a gain of 7% or more over baseline weight was observed in 9% of LYRICAtreated patients and 2% of placebo-treated patients. Few patients treated with LYRICA (0.3%) withdrew from controlled trials due to weight gain. LYRICA associated weight gain was related to dose and duration of exposure, but did not appear to be associated with baseline BMI, gender, or age. Weight gain was not limited to patients with edema [see Warnings and Precautions, Peripheral Edema]. Although weight gain was not associated with clinically important changes in blood pressure in short-term controlled studies, the long-term cardiovascular effects of LYRICA-associated weight gain are unknown. Among diabetic patients, LYRICA-treated patients gained an average of 1.6 kg (range: -16 to 16 kg), compared to an average 0.3 kg (range: -10 to 9 kg) weight gain in placebo patients. In a cohort of 333 diabetic patients who received LYRICA for at least 2 years, the average weight gain was 5.2 kg. While the effects of LYRICAassociated weight gain on glycemic control have not been systematically assessed, in controlled and longer-term open label clinical trials with diabetic patients, LYRICA treatment did not appear to be associated with loss of glycemic control (as measured by HbA1C). Abrupt or Rapid Discontinuation Following abrupt or rapid discontinuation of LYRICA, some patients reported symptoms including insomnia, nausea, headache, and diarrhea. Taper LYRICA gradually over a minimum of 1 week rather than discontinuing the drug abruptly. Tumorigenic Potential In standard preclinical in vivo lifetime carcinogenicity studies of LYRICA, an unexpectedly high incidence of hemangiosarcoma was identified in two different strains of mice [see Nonclinical Toxicology, Carcinogenesis, Mutagenesis, Impairment of Fertility]. The clinical significance of this finding is unknown. Clinical experience during LYRICA's premarketing development provides no direct means to assess its potential for inducing tumors in humans. In clinical studies across various patient populations, comprising 6396 patient-years of exposure in patients >12 years of age, new or worsening-preexisting tumors were reported in 57 patients. Without knowledge of the background incidence and recurrence in similar populations not treated with LYRICA, it is impossible to know whether the incidence seen in these cohorts is or is not affected by treatment. Ophthalmological Effects In controlled studies, a higher proportion of patients treated with LYRICA reported blurred vision (7%) than did patients treated with placebo (2%), which resolved in a majority of cases with continued dosing. Less than 1% of patients discontinued LYRICA treatment due to vision-related events (primarily blurred vision). Prospectively planned ophthalmologic testing, including visual acuity testing, formal visual field testing and dilated funduscopic examination, was performed in over 3600 patients. In these patients, visual acuity was reduced in 7% of patients treated with LYRICA, and 5% of placebo-treated patients. Visual field changes were detected in 13% of LYRICAtreated, and 12% of placebo-treated patients. Funduscopic changes were observed in 2% of LYRICA-treated and 2% of placebo-treated patients. Although the clinical significance of the ophthalmologic findings is unknown, inform patients to notify their physician if changes in vision occur. If visual disturbance persists, consider further assessment. Consider more frequent assessment for patients who are already routinely monitored for ocular conditions. Creatine Kinase Elevations LYRICA treatment was associated with creatine kinase elevations. Mean changes in creatine kinase from baseline to the maximum value were 60 U/L for LYRICA-treated patients and 28 U/L for the placebo patients. In all controlled trials across multiple patient populations, 1.5% of patients on LYRICA and 0.7% of placebo patients had a value of creatine kinase at least three times the upper limit of normal. Three LYRICA-treated subjects had events reported as rhabdomyolysis in premarketing clinical trials. The relationship between these myopathy events and LYRICA is not completely understood because the cases had documented factors that may have caused or contributed to these events. Instruct patients to promptly report unexplained muscle pain, tenderness, or weakness, particularly if these muscle symptoms are accompanied by malaise or fever. Discontinue treatment with LYRICA if myopathy is diagnosed or suspected or if markedly elevated creatine kinase levels occur. Decreased Platelet Count LYRICA treatment was associated with a decrease in platelet count. LYRICA-treated subjects experienced a mean maximal decrease in platelet count of 20 x 10 3/�L, compared to 11 x 10 3/�L in placebo patients. In the overall database of controlled trials, 2% of placebo patients and 3% of LYRICA patients experienced a potentially clinically significant decrease in platelets, defined as 20% below baseline value and <150 x 10 3/�L. A single LYRICA treated subject developed severe thrombocytopenia with a platelet count less than 20 x 103/�L. In randomized controlled trials, LYRICA was not associated with an increase in bleeding-related adverse reactions. PR Interval Prolongation LYRICA treatment was associated with PR interval prolongation. In analyses of clinical trial ECG data, the mean PR interval increase was 3�6 msec at LYRICA doses 300 mg/day. This mean change difference was not associated with an increased risk of PR increase 25% from baseline, an increased percentage of subjects with on-treatment PR >200 msec, or an increased risk of adverse reactions of second or third degree AV block. Subgroup analyses did not identify an increased risk of PR prolongation in patients with baseline PR prolongation or in patients taking other PR prolonging medications. However, these analyses cannot be considered definitive because of the limited number of patients in these categories. ADVERSE REACTIONS Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In all controlled and uncontrolled trials across various patient populations during the premarketing development of LYRICA, more than 10,000 patients have received LYRICA. Approximately 5000 patients were treated for 6 months or more, over 3100 patients were treated for 1 year or longer, and over 1400 patients were treated for at least 2 years. Adverse Reactions Most Commonly Leading to Discontinuation in All Premarketing Controlled Clinical Studies In premarketing controlled trials of all populations combined, 14% of patients treated with LYRICA and 7% of patients treated with placebo discontinued prematurely due to adverse reactions. In the LYRICA treatment group, the adverse reactions most frequently leading to discontinuation were dizziness (4%) and somnolence (3%). In the placebo group, 1% of patients withdrew due to dizziness and <1% withdrew due to somnolence. Other adverse reactions that led to discontinuation from controlled trials more frequently in the LYRICA group compared to the placebo group were ataxia, confusion, asthenia, thinking abnormal, blurred vision, incoordination, and peripheral edema (1% each). Most Common Adverse Reactions in All Premarketing Controlled Clinical Studies In premarketing controlled trials of all patient populations combined, dizziness, somnolence, dry mouth, edema, blurred vision, weight gain, and "thinking abnormal" (primarily difficulty with concentration/attention) were more commonly reported by subjects treated with LYRICA than by subjects treated with placebo (5% and twice the rate of that seen in placebo). Controlled Studies with Neuropathic Pain Associated with Diabetic Peripheral Neuropathy Adverse Reactions Leading to Discontinuation In clinical trials in patients with neuropathic pain associated with diabetic peripheral neuropathy, 9% of patients treated with LYRICA and 4% of patients treated with placebo discontinued prematurely due to adverse reactions. In the LYRICA treatment group, the most common reasons for discontinuation due to adverse reactions were dizziness (3%) and somnolence (2%). In comparison, <1% of placebo patients withdrew due to dizziness and somnolence. Other reasons for discontinuation from the trials, occurring with greater frequency in the LYRICA group than in the placebo group, were asthenia, confusion, and peripheral edema. Each of these events led to withdrawal in approximately 1% of patients. Most Common Adverse Reactions Table 3 lists all adverse reactions, regardless of causality, occurring in 1% of patients with neuropathic pain associated with diabetic neuropathy in the combined LYRICA group for which the incidence was greater in this combined LYRICA group than in the placebo group. A majority of pregabalin-treated patients in clinical studies had adverse reactions with a maximum intensity of "mild" or "moderate". Newsline J U LY 2 0 12 Ten-year review of menopausal hormone therapy page 20 One in 30 boomers infected with hepatitis C page 21 Vitamin D may not be effective against fractures page 21 Studies look at food and physical fitness Metabolic cycles that are tied to the circadian rhythms of various organs can be made less efficient when food is consumed throughout the day and night, having a negative impact on such processes as cholesterol breakdown and insulin production. A timerestricted eating regimen appears to be a useful nonpharmacologic strategy against obesity and associated diseases. Another study focusing on fat intake revealed that cholesterol levels rose when people switched to a low-carbohydrate diet. Ingegerd Johansson and colleagues reported in Nutrition Journal (2012;11:40) that among 140,000 adults in northern Sweden, fat intake decreased between 1986 and 1992, and then began to rise again beginning in 2002 (among women) and 2004 (among men). These increases coincided with the introduction of positive media support for a low-carbohydrate/ high-fat diet. BMI increased continuously for both sexes, but serum cholesterol levels decreased during the 1986-2004 period, remained unchanged until 2007, and then began to rise. The increase in serum cholesterol occurred with the increase in fat intake, particularly with intake of saturated fat and fats used for cooking and as bread spreads. Johansson commented in a separate statement, that although lowcarbohydrate/high-fat diets may help with short-term weight loss, the group's fi ndings show that long-term weight loss is not maintained and that this diet increases blood cholesterol, which has a major impact on cardiovascular disease risk. � THINKSTOCK HELPING YOUR patients stay fit might have more to do with when they eat than what they eat, a recent study indicates. Dietinduced obesity has been exclusively attributed to increased caloric intake from fat, according to the study authors (Cell Metab. 2012;15:848-860). However, they learned that when mice on a high-fat diet were allowed to eat for only eight hours per day, they ate just as much as mice that were allowed to eat around the clock (outside their normal feeding cycle), yet the time-restricted mice showed improvements in their metabolic and physiological rhythms. For example, compared with the around-the-clock mice, the time-restricted mice gained less weight, suffered less liver damage, had less hyperinsulinemia and lower levels of inflammation, and experienced improved motor coordination. Saturated fats had a direct effect on serum cholesterol levels and BMI. Lyme disease cases by month of onset, 2001-2010 According to the CDC, Lyme disease patients are most likely to have illness onset in June, July, or August. Source: CDC, Division of Vector-Borne Diseases ( www.cdc. gov/ncezid/dvbd/) 80,000 70,000 60,000 50,000 40,000 30,000 20,000 10,000 0 Month of disease onset 18 THE CLINICAL ADVISOR � JULY 2012 � www.ClinicalAdvisor.com THERAP EUTIC NUTRITION For the varying needs of your pediatric patients. POLYMERIC (INTACT PROTEIN) PEPTIDE AGES: 1�13 AMINO ACID AGE: BIRTH TO 12 MONTHS AGE: 1 YEAR AND UP Abbott Nutrition Pediatric Therapeutic Nutrition AGES: 1�13 Complete nutrition for your patients' unique needs. Trust the Abbott portfolio of nutritional products to help maximize each patients' potential. As they grow and experience new challenges, there's a formula that can help support their nutritional needs. USE UNDER MEDICAL SUPERVISION. EleCare�, EleCare� Jr, and PediaSure� are trademarks of Abbott Laboratories. � 2012 Abbott Laboratories 79489.001/JUNE 2012 LITHO IN USA Newsline Probiotics ease antibiotic GI side effect POOLED EVIDENCE from a recent systematic review and meta-analysis suggests that probiotics may reduce antibioticassociated diarrhea by as much as nearly 50%. Probiotics--live microorganisms intended to have a health benefit when consumed--can maintain or restore gut microecology during or after antibiotic treatment in several ways, such as by competing for nutrients, inhibiting epithelial and mucosal adherence of pathogens, and introducing lower colonic pH that favors the growth of nonpathogenic species. The majority of 63 randomized controlled trials (involving 11,811 participants) included in the current review used Lactobacillus based interventions alone or in combination with other probiotics, including Bifidobacterium, Saccharomyces, Streptococcus, Enterococcus, and/or Bacillus ( JAMA. 2012;307:1959-1969). Probiotic use was associated with a 42% lower risk of developing diarrhea compared with control patients not using probiotics. Although this result was consistent across a number of subgroup and sensitivity analyses, the investigators noted that significant differences across studies existed and that the evidence is insufficient to determine whether this association varies systematically by population, by antibiotic characteristic, or by probiotic preparation. The researchers also pointed out that in rare cases, probiotics have been linked to such serious adverse effects as Bifidobacterium (orange) exist naturally in the GI system. fungemia and bacterial sepsis. Nevertheless, the evidence was strong enough to allow the investigators to conclude that probiotic administration is associated with a reduced risk of antibioticassociated diarrhea. Hormone therapy undergoes 10-year review A SYSTEMATIC review of nine randomized, placebo-controlled trials published to assess the effectiveness of menopausal hormone therapy in the prevention of chronic conditions revealed: estrogen plus progestin and estrogen alone decreased risk for fractures but increased risk for stroke, thromboembolic events, gallbladder disease, and urinary incontinence; estrogen plus progestin increased risk for breast cancer and probable dementia; and estrogen alone decreased risk for breast cancer. At one time, menopausal hormone therapy was routinely used by postmenopausal women to prevent cardiovascular disease, dementia, osteoporosis, and other chronic conditions. However, once initial results of the Women's Health Initiative (WHI) trials emerged in 2002 indicating important adverse health effects of this treatment, the U.S. Preventive Services Task Force (USPSTF) issued recommendations against using hormone therapy to prevent chronic conditions for estrogen plus progestin in 2002, and for estrogen only in 2005. Other groups provided similar recommendations, and currently, the FDA indications for hormone therapy use include short-term treatment of menopausal symptoms, such as vasomotor hot flashes or urogenital atrophy, and prevention of osteoporosis. Heidi D. Nelson, MD, MPH, and colleagues undertook the current systematic review for the USPSTF to update the group's recommendations. The investigator's fi ndings, which were published online ahead of print in Annals of Internal Medicine, will inform an upcoming USPSTF recommendation for menopausal hormone therapy. � PHOTO RESEARCHERS, INC / CAROLYN A. MCKEONE Estrogen alone decreased risk for breast cancer. 20 THE CLINICAL ADVISOR � JULY 2012 � www.ClinicalAdvisor.com � PHOTO RESEARCHERS, INC / SCIMAT Vitamin D for fall prevention Combo best CLINICIANS SHOULD recommend vitamin D supplementation as well as exercise or physical therapy in communitydwelling adults aged 65 years or older who are at increased risk for falls, advised the United States Preventive Services Task Force (USPSTF) in a recommendation appearing online ahead of print in Annals of Internal Medicine. However, in a separate draft recom mendation statement that has yet to be finalized, the USPSTF expressed more hesitation about other uses of vitamin D supplementation. Specifically, the group found that currently, there is insufficient evidence to assess the balance of the benefits and harms of the following: combined vitamin D and calcium supplementation for the primary prevention of fractures in premenopausal women or men; and daily supplementation with more than 400 IU of vitamin D3 and 1,000 mg of calcium for the primary prevention of fractures in noninstitutionalized postmenopausal women. In addition, the USPSTF draft statement recommends against daily supplementation with up to 400 IU of vitamin D3 and 1,000 mg of calcium carbonate for the primary prevention of fractures in noninstitutionalized postmenopausal women. Older adults may need more vitamin D to prevent mobility difficulties, according to data from 2,099 community-dwelling men and women aged 70 to 79 years reported online ahead of print in The Journal of Gerontology: Medical Sciences. Over the course of six years, Denise K. Houston, PhD, and colleagues observed an estimated 30% increased risk of mobility limitations for the participants with low levels of vitamin D--that is, levels of 25-hydroxyvitamin D (25[OH] D) lower than 75 nmol/L--and almost a twofold higher risk of mobility disability for those individuals. for youths with type 2 diabetes COMBINING rosiglitazone (Avandia) with metformin helped children and adolescents with new-onset type 2 diabetes achieve glycemic control more effectively than metformin alone in a recent study. Adding an intensive lifestyle intervention to metformin provided no more benefit than metformin therapy alone. Despite the increasing prevalence of type 2 diabetes in youth, few data are available to guide treatment, wrote Phil Zeitler, MD, PhD, and other members of the TODAY Study Group in The New England Journal of Medicine, which published the study findings online ahead of print. They studied 699 youths aged 10 to 17 years, with a mean duration of diagnosed type 2 diabetes of 7.8 months, who had been randomized to metformin 1,000 mg b.i.d., or to metformin combined with rosiglitazone 4 mg b.i.d., or to metformin plus intensive lifestyle changes designed to help participants lose weight and increase physical activity. Metformin alone proved to be inadequate for maintaining acceptable, long-term blood glucose control in 51.7% of the patients over an average follow-up of 46 months. The failure rate was 46.6% in the metformin-plus-lifestyle group, but only 38.6% in the metforminand-rosiglitazone group. Older adults may need more vitamin D to prevent mobility difficulties. Be sure to test baby-boomers for hepatitis C The CDC has proposed that all adults born between 1945 and 1965 undergo a one-time test for hepatitis C, noting that one in 30 members of this generation has been infected. Similarly, the American Gastroenterological Association (AGA) has launched the "I.D. Hep C" campaign (www.IDHepC.org) to educate people, particularly baby-boomers, about hepatitis C and encourage them to get tested. According to results of an AGA survey, 74% of baby-boomers have never been tested for the illness or are unsure as to whether they have been tested. The survey also revealed that 83% of baby-boomers don't realize that their generation is most likely to have hepatitis C. In fact, of the nearly 5 million Americans infected with hepatitis C, 82% are babyboomers, but three in four people don't know they have it, contend AGA representatives in a statement issued by the organization. www.ClinicalAdvisor.com � THE CLINICAL ADVISOR � JULY 2012 21 � THINKSTOCK CME CE PROGRAM OUTLINE JULY 2012 0.5 CREDITS Page 23 FEATURE Evaluating and managing pediatric food allergy Cathy C. Ruff, MS, PA-C Cathy C. Ruff, MS, PA-C, has no relationships to disclose relating to the content of this article. LEARNING OBJECTIVES: � Name the most common allergenic food in the United States. � List symptoms associated with an immunoglobulin-E-mediated hypersensitivity response. � Identify the pediatric food allergies that are typically not outgrown. � Name the vaccines that are contraindicated in egg-allergic patients. 0.5 CREDITS Page 47 DERMATOLOGY CLINIC Blue-black mole with regular borders Kerri Robbins, MD Kerri Robbins, MD, has no relationships to disclose relating to the content of this article. Extremely pruritic hyperkeratotic papules Adam J. Carter and Julia R. Nunley, MD Adam J. Carter and Julia R. Nunley, MD, have no relationships to disclose relating to the content of this article. LEARNING OBJECTIVES: � To identify and diagnose dermatologic conditions and review up-to-date treatment. Page 53 DERMATOLOGIC LOOK-ALIKES Erythematous palmar lesions Kerri Robbins, MD Kerri Robbins, MD has no relationships to disclose relating to the content of this article. LEARNING OBJECTIVE: � To distinguish and properly treat dermatologic conditions with similar presentations. Page 57 POSTTEST This program has been reviewed and is approved for a maximum of 1 hour of AAPA Category I CME credit by the Physician Assistant Review Panel. Approval is valid for one year from the issue date of July 2012. Participants may submit the self-assessment at any time during that period. This program was planned in accordance with AAPA's CME Standards for Enduring Material Programs and for Commercial Support of Enduring Material Programs. Nurse Practitioner Associates for Continuing Education (NPACE) is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's Commission on Accreditation. NPACE designates this educational activity for a maximum of 1 contact hour of credit. Participants should only claim credit commensurate with the extent of their participation in the activity. 22 THE CLINICAL ADVISOR � JULY 2012 � www.ClinicalAdvisor.com LEARNING OBJECTIVES : CME CE FEATURE CATHY C. RUFF, MS, PA-C � Name the most common allergenic food in the United States. � List symptoms associated with an immunoglobulin-E-mediated hypersensitivity response. � Identify the pediatric food allergies that are typically not outgrown. � Name the vaccines that are contraindicated in egg-allergic patients. COMPLETE THE POSTTEST: Page 57 ADDITIONAL CME/CE: Pages 47, 53 Turn to page 22 for additional information on this month's CME/CE courses. Evaluating and managing pediatric food allergy An approach involving primary-care clinicians, and specialists--including allergists, gastroenterologists, nutritionists, and counselors--is crucial. Angioedema of the lip (shown) may be a symptom of an Ig-E-mediated allergic reaction. A lthough food allergy is seen in patients of all ages, it presents unique and specific concerns for the pediatric population. The National Institute of Allergy and Infectious Diseases has clinical guidelines in place for the evaluation and management of food allergy.1 The guidelines most pertinent to the pediatric population are outlined in this article. Food allergy defined � PHOTOTAKE / DR. ALLAN HARRIS Food allergy is an adverse health effect arising from a specific immune response that occurs reproducibly after exposure to a given food. Immunologic reactivity may be either immunoglobulin (Ig) E-mediated or non-IgE-mediated. In contrast, food intolerance is a nonimmunologic adverse reaction (e.g., the inability to digest lactose). A diagnosis of IgE-mediated food allergy requires the presence of allergen-specific IgE, which is produced during the process known as "sensitization," and onset of clinical symptoms after exposure to the allergen. Continued on page 24 www.ClinicalAdvisor.com � THE CLINICAL ADVISOR � JULY 2012 23 CME CE PEDIATRIC FOOD ALLERGY The primary risk factor for development of food allergy in a child is having a biological parent or sibling with a history of allergic disease. Food allergens are specific components of food (or an ingredient in food)--typically proteins--that are recognized by allergen-specific immune cells. The allergens elicit immunologic reactions. Some allergens cause reactions primarily if eaten raw, but most can cause reactions even after being cooked digested. Prevalence Methods for reporting food allergy vary, making determination of prevalence difficult. A 2007 meta-analysis found the overall prevalence of allergy to cow's milk, egg, peanut, fish, or shellfish to be 12% in children who self-reported symptoms.2 Prevalence is much lower--2.5% for adults and children combined--when self-reported symptoms and evidence of sensitization are considered. In the United States, the prevalence of allergy to the most commonly allergenic foods is estimated as follows: peanut, 1.3%; tree nut, 1.2%; seafood (children), 0.2%; cow's milk, 0.4%; and eggs, 0.2%.3,4 The primary risk factor for development of food allergy in a child is having a biological parent or sibling with a history of allergic disease. Allergic diseases include allergic rhinitis, atopic dermatitis, asthma, and food allergy. Children at highest risk have preexisting severe allergic disease (significant atopic dermatitis or asthma) or a family history of food allergy. Approximately one-third of children younger than age 5 years who have moderate-to-severe atopic dermatitis develop IgE-mediated food allergy.5 Whether food allergy can exacerbate atopic dermatitis and what the mechanism might be is unclear. Associated conditions has a 92% likelihood of having an allergy to goat's milk or that a patient with a tree-nut allergy has a 37% likelihood of being allergic to other tree nuts (e.g., walnuts and pecans are related).6 Perhaps a less obvious example of cross-reactivity is the patient who is allergic to cow's milk as well as beef (13%-20% chance7) or the egg-allergic patient who cannot tolerate poultry. Interestingly, some fruits (e.g., kiwi, banana, avocado) are allergenically related to latex. Therefore, patients who cannot tolerate these fruits must be questioned about their tolerance to latex because of the dangers that might be posed when children are exposed to balloons. In short, patients allergic to one food may be allergic to another, with a higher propensity of allergy toward foods that are similar to one another. Severity of allergic reactions is multifactorial and variable. The severity of a reaction cannot be accurately predicted, and the severity of past reactions does not predict severity of future reactions. Similarly, one cannot predict severity based upon food-specific IgE level or the wheal size in a skin-prick test (SPT). The factor most commonly identified with severe reactions is coexistence of asthma, especially when the child has a peanut or tree-nut allergy. IgE-mediated vs. non-IgE-mediated reactions Other allergic conditions are commonly seen in children with food allergy. For example, children with food allergy are four times more likely to have asthma, two times more likely to have atopic dermatitis, and nearly four times more likely to have respiratory allergies compared with children who have no food allergy. In children with asthma, coexistence of food allergy may be a risk factor for severe asthma exacerbations. Therefore, management of asthma in these children becomes extremely important. Allergic responses can also occur following exposure to a food allergen that shares structural similarity with a different food or an aeroallergen. This cross-reactivity is demonstrated by the finding that a patient who is allergic to cow's milk Allergic hypersensitivity--a response in which an immunologic mechanism is defi ned or strongly suspected--can be either IgE-mediated or non-IgE-mediated. IgE-mediated responses are either nonatopic or atopic in nature. Nonatopic responses include insect stings, drug reactions, and helminth infiltration. Atopic reactions include allergic diseases. In IgE-mediated hypersensitivity, antibodies develop in response to antigen. With regard to food allergy, IgEmediated reactions include food-induced anaphylaxis, oral allergy syndrome, and allergic gastroenteritis. Non-IgE-mediated hypersensitivity responses include T-cell, eosinophil, and IgG-mediated reactions, such as allergic eosinophilic esophagitis (EoE), food protein-induced enterocolitis syndrome (FPIES), proctocolitis, and celiac disease (gluten-sensitive enteropathy). To complicate matters, each of these illnesses may be accompanied by an IgEmediated component. Diagnostic findings Distinguishing between IgE-mediated and non-IgEmediated reactions can be difficult. While symptoms vary 24 THE CLINICAL ADVISOR � JULY 2012 � www.ClinicalAdvisor.com Patients who have non-IgE-mediated disease will present with symptoms of gastroesophageal reflux, excessive spitting up, or emesis. from patient to patient, IgE-mediated symptoms generally include acute nausea, abdominal pain, and vomiting. These symptoms typically occur with allergic manifestations in other target organs. Physical findings may include cutaneous reactions, such as urticaria, angioedema, rashes, and flushing (Figure 1). Common respiratory manifestations include acute rhinoconjunctivitis and bronchospasm. Patients with non-IgE-mediated disease will present with symptoms of gastroesophageal reflux, excessive spitting up, or emesis. In addition, the symptoms of EoE include dysphagia, intermittent abdominal pain, irritability, sleep disturbance, and failure to respond to conventional reflux medications. Children with eosinophilic gastroenteritis may also have a history of early satiety, failure to thrive, and/or weight loss. Patients with food protein-induced enteropathies (including proctocolitis and enterocolitis) present very differently. The most common symptoms of proctocolitis include gross or occult blood in the stool; the disorder is most commonly seen in the first few months of life in an infant who is typically thriving. In FPIES, however, the infant may present with protracted vomiting and diarrhea that may or may not contain blood, dehydration, abdominal distention, and failure to thrive. Of note, vomiting typically is delayed for up to one to three hours after feeding. Patients with celiac disease typically have diarrhea or steatorrhea, abdominal distention, flatulence, weight loss or failure to thrive, oral ulcers, and possibly nausea and vomiting. Historical information that is important in determining the type of hypersensitivity reaction includes the route of exposure--for example, was the food ingested or inhaled, or was there just skin contact? The quantity of food ingested is also significant: Was the amount minute, small, or large? How was the food prepared? Was it raw or cooked? Has the patient had previous reactions to the food in its raw and cooked forms? Asking about spices or whether the food was mixed with other potential allergenic components is also necessary. Information about whether or not someone else ate the same food and had a similar reaction would help to rule in or out infectious causes. A review of the patient's current diet should include questioning as to whether the suspected allergen had been eaten again without reaction. IgE-mediated allergy should be suspected when symptoms begin within minutes to hours of ingesting a food, occur repeatedly or in young children, or develop in an infant or young child who has been diagnosed with any of the following: FIGURE 1. Urticaria is a response of the body's immune system and a common cutaneous finding of IgE-mediated reactions. moderate-to-severe atopic dermatitis, EoE, gastritis, enteritis/ enterocolitis/enteropathy, or allergic proctitis. Laboratory studies Although the medical history and physical exam are the mainstays in establishing food allergy, the diagnosis can only be made when those findings are considered in combination with diagnostic testing. The most common lab studies include the SPT, IgE levels to specific antigens as determined by ImmunoCAP testing (Phadia, Uppsala, Sweden), total serum IgE, intradermal testing, and atopy patch testing. Intradermal testing, total serum IgE, and atopy patch testing should not be used in routine evaluation of food allergy. SPT and serum measurements of specific IgE levels are recommended for identifying foods that may provoke allergic reactions, but they are not diagnostic. For example, a patient who has a positive result on SPT to wheat and an elevated serum IgE to wheat may not necessarily have clinical symptoms that are reproducible. SPT may be available in a primary-care setting but is more likely performed by an allergist. The primary-care provider can order specific IgE levels, based on the patient's clinical picture. Continued on page 26 www.ClinicalAdvisor.com � THE CLINICAL ADVISOR � JULY 2012 25 � BSIP / PHOTOTAKE CME CE PEDIATRIC FOOD ALLERGY While there are different types of avoidance or elimination diets, the basic concept is to remove the suspected food for two to eight weeks. Patient history and physical examination findings are also crucial components of the diagnosis of non-IgE-mediated reactions, but the recommended diagnostic studies vary according to suspected illness. In patients thought to have EoE, the atopy patch test can be helpful in identifying the culprit foods. This should be done in combination with SPT and specific serum IgE tests. The atopy patch test requires placement of a small quantity of each suspected allergen in an individual square chamber that is applied to the upper back. A patch is then adhered over the allergen and left in place for at least 48 hours. A positive reading includes erythema, infiltration of the surrounding skin, and occasionally papules. The dosing for atopy patches is not standardized, but the test seems to be useful in identifying late-phase clinical reactions. Diagnostic studies are not commonly used to identify non-IgE-mediated FPIES. A medical history that includes the absence of symptoms after the suspected food is removed from the diet may be all that is necessary to diagnose FPIES. An oral food challenge can be useful--unless there is a history of hypotensive episodes. Similarly, the diagnosis of food protein-induced allergic proctocolitis is typically based upon a medical history that includes resolution of symptoms after eliminating the causative food. The gold standard The oral food challenge is the gold standard for diagnosing food allergy.1,8 Because a severe reaction can occur with minute portions, any food suspected of triggering a reaction should be given in a setting by providers who can manage a potential anaphylactic event. Ideally, a doubleblind, placebo-controlled food challenge is performed in a medical facility with appropriate supervision and medical treatments available. Patients should never be instructed to go home and "give the food a try." Whenever possible, neither the provider, the patient, nor the parent should know which food is being served. This eliminates any possibility that anticipation of a response may impact the results of the challenge. Open food challenges can be useful if a child is thought to be outgrowing an allergy. Management Food allergy in children can be managed with dietary avoidance, nutritional counseling, and education for the patient and family. Dietary avoidance is recommended for children with documented IgE- or non-IgE-mediated food allergy (i.e., positive results on the history, physical examination, laboratory findings, and oral food challenge). Dietary avoidance is not recommended for children without documented allergy, nor is it suggested in the management of atopic dermatitis or asthma as a means to decrease to prevent potential food allergy. While there are different types of avoidance or elimination diets, the basic concept is to remove the suspected food for two to eight weeks. Symptoms will resolve if they are food-related and remain if they are not food-related. The diet must be monitored for nutritional adequacy; duration depends on the disease as well as on how well the patient's nutritional needs are being met. Limited elimination diets are typically employed when the provider suspects one of the more commonly allergenic foods (cow's milk, egg, wheat, soy, fish) and the patient has either a positive result on SPT or a specific serum IgE level >0.35 ISAAC standardized units on ImmunoCAP testing. Oligoantigenic elimination diets are useful when allergy to a large number of foods is suspected. This diet includes only those foods that have a low likelihood of allergenicity. The elemental diet, which can be most useful for infants, consists of a hypoallergenic (amino acid-based) formula with a few "safe" foods added, depending on the patient's age. This is useful when allergy to a large number of foods is suspected or for infants who are not yet eating solid food. Compliance is an issue after infancy because children outside early infancy are less likely to transition easily to a hypoallergenic formula, and older children and their parents will have difficulty with a diet that includes very few foods. Nutritional counseling consists of instruction on which specific foods to avoid and on proper reading of food labels and information on avoidance of those foods labeled as "this product may contain trace elements" of the identified allergen. The reason for avoiding such foods is that there is no way to know now much allergen might be present in the packaged food. There may be none, or there may be a large amount. This means the patient may be able to eat the food on one occasion, feel safe in eating it again, and then get a package with a much larger volume of allergen the next time. The potential for severe reaction may then be more likely. Children with multiple food allergies should be referred to a dietitian or nutritionist 26 THE CLINICAL ADVISOR � JULY 2012 � www.ClinicalAdvisor.com to ensure that their dietary needs are being met. From a primary-care perspective, the child must have regular growth monitoring. Because food allergy carries a risk of severe reaction and, potentially, death, patients and their families must have psychological support. Connecting families with support groups, counseling, or others with similar concerns is vital. Medications Outgrowing food allergy While no preventive measures are currently recommended, patients with food allergy must be prescribed epinephrine, typically in the form of an auto-injectable unit for ease of use. Epinephrine is indicated in the treatment of acute, systemic allergic reactions. Antihistamines are used for managing nonsevere allergic reactions. Bronchodilators should be used if respiratory symptoms occur with exposure to the suspected food. Allergen-specific oral and sublingual immunotherapy is currently under study for inducing clinical desensitization but is not recommended for use in clinical practice. Patients should be instructed to use an antihistamine if physical contact with an allergenic food causes cutaneous, ocular, or upper-respiratory-tract symptoms. Diphenhydramine is the antihistamine of choice and should be administered in liquid or chewable form for most rapid effect; the dose in children is 1-2 mg/kg. Patients who have asthma should be given a prescription for a rapidonset bronchodilator as well as other asthma medications, depending on the severity of their disease. Auto-injectable epinephrine must be administered promptly after the ingestion of an allergenic food. This is first-line treatment in all cases of suspected anaphylaxis. Delayed or improper use of the auto-injectable unit is a major cause of death. Beyond inappropriate use of epinephrine, individuals who are at highest risk of death are adolescents and young adults, people with known food allergy and previous history of anaphylaxis, people with asthma (especially if poorly controlled), and people with peanut or tree-nut allergies. In addition to these medication recommendations, providers should suggest that patients wear a medical alert bracelet and provide them with an appropriate action plan. An example of such a plan is available from the Food Allergy and Anaphylaxis Network (available at www.foodallergy. org/fi les/FAAP.pdf, accessed June 15, 2012). The purpose of the action plan is to outline the early signs and symptoms of a reaction, when it is appropriate to use antihistamines, when to use epinephrine, and when to call 911. Tolerance is defined as either having naturally outgrown a food allergy or having received therapy so clinical symptoms no longer develop following ingestion of the food. In general, symptoms and exposure (accidental or not) are monitored over time. There are currently no specific recommendations for when to retest via SPT or ImmunoCAP levels. However, many specialists will perform annual serum testing in children who have cow's milk, egg, soy, or wheat allergies because these are commonly outgrown by the age of 5 years. Testing for peanut, tree-nut, fish, and shellfish allergies may be performed every two to three years, as these allergies are typically not outgrown. Remember that these are not specific recommendations; rather, they represent the approach taken most commonly by allergists. The reason for retesting is to acquire data on specific IgE levels. With food allergies that are more commonly outgrown, the clinician will see a gradual decline in specific IgE levels over time. One may consider repeating an oral food challenge based on the lowered levels. Rechallenge also might be considered when a child enters kindergarten. If the child has not already outgrown the allergy, parents may wish to know whether the youth will react if exposed to the food in question. In addition, the parent will have less control over what the child eats once he or she reaches school age, so a clearer understanding of what might happen upon exposure is key for both the child and the family. When considering whether or not to rechallenge a child, consultation with a provider who specializes in the treatment and management of food allergy is recommended. Special considerations Maternal diet, introduction of solids, and whether to breastfeed or bottle-feed are important issues to consider in the treatment and management of pediatric food allergy. Recommendations regarding maternal diet during pregnancy have changed over the years. The current recommendation is to not use restriction of maternal diet during pregnancy or lactation as a means of preventing food allergy. Furthermore, there is no evidence to suggest that pregnant women should replace cow's milk with soy milk WHAT DO YOU THINK? Add your comments to this article --or any article -- by going to www.ClinicalAdvisor.com.You will also see what your colleagues are saying. www.ClinicalAdvisor.com � THE CLINICAL ADVISOR � JULY 2012 27 CME CE PEDIATRIC FOOD ALLERGY There is no evidence to suggest that pregnant women should replace cow's milk with soy milk to prevent food allergy in their newborn. to prevent food allergy in their newborn. Women wishing to breastfeed should do so for four to six months according to usual guidelines. Women who choose to bottle-feed should be encouraged to use a hydrolyzed infant formula (as opposed to cow's milk) to help prevent development of food allergy in those infants at risk. With regard to solid food, there are no longer any recommendations to delay introduction. In fact, current guidelines suggest that even potentially allergenic foods may be introduced at the usual time solids enter the diet (age 4-6 months). Primary-care clinicians often have questions about which immunizations can be safely administered to patients with food allergies. Even for patients allergic to egg, some egg-containing vaccines are safe to give in the primary-care setting. The measles, mumps, and rubella vaccine has been found safe even for those patients with severe egg allergy. However, other vaccines are contraindicated or may be used only after they have been "pretested." Currently, information is limited regarding the safety of administering the influenza vaccine in the primary-care setting. Influenza vaccine is recommended for those children most at risk for developing food allergy (e.g., children with asthma). In the high-risk child with egg allergy, a specialist should administer the influenza vaccine. While there are no current recommendations on exactly how to administer the vaccine, many specialists will perform SPT with the vaccine, and then split the dose in half, with each half administered separately. Yellow fever and rabies vaccines are contraindicated in egg-allergic patients.1 Lesser-known allergic entities must also be considered. Oral, or pollen-food, allergy syndrome is an IgE-mediated allergic disorder that is typically caused by a cross-reaction of food allergens with airborne allergens. Symptoms include mild pruritus, tingling, and/or angioedema of the lips, palate, tongue, or oropharynx. Occasionally patients will complain of a sensation of tightness in the throat, but they rarely have systemic symptoms. Diagnosis is based on the clinical history and positive SPT responses to relevant food proteins. Oral challenges have negligible value: Results are often positive when fresh foods are used but may be negative if the food is cooked. As an example, bananas and melons are related to each other and to ragweed. A patient who is allergic to ragweed may have oral symptoms after eating banana or melon. Because ragweed pollen peaks in the fall, patients may have more oral symptoms during that time. Another example is birch, which is structurally similar to several fruits and vegetables (e.g., carrot, celery, apple, pear, kiwi, potato). Therefore, patients allergic to birch may have oral symptoms of tingling and itching when they eat any of the related fruits and vegetables.9,10 Food-dependent exercise-induced anaphylaxis is defined as anaphylaxis with exercise following specific food ingestion. For example, the patient might follow a shrimp lunch with an afternoon jog that ends in an anaphylactic event. While relatively uncommon, this form of anaphylaxis is seen most often in adolescents and adults younger than age 40 years, although the age range may vary from younger than age 5 years to older than age 75 years.11,12 Females are more commonly affected than males. The mechanism is still unknown. The point of mentioning these disorders is to remind the clinician that a thorough history is key when evaluating a patient for food allergy. Referral While primary-care providers are certainly equipped with the knowledge to identify patients with food allergy, there are times when a specialist can be a valuable collaborator in providing the best care to patients and families. If the patient has severe or persistent disease, multiple food sensitivities, or coexisting allergic disease, the specialist may be most able to identify the best diagnostic and treatment options. In addition, test interpretation can be just as complicated as performing food challenges. The specialist often has easier access to dietitians and nutritionists who are experienced in the development of targeted elimination diets. And, as with all chronic disease, comprehensive patient education is extremely important. The specialist can reinforce the primary-care provider's educational plan or offer education when time constraints limit the primary-care clinician's ability to do so. Primary-care providers are frequently the first clinician to identify and treat food allergy. These clinicians must have a good understanding of what constitutes food allergy, what the different types of immunologic responses are, and who is at risk for developing food allergy. This information will allow the provider to complete a thorough history and physical examination as well as identify the most useful diagnostic studies. Key to the patient's success is an understanding of 28 THE CLINICAL ADVISOR � JULY 2012 � www.ClinicalAdvisor.com the illness, the importance of diet, and early treatment if there is a history of severe allergic reaction. Education and emotional support are also crucial. Pediatric food allergy can be challenging, but by working collaboratively with the family, nutritional experts, counselors, and a specialist, care can be optimized. Ms. Ruff is an associate professor in the Child Health Associate/ Physician Assistant Program, Department of Pediatrics, University of Colorado at Anschutz Medical Center in Aurora. She practices clinically in the pediatric outpatient clinic at National Jewish Health in Denver. References 1. Boyce JA, Assa'ad A, Burks AW, et al. Guidelines for the diagnosis and management of food allergy in the United States: summary of the NIAIDsponsored Expert Panel Report. J Allergy Clin Immunol. 2010;126:1105-1118. 2. Rona RJ, Keil T, Summers C, et al. The prevalence of food allergy: a meta-analysis. J Allergy Clin Immunol. 2007;120:638-646. 3. American Academy of Allergy Asthma & Immunology. Allergy statistics. Available at www.aaaai.org/about-the-aaaai/newsroom/allergy-statistics .aspx#Food_Allergy. 4, Liu AH, Jaramillo R, Sicherer SH, et al. National prevalence and risk factors for food allergy and relationship to asthma: results from the National Health and Nutrition Examination Survey 2005-2006. J Allergy Clin Immunol. 2010;126:798-806. 5. Eigenmann PA, Sicherer SH, Borkowski TA, et al. Prevalence of IgE-mediated food allergy among children with atopic dermatitis. Pediatrics. 1998;101:E8. Available at pediatrics.aappublications.org/content/101/3/e8.long. 6. Crespo JF, James JM, Fernandez-Rodriguez C, Rodriguez J. Food allergy: nuts and tree nuts. Br J Nutr. 2006;96 Suppl 2:S95-S102. 7. Martelli A, De Chiara A, Corvro M, et al. Beef allergy in children with cow's milk allergy; cow's milk allergy in children with beef allergy. Ann Allergy Asthma Immunol. 2002;89(6 Suppl 1):38-43. 8. Sampson HA. Update on food allergy. J Allergy Clin Immunol. 2004;113:805-819. 9. Sloane D, Sheffer A. Oral allergy syndrome. Allergy Asthma Proc. 2001;22:321-325. 10. van Ree R. Clinical importance of cross-reactivity in food allergy. Curr Opin Allergy Clin Immunol. 2004;4:235-240. 11. Morita E, Kunie K, Matsuo H. Food-dependent exercise-induced anaphylaxis. J Dermatol Sci. 2007;47:109-117. 12. Barg W, Medrala W, Wolanczyk-Medrala A. Exercise-induced anaphylaxis: an update on diagnosis and treament. Curr Allergy Asthma Rep. 2011;11:45-51. Available at www.ncbi.nlm.nih.gov/pmc/articles/ PMC3020292/. All electronic documents accessed June 15, 2012. � The New Yorker Collection 2012 from cartoonbank.com. All Rights Reserved. "In the future, everybody will have fifteen minutes of health-care coverage." "Well, Bob, it looks like a paper cut, but just to be sure let's do lots of tests." "That's an excellent prescreened question, but before I give you my stock answer I'd like to try to disarm everyone with a carefully rehearsed joke." www.ClinicalAdvisor.com � THE CLINICAL ADVISOR � JULY 2012 29 FEATURE: LORRAINE W. BOCK, MSN, CRNP, CEN Mixing herbal and prescription meds Patients often consider supplements and herbs harmless, but combining them with other drugs can have devastating consequences. Consumers spend $17 billion a year on dietary supplements and herbs. H erbal preparations have been used by mankind for medicinal purposes for more than 60,000 years. Moreover, field biologists have observed that sick animals change their diet, ingesting small amounts of bitter herbs and plants that they would otherwise avoid, to help facilitate healing.1 There is little question that herbal preparations and dietary supplements can have a significant impact on health and wellness. Beware, however: All that is natural is not necessarily safe, especially when combined with other pharmaceutical-grade medications or nonprescription dietary supplements. This article will discuss the magnitude of supplement and herb use in the United States today, review the most commonly used herbs and supplements and their purposes, and identify the most common pharmaceuticals that pose significant risk of drug/herb interaction. Big business The use of complementary alternative medicine, including nonprescription drugs and supplements, is a booming business in the United States. An estimated $33.9 billion a year is spent by consumers on nonprescription herbal supplements, natural/organic foods, natural personal care products, functional foods, and other complementary and alternative medicine practices. With about $17 billion of this money spent exclusively on dietary supplements and herbs, this is big business.2 Such purchases account for roughly 11% of all health-care drug spending and equal about 33% of what is being 30 THE CLINICAL ADVISOR � JULY 2012 � www.ClinicalAdvisor.com � THINKSTOCK HERBAL INTERACTIONS Manufacturers do not need to obtain FDA approval prior to marketing a product, and there is no requirement for reporting adverse events. spent on prescription medications.3,4 Consumers are being bombarded on television, in magazines, and by direct mail with information encouraging them to use "natural products" to lose weight, control their cholesterol, give them more energy, improve their sexual health, and fulfi ll many other claims. According to its company profi le, in 2011, General Nutrition Centers, Inc., (GNC) spent nearly $53 million on advertising the nonprescription supplements and other health and wellness products sold in its more than 7,500 stores.5 Tracking safety Supplements and herbal preparations fall under the jurisdiction of the Food and Drug Administration (FDA) via the Dietary Supplement Health and Education Act of 1994 (an amendment to the Federal Food, Drug, and Cosmetic Act).6 Requirements in the 1994 act specify that a product must be safe and that advertising claims must be truthful. Unfortunately, the act falls short of a few provisions that would provide additional protection for consumers. Currently, manufacturers do not need to register with the FDA or obtain FDA approval prior to marketing a product, and there is no requirement for reporting adverse events. Any claims against herb and supplement manufacturers are handled primarily through the Federal Trade Commission, including claims of false or misleading advertising and complaints of adverse medical events. Effects of commonly used supplements children's vitamins to preparations for the senior citizen, a vitamin and/or mineral supplement can be found for almost every health and wellness situation. The intended purpose is to provide added vitamins and minerals to one's diet and to supplement nutrition. To avoid overdosing on any one component, consumers should be taking only one multivitamin or multimineral supplement at a time and should be aware of the ingredients if they intend to supplement with any other vitamin or mineral product. These products should not be taken with milk and or at the same time as an antacid.8 Furthermore, to avoid a dangerous increase in potassium, patients taking multiminerals should not use salt substitutes, as most salt substitutes are made with potassium chloride. Multivitamins and multiminerals can alter the effects of BP medications, diuretics, sulfa drugs, nonsteroidal antiTABLE 1. Most commonly used vitamins, herbs, and supplements Calcium Echinacea Fish oils/omega-3 fatty acids/DHA Flaxseed Ginseng Glucosamine/glucosamine chondroitin Multivitamins/multiminerals Vitamins � B complex, E, & C Key: DHA=dihydroxyacetone docosahexaenoic acid. Approximately 20% of the U.S. population reports taking at least one supplement or herbal preparation daily, and more than 50% of the population claims to have used a natural preparation for medicinal purposes in the past 30 days.7 Therefore, understanding the purpose of the most commonly used substances and potential interactions with other supplements and prescription medications is critically important for health-care practitioners. What exactly are we talking about? The discussion in this article will focus on any substance intended to be taken by mouth for the purpose of supplementing the diet and containing one or more of the following substances: vitamins, minerals, herbs, botanicals, amino acids, or natural products, and/or any product labeled as a dietary supplement. Table 1 lists the most commonly used vitamins, herbs, and supplements. Multivitamins and multiminerals. The most widely used of all the dietary supplements by far, multivitamins and multiminerals come in the greatest number of varieties. From TABLE 2. Pharmaceuticals with high potential to interact with vitamins, herbs, and supplements BP medications, especially beta blockers and calcium channel blockers Corticosteroids Cyclosporine (Gengraf, Neoral, Restasis, Sandimmune) Digoxin (Lanoxin) Lithium (Lithobid) Nonsteroidal anti-inflammatory drugs Oral diabetes agents Phenobarbital (Solfoton) Phenytoin (Dilantin, Phenytek) Thiazide diuretics Thyroid medications Warfarin www.ClinicalAdvisor.com � THE CLINICAL ADVISOR � JULY 2012 33 HERBAL INTERACTIONS inflammatory drugs (NSAIDs), and tretinoin (Avita, Renova, Retin-A) and isotretinoin (Anisteem, Claravis, Myorisan, Sotret). Tretinoin and isotretinoin, also known as retinoic acid, are forms of vitamin A normally used to treat acne. Fish oil, omega-3 fatty acids, and dihydroxyacetone docosahexaenoic acid (DHA). These organic compounds, which are obtained primarily from fish and plants, have been shown to provide mild reductions in BP, reduce triglyceride levels, and decrease clotting time, therefore providing a cardiovascular benefit. Reduced inflammation and mild dilatation of the blood vessels have also been seen in studies involving fish oil and omega-3 fatty acids. However, there is some evidence that ingesting excessive amounts of fish oils can increase the risk of stroke. All these compounds can worsen diabetes control and contribute to immune suppression, so their use in persons with autoimmune and immune-deficient conditions should be avoided. Fish oil, omega-3 fatty acids, and DHA can alter the effectiveness of NSAIDs, celecoxib (Celebrex), clopidogrel (Plavix), warfarin (Coumadin, Jantoven), heparin, enoxaparin (Lovenox), orlistat (Alli, Xenical), and some BP medications. Glucosamine and glucosamine and chondroitin. While glucosamine and glucosamine chondroitin are primarily indicated for osteoarthritis and other joint problems, some effect has also been reported in persons with irritable bowel disorder. Glucosamine is an amino acid compound derived primarily from proteins and shellfish. Therefore, persons with shellfish allergies must be diligent in checking labels to make sure they are not at risk for anaphylaxis from the ingredients, and emergency-medicine providers need to question patients with no identifiable risk about supplements that might contain shellfish components. Glucosamine can alter the effectiveness of NSAIDs and diabetes agents, including insulin, and should be used cautiously in individuals taking potassium supplements and anticoagulants. Echinacea. Documented uses for echinacea can be traced to the Sioux Indians, who used it to treat snakebites, rabies, and other systemic poisonings. Also known as purple cornflower and black sampson, echinacea is primarily used today for combating viral illness and as an immunity builder. It is POLL POSITION n=151 Do you always discuss potential medication and supplement interactions with your patients? 3% 8% Yes No Other 89% For more polls, visit www.ClinicalAdvisor/polls often combined in preparations with the herb goldenseal. Echinacea should not be used by patients with immune disorders, such as multiple sclerosis, HIV disease, or lupus, or by organ-transplant recipients. Echinacea can also affect the actions of corticosteroids, antibiotics, and diabetes medications. Neither echinacea nor goldenseal should ever be taken during pregnancy. Flaxseed. Given its long list of health benefits, flaxseed is a popular supplement and readily available for use, coming in a variety of preparations, including capsules, oils, teas, ground flour, and whole seeds. It is often used in salad dressings and sprinkled on foods for easy consumption. Flaxseed has been recommended for use in asthma and for colon health, cancer prevention, and heart health, and as an anti-inflammatory agent. It can slow the absorption of all medications and may alter the effects of blood thinners, diabetes medications, contraceptives, hormones, and antihyperlipidemic agents. Immature seed pods can be poisonous, so consumers should buy flaxseeds only from reputable vendors. Ginseng. Patients looking to counteract fatigue often try ginseng, which has been identified as a stimulant in both Asian and North American cultures. Available in a host of preparations, ginseng is used to treat multiple complaints, For more information on herbs, supplements, and other alternative treatments, visit the website and check out The Clinical Advisor's Alt Med Index (ClinicalAdvisor.com/glossary/). You'll find a complete glossary of terms as well as links to past Alternative Meds Update columns. 34 THE CLINICAL ADVISOR � JULY 2012 � www.ClinicalAdvisor.com including sexual dysfunction, stomach disorders, fatigue, and asthma. Ginseng does not seem to have any beneficial effect on persons who are already active or energetic, and it should not be taken in combination with products containing caffeine. The drug/drug interaction potential of ginseng extends to diabetes medications, psychiatric drugs, opiate pain medications, blood thinners and thrombolytics, calcium channel blockers, and NSAIDs. Vitamins. Vitamin-B complex is also sold as an energy booster, and while having no scientific evidence to back the claim, vitamin B12 injections have a legendary anecdotal reputation of being a powerful fatigue fighter. One welldocumented recommendation is that folic acid (vitamin B6) be used prior to and during pregnancy to lower the risk of neural tube defects, including spina bifida and anencephaly, by at least 50%.9 B-complex supplements are also recommended for treating skin disorders, peripheral neuropathies, and abnormalities in sensation of the tongue. B-vitamin preparations can alter the effects of antidepressants, medications for gastroesophageal reflux, tetracycline, chemotherapy agents, metformin (Fortamet, Glucophage, Glumetza, Riomet), bile-acid sequestrants, levodopa, and erythropoietin. Vitamin E has been touted for a variety of health concerns, including skin problems, menopausal symptoms, fibrocystic breast disease, diabetes, cardiovascular disease, and cancer. Because vitamin E is fat-soluble, overdosing is possible, and the recommended dose of up to 10-30 mg daily should not be exceeded. Even in recommended doses, vitamin E can contribute to thrombophlebitis, pulmonary embolism, and gynecomastia. Iron supplementation can increase the need AT A GLANCE CLINICAL SLIDESHOW Nutrient deficiencies occur most often among infants, the elderly, the poor, and people with eating disorders. Visit ClinicalAdvisor.com/NutritionSlideshow. Herbal preparations and dietary supplements can have a significant impact on health and wellness. All that is natural is not necessarily safe, especially when combined with other pharmaceutical-grade medications or nonprescription dietary supplements. In order to avoid overdosing on any one component, consumers should be taking only one multivitamin or multimineral supplement at a time and should be aware of the ingredients if they intend to supplement with any other vitamin or mineral product. Manufacturers do not need to register with the FDA or obtain FDA approval prior to marketing a product, and there is no requirement for reporting adverse events. Having reference materials available to check unfamiliar products and to provide education to patients on the latest and greatest health-enhancement product is critical. for vitamin E. Drugs that can be affected by concomitant use with vitamin E include antidepressants, beta blockers, anticoagulants, cholesterol medications, female replacement hormones, phenothiazines, and others. Like vitamins B and E, vitamin C (ascorbic acid) also has a long list of beneficial uses as a natural medicine. Best known for reportedly helping to prevent or cure the common cold, vitamin C also enhances the absorption of iron and is considered to be useful in cancer treatment.10 Additionally, some protocols for treatment of Lyme disease use high doses of vitamin C in an IV solution. Vitamin C has also been used for the relief of menopausal symptoms, particularly hot flashes. Ingestion of vitamin C can interfere with or enhance the effects of NSAIDs, acetaminophen, aluminum-containing antacids, chemotherapy drugs, female hormone replacement, barbiturates, tetracycline, indinavir (Crixivan), and warfarin. Calcium. Best-known for assisting in the prevention osteoporosis and enhancing bone health, calcium should be administered in commonly recommended doses of 1,2002,000 mg/day along with vitamin D. Calcium should be ingested in 500-mg doses to provide the best absorption. Some studies link calcium to improved cardiovascular status, lower BP, weight loss, and reduced incidence of colon cancer. Calcium deficiency can be associated with muscle cramping and weakness. Caution should be exercised in supplementing the diet with calcium when the patient is taking calcium channel blockers for hypertension or other cardiovascular disease. Additional medications that can potentially interact with calcium include aluminum-containing antacids, beta blockers, bile acid sequestrants, corticosteroids, estrogen supplements, some antibiotics, anticonvulsants, diuretics, and thyroid supplements. The hypothesis that taking calcium supplements leads to development of gallstones or kidney stones is unsubstantiated. Interactions from another perspective Just as clinicians should be aware of the possible effects of vitamins, herbs, and supplements their patients report using, www.ClinicalAdvisor.com � THE CLINICAL ADVISOR � JULY 2012 35 HERBAL INTERACTIONS they must also be aware of the potential for medications they prescribe to interact with those products. Table 2 provides a list of drugs with a high potential for drug/drug or drug/ food interaction as well. Conclusion References 1. Solecki R. Shanidar IV. A Neanderthal flower burial in Northern Iraq. Science. 1975;190:880-881. 2. National Center for Complementary and Alternative Medicine. Americans spent $33.9 billion out-of-pocket on complementary and alternative medicine. Available at nccam.nih.gov/news/2009/073009.htm. 3. National Center for Complementary and Alternative Medicine. The use of complementary and alternative medicine in the United States: cost data. Available at nccam.nih.gov/news/camstats/costs/costdatafs.htm#overall. 4. Consumer Healthcare Products Association. OTC medicines/dietary supplements facts and figures. Available at www.chpa-info.org/pressroom/ OTC_FactsFigures.aspx. 5. GNC Holdings, Inc. GNC 10-K Annual Report. Filed on February 27, 2012. Available at phx.corporate-ir.net/phoenix.zhtml?c=88669&p=irolinvestorhome. 6. National Institutes of Health Office of Dietary Supplements. Dietary Supplement Health and Education Act of 1994. Public Law 103-471. 103rd Congress. Available at ods.od.nih.gov/About/DSHEA_Wording.aspx. 7. Mann D. Use of dietary supplements on the rise. Available at www. webmd.com/diet/news/20110413/use-of-dietary-supplements-on-the-rise. 8. Sulli MM, Ezzo DC. Drug interactions with vitamins and minerals. US Pharm. 2007;1:42-55. Available at www.uspharmacist.com/content/d/featured articles/c/10439/. 9. Centers for Disease Control and Prevention. Spina bifida and anencephaly before and after folic acid mandate--United States, 1995-1996 and 1999-2000. MMWR . 2004;53(17):362-365. Available at www.cdc.gov/ mmwr/preview/mmwrhtml/mm5317a3.htm. 10. Zelman KM. The benefi ts of vitamin C. Available at www.webmd.com/ diet/guide/the-benefi ts-of-vitamin-c. All electronic documents accessed June 15, 2012. � The New Yorker Collection 2012 from cartoonbank.com. All Rights Reserved. Patients are using more and more nonprescription herbs, vitamins, and supplements, and health-care providers are recognizing the contributions and benefit of using nonpharmaceutical supplementation in the treatment of certain illnesses and following injuries. These products can enhance or inhibit the potential effects of other substances patients are ingesting. Many times, patients are reluctant to tell their clinician that they are using these OTC products. The patient may believe that the supplements are without risk, that the health-care provider may react negatively to use of nonprescription treatments, or that the information is not important enough to share with their regular practitioner. Whatever the reason, the likelihood is that your patient will use a vitamin, herb, or dietary supplement of some sort in an attempt to improve his or her health in the next year. As the health-care provider, you should be ready to question what products he or she is using and have a basic understanding of the effects these products can have--both beneficial and harmful. You should also have a general understanding of dangerous combinations, sideeffect profi les, and the unregulated nature of supplement production. Having reference materials available to check unfamiliar products and to provide education to patients on the latest and greatest health-enhancement product is critical to helping the patient maintain optimum health status and avoid untoward drug/drug, drug/food, and drug/supplement interactions. This article should not be construed as a complete or total list of potential vitamin, herb, or supplement uses or interactions with other drugs, foods, or supplements. It is simply an introduction to some common potential interactions and should serve as a resource to encourage providers to continue their education on this very important topic. Ms. Bock is Director of Legislative Health Services, Pennsylvania House of Representatives. She specializes in family medicine and is the owner of Bock CRNP Services in Harrisburg. MAKING CONTACT Follow us on Twitter @ClinicalAdvisor Like us on Facebook facebook.com/TheClinicalAdvisor Visit us on the web ClinicalAdvisor.com Go mobile with us mobile.ClinicalAdvisor.com 36 THE CLINICAL ADVISOR � JULY 2012 � www.ClinicalAdvisor.com Advisor Forum These are letters from practitioners around the country who want to share their clinical problems and successes, observations, and pearls with their colleagues. Responding consultants are identified below. We invite you to participate. Inside the Forum J U LY 2 0 1 2 Send us your letters with questions and comments to: Advisor Forum, The Clinical Advisor, 114 West 26th Street, 4th Floor, New York, NY 10001. You may also fax (646) 638-6117, or contact us by e-mail at letters@ clinicaladvisor.com. If you are writing in response to a published letter, please indicate so by including the number in parentheses at the end of each item. Letters are edited for length and clarity. The Clinical Advisor's policy is to print the author's name with the letter. No anonymous contributions will be accepted. CONSULTATIONS BREASTFEEDING WITH A POSITIVE THYROID PEROXIDASE A breastfeeding mother has a positive thyroid peroxidase (TPO) and an otherwise normal thyroid panel. Could this adversely affect her milk supply? What treatment is recommended?--CAROLINE CONNEEN, MSN, FNPBC, Fredericksburg, Va. TPO is one of several antibodies associated with chronic autoimmune thyroiditis (Hashimoto disease). The breast milk of a patient like the one described should not be affected by a postive TPO, and no treatment is necessary. I recommend this patient have her thyroidstimulating hormone checked annually--or sooner if she becomes symptomatic (e.g., low milk supply), as the presence of antithyroid antibodies suggests an increased risk of developing overt hypothyroidism in the future.--Mary Newberry, CNM, MSN (165-1) Consultations Breastfeeding with a positive thyroid peroxidase . . . . . . . . . . . . . .38 Reversing childhood obesity . . . . . . .38 When is surgical intervention advisable for Parkinson disease?. . . . .39 Causes of thinning hair in a postmenopausal woman . . . . . . . . . .39 Clinical Pearls Show--don't tell--when it comes to weight loss . . . . . . . . . . . . . . . . .40 Getting the cervix in view . . . . . . . . .40 Sources of comfort for those with dementia. . . . . . . . . . . . . . . . . . . 40 Your Comments School clinician should be thankful for jury's decision . . . . . . . .40 REVERSING CHILDHOOD OBESITY A boy, aged 7 years, is of normal height and well over the top of the developmental chart for weight. He is happy, active, and does well in school. His father is large, and his siblings are of normal weight. I did a lipid profile and do not know how to follow up. His parents cannot afford a pediatrician, and driving all the way to the nearest pediatric endocrinologist OUR CONSULTANTS Rebecca H. Bryan, APRN, CNP, Eileen Campbell, MSN, CRNP, Philip R. Cohen, MD, is a lecturer in the Family Health NP Program, University of Pennsylvania School of Nursing, Philadelphia. is associate program director, Family Health NP Program, University of Pennsylvania School of Nursing, Philadelphia. is clinical associate professor of dermatology, University of Texas Medical Center, Houston. Deborah L. Cross, MPH, CRNP, ANP-BC, is associate program Maria Kidner, DNP, FNP-C, director, Gerontology NP Program, University of Pennsylvania School of Nursing, Philadelphia. is a nurse practitioner with Cheyenne Cardiology Associates in Cheyenne, Wyo. 38 THE CLINICAL ADVISOR � JULY 2012 � www.ClinicalAdvisor.com would be a hardship. A consult with a dietitian does not seem worthwhile because the family seems to have a healthy diet. --MARYLOU POTTS, ARNP, Ocala, Fla. Based on the information presented, there seems to be no reason to suspect an endocrine disorder. Most overweight children can be cared for within the context of primary care. A lipid profile was in order; however, even if it is abnormal, the first-line recommendations for this child are lifestyle modifications (Pediatrics. 2008;122:198-208; available at pediatrics.aappublications.org/content/122/1/198.long, accessed June 15, 2012). Principles for motivational interviewing may help you determine if the family members perceive the boy's weight as a problem and if they are interested in and feel like they are capable of making changes in diet and behaviors to impact this unhealthy weight. At this child's age, the family must be committed, or change will not occur. The American Academy of Pediatrics has guidelines for management of elevated lipids that you can follow as a primary-care provider (Rollnick S, Miller WR, Butler CC. Motivational Interviewing in Health Care: Helping Patients Change Behavior. New York, N.Y.: Guilford Press; 2008). These guidelines include the use of the American Heart Association dietary recommendations.--Julee B. Waldrop, DNP (165-2) frequently performed surgical procedure on individuals with medically intractable motor fluctuations of PD. Accumulating evidence suggests that DBS of the STN and GPi provides persistent beneficial antiparkinson effect for at least three to five years after electrode implantation. There is no evidence that it slows the progression of the underlying neurodegenerative process. The best candidates are those with idiopathic PD who have been responsive to levodopa prior to surgery, are cognitively intact, and do not have end-stage disease. It is best to seek consultation with a neurologist in a movement-disorder center before recommending the procedure.--Deborah L. Cross, MPH, CRNP, ANP-BC (165-3) CAUSES OF THINNING HAIR IN A POSTMENOPAUSAL WOMAN A woman aged 59 years complains of thinning hair on her scalp. She has been on a vegetarian diet for the past two years and takes no prescription medications but is currently on hormone replacement therapy. Could her diet be causing hair loss?--ANNE RICH, CNP, St. Cloud, Minn. Diffuse hair loss in postmenopausal women may be multifactorial. Hair density decreases with age. Menopause can be associated with changes in hair growth rate, percentage of anagen hairs, and hair diameter; all of these changes heighten the perception of decreased scalp coverage in postmenopausal women (Br J Dermatol. 2011;165[Suppl 3]:2-6 and Br J Dermatol. 2011;165[Suppl 3]:7-11). Indeed, androgenic alopecia may worsen following menopause, and such other causes of hair loss as telogen effluvium may be superimposed upon female-pattern hair loss. Diffuse telogen effluvium hair loss may be triggered by physiologic stress, emotional stress, medical conditions, and diet. Deficiency of zinc, iron, vitamin D, biotin, or essential fatty acids can result in diffuse telogen hair loss. Telogen hair shedding can also be precipitated by malabsorption syndromes, crash dieting, and WHEN IS SURGICAL INTERVENTION ADVISABLE FOR PARKINSON DISEASE? When should patients with Parkinson disease (PD) be referred to a movement-disorder center for evaluation of a surgical intervention? Is there a window of opportunity when such intervention is most successful?--PAULINE RANKIN, CRNP, Emlenton, Pa. Deep brain stimulation (DBS) of either the subthalmic nucleus (STN) or the globus pallidus pars interna (GPi) is currently the most Debra August King, PHD, PA, Mary Newberry, CNM, MSN Claire O'Connell, MPH, PA-C, Sherril Sego, FNP-C, DNP , Julee B.Waldrop, DNP , is senior physician assistant of the Department of Cardiothoracic Surgery, Lenox Hill Hospital, New York City. provides well-woman gynecologic care as a midwife with Prima Medical Group, Greenbrae, Calif. teaches in the PA Program at the New Jersey Medical School and Rutgers University, Piscataway, N.J. is a primary-care nurse practitioner at the Department of Veterans Affairs Medical Center in Kansas City, Mo. teaches at the University of North Carolina School of Nursing in Chapel Hill and practices pediatrics at UNC Hospitals. www.ClinicalAdvisor.com � THE CLINICAL ADVISOR � JULY 2012 39 Advisor Forum for a woman to scoot down far enough while sitting up. You must ask the patient to remain supine with her legs bent at the knees and move down toward the end of the table. It helps if you put your hand at the edge of the table and ask her to keep moving downward until she feels her buttocks bump your hand. Rest assured, she will then shift slightly back toward the head of the table. Once you are seated in position to perform the exam, ask the patient to come "one more scoot" toward you. Getting the buttocks slightly off the edge of the table allows the cervix to be visualized with very little effort.--JUDY WINTER, WHCNP, RN-C, Alice, Tex. (165-6) � C.M.S.P. Androgenic alopecia (shown here) may worsen after menopause. chronic starvation associated with severe restriction of calories, fatty acids, and protein (Cleveland Clinic J Med. 2009;76:361-367; available at www.ccjm.org/content/76/6/361.long, accessed June 15, 2012). Although alopecia areata (and it variants alopecia totalis and alopecia universalis) are less common in postmenopausal women, trichotillomania--associated with such concomitant conditions as depression, anxiety disorders, obsessive-compulsive disorders, panic attacks, and psychosis--is being observed more commonly in older women (Eur J Dermatol. 2010;20:145-151; available at www.jle. com/en/revues/medecine/ejd/e-docs/00/04/55/9C/article.phtml, accessed June 15, 2012).--Philip R. Cohen, MD (165-4) SOURCES OF COMFORT FOR THOSE WITH DEMENTIA Older women with dementia often become distressed and claim to be "looking for baby." These women showed immediate relaxation and less agitation when given a soft toy doll wrapped in a simple flannel blanket. As for men with dementia, many are comforted by a soft billfold that fits in their shirt pocket and contains a laminated picture of themselves, a loved one, or both. Avoid anything with small writing, as that seems to confuse them.--TERESA HARTZ, FNP, Henderson, Nev. (165-7) YOUR COMMENTS CLINICAL PEARLS SHOW--DON'T TELL--WHEN IT COMES TO WEIGHT LOSS Conversations about weight loss can contribute tremendously to behavioral changes, but tangible examples may be even more effective. Place a few 5-lb bags of sugar in the patient's lap so the individual can actually feel how much extra weight he or she is carrying. The sensation of 25 lbs in their lap will surprise many with regard to how much extra stress the weight has on their body, especially on the bones and joints of the legs.--DEANA GOLDIN, DNP, ARNP, FNP-BC, Miami (165-5) SCHOOL CLINICIAN SHOULD BE THANKFUL FOR JURY'S DECISION As a nationally certified school nurse with more than 20 years of experience, I have to weigh in on the Legal Advisor case about the clinician who examined a minor without verbal consent ("How do you handle the parents?" June 2012). The article states that the clinician came from a primary-care setting, but was she a nurse practitioner or a physician assistant? Was the health office run as a facility that provides ongoing treatment for students, hence the "consent to treat" form? Some schools have clinics run by NPs that examine, treat, and prescribe for students. The clinician in this case stepped way outside the scope of practice, even if she were able to treat a urinary tract infection in a school setting. Prudence and experience should have told her to stop long before she ever considered a further exam. The outcome was fortunate for this provider. A true jury of her peers would have likely decided differently.--ANNE MARIE HEFFERNAN, RN, PA, NCSN, Tempe, Ariz. (165-8) GETTING THE CERVIX IN VIEW The most important thing to do to ensure proper visualization of a woman's cervix is to make certain her buttocks are just over the edge of the exam table. However, it is impossible 40 THE CLINICAL ADVISOR � JULY 2012 � www.ClinicalAdvisor.com New Online Course for Civilian Health Care Providers Identifying and Treating Concussion/Mild Traumatic Brain Injury in Service Members and Veterans t5XPIPVS TFMGQBDFE NVMUJNFEJBPOMJOFDPVSTFGFBUVSJOH QBUJFOUJOUFSWJFXT SFMBUFEMJOLT BOEDPNQMFYQSFTFOUBUJPOT t(PUPXXX#SBJO-JOF.JMJUBSZPSHDPODVTTJPO@DPVSTFUP MFBSONPSFBCPVUUIFEFUFDUJPOBOEUSFBUNFOUPG5#* BO JOWJTJCMFXPVOEPGXBS "Knowing if your patient has been to war can help \RXRHUEHWWHUFDUH&RQFXVVLRQVDUHWUHDWDEOH WKHSURJQRVLVLVJRRGDQGWKLVFRXUVHZLOOJHW\RXVWDUWHG &$37-/+DQFRFN3K\VLFLDQDQG1DYDO2FHU Transforming the Lives of Service Members with TBI TBI. Clinical Care. Education. Research. That's DVBIC. DVBIC.ORG BRAINLINEMILITARY.ORG INFO@DVBIC.ORG "This patient has a rare form of medical insurance." "Those who can't do, comment." www.ClinicalAdvisor.com � THE CLINICAL ADVISOR � JULY 2012 41 � The New Yorker Collection 2012 from cartoonbank.com. All Rights Reserved. NPSecure� Because Your Own Malpractice Policy Is Your Best Protection. n n n Competitive Premiums Occurrence Policy Available In 50 States Portable, Seamless Protection Wherever You Work Or Volunteer No Conflict Of Interest In The Event Of A Claim Involving Multiple Providers Coverage For All Specialties Including High Risk Classes Employed, SelfEmployed & Student Coverage Options HIPAA Coverage License Protection Coverage Defense Expenses Coverage n n n n n n 99 Hudson Street, 12th Floor New York, NY 100132815 Tel: 18002214904 Email: email@example.com VISA/MasterCard www.NPSecure.com PA Protect Because Your Own Malpractice Policy Is Your Best Protection. n � Portable, Seamless Protection Wherever You Work Or Volunteer No Conflict Of Interest In The Event Of A Claim Involving Multiple Providers Full Time, Part Time & Moonlighting Coverage Options Occurrence Policy Claims Made Conversion To Occurrence Available (No Tail) HIPAA Coverage License Protection Coverage Defense Expenses Coverage 10% AAPAEndorsed Risk Management Credit n n n n n n n n 11 South LaSalle Street, Suite 2300 Chicago, IL 606031333 Tel: 18773562272 Fax: 3125789556 Email: firstname.lastname@example.org VISA/MasterCard www.PAProtect.com Derm Dx EXCLUSIVE TO THE WEB INTERACT WITH YOUR PEERS by viewing the images and offering your diagnosis and comments. To post your answer, obtain more clues, or view similar cases, visit ClinicalAdvisor.com/DermDx. Learn more about diagnosing and treating these conditions, and see how you compare with your fellow colleagues. White papule on the side of the nose A patient presents with a whitish papule on his nasal sidewall. He is uncertain how long it has been present but complains that it is embarrassing. WHAT IS YOUR DIAGNOSIS? � � � � Basal cell carcinoma Pilar cyst Metastatic renal cell carcinoma Milium See the full case at ClinicalAdvisor.com/DermDx0712A A 25-year history of red spots A 60-year-old white man presents with a chief complaint of red spots on his trunk and extremities that have developed during the past 25 years. WHAT IS YOUR DIAGNOSIS? � � � � Ataxia telangiectasia Hereditary hemorrhagic telangiectasia Unilateral nevoid telangiectasia Generalized essential telangiectasia See the full case at ClinicalAdvisor.com/DermDx0712B Have you missed any recent Derm Dx cases? Go to ClinicalAdvisor.com/DermDx for a complete archive of past quizzes as well as additional images of last month's other cases. Painful facial eruptions Skin changes with tendinitis 42 THE CLINICAL ADVISOR � JULY 2012 � www.ClinicalAdvisor.com LEGAL ADVISOR CASE Pancreatitis leads to foot amputation Was a clinician negligent in the administration of a standard drug used for treating pancreatitis? � THNKSTOCK / THOMAS NORTHCUT BY ANN W. LATNER, JD Early in the course of her career as a nurse practitioner, Ms. V was given some invaluable advice that has guided her throughout her professional life. Her first supervisor, a clinician with substantial experience, took Ms. V under her wing early on and imparted a pivotal piece of information. "In the course of patient management, always take very detailed nursing notes. Whatever you do, write it down," Ms. V's mentor insisted. "Whether it's recording medications dispensed, tests performed, a patient's reactions, or your personal observations--these can all be critical." Now a veteran at age 52 years, Ms. V supervised a nursing staff at a regional suburban hospital, a post she held for almost 20 years. Ms. V thrived in a hospital setting. She enjoyed the diversity of the work, her supervisory duties, and the fact that she could now mentor some of the younger nurses in the same way she was trained. One of Ms. V's patients, a 48-year-old woman named Mrs. W, had been in and out of the hospital for the past several years with a history of chronic pancreatitis. Ms. V came into work one morning to find that Mrs. W had been admitted The clinician checked on the patient frequently throughout the day to make sure the medication was infusing properly. again. In past episodes, Mrs. W had always needed IV pain relievers, and this time was no different. The attending physician had ordered IV meperidine (Demerol) and promethazine (Phenergan). Unable to start an IV in Mrs. W's upper extremities, Ms. V started the IV in the patient's left foot instead. She inserted the IV into the vein, flushed the line, and started the medication drip. Ms. V made careful notes in the patient's chart regarding the IV placement, and over the course of the day she checked back frequently to make sure that Mrs. W's medication was infusing properly. Whenever she checked on her patient, Ms. V would indicate this on the chart. The next morning, Mrs. W complained of pain in the foot where the IV was inserted. Ms. V immediately stopped the IV drip and checked the line for return of blood to make sure that the IV had been properly Cases presented are based on actual occurrences. Names of participants and details have been changed. Cases are informational only; no specific legal advice is intended. Persons pictured are not the actual individuals mentioned in the article. 44 THE CLINICAL ADVISOR � JULY 2012 � www.ClinicalAdvisor.com LEGAL ADVISOR inserted. She then removed the IV and informed the physician. Ms. V noted in the chart that she had checked the IV line and that it had been properly placed. Over the course of the next few weeks, Mrs. W developed gangrene in her left foot, and the foot eventually had to be amputated. Mrs. W was released from the hospital and immediately contacted an attorney. She explained how she had been admitted to the hospital for pancreatitis treatment and ended up losing a foot. Furious and distraught, Mrs. W asked whether or not she had a case. "There is absolutely no reason an individual should be hospitalized for pancreatitis and end up losing an extremity," said the defense attorney. He fi led a lawsuit against the hospital, suing for $3.5 million in damages for nursing negligence in IV administration. Her attorney introduced several experts who testified that the IV must have been improperly inserted. Hence, the medication --specifically promethazine--was probably infused into the surrounding tissue, causing damage and ultimately requiring amputation of the foot. The defense introduced its own expert witness, a vascular surgeon who testified that the nursing care was appropriate in all respects. The surgeon testified that the tissue damage was more likely an unavoidable complication related to the caustic nature of promethazine when administered directly into a vein. Ms. V was called to testify and she explained the IV insertion process and how she had checked to make sure the line was properly introduced. Ms. V made a point of noting how she repeatedly checked on the patient and noticed no redness or edema at the IV site. The nursing notes, which corroborated Ms. V's testimony, were admitted into evidence as exhibits for the jury to peruse. The jury deliberated for several hours, finding no negligence on the part of the hospital or Ms. V and her staff, and ultimately awarded no damages to the patient. Legal background A jury will give considerable weight to documents that were updated regularly during the course of treatment. The hospital informed Ms. V of the suit, noting that she would undoubtedly be called to testify in court if the case went to trial. Ms. V was advised to consult with the hospital's malpractice attorney. Ms. V brought copies of her nursing notes to the meeting with her defense attorney. The counselor studied the notes carefully before asking her a few questions. "Did you take these notes during the course of the treatment, or did you go back and fill them in later?" Ms. V assured the attorney that she always kept records during the course of treatment. "Do you always take these sorts of detailed notes," he asked, "or was there something unusual about this case?" "No," replied Ms. V. "I always take notes like these. It's how I was trained. If you look at the chart notes for any of my patients, you'll see that they contain the same level of detail." The attorney seemed satisfied and told Ms. V that she would hear from him if the case actually went to trial. After months of discovery, depositions, and futile settlement discussions, the case did, in fact, go to trial. At trial, the plaintiff, Mrs. W, took the stand and testified about how difficult life was without a foot. She testified tearfully about not being able to play sports with her children, run with her dog, or engage in the simplest of daily activities. Evidence is powerful in a trial--especially such physical evidence as chart notes. A jury will give considerable weight to documents that were updated regularly during the course of treatment. In the absence of notes or supporting documentation, the jury has to make a decision based on the testimony of expert witnesses. The jury might have chosen to believe the theory promulgated by the plaintiff's expert, but Ms. V's notes were her strongest defense. With details about the placement of the IV, a record of periodic and timely visits to check on the patient, and additional notes indicating no redness or edema at the IV site, Ms. V's chart notes convinced the jury that she had acted with the appropriate standard of care. Protecting yourself Ms. V's early mentor had given her excellent advice. Document everything carefully and thoroughly, and you will be protected in the long run. Unfortunately, promethazine administered intravenously can result in serious complications, ranging from paralysis to tissue necrosis. Ms. V, however, was not the one who called for promethazine; the attending physician gave the medication orders. Ms. V was actually following the physician's instructions and keeping watch to the best of her ability. Ms. Latner, a former criminal defense attorney, is a freelance medical writer in Port Washington, N.Y. 46 THE CLINICAL ADVISOR � JULY 2012 � www.ClinicalAdvisor.com CME CE CASE #1 Dermatology Clinic LEARNING OBJECTIVES: To identify and diagnose dermatologic conditions and review up-to-date treatment. COMPLETE THE POSTTEST: Page 57 ADDITIONAL CME/CE: Pages 23, 53 Turn to page 22 for additional information on this month's CME/CE courses. Blue-black mole with regular borders KERRI ROBBINS, MD A 12-year-old Asian girl presented to the dermatology clinic because she was concerned about a new mole on her left dorsal hand. Since its appearance approximately one year ago, the mole's growth had stabilized, and no significant change in the lesion had been noted for the past six months. No pain, pruritus, or spontaneous bleeding was reported. There was no family history of malignant melanoma. The girl had no prior history of blistering sunburns. On physical examination, a 6-mm blue-black papule with regular borders and no color variegation was appreciated on the left dorsal hand. What is your diagnosis? Turn to page 48 CASE #2 Extremely pruritic hyperkeratotic papules ADAM J. CARTER AND JULIA R. NUNLEY, MD A black man, aged 55 years, presented with a 10-year history of a very itchy rash on both lower legs. He admitted to scratching and reported that several courses of prednisone had provided no relief. Seasonal allergies and asthma as an infant were his only medical issues. No cardiac, GI, or other skin problems were detected. The man works as a trainer at an athletic club. Physical examination revealed 3- to 4-mm hyperkeratotic and hyperpigmented papules coalescing into plaques on the anterior portions of both lower legs. What is your diagnosis? Turn to page 49 www.ClinicalAdvisor.com � THE CLINICAL ADVISOR � JULY 2012 47 CME CE Dermatology Clinic Malignant blue nevus is the rarest of all the variants. These nevi mostly arise in conjunction with cellular blue nevi. Unlike the other nevi, the malignant lesions progressively get larger until they are a few centimeters in diameter. They may also become multinodular and have a plaque-like resemblance.6 Malignant blue nevi are most commonly seen on the scalp and usually metastasize to the lymph nodes.7 Observations from a biopsy of cellular blue nevus will demonstrate deeply pigmented dendritic melanocytes, which are associated with nests and fascicles of spindle- CASE #1 Blue nevus The three clinically distinct forms of blue nevi are common blue nevi, cellular blue nevi, and malignant blue nevi. The former was first described in 1906.1 The cellular blue nevus was first considered a variant of melanoma; however, it was later classified as a branch of blue nevi. Malignant blue nevi are the rarest form and often arise in conjunction with cellular blue nevi. Asian populations seem to be affected by blue nevi the most, with 3% -5% of the adult population having the disorder.2 About 1% -2% of white adults have the disorder, and blacks are rarely affected.2 Approximately 75% of blue nevi cases arise during childhood and adolescence.2 The other 25% may present with blue nevi during adulthood.2 Although congenital blue nevi are rare, congenital common blue nevi account for one out of every four cases. Blue nevi are twice as common in females as in males.2 Although the etiology is not defi nitive, blue nevi are believed to be caused by dermal arrest in embryonic migration of neural-crest melanocytes. Genetic predisposition has been suspected due to variations in different populations. However, this notion has been dismissed since evidence of familial trends is lacking.3 Common blue nevi are well-circumscribed, dome-shaped papules. The papules are blue, blue-gray, or blue-black in color and typically measure less than 1 cm in diameter.2 The dorsal surfaces of the hands and feet are frequent locations for the lesions, accounting for 50% of all common blue nevi.2,4 Other common sites include the face and scalp. The papules can occur in multiples, but this is rare. They may also arise with such other nevi as nevus spilus.2 Cellular blue nevi are blue to blue-gray or black nodules or plaques. They generally range from 1 cm to 3 cm in diameter; however, occasionally they will be larger than 3 cm.2 The plaques can be found on various parts of the body, including the buttocks, scalp, face, and feet. Their surface is usually smooth but can at times be irregular. This type of blue nevi is fairly uncommon, with the ratio of cellular blue nevi to common blue nevi being 1:5.2 Congenital cellular blue nevi have been known to contain satellite lesions. A congenital melanocytic nevi may also develop a benign or malignant cellular blue nevus within it.2,5 The dorsal surfaces of the hands and feet are frequent locations for lesions, accounting for 50% of all common blue nevi. shaped cells. The bundles of spindle cells intersect with one another and extend in all directions, giving it a storiform pattern. These cells often have abundant cytoplasm that appears pale in color with little or no melanin.8 For common blue nevi, a histologic examination will reveal wavy, elongated melanocytes with long branching dendrites. These melanocytes will bundle in the mid dermis, occasionally extending into the subcutaneous tissue. The nuclei of the melanocytes are rarely seen because the cells are fi lled with fine melanin granules that obscure their nuclei. This gives the papules their blue-gray to blue-black appearance. Also, the histologic fibrotic appearance is attributable to the high amount of collagen in the lesion.8 Malignant blue nevi will show various features of melanoma or other cancerous lesions, such as large size, asymmetry, ulceration, infi ltration, cytologic atypia, mitoses, and necrosis.2 A cellular blue nevus with satellitosis must be differentiated from a malignant blue nevus. If the lesion is located on the face, nevus of Ota should also be considered. The differential diagnosis of common blue nevus is broad and includes tattoo ink, combined nevus, vascular lesions, sclerosing hemangioma, primary and metastatic melanoma, atypical nevus, pigmented spindle cell nevus, dermatofibroma, papular basal cell carcinoma, and glomus tumor.2,9 If the blue nevi appear to be benign--meaning their diameter is less than 1 cm and they are clinically stable with no atypical features--no excision is necessary. In such other cases as the appearance of plaque-like lesions, 48 THE CLINICAL ADVISOR � JULY 2012 � www.ClinicalAdvisor.com multinodular lesions, evolving lesions, or de novo lesions, the blue nevi should be considered for excision. Because of the potential risk for malignant transformation, cellular blue nevi should be excised in most cases.2,4 Patient prognosis for this condition is excellent. Once present, blue nevi tend to remain unchanged throughout the patient's life. Depending on the age of the lesion, blue nevi tend to flatten and fade in color. Common blue nevi are clinically benign. Cellular blue nevi are also benign but very rarely can undergo malignant transformation. If a patient has been diagnosed with a cellular blue nevus, discuss resection of the lesion to prevent recurrence and the misdiagnosis of malignant blue nevus and to lower the risk of malignant transformation. The blue nevi are not aesthetically pleasing, and patients may desire excision for cosmetic reasons. Clinically, the lesion in this case was felt to be a common blue nevus, especially considering its small size and stable clinical appearance. After discussing the diagnosis with the patient and her mother--and given the patient's concern for cosmesis--the area was biopsied with a 6-mm punch biopsy. The pathology was read as a common blue nevus. Dr. Robbins is a resident in the Department of Dermatology at Baylor College of Medicine in Houston. References 1. Tieche M. Uber benigne melanome (chromatophorome) der haut "blaue naevi." Arch Pathol Anat. 1906;186:212-229. 2. Bolognia JL, Jorizzo JL, Rapini RP eds. Dermatology. 2nd ed. St. Louis, Mo.: Elsevier-Mosby; 2008:1722-1723. 3. Maize JC, Ackerman AB, eds. Pigmented Lesions of the Skin. Philadelphia, Pa.: Lea & Febiger; 1987:137. 4. Montgomery H, Kahler JE. The blue nevus (Jadassohn-Tieche): its distinction from ordinary moles and malignant melanomas. Am J Cancer. 1939;36:527-539. 5. Leopold JG, Richards DB. Cellular blue nevi. J Pathol Bacteriol. 1967;94:247-255. 6. Paller AS, Mancini AJ. Hurwitz Clinical Pediatric Dermatology. 3rd ed. Philadelphia, Pa.: Elsevier Saunders; 2006:298-299. 7. Fitzpatrick TB, Johnson RA, Wolff K, Suurmond R, eds. Color Atlas and Synopsis of Clinical Dermatology, 5th ed. New York, N.Y.: McGraw-Hill; 2005:171-172. 8. Elder DE, Elenitsas R, Johnson BL, et al, eds. Lever's Histopathology of the Skin. 10th ed. Philadelphia, Pa.: Lippincott Williams & Wilkins; 2009:701-704. 9. Habif TP. Skin Disease: Diagnosis and Treatment. 2nd ed., Philadelphia, Pa.: Elsevier Mosby; 2005:464, 480-482. CASE #2 Lichen amyloidosis A punch biopsy of one of the papules revealed epidermal hyperkeratosis and acanthosis of the epidermis with eosinophilic deposits in the papillary dermis. Congo red staining of the dermal deposits demonstrated apple-green birefringence under polarized light, which is diagnostic of amyloidosis. Laboratory testing for an abnormal immunoglobin spike was negative. The clinical and histologic findings were consistent with the diagnosis of lichen amyloidosis, a type of primary localized cutaneous amyloidosis. Amyloidosis is not a single disease but rather a group of diseases, each of which is characterized by the deposition of extracellular amyloid, a fibrillar proteinaceous material derived from various sources. Amyloidosis may occur as a systemic disease or be limited to a specific organ. Systemic amyloidosis may be primary or secondary. Primary amyloidosis occurs in the setting of a plasma-cell dyscrasia, such as myeloma, and the resultant amyloid is from the abnormally produced light chains classified as "AL." Secondary systemic amyloidosis is seen in association with a variety of chronic inflammatory conditions (e.g., rheumatoid arthritis) or inherited conditions (e.g., familial Mediterranean fever); in these situations the amyloid produced is termed "AA." Primary localized cutaneous amyloidosis is skin-limited and can be classified into the subsets lichen amyloidosis, macular amyloidosis, nodular amyloidosis, and familial amyloidosis. Of these subsets, lichen amyloidosis is the most common. First described in 1928 by Gutmann, lichen amyloidosis is seen most often in individuals of Chinese, Southeast Asian, or South American descent.1 It is more common in men and typically presents in the fifth or sixth decade of life. The initial presentation appears to be an intense itch that causes the patient to scratch relentlessly. This constant scratching causes significant mechanical trauma to the keratinocytes of the epidermis. Subsequently, filamentous degradation and apoptosis of the basal keratinocytes eventually forms colloid bodies. These colloid bodies are ultimately broken down into amyloid K, or "AK" (for keratinocyte), which remains within the papillary dermis.2 Over time, these deposits accumulate, causing the characteristic small, numerous, red-brown, hyperkeratotic papules that may coalesce into plaques. Whereas the most common location for lichen www.ClinicalAdvisor.com � THE CLINICAL ADVISOR � JULY 2012 49 CME CE Dermatology Clinic Relief of pruritus is the main treatment goal. Some of the more effective medications include the sedating antihistamines, topical ultra-potent corticosteroids, topical immune modulators, and topical dimethylsulfoxide.4 Phototherapy and dermabrasion have also been used.6 Broadband UVB, narrowband UVB, and photochemotherapy with psoralen plus UVA reportedly have the same success rate as that of topical steroids.6 Unfortunately, this disease remains very difficult to treat, and complete remission is rare.4 This patient was treated with the topical ultra-potent steroid clobetasol applied b.i.d. Minimal improvement was noted amyloidosis is the pretibial area, other areas affected include the calves, ankles, thighs, dorsal feet, forearms, concha of the ears, anosacral area, and interscapular areas.3,4 The pathogenesis of lichen amyloidosis is not fully understood. Most cases are sporadic, but up to 10% of patients report a family history, suggesting a genetic predisposition.4 Lichen amyloidosis has been reported in association with a variety of cutaneous disorders, many of which are pruritic dermatoses, including atopic dermatitis, lichen planus, and notalgia paresthetica. However, recent data have cast some doubt on the itch-scratch pathogenesis of the condition. A skin biopsy will establish the diagnosis. Routine hematoxylin and eosin staining demonstrates hyperkeratosis and acanthosis of the epidermis with eosinophilic deposits in the papillary dermis; increased numbers of melanophages and fibroblasts may be seen in the papillary dermis as well.3 Congo red staining identifies the deposits as amyloid via the characteristic apple-green birefringence under polarized light. Additional stains can be used for confirmation; methyl violet or crystal violet will stain amyloid metachromatically, and thioflavin T will confer amyloid with a yellow-green birefringence under fluorescence microscope.4 The differential diagnosis of the hyperpigmented pruritic papules and plaques seen in lichen amyloidosis is broad and includes macular amyloidosis, nodular amyloidosis, systemic amyloidosis, lichen simplex chronicus, lichen planus, and prurigo nodularis. Although macular and lichen amyloidosis are somewhat similar in presentation, they may be differentiated histologically. Whereas both conditions demonstrate amyloid deposition with special staining, lichen amyloidosis manifests hyperkeratosis and acanthosis, which is minimal or absent in macular amyloidosis.4 Interestingly, the two conditions occasionally coexist, a diagnosis known as biphasic amyloidosis. Nodular amyloidosis is distinguished by the presence of plasma cells. Although histologically similar, the amyloid of nodular amyloidosis is chemically distinct from either macular or lichen amyloidosis. By definition, none of the primary localized cutaneous amyloidoses have systemic involvement. However, various organ systems are affected in systemic amyloidosis, most commonly the heart, GI tract, and skin. A thorough review of symptoms should be part of the initial evaluation of all patients suspected of amyloidosis. Pruritus, extremely common in lichen and macular amyloidosis, is generally absent in systemic amyloidosis.5 The most common skin finding of systemic amyloidosis is purpura caused by vessel involvement and interference with clotting factor X. Various organ systems are affected in systemic amyloidosis, most commonly the heart, GI tract, and skin. after four weeks. Sedating antihistamines interfered with his work, and nonsedating antihistamines were minimally effective. Narrow-band UVB phototherapy appeared to be the most effective, but returning to the clinic two to three times a week for treatment has been costly and inconvenient. Mr. Carter is a fourth-year medical student at Virginia Commonwealth University School of Medicine in Richmond. Dr. Nunley is professor of dermatology at Medical College of Virgina Hospitals, also in Richmond. References 1. Gutmann C. Amyloidosis of the skin. Ned Tijdschr Geneeskd. 1928;2: 4480-4483. 2. Huilgol SC, Ramnarain N, Carrington P, et al. Cytokeratins in primary cutaneous amyloidosis. Australas J Dermatol. 1998;39:81-85. 3. Oiso N, Yudate T, Kawara S, Kawada A. Successful treatment of lichen amyloidosus associated with atopic dermatitis using a combination of narrowband ultraviolet B phototherapy, topical corticosteroids and an antihistamine. Clin Exp Dermatol. 2009;34:e833-e836. 4. Tanaka A, Arita K, Lai-Cheong JE, et al. New insight into mechanisms of pruritus from molecular studies on familial primary localized cutaneous amyloidosis. Br J Dermatol. 2009;161:1217-1224. 5. Weyers W, Weyers I, Bonczkowitz M, et al. Lichen amyloidosus: a consequence of scratching. J Am Acad Dermatol. 1997;37:923-928. 6. Jin AG, Por A, Wee LK, et al. Comparative study of phototherapy (UVB) vs. photochemotherapy (PUVA) vs. topical steroids in the treatment of primary cutaneous lichen amyloidosis. Photodermatol Photoimmunol Photomed. 2001;17:42-43. 50 THE CLINICAL ADVISOR � JULY 2012 � www.ClinicalAdvisor.com ALTERNATIVE MEDS UPDATE What you should know about the herbs and supplements patients use By Sherril Sego, FNP-C, DNP. Ms. Sego is a staff clinician at the VA Hospital in Kansas City, Mo., where she practices adult medicine and women's health. She also teaches at the nursing schools of the University of Missouri and the University of Kansas. Acupuncture In some respects, James Reston put acupuncture on the map of postmodern western consciousness. Many Americans remember that Reston traveled to China in 1971 with President Nixon's secretary of state, Henry A. Kissinger. At the time, Reston was a journalist for The New York Times.While in China, Reston fell ill and ended up in a Beijing hospital, where he had an emergency appendectomy.What was striking is that he was treated with acupuncture postoperatively as a means of pain management. His article in the Times describing his experience was the first in-depth look many Americans had at acupuncture treatment.1 � THINKSTOCK Background Historians date the origin of acupuncture in East Asian medicine to the first or second century B.C.2 Acupuncture deals with keeping the body and its internal forces in harmony.2 As the practice was refined, actual conduits, or meridians, were identified along specific anatomical points. These meridians were thought to control the flow of energy balance.2 In North America, The National Institutes of Health noted that there is enough scientific evidence of acupuncture's efficacy to warrant its use in certain clinical situations.2 Science Acupuncture is a standard therapy used in Chinese medicine. It involves the use of sharp, thin needles that are inserted into the body at meridian points. By using meridian points, the qi--or vital energy and life force in eastern philosophy-- is harnessed to control the flow of energy. Acupuncture is believed to adjust and alter the body's energy flow into healthier patterns, and is used to treat a wide variety of illnesses and health conditions. Acupuncturists use very fine sterile, disposable, stainless steel needles (0.18-0.51 mm) with the upper part of the needle shaft covered in plastic to give the practitioner a handle of sorts.3 The actual depth of insertion and choice of trigger points along the meridians, or energy pathways, is determined at the discretion of the individual practitioner.4 Although ancient acupuncturists had no way of understanding the biochemical actions of acupuncture, recent researchers have postulated a mechanism of action. In many scientific papers discussing the methodology of acupuncture, the needling is thought to stimulate fine nerve endings that, in turn, activate endogenous monoamines and neuropeptides.2,5,6 Research shows that this system prompts the activation of electromagnetic signals that may direct immune cells and other neurohormones to the area of injury.2,5,6 Continues on page 52 www.ClinicalAdvisor.com � THE CLINICAL ADVISOR � JULY 2012 51 ALTERNATIVE MEDS UPDATE In a meta-analysis, researchers noted that the majority of reviews considering acupuncture showed positive impacts on pain reduction in a variety of conditions. The most persistent positive outcomes were in the management of chronic low back pain and osteoarthritis.7 Multiple other conditions have shown mixed results in multiple clinical trials. Asthma, fibromyalgia, migraines, postoperative nausea and vomiting, and temporomandibular joint syndrome are on the lengthy list of conditions that may or may not be alleviated by acupuncture.7 The American Academy of Medical Acupuncture, however, expands significantly the number of conditions that may benefit from acupuncture therapy, including not only those listed but at least 31 others.2 A significant trial conducted in London examined 80 clients of general-practice clinics who were considered frequent patients with medically unexplained physical symptoms.8 These patients were randomized to receive 12 sessions of acupuncture starting either immediately or after six months.8 At the end of the acupuncture course, scores on a standardized medical-outcomes profi le for those who received immediate treatment exceeded those recorded in the delayed-treatment group.8 However, at the end of one year, the delayed-treatment group's scores had risen to nearly the same as the immediate-treatment cohort, indicating the positive impact of adding the acupuncture therapy.8 Cost The costs of acupuncture can be very prohibitive, with the average charge for eight to 10 treatment sessions ranging from $600-$1,200.11 Summary When administered by a properly trained professional, acupuncture is a safe and effective practice that may provide pain management in lieu of or in combination with more traditional therapy. Acupuncture has been used to alleviate low back pain. References 1. Reston J. Now, let me tell you about my appendectomy in Peking. New York Times. July 26, 1971:1. 2. Braverman S. Medical acupuncture review: Safety, efficacy, and treatment practices. Medical Acupuncture. 2004;15:12-16. 3. Ernst E, Pittler M, Wider B, Boddy K. Acupuncture: its evidence-base is changing. Am J Chinese Med. 2007; 35:21-28. 4. Dorsher P. Can classical acupuncture points and trigger points be compared in the treatment of pain disorders? Birch's analysis revisited. J Alt Comp Med. 2008;14:353-359. 5. Goldman N, Chen M, Fujita T, et al. Adenosine A1 receptors mediate local anti-nociceptive effects of acupuncture. Nat Neurosci. 2010;13:883-888. 6. Kavoussi B, Ross BE. The neuroimmune basis of antiinflammatory acupuncture. Integr Cancer Ther. 2007;6:251-257. 7. Ernst E. Acupuncture: A critical analysis. J Intern Med. 2006;259:125-137. 8. Paterson C, Taylor RS, Griffiths P, et al. Acupuncture for "frequent attenders" with medically unexplained symptoms: a randomized controlled trial (CACTUS study). Br J Gen Pract. 2011;61:e295-e305. 9. Ernst E, Lee MS, Choi TY. Acupuncture: Does it alleviate pain and are there serious risks? A review of reviews. Pain. 2011;152:755-764. 10. Witt CM, Pach D, Brinkhaus B, et al. Safety of acupuncture: results of a prospective observational study with 229,230 patients and introduction of a medical information and consent form. Forsch Komplementmed. 2009;16:91-97. 11. Cherkin DC, Sherman KJ, Avins AL, et al. A randomized trial comparing acupuncture, simulated acupuncture, and usual care for chronic low back pain. Arch Intern Med. 2009;169:858-866. � THINKSTOCK Minor side effects from acupunture treatment, such as needle site pain and bleeding, occur in roughly 11% of cases. Safety, interactions Typically, acupuncture is perceived to carry a low risk for adverse events. However, the risk of infection is always present when a foreign object is being inserted into the body. Such minor side effects of acupuncture as needle-site pain and bleeding occur in up to 11% of cases.9,10 In rare cases, serious adverse events do occur. Pneumothorax and cardiac tamponade were noted in studies, as were hepatitis C and HIV infection.9,10 The risk for hepatitis and HIV, however, were directly correlated to the individual acupuncturist.9,10 52 THE CLINICAL ADVISOR � JULY 2012 � www.ClinicalAdvisor.com CME CE Dermatologic Look-Alikes LEARNING OBJECTIVE: To distinguish and properly treat dermatologic conditions with similar presentations. COMPLETE THE POSTTEST: Page 57 ADDITIONAL CME/CE: Pages 23, 47 Turn to page 22 for additional information on this month's CME/CE courses. Erythematous palmar lesions KERRI ROBBINS, MD CASE #1 CASE #2 A white, HIV-positive man, aged 41 years, presented to the dermatology clinic with complaints of a localized eruption on his bilateral palms. The eruption began one week earlier, and there was no associated pruritus or pain. The man had applied petroleum jelly to the lesions without significant improvement. No history of genital ulceration or any other rashes on the body were reported. On physical examination, erythematous scaling papules and plaques were appreciated on bilateral palms. The remainder of the physical exam was within normal limits. A 35-year-old black woman with a history of systemic lupus erythematosus (SLE) presented with lesions on her bilateral palms, which had been present for five months. Similar lesions were noted on her face, ears, and forearms. There was no associated pain or pruritus and no alleviating or aggravating factors. The woman was taking hydroxychloroquine (Plaquenil, Quineprox) for her SLE but had not been given any treatments for the current cutaneous eruption. Erythematous scaling plaques--some with surrounding hyperpigmentation--were noted on the cheeks, conchal bowls, forearms, and palms. www.ClinicalAdvisor.com � THE CLINICAL ADVISOR � JULY 2012 53 CME CE Dermatologic Look-Alikes nearly a quarter of patients will relapse. After lesions heal, the patient goes into an asymptomatic state known as the latency period, which can last for years and is defined as the period between the healing of the clinical lesions and the appearance of late manifestations. During the latency period of syphilis, patients will display no clinical symptoms but will exhibit positive serologic reactivity to a rapid plasma regain (RPR) or venereal disease research laboratory (VDRL) assay, and/or a microhemagglutination assay for T. pallidum antibodies (MHA-TP) or fluorescent treponemal antibody absorbed (FTA-ABS) test. Tertiary syphilis may appear months or years after infection and can also have a range of presentations. Nearly half of all patients will present with arciform, erythematous eroded plaques with central scarring referred to as cutaneous gummas. Some patients also may go on to develop skeletal, cardiovascular, and/or neurologic manifestations. CASE #1 Syphilis Syphilis is a sexually transmitted infection that dates back to the late 15th century. Theories as to the spread of syphilis can be debated but the true culprit cannot. It is now known that the pathogen Treponema pallidum is responsible for the infection. This pathogen was first isolated and identified in 1905 by Schaudinn and Hoffmann.1 The infection may be congenitally or sexually acquired and is a chronic, cutaneous, and systemic disease. Syphilis progresses through three stages: primary, secondary, and tertiary. T. pallidum penetrates the body's main defenses through mucosal surfaces and abraded skin. Once inside the host, it will attach to cells, multiply within hours, and then spread to regional lymph nodes and internal organs. This spread marks the start of the incubation period, which can last 10 to 90 days. On average, primary syphilis develops three weeks after the initial infection with T. pallidum. During the primary stage or up to six months after the primary lesions have healed, the onset of secondary syphilis occurs. Nearly every patient will develop secondary syphilis if not treated appropriately during the primary stage. During this time, T. pallidum undergoes hematogenous dissemination and multiplication. This stage is generally accompanied by fever, malaise, and enlargement of the lymph nodes. The tertiary stage is the final stage of syphilis and occurs in approximately one-third of untreated individuals. Primary syphilis begins as a painless papule, that enlarges and develops into an ulcer (chancre) within a few days. During this stage, patients will often have enlarged regional lymph nodes. Untreated, the ulceration will heal within a few weeks. Secondary syphilis most commonly presents with nonpruritic, generalized, papulosquamous lesions. Often, these lesions are seen on the palms and soles, which should alert the clinician to consider the diagnosis of syphilis. Patients may also present with annular plaques with central hyperpigmentation, mucosal ulcerations, anogenital condyloma lata, nonscarring moth-eaten alopecia, split papules at the oral commisures, and granulomatous nodules and plaques. Patients who present with disseminated lesions that resemble the primary chancre are given the diagnosis of malignant syphilis. Secondary syphilis generally resolves within three to 12 weeks; however, Secondary syphilis most commonly presents with nonpruritic, generalized, papulosquamous lesions. During the primary stage of syphilis, the epidermis is ulcerated and a diffuse infiltrate of plasma cells, lymphocytes, and histiocytes can be appreciated. Endothelial swelling and proliferation can also be observed. During the secondary stage, the epidermis may appear hyperkeratotic or ulcerated, but most commonly is psoriasiform.2 A perivascular or lichenoid infiltrate of many plasma cells, histiocytes, and lymphocytes is present as well. A granulomatous infi ltrate may be present in older lesions. Tertiary syphilis will exhibit tuberculoid granulomas, often with plasma cells. The epidermis may appear normal, hyperplastic, or atrophic, and fibrosis has been noted in some lesions. T. pallidum may be detected using the Warthin-Starry stain during the primary and secondary stages; however, spirochetes are usually not easily identified during the tertiary stage.2,3 Because of its vast expanse of clinical manifestations, syphilis is known as the great imitator and therefore has an extensive list of differential diagnoses. Consider other causes of anogenital ulcerations when differentiating primary syphilis from genital herpes, genital trauma, Behcet's disease, genital carcinoma, chancroid, and lymphogranuloma venereum. Cutaneous lesions of secondary syphilis may be confused with pityriasis rosea, eczema, psoriasis, 54 THE CLINICAL ADVISOR � JULY 2012 � www.ClinicalAdvisor.com lichen planus, primary HIV infection, and drug eruption. Lesions on the hands and feet may be confused with psoriasis, eczema, and discoid lupus erythematosus. Finally, tertiary syphilis may resemble sarcoidosis, tumors, lupus vulgaris, mycosis fungoides, and fungal infections. Penicillin G is still the treatment of choice for all stages of syphilis. The dose varies depending on the stage of the disease. Thus far, penicillin resistance to T. pallidum has not been detected. If a person is allergic to penicillin, a tetracycline may be used. Follow-up examinations are recommended at months 1, 3, 6, and 12 following antibiotic treatment of early syphilis, then every six months for two years. Patients with late syphilis should be followed for three years. Due to the sexually transmitted nature of this disease, many countries require documentation and notification of previous sexual partners.4 Given that this patient also had concurrent HIV infection, he was treated with benzathine (Bicillin) penicillin 2.4 million units intramuscular weekly for three doses. The rash resolved, and repeat serologic examination one month following antibiotic treatment was within normal limits. The patient will be followed for at least two years. CASE #2 Discoid lupus erythematosus Lupus erythematosus is a multisystem disorder that prominently involves the skin. In some, the cutaneous lesions also may serve as an indicator of underlying systemic disease. There are three major forms of cutaneous lupus. The first is acute cutaneous lupus erythematosus (ACLE), which is characterized by the classic malar erythema, or butterfly rash. ACLE is most commonly associated with underlying SLE. The second variant is subacute cutaneous lupus erythematosus (SCLE), which is a photosensitive eruption that is longerlasting than classic ACLE. Discoid lupus erythematosus (DLE) falls under the category of chronic cutaneous lupus, and these lesions are often long-lasting and scarring. Cazenave was the fi rst to describe and name lupus erythematosus in the mid-1800s.5 It was not until 1964 that Dubois categorized the disorder into a spectrum of disease ranging from cutaneous lesions to life-threatening internal disease. In 1981 and 1982, Weston and Sontheimer found that anti-Ro antibodies were associated with neonatal lupus and SCLE, respectively.6,7 Lupus erythematosus is an autoimmune disorder that is believed to have a genetic predisposition with an environmental activator.8 Some propose that in the appropriate context, an immune response to a foreign antigen may lead to a limited and then broader autoimmune response. Ultimately, this ends with tissue injury. Certain autoantibodies are associated with certain skin diseases. For example, antibodies to double-stranded DNA (dsDNA) are seen in those with ACLE and antibodies to Ro are seen in those with SCLE. DLE is the most common type of cutaneous lupus and may involve the epidermis, upper dermis, and lower dermis. There is a much lower female-to-male ratio with discoid lupus (2:1) than with to systemic lupus (8:1). Lesions are most commonly found on the face, scalp, and ears, but may also be seen in a widespread distribution. It is unusual for DLE to be present below the neck without lesions also being present above the neck.9 Unlike other forms of lupus, there is no clear association between sun exposure and the development of DLE. Lesions may present with erythema, scaling, atrophy, dyspigmentation, and scarring. Active lesions may feel indurated due to the intense inflammatory infi ltrate in both the superficial and deep dermis. Follicular plugging and alopecia are other common features. The dyspigmentation is most often characterized by hyperpigmentation of the periphery with central hypopigmentation. Lesions on the palms and soles may be ulcerative or keratotic. Discoid lesions have potential for scarring and given enough time, most patients will develop disfiguring scars, which may impact their quality of life. The majority (90%-95%) of patients with DLE do not develop SLE. Those with widespread lesions may be at greater risk of systemic involvement. There are different histologic patterns that correspond to the various forms of cutaneous lupus. This write-up will discuss only the histopathologic findings seen in DLE. There is often marked hyperkeratosis and follicular plugging of the epidermis. The dermal-epidermal basement membrane zone is visibly thickened and obscured due to liquefaction degeneration. The thickening may be more apparent on periodic acid Schiff-stained sections. A lymphohistiocytic infi ltrate is seen in the superficial and deep dermis in both a perivascular and periadnexal distribution. The differential diagnosis of early lesions of DLE may be confused with syphilis, Jessner's lymphocytis infiltrate, polymorphous light eruption, lymphocytoma cutis, lymphoma www.ClinicalAdvisor.com � THE CLINICAL ADVISOR � JULY 2012 55 CME CE Dermatologic Look-Alikes depression and isolation. These patients must be followed closely, as the treatment of early lesions may be preventive. Exacerbation is possible in the spring and summer due to increasing sun activity and exposure. During this time, patients must take the appropriate precautions and minimize sun exposure. Serious systemic disease rarely develops with DLE, but when it occurs, patients may need to seek consultation with an internist, a rheumatologist, and/or a nephrologist. This patient had been evaluated previously by rheumatology and was already on hydroxychloroquine 200 mg b.i.d., given the known history of SLE. After evaluation by dermatology, she was additionally prescribed clobetasol 0.05% ointment to be used b.i.d. on bilateral palms. A few lesions of DLE on the face were treated with intralesional triamcinolone in a concentration of 4 mg/mL. Dr. Robbins is a resident in the Department of Dermatology at Baylor College of Medicine in Houston. References 1. NR Krieg, JG Holt, eds. Bergey's Manual of Systematic Bacteriology, cutis, granuloma faciale, and sarcoidosis. Palm and sole lesions may be mistaken for lichen planus or secondary syphilis, and the presence of classic DLE lesions above the neck may be helpful in ascertaining the correct diagnosis. Scalp and oral lesions must also be differentiated from lichen planus. When evaluating a patient with DLE for the presence of systemic disease, a detailed history, physical examination, and certain blood and urine testing should be performed. Laboratory tests to include in the systemic lupus-screening panel include an antinuclear antibody (ANA) with profi le (dsDNA, Sm), urinalysis, complete blood count with differential, chemistries, erythrocyte sedimentation rate, and complement levels (C3, C4). It is very rare for a patient with systemic lupus to have a negative ANA. On the other hand, a positive ANA does not signify systemic lupus and may be positive in patients with cutaneous lesions or with other diseases, or in a subset of normal individuals. Refer to the American College of Rheumatology 1982 revised criteria for guidelines on the classification of SLE.10 Educate patients with DLE on the risks of corticosteroid therapy, and monitor the skin for any side effects. High-potency topical or intralesional corticosteroids are the safest treatment for DLE. Discoid lupus is one of a very few instances in which it is safe to use a high-potency corticosteroid on the face (if lesions are present at that location). It is important to educate patients on the risks of corticosteroid therapy and to monitor the skin for any side effects. Sun protection is also a mainstay of treatment, and patients should use a broad-spectrum, high-SPF sunscreen. Because of the scarring nature of DLE, cosmetic cover-up may be the best treatment for patients with hyper- and hypopigmented lesions. Antimalarial therapy is the gold standard. Hydroxychloroquine (Plaquenil, Quineprox) is most commonly used and is generally well-tolerated. The usual dose is 200 mg once or twice daily. Eye toxicity is unlikely if the maximum dose does not exceed 6.5 mg/kg ideal body weight. Chloroquine (Aralen) and quinacrine are alternatives. Quinacrine is often added to the regimen of hydroxychloroquine in those who are not responding. Individuals with an allergy to hydroxychloroquine may still take chloroquine. The prognosis of patients with DLE is favorable; however, many experience scarring and disfigurement, leading to Volume 1, Baltimore, Md.: Lippincott Williams & Wilkins; 1984:49-57. 2. RP Rapini. Practical Dermatopathology. Philadelphia, Pa.: Elsevier Mosby; 2005:165-168, 225-227. 3. Elder DE, Elenitsas R, Johnson BL, et al, eds. Lever's Histopathology of the Skin. 10th ed. Philadelphia, Pa.: Lippincott Williams & Wilkins; 2009:579-583. 4. Centers for Disease Control and Prevention, Workowski KA, Berman SM. Sexually transmitted diseases treatment guidelines, 2006. MMWR Recomm Rep. 2006;55(RR-11):1-94. Available at www.cdc.gov/mmwr /preview/mmwrhtml/rr5511a1.htm. 5. Cazenave PLA. Lupus erthemateux (erythema centrifuge). Ann Malad Peau Syph. 1851;3:297-299. 6. Franco HL, Weston WL, Peebles C, et al. Autoantibodies directed against sicca syndrome antigens in the neonatal lupus syndrome. J Am Acad Dermatol. 1981;4:67-72. 7. Sontheimer RD, Maddison PJ, Reichlin M, et al. Serologic and HLA associations in subacute cutaneous lupus erythematosus, a clinical subset of lupus erythematosus. Ann Intern Med. 1982;97:664-671. 8. Nath SK, Kilpatrick J, Harley JB. Genetics of human systemic lupus erythematosus: the emerging picture. Curr Opin Immunol. 2004;16:794-800. 9. Prystowsky SD, Herndon JH Jr, Gilliam JN. Chronic cutaneous lupus erythematosus (DLE)--a clinical and laboratory investigation of 80 patients. Medicine (Baltimore). 1976;55:183-191. 10. American College of Rheumatology. The 1982 revised criteria for classification of systemic lupus erythematosus. Available at www.rheumatology.org/practice/clinical/classification/SLE/sle.asp. All electronic documents accessed June 15, 2012. 56 THE CLINICAL ADVISOR � JULY 2012 � www.ClinicalAdvisor.com CE POSTTEST Expiration date: July 2013 Nurse Practitioner Associates for Continuing Education (NPACE) is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's Commission on Accreditation. The Nurse Practitioner Associates for Continuing Education designates this educational activity for a maximum of 1.0 contact hours of credit. Participants should only claim credit commensurate with the extent of their participation in the activity. Posttests must be completed and submitted online. NPs may register at no charge at www.myCME.com.You must receive a score of 70% or better on each test taken to obtain credit. CREDITS: 0.5 CREDITS: 0.5 Feature page 23 Dermatology Clinic page 47 Dermatologic Look-Alikes page 53 Evaluating and managing pediatric food allergy 1. What is the most common allergenic food in the United States? a. Seafood b. Cow's milk c. Peanut d. Egg 2. What symptom is associated with an immunoglobulin-E-mediated hypersensitivity response? a. Acute nausea b. Abdominal pain c. Vomiting d. All of the above 3. Which allergy is typically not outgrown? a. Soy b. Shellfish c. Wheat d. Cow's milk 4. What vaccine is contraindicated in egg-allergic patients? a. Rabies b. Measles c. Mumps d. Rubella Blue nevus 1. Which population seems to be most affected by blue nevi? a. Asians b. Blacks c. Hispanics d. Whites 2. What is a feature of malignant blue nevi? a. Cytologic atypia b. Mitoses c. Large size d. All of the above Lichen amyloidosis 3. What is a feature of the initial presentation of lichen amyloidosis? a. Polyarticular migratory arthritis b. Intense itch that causes the patient to scratch relentlessly c. Spiking temperature with severe myalgias d. Generalized painless lymphadenopathy 4. What is used topically to treat lichen amyloidosis? a. Retinoid b. Calcipotriol c. Fluorouracil d. Corticosteroid Syphilis 1. Secondary syphilis most commonly presents with a. Nonpruritic, generalized, papulosquamous lesions b. A painless papule that develops into a chancre c. Erythematous eroded plaques with central scarring d. Tuberculoid granulomas, often with plasma cells 2. What is the treatment of choice for all stages of syphilis? a. Azithromycin (Zithromax, Zmax) b. Cephalexin c. Penicillin G d. Ciprofloxacin (Cipro, Proquin) Discoid lupus erythematosus (DLE) 3. The presence of classic DLE lesions in which location may help ascertain the correct diagnosis? a. At flexural surfaces b. Above the neck c. In the oropharynx d. Below the knees 4. What is the most commonly used medication for systemic therapy? a. Hydroxychloroquine b. Methotrexate (Rheumatrex, Trexall) c. Rituximab (Rituxan) d. Hydroxyurea (Droxia, Hydrea) TO TAKE THE POSTTEST please go to ClinicalAdvisor.com/CMEFeatureJuly2012 TO TAKE THE POSTTEST please go to ClinicalAdvisor.com/DermJuly2012 www.ClinicalAdvisor.com � THE CLINICAL ADVISOR � JULY 2012 57 COMMENTARY Rachael Buitrago, CPNP, is an ANCC-board-certified pediatric nurse practitioner in a private office in South Florida, and has taught as adjunct nursing faculty at local universities. EMR: It will get better! Of the many changes that have occurred in our health-care system, one that particularly affects most providers is the advent of electronic medical records (EMRs). Although hospitals have been charting electronically for years, medical offices have not been as quick to adopt this initiative. However, due to changes in the business of health care, medical offices are now seeking out acceptable and affordable EMR programs and receiving incentives to implement them. The idea behind electronic medical records is easy accessibility for health-care providers and patients alike. Having medical information at one's fingertips is a great asset for continuity of care. Going "live" with your practice's EMR program could mean decreased productivity for an average of six to 12 months. Practitioners can access old records once those documents have been scanned into the computer system, and newly acquired health information is placed directly into an electronic chart. Legible handwriting is no longer a concern with typed data. Laboratory and diagnostic test results may be fi led directly to the patient's chart with no loss of paperwork. Health history, allergies, and lifestyle information, all at a click of the key. This system allows for greater use of the heath-care provider's time. Along with all the positive aspects of new technology are bound to be some drawbacks. For example, costs for EMR programs are steep, ranging from acquiring computers for all providers, to scanning fees, to the extra time that may be required to complete one's day of charting (in the beginning phase). It will also cost you time in other ways: Going "live" with your practice's EMR program will probably mean decreased productivity for an average period of six to 12 months. The standard 15-minute time slot allotted for each patient will likely double. At first, it's not that easy or quick to navigate through the areas of information that need to be completed in the new computer system for each initial visit. Waiting for patient charts to be scanned, saved, and uploaded to the new system is a disruption for the entire office staff. Much time is spent trying to locate previous medical information. Patients wonder why you are asking all these questions that they have already answered on previous visits, and they are not at all happy to know their wait time will be longer due to the new system. The good news is, there is a rainbow at the end of this EMR storm. One grand benefit of EMR implementation is the meaningful-use incentives from the Centers for Medicare & Medicaid Services (www.cms.gov/Regulations-andGuidance/Legislation/EHRIncentivePrograms/ index.html, accessed June 15, 2012). The incentive is a great way for small practices to finance an affordable EMR program. Additional benefits of EMR implementation include being able to read your colleagues' notes, patients having access to their own medical records and becoming active participants in their own care, educational material being just a click away, being able to prescribe medications with just a few clicks, easily recording and tracking immunizations through statewide programs, and collaborating/consulting with other health-care providers more efficiently. Like all shiny new toys, the novelty of EMR will wear off, and computer charting will become second nature. When all the kinks have been worked out and health-care providers are pros, we will ponder the days we didn't have an EMR system and laugh at how we could have possibly ever gotten by without it. 58 THE CLINICAL ADVISOR � JULY 2012 � www.ClinicalAdvisor.com For advertising information, contact: Russell Johns Associates, LLC 1001 S Myrtle Ave, #7, Clearwater, FL 33756 Phone: 877.394.1388 or 727.443.7667 � Fax: 727.445.9380 � E-mail: email@example.com CLASSIFIEDS NP/PA WANTED NP WANTED Flagstaff Medical Center was recently ranked as a Best Regional Hospital by US News and World Report. With our Heart and Vascular Center, bariatric and spine/joint surgery centers and a variety of in- and out-patient services, we offer medically challenging and stimulating learning opportunities within a patient- and family-focused care model. In addition to world class care, we strive to promote a strong work-life balance for our employees. Colleagues have access to a variety of continuing education opportunities, anG extensive wellness and employee assistance programs. Away from work, enjoy the four-season climate; breathtaking scenery; warm, friendly communities; and recreational pleasures that make Northern Arizona a wonderful place to live, work and play. Silver Health CARE, a dynamic practice in southwestern New Mexico, is recruiting for THREE physician assistants/nurse practitioners in urgent care and primary care at its Silver City, Deming, and Las Cruces locations. Quality-driven and serviceoriented with an excellent reputation, established 38 years ago. Excellent salary and benefits. Enjoy mild weather, beautiful mountain scenery, easy access to outdoor recreational opportunities, four-year colleges with graduate programs, a vibrant arts scene, rich and diverse cultural heritage. Please e-mail or fax CV to: Cindy Donatelli, Recruiter (575) 388-3373 firstname.lastname@example.org We are currently seeking Nurse Practitioners in Trauma Services, PACU, Children's Health Center and the Heart and Vascular Center. For information about our fantastic career opportunities, extensive wellness SURJUDPDQGEHQH�WSDFNDJHVWKDWLQFOXGHDVKRUWWHUPLQFHQWLYHSURJUDPYLVLW www.nahealth.com/careers. Follow us on: www.silverhealthcare.org PA WANTED CONFERENCES Champlain Valley Heart Center, located in Plattsburgh, NY, is seeking a Staff PA for our Cardiothoracic Surgical program. The heart surgical program at CVPH was begun in 2005 and continues to grow, surrounded by the very best in advanced technology. We performed 739 PCI's and 130 Open Hearts in 2011; an additional 100+ general thoracic procedures are performed annually, with anticipated growth. Our cardiology and cardiac surgical services have received numerous national and state awards and recognitions for both clinical excellence and outcomes. Join the CVPH cardiothoracic surgical team at CVPH! Interested Staff PA candidates must have at least two to three years of cardiac surgical experience with the desire to become proficient with Endoscopic Vein Harvesting (EVH), surgical first-assisting, and to work collaboratively as part of the Cardiac Surgery team to provide excellent patient care. With a generous annual compensation and benefits package, we're very competitive with other cardiac surgical programs. The benefit package includes relocation up to $10K. In addition, CVPH will offer either a sign-on bonus or up to $20,000 in loan forgiveness for a 2-year employment commitment. Plattsburgh is a picturesque community of 38,000 located on Lake Champlain and at the foothills of the Adirondack Mountains. We live where others vacation! Contact: Becky Larkin, CVPH Medical Center 75 Beekman Street � Plattsburgh, NY 12901 Phone: 518-314-3025 � Email: email@example.com Website: www.cvph.org, select "Careers" in upper left column. www.ClinicalAdvisor.com � THE CLINICAL ADVISOR � JULY 2012 59 CLASSIFIEDS PA WANTED For advertising information, contact: Russell Johns Associates, LLC 1001 S Myrtle Ave, #7, Clearwater, FL 33756 Phone: 877.394.1388 or 727.443.7667 � Fax: 727.445.9380 � E-mail: firstname.lastname@example.org MEDICAL EDUCATION Clarkson University's Department of PA Studies is seeking a faculty member to join our growing program. This is a relatively new program that uses lecture, problem-based learning, and simulation to enhance our patient-centered focus. Our class size is small and will remain that way. This is a wonderful opportunity for a PA who is looking for a chance to join the academic world while giving back to our profession. The assistant professor will be a member of the principal faculty of the PA program. Responsibilities include providing student instruction, evaluating student performance, academic counseling of students, admissions, assisting in developing, coordinating and evaluating curriculum as well as program evaluation. The faculty member will also assist the Director of Clinical Education with procurement and assessment of clinical sites. One day per week is allowed for clinical practice. Minimum Qualifications � Master's degree in a health related discipline (Bachelor's may be considered for the right candidate) � Three years of experience as a clinician � Experience teaching medical subjects Preferred Qualifications � Doctorate degree in a health related discipline � Experience in PA education � Licensed/Registered (or eligible) in NY State as a PA � 5 or more years as a clinician Clarkson University is located in Potsdam NY. The area has 4 universities, 4 seasons of sports and activities, and is a small, safe community. Clarkson University is the highest ranked research university of its size in NY State. Come join us as we prepare the next generation of PAs. Please contact Dr. Michael Whitehead, program chair, email@example.com for more information. MEDICAL EDUCATION MEDICAL EDUCATION )LQG\RXUQH[W VWDUHPSOR\HH RQ&OLQLFDO -RE$GYLVRU WRGD\ $VHUYLFHSURYLGHGE\ ZZZ&OLQLFDO-RE$GYLVRUFRP VDOHV#FOLQLFDOMREDGYLVRUFRP 60 THE CLINICAL ADVISOR � JULY 2012 � www.ClinicalAdvisor.com Available at myCME.com/UMDNJ NEW for 2011-2012 To listen on the go, download audio files to your MP3 player or burn them to a CD PANCE/PANRE ONLINE REVIEW COURSE Convenient: Study where and when you want. Practice examination questions at the end of each module. Download all slides and handouts to print or review. Comprehensive: All topics on the NCCPA examination blueprint are covered in more than 27 hours of instruction. Self-reported 98.6% pass rate. Cost-effective: Only $349 for all 5 modules or $99 for an individual module. DELIVERED VIA 5 MODULES FOR EASY REVIEW EACH MODULE IS INDIVIDUALLY ACCREDITED | ACCESS AT MYCME.COM/UMDNJ Module 1 Module 2 Module 3 Module 4 Module 5 Cardiology/EKG Review Pulmonology, Pediatrics, Ophthalmology, Otorhinolaryngology Orthopedics, Neurology, Psychiatry Infectious Disease, Gastroenterology, Dermatology Reproductive System, Endocrinology, Genitourinary System, Hematology ACCREDITATION INFORMATION This program has been reviewed and is approved for a maximum of 27.25 hours of AAPA Category 1 CME credit by the Physician Assistant Review Panel. Approval is valid for one year from the issue date of October 17, 2011. Participants may submit the self-assessment at any time during that period. This program was planned in accordance with the AAPA's CME Standards for Enduring Material Programs and for Commercial Support of Enduring Material Programs. This program has been planned without commercial support. Developed by Posted on Sponsored by Scan here to learn more