May 2020 Clinical Advisor

A P E E R - R E V I E W E D F O RU M F O R N U R S E P R AC T I T I O N E R S

NEWSLINE

■■ Telehealth Update ■■ Lifestyle Modifications ■■ Cellphone and Migraine ■■ Baseline Colonoscopy LEGAL ADVISOR

Delays Lead to Sepsis and Death FEATURE

Latent Autoimmune Diabetes in Adults: A Less Common Form of Disease

DERMATOLOGY CLINIC

Papulosquamous Cutaneous Lesions on Arms and Hands

DERMATOLOGIC LOOK-ALIKES

Congenital Nevi in Infants

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M AY 2 02 0

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MOTOR NEURON DISEASE

Amyotrophic Lateral Sclerosis: Insights Into Early Signs, Symptoms

Director Nikki Kean nikki.kean@haymarketmedia.com Associate editor Madeline Morr

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During this time of uncertainty, we wanted to express our gratitude to all the NPs and PAs who are working on the frontlines of this pandemic.

We also want to thank those who have made the switch to telehealth to continue to provide care to COVID-19 and non-COVID patients with chronic conditions.

The Clinical Advisor surveyed our readers on April 6 about how the novel coronavirus has affected practice. Here are some stories from the frontlines.

Throughout New York City, practitioners described controlled chaos. From a reader in the Bronx: “Everyone was caught short with inventories of equipment because of the large influx of patients the last couple of weeks. Our i­nstitution is in better shape now than 7 or 10 days ago.” From another reader in the Bronx: “We have suffered tremendous stress and fear as we see the reality of this on an hour-to-hour basis. Many of those who were in the front line will need mental health assistance once this calms down.”

The switch to telehealth has been easy for some and a challenge for others. A clinician from Georgia wrote, “It has been interesting making the switch from in-person patient visits to doing everything by telehealth. I think that the use of telehealth will remain relatively high even after the pandemic is over.” A clinician in New Mexico wrote, “There will be a need for clear guidelines for telehealth visits, especially in the area of pediatrics. There is quite a bit that can be learned from the VA and military about remote healthcare provision and limitations.” And then there’s this call from a clinician in Florida to enlist younger relatives to help their parents and grandparents adjust to telehealth: “Telemedicine is hell with a geriatric population who have no idea how to use a smart phone. I urge the media to encourage people to help their elders as my office is overwhelmed with helping patients.”

Although some practitioners are working overtime, others have seen their practices shuttered and their colleagues furloughed.

All healthcare practitioners have been affected by this pandemic. We are here for you, to report your stories, to stay connected, and to continue to produce peer-reviewed articles that you have come to depend on.

Please stay safe.

Nikki Kean, Director The Clinical Advisor www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • MAY 2020 1

CONTENTS M AY 2 0 2 0

NEWS 6

Newsline ■■NPs, PAs Granted Telehealth Provisions Through Medicare ■■Lifestyle Modification Program May Lower the Risk for T2D ■■Smartphone Use and Headache: What’s the Link?

■■Baseline Colonoscopy Findings Key for Identifying

Future Outcomes 8 Baseline colonoscopy predicts future risk

FEATURES 9

AANP and AAPA Presidents Tackle COVID-19 Interview with Sophia L. Thomas and David E. Mittman.

13 Insights Into Diagnosis and Treatment of ALS Early diagnosis often overlooked by clinicians.

1 Latent Autoimmune Diabetes in Adults: A Less 2 Common Form of Disease Low C-peptide level key to appropriate diagnosis.

21 Older adults and new-onset diabetes

DEPARTMENTS 4

29

Web Roundup A summary of our most recent opinion, news, and multimedia content from ClinicalAdvisor.com.

Dermatology Clinic ■■Hyperpigmented Scaly Plaque on Midline of Back ■■Papulosquamous Cutaneous Lesions on Arms and Hands

29 Obesity-linked skin disorder

39 Surgical delay leads to patient death

33

Dermatologic Look-Alikes ■■Congenital Nevi in Infants

39

Legal Advisor ■■Delays Lead to Sepsis and Death

Follow us on Twitter @ClinicalAdvisor

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ClinicalAdvisor.com

NEWS

FEATURES

ClinicalAdvisor.com/News

ClinicalAdvisor.com/Features

CBT for Health Anxiety Shows Benefit Over 8 Years

Reproductive Health in Rheumatic and Musculoskeletal Diseases American College of Rheumatology provides recommendations on contraception, assisted reproductive technologies, fertility preservation, menopausal hormone replacement therapy, pregnancy, and medication use in women with rheumatic and musculoskeletal diseases.

Cognitive behavioral therapy adapted for health anxiety (CBT-HA) may be a highly effective long-term treatment for pathological health anxiety.

Universal FLU-v Influenza Vaccine Shows Promise, Warrants Further Testing The adjuvanted, broad-spectrum influenza vaccine FLU-v was found to be immunogenic and merits phase 3 development to explore efficacy.

Study Evaluates Effectiveness of Telemedicine in Dx MI

THE WAITING ROOM

Official Blog of The Clinical Advisor ClinicalAdvisor.com/WaitingRoom Jim Anderson, MPAS, PA-C, DFAAPA Do Words Matter When We Talk to Our Patients?

It’s important to speak to patients in language they can understand to improve communication of their diagnosis and treatment plan.

Time to telemedicine diagnosis was found to be a useful parameter in assessing the effectiveness of telemedicine in identifying patients who have experienced acute myocardial infarction.

Marijuana Vaping Trends in Adolescents Increasing Two studies report a significant increase in the amount of self-reported marijuana e-cigarette use among middle school and high school students between 2017 and 2019.

Tackling Sleep Problems From Self-Isolation and Stress During COVID-19 Pandemic As people face prolonged periods of confi nement during the COVID-19 pandemic, stress levels may disrupt sleep patterns and worsen mental health. CBT-I may be useful in treating acute episodes of insomnia related to immediate stress.

CASE STUDY ClinicalAdvisor.com/CaseStudy Brady Pregerson, MD Eye Pain, Drainage, Headache, and Blurry Vision A 72-year-old woman presents with a 4-day history of worsening pain and clear drainage of her right eye; she also complains of a 2-day history of right-sided gradual-onset headache associated with blurry vision.

See the full case at ClinicalAdvisor.com/ CaseStudyMay20

4 THE CLINICAL ADVISOR • MAY 2020 • www.ClinicalAdvisor.com

© TOP, MIDDLE: GETTY IMAGES

EXCLUSIVE TO THE WEB AT

Advisor Dx 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/AdvisorDx. Learn more about diagnosing and treating these conditions, and see how you compare with your fellow colleagues.

Check out some of our latest cases below!

DERM DX

Asymptomatic Growth on the Nose A 52-year-old man requests removal of an asymptomatic growth on his nose. He denies history of skin cancer or warts. Examination reveals a 2-mm flesh-colored papule. Scattered skin tags are noted on his face, and seborrheic keratoses are found on his back.

CAN YOU DIAGNOSE THIS CONDITION?

• Verruca • Neurofibroma • Neurothekeoma • Trichofolliculoma ● See the full case at ClinicalAdvisor.com/DermDx_May20

ORTHO DX

In partnership with

TheJopa.org

Journal of Orthopedics for Physician Assistants

Painful Callus on Fifth Toe A 56-year-old woman presents with pain in her left foot. She reports that the pain intensifies when she wears dress shoes but seems to improve when she walks barefoot. On physical examination, a skin callus identified at the fifth metatarsophalangeal (MTP) joint creates a lateral prominence and she has pain on palpation.

WHAT IS THE BEST TREATMENT OPTION?

• Toe spacer • Wide toe box shoes • Custom orthotic • Corticosteroid injection ● See the full case at ClinicalAdvisor.com/OrthoDx_May20

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • MAY 2020 5

Newsline THE CENTERS for Medicare and Medicaid Services announced a waiver of certain Medicare telehealth provisions granted by the Coronavirus Preparedness and Response Supplemental Appropri­ ations Act (Coronavirus Act), which was signed into law on March 6, 2020. The waiver was announced on March 17.

The waiver removes the Medicare limi­ tations on telehealth only being authorized in rural areas. It removes the restrictions on telehealth originating sites, allowing for patient’s homes to be considered an originating site and will apply to a broad category of “non-face-to-face services furnished through various modalities, including telehealth visits, virtual checkin services, e-visits, monthly remote care management, and monthly remote patient monitoring,” according to US Department

of Health and Human Services (HHS) Office of the Inspector General (OIG).

HHS has also announced that it will not enforce the requirement of an exist­ ing relationship between a patient and a provider to furnish telehealth services.

Additionally, the HHS will waive penal­ ties for HIPAA violations against health providers who serve patients in good faith through everyday communication technologies such as FaceTime. Health care providers also have the authority to reduce or waive cost-sharing for tele­ health visits paid by Medicare.

The waiver is specific to the Medicare program and does not waive any existing state telehealth requirements, exempt nurse practitioners from state collab­ orative/supervision requirements in the states that mandate them, or waive the

© JOHN FEDELE / GETTY IMAGES

NPs, PAs Granted Telehealth Provisions Through Medicare

The waiver removes Medicare limitations on telehealth originating sites.

requirements of other insurers including Medicaid. The waiver applies broadly throughout the Medicare program and is not specific for patients being treated for the coronavirus.

The waiver will be retroactive to ser­ vices provided beginning on March 6, 2020, and will be effective until the end of the public health emergency.

Lifestyle Modification Program May Lower the Risk for Type 2 Diabetes MONTGOMERY COUNTY, Alabama, has one of highest rates of obesity (35%) and diabetes (13%) in the nation, with up to 7% of the population at risk of developing diabetes. To improve access, outcomes, and quality of care in patients with prediabetes, researchers at a clinic in Montgomery County developed a 3-month lifestyle modification program, according to a study published in the Journal of the American Association of Nurse Practitioners.

Patients aged 18 to 80 years with a diagnosis of prediabetes, a body mass index of ≥25, and a glycated hemoglobin (HbA1c) between 5.7% and 6.4% were included in the study. A total of 24 patients attended prediabetes sessions and the 3-month ­follow-up appointment, with the goal of ≥2.5% loss of body weight within 3 months. Participants were encouraged to perform

at least 150 minutes of moderate- to high-intensity physical activity every week. Eating habits and physical activity levels were evaluated using the Rapid Eating Assessment for Patients (REAP) and the REAP-Physical Activity (REAP-PA) tools.

A total of 14 of the 24 patients (58%) lost ≥2.5% of baseline weight; 4 patients showed an increase in weight. There was not a statistically significant change in HbA1c levels during the study. The pre-intervention HbA1c mean was 6.0% compared with a post-intervention mean of 5.9%. However, there were significant changes in REAP and REAP-PA scores: mean preintervention REAP score was 55.5 compared with 45.0 postintervention and mean pre-intervention REAP-PA was 2.2 compared with 1.6 post-intervention.

6 THE CLINICAL ADVISOR • MAY 2020 • www.ClinicalAdvisor.com

Newsline Smartphone Use and Headache: What’s the Link?

INCREASED SMARTPHONE use was found to be associated with an increased requirement of acute medication and less relief from medication for primary headache, but not an increase in frequency or duration of headaches, according to research published in Neurology Clinical Practice.

“Although the course of headache, frequency of episodes, and the pain scores were similar in [non-smartphone users] and [smartphone users; SU], the SU group had higher frequency of medications for acute attacks with poor response to analgesics,” the authors wrote.

The study was conducted between June 2017 and December 2018 in India, and included patients aged ≥14 years with primary headache. Patients were divided into non-smartphone users (NSUs; either did not use a cell phone or non-smartphone user) and SUs.The primary objective was to determine the

association between mobile phone usage and new-onset headache or increases in severity of primary headache.

A total of 400 patients were included in the study (194 NSU; 206 SU). Of the 194 NSU patients, 76 were not using any phone and 130 were using nonsmartphones. The majority of patients

the course of headache was similar in both groups (worsened: NSUs, 71.6% vs SUs, 71.8%).

Patients in the NSU group had similar duration of episodes compared with SU patients, as well as the number of episodes of headache per month (NSU, 7.3 vs SU, 7.1). Patients in the SU group

Smartphone users had more auras and poorer response to treatment, but headache course, frequency of episodes, and pain scores were similar to non-smartphone users. with headache were women (269/400); however, more men were in the SU group compared with the NSU group (39.3% vs 25.8%).

The most common headache type was migraine, followed by chronic migraine and chronic tension-type headache. More patients in the SU group reported more auras compared with the NSU group (17.5% vs 7.7%), but

took a higher number of pills for acute treatment with a median pill intake of 8 per month compared with 5 per month in the NSU group. A higher proportion of patients in the NSU group had relief with acute medications compared with the SU group, but the proportions of patients taking prophylactic medication and the median duration of prophylaxis were similar in both groups.

Baseline Colonoscopy Findings Key for Identifying Future Outcomes

© SCIENCE PHOTO LIBRARY / GETTY IMAGES

BASELINE RESULTS FROM screening colonoscopy have been found to be highly predictive of 10-year outcomes, including identifying people at high risk of developing advanced

Baseline colonoscopy identified patients at risk of developing cancer within 10 years.

neoplasia, according to a study published in Gastroenterology.

Data were collected from the Department of Veterans Affairs Cooperative Studies Program, which screened 3121 asymptomatic individuals aged 50 to 75 years who underwent a screening colonoscopy from 1994 through 1997 at 13 Veterans Affairs medical centers.

Through 10 years of follow-up, there were 146 individuals among all baseline colonoscopy groups found to have at least 1 incident of advanced neoplasia.

The cumulative 10-year incidence of advanced neoplasia was highest among those with baseline colorectal cancer (CRC; 43.7%), followed by those with baseline advanced adenoma (21.9%).

8 THE CLINICAL ADVISOR • MAY 2020 • www.ClinicalAdvisor.com

The cumulative 10-year incidence of advanced neoplasia was 6.3% and 4.1% for patients with 1 to 2 small adenomas (<1 cm) and no neoplasia at baseline, respectively.

After adjusting for prior surveillance, the risk for advanced neoplasia at each subsequent examination was not significantly increased in veterans with 1 or 2 small adenomas at baseline compared with veterans with no baseline neoplasia.

“Given the strong association of baseline findings with findings at subsequent examinations and the limited impact of known clinical factors, we hypothesize that genomic analysis may further clarify risk for CRC beyond the results of the baseline colonoscopy,” the authors concluded. ■

FEATURE: NIKKI KEAN

AANP, AAPA Presidents Discuss Legislative Wins, Challenges During COVID Passage of the COVID-19 stimulus package has removed practice barriers for NPs and PAs at both the state and federal levels.

S

ophia L. Thomas, DNP, APRN, FNPBC, PPCNP-BC, FNAP, FAANP, president of the American Association of Nurse Practitioners, and David E. Mittman, PA, DFAAPA, president and chair of the American Academy of Physician Assistants board of directors, spoke with The Clinical Advisor about how their associations have stepped up to address the novel coronavirus (COVID-19) pandemic in the United States.

© MISHA FRIEDMAN / STRINGER / GETTY IMAGES

The Clinical Advisor: How has the federal passage of the COVID-19 stimulus package affected how nurse practitioners (NPs) and physician assistants (PAs) are able to serve their patients amid the ongoing pandemic?

NPs and PAs are at the frontlines of the COVID-19 pandemic.

PA Mittman: Right now, our top priority is empowering the PA workforce in its response to COVID-19. That objective is driving all our efforts to remove barriers to patient care on both the state and federal levels through modernizing PA laws and regulations, and in supporting PAs so they can provide optimal care to their patients.

On March 28, the president signed the Coronavirus Aid, Relief, and Economic Security Act or the CARES Act (H.R. 748) into law.

AAPA and AANP were successful in securing the Home Health Care Planning Improvement Act (S. 296/H.R. 2150) as an inclusion in this emergency legislation. Including the Home www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • MAY 2020 9

AANP AND AAPA PRESIDENTS TACKLE COVID-19

Four thousand NPs stepped up to serve on the frontlines in New York City as part of the response to combat the spread of COVID-19.

Health Care Planning Improvement Act in the CARES Act permanently authorizes PAs and NPs to order home health care services for Medicare patients (in a manner consistent with state law). As health care facilities gird for an influx of patients with COVID-19, capacity will become a critical issue, and this authorization will ease some of that burden.

Dr Thomas: The lack of access to care has been an ongoing issue. At the start of the pandemic, AANP requested that the National Governors Association work with states to address the need for a surge in health care providers by encouraging states to expand emergency health care workforce declarations.

In 22 states, Washington, DC, 2 US territories, the Veterans Health Administration, and the Indian Health Service, NPs are authorized to directly provide these services. In the remaining jurisdictions, outdated regulation needlessly bottlenecks the workforce by making it illegal for NPs to provide these services unless they maintain a collaborative or supervisory contract with a physician.

Since the outbreak of the pandemic, several governors have issued emergency declarations that have waived restrictions and allowed NPs to practice to the full extent of their education and training. The first governor to do so was Andrew Cuomo of NY, who immediately had 4000 NPs relocate to serve on the frontline as part of the robust response to combat the spread of COVID-19.

We hope these waivers will be looked at again after the crisis, and that NPs will have the authority to practice in many of these states without collaborative or supervisory contracts with a physician.

The Clinical Advisor:What have been the biggest barriers to states adopting new legislation regarding PAs? PA Mittman: I’d say understanding what PAs do and who we are is a big challenge. That’s something we hear from PAs at the state level. Unfortunately, we continue to deal with the misperception that PAs are literally “assistants” to physicians.

Fifty years ago, we were more of an experiment, but were never an assistant, even in those years.Today, our title confuses legislators, patients, and all others. It is just not an accurate way to describe our profession.

PAs practice medicine in all specialties with great autonomy, and often serve as a patient’s principal health care provider.

Many PAs manage their own panels of patients. Unfortunately, physician organizations have not always recognized the breadth of clinical services that PAs provide, in part because they also misunderstand our title, education, and clinical training.

The Clinical Advisor: The COVID-19 pandemic has again shone a spotlight on health care disparities in the United States. How has your organization helped its members address this issue?

PA Mittman: One of AAPA’s core values is eliminating disparities and barriers to quality health, and AAPA’s policy speaks directly to this issue in numerous ways. That vision and those policies guide our everyday work. For example, a lot of our AAPA CME addresses disparities. That way, we know PAs are being reminded that it’s part of our job as a profession to work toward eliminating health disparities.

Most recently, AAPA staff and other PAs assessed a quality improvement initiative designed to highlight awareness of health disparities and improve health care practices among participants. This work resulted in an article published in the Journal of the American Academy of PAs (“Improving health disparities in PA practices:A quality improvement initiative”).

Dr Thomas: The health care system in this country is not working to address these health disparities. In New Orleans where I practice, approximately 70% of the deaths from COVID-19 have been in the black community, which has the highest level of patients with high blood pressure, kidney disease, and diabetes. We know that patients with comorbidities have more complications with COVID-19, so the health disparities are really being highlighted by this crisis.

David E. Mittman, PA

Sophia L. Thomas, DNP

10 THE CLINICAL ADVISOR • MONTH 20xx • www.ClinicalAdvisor.com

Continues on page 12

AANP AND AAPA PRESIDENTS TACKLE COVID-19

“Although there are some barriers … PAs have proven beyond a shadow of a doubt that they are more than ready to jump in during an emergency.”

We are going to have to do more on national and state levels to have an effect in these underserved communities to improve overall health. Louisiana is one of the least healthy states, and we have a large black population and people of Hispanic descent who are not faring well during COVID-19 because of these health disparities. It is time now to fight these issues head on, and to have health care providers working with these populations, who understand the culture, and who can play a role in helping to devise, design, and develop programs that will actually work at the primary care level.

The Clinical Advisor: What has the COVID-19 pandemic taught you about our readiness for an emergency?

PA Mittman: The past few weeks have been extremely difficult for a lot of people, but particularly for PAs on the frontlines, which in some way has become almost all of us. I have been so inspired by PAs...by their overwhelming desire to respond to the COVID-19 pandemic.

So, although there are some barriers we’re working to address at the state and federal levels, PAs have proven beyond a shadow of a doubt that they are more than ready to jump in during an emergency. PAs are trained as medical generalists, so they are more than capable of testing, diagnosing, and treating patients with COVID-19. I’ve also seen so many PAs working together to figure out how they can do more, sharing resources, and providing moral support for each other.

Unfortunately, in many states and the VA, PAs are required to have a supervisory or collaborative agreement with a physician to practice. These agreements complicate where and how PAs may practice, sometimes preventing them from stepping in where they’re needed most. Just 6 states (Louisiana, Maine, Michigan, New Jersey, NewYork, and Tennessee) have recently waved physician supervision requirements in executive orders related to COVID-19. And although 13 states have previously removed physician supervision requirements for PAs during emergencies or disasters, that still leaves the majority of states without this crucial provision.

To mobilize the full PA workforce, more states need to waive these supervision or collaboration requirements, and they need to do it immediately. AAPA is calling on all governors to include language in executive orders waiving physician supervision or collaboration requirements during a declared public health emergency or disaster. There is no time to lose.

The PA community is incredibly strong and brave, and they all know that their job is to do whatever they can to care for

the patients who need them. We will continue to do that.We will continue to be a significant factor in healing our fellow citizens. It’s in our DNA. It’s who we are and what we do.

To help PAs through the COVID-19 pandemic, we’ve created a resources center that we’re updating daily to ensure that PAs have access to all of the latest information from reliable sources, such as the Centers for Disease Control and Prevention and the National Institutes of Health, as well as through our daily clinical e-newsletter.

Dr Thomas: We are still hearing reports from our members about the basic lack of personal protective equipment (PPEs) in certain parts of the country, the lack of the ability to test for the virus, and that many NPs have been furloughed—the census is down, patients are not coming to the office, and many offices have switched to telehealth.

The Trump administration has already taken important steps to lift federal barriers within Medicare and Medicaid so that NPs can combat this crisis. Now, it’s critical that states answer the call to suspend state barriers to care so that NPs can meet the urgent needs of patients and address this challenge head on.

Addressing our nation’s needs will require all hands on deck.

Given the nationwide scale of COVID-19 cases, states will not be able to rely on neighboring states to send health care providers to meet the demand. Authorizing recent retirees to return to the workforce offers a way to bolster our reserves and utilize the qualified clinicians already in our communities.

The legislation passed by the Senate and House, and now signed into law by the president, includes a provision authorizing NPs to certify and recertify home health care services for Medicare patients. Once implemented, this will ensure that millions of seniors are able to receive critical health care services at home during this crucial time. Not only will the new law help make certain seniors have timely access to home health care services, it will also help ensure they are less likely to be exposed to COVID-19.

Lifting state restrictions that prevent NPs from providing home health care will not only improve care for seniors and limit the spread of COVID-19 but will also maximize the availability of hospital beds for those with COVID-19.

But in general, the census and flow has not been what it was before COVID-19. In states that have emergency declarations, the furloughed NPs have been able to go to other areas where they are needed. But in states without these declarations, the NPs’ hands are tied. ■

12 THE CLINICAL ADVISOR • MAY 2020 • www.ClinicalAdvisor.com

FEATURE: KATHERINE SALTER HUFF, MPAS, PA-C; ALICIA ELAM, PHARMD

Insights Into Diagnosis and Treatment of Amyotrophic Lateral Sclerosis A diagnosis of amyotrophic lateral sclerosis can be overlooked by clinicians unfamiliar with the various signs of the disease.

A

myotrophic lateral sclerosis (ALS) is a progressive motor neuron disease involving muscle weakness and wasting. The prevalence of ALS has been estimated at 5.2 cases per 100,000 population and affects approximately 16,500 individuals in the United States.1 ALS is usually diagnosed in patients between the ages of 40 and 70 years, although diagnosis can also occur as early as age 20 and in those aged >80 years.2 ALS is more common in men until the seventh decade, after which women and men are equally affected by the disease.2 ALS is categorized into 2 types: sporadic and familial. Sporadic ALS comprises 90% to 95% of cases without a known genetic or environmental cause.3 Potential causes of sporadic ALS include excess glutamate production, viral infections, and inflammatory processes.4 Alternatively, familial ALS has an autosomal-dominant inheritance pattern and presents similarly to sporadic ALS.2 Two genetic mutations are known to cause familial ALS: C9orf72 gene mutation, which is located on the ninth chromosome, and superoxide dismutase type 1 (SOD1) gene mutation on the 22nd chromosome.5-7

© MOLLY BORMAN

History and Physical Findings ALS is purely a motor neuron disease; sensory neurons are not affected.

ALS is purely a motor neuron disease; sensory neurons are not affected.4 A diagnosis of ALS can be overlooked by clinicians unfamiliar with the various signs of the disease. Although a number of diseases affect either the upper motor neurons www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • MAY 2020 13

DIAGNOSIS AND TREATMENT OF ALS

(ie, primary lateral sclerosis) or the lower motor neurons (ie, progressive bulbar palsy), ALS characteristically affects both upper and lower motor neurons simultaneously, which is a unique trait of this disease.2,4 The majority of patients with ALS present with asymmetric muscle weakness and wasting in an upper limb that progresses to a lower limb.8-10 Upper motor neuron lesions can be identified during physical examination by observing the Babinski sign, slowed rapid alternating movements, and increased deep tendon reflexes. Upper motor neuron lesion complaints include difficulty picking up delicate objects or fastening buttons, tripping, stumbling, and difficulty coordinating leg movements.11 Lower motor neuron complaints usually involve upper and lower extremity muscle atrophy, weakness, twitching, and cramping.2 Lower motor neuron lesions contribute to difficulty squatting, foot drop, waddling gate, muscle atrophy, and fasciculations.2 Signs and symptoms of ALS are reviewed in Table 1.2 Approximately 30% of patients with ALS present with bulbar signs and symptoms (Table 2).8-10 Dysphagia, excessive salivation, and exaggerated emotional responses are types of upper and lower motor neuron bulbar symptoms experienced by patients with ALS.4 Excess salivation and drooling are directly related to a patient’s difficulty swallowing saliva and liquids; they often experience less difficulty swallowing solids.2 Difficult articulation, hoarseness, and diminished volume are speech defects that cause communication challenges for patients with ALS and may eventually progress to the inability to speak.2,4 Patients with ALS also tend to experience pseudobulbar affect, or brief episodes of exaggerated emotional responses consisting of laughter or crying that emerge rapidly, without warning.2,12 During physical examination, bulbar symptoms present with facial weakness and atrophy, slow tongue movements, and poor soft palate and uvula rise upon phonation.

As ALS progresses, respiratory muscle involvement increases resulting in respiratory failure, which is the most common cause of death related to ALS.13,14 Signs of respiratory distress include tachypnea, use of accessory respiratory muscles, and abdominal paradox, while symptoms of respiratory distress include dyspnea, weak cough, and sleep-disordered breathing.2 Though unlikely, patients may initially present with the previously stated respiratory symptoms or axial symptoms (ie, difficulty holding head upright or maintaining an upright seated position, imbalance, and abdominal protuberance) due to weak abdominal muscles.2 Extraocular muscle movements, bladder and bowel movements, or sensory function are not affected by ALS.4 Additionally, patients with ALS do not experience skin integrity issues; however, they may develop pressure ulcers from immobility.4

Workup

The El Escorial World Federation of Neurology diagnostic criteria are considered the clinical gold standard for diagnosing ALS.15 The criteria state that an ALS diagnosis requires the absence of other disease processes that could be responsible for the clinical signs and the presence of 3 benchmarks: lower motor neuron degeneration, upper motor neuron degeneration, and symptoms that progressively spread either within one body region or from one region to another.15 The Awaji criteria16 use electrodiagnostic studies to allow an earlier diagnosis of ALS and to decrease the number of Continues on page 18

TABLE 1. Physical Signs and Symptoms of ALS2 Signs

Symptoms

UPPER MOTOR NEURON • Positive Babinski sign • Increased deep tendon reflexes • Slow or rapid alternating movements

• Lack of coordination with movements • Poor balance • Stiffness with upper and lower extremity movement

LOWER MOTOR NEURON • Difficulty squatting and rising from chair • Foot drop • Muscle atrophy in upper and lower extremities • Waddling gait • Fasciculations

• Muscle cramps • Fasciculations • Weakness in upper and lower extremities

TABLE 2. Common ALS Bulbar Signs and Symptoms2 Signs

Symptoms

UPPER MOTOR NEURON • Facial weakness • Poor soft palate rise upon phonation • Slow tongue movements

• Sialorrhea • Dysphagia • Dysarthria • Pseudobulbar affect • Jaw stiffness • Spontaneous jaw clenching • Laryngospasm

LOWER MOTOR NEURON • Facial weakness • Muscle atrophy • Poor soft palate rise upon phonation • Tongue weakness

14 THE CLINICAL ADVISOR • MAY 2020 • www.ClinicalAdvisor.com

• Dysarthria • Dysphagia • Hoarseness • Incomplete eye closure • Poor lip closure

DIAGNOSIS AND TREATMENT OF ALS

The El Escorial World Federation of Neurology diagnostic criteria, which was revised in 2000, is the clinical gold standard for diagnosing ALS. patients who fail to meet the El Escorial criteria.15-17 Since publication of the Awaji criteria, electromyography (EMG) and nerve conduction studies are routinely employed by providers for evaluation of ALS.16,17 EMG studies document the presence of denervation: fibrillations and positive sharp waves, as well as large-amplitude, long-duration, and complex motor unit action potentials.16,17 Nerve conduction studies assess the number of viable motor axons innervating the muscles of the hands and feet and can identify decreases prior to patients experiencing weakness.This information can assist providers in gauging areas of progressing weakness.2 Both studies prove to be most beneficial when bolstering limited clinical findings to support a diagnosis of ALS.16

Treatment

Treatment options for ALS are limited, and currently there are no pharmacologic cures for the disease. The US Food and Drug Administration (FDA) has approved 3 drugs for the treatment of ALS: riluzole, edaravone, and a combination of dextromethorphan and quinidine.The approval of riluzole, an oral glutamate blocker, was based on its positive impact on survival rates for patients with ALS.4,18 Along with inhibiting glutamate release, riluzole deactivates the voltage-dependent sodium channels and interferes with cellular events to inhibit binding at excitatory amino acid receptors.18 Early diagnosis of ALS is critical when considering the initiation of riluzole therapy and its role in decelerating the inevitable progression of ALS symptoms.

CASE PRESENTATION

Misdiagnosis of Parkinson-Plus Syndrome in a Patient With ALS Henry P, a 78-year-old white man, presents for evaluation because he recently fell while crossing the street. He states that he lost his balance on a windy day but is not sure what caused him to fall. Mr P states he has been having difficulty lifting his grapefruit spoon with his left hand in the morning.

He also complains that he has noticed his signature has gotten smaller over the last year and that he struggles to button and unbutton his dress shirt.

Mr P’s vital signs are as follows: temperature, 97.8°F; heart rate, 65 beats/min; respiratory rate, 14 beats/min; and blood pressure, 115/80 mm Hg. Mr P’s physical examination is unremarkable except for minor fasciculations in his upper extremities and positive Babinski sign during the musculoskeletal examination. Mr P does not have a significant medical or family history, and he has not traveled recently. He denies smoking and recreational drug use, and he states that he exercises regularly and eats a clean diet.

Mr P is diagnosed with Parkinson-plus syndrome and corticobasal ganglionic degeneration based on the results of electromyography (EMG), which does not show denervation.

Three Years Later

At the time of his initial presentation, Mr P was experiencing balance issues, asymmetric upper extremity weakness, difficulty with fine motor movements, fasciculations, and hyperactive superficial reflexes. Even though these symptoms may be indistinct separately, together they suggest the onset of ALS

and should have been further investigated by his primary care provider.

Falling on a windy day and a positive Babinski sign suggest balance deficiencies and lack of coordination, while difficulty buttoning his shirt and smaller handwriting demonstrate stiffness with fine motor movements of the upper extremities; all of these findings are suggestive of an upper motor neuron lesion. Fasciculations in the upper extremities and Mr P’s complaint of difficulty lifting a grapefruit spoon with one hand — indicative of asymmetric upper extremity weakness — suggest a lower motor neuron lesion.Therefore, signs of both upper and lower motor neuron lesions were present at Mr P’s initial appointment. Although these symptoms could be reflective of the patient’s advanced age, Mr P should have been evaluated for progression of these symptoms with periodical physical examinations, EMGs, and nerve conduction studies to either rule out or confirm a diagnosis of ALS. By the time Mr P was diagnosed with ALS, which was 3 years after his initial presentation, he had lost his ability to speak or move his left arm, and swallowing had become more difficult.

Because of his delayed diagnosis, Mr P received limited benefit from appropriate pharmacologic and therapeutic interventions, including the ALS clinic.

At the end stages of his disease, Mr P decided to halt nutrition intake and only continue comfort measures for treatment. He died 10 months after being diagnosed with ALS and 4 years after receiving the initial neurodegenerative diagnosis of corticobasal ganglionic degeneration.

18 THE CLINICAL ADVISOR • MAY 2020 • www.ClinicalAdvisor.com

Treatment options for ALS are limited; currently there are no pharmacologic cures and treatments are aimed at slowing disease progression.

Adverse events associated with riluzole include dizziness, fatigue, abdominal pain, diarrhea, headaches, and muscle weakness.19 Riluzole can cause an increase in liver enzymes; therefore, patients who are prescribed riluzole should undergo monthly liver function tests for the first 3 months of therapy, and then quarterly from that point forward.19 Patients being treated with riluzole require monitoring for neutropenia and interstitial lung disease, which are 2 additional side effects of the drug.20 Because the drug’s absorption is decreased by meals with high fat content, patients must take riluzole at least 1 hour before or 2 hours after a meal.18 The FDA approved edaravone as an adjunct therapy to riluzole with the intention to reduce oxidative stress and slow functional deterioration in patients with ALS.21,22 Edaravone 60 mg is administered via intravenous infusion over 60 ­minutes daily for 14 days, followed by a 14-day infusion-free period.22 Adverse effects associated with edaravone include headaches, gait disturbances, and injection-site contusions.21 A third FDA-approved treatment is a combination of dextromethorphan and quinidine (Nuedexta®). The combination is indicated for the treatment of pseudobulbar affect in patients with ALS.23 As the number of prescribed pharmacologic treatments specifically targeting ALS is limited, over-the-counter medications are often employed to relieve secondary complications including pain, acid reflux, and insomnia.

with disease progression; therefore, primary care providers should collaborate with all specialists involved in the care of the ALS patient to ensure all clinicians are fully informed about the patient’s care plan.

Prognosis

The outlook for patients with ALS is poor; life expectancy for most patients is 2 to 5 years from diagnosis, and patients typically die from respiratory failure.1,2 A subset of patients with ALS have been reported to experience improved survival rates: when the age of onset is 40 years, the mean duration of disease is longer, 8.2 ± 5.0 years compared with 2.6 ± 1.4 years for patients aged 61 to 70 years (P > .001). Contributors to these long-term survival rates include the rationale that younger age at onset translates to living longer with the disease.25 In conclusion, patients with ALS require appropriate education regarding their diagnosis and specific prognosis. Every patient’s experience with ALS is unique, and providers should ensure their patients are supported both medically and emotionally through each stage of this devastating disease. ■ Katherine Salter Huff, MPAS, PA-C, is a physician assistant at Blue Ridge Orthopedics in Anderson, South Carolina, and Alicia Elam, PharmD, is associate professor in the Physician Assistant Department at Augusta University in Augusta, Georgia.

References

Multidisciplinary Approach

1. Mehta P, Kaye W, Raymond J, et al. Prevalence of amyotrophic ­lateral sclerosis

Patients with ALS benefit from a multidisciplinary approach to care. Physical therapists, respiratory therapists, occupational therapists, psychiatrists, and dietitians improve patients’ quality of life.24 Respiratory therapists use noninvasive positive pressure ventilation to assist patients who are experiencing respiratory distress.24 Physical therapists engage to maintain muscle function, and occupational therapists aid in easing the transition as patients experience worsening symptoms with disease progression.24 Many patients with ALS suffer from depression and anxiety.

Patients may benefit from speaking with a psychiatrist, psychologist, and chaplain throughout the course of their disease.24 As swallowing becomes more of a challenge, dietitians can educate patients about foods that are easier to swallow as well as how to thicken foods. However, most patients will eventually need a percutaneous endoscopic gastrostomy tube for nutrition.2,11 Pharmacologic and therapeutic regimens for ALS are individualized according to each patient and constantly evolve

— United States, 2015. MMWR Morb Mortal Wkly Rep. 2018;67(46):1285-1289.

2. For people with ALS and Caregivers. ALS Association website. http://www.alsa.org/als-care/. Accessed April 7, 2020.

3. Zarei S, Carr K, Reiley L, et al. A comprehensive review of amyotrophic lateral sclerosis. Surg Neurol Int. 2015;6:171.

4. Motor neuron diseases fact sheet. National Institute of Neurological Disorders and Stroke website. https://www.ninds.nih.gov/Disorders/PatientCaregiver-Education/Fact-Sheets/Motor-Neuron-Diseases-Fact-Sheet.

Updated March 16, 2020. Accessed April 7, 2020.

5. Morita M, Al-Chalabi A, Andersen PM, et al. A locus on chromosome 9p confers susceptibility to ALS and frontotemporal dementia. Neurology.

2006;66(6):839-844.

6. Renton AE, Majounie E, Waite A, et al. A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron.

2011;72(2):257-268.

7. Rosen DR, Siddique T, Patterson D, et al. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis.

Nature. 1993;362:59-62.

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • MAY 2020 19

DIAGNOSIS AND TREATMENT OF ALS

8. Shellikeri S, Karthikeyan V, Martino R, et al.The neuropathological ­signature of

16. de Carvalho M, Dengler R, Eisen A, et al. Electrodiagnostic criteria for

bulbar-onset ALS: a systematic review. Neurosci Biobehav Rev. 2017;75:378-392.

diagnosis of ALS. Clin Neurophysiol. 2008;119(3):497-503.

9. McConnell T. The Nature of Disease: Pathology for the Health Professions.

17. Costa J, Swash M, de Carvalho M. Awaji criteria for the diagnosis of

2nd ed. Lippincott Williams and Wilkins; 2014.

amyotrophic lateral sclerosis. Arch Neurol. 2012;69(11):1410-1416.

10. Papadakis M, McPhee S, Rabow M. Current Medical Diagnosis & Treatment

18. Hinchcliffe M, Smith A. Riluzole: real-world evidence supports significant

2017. 56th ed. McGraw Hill Education; 2017.

extension of median survival times in patients with amyotrophic lateral

11. Walling A. Amyotrophic lateral sclerosis: Lou Gehrig’s disease. Am Fam

sclerosis. Degener Neurol Neuromuscul Dis. 2017;7:61-70.

Physician. 1999;59(6):1489-1496.

19. Roch-Torreilles I, Camu W, Hillaire-Buys D. Adverse effects of ­riluzole

12. Rosen HJ, Cummings J. A real reason for patients with pseudobulbar affect

(Rilutek) in the treatment of amyotrophic lateral sclerosis. Therapie.

to smile. Ann Neurol. 2007;61(2):92-96.

2000;55(2):303-312.

13. Gilani A, Hinn A, Jacobson PL. Management of respiratory failure in ALS.

20. Weber G, Bitterman H. Riluzole-induced neutropenia. Neurology.

Palliative Care Network of Wisconsin website. https://www.mypcnow.org/

2004;62(9):1648.

fast-fact/manage ment-of-respiratory-failure-in-als/. Updated May 2015.

21. Radicava [package insert]. Mitsubishi Tanabe Pharma Corporation; 2018

Accessed April 7, 2020.

22. FDA approves drug to treat ALS. US Food & Drug Administration

14. Shoesmith CL, Findlater K, Rowe A, Strong MJ. Prognosis of amyotrophic

website. https://www.fda.gov/news-events/press-announcements/fda-

lateral sclerosis with respiratory onset. J Neurol Neurosurg Psychiatry. 2007;

approves-drug-treat-als. Published May 5, 2017. Accessed April 7, 2020.

78(6):629-631.

23. Nuedexta [package insert]. Avanir Pharmaceuticals, Inc; 2019.

15. Brooks BR, Miller RG, Swash M, Munsat TL; for the World Federation

24. Ng L, Khan F. Multidisciplinary rehabilitation in amyotrophic lateral

of Neurology Research Group on Motor Neuron Diseases. El Escorial

sclerosis. In: Amyotrophic Lateral Sclerosis. InTech-Open Access; 2012.

revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis.

25. Eisen A, Schulzer M, MacNeil M, Pant B, Mak E. Duration of amyotrophic

Amyotroph Lateral Scler Other Motor Neuron Disord. 2000;1(5):293-299.

lateral sclerosis is age dependent. Muscle Nerve. 1993;16(1):27-32.

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20 THE CLINICAL ADVISOR • MAY 2020 • www.ClinicalAdvisor.com

FEATURE: JENNIFER L. DELTOUR, MSN, FNP-C, BC-ADM

Latent Autoimmune Diabetes in Adults: A Less Common Form of Disease Primary care providers should be aware of less common forms of diabetes and features that would prompt suspicion of an unusual diagnosis.

© ARIEL SKELLEY / GETTY IMAGES

A

LADA patients lack metabolic symptoms typical in patients with type 2 diabetes.

41-year-old woman presents to her primary care provider complaining of fatigue and an unintentional 7-lb weight loss occurring over 2 weeks. The patient denies recent travel, changes in her diet, or the addition of any new supplements or over-the-counter medications. She reports increased thirst and hunger but no fever, chills, or night sweats. She has experienced no changes in her bowel or bladder habits, nor has she had any nausea, vomiting, or abdominal pain. She also reports no palpitations or tachycardia, and no psychological symptoms, such as depression or anxiety.

The patient has a history of autoimmune thyroid disease (Hashimoto thyroiditis) and seasonal allergies. She reports recent uveitis of her right eye that resolved with treatment. She has no surgical history. Her medications include levothyroxine 112 mcg/d and loratadine 10 mg as needed. She is up to date with recommended health maintenance and annual wellness checks. Her family history is significant for Graves disease in her maternal grandfather and Hashimoto thyroiditis in her mother and 2 maternal aunts. She has no family history of diabetes, cardiovascular disease, or cancer.

Physical examination reveals a healthy woman in no apparent distress, with moist mucous membranes, no palpable thyroid mass or nodule, a regular heart rate and rhythm, and clear lung sounds. Her abdomen is soft and nontender, with positive bowel sounds in all quadrants. Laboratory tests Continues on page 24

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • MAY 2020 21

LATENT AUTOIMMUNE DIABETES IN ADULTS

indicate the patient is biochemically euthyroid, with unremarkable complete blood cell count and comprehensive metabolic panel except for increased nonfasting glucose level at 324 mg/dL and increased glycated hemoglobin (HbA1c) at 12.1% (Table 1).

The patient is diagnosed with type 2 diabetes (T2D) and started on metformin 500 mg twice a day, with the dosage increase to 1000 mg twice a day after 1 week, and insulin glargine 20 units every evening, titrating up by 2 units every other night to a goal fasting blood sugar level between 80 and 130 mg/dL. She is advised about lifestyle modifications including a healthy diet and exercise regimen, provided with a glucometer and logbook, and asked to check her fasting blood glucose level daily.

She returns to the clinic 4 weeks later on her current dose of insulin glargine (22 units) and reports documenting fasting blood glucose levels between 70 to 150 mg/dL. She notes that she gained 3 lb and her fatigue, appetite, and thirst decreased.

The patient reports that she does not feel comfortable with her diagnosis and requests referral to an endocrinologist.

The patient undergoes evaluation by an endocrinologist, who orders a pancreatic islet cell autoantibody panel and TABLE 1. Summary of Patient’s Vital Signs and Abnormal Laboratory Tests Vital Signs

Result

Height

5’8”

Weight, kg

71.2

BMI, kg/m2

23

Waist circumference

29”

Temperature, °C

37

Blood pressure, mm Hg

118/72

Heart rate, beats/min

89

Respiratory rate, breaths/min

16

Laboratory Test

Results

Thyroid-stimulating hormone, mIU/L

2.86

T4, ng/dL

1.0

Non-fasting glucose level, mg/dL

324

Hemoglobin A1C, %

12.1

BMI, body mass index; T4, free thyroxine

C-peptide level. Test results are reported as positive for glutamic acid decarboxylase autoantibody (GAD65) at a level of 0.06 nmol/L (normal is <0.02 nmol/L), and the patient is determined to have a low-normal fasting C-peptide level of 1.0 ng/mL (range, 0.8-3.6 ng/mL). Based on these results, she is diagnosed with latent autoimmune diabetes in adults (LADA), a form of type 1 diabetes (T1D).

Metformin is discontinued, and she is started on a glucagonlike peptide-1 (GLP-1) receptor agonist and continued on insulin glargine 18 units nightly.Three months after the patient’s initial diagnosis, her HbA1c level decreased to 5.8%. Due to some preserved β-cell function, she is able to use only basal insulin and the GLP-1 receptor agonist for the next 8 months, at which time she is switched to intensive basal-bolus therapy via an insulin pump when her HbA1c increases to 7.8%.

With this regimen, she has kept her HbA1c in the 6.5% to 7.8 % range for the past 3 years and does not have any diabetes complications.

Latent Autoimmune Diabetes in Adults

The most prevalent type of diabetes is T2D, which accounts for approximately 90% to 95% of cases.1 Therefore, it is easy to suppose that middle-aged and older adults who present with new-onset diabetes have T2D. However, multiple recent studies indicate that between 5% and 10% of adults diagnosed with T2D may be misdiagnosed and may have LADA.2-5 LADA is considered a subset of T1D. In both T1D and LADA, the immune system attacks the insulin-producing β cells of the pancreas. However, in LADA, the disease progression is much slower than that of traditional T1D.5-8 One or more pancreatic autoantibodies will be positive and C-peptide typically will be low in patients with LADA.5 Individuals with LADA also tend to be slimmer than patients with T2D, although patients with LADA can be overweight or obese.

Patients with LADA have fewer metabolic features such as dysli­pid­emia and increased waist circumference and body mass index (BMI) than patients with T2D.3-5,8 Family or personal history of autoimmune diseases should prompt suspicion for LADA because the condition has a strong genetic component.5 Autoimmune thyroid disease (Hashimoto thyroiditis and Graves disease), pernicious anemia, and Addison disease are the most frequently co-occurring autoimmune diseases in patients with LADA.6,9 Like T2D, LADA usually occurs in adults, typically developing in those >30 years of age. As often seen with patients with T2D, patients with newly diagnosed LADA initially may not require insulin; however, with increase in β-cell failure, insulin therapy usually becomes necessary. Family history of diabetes does not appear to play as big a role in LADA and may or may not be present.5,10

24 THE CLINICAL ADVISOR • MAY 2020 • www.ClinicalAdvisor.com

LADA Diagnosis

Primary care providers often are the first to diagnose and treat patients with new-onset diabetes.They can test for type when the diagnosis is uncertain. One or more positive autoantibodies confers the diagnosis of autoimmune diabetes.5,6 These tests often can be ordered together in an autoimmune diabetes panel.

Autoantibodies include islet cell cytoplasmic autoantibodies, zinc transporter 8, insulin autoantibodies, insulinoma-associated-2 autoantibodies, and GAD65, which is the most prevalent of the autoantibodies in those with autoimmune diabetes.5 C-peptide, or connecting peptide, is produced in equal amounts with insulin in the β cell and is cleaved from proinsulin in the final step before insulin release.11 Because C-peptide is degraded more slowly than insulin and is not skewed by exogenous insulin, the C-peptide level is an excellent indicator of β-cell function.5,6,11 In patients with T2D, C-peptide level is typically increased because this is a disease of insulin resistance and subsequent overproduction of insulin. In patients with LADA or T1D, C-peptide level will be low to undetectable.5,6,11 Clues in the Case Presentation

Reviewing the patient’s presentation along with diabetes characteristics (Table 2), clues exist that would prompt the practitioner to suspect that this was not a typical case of T2D.The patient

was of normal weight and presented acutely with classic symptoms of hyperglycemia more commonly seen in autoimmune diabetes: weight loss, polyphagia, and polydipsia. She had no family history of diabetes, but she did have a family and personal history of autoimmune thyroid disease. The patient did not have any features of metabolic syndrome, which is prevalent in T2D; hypertension and dyslipidemia were absent, and her waist circumference was in a healthy range.Additionally, her HbA1c was markedly elevated, which is a more common initial presentation for patients with T1D or LADA than for those with T2D.5 Implications for the Primary Care Provider

Primary care providers should be aware of less common forms of diabetes and features that would prompt suspicion of an unusual diagnosis. If the patient does not seem to fit into a typical type of diabetes, then further investigation is imperative.12 (See sidebar on MODY, page 26, another rare type of diabetes).

Knowing the type of diabetes helps guide pharmacologic therapy and aids in the delay or prevention of diabetes complications. For patients with LADA, basal/bolus insulin is considered the mainstay of treatment, although it may not be needed initially.13 Recent evidence suggests that medications such as dipeptidyl peptidase-4 (DPP-4) inhibitors and/or Continues on page 28

TABLE 2. Characteristic Differences in Types of Diabetes2-7,9,10,11,17 Latent Autoimmune Diabetes of Adults

Type 1 Diabetes

Type 2 Diabetes

Age at onset, y

30-50 typical but may occur at any age

<30 typical but may occur at any age

>25 typical but increasingly seen in children/teens/young adults

Symptoms at onset

Acute or subclinical; rarely DKA

Acute; may be in DKA

None or subclinical

Typical weight

Normal to overweight

Normal

Overweight or obese

Antibody presence

Yes

Yes

No

C-peptide level

Low to normal (decreasing to undetectable as disease advances)

Low to undetectable

Normal to high (decreasing to low as disease advances)

Family history of diabetes

Family presence of type 1 or 2 diabetes may be present but less common

Family presence of type 1 or 2 diabetes may be present but less common

Strong family presence of type 2 diabetes common

Autoimmune disease and/or family history of autoimmune disease presence

Common

Common

Less common

Progression to insulin requirement

Slow (months to years)

Immediate

Slow to never

DKA, diabetic ketoacidosis

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • MAY 2020 25

STRONG FAMILY HISTORY

Maturity-Onset Diabetes of the Young: A Rare Type of Diabetes Another less common form of diabetes is maturity-onset diabetes of the young (MODY), which is a monogenic diabetes that leads to a defect in β cell insulin secretion.1-3 Patients with MODY may be misdiagnosed with either type 1 diabetes (T1D) or type 2 diabetes (T2D) depending on age and presentation (Table).

MODY is categorized into 14 known subtypes based on the genes affected.The 2 most common are MODY 2 and MODY 3, which result from defects in the glucokinase and hepatocyte nuclear factor-1α genes, respectively.1-3 Typically diagnosed when they are <25 years of age, patients with MODY lack insulin resistance and overweight/obesity commonly associated with T2D and autoantibodies associated with T1D.

Patients with MODY have a strong family history of diabetes in an autosomal-dominant pattern (more than 2 generations).

Genetic testing confirms the diagnosis.1,2 Lifestyle modification is appropriate for both MODY 2 and 3, and patients with MODY 3 respond well to treatment with sulfonylurea agents.

Progression to insulin dependence is infrequent in patients with MODY.2,3 1. Carlsson A, Shepherd M, Ellard S, et al. Absence of islet autoantibodies and modestly raised glucose values at diabetes diagnosis should lead to testing for MODY: lessons from a 5-year pediatric Swedish national cohort study. Diabetes Care. 2020;43(1):82-89.

2. Delvecchio M, Salzano G, Bonura C, et al. Can HbA1c combined with fasting plasma glucose help to assess priority for GCK-MODY vs HNF1A-MODY genetic testing?

Acta Diabetol. 2018;55(9):981-983.

3. Urakami T. Maturity-onset diabetes of the young (MODY): current perspectives on diagnosis and treatment. Diabetes Metab Syndr Obes. 2019;12:1047-1056.

TABLE. Characteristic Differences Between MODY and Type 1 and 2 Diabetes Maturity Onset Diabetes of the Young (MODY)

Type 1 Diabetes

Type 2 Diabetes

Age at onset, y

<25 typical though may go undetected

<30 typical but may occur at any age

>25 typical but increasingly seen in children/teens/young adults

Symptoms at onset

None or subclinical

Acute; may be in DKA

None or subclinical

Typical weight

Normal to overweight

Normal

Overweight or obese

Antibody presence

No

Yes

No

C-peptide level

Normal

Low to undetectable

Normal to high (decreasing to low as disease advances)

Family history of diabetes

Strong multigenerational family presence of diabetes

Family presence of type 1 or 2 diabetes may be present but less common

Strong family presence of type 2 diabetes common

Autoimmune disease and/or family history of autoimmune disease presence

Less common

Common

Less common

Progression to insulin requirement

Slow to never

Immediate

Slow to never

DKA, diabetic ketoacidosis

26 THE CLINICAL ADVISOR • MAY 2020 • www.ClinicalAdvisor.com

LATENT AUTOIMMUNE DIABETES IN ADULTS

Jennifer L. Deltour, MSN, FNP-C, BC-ADM, is a nurse practitioner in primary care and endocrinology with Asante Physician Partners Family Medicine and Asante Physician Partners Endocrinology in Medford, Oregon.

POLL POSITION What feature is not characteristic of latent autoimmune diabetes in adults?

■ Family history of autoimmune disease

14.11%

12.88%

References 4.65%

Report, 2020. Atlanta, GA: Centers for Disease Control and Prevention, US Department of Health and Human Services; 2020.

2. Mishra R, Hodge KM, Cousminer DL, Leslie RD, Grant SF. A global perspective of

■ Elevated HbA1c ■ Normal to high C-peptide level

1. Centers for Disease Control and Prevention. National Diabetes Statistics

latent autoimmune diabetes in adults. Trends Endocrinol Metab. 2018;29(9):638-650.

70.25%

■ Presence of autoantibodies

3. Pozzilli P, Pieralice S. Latent autoimmune diabetes in adults: current status and new horizons. Endocrinol Metab. 2018;33(2):147-159.

4. Thomas NJ, Lynam AL, Hill AV, et al. Type 1 diabetes defined by severe insulin deficiency occurs after 30 years of age and is commonly treated as

For more polls, visit ClinicalAdvisor.com/Polls.

type 2 diabetes. Diabetologia. 2019;62(7):1167-1172.

5. Carlsson S. Etiology and pathogenesis of latent autoimmune diabetes in adults (LADA) compared to type 2 diabetes. Front Physiol. 2019;10:320.

6. American Diabetes Association. 2. Classification and diagnosis of diabetes: Standards of Medical Care in Diabetes-2020. Diabetes Care. 2020;

GLP-1 receptor agonists may help preserve β-cell function and delay the need for intensive basal or bolus therapy though these medications are considered investigational and are not yet approved by the US Food and Drug Administration for patients with T1D or LADA.14-17 Metformin may be considered in the treatment of patients with LADA if insulin resistance is a concern. Medications that stimulate insulin production, such as sulfonylurea agents, are thought to hasten the demise of remaining functioning β cells and generally should be avoided.14,18 As the disease advances, a patient with LADA will progress to full insulin dependence and warrants close follow-up.When starting insulin therapy in patients with T1D or LADA, the dosage typically is weight based and ranges from 0.4 to 1.0 units/kg/d. Basal insulin requirements classically are 50% of the total daily dose. The remaining insulin is used for mealtime coverage of carbohydrates and as a bolus to correct hyperglycemia.13 Patients with LADA may be insulin-sensitive, so starting slowly and titrating upward based on response is advised.

Management with an endocrinology provider is appropriate.

Proper diagnosis is essential because it ensures that patients are appropriately educated about their disease including sick-day rules (including frequently checking blood glucose and ketone levels) and the potential for ketoacidosis. A correct diagnosis also ensures that patients have access to technologies such as insulin pumps and continuous glucose monitors that often are not covered by insurance for patients with T2D but are covered for patients with LADA. A diagnosis of LADA alerts the provider to screen patients appropriately for other autoimmune diseases and leads to heightened awareness of both patient and provider when considering the health of the family.5,6,18 ■

43(suppl 1):S14-S31.

7. O’Neal KS, Johnson JL, Panak RL. Recognizing and appropriately treating latent autoimmune diabetes in adults. Diabetes Spectr. 2016;29(4):249-252.

8. Pieralice S, Pozzilli P. Latent autoimmune diabetes in adults: a review on clinical implications and management. Diabetes Metab J. 2018;42(6):451-464.

9. Kawasaki E. Type 1 diabetes and autoimmunity. Clin Pediatr Endocrinol.

2014;23(4):99-105.

10. Hjort R, Alfredsson L, Andersson T, et al. Family history of type 1 and type 2 diabetes and risk of latent autoimmune diabetes in adults (LADA). Diabetes Metab. 2017;43(6):536-542.

11. Leighton E, Sainsbury CA, Jones GC. A practical review of C-peptide testing in diabetes. Diabetes Ther. 2017;8(3):475-487.

12. Giese KK. Adult diabetes mellitus: thinking beyond type 2. Nurse Pract.

2016;41(5):40-45.

13. American Diabetes Association. 9. Pharmacologic approaches to glycemic treatment: Standards of Medical Care in Diabetes-2020. Diabetes Care.

2020;43(suppl 1):S98-S110.

14. Buzzetti R, Pozzilli P, Frederich R, Iqbal N, Hirshberg B. Saxagliptin improves glycaemic control and C-peptide secretion in latent autoimmune diabetes in adults (LADA). Diabetes Metab Res Rev. 2016;32(3):289-296.

15. Chatzianagnostou K, Iervasi G, Vassalle C. Challenges of LADA diagnosis and treatment: lessons from 2 case reports. Am J Ther. 2016;23(5):e1270-e1274.

16. Pozzilli P, Leslie RD, Peters AL, et al. Dulaglutide treatment results in effective glycaemic control in latent autoimmune diabetes in adults (LADA): a post-hoc analysis of the AWARD-2, -4 and -5 trials. Diabetes Obes Metab. 2018;20(6):1490-1498.

17. Zhao Y,Yang L, Xiang Y, et al. Dipeptidyl peptidase 4 inhibitor sitagliptin maintains β-cell function in patients with recent-onset latent autoimmune diabetes in adults: one year prospective study. J Clin Endocrinol Metab. 2014;99(5):E876-E880.

18. Kreider KE. The diagnosis and management of atypical types of diabetes.

J Nurse Practition. 2019;15(2):171-176.

28 THE CLINICAL ADVISOR • MAY 2020 • www.ClinicalAdvisor.com

Dermatology Clinic CASE #1

Hyperpigmented Scaly Plaque on Midline of Back JOANNE JACOB, BS; EMILY BURNS, BA; CHRISTOPHER RIZK, MD

A 15-year-old white adolescent presents to the dermatology clinic with an asymptomatic rash on his upper back that has persisted for 4 months. Physical examination reveals hyperpigmented scaly papules coalescing into confluent plaques with peripheral reticulated papillomatosis. The boy is overweight but has no history of any other medical conditions.

What is your diagnosis? Turn to page 30

CASE #2

Papulosquamous Cutaneous Lesions on Arms and Hands KADON CASKEY, BS; ELEANOR JOHNSON, BA; CHRISTOPHER RIZK, MD

A 48-year-old white man presents with papulosquamous cutaneous lesions that recently appeared on his chest, arms, and the dorsal aspects of his hands. He has a family history of autoimmune disorders, including systemic lupus erythematosus (SLE). Physical examination reveals lesions that lack induration and scarring. Biopsy reveals mild inflammatory infiltrate.

Direct immunofluorescence shows a granular deposition at the dermal-epidermal junction. Serology indicates that the patient is positive for anti-Ro/SSA (Sjögren-syndrome-related antigen A).

What is your diagnosis? Turn to page 31 www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • MAY 2020 29

Dermatology Clinic CASE #1

Confluent and Reticulated Papillomatosis

Confluent and reticulated papillomatosis (CARP) is a relatively rare form of dermatosis that occurs in both sexes and all ethnic groups.1 However, 2 recent studies suggest that CARP occurs more commonly in white patients and ethnicities with lighter skin.1,2 In addition, the average age of onset and sex of CARP patients varies by ethnicity. Although CARP can occur in patients ranging in age from 5 to 63 years, the average age of onset is 15 years in predominantly white populations and 29 years in Southeast Asian populations.2,3 The condition presents more often in white women than white men but more often in Asian men than Asian women.1,3 Many theories have been proposed to explain the etiology and pathogenesis of CARP. The condition originally was thought to be caused exclusively by the fungal organism Malassezia furfur. However, not all cases of CARP respond to antifungal medications, and the organism may not be identified on microscopic examination.4 For these reasons, alternative etiologies for this condition, including bacterial infection, have been suggested.1 In one study, Natarajan et al isolated Dietzia, a bacterial genus that is susceptible to minocycline, which is commonly used in the treatment of CARP.5 However, another study reported that not one consistent organism has been identified from skin scrapings.6 The efficacy of antibacterial therapies may be due to their anti-inflammatory properties.4,6 Another potential causal mechanism is an acquired or genetic pathologic process of keratinization, which can be seen on histologic examination.1 However, this model does not account for cases of CARP that resolve with antibacterial therapy alone, even when no bacterial organisms were seen on microscopic examination.

A correlation exists between CARP and medical conditions such as obesity and diabetes mellitus.1,6 Increased body habitus has been identified as an independent risk factor for the development of CARP, and subsequent insulin resistance has been theorized to trigger epidermal proliferation.

Increased circulating insulin may bind to epidermal and fibroblast growth factors, contributing to reduced apoptosis of epidermal cells.6 Therefore, obesity and diabetes may be risk factors for CARP.Thus, CARP may not be attributable to one causative factor but may result from a variable interplay of the aforementioned factors.7

CARP is largely asymptomatic and limited to the skin, with no systemic involvement.6 The lesions are found mostly on the upper trunk and axillae and very rarely on the lower limbs. In women, the patches can appear in the axillae or submammary creases with a velvety texture.6 Clinical diagnosis of CARP is made largely by physical examination, with confirmation by histologic examination.

The general morphologic characteristics of CARP involve hyperkeratotic brown scaly patches with reticulation and papillomatosis in at least a portion of the lesions.2 On dermoscopy, CARP classically displays increased melanin pigmentation and basket-weave hyperkeratosis that invaginates into the epidermis.

A white scale may overlay brown pigmentation, and this may be a unique finding of CARP that can eliminate other similar conditions from the differential diagnosis.6 The patches may display rippling or reticulation in a “sulci and gyri” pattern.7 Cobblestone patterns due to basal hyperpigmentation and papillomatosis also are possible.8 Acanthosis nigricans has a similar appearance on physical examination and is closely associated with CARP. Notably, a unique feature of CARP is the presence of beading elastic fibers around mildly dilated vasculature. These findings are not present in acanthosis nigricans, and, thus, this histologic feature often is used to differentiate the 2 conditions.1 The presence of follicular plugging and anastomosis of rete ridges in CARP also may help to differentiate CARP from acanthosis nigricans.9

The diagnosis of CARP is made clinically by physical examination, with confirmation by histologic examination.

Other conditions with similar appearance include tinea (pityriasis) versicolor, amyloidosis cutis dyschromica, lichen planus pigmentosus, Dowling-Degos disease, terra firma-forme dermatosis, and prurigo pigmentosa.3,10 A diagnosis of tinea versicolor is dependent on microscopic findings of hyphae of M furfur, which are not consistently present in CARP.9 Although CARP may appear with similar coloration to amyloidosis cutis dyschromica, the reticulation found in CARP is distinct from the rippling pattern seen in amyloidosis. In addition, CARP does not display amyloid deposits on histopathology.6 Lichen planus pigmentosus may appear similar grossly but displays coarse gray-blue and brown globules when examined by dermoscopy.8 Dowling-Degos disease notably lacks papillomatosis and tends to affect intertriginous areas.10

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Terra firma-forme dermatosis presents with verrucous plaques and retention hyperkeratosis; the latter can be lightened with alcohol, which is not a characteristic of CARP.4 If a patient presents with complaint of pruritus, a diagnosis of prurigo pigmentosa may be more likely and can be confirmed by histologic examination for lymphocytic infiltrate.1 Numerous treatment options are suggested for management of CARP. Antibiotics (especially minocycline and azithromycin) and antifungals are used most commonly2; they are associated with variable success and high rates of recurrence. Carrozzo et al reported calcipotriol ointment to be an effective topical treatment that may reduce risk of recurrence.10 CARP has been successfully treated with retinoids and vitamin D, which often are used in disorders of keratinization.1 Bernardes Filho et al suggest that weight loss may contribute to greater therapeutic success and minimize the recurrence of the condition.7 The patient in this case was prescribed a 6-week trial of minocycline, and the lesion regressed.

Joanne Jacob, BS, and Emily Burns, BA, are medical student at Baylor College of Medicine, and Christopher Rizk, MD, is a dermatologist at Elite Dermatology in Houston,Texas.

References 1. Scheinfeld N. Confluent and reticulated papillomatosis. Am J Clin Dermatol.

2006;7(5):305-313.

2. Davis MD, Weenig RH, Camilleri MJ. Confluent and reticulate papillomatosis (Gougerot-Carteaud syndrome): a minocycline-responsive dermatosis without evidence for yeast in pathogenesis. A study of 39 patients and a proposal of diagnostic criteria. Br J Dermatol. 2006;154(2):287-293.

3. Huang W, Ong G, Chong WS. Clinicopathological and diagnostic characterization of confluent and reticulate papillomatosis of Gougerot and Carteaud: a retrospective study in a South-East Asian population. Am J Clin Dermatol.

2015;16(2):131-136.

4. Pascoe D, Morrell DS. Progressive truncal “dirty skin”: confluent and reticulated papillomatosis. Pediatr Ann. 2007;36(12):810-813.

5. Natarajan S, Milne D, Jones AL, Goodfellow M, Perry J, Koerner RJ. Dietzia strain X: a newly described actinomycete isolated from confluent and reticulated papillomatosis. Br J Dermatol. 2005;153(4):825-827.

6. Lim JH, Tey HL, Chong WS. Confluent and reticulated papillomatosis: diagnostic and treatment challenges. Clin Cosmet Investig Dermatol.

2016;9:217-223.

7. Bernardes Filho F, Quaresma MV, Rezende FC, Kac BK, Nery JA, AzulayAbulafia L. Confluent and reticulate papillomatosis of Gougerot-Carteaud and obesity: dermoscopic findings. An Bras Dermatol. 2014;89(3):507-509.

8. Errichetti E, Maione V, Stinco G. Dermatoscopy of confluent and reticulated papillomatosis (Gougerot-Carteaud syndrome). J Dtsch Dermatol Ges. 2017;15(8):836-838.

9. Tamraz H, Raffoul M, Kurban M, Kibbi AG, Abbas O. Confluent and reticulated papillomatosis: clinical and histopathological study of 10 cases from Lebanon. J Eur Acad Dermatol Venereol. 2013;27(1):e119-e123.

10. Carrozzo AM, Gatti S, Ferranti G, Primavera G, Vidolin AP, Nini G. Calcipotriol treatment of confluent and reticulated papillomatosis (GougerotCarteaud syndrome). J Eur Acad Dermatol Venereol. 2000;14(2):131-133.

CASE #2

Subacute Cutaneous Lupus Erythematosus

Subacute cutaneous lupus erythematosus (SCLE) was first described in 1880 by Jonathan Hutchinson as a potential case of “lupus marginatus.”1 In a paper published in 1979, the condition was redefined as a subtype of cutaneous lupus erythematosus (CLE).2 SCLE often is diagnosed based on clinical, histologic, laboratory, and genetic findings. In classic cases, patients present with papulosquamous rash in photosensitive areas and have positive serologies for autoimmune markers such as anti-Ro/SSA.1-2 Like SLE, most cases of SCLE are idiopathic in origin.The average age of SCLE onset is during the fifth decade.1 Women are affected at a much higher rate than men, and a vast majority of SCLE patients are white.1,3 Ten percent to 20% of SCLE cases are drug induced,3-5 with the most common offenders including antihypertensive and antifungal medications, specifically hydrochlorothiazide, angiotensin-converting enzyme inhibitors, and terbinafine.3-6 Recently, the incidence of druginduced SCLE has been increasing.6 However, it is unknown whether this rise is due to increased identification of SCLE or a true increase in the number of drug-induced SCLE cases.

Genetic and environmental factors can predispose patients to develop SCLE.The human leukocyte antigen (HLA) A1, B8, and DR3 haplotypes are associated strongly with this condition.1,2,7 Genetic mutations that also can increase the risk for developing SCLE include single nucleotide polymorphisms in the tumor necrosis factor α gene promoter (-308A) or C1qA, a molecule involved in the classical complement pathway.1 Psychological stress has been linked with the development of SCLE, but this correlation has not yet been systematically investigated.1 Sun exposure and smoking exacerbate this condition, and smoking is associated with increased disease severity and decreased quality of life.1,8 Clinically, SCLE presents as annular erythematous plaques or papulosquamous lesions.1,5,9,10 These lesions are distributed

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Dermatology Clinic across sun-exposed areas of the upper body, including the “V” area of the neck, extensors of the upper extremities, and dorsum of the hands.1,9 The face and scalp often are spared.9 The lesions are nonindurated and nonscarring.1 Some patients may experience mild extracutaneous symptoms, including arthralgias and Raynaud phenomenon.10 Less than 10% of patients with SCLE experience severe systemic symptoms such as central nervous system lupus and nephritis.9 A number of key histologic, immunologic, and serologic findings indicate a diagnosis of SCLE. Histologically, a biopsied skin lesion can feature hydropic changes, mild superficial infiltration of inflammatory cells, hyperkeratosis, and follicular plugging.9 Direct immunofluorescence shows a granular or particulate deposition of immunoglobulin (Ig) M, IgG, and C3 at the dermal-epidermal junction.6,9,10 Approximately 70% to 99% of patients with SCLE are positive for anti-Ro/SSA antibodies, making this a useful, although nonspecific, marker in patients suspected of having this disease.1,3 In addition, antinuclear antibodies are found in 70% of SCLE patients, but these also are nonspecific.1 Other serologic markers, such as rheumatoid factor, citrullinated peptide, and anti-La/ SSB antibody, are found in patients with SCLE at lower rates.3

cutaneous lesions. Systemic therapy with the antimalarial agent hydroxychloroquine has been found to be effective in treating SCLE, with approximately 75% of patients responding to this treatment.1,3 If treatment with hydroxychloroquine is not effective or tolerated, systemic steroid therapy and immunosuppressive agents such as methotrexate may be considered.1,3 Most cases of SCLE resolve within 1 year of treatment.1 In drug-induced SCLE, cessation of the offending drug alone can lead to resolution of SCLE.3 Clothing to cover sun-exposed areas and broad-spectrum sunscreen can reduce the severity of disease and prevent exacerbations.1 For the patient in our case, clinical, serologic, and immunohistologic findings were consistent with SCLE. The patient was treated with hydroxychloroquine and topical steroids, and the cutaneous lesions resolved. ■ Kadon Caskey, BS, and Eleanor Johnson, BA, are medical students at Baylor College of Medicine, and Christopher Rizk, MD, is a dermatologist at Elite Dermatology in Houston,Texas.

References 1. Sontheimer RD. Subacute cutaneous lupus erythematosus: 25-year evolution of a prototypic subset (subphenotype) of lupus erythematosus

Subacute cutaneous lupus erythematosus may occur in the context of autoimmune connective tissue disorders.

defined by characteristic cutaneous, pathological, immunological, and genetic findings. Autoimmun Rev. 2005;4(5):253-263.

2. Sontheimer RD, Thomas JR, Gilliam JN. Subacute cutaneous lupus erythematosus: a cutaneous marker for a distinct lupus erythematosus subset. Arch Dermatol. 1979;115(12):1409-1415.

3 Alniemi DT, Gutierrez A Jr, Drage LA, Wetter DA. Subacute cutaneous lupus erythematosus: clinical characteristics, disease associations, treatments,

SCLE may occur in the context of autoimmune connective tissue disorders.The most common conditions associated with SCLE include SLE, Sjögren syndrome, and rheumatoid arthritis.3 Approximately 50% of patients with SCLE meet at least 4 classification criteria from the American Rheumatism Association for SLE.1 This disorder also can present in association with other CLE manifestations, such as discoid lesions, butterfly rash on the face, or a generalized SLE rash.1 There are numerous conditions to consider when formulating a differential diagnosis for SCLE, including other forms of CLE such as discoid lupus erythematosus,10 as well as dermatomyositis, tinea corporis, granuloma annulare, pemphigus foliaceus, photolichenoid drug eruptions, and cutaneous T-cell lymphoma.9 Histologic and immunologic examination of a biopsied lesion is useful in differentiating these diseases.9 Recommendations for the initial treatment of SCLE include topical corticosteroids or other topical anti-inflammatory agents because they are associated with fewer side effects1; however, most patients will require systemic treatment to resolve

and outcomes in a series of 90 patients at Mayo Clinic, 1996-2011. Mayo Clin Proc. 2017;92(3):406-414.

4. Wilkerson E, Hazey MA, Bahrami S, Callen JP. Golimumab-exacerbated subacute cutaneous lupus erythematosus. Arch Dermatol. 2012;148(10):1186-1190.

5. Hazey M, Callen J. Subacute cutaneous lupus erythematosus exacerbated by golimumab. J Am Acad Dermatol. 2012;66(4 suppl 1):AB67.

6. Lowe GC, Henderson CL, Grau RH, Hansen CB, Sontheimer RD. A systematic review of drug-induced subacute cutaneous lupus erythematosus.

Br J Dermatol. 2011;164(3):465-472.

7. Sontheimer RD, Stastny P, Gilliam JN. Human histocompatibility antigen associations in subacute cutaneous lupus erythematosus. J Clin Invest. 1981;67(1):312-316.

8. Piette EW, Foering KP, Chang AY, et al. Impact of smoking in cutaneous lupus erythematosus. Arch Dermatol. 2012;148(3):317-322.

9. Okon LG, Werth VP. Cutaneous lupus erythematosus: diagnosis and treatment. Best Pract Res Clin Rheumatol. 2013;27(3):391-404.

10. Vera-Recabarren MA, García-Carrasco M, Ramos-Casals M, Herrero C. Comparative analysis of subacute cutaneous lupus erythematosus and chronic cutaneous lupus erythematosus: clinical and immunological study of 270 patients. Br J Dermatol. 2010;162(1):91-101.

32 THE CLINICAL ADVISOR • MAY 2020 • www.ClinicalAdvisor.com

Dermatologic Look-Alikes Congenital Nevi in Infants NIKI IRANPOUR, BS; EMILY BURNS, BA; CHRISTOPHER RIZK, MD

CASE #1

CASE #2

A 3-month-old infant of Hispanic descent presents with bluish-green lesions on his lower back and gluteal area.

His parents indicate the discolorations were present at birth. The lesions are irregularly shaped with ill-defined borders and measures 4 cm in greatest diameter. No additional lesions are noted anywhere else on the baby’s body.The patient is otherwise healthy, and the lesions are not causing him pain or discomfort. His parents report that his 8-year-old brother had a similar lesion during infancy that disappeared several years ago.

An 8-week-old black infant is brought to the dermatology clinic by his parents for evaluation of a brown lesion on his lower back that measures approximately 10 cm in diameter. His parents report that the discoloration was present at birth but has become darker and rougher in appearance as the child has grown older. The patient is otherwise healthy, and the lesion is not causing him any pain or discomfort. Physical examination reveals a lesion with small, dark macules within the larger smoother lesion, giving it a pebbly appearance.

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Dermatologic Look-Alikes CASE #1

Congenital Dermal Melanocytosis

Dermal melanocytosis is a clinical spectrum of pigmented lesions characterized by an increased depth and number of melanocytes in the dermis.1 Dermal melanocytosis can be classified by the anatomic location of lesions into subtypes that share similar histopathologic features.2 The most common subtypes include congenital dermal melanocytosis (formerly known as Mongolian spot), nevus fuscoceruleus maxillofacialis (nevus of Ota), and nevus fuscoceruleus acromiodeltoideus (nevus of Ito).1 Congenital dermal melanocytosis is a nonblanching benign birthmark typically found on the lumbosacral and gluteal areas of infants at birth or within the first few weeks of life.2,3 These lesions tend to be irregularly shaped and bluish-green to black in color.3 The pigmentation of the lesions is darkest at age 1 and tends to lighten over approximately 6 years.4 The size of the lesions can range from a few centimeters to more than 20 cm.4 Congenital dermal melanocytosis, which is seen in boys and girls with equal incidence,3 is most commonly found in Asian, black, and Native American populations and is less common in white individuals.3 This racial phenomenon is not well understood, but it has been postulated that the melanocytes of white people contain incompletely melanized melanosomes and that the duration of dermal melanocyte production is more extensive in other races, particularly in Asian individuals.5 Melanocytes arise from neural crest cells and populate the epidermis through migration. In all dermal melanocytosis subtypes, melanocyte migration is believed to be arrested in the dermis, leading to entrapment of melanocytes in this layer of skin.1 Several factors play a role in the color of the lesions, including the amount of melanin within the melanocytes and the number and depth of these melanin-producing cells in the dermis.5 The blue color of the lesions is produced secondary to the Tyndall effect, in which shorter-wavelength colors, such as grey and blue, are reflected to the skin surface by the scattering of light.4 Colors with a longer wavelength, such as red, are not reflected but instead continue deeper into the skin.2 Congenital dermal melanocytosis is thought to be a benign condition without systemic involvement, but recent evidence shows that these lesions may be associated with inborn errors of metabolism and neurocristopathies, which are disorders related to abnormalities in neural crest migration, growth, and differentiation.3,4 Phacomatosis pigmentovascularis is a neurocristopathy that may result in the occurrence of

dermal melanocytosis and cutaneous vascular malformations in the same patient.6 The 2 most common lysosomal storage disorders related to inborn errors of metabolism are Hurler syndrome and GM1 (β-galactosidase) gangliosidosis.6 These associations typically are present only when the lesions of congenital dermal melanocytosis are extensively pigmented, persistent, or progressive.6 Histologically, all subtypes of dermal melanocytosis show a sparse melanocytic infiltrate among relatively undisturbed collagen fibers in the dermis.7 These melanocytes are elongated and have thin, pigmented dendrites.7 Under low magnification, the mid-lower dermis shows elongated and spindle-shaped dendritic cells lying parallel to the skin surface.3 At higher magnification, the cells are shown to contain melanin granules and stain positive with Fontana-Masson silver stain.3 The differential diagnosis of congenital dermal melanocytosis includes other dermal melanocytosis subtypes, as well as congenital melanocytic nevus, blue nevus, and potential physical abuse.2

Pigmentation of the lesions is darkest at age 1 and tends to lighten over approximately 6 years.

Because nevus of Ota and nevus of Ito share similar clinical and histologic features with congenital dermal melanocytosis, they can be distinguished by the anatomic location of the lesions. Lesions of nevus of Ota appear in areas innervated by the first and second branches of the trigeminal nerve.8 Bluegrey pigmentation of conjunctiva and sclera may be seen, and glaucoma may occur in some cases.3 Lesions of nevus of Ito are located in areas of the skin that are innervated by the posterior subclavian and brachial-cutaneous nerves.7 Both nevi may occur separately or in conjunction with one another and extensive types of congenital dermal melanocytosis.3 Unlike the lesions of congenital dermal melanocytosis, nevus of Ito and nevus of Ota do not spontaneously regress during childhood and may even darken with age.1 Congenital melanocytic nevus is another pigmented lesion caused by abnormal proliferative capacity and migration of melanocytes.9 Lesions typically are dark brown in color. They are papillated or verrucous on the surface and occasionally can be keratotic.7 The lesions can change in color and develop overlying hair.9 It is imperative to distinguish congenital melanocytic nevus from other lesions due to its association with neurocutaneous melanocytosis, melanoma, and psychosocial impairment.9

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Blue nevus is another pigmented lesion that often presents in the second decade of life but occasionally can be congenital.3 Common blue nevus appears as a bluish-black macule, papule, or plaque.10 The most common locations for these lesions are the head, neck, presacral area, and distal extremities.10 These lesions are much smaller than those of congenital dermal melanocytosis, commonly measuring <1Â cm in diameter.4 The lesions of congenital dermal melanocytosis may be mistaken for bruises from physical abuse, especially if they present in unusual locations. The lesions are distinguished from bruises by the absence of tenderness, a lack of color change or evolution with time, and a time period of several months to years for the lesion to disappear.2 The diagnosis of congenital dermal melanocytosis is made clinically largely based on onset, location, and evolution of the lesions, with assistance from analysis of biopsy specimens.4 Because the lesions of congenital dermal melanocytosis typically resolve by early childhood, no treatment is necessary if they are located in the typical lumbosacral region. If the lesions are extrasacral, large, or extensively pigmented, Q-switched alexandrite lasers (755 nm) can be used to lighten the lesion.4 However, persistent lesions may indicate the presence of the aforementioned systemic complications and the patient should be examined for such.

For the patient in our case, clinical presentation and biopsy of the lesion were consistent with congenital dermal melanocytosis. Because the lesion was typical in presentation, no treatment was initiated. The patient was observed, and the lesion regressed over the following year.There were no complications.

CASE #2

Congenital Melanocytic Nevus

First described in 1835, congenital melanocytic nevi (CMN) are benign proliferations of melanocytes that can be detected in utero but usually appear within the first few months of life.11,12 CMN occur in 1% to 6% of newborns,13 and they may occur at any location throughout the body.13,14 CMN are subdivided by their diameter: small (<1.5 cm), medium (1.5-20 cm), large (20-40 cm), and giant (>40 cm).15 Giant CMN can be further categorized by the number of satellite lesions. Small congenital nevi are the most common, whereas large and giant nevi carry the greatest risk for complications such as melanoma.15

The size and appearance of a nevus can change as a patient ages. At birth, CMN usually are sharply demarcated, flat, and a pale tan color.14 Small, dark brown macules can occur within the light-tan parent lesion during infancy. As the patient ages, CMN may become consistently darker and develop thick, coarse hair. Lesions also can become hypopigmented but rarely regress.

The texture of the lesion may become pebbly, verrucous, or cerebriform, and the extent of textural change can differ from patient to patient.13,14 Nodules or irregular borders can form, particularly in large- and giant-sized CMN, and these changes must be monitored by clinicians for neoplastic transformation.16

Congenital melanocytic nevi usually are of small or medium size and can occur throughout the body.

The dermoscopic patterns of CMN vary and are associated with the locations of nevi and age of the patient. Globular, reticular, and reticuloglobular patterns are seen as well as hypertrichosis.17 Patients <12 years of age are more likely to present without a predominant pattern or globules. Reticular patterns typically are seen in individuals aged >12 years.17 Reticular lesions are more likely to be present in the lower extremities than in the head, neck, and trunk. Globular lesions are more likely to be present in the head, neck, and trunk than in the extremities.17,18 On histologic examination, CMN share some features with acquired nevi; however, these conditions have unique histologic characteristics that allow for distinction between the two. In CMN, nevus cells extend into the lower two-thirds of the dermis and subcutaneous tissue.19 They tend to occur around nerves, vessel walls, hair follicles, and sebaceous glands.

Nevus cells also are located between collagen bundles in cords of cells or in single-file lines.13,14,19 The depth and pattern of distribution of the nevus cells are established early in life and typically do not change as the patient ages.14 CMN is associated with increased risk for melanoma and, rarely, risk for neurocutaneous melanosis. The risk for neoplastic transformation in small- and medium-sized CMN is estimated to be <1% over a lifetime, but that estimate is controversial. On the other hand, the association between large- and giant-sized CMN and melanoma is well established, with the estimated lifetime risk of patients with these CMN developing melanoma being approximately 5%.13,14 Patients with multiple medium-sized lesions or several satellite nevi

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Dermatologic Look-Alikes TABLE. Congenital Dermal Melanocytosis vs Congenital Melanocytic Nevus Congenital Dermal Melanocytosis1-10

Congenital Melanocytic Nevi11-21

Dermatologic Presentation

• Irregularly shaped, bluish-green to black lesions • Pigmentation is darkest at 1 year of age and regresses over approximately a 6-year period

• Regular to irregularly shaped tan to black lesions • May have thick, coarse hairs or satellite nevi • Usually <20 cm but can be >60 cm (rarely) • Enlarge as child grows and typically do not regress

Associations

• Seen more commonly in Asian, black, and Native American populations • Systemic involvement is uncommon but includes lysosomal storage disorders • Can also be associated with neurocristopathies

• Can progress to melanoma (particularly large or giant lesions) • Rarely associated with neurocutaneous melanosis

Etiology

• Entrapment of melanin-producing melanocytes in the dermis of the skin

• Proliferations of nevi in reticular dermis and subcutaneous tissues that occur during embryogenesis

Characteristic Location

• Most commonly seen in the lumbosacral and gluteal areas of newborns

• May occur anywhere on the body

Histology

• Melanocytic infiltrate among undisturbed collagen fibers in the dermis • Low magnification: elongated, spindle-shaped dendritic cells in mid-lower dermis parallel to skin surface • High magnification: cells show melanin granules and stain positive with Fontana-Masson silver stain

• Nevus cells located in reticular dermis and frequently subcutaneous tissue • Commonly involve vessels, nerves, and hair follicles • Located between collagen bundles in cords of cells or in single-file lines

Diagnosis

• History and physical examination • Largely made clinically on the basis of onset, distribution, evolution of lesions

• History and physical examination • Distinguished from acquired nevi via dermoscopy and/or histologic examination

Treatment

• No treatment necessary for typical clinical presentation • Q-switched alexandrite lasers used to lighten extensive lesions • Patients with extensive or persistent lesions should be examined for systemic complications

• Longitudinal observation for melanoma • Laser therapy, curettage, and dermabrasion for cosmetic concerns • Large lesions may be removed surgically

are at increased risk of developing melanoma. Melanoma typically occurs in the parent lesion rather than the satellite lesions.13 Individual considerations dictate the management of smalland medium-sized CMN. Functional or cosmetic concerns may warrant simple excision. Baseline photographs and longitudinal monitoring are necessary due to the risk for melanoma. In small- and medium-sized CMN, melanomas typically develop at the dermal-epidermal junction, so they can easily be recognized by clinicians.13,18 Parents and patients should be taught to examine the lesion and report changes in texture, color, or border. In addition, patients should be instructed to protect their skin from sun damage.

Dermabrasion, laser therapy, and curettage may provide cosmetic benefit when surgery is not feasible.13,14 Prophylactic early surgical removal of large- and giant-sized CMN is recommended due to the risk for melanoma and emotional and behavioral issues. Due to deep penetration of nevus cells in large- and giant-sized CMN, melanoma can develop deep within the parent lesion, making them more difficult to detect clinically.13,18 Large CMN are associated with emotional and behavioral problems in up to 30% of patients due to the cosmetic appearance of the lesion, anxiety about melanoma risk, and pain from surgery.13 Complete surgical resection of CMN is challenging because of nevus cell

36 THE CLINICAL ADVISOR • MAY 2020 • www.ClinicalAdvisor.com

Continues on page 38

Dermatologic Look-Alikes penetration into underlying fat, fascia, and potentially muscle.

Therefore, longitudinal observation is required after surgery.16 Patients with large- or giant-sized CMN, or multiple medium-sized CMN, should be screened for neurocutaneous melanocytosis. Gadolinium-enhanced magnetic resonance imaging of the central nervous system should be performed 4 to 6 months after birth. In addition, patients require longitudinal neurologic examinations.16 The differential diagnosis of CMN includes congenital dermal melanocytosis, plexiform neurofibroma, café au lait macule, acquired nevus, and mastocytoma. Plexiform neurofibromas usually present with other signs and symptoms that suggest neurofibromatosis-1 and have discrete nodules along the tracks of nerves.20 Café au lait macules typically are lighter in color than CMN. Mastocytomas can be differentiated from CMN by skin biopsy or the presence of a Darier sign.21 CMN and acquired nevi can be differentiated histologically, as described above. Congenital dermal melanocytosis lesions typically appear more green or blue and have less-definite borders.

After discussing various therapies, the patient’s parents decided to forgo surgery and continue with longitudinal observation with a dermatologist and pediatrician for neoplastic and neurologic changes. ■

10. Soyer HP, Argenziano G, Hofmann-Wellenof R, John RH. Color Atlas of Melanocytic Lesions of the Skin. 1st ed. Berlin, Germany: Springer-Verlag Berlin Heidelberg; 2007:78-86.

11. Shahi V, Brewer JD. Melanocytic nevi. In: Evidence-Based Dermatology. 3rd ed. Hoboken, NJ: John Wiley & Sons, Inc.; 2014:313-319.

12. Alibert J-L. Monographie des Dermatoses, ou Précis Théorique et Pratique des Maladies de la Peau. 2nd ed. Paris, France: Hachette Livre-BNF; 1835.

13. Marghoob AA. Congenital melanocytic nevi. Evaluation and management.

Dermatol Clin. 2002;20(4):607-616.

14. Tannous ZS, Mihm MC Jr, Sober AJ, Duncan LM. Congenital melanocytic nevi: clinical and histopathologic features, risk of melanoma, and clinical management. J Am Acad Dermatol. 2005;52(2):197-203.

15. Soyer HP, Argenziano G, Hofmann-Wellenhof R, Johr RH, eds. Congenital melanocytic nevi. In: Color Atlas of Melanocytic Lesions of the Skin. 1st ed. Berlin, Germany: Springer-Verlag Berlin Heidelberg; 2007:106-118.

16. Price HN, Schaffer JV. Congenital melanocytic nevi-when to worry and how to treat: facts and controversies. Clin Dermatol. 2010;28(3):293-302.

17. Changchien L, Dusza SW, Agero AL, et al. Age- and site-specific variation in the dermoscopic patterns of congenital melanocytic nevi: an aid to accurate classification and assessment of melanocytic nevi. Arch Dermatol.

2007;143(8):1007-1014.

18. Haliasos EC, Kerner M, Jaimes N, et al, Dermoscopy for the pediatric dermatologist part III: dermoscopy of melanocytic lesions. Pediatr Dermatol.

2013;30(3):281-293.

Niki Iranpour, BS, and Emily Burns, BA, are medical students at Baylor College of Medicine, and Christopher Rizk, MD, is a dermatologist at Elite Dermatology in Houston,Texas.

19. Mark GJ, Mihm MC, Liteplo MG, Reed RJ, Clark WH. Congenital melanocytic nevi of the small and garment type. Clinical histologic, and ultrastructural studies. Hum Pathol. 1973;4(3):395-418.

20. Ferner RE, Huson SM,Thomas N, et al. Guidelines for the diagnosis and man-

References

agement of individuals with neurofibromatosis 1. J Med Genet. 2007;44(2):81-88.

1. Franceschini D, Dinulos J G. Dermal melanocytosis and associated

21. Valent P, Sperr WR, Schwartz LB, Horny HP. Diagnosis and classification of

disorders. Curr Opin Pediatr. 2015;27(4):480-485.

mast cell proliferative disorders: delineation from immunologic diseases and

2. Gupta D, Thappa DM. Mongolian spots: how important are they? World J

non-mast cell hematopoietic neoplasms. J Allergy Clin Immunol. 2004;114(1):3-11.

Clin Cases. 2013;1(8):230-232.

3. Baykal C, Yılmaz Z, Sun GP, Büyükbabani N. The spectrum of benign dermal dendritic melanocytic proliferations. J Eur Acad Dermatol Venereol.

2019;33(6):1029-1041.

4. Gupta D, Thappa DM. Mongolian spots. Indian J Dermatol Venereol Leprol.

2013;79(4):469-478.

5. Kikuchi I. What is a Mongolian spot? Int J Dermatol. 1982;21(3):131-133.

6. Hanson M, Lupski JR, Hicks J, Metry D. Association of dermal melanocytosis with lysosomal storage disease: clinical features and hypotheses regarding pathogenesis. Arch Dermatol. 2003;139(7):916-920.

7. Massi G, LeBoit PE. Histological Diagnosis of Nevi and Melanoma. 2nd ed.

Berlin, Germany: Springer-Verlag Berlin Heidelberg; 2014.

8. Mukhopadhyay AK. Unilateral nevus of Ota with bilateral nevus of Ito and palatal lesion: a case report with a proposed clinical modification of Tanino’s classification. Indian J Dermatol. 2013;58(4):286-289.

9. Habeshian KA, Kirkorian AY. Common neonatal skin lesions: melanocytic nevi, pigment alterations, and nonmelanocytic nevi. Pediatr Ann. 2019;48(1):e23-e29.

38 THE CLINICAL ADVISOR • MAY 2020 • www.ClinicalAdvisor.com

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LEGAL ADVISOR CASE

© PETER DAZELEY / GETTY IMAGES

Delays Lead to Sepsis and Death After 5 hours, with the patient’s vital signs worsening, the rapid response team was called.

BY ANN W. LATNER, JD

Mr M, a 49-year-old man, presented to the emergency department with complaints of abdominal pain. He was diagnosed with diverticulitis and a perforated colon and underwent a sigmoid colectomy and colostomy.

Six weeks later, Dr A performed surgery to reverse the patient’s colostomy. The patient was kept in the hospital postoperatively for observation.

During the days after the reversal surgery, Mr M’s recovery appeared to be progressing normally.

Dr A was involved in the patient’s postoperative care and saw Mr M several times at the hospital.

However, during the fourth night after the surgery, Mr M complained to the night shift nurses that he was experiencing pain. He called his 75-year-old mother at 5:30 AM, told her that he was in terrible pain, and asked her to come to the hospital as quickly as possible.

His mother, Mrs M, arrived at the hospital at 6:45 AM and went to her son’s room, where, she later testified, she saw him panting, breathing heavily, and vomiting bile. Mrs M reported this to the nurses.

At 7:00 AM, Nurse N took over as the day shift nurse. She was told by the overnight nurse that

Negligence was alleged on the part of a surgeon and a nurse caring for a patient following colostomy reversal surgery.

Mr M had been complaining of pain. Nurse N evaluated the patient and observed that his stomach was distended and tender to the touch. Knowing that this was not normal for a postoperative patient, Nurse N called the surgeon and informed him that Mr M had pain, abdominal distension, and tenderness and was complaining of shortness of breath.

Dr A expressed concern about the abdominal distension. He had seen the patient the night before, and these symptoms indicated a sudden change in Mr M’s condition. He ordered an urgent radiograph and instructed Nurse N not to let the patient have anything by mouth except ice chips.

At 7:30 AM, Nurse N entered the order for the abdominal radiograph. A few minutes later, Mr M’s mother, becoming increasingly distressed, asked when the physician would arrive.

At 8:00 AM, Nurse N again called Dr A. She asked the surgeon when he would arrive at the 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.

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • MAY 2020 39

LEGAL ADVISOR hospital and advised him that Mr M had not been taken yet for his radiograph.The surgeon told her that he was on his way.

After her phone call with the surgeon, Nurse N evaluated the patient again.At this time, Mr M showed abnormal vital signs, including a high respiratory rate, labored breathing, elevated body temperature, high peripheral pulse rate, and low blood pressure.

Dr A had not arrived at the hospital by 9:00 AM, and the patient’s mother was distraught. Nurse N called the surgeon again and was told that he was on his way. Nurse N then transferred the call to the patient’s mother so she could speak to the physician directly.“My son is in a lot of pain,” Mrs M told Dr A, as she relayed Mr M’s symptoms.“I’m really concerned because things keep getting worse and worse.” Mrs M urged the surgeon to get to the hospital as soon as possible. “I will be there at 10:00 to see you,” replied Dr A. The patient was taken for a radiograph at 9:20 AM. When he returned approximately 30 minutes later, he was having increasing difficulty breathing. Since lying down made breathing more difficult, he sat in the chair in his room. His mother remained with him.

Nurse N was contemplating calling Dr A for the fourth time when she heard Mrs M calling for her. When she arrived to the patient’s room, she saw that he was unconscious. According to his mother, “he had stopped breathing as we were talking, and then he began foaming at the mouth and his eyes rolled back.” Nurse N called the rapid response team at 10:49 AM and a Code Blue was activated.

The team attempted to revive the patient. The hospitalist called Dr A, who had still not arrived, to inform him that Mr M had coded. The hospitalist was told that the surgeon was on his way.The patient could not be revived and was pronounced dead at 11:09 AM. Dr A did not arrive to the hospital until 11:30 AM, approximately 20 minutes after the patient had died.

The patient’s mother had a private autopsy performed to learn the cause of death, which was identified as sepsis caused by a leaking anastomosis. Mrs M sued Dr A and the hospital.

The hospital was sued solely based on the alleged negligence of its employee, Nurse N.

of command policy requiring Nurse N to seek immediate help if her patient’s condition was deteriorating. The expert nurse testified that Nurse N should have moved up the chain of command by 8:30 AM due to Mr M’s shortness of breath, abdominal pain, sweating, and extremely concerning vital signs.

The defense moved to have the case dismissed, claiming that the patient’s mother had the patient cremated and thus “spoiled the evidence.”

The court held that “the lawful cremation of a family member’s remains is not an act of destruction of evidence, nor does Mrs. M’s decision to have her son’s remains cremated evince

At trial, experts testified that this was a surgical emergency, and the patient should have been operated on by 10:00 AM. an intent to destroy evidence.” The judge allowed the case to go to the jury. After deliberation, the jury found for the plaintiff and awarded a judgment of $1,350,000.

Protecting Yourself

Nurse N failed to advocate for her patient in this case. After the first 2 phone calls with the surgeon, once the patient’s vital signs worsened, she should have suspected an anastomotic leak and called for help within the hospital, rather than waiting for Dr A to arrive. ■ Ann W. Latner, JD, a former criminal defense attorney, is a freelance medical writer in Port Washington, New York.

The case went to trial. At trial, experts testified that this was a surgical emergency, and the patient should have been transported to the operating room by 9:00 AM, or 10:00 AM at the latest. The experts testified that had the incision been reopened, the abdomen washed, and a new colostomy performed by 10:00 AM, the patient would still be alive.

A nurse testified that Nurse N breached the standard of care by failing to properly escalate the situation by timely calling the rapid response team at the hospital. The hospital had a chain 40 THE CLINICAL ADVISOR • MAY 2020 • www.ClinicalAdvisor.com

© Harley Schwadron 2019

Legal Background