June 2016 by ejima

Volume 114 u Number 06 u Kolkata u June 2016

June 2016 JIMA Advertiser

Dr S S Agarwal

Dr K K Aggarwal

Dr Debasish Mukherjee

Dr Santanu Sen

National President, IMA

Honorary Secretary General, IMA

Honorary Editor, JIMA

Honorary Secretary, JIMA

Volume 114 u Number 06 u Kolkata u June 2016

CONTENTS Editorial : u Environmental pollution and its effects — Debasish Mukherjee .....................................................85 Originals and Papers : u Efficacy of low dose cyclophosphamide induction regimen in proliferative lupus nephritis : a prospective study — Ananta Kumar Datta, Manoj Soren, Jyotirmoy Pal, Prasun Roy, Anirban De, Sattik Siddhanta, Partha Pratim Mukherjee ...................87 u Knowledge, attitude and practice of contraception : a study from rural tertiary care centre — Beenu Kushwah, Sonal Agrawal ...............................................................................90 u Ocular manifestations of thalassaemia patients with repeated blood transfusion and long term use of chelating agent — Badal Chandra Gorain, Piyali Sarkar, Kumaresh Chandra Sarkar, Jyotirmoy Dutta....................................................................................94 Practitioners’ Series : u Human oto-acariasis : 440 cases of intra-aural tick infestation managed in rural belt of Sullia — Sudhir M Naik, Sarika S Naik...........................................................................................98 Current Topic : u Co-formed consent : a case of rightful application — Munawwar Husain, Arshad Anjum, Amir Usmani, Mubarak Alshraim, Jawed A Usmani ................................................101 GP Forums : u Drug review : febuxostat — Kiran Kumar Singal, Sunder Goyal, Parveen Gupta, Ram Gopal Sharma ................................................................................................103 u Retrospective analysis on diagnosis of malaria — a need for developing community — Nilotpal Banerjee, Sujit Bhattacharjee.....................................................................105 Case Notes : u Emphysematous pyelonephritis – in a non-diabetic young women — a rare association — Y S Ravikumar, K M Srinath, L S Adarsh, Manjunath S Shetty, Subrahmanyam Karuturi, B Balaji Kirushnan .................................................108 u Rhinocerebral mucormycosis : report of two cases and review of literature — Gopee E Makwana, Vikash Jain, Nandini Bahri, Mala Sinha, Manish Kumar Mathur.................110 u Harlequin ichthyosis — a case report — Sendhil Coumary A, Seethesh Ghose .................................113 82

Supplement ..............................................................................................................................................116 83

June 2016 JIMA

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We, the members of Indian Medical Association Stand here to salute our National Flag. Its honour and glory shall be our light and strength And its course shall be our course. We pledge our allegiance to it And realizing our responsibilities as the accredited members of this national organization, We swear We will dedicate everything in our power To see it fly high in the comity of nations. JAI HIND LONG LIVE IMA!

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Office bearers for the year 2015-16 IMA Headquarters Dr SS Agarwal (National President) Prof (Dr) A Marthanda Pillai (Imm Past National President) Dr Shailendra N Vora (National Vice President) Dr K Prameela Surender Rao (National Vice President) Dr Om Parkash Singh Kande (National Vice President) Dr Sharad Kumar Agarwal (National Vice President) Dr KK Aggarwal (Hony. Secretary General) Dr RN Tandon (Hony. Finance Secretary) Dr Rajeev Ardey (Hony. Jt. Secretary) Dr Ravi Malik (Hony. Jt. Secretary), Dr Ramesh Kumar Datta (Hony. Jt. Secretary) Dr Sanjoy Banerjee (Hony. Jt. Secretary, Calcutta) Dr Pravin Gogia (Hony. Jt. Secretary) Dr Hans Raj Satija (Hony. Asst. Secretary) Dr Manjul Mehta (Hony. Asst. Secretary) Dr Harish Gupta (Hony. Jt. Fin. Secretary) Dr Ujjwal Kr Sengupta (Hony. Jt. Fin. Secretary, Calcutta) IMA CGP DrVinod Kumar Monga (Dean of Studies) Dr A Raja Rajeshwar (Hony. Secretary)

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Apka Swasthya Dr Prabhat Kumar Tewari (Hony. Editor) Dr Arvind Singh (Hony. Secretary)

Environmental pollution and its effects

Dr Debasish Mukherjee

ne of the greatest problems that the world is facing today is that of environmental pollution, increasing with every passing year and causing grave and irreparable damage to the earth. Environmental pollution consists of five basic types of pollution, namely, air, water, soil, noise and light.

MBBS, DLO, MS Honorary Editor, JIMA

Air pollution is by far the most harmful form of pollution in our environment. Air pollution is cause by the injurious smoke emitted by cars, buses, trucks, trains, and factories, namely sulphur dioxide, carbon monoxide and nitrogen oxides. Even smoke from burning leaves and cigarettes are harmful to the environment causing a lot of damage to man and the atmosphere. Evidence of increasing air pollution is seen in lung cancer, asthma, allergies, and variousbreathing problems along with severe and irreparable damage to flora and fauna. Even the most natural phenomenon of migratory birds has been hampered, with severe air pollution preventing them from reaching their seasonal metropolitan destinations of centuries. Chlorofluorocarbons (CFC), released from refrigerators, air-conditioners, deodorants and insect repellents cause severe damage to the Earth’s environment. This gas has slowly damaged the atmosphere and depleted the ozone layer leading to global warming. Environmental pollution has existed for centuries but only started to be significant following the industrial revolution in the 19th century. Pollution occurs when the natural environment cannot destroy an element without creating harm or damage to itself. The elements involved are not produced by nature, and the destroying process can vary from a few days to thousands of years (that is, for instance, the case for radioactive pollutants). In other words, pollution takes place when nature does not know how to decompose an element that has been brought to it in an unnatural way. Pollution must be taken seriously, as it has a negative effect on natural elements that are an absolute need for life to exist on earth, such as water and air. Indeed, without it, or if they were present on different quantities, animals – including humans – and plants could not survive. We can identify several types of pollution on Earth: air pollution, water pollution andsoil pollution. Causes of Environmental Pollution :

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Your Health Dr Amitabha Bhattacharya (Hony. Editor) Dr Rahul Dutta (Hony. Secretary)

Editorial

IMA National Health Scheme Dr Ashok S Adhao (Chairman) Dr Alex Franklin (Hony. Secretary) IMA National Pension Scheme Dr Sudipto Roy (Chairman) Dr KV Devadas (Hony. Secretary)

(1) Industries: Industries have been polluting our environment especially since the beginning of the industrial revolution, as mentioned above, notably due to the increasing use of fossil fuels. In the 19th century and for a significant part of the 20th century, coal has been use to make machines work faster, replacing human force. Though pollution by industries mainly causes air pollution, soil and water contamination can also occur. This is particularly the case for powergenerating industries, such as plants producing electricity (May they be a dam, a nuclear reactor or some other type of plant). Also, the transportation of this energy can be harmful to the environment. We can take as an example the transportation of petrol through pipelines; if there is a leak in the pipeline, soil will automatically be polluted. At the same time, if the tanker transporting the petrol from its production plant to the place where it will be consumed leaks or sinks, the water will get contaminated. (2) Transportation : Ever since men abandoned animal power to travel, pollution of the environment has become higher and higher. Its levels have only been increasing until now. Similarly to industries, pollution caused by transport can mainly be attributed to fossil fuels. Indeed, humans went from horse carriages to cars, trains (which, before electricity, used to be propelled by coal), and airplanes. As the traffic is increasing every day, pollution follows that evolution. (3) Agricultural Activities : Agriculture is mainly responsible for the contamination of water and soil. This is caused by the increased use of pesticides, as well as by the intensive character of its production. Almost all pesticides 85

J INDIAN MED ASSOC, VOL 114, NO 6, JUNE 2016

are made from chemical substances and are meant to keep diseases and threatening animals away from the crops. However, by keeping these forms of life away, harm is almost always made to the surrounding environment as well. Furthermore, as agriculture gets more and more intensive to feed the increasing world population, more environments and ecosystems are destroyed to make space for the crops. Some of them, like rapeseed –used to make oil – demand a lot of space for a relatively small output. (4) Trading Activities: Trading activities including the production and exchange of goods and services. Concerning goods, pollution can be caused by packaging (which often involves the use of plastic, which is made from fossil fuels) or transport, mainly. (5) Residences : Finally, residential areas provide their fair share of pollution as well. First, to be able to build homes, natural environment has to be destroyed in one way or another. Wildlife and plants are driven away and replaced by human constructions. As it requires the work of industries, construction itself is also a source of contamination of the environment. Then, when people settle in, they will produce waste every day, including a part that cannot be processed by the environment without harm yet. Effects of Environmental Pollution Now that we have identified the main causes of environmental pollution, let us study the negative effects it has: (1) Effects on Humans: The effects of environmental pollution on humans are mainly physical, but can also turn into neuro-affections in the long term. The best-known troubles to us are respiratory, in the form of allergies, asthma, irritation of the eyes and nasal passages, or other

Originals and Papers forms of respiratory infections. Notably, these well spread affections can be observed when air pollution is high in cities, when the weather gets hot, for instance. On top of that, environmental pollution has been proven to be a major factor in the development of cancer. This can happen for example when we eat reminiscences of pollutants used in the production of processed foods, or pesticides from the crops. Other, rarer, diseases include hepatitis, typhoid affections, diarrhoea and hormonal disruptions. (2) Effects on Animals: Environmental pollution mainly affects animal by causing harm to their living environment, making it toxic for them to live in. Acid rains can change the composition of rivers and seas, making them toxic for fishes, an important quantity of ozone in the lower parts of the atmosphere can cause lung problems to all animals. Nitrogen and phosphates in water will cause overgrowth of toxic algae, preventing other forms of life to follow their normal course. Eventually, soil pollution will cause harm and sometimes even the destruction of microorganisms, which can have the dramatic effect of killing the first layers of the primary food chain. (3) Effects on Plants : As for animals, plants, and especially trees, can be destroyed by acid rains (and this will also have a negative effect on animals as well, as their natural environment will be modified), ozone in the lower atmosphere block the plant respiration, and harmful pollutants can be absorbed from the water or soil. (4) Effects on the Ecosystem : In short, environmental pollution, almost exclusively created by human activities, has a negative effect on the ecosystem, destroying crucial layers of it and causing an even more negative effect on the upper layers.

Efficacy of low dose cyclophosphamide induction regimen in proliferative lupus nephritis : a prospective study Ananta Kumar Datta1, Manoj Soren2, Jyotirmoy Pal3, Prasun Roy2, Anirban De4, Sattik Siddhanta5, Partha Pratim Mukherjee6

An extended course of high-dose (cumulative dose usually > 6g over 6 months) intravenous (IV) cyclophosphamide (CYC), in combination with glucocorticoid, had been the standard treatment regimen (NIH protocol) for proliferative lupus glomerulonephritis. An alternative to prolonged intense immunosuppression, there are studies which showed successful treatment with low dose IV CYC (cumulative dose 3 g in 3 months) and IV glucocoticoid as a remission-inducing agent, followed by azathioprine (AZA) as a long-term remission-maintaining agent. Thirty consecutive patients with Lupus Nephritis class III and IV (RPS/ISN) or class V with III or IV were included. They were given Induction therapy by 6 cycles of low dose (500mg) i.v. pulse cyclophosphamide and 3 doses of 1g methylprednisolone followed by maintenance azathioprine. The present study is a “before and after comparison study”. Mean age of patients was 25.3 ±6.2 years. All were female. Of them, 73.3 %( n=22) were of stage 4, 23.3 %( n=7) of stage 3 and 3.33 %( n=1) of stage 5. At the end of induction regimen, creatinine reduced significantly from 1.06±0.54 to 0.74±0.17 (p= 0.0041) and urine became free from any active sediments (p<0.05). The urinary 24 hour protein excretion reduced significantly (4206.3±1155.5 mg vs 155.6±72.7 mg; p<0.0001). Induction regimen with low dose cyclophosphamide was found to be effective in proliferative lupus nephritis in our population. [J Indian Med Assoc 2016; 114: 87-9 & 93]

Key words : Lupus, Nephritis, Cyclophosphamide, Low dose.

Therefore, aggressive immunosuppression is indicated (usually systemic glucocorticoids plus a cytotoxic drug). An extended course of high-dose intravenous(IV) cyclophosphamide (CYC), in combination with glucocorticoids, has become the standard treatment of proliferative lupus glomerulonephritis since the pioneering prospective trials performed by the National Institutes of Health (NIH) group that demonstrated the superiority of this regimen over oral or IV glucocorticoid therapy alone. Several investigators have, however, raised some concerns about the indiscriminate use of the socalled “NIH regimen” to treat all lupus nephritis patients First, the results of the NIH studies, as well as a recent meta-analysis of all randomized trials in lupus nephritis , failed to demonstrate that an extended course of IV CYC was superior in terms of renal outcome and survival to other regimens of oral or IV cytotoxic drug(s). Second, high-dose IV CYC treatment is highly toxic; up to 25% of patients develop herpes zoster infection, up to 26% experience a severe infection, and up to 52% of women at risk have ovarian failure . As an alternative to prolonged intense immunosuppression, there are studies which

n established SLE median life expectancy is less than general population. While disability in patients with SLE is common due primarily to chronic fatigue, arthritis, and pain, the leading causes of death in the first decade of disease are systemic disease activity, renal failure, and infections. To date, most experts agree that the treatment of moderate-to-severe SLE consists of a period of intensive immunosuppressive therapy (induction therapy) followed by a longer period of less intensive maintenance therapy . Patients with proliferative forms of glomerular damage (ISN III and IV) usually have microscopic hematuria and proteinuria (>500 mg per 24 h); If untreated, virtually patients develop ESRD within 2 years of diagnosis.

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Disclaimer The information and opinions presented in the Journal reflect the views of the authors and not of the Journal or its Editorial Board or the Publisher. Publication does not constitute endorsement by the journal. JIMA assumes no responsibility for the authenticity or reliability of any product, equipment, gadget or any claim by medical establishments/institutions/manufacturers or any training programme in the form of advertisements appearing in JIMA and also does not endorse or give any guarantee to such products or training programme or promote any such thing or claims made so after.

— Hony Editor

MD (Gen Med) Associate Professor, Department of General Medicine, IPGME&R, Kolkata 700020 2 MD (Gen Med) RMO Cum Clinical Tutor, Department of General Medicine, Burdwan Medical College & Hospital, Burdwan 713104 3 MD (Gen Med) Professor, Department of General Medicine, RG Kar Medical College & Hospital, Kolkata 700004 4 MD (Gen Med) RMO Cum Clinical Tutor, Departmet of General Medicine, NRS Medical College & Hospital, Kolkata 700014 5 MD (Gen Med) Assistant Professor, Department of General Medicine, IPGME&R, Kolkata 700020 6 MD (Gen Med) Professor, Department of General Medicine, Calcutta National Medical College & Hospital, Kolkata 700014

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J INDIAN MED ASSOC, VOL 114, NO 6, JUNE 2016

EFFICACY OF LOW DOSE CYCLOPHOSPHAMIDE INDUCTION REGIMEN — DATTA ET AL

The Euro-Lupus Nephritis Trial studied 90 SLE patients with proliferative glomerulonephritis who were assigned to a high-dose IV CYC regimen (6 monthly pulses and 2 quarterly pulses; doses increased according to the white blood cell count nadir) or a low-dose IV CYC regimen (6 fortnightly pulses at a fixed dose of 500 mg), each of which was followed by AZA. Follow up continued for a median of 41.3 months in the low-dose group and 41 months in the high- dose group. Renal remission was achieved in 71% of the low-dose group and 54% of the high-dose group (not statistically significant). Renal flares were noted in 27% of the low-dose group and 29% of the high-dose group. Although episodes of severe infection were more than twice as frequent in the high-dose group, the difference was not statistically significant. The results of the trial indicate that there was no significantly greater cumulative probability of treatment failure in patients taking a low-dose IV CYC regimen than in those taking a high-dose regimen, and the cumulative probability of achieving renal remission was similar in both groups. In another study done in Egypt by Sabry A, Abo-Zenah H . Fourtysix SLE patients with diffuse proliferative glomerulonephritis were asigned to either a high-dose (a maximum of 1 g/dose) of IV CYC (HD-CYC) for six monthly pulses followed by two quarterly pulses or a fixed low-dose (500 mg/dose) of IV CYC (LD-CYC) for six fortnightly pulses with a cumulative dose of 3 g. At the end of the study (1 year after starting therapy), there was no difference either in patients' or in renal survival in both groups. Another study was conducted by M. A. Frutos, A. Martín Gómez where they studied with intermittent pulse therapy with intravenous cyclophosphamide (IC) in 97 patients (75 female) aged over 20 years. The series was divided into three groups. Group A (n = 39) received monthly IC pulses (begin 1 g) for up to 24 months between 1985-1991, Group B (n = 47) received monthly IC pulses (1g) for six months with additional quarterly doses for a maximum of 18 months, depending on the therapeutic response (from 1991) and from 1999, Group C (n = 11) patients were treated with low-dose IC (3 g in three months) followed by azathioprine (2 mg/kg) or mycophenolate mofetil (1.5-2.0 g/day) for 12-18 months. Comparison of the values at baseline and after 24 months showed that the serum creatinine (mg/dl) fell in Group A from 1.77 ± 1.06 to 1.09 ± 0.63, in Group B from 1.22 ± 0.85 to 0.95 ± 0.45, and in Group C from 0.90 ± 0.23 to 1.17 ± 0.54 (p < 0.05). In the same period, proteinuria (g/day) fell in Group A from 6.19 ± 4.31 to 0.79 ± 1.76, in Group B from 4.43 ± 3.17 to 2.08 ± 3.65, and in GroupC from 5.43 ± 3.37 to 3.22 ± 4.00 (p < 0.05). There was no differences between the three groups in both variables .In our study; there is significant fall in proteinuria from 206.33± 1155.51 with a maximum of 8100mg and 11

showed successful treatment of lupus nephritis patients with a sequential regimen consisting of low dose IV CYC (cumulative dose 3 gm) and IV glucocoticoid as a remission-inducing agent, followed by azathioprine (AZA) as a long-term remission-maintaining agent . Hence this study is undertaken to find out the response to such low dose cyclophosphamide plus corticosteroids in patients with proliferative glomerulonephritis for remission induction. 8

MATERIALS AND METHODS

Location: Thirty consecutive patients fulfilling the criteria and willing to participate in the study were selected from patients admitted in General medicine ward and attending Rheumatology clinic of Calcutta National Medical College and Hospital. Inclusion criteria: Lupus Nephritis class III and IV (RPS/ISN) or class V with III or IV. Exclusion criteria: Patients with any other form of renal disease like associated diabetes mellitus, preexisting hypertension, and chronic kidney disease due to causes other than SLE were excluded. Patients having bone marrow suppression, very low platelet count, or who had taken CYC or AZA during the previous year or had taken >15 mg/day of prednisolone (or equivalent) during the previous month were excluded (except for a course of glucocorticoids for a maximum of 10 days before referral were also excluded. Patients with age less than 12 years and pregnancy were excluded. Study methodology: All the patients thus diagnosed to have lupus nephritis of class III and class IV, as well as class V accompanied by III or IV disease were given Induction therapy by 6 cycles of chemotherapy each consisting of low dose (500mg) i.v. pulse cyclophosphamide and 3 doses of 1gm methylprednisolone. This was followed by maintenance therapy consist of prednisolone and azathioprine in the treatment protocol .Each patient was counselled about this therapy and consent taken. Evaluation for disease activity is performed by using renal function, urine microscopy and 24 hour urinary albumin excretion. The present study is a “before and after comparison study” in which different laboratory parameters before the introduction of Low dose pulse cyclophosphamide and methylprednisolone were compared with their values after 3 months of the same therapy. Significance of difference in means was calculated by “paired t test”. A value of p< 0.05 was considered significant. RESULTS AND ANALYSIS

Total 30 patients of SLE with grade III or IV were included. The mean age of the patients was 25.33yrs± 6.177yrs, maximum age is 38 yrs and minimum is 17 yrs.

All patients were female. 73.3 % (n=22) are of stage 4, 23.3 %( n=7) are of stage 3 and 3.33 %( n=1) is of stage 5. The results are summarised in Table 1. The mean urea was 46.3± 25.775 mg/dl with a maximum of 120mg/dl and minimum of 17 mg/dl. The mean creatinine was 1.062± 0.538 mg/dl with a maximum of 2.85mg/dl and minimum of 0.4 mg/dl. At initial visit, the mean 24Hr urinary protein was 4206.33± 1155.51with a maximum of 8100mg and minimum of 3600 mg. At the end of remission induction regimen, the mean 24Hr urinary protein was 155.567± 72.72with a maximum of 436 mg and minimum of 80 mg. The mean urea was 28± 12.98 mg/dl with a maximum of 70mg/dl and minimum of 16 mg/dl. The mean creatinine was 0.742± 0.172 mg/dl with a maximum of 1.2mg/dl and minimum of 0.4 mg/dl. At initial visit urine microscopy revealed 3 patients have urinary cast and 10 have microscopic hematuria. At the end of intensive phase (3 months) urine microscopy revealed no cast or hematuria in any of the patient. DISCUSSION

Cytotoxic/immunosuppressive agents added to glucocorticoids are recommended to treat serious SLE like nephritis. Almost all prospective controlled trials in SLE involving cytotoxic agents have been conducted in combination with glucocorticoids in patients with lupus nephritis. In patients whose renal biopsies show ISN grade III or IV disease, early treatment with combinations of glucocorticoids and cyclophosphamide reduces progression to ESRD and improves survival . If cyclophosphamide is used for induction therapy, the recommended "National Institutes of Health (NIH)" dose (based on clinical trials at that institution) is 500–750 mg/m intravenously, monthly for 6 months, followed by maintenance with daily oral mycophenolate or azathioprine . Since cyclophosphamide has many adverse effects and is generally disliked by patients, alternative approaches using lower doses have been tested. European studies have shown that IV cyclophosphamide at doses of 500 mg every 2 weeks for six doses ("low dose") is as effective as the recommended higher dose given for a longer duration in the NIH regimen ("high dose") . Followup studies have shown no differences in the high-dose and low-dose groups (death or ESRD in 9–20% in each group). 9

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Table 1 — Results of the study Baseline (n=30) After 3 months (n=30) P value Serum urea 46.3±25.775 Serum creatinine 1.062±0.538 Urine microscopy: Red cells; Cast 10; 03 Urinary 24 h protein 4206.33±1155.51

28±12.98 0.742±0.172

0.0018 0.0041

0; 0

<0.05

155.567±72.72

<0.0001

minimum of 3600 mg to 155.567± 72.72. So average improvement for mean 24 Hr urinary protein is 96.3% (n=30, p <0.0001). However, another study from Puerto Rico has shown that the standard dose cyclophosphamide therapy appears to be more effective, and similar in terms of drug safety, than the low-dose regime for lupus nephritis. In fact, poor outcomes have been reported in African Americans and Hispanics compared to Caucasians with lupus nephritis and thus might merit high or standard dose regimen . Further, genetic polymorphism of cytochrome P 450 may also lead to differential results of two regimens of cyclophosphamide in different ethnic groups. However, our study showed both groups to be similar, which is consistent with earlier larger studies, alluded above. 14

CONCLUSION

Thus before and after comparative study with induction regimen of 6 doses of 500 gms IV cyclophosphamide along with intravenous methylprednisolone for patients with proliferative lupus nephritis showed significant improvement in renal function. REFERENCES: 1 Boumpas DT, Sidiropoulos P, Bertsias G — Optimum therapeutic approaches for lupus nephritis: What therapy and for whom? Nat Clin Pract Rheumatol 2005; 1: 22-30. 2 Austin HA iii,Klippel JH,Balow JE, le Riche NG, Steinberg AD, Plotz PH, et al — Therapy of lupus nephritis: controlled trial of prednisone and cytotoxic drugs. N Engl J Med 1986;314:614-9. 3 Boumpas DT, Austin HA III, Vaughan EM, Klippel JH, Steinberg AD, Yarboro CH, et al — Controlled trial of pulse methylprednisolone versus two regimens of pulse cyclophosphamide in severe lupus nephritis. Lancet 1992; 340: 741–5. 4 Gourley MF, Austin HA III, Scott D, Yarboro CH, Vaughan EM, Muir J, et al — Methylprednisolone and cyclophosphamide, alone or in combination, in patients with lupus nephritis. Ann Intern Med 1996;125: 549-57. 5 Urowitz MB. Is “aggressive” therapy necessary for systemic lupus erythematosus? Rheum Dis Clin North Am 1993;19:263-70. 6 Ponticelli C. Treatment of lupus nephritis: the advantages of a flexible approach. Nephrol Dial Transplant 1997;12:2057–9. 7 Bansal VK, Beto JA — Treatment of lupus nephritis: a metaanalysis of clinical trials. Am J Kidney Dis 1997;29:193-9. 8 Houssiau FA, Vasconcelos C, D’Cruz D — Early response to immunosuppressive therapy predicts good renal outcome in lupus nephritis: lessons from long-term followup of patients in the Euro- Lupus Nephritis Trial, Arthritis Rheum 50: 393440, 2004. 9 Bevra H Hahn —Treatment of life-threatening SLE: Proliferative forms of lupus nephritis. Longo, Fauci, Kasper, Hauser, Jameson, Loscalzo. Harrison’s Principles of Internal Medicine. 18th edition, volume-2, 319: 2733. 10 Steinberg AD, Steinberg SC — Long-term preservation of renal function in patients with lupus nephritis receiving treatment that includes cyclophosphamide versus those treated with prednisone only. Arthritis Rheum 1991; 34: 94550. 11 Houssiau FA, Vasconcelos C, D’Cruz D, Sebastiani GD, Garrido E, Danieli MG, et al — Immunosuppressive therapy in (Continued on page 93)

Originals and Papers

KNOWLEDGE, ATTITUDE AND PRACTICE OF CONTRACEPTION — KUSHWAH AND AGRAWAL 1

Knowledge, attitude and practice of contraception : a study from rural tertiary care centre Beenu Kushwah1, Sonal Agrawal2

Realizing the ill effects of increasing population, India was the first country to have started a state sponsored Family Planning Programme, long back in 1952; India is the second most populous country of the world only after China. To attain the required targets India needs nationwide surveys to assess the practices of contraception especially in poor performing states in order to utilize the available resources according to local needs. Hospital based, cross-sectional survey conducted amongst the women of post natal ward of a referral hospital mainly catering rural population. Knowledge, Attitude and Practice survey of family planning was conducted amongst these women. A total of 4221 subjects were interviewed.58% of these women were aware of contraceptive methods, mostly Permanent followed by IUCD, Condom, least of oral pills. Spacing methods are less known amongst rural women while the use is even lower which calls for further strengthening of the existing awareness programmes. [J Indian Med Assoc 2016; 114: 90-3]

study, 78% belonged to 18-22 years age group. Sixtytwo per cent women were illiterate, 24% were literate but without any formal schooling, 11% were literate till primary and rest had studied above primary. Only 3% were employed with regular source of income, 16% were running some home business, 12% were working as helper’s at others’ houses both with irregular income and 20% were farmers and were helping their husbands (Table 1). On assessing the knowledge it was found that 58% of women were aware of at least one of the available family planning methods, maximum knowledge was for permanent method (Tubectomy-56%, Vasectomy-6%), followed by IUCD (30%), Condoms (28%), and oral pills (11%) (Fig 1). Although majority (71%) of all women who had knowledge of any family planning methods showed positive attitude towards use but only 6% of these had actually used any method ever, of which majority (53%) had used IUCD, 33% condoms and only 14% had used oral pills resulting in a very high knowledge-practice gap i.e. 96%. None of the Participants were aware of emergency contraceptive method (i-pill) (Figs 2 and 3).

being 2.3 against the National average of 2.9 and 2 respectively .

n First March 2011, Indian’s population stood at 1.21 Billion which is projected to be 1.4 Billion in 2026 . India which accounts for world’s 17.5% population is the second most populous country in the world next only to China (19.4%). Of the 1.21 Billion Indians, 68.84% live in rural area while 31.6% live in Urban areas, as per the census 2011 . Therefore more than half of the total population reside in rural areas in this country.

One of the main objectives of the family planning programme is to spread the knowledge of contraceptive methods and develop, among the people, an attitude favourable for adoption of contraceptive method. The progress achieved in this sphere is normally assessed from the results of Knowledge, Attitude and Practice survey .

Despite the fact that India was the first country to have started state sponsored Family Planning Programme in 1952, decline in the rate of Total Fertility Rate (TFR) has not been to the extent as was aimed, especially in rural areas . For historical reasons some states in India depicted a tendency of higher growth of population. In order to facilitate the creation of area specific programmes, Government of India in 2001 constituted a group of eight states which were lagging behind in improving their fertility indicators. This group is called as Empowered Action Group (EAG).

No of females in percentage*

Key words : Contraception, Total Fertility Rate, Family planning.

Present study was conducted amongst the women of post natal ward of one of the Tertiary Health care Centres of Madhya Pradesh. Department of Obstetrics and Gynaecology of Gandhi Memorial Hospital had total 4927 deliveries (Vaginal and caesarean both) during last 6 months period, 90% of these women come from rural areas as there is no other equipped government run Health Care Centre is available across a wide area.

Fig 1 : Knowledge regarding each FP method

MATERIAL AND METHOD

Present study was conducted in the state of Madhya Pradesh (MP), one of the members of EAG. Total Fertility Rate (TFR) of MP in 2009 was 3.3, against the National average of 2.6 with even bigger difference between Rural and Urban areas, Rural TFR being3.6 and Urban TFR Department of Obstetrics and Gynaecology, Shyam Shah Medical College and Associated Sanjay Gandhi and Gandhi Memorial Hospital, Rewa 486001 MD, DNB, Assistant professor, MBBS, Junior Resident 90

Number of females Percentage (N=4221) (%)

Present Age (in yrs ) : <18 42 18-22 3292 23-27 760 >27 127 Level of Education : Illiterate 2617 Literate (No formal Schooling) 1013 Literate (till Primary) 464 Literate (>Primary) 127 Occupation : Employed with regular income 127 Home business (irregular income) 675 Helper at other houses (irregular income) 507 Farmers (irregular income) 844 Housewife (No income) 2068 Parity : One 1646 Two 971 Three 1140 > Three 464

1.0 78.0 18.0 3.0 62.0 24.0 11.0 3.0 3.0 16.0 12.0 20.0 49.0 39.0 23.0 27.0 11.0

There was no reliable source of information for majority of participants (72%), while Health professionals contributed to only 12% and media to 16%. Only 7% were satisfied with their current method of use (Fig 4). Main reason for not practicing any one of family planning methods was inefficient accessibility to right information and follow up facility if needed (69%), rest were not using any method because of non cooperation by their husbands and lesser role in decision making. While majority of participants (67%) were willing to use contraceptive method in future, 9% refused to use any method while 24% were not able to decide. Amongst those who had positive attitude, majority (64%) wanted to use condom followed by IUCD (28%) and only 8% liked pills. In our study maximum awareness was for permanent method of family planning and nil for emergency contraception while Knowledge for temporary methods in present study was relatively low, which is comparable with another study from India , while it was almost same for all methods in developed regions of world . In present study oral pills were used by only 4% women in contrast to the women of the United State where oral pills are the most popular reversible method of contraception. Other study from ICMR also showed low use of oral pills by Indian females, which is com4-6

OBSERVATIONS

Women of age group 18-35 years, were included in the

Characteristics

Table 1 — Showing base line characteristics of study population

DISCUSSION

No of females in percentage*

This was a Hospital based, Cross Sectional, Observational, Descriptive study during a period of 6 months from June to November 2011. After taking informed consents and briefing about the aim of study, A Total of 4221 women of post natal ward of our department consented to be interviewed. A 20 point, Semi-structured questionnaire was read out to the subjects. Data were collected regarding socio-demographic features, knowledge, attitude and practices of various family planning methods.

Fig 2 : Practice of each FP method

KNOWLEDGE, ATTITUDE AND PRACTICE OF CONTRACEPTION — KUSHWAH AND AGRAWAL

J INDIAN MED ASSOC, VOL 114, NO 6, JUNE 2016

A study from Reddy showed relatively low contribution of health care personnel in providing family planning knowledge, which was observed in our study as well. The role of health care personnel in providing contraceptive knowledge should be emphasized as it’s a two way communication process. Sixtyone per cent women of our study were Para three and above and 46% had underwent unconventional methods for termination of pregnancy at least once before present pregnancy, while 26% had actually wished for termination of present pregnancy but had to continue because of non availability of the facilities nearby. These findings from our study are an indirect reflection for the need of termination of pregnancy because of poor knowledge and even lesser practice of contraception. According to one study on an average 5 million legal and illegal abortions per annum could be abortion rate of India for current decade . The Indian Survey of Death reports that nearly 18% of maternal deaths result from abortion .Majority of these abortions were illegal and indirectly reflect the significant burden of unmet need of family planning methods available to the women from rural and remote areas. 16

147(6.0%)

2301(94.0%)

Practicing females Knowledge practice gap Fig 3 : Showing knowledge practice gap (total knowledgeable females = 2448)

No reliable information Through Health Professionals Through Media

CONCLUSION

In recent years, the need for studies for assessing prevailing contraceptive practices is very important across various regions of this country to know about regional needs. Results of present study clearly reflect an urgent need for facilitating the access to more information, education and communication with the reproductive couples according to individual needs. This study indicates a pressing need for effective intervention strategies, both at the community and clinic level, backed with efficient counselling, motivation and provision of services in Rural and Remote areas.

16.0%

12.0% 72%

Fig 4 : Showing contribution by different sources of information

parable to other studies . The huge knowledge and practice gap of our study has also been observed by others , factors which could be identified for this were; wrong information regarding side effects, scarcity of health care facility to consult if required and lesser role in decision making, all of these are directly related with low literacy levels and inadequate inclusion of the educational sessions related with family planning methods by the health professionals. Findings of study from India observed similar gap because of factors directly related with socio economic development . 9-11

12-14

REFERENCES 1 Family Welfare Statistics in India 2011: Statistics Division, Ministry of Health and Family Welfare, Government of India. 2 J Mao: Knowledge, Attitude and Practices of Family Planning: A study of Tezu Village, Manipur (India). The Internet Journal of Biological Anthropology, 2007 Volume 1 (1). 3 Srivastava Reena, Srivastava Dhirendra Kumar, Jina Radha, Srivastava Kumkum, Sharma Neela, Saha Sushmita — Contraceptive knowledge, attitude and practice (KAP) survey. Journal of Obstet Gynecol India 2005; 55: 546-50. 4 Young LK, Farguhar CM, Mc Cowan LME — The Contraceptive practice of women seeking termination of pregnancy in Aukland clinic. NZ Med J 1994; 107: 189-91. 5 Aneblom G, Larson M, Odlind V — Knowledge, use and attitudes towards emergency contraceptive pills among Swedish women presenting for induced abortion. BJOG 2002; 109: 155-60. 6 Bromham DR, Cartmill RS — Knowledge and use of secondary contraception among patients requesting termination of pregnancy. BMJ 1993; 306: 556-7. 7 Johansson ED — Future developments in hormonal contraception. Am J Obstet Gynecol 2004; 4: s69-s71.

8 Baveja R, Buckshee K, Das K, Das SK, Hazra MN, Gopalan S et al — Evaluating contraceptive choice through the method –mix approach (An ICMR Task Force Study). Contraception 2000; 61: 113-9. 9 Takkar N, Goel P, Saha PK, Dua D — Contraceptive practices and awareness of emergency contraception in educated working women. Indian J MedSci 2005; 59: 14349. 10 Mittal S, Bahadur A, Sharma JB — Survey of knowledge, attitude and practice of contraception and medical abortion in women attending family planning clinic. J Turkish German Gynecol Assoc 2007; 8: 3. 11 Kanojia JK, Nirbhavane NC, Toddywala VS, Betrabet SS, Patel SB, Datte S, et al — Dynamics of contraceptive practice amongst urban Indian women. Natl Med J India1996; 9: 10912. 12 Mahawar Priyanka, Anand Shweta, Raghunath Deepa, Dixit Sanjay — Contraceptive Knowledge, Attitude and Practices

in mothers of Infants: A Cross Sectional study. National Journal of Community Medicine 2011; 2: 105-7. Sharma A, Sharma V — Training of opinion leaders in family planning in India: Does it serve any purpose. Rev Epidemiol Sante Publique 1996; 44: 173-80. Sharma V, Sharma A — Family planning practices among tribals of South Rajasthan, India. J Res Educ Indian Med 1991; 10: 5-9. Gautam AC, Seth PK — Appraisal of the knowledge, attitude and practices (KAP) of family control devices among rural rajputs and Scheduled caste of Hatwar area of Bilaspur district, Himachal Pradesh. Anthropologist 2001; 4(4): 289-292. R Reddy S, K C Premrajan, K A Narayan, Akshaya Kumar Mishra — Rapid appraisal of knowledge, attitude and practices related to family planning methods among men within 5 years of married life. J Prev Soc Med 2003; 34: 63-6.

(Continued from page 89) lupus nephritis. The Euro-Lupus Nephritis Trial, a Randomized Trial of Low-Dose Versus High-Dose Intravenous Cyclophosphamide. Arthritis Rheum 2002; 46: 2121-31. 12 Sabry A, Abo-Zenah H, Medhat T — A comparative study of two intensified pulse cyclophosphamide remission-inducing regimens for diffuse proliferative lupus nephritis: an Egyptian experience. Int Urol Nephrol 2009; 41: 153-61. 13 M A F r u t o s , A M a r t í n G ó m e z — I n t r a v e n o u s Cyclophosphamide for lupus nephritis: twenty years reducing the dose. NEFROLOGÍA. Volumen 27. Número 1. 2007

14 Castro-Santana LE, Colón M, Molina MJ, Rodríguez VE, Mayor AM, Vilá LM — Efficacy of two cyclophosphamide regimens for the treatment of lupus nephritis in Puerto Ricans: low versus standard dose. Ethnicity & disease 2010; 20: S1-116-21. 15 Contreras G, Lenz O, Pardo V, Borja E, Cely C, Iqbal K, Nahar N, de La Cuesta C, Hurtado A, Fornoni A, BeltranGarcia L, Asif A, Young L, Diego J, Zachariah M, SmithNorwood B — Outcomes in African Americans and Hispanics with lupus nephritis. Kidney Int 2006; 69: 1846-51

Originals and Papers

OCULAR MANIFESTATIONS OF THALASSAEMIA PATIENTS WITH REPEATED BLOOD TRANSFUSION — GORAIN ET AL

Ocular manifestations of thalassaemia patients with repeated blood transfusion and long term use of chelating agent Badal Chandra Gorain1, Piyali Sarkar2, Kumaresh Chandra Sarkar3, Jyotirmoy Dutta4

To study the ocular manifestations in beta-thalassaemia major patients with multiple blood transfusions, ocular side-effects of iron chelating agents and to find out any correlation of the side-effects of iron chelating agents with age and sex, a prospective observational study was undertaken which included 100 bthalassaemia major patients, who were divided into 2 groups based on thalassaemia treatment regimens received at the time of presentation. Proper medical history, thorough physical and ocular examinations were done to determine the prevalence of ocular manifestations and to correlate these manifestations with iron chelating agents. In 100 patients (56 males, 44 females) with age ranging between 6 months and 15 years, ocular involvements were detected in 52 cases in the form of lens opacity, decreased visual acuity, retinal pigment epithelium degeneration and disc hyperaemia, more in group receiving blood and deferriprone therapy. Retinal pigment epithelium degeneration and mottling were found significantly associated with patients receiving oral chelating agents but there was no significant correlation with lens opacity or decreased visual acuity. A large number of thalassaemic children were found to have ocular complications despite moderate doses of deferriprone and in the presence of high serum ferritin levels, which implicate a role of iron in ocular pathology in thalassaemia. Most of the ocular changes of beta-thalassaemia were attributed to longer duration of disease. These changes had slight male preponderance. Retinal pigment epithelium degenerations and mottling, venous tortuosity, disc hyperaemia were found significantly more in patients on long term oral chelating agents (deferriprone). [J Indian Med Assoc 2016; 114: 94-7]

Key words : Beta-thalassaemia, deferriprone, ocular complications.

Although blood transfusions therapy alleviates halassaemia is a heterogeneous group of genetic dis order resulting from defects in genes producing α - or anaemia, they lead to massive tissue deposition of iron and β -globin chains of haemoglobin. Beta-thalassaemia may eventually result in multiorgan dysfunction. Iron results from a defect in β -globulin chain production and overload occurs either due to excess gastro-intestinal ranges from clinically silent heterogeneous thalassaemia absorption or secondary to repeated blood transfusions. minor to severe transfusion-dependent thalassaemia Transfusional iron leads to iron deposition in the reticulomajor . These are the most common single gene disorder endothelial system of the spleen, liver, bone marrow and worldwide . Mutations involving the beta-globin gene in eye. In advanced cases, iron also accumulates in beta-thalassaemia cause disruption in red blood cell parenchymal cells of the liver, heart, pancreas and maturation leading to ineffective erythropoiesis and endocrine organs, which are sensitive to the toxic effects multisystem involvement . It is estimated that 1.5 % of the of iron. Adverse ocular changes include cataract, world population, ie, 200 million people are carriers of the pigmentary retinopathy, optic neuropathy, thinning and β -thalassaemia gene. In India, the mean prevalence of the tortuosity of retinal vessels and vitreoretinal haemorrhages which are due to the disease itself or as β -thalassaemia gene is 3.3 %; 1,000 children are born with side-effects of the iron chelating agents . β -thalassaemia major each year in India. Worldwide MATERIAL AND METHOD incidence is 60000 per year which are mostly in This prospective observational study was conducted developing world . on 100 beta-thalassaemia major patients who attended 1

thalassaemia clinic, Calcutta National Medical College & Hospital, Kolkata during the period of September 2010 to March 2012. All patients were informed about the nature of the study and an informed consent for participation obtained. In case of minors, consent was taken from their parents. The diagnosis of beta-thalassaemia major was

Department of Ophthalmology, Calcutta National Medical College, Kolkata 700014 1 MS, Medical Teacher on Trainee Reserve 2 MS, DNB, MNAMS, Associate Professor 3 MS, Assistant Professor 4 MS, Professor and Head of the Department 94

confirmed by clinical and haematological examinations at CNMC paediatric outpatient's department (OPD). All patients received scheduled blood transfusions at three to four weeks intervals. The study included children aged <15years who were diagnosed as cases of betathalassaemia major, receiving multiple blood transfusions with or without chelating therapy. Patients >15 years of age, or having haemoglobinopathies other than betathalassaemia major, anaemia due to other causes or other congenital diseases were excluded from the study. The patients were divided into 2 groups. Group A received blood transfusion but no iron chelating therapy and group B received combination regimen of blood transfusion and oral deferriprone. Paediatrician elicited a complete general history (including family history and details of previous blood transfusions and iron chelation therapy) and performed systemic examination, especially for presence of pallor, icterus, frontal bossing, prominent maxilla, skin hyperpigmentation and hepatosplenomegaly. Laboratory investigations included baseline complete blood counts and serum ferritin estimation. The ophthalmologist elicited a complete ophthalmic history and performed ocular examination. Ocular examination included near and distance visual acuity assessment with and without glasses in all children using preferential looking test, picture cards and Snellen's charts as applicable, external examination with diffuse illumination, slit-lamp examination, direct and indirect ophthalmoscopy and fundus fluorescein angiography (FFA) in selected patients. The patients were followed up at three-monthly intervals during which complete ocular assessment was done and progression in ocular changes, if any, noted. Serum ferritin levels were assessed at sixmonthly intervals. Ocular findings at follow-up visits were correlated with the age and sex of the patient, serum ferritin level and use of iron chelating agent (deferriprone). A p-value less than 0.05 was considered statistically significant. Statistical analyses were performed using software SPSS (version 12). For correlation of sex with lenticular opacities, retinal pigment epithelium (RPE) degeneration and RPE mottling, Chi test was used. Correlation of lens opacities, RPE degeneration and RPE mottling with serum ferritin levels, was done by Pearson's correlational analysis with p-value <0.05 taken as significant. Correlation of lens opacities, RPE degeneration and RPE mottling with dose of deferriprone in various groups too was obtained by Pearson's correlational analysis. 2

Group A included 45patients (45%) who received only blood transfusion but no iron chelating agents. Group B included 55patients (55%) who received blood transfusions and oral chelating agent (deferriprone 75-100 mg/kg/day). Eighteen (85.71%) and 3 patients (14.29%) below five years of age, 17 (38.63%) and 27 patients (61.37%) between 6 and 10 years of age and 10 (28.57%) and 25 patients (71.43%) between 11 and 15 years of age were in group A and B respectively (Table 1). Ocular involvement was observed in 52 patients (52%), whereas 48 patients (48%) showed no ocular involvement. It had been seen that ocular changes were increased in older than in younger children (91.42% in 11-15 years and 19.04% in <5 years of age groups). The fundus changes (68.57%) were also more in 11-15 years age group (Table 2). Ocular involvements in relation to sex are not significant (p=0.125).There were 30 male patients (57.69%) and 22 female patients (42.31%) having ocular involvement respectively. It had been seen that ocular involvements were more common in group B (n=45; 81.82 %) than in group A (n=7, 15.56%). Ocular involvements were significant (p<0.0001) in relation to treatment regimen groups. Decrease in visual acuity were more in group B (n=16; 29.09%) than group A (n=6; 13.33%) thalassaemia patients. Significant correlation of deferriprone therapy with RPE degeneration (p=0.003) and RPE mottling (p=0.001)was observed but not with decreased visual acuity (p=0.058), lens opacity (p=0.928), venous tortuosity (p=0.093) and disc hyperaemia (p=0.249) (Table 3). The study showed that the average serum ferritin levels were increased in thalassaemia patients who had ocular changes and decreased visual acuity. It was observed that ocular changes (p<0.001) were significantly associated with high serum ferritin level in the form of decreased

Table 1 — Distribution of Thalassaemia Cases according to Treatment Regimen in Various Age and Sex Groups Age/sex Group A (without Group B (with Total iron chelating chelating agent(n=100) agent) (n=45) deferriprone) (n=55) Age group (in years) : <5 18(85.71%) 3(14.29%) 21(21%) 6-10 17(38.63%) 27(61.37%) 44(44%) 11-15 10(28.57%) 25(71.43%) 35(35%) Sex : Male 24(42.86%) 32(57.14%) 56(56%) Female 21(47.72%) 23(52.27%) 44(44%)

OBSERVATIONS

In this study, there were 56 male patients (56%) and 44 females (44%)(Table 1). Their age ranged from six months to fifteen years. Among them, 21 patients were <5 years, 44 between 6 -10 years and 35 between 11-15 years. They were assigned in two groups according to treatment regimens.

Table 2 — Distribution of Cases according to Ocular Manifestations Age (years)

Ocular involvement (%) <5 (n=21) 4(19.04%) 6-10 (n=44) 16(36.36%) 11-15 (n=35) 32(91.42%) Total (n=100) 52(52%)

Decreased VA(<6/9)(%) 1(4.76%) 3(6.81%) 18(51.42%) 22(22%)

Lens opacity(%) 0 7(15.91%) 6(17.14%) 13(13%)

Fundus changes (%) 3(14.28%) 4(9.09%) 24(68.57%) 30(30%)

OCULAR MANIFESTATIONS OF THALASSAEMIA PATIENTS WITH REPEATED BLOOD TRANSFUSION — GORAIN ET AL

J INDIAN MED ASSOC, VOL 114, NO 6, JUNE 2016

Table 3 — Groupwise Distribution of Thalassaemia Patients with Ocular Manifestations in the Two Treatment Regimen Groups Manifestations Group A Group B Total (%) P-value (without iron (with deferriprone) chelating) (n=45) (n=55) Ocular involvement : Present 7(15.56 %) 45(81.82 %) 52(52%) <0.0001 Absent 38(84.44 %) 10(18.18 %) 48(48%) Best corrected visual acuity : Normal 39(86.67 %) 39(70.91 %) 78(78%) 0.058 Decreased 6(13.33 %) 16(29.09 %) 22(22%) Lens opacity : Present 6(13.33%) 7(12.73%) 13(13%) 0.928 Absent 39(86.67%) 48(87.27%) 87(87%) RPE degeneration : Present 1(2.22%) 12(21.82%) 13(13%) 0.003 Absent 44(97.78%) 43(78.18%) 87(87%) RPE mottling : Present 2(4.44%) 16(29.09%) 18(18%) 0.001 Absent 43(95.56%) 39(70.91%) 82(82%) Venous tortuosity : Present 2(4.44 %) 8(14.55 %) 10(10%) 0.093 Absent 43(95.56 %) 47(85.45 %) 90(90%) Disc hyperaemia : Present 1(2.22 %) 4(7.27 %) 5(5%) 0.249 Absent 44(97.78 %) 51(92.73 %) 95(95%)

world had also been performed in patients of up to 45 years of age. This age disparity can be attributed to lower survival rates among thalassaemia patients in India; reasons for this seem to be poor compliance with therapy, difficulty in obtaining regular blood transfusions and high cost of iron chelation therapy. This study showed a slight male preponderance (1.25:1). This is consistent with studies of Gartaganis , Gaba and Taneja where ratios of 1.07:1, 1.33:1 and 1.25:1 respectively, were observed. Ocular involvement was seen in 52% of patients. Gartagantis , Gaba , Taneja , Dewan and Abdel-Malak , reported figures of 41.3%, 58% , 71.4%,36% and 68% respectively. Gartaganis , Gaba and Taneja in their studies, found lens opacities in 13.85%, 45.7% and 40% respectively. 6

Thirteen out of 100 subjects in this study had lenticular opacities (13%). No significant correlation was found between the occurrence of lens opacity and deferriprone therapy. Lens opacities were correlated significantly with higher average serum iron levels and serum ferritin levels. This is in contrast with studies of Gartaganis where no correlation between the BCVA(P<0.001), RPE degeneration (p<0.001), RPE occurrence of lens opacity and mottling (p<0.01) and venous raised serum ferritin was found. tortuosity (p<0.025) (Table 4). Table 4 — Relation of Mean Serum Ferritin Level with Dewan found that 20% of patients DISCUSSION Different Ocular Manifestation among Different had cataract that was associated Thalassaemia is a hereditary Thalassaemia Patients with raised serum ferritin levels. disorder characterised by Manifestations No of Mean serum P-value Decreased visual acuity was found reduction in the synthesis of cases ferritin (ng/ml) in 22 patients (22%). Sixteen globin chains (α or β ). Reduced Ocular involvement : patients receiving deferriprone had Yes 52 2509.92±480.508 <0.001 globin chain synthesis causes No 48 2036.67±675.656 decreased visual acuity (29.1%). reduced haemoglobin synthesis Best corrected visual acuity : Six patients not receiving iron and eventually produces a Decreased 22 2699.55±529.492 <0.001 chelation had decreased visual Normal 78 2165.21±603.395 hypochromic microcytic acuity (13.4%). Thus, iron Lens opacity : anaemia because of defective Present 13 2330.77±664.700 0.769 c h e l a t i o n showed minimal hemoglobinisation of red blood Absent 87 2275.59±256.611 statistical significance regarding cells. Patients suffering from RPE degeneration : decreased visual acuity (p=0.058). beta-thalassaemia major present Present 13 2889.62± 549.873 <0.001 This observation is consistent with Absent 87 2192.08±587.569 with varied ocular and systemic RPE mottling : the findings of Taneja and Taher . manifestations. Present 18 2628.61±580.580 0.010 Regarding the fundus changes of Ocular findings range from Absent 82 2206.84±613.287 the thalassaemia patients in this decreased visual acuity, colour Venous tortuosity : study, RPE degeneration was Present 10 2516.67±441.942 0.025 vision anomalies and night observed in 13% (p=0.003), RPE Absent 90 2163.90±641.000 blindness, cataract, visual field Disc hyperaemia : mottling in 18% (p=0.001) and disc defects and optic neuropathy. Present 5 2635.00±553.286 0.212 hyperaemia in 5% of patients Iron-chelating agents like Absent 95 2264.22±626.915 (p=0.249). desferrioxamine and 6

deferriprone are reported to cause many of these ocular changes. In this study, various ocular manifestations of β -thalassaemia and the effects of various iron chelating agents on the eyes were found. The results of this study were based on data obtained from 100 thalassaemia cases (56% males and 44% females). In this study, patients belonged to age group six months to fifteen years. However, similar studies in the western

This observation is consistent with the findings of Abdel-Malak who found RPE degeneration in 17.7% and RPE mottling in 25%. RPE degenerations were found in 21.82 % of the patients receiving deferriprone therapy (Abdel-Malak found RPE degenerations in 27.8% of patients). Deferriprone may be contributory to the occurrence of RPE degeneration. These findings are consistent with 10

Taher who found that patients on deferriprone were four times more likely to have RPE degenerations as compared to patients on desferrioxamine. RPE mottling was detected more in the patients receiving deferriprone therapy (29.09%). This result was found to be consistent with Taneja (10%) and Abdel-Malak (33.3%). Retinal venous tortuosity was observed in 10% of patients. This incidence is less when compared to the incidence reported by Gaba (17.14%) and Taher (17.9%) but quite similar to Taneja (11%). Disc hyperaemia was found in 5% of patients which is consistent with the findings of Taneja and Dewan who found it in 7% and 8% patients respectively. It has been seen that the average serum ferritin levels were increased in thalassaemia patients who had ocular changes and decreased visual acuity. Correlation of serum ferritin levels with retinal venous tortuosity was statistically significant (p=0.03). This is consistent with observations of Gaba and Taneja . Patients with thalassaemia have been found to have a higher labile iron pool, and it has been proposed that this mediates cellular damage. Iron causes oxidative damage to proteins, lipids and DNA through the generation of free radicals in the Fenton reaction, and it has been shown to disrupt the blood retinal barrier. Iron is potentially related to several ocular diseases, including glaucoma, cataract, age related macular degeneration and intra-ocular haemorrhage. Raised serum ferritin is a surrogate marker of transfusion haemosiderosis, which may predispose thalassaemia patients to the toxic effects of iron. The specific role of iron in ocular involvements in thalassaemia needs to be studied. A larger number of thalassaemic children were found to have ocular abnormalities despite moderate doses of deferriprone and presence of high serum ferritin levels, which implicate a role of iron in ocular pathology in thalassaemia. A larger study to evaluate the role of iron in ocular involvement in these patients is recommended. The reversibility of ocular changes should also be studied by 11

changing the chelating agent or altering its' dose. A limitation of the present study is that it cannot conclusively establish whether ocular changes are a result of the disease or due to iron chelating agents. It may be kept in mind that iron overload and iron chelating agents both may be mutually confounding factors in the causation of ocular changes of thalassaemia. REFERENCES 1 Chaston TB, Richardson DR — Iron chelators for the treatment of iron overload disease relationship between structure, redox activity and toxicity. Am J Hematol 2003; 73: 200-10. 2 Lokeshwar MR, Shah N, Kanika S, Manglani M, editors — IAP Textbook of Paediatrics. 3rd ed. New Delhi: Jaypee Publishers, 2006: 622-30. 3 Greer JP, Foerster J, Lukens JN, editors — Wintrobe's Clinical Hematology. 11th ed. Vol 1. Phladelphia: Lippincott Williams and Wilkins Publishers, 2009: 1083-131. 4 Choudhry VP, Naithani R — Current status of iron overload and chelation with deferasirox. Indian J Pediatr 2007; 4: 5964. 5 Wong RW, Richa DC, Hahn P, Green WR, Dunaief JL —Iron toxicity as a potential factor, in AMD. Retina 2007; 27: 9971003. 6 Garataganis SP, Zoumbos N, Koilopoulos JX, Mela EK — Contrast sensitivity function in patients with beta thalassemia major. Acta Ophththalmol 2000; 78: 512-5. 7 Gaba A, Souza PD, Chandra J, Narayan S, Sen S — Ocular abnormalities in patients with beta thalassemia. Am J Ophthalmol 1998; 108: 699-703. 8 Taneja R, Malik P, Sharma M, Agarwal MC — Multiple transfused thalassemias major: ocular manifestations in a hospital based population. Indian J Ophthalmol 2010; 58: 125-30. 9 Dewan P, Gomber S, Chawla H, Rohatgi J — Ocular changes in multi-transfused children with b- thalassaemia receiving desferrioxamine: a case control study. SAJCH 2001; 5: 11-4. 10 Abdel-Malak DSM, Dabbous OAE, Saif MYS, Saif ATS — Ocular manifestations in children with b- thalassemia major and visual toxicity of iron chelating agents. J Am Sci 2012; 8: 633-8. 11 Taher A, Bashshur Z, Shamseddeen WA, Abdulnour RE, Aoun E, Koussa S, et al — Ocular findings among thalassemia patients. Am J Ophthalmol 2006; 142: 704-5.

Practitioners' Series

HUMAN OTO-ACARIASIS : 440 CASES OF INTRA-AURAL TICK INFESTATION MANAGED— NAIK AND NAIK

Comments :

Sudhir M Naik1, Sarika S Naik2

Soft tick in the ear is a very common acute painful and distressing condition in the flowering months of October to March. It’s a common condition in the rubber growing belt of Sullia. The mouthparts of the tick grips firmly the skin of the external auditory canal or the tympanic membrane and sucks blood and swells up. Otoscopy and removal of the tick from the ear can be done in outpatients in adults and is difficult in a frightened irritable child. To emphasise the need for prompt management by an experienced otolaryngologist in all such cases of intra-aural tick infestation, a retrospective study of 440 cases (173 males and 267 females) who attended the department of ENT, KVG Medical College, Hospital, Sullia with history of intra-aural ticks was conducted over a period of 48 months. Out of 440 cases of intra-aural ticks, 215 cases were treated in the outpatient department and 223 cases under short general anaesthesia with otomicroscopy. Intra-aural tick infestation is an acute painful condition which needs prompt management by an experienced otolaryngologist. Proper visualisation and instrumentation is necessary to avoid complications. [J Indian Med Assoc 2016; 114: 98-100 & 107]

Key words : Intra-aural tick, otalgia, otomicroscopy, general anaesthesia.

Ticks are obligate blood sucking arachnids and are easily transmitted through domestic animals and pets to humans . The two major types of ticks, based on the presence or absence of a hard shield called scutum, are ixodidae (hard ticks) and argasidae (soft ticks) . Soft tick attaches to its' host with its mouthpart, which not Fig 1 — Showing Monthly Distribution of Intra-aural Tick Infestation During the Last Four Years only is embedded in the skin but is also glued into place with forceps under magnification. a cement like secretion . The tick All the patients managed in can voluntarily detach from its' OPD were observed for an hour host, but when forced off, it may leave the attached mouthpart and discharged with antibiotics embedded in the skin . As long as and analgesics for one week. the mouthpart is attached to the Patients managed under patient, the patient remains at risk general anaesthesia were for tick borne diseases . Removal observed for a day and of an intra-aural tick is a painful discharged on next day with experience to patients, especially antibiotics and analgesics. children . Most of the times, the Analysis : removal is made difficult by the swollen and narrowed canal from All the ticks located on the previous multiple attempts by pinna were removed in the inexperienced medical personnel OPD (11 males and 19 with inadequate instruments . females). Out of the 153 cases The tick swells up after sucking of ticks in the cartilaginous blood and the engorged tick is easy external auditory canal 92 to detect in narrow ear canal . The cases co-operated for removal unfed tick situated at the anterior in OPD (62%) and in 58 cases fornix of the external ear canal is ticks were removed under seen with difficulty on otoscopy . general anaesthesia with The anterior bony hump of the ear otomicroscopy (38%). Out of canal may block the view to that the 181 cases of ticks in the particular area . bony external auditory canal, Cerumen(wax) in the canal can 90 co-operated for removal in hinder tick visualisation . The tick OPD (49.72%) and in 91 cases stands out as a shiny surface ticks were removed under making it conspicuous within the general anaesthesia with Fig 2 — Showing Ticks in the Cartilaginous wax . The dark brown colour of the otomicroscopy (50.28%) External Auditory Canal tick faecal matter which is digested (Table 1 and Fig 3). All ticks (76 cases) located on the tympanic membrane blood might mix with the wax and create a confusing were removed under general anaesthesia with picture . Otomicroscopy should be done to confirm the otomicroscopy. Here 2 females refused removal under diagnosis . A tick which is easily visualised should be general anaesthesia. Small perforations were seen after grasped by a crocodile or cupped ear forceps and pulled out removal of the ticks located on the tympanic membranes in steadily . Rotating the tick during removal may break off 2 males and 4 females. No other complications were seen the mouthparts leaving the sequelae of infection and irritation of the ear canal . in rest of the cases.

No of Cases of Intra-aural Tick Infestation

Human oto-acariasis : 440 cases of intra-aural tick infestation managed in rural belt of Sullia

Children and anxious adults will not co-operate for ear examination or otoscopy and forceful examination may cause damage to the external ear and tympanum . So, examination of the ear using an otoscope or otomicroscope and exact visualisation of the tick is very important before attempting to remove it . Its an acute painful condition which needs urgent intervention . Cooperative patients can be managed in the outpatient only meanwhile anxious and paediatric patients were managed with oto-microscopy under general anaesthesia .

uman oto-acariasis is the infestation of the ear canal by ticks or mites . It is rare in humans and commonly seen in livestock and domestic animals .These intra-aural ticks can perforate the tympanic membrane, cause suppurative otitis media, subluxation of the incudomalleal or incudostapedial joints and the dislocation of the stapes from the oval window, bleeding from the ear canal and rarely facial paralysis . This intra-aural tick infestation is a common condition seen in rubber growing population of Sullia. It is a common painful condition presenting to the otologist during the flowering months of October to March (Fig 1). Animate foreign bodies are comparatively rare and inanimate foreign bodies account to around 84%. Majority of the animate foreign objects are small cockroaches . Most of the patients present with acute severe pain in the ear. The condition affects all age groups . It is diagnosed by performing an otoscopic canal examination or ear endoscopy which will show the presence of tick or its' blackish faecal particle (Fig 2). The intense pain is because of firm gripping of the skin of the external auditory canal and the tympanic membrane by its' mouthparts . 1-3

1-3

4-6

The Study :

A retrospective analysis of 440 patients who had intraaural tick infestation were included in the study. One hundred and seventy-three males and 267 females were included under the study. The youngest patient was a 3-year-old girl and oldest was a 79-year-old woman. The study period was of 48 months from January 2007 to April 2011. All patients with intra-aural tick infestation were included in the study. All patients had excruciating pain in ear as presenting complaint. Otoscopic examination was done to confirm the living tick foreign body. Tick removal was done under 4% topical anaesthesia in co-operative adult patients in the outpatient department. General anaesthesia was preferred for anxious and younger patients. Under short general anaesthesia otomicroscopy was done and the ticks removed by cupped

Department of ENT, Head and Neck Surgery, KVG Medical College, Sullia 574327 1 MBBS, MS (ENT), Associate Professor 2 MBBS, DA, Senior Resident, Department of Anaesthesia 98

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Tick removal is a very painful experience to the patient because of the sensitivity of the ear canal . Patients in the paediatric age group never allow removal without anaesthesia . Swollen and narrowed ear canal due to tick bite trauma and previous attempts at removal by inexperienced medical personnel with inadequate instruments make removal even in experienced hands difficult . Always institutional management where adequate facilities and expertise are available should be sought . Ticks can be removed by manual Fig 3 — Showing Distribution of Cases according to Location of Intra-aural Ticks forceps or by applying noxious stimuli so that the tick detaches spontaneously . Many reagents have been used to induce a localised manifestation such as facial nerve paralysis. noxious stimulus with varying results . Some practitioners Tick paralysis is a known complication of tick infestation used spirit eardrops for 3 days before syringing the tick out anywhere in the body and has been reported particularly in on day 4 . Some used 4% lignocaine instead, but only northern America and Australia, but instilled the canal for 10 was rarely encountered in this region . Table 1 — Showing Distribution of Cases minutes . Olive oil, sodium according to Method of Removal of Intra-aural Ticks People from this tropical climate are bicarbonate, petroleum jelly more frequently exposed to tick bite No of cases and liquid paraffin are among Location and have developed some immunity OPD Otomicroscopic various preparations used to to it's toxin . However, cases of removal removal (GA) facilitate tick removal with isolated local paralysis; usually Pinna 30 0 none of them proven to be Cartilaginous EAC 95 58 involving facial nerve, have been superior to another . Bony EAC 90 91 reported although less commonly In the above study 4% Tympanic membrane 0 74 reported in the literature . 215 223 lidocaine was instilled in the Total patient’s ear canal for 10 The tick salivary secretions minutes and it was found that contain a neurotoxin and the the tick can be removed easily by doing ear suction or paralysing effect of the tick is attributed to it . This toxin is using forceps under microscopy. Cocaine if available can found to interfere with the liberation or synthesis of be instilled which anaesthetises and disengages the tick acetylcholine at the motor end plate of muscle fibres . The from the tympanic membrane and also decongests the severity of paralysis is independent of the number of ticks swollen canal and reduces the pain, thus calming the infested . But a correlation between the duration of tick patient down . However, in non-cooperative children, attachment and the likelihood of transmission of toxin or removal under general anaesthesia is safer and less infection is reported . Several theories have been put forth traumatic to the patients. The most commonly to explain the pathophysiology of localised facial nerve recommended and successful tick removal method is palsy in an intra-aural tick infestation . manual extraction of the tick . It is seen that the tick would The presence of tympanic membrane perforation may best be removed by grasping it close to the skin and enable the tick saliva (with toxin) to enter the middle ear exerting a steady, even pressure without rotating . Another author proposed a technique of mechanical and reach the facial nerve probably through a natural removal involving rotation instead of traction, which he dehiscence of the fallopian canal causing paralysis . In claimed more reliable for rapid and painless removal of the cases where the tympanic membrane is intact, direct entire tick, including the head, not leaving the mouthpart extension of the inflammatory process to the fallopian behind . After the removal of tick, its faecal particle should canal is via persistent dehiscence or direct invasion of the also be cleared off the ear canal since tick faeces and body infectious organisms into the facial canal through the fluids can also be contaminated . Antibiotics and middle ear which results in oedema of the inflamed nerve analgesics should be prescribed for a week to reduce within the canal . secondary infection in the site of trauma. Abundant cattle ticks in the agricultural areas of Sullia, The neurological complications of intra-aural tick is the cause of these abundant intra-aural ticks . Marina infestation may occur, where they usually present as a

Current Topic

No of Cases

Co-formed consent : a case of rightful application Munawwar Husain1, Arshad Anjum2, Amir Usmani3, Mubarak Alshraim4, Jawed A Usmani5 Informed consent has its roots on certain principles of bioethics and law. It has succeeded in eliminating discrepancies in medical practice. However, lately certain misgivings have started creeping in this hypothesis and therefore it was felt to revisit it. In the process a new concept has emerged which of course needs to be debated. There is an instance in which the Consumer Court in India held the surgeon negligent for conducting sterilization operation during caesarian section without obtaining prior consent, particularly when there was no urgency for the same . This raises another question on the chivalry of the doctor. The authors are sure that the concept of co-formed consent is more robust and would stand a better chance of survival in the highly meshed world of technology and suspicion. Incidences of obtaining consent as an eye wash shall decrease if not totally eliminated. The concept is discussed below. 1

[J Indian Med Assoc 2016; 114: 101-2]

Key words : Consent, informed consent, co-formed consent, consent audit, truth commission, reformed consent

(Continued on page 107)

own rights and the Bill of Patients’ Rights was introduced . Since everything came at a price the patient became demanding leading to the creation of hostile patient . The concept and practice of defensive medicine came into existence . The patient was the end loser. Subsequently a need was felt to reform the informed consent which did not prove a panacea. During this commotion of mental conflict, allegiance wrestling and the compulsion to incorporate ethics into practice, the informed consent lost some of its sheen. Convention now faced rock stable contradiction. The essential ingredients of informed consent like full and timely disclosure of risks and benefits by the physician to the patient and then obtaining the voluntary consent after adequate supply of information became a legal embodiment rather than a crusade against unprofessionalism. This has sown the seed of co-formed consent which is discussed next.

hen a patient interacts with the doctor for treatment, whether it is medical or surgical, it involves interference with human body. To avoid legal ensnarement for battery which is “the application of force to the person of another without lawful justification” , and that of an assault which is “an act of the defendant which causes to the plaintiff reasonable apprehension of the infliction of a battery on him by the defendant” , it is obviously transparent that informed consent should be taken by the treating doctor to satisfy the appetite of law. The origin of informed consent can be traced to the principle of autonomy and self-bodily integrity . The concept caught on partly propelled by the advent of high technology in medical sphere and the cost involved . The physician as well as the patient benefited because it created choice for the patient. However, in due course of time it was realized that medical profession has become complicated with too many stakes involved. Professionalism got a down-beating. Some where along the line the patient became conscious of his

6,7

Co-formed Consent : Co-formed consent may be defined as “a mutually formed consent between the physician and the patient based on the understanding that allegiance to one’s interest would be subservient to end-goal and in the process protecting the institution of professional ethics, humane endeavor and autonomy without resorting to ill-conceived chivalry in a bid to establish one’s own genuineness of desire and action”. A large chunk of onus rests on the shoulders of the physician.

Department of Forensic Medicine, Jawaharlal Nehru Medical College, Aligarh 202002 MD, DNB, MNAMS, Associate Professor, Chairman & Former Medical Superintendent DCH, Assistant Professor MD (Psychiatry), Assistant Professor, Department of Psychiatry MBBS, FRCP (Path), Associate Professor, Department of Pathology, King Khalid University, Abha, Kingdom of Saudi Arabia MD (Path), MD (Med), Professor 1

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The essential elements of co-formed consent would include the following: (1) Full disclosure by the physician to the patient without encumbrance of one’s own interest. (2) The doctor’s allegiance to his professional body must not hold sway while eliciting informed consent. (3) The conflict of interest must never be involved. The tricky domains in this context would be the hospital to which the physician is attached and to which he is obligated, the unsolicited marketing of products, a bid to raise the banner of reputation high, desire to oblige one’s own brothers-in-profession, and above all the urge to inflate one’s own coffer. (4) While obtaining co-formed consent there should not be an iota of lingering doubt that consent has not been cleanly obtained. Medicomoral duty and obligation must be met indisputably.

Process of Evaluation and Re-evaluation : Redundancy sets in whenever change is not timely brought or sought. Similar to informed consent now being questioned the concept and practice of principles of co-formed consent would also receive a beating if safeguards are not created for its healthy flourishing. In this context two suggestions are put forth. (a) Consent Audit: Similar to the audit of inventory and stock, clinical audit in large hospitals and the audit of the procedure and practice of biomedical research there should be the audit of co-formed consent. A proforma may be designed which would have the capacity to evaluate the covert and overt action of the physician. Likewise the patient informed consent could be evaluated on an acceptable scale. (b) Truth Commission: A periodical Truth Commission could be asked to convene and evaluate the co-formed consent audit itself. This Truth Commission could be in line with the Truth and Reconciliation Commission formed at the end of apartheid government in South Africa. There the guilty and the suspect were given the chance to come out clean and disclose voluntarily their involvement in racial discrimination and debased action during pre-Mandela era with an option of receiving an amnesty . The mandate of Truth Commission in this case would be to track incorrigible cases violating co-formed consent procedure repeatedly while at the same time giving a chance to reform for first time offenders. 13

Conclusion : Co-formed consent is a not a product of fantasy. In fact it is one step forward to informed consent. This would expose the subtle desire and motivation – seen and unseen – of the physician and would be able to question his sin

cerity in getting the consent. Provision for legal action should be incorporated. Meticulous record keeping is a must for the co-formed consent procedure to succeed. REFERENCES: 1 Dr Janaki S — Kumar v Mrs Sarafunnisa 1999 (3) CPR 472 (ker); I (2000) CPJ 66 (Ker). 2 Salmond & Heuston on The Law of Torts [20th ed, 1992, Third Indian Reprint (1999)] 3 Winfield & Jolowicz on ort, 15th ed, p63. 4 Mallardi V — The origin of informed consent. Acta Otorhinolaryngol Ital. 2005; 25: 312-27. 5 Francisco V — Ethical problems of medical technology. Bulletin of PAHO, 1990; 24: 379-85. 6 Kumar L, Husain M, Ahmad I — Level of accessibility of radiological diagnostic tools of high technology and its effect on human health: study of Ultrasonography, CT scan and MRI in different perspective. J Ind Med Assoc 2012; 110: 148-52. 7 Judith LW — The implications of cost-effectiveness analysis of medical technology. Office of Technology Assessment, US Government Printing Office, Washington, DC, 1981; pp 1-24 8 Patients Bill of Rights. Declaration of Lisbon on the Rights of the Patient. Adopted by the 34th World Medical Association (Lisbon, September/October 1981) 9 Kramer CH, Kramer JR — Managing the hostile patient. Geriatr Nurs 1976; 2: 35-7. 10 John EM, Arnold RJ — Physician responsibility for the cost of unnecessary medical services (special article). NEJM 1978; 299: 76-80. 11 Henry J, Balmer PW, Lawrence P — Reformed Consent: Adapting to new media and research participant preferences. Accessed at http://hastingscenter.org/ Publications/IRB/detail.aspx?id=3288 12 Informed Consent. Stanford Encyclopedia of Philosophy. Accessed at http://plato.stanford.edu/entries/informedconsent/ 13 United States Institute of Peace. Truth and reconciliation Commission (TRC). Accessed at http://www.usip.org/ publications/truth-commission-south-africa

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GP Forum Drug review : febuxostat Kiran Kumar Singal1, Sunder Goyal2, Parveen Gupta3, Ram Gopal Sharma4 Gout is the most common type of inflammatory arthritis in men over the age of 40 years affecting approximately 0.8% of the population. There have been relatively few advances in treatment and prevention of gout over the last forty years. Febuxostat has been recently approved by FDA. Febuxostat is a selective and potent inhibitor of xanthine oxidase. The drug has come 40 years after the commonly used drug allopurinol. No dose adjustments are required in patients with mild to moderate renal or hepatic impairment. [J Indian Med Assoc 2016; 114: 103-4]

Key words : Gout, uric acid, febuxostat, allopurinol, xanthine oxidase inhibitor.

effects . Al lopurinol, the most commonly used drug for gout prevention, can be effective at decreasing uric acid levels and reducing acute flares. Rare but serious adverse events can occur from allopurinol, including a potentially fatal hypersensitivity syndrome (rash, fever, hepatitis), more commonly seen in patients with renal failure and those receiving diuretics . Dosing of allopurinol is difficult in patients with renal failure, those most in need of uric acid lowering therapy. Even if allopurinol is well tolerated, it is often ineffective for gout because it is used intermittently or its' dose is not adequately adjusted to achieve appropriately low uric acid levels (usually<6 mg/dl). Thus, the medical community needs to be better educated about the use of current drugs for gout as we need more effective and safer drugs for management of gout. For treatment of hyperuricaemia and gout, febuxostat has been recently approved by FDA. Febuxostat is similar to allopurinol as it also inhibits the enzyme xanthine oxidase . Febuxostat is a non-purine xanthine oxidase inhibitor for the long term management of hyperuricaemia in patients of gout. Its' major goal in the management of hyperuricaemia and gout is long term reduction in serum urate concentrations to levels below the limit of urate solubility (about 6.8mg/dl) because such a reduction over time will prevent or reverse the formation and deposition of urate crystals. 2

out is the most common type of inflammatory arthritis in men over the age of 40 years. It affects approximately 0.8 % of population . It is a chronic, often progressive condition characterised by attacks or flares, that are marked by intense pain, redness and swelling in affected joints. Symptoms result from an acute inflammatory response to elevated uric acid level in joints. Significant amount of the pathogenesis of gout is known but despite the prevalence and morbidity of this disease, there have been relatively few advances in treatment and prevention of gout over the last forty years. At this time, therapies for gout are divided roughly into those for acute treatment namely non-steroidal anti-inflammatory drugs (NSAIDs), colchicines, corticosteroids and preventive therapies namely prophylactic colchicines or corticosteroids, probenecid, allopurinol. Unfortunately, these medications are often misused for gout or have significant adverse reactions. For treatment of acute gout, gastro-intestinal and renal side effects of NSAIDs are well known. Colchicine given orally for acute treatment of gout can lead to significant gastro-intestinal toxicity, and the intravenous (IV) form of colchicine has been associated with serious safety concerns, including death, especially in elderly patients or those with renal failure. Systemic corticosteroids are effective but have serious side effects, and not all physicians are comfortable with potentially safer intra-articular use of corticosteroids. Most patients with gout under excrete uric acid; therefore, probenecid is often indicated for preventing acute gout in patients without tophi or renal stones. However, this uricosuric agent is seldom used, and is poorly tolerated because of rash or gastro-intestinal side1

Mechanism of Action : Febuxostat is a selective and potent inhibitor of xanthine oxidase, the drug setting in the access channel to the molybdenumpterin active site of the enzyme. It has minimal effects on other enzymes involved in purine and pyrimidine metabolism [5,6]. Febuxostat does not have a purine like backbone, unlike allopurinol and oxypurinol. Xanthine oxidase is needed to successively oxidate both hypoxanthine and xanthine to uric acid, hence inhibition of xanthine oxidase by febuxostat reduces the production of uric acid.

Department of Medicine, MM Institute of Medical Sciences and Research, Ambala 134203 MBBS, MD (Med), Assistant Professor MBBS, MS (Gen Surg), Associate Professor of Surgery MBBS, MD (Med), Associate Professor MBBS, MS (Gen Surg), Assistant Professor of Surgery 1

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Spectrum : Febuxostat has been approved of use in gout in Europe and USA. Febuxostat is a particularly appropriate second line option to allopurinol where this uricosuric is contraindicated, as in stage three or worse chronic renal disease and in patients with a history of urolithiasis, an inability to adequately increase hydration or with identified uric acid overproduction.

Pharmacokinetics : Like allopurinol, febuxostat lowers plasma uric acid levels by inhibiting enzyme xanthine oxidase. Febuxostat is about 50% absorbed, giving a Cmax at 1 to 1.5 hours. It is metabolised by conjugation via the uridine dephosphate glucorosyl transferase (UGT) iso-enzymes UGT1A1, 1A3, 1A9 AND 2B7 and by oxidation via CYP450 isoenzymes 1A2, 2C8 and 2C9.Metabolism leads to four active metabolites. Febuxostat undergoes hepatic elimination (45%) and renal elimination (49%).

Indications : The only indication for febuxostat usage is in management of hyperuricaemia in patients with gout. The drug is not recommended for the management of asymptomatic hyperuricaemia. The drug has come 40 years after the commonly used drug allopurinol. This drug was approved in the year 2009 in Europe and USA for management of hyperuricaemia.

Precautions and Contra-indications Febuxostat can cause allergic reactions and should be avoided in patients allergic to it. During pregnancy this drug should be used only when clearly indicated. This drug should be used with caution in patients with underlying cancer, heart disease, liver disease, kidney disease, organ transplant and stroke. Febuxostat is contra-indicated in patients taking theophylline, azathiapurine and mercaptopurine.

Adverse Effects : Most frequent : Skin rash Less frequent : Abdominal pain with cramps, abnormal hepatic function tests Rare : Allergic dermatitis, alopecia, anaemia, angina, angiodema, appetite changes, biliary calculus, blurred vision, bone marrow depression, cerebrovasular accident, conduction disorders of the heart, constipation, dehydration, disorders of hair colour, hepatitis, dyspepsia, oedema, epistaxis, fatigue, flu like symptoms, gastritis, general weakness, hearing disorder, haematuria, hypersensitivity drug reaction, kidney stone, leucocytosis, libido changes, mood changes, myalgia, pancreatitis, parasthesias, peptic ulcer, pruritis of skin, purpura, renal

failure, photosensitivity, thrombocytopaenic disorder, thrombo-embolic disorder, tremors, urticaria, vertigo. vomiting, xerostomia.

Dosage and Administration : Febuxostat is supplied as 40 mg and 80 mg tablets. The tablet can be taken without regard to food or antacid use. Recommended starting dose is 40 mg once daily. The dose may be increased to 80 mg/day in patients who do not achieve uric acid level <6 mg/dl after two weeks on lower dose. Febuxostat significantly reduces uric acid levels within 2 weeks after initiation of therapy and upto 48% by the end of 104 weeks of therapy. The main aim of therapy is to achieve the primary goal of serum uric acid less than 6 mg/dl, 60% of patients achieved this goal with a dose of 80 mg/day or 120 mg/day in the study . No dose adjustments are required in patients with mild to moderate renal or hepatic impairment. Caution is recommended if febuxostat is administered in severe renal or hepatic impairment. 7

Place in Therapy : The only indication for this drug is in treatment of gout.

Retrospective analysis on diagnosis of malaria — a need for developing community Nilotpal Banerjee1, Sujit Bhattacharjee2

Today the attention has shifted from the slide examination to newer methods on Malaria. The methods today, based on newer techniques have not produced any signifant impact on health care. Most newer methods are difficult for 80% of population. Statistics prove the diagnostic value of the slides. Business on health care have made the services costly without significant change for the masses. As the attention shifted today, we find that the skilled Malaria technicians have virtually disappeared to the point of extinct. Though training courses obviously include slide examination on Malaria, the institutions seem to have lost interest and consequently attitude, aptitude for meticulous slide examination on Malaria. Economic pressure of the newer tests for Malaria on the masses are huge but doctors too, have been advising newer test methods, finding lack of quality in slide methods. Malaria exists more than ever before. The drug resistance problem is of course another important concern for Malaria. Prevention aspects are multisectoral. The Gov’t of India has rightly maintained slide methods for Malaria as the gold standard. There exists separate value of supplement and substitute for the benefit of the masses as the very aim is appropriate service. The substitutes are required to be found for treatment, not for diagnosis on Malaria, as records of service studies speak volumes on success projected in this analysis.

Recommendations :

[J Indian Med Assoc 2016; 114: 105-7]

In a random trial of 762 patients, febuxostat, at a daily dose of 80 mg or 120 mg, was more effective than allopurinol at the commonly used fixed daily dose of 300 mg in lowering serum urate .

Key words : Slide methods, Immune fluorescence, Rapid diagnostic tests.

REFERENCES Lawrence RC, Helmick CG, Arnett FC — Estimates of the prevalence of arthritis and selected musculoskeletal disorders in the United States (Abstract). Arthritis Rheum 1998; 41: 778-99. Ferraz MB — An evidence based appraisal of the management of non-tophaceous interval gout (Abstract). J Rheumatol 1995; 22: 1618-9. Singer JZ, Wallace SL — The allopurinol hypersensitivity syndrome. Unnecessary morbidity and mortality (Abstract). Arthritis Rheum 1986; 29: 82-7. Sundy JS, Hershfield MS — Uricase and other novel agents for the management of patients with treatment-failure gout (Abstract). Curr Rheumatol Rep 2007; 9: 258-64. Okamoto K, Eger BT, Nishino T, Kondo S, Pai EF, Nishino T — An extremely potent inhibitor of xanthine oxidoreductase: crystal structure of the enzyme inhibitor complex and mechanism of inhibition. J Biol Chem 2003; 278: 1848-55. Becker MA, Kisicki J, Khosraven R — Febuxostat (TMX-67), a novel, non-purine, selective inhibitor of xanthine oxidase, is safe and decreases serum urate in healthy volunteers. Nucleos Nucleol 2004; 23: 1111-6. Bruce SP — Febuxostat: a selective xanthine oxidase inhibitor for the treatment of hyperuricaemia and gout. Ann Pharmacother 2006; 40: 2187-94. Becker MA, Schumacher HR Jr, Wortmann RL, MacDonald PA, Eustace D, Palo WA, et al —Febuxostat compared with allopurinol in patients with hyperuricaemia and gout. N Engl

Scenario mentioned above, reveal serious magnitude of Malaria fever cases in this geographically isolated state. The network from the city to the periphery reveal the laboratory diagnosis of Malaria that was commendable success story of cost-effective diagnosis.

his study of comparison was attempted, driven by sheer need of the masses which probably is the nuchcus that cannot be ignored considering the poverty of health care taker groups in Indian scenario.

Shifting of Attention :

Projection on 7 years of Retrospective scenario on Tripura State service result on Malaria slide examination Year

Blood slideslide collection

Blood Positive cases percentage examination

Today various types of diagnostic procedures have been adopted along with availability in the market and their adoption. Less of skill and more of relaxation comfort have been achieved. The rapid test methods have almost replaced the old golden labour. The eyestrain lessened, more paramedics and medics are being produced but these developments have brought the skill of this laboratory technique to “drop test service” in tertiary care hospitals too. The slide skill has almost vanished, an anticommunity development and matter of concern as at least 400 million acute cases of Malaria occur worldwide each year, causes at least 100 million deaths every year.

P.F cases and

1998

244080

231187

12595

10507

83%

1999

212056

14408

11889

82%

2000

204322

12245

9480

77%

2001

291652

18502

14629

79%

2002

245406

13319

10863

81%

2003

252339

13807

10800

78%

2004

251146

17455

15182

87%

Why Amear Method Ideal :

Source: Gov’t of Tripura release- 7years of “Success” A Health Bulletin.

A method of choice for masses is evaluated, selected on the basis of the following yard sticks: (1) The method that is easy to perform. (2) The method that is simple to perform. (3) The method that is rapid to deliver.

Department of Microbiology, Tripura Medical College & Dr BRAM Teaching Hospital, Agartala 799014 MD (Microbol), Assistant professor MD, Professor and Head 1

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(4) (5) (6)

The method that gives good sensitivity. The method that gives good specificity. A method that needs minimum general and technical infrastructural back up support. (7) A method that is easily available by the instititions. (8) A method that is easily affordable both by the institutions and the masses. (9) A method that can be quickly supported depending on the location of testing. (10) A method that involves inner skill, culminating in “Eureka” jubilation on success-self motivating. (11) A method that may not depend on power supply. (12) A method that is easily demonstrable. (13) A method that invites the art and science of search finding to create interest among learners. (14) A method that gives lesser false result. (15) A method that gives satisfaction among professionals. (16) A method that has the faithstrength for adoption by clinician for prescription request. (17) A method that invokes inner quality to be rapidly spread and communicated. (18) A method that automatically creates interest among production personnel to capture market because of mass need requirement both for business houses of production, its marketing availability and health care teacher and provider groups. (19) Above all, cost-effectivity and cost-benefit aspects for the Indian community. A comparative analysis highlighted in Clinical Microbiology review is as below :-

GP FORUM ANALYSIS AND INTERPRETATION

Along with the introduction of newer diagnostic systems, the slide methods have lost the zeal and lustre of searching and finding aspects, by the laboratory Technician, supervised by the branch specialist that always carried adventurous life saving effort, lingering prognostic enquiry, hardly pulsed today. The inbuilt process of achievement was seen peeping through. Involvement was a treat to watch. No special infrastructure was required. Today, the high cost systems including maintenance engulfed by the institutions, do save the patient but absorb the pocket of the families with no special advantage for the customer. Bending and benting for newer methods and techniques therefore have serious adverse effect on the community of a country like India. Thrust upon test procedures needs to be seriously reviewed and debated upon by the Institutions, equally also to produce skilled technician for slide methods so that, desert surrounding the gold standard, can be averted from quality point of view, probably felt as need of the hour. Nevertheless, all the systems have specific areas of application. So nothing is discredited upon, rather encouraged on its area of use and application whether screening or diagnostic or survey or research fields. DISCUSSION AND SUGGESTIONS

India is classified under developing nation. The population is plagued with multi dimensional problems and Malaria is one rampant. So, the health care providers need to review seriously about the cost of laboratory diagnosis. The rapidity in diagnosis, the easy procedural pattern, the simple procedure need to be balanced with

Comparison of methods for diagnosing plasmodium infection in blood Parameter

Microscopy

PCR

Fluorescence

Dipstick HRP-2

Dipstick Pldh, ict pf/pv

>100

All species

All species good, others difficult

P. falciparum only

P. falciparum p. vivax good, and ovale and p. malariae only with Pldh

P. falciparum and

Parasite density or parasitemia Yes Time for result 30-60 min

No 24 h

No 30-60 min

Crude estimation 20 min

Skill Level

High

Moderate

Low

Equipment

Microscope

PCR apparatus direct fluorescence microscope

QBC apparatus or

Kit only

Low

High

Moderate/low

Moderate

Sensitivity (parasites/µl) Specificity

Cost/test

Source : Reference number 01 of references.

economic burden of the health care taker, coccooned in the shell of care service. Money earning and Malaria care cannot tune together. Another option may be reduction of the cost of modern diagnosis of Malaria by the private sectors, by keeping a very thin profit margin considering the magnitude gasped, by the Indian community. Cost –effectiveness may be redefined, because many sufferers do not come for the second time or return on hearing the cost in the first consultation. These lot become non responder to care service and prefer to suffering as they cannot afford to. CONCLUSION

(1) The institutions today probably lack interest to produce good slide technician for Malaria. (2) Qualified technicians today, therefore lack skill for slide examination. (3) Indian community can not afford high cost systems. (4) There is no substitute to slide skill and slide service care. (5) Equally easy, simple, rapid methods today are loaded with economic burden particularly for the community.

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(6) Our apathy cannot and should not engulf the patient and community. (7) The country needs to adopt and adapt patient – friendly cheaper approach. (8) Turning away faces from golden basics have disastrous effect on community. (9) The conclusion is more inscribed as the dreadful Plasmodium Falciparum is so rampant in the community, already a store house of poverty, ignorance and unemployment, hunting for two square meals a day. (10) Growth without targetted focus on basics is no growth, only imbalances the common care services. REFERENCES 1 Anthony Moody — 2002 Rapid Diagnostic Tests for Malaria Parasites. Clinical Microbiology Reviews. Vol 15. No 1, page-66-78. 2 Henry’s Clinical Diagnosis and Management by Laboratory Methods. 21st edition. Page-1134. 3 Wallach’s — Interpretation of Diagnostic tests. 9 edition, Page-1030. 4 “Saphalya” Bulletin. Gov’t of Tripura. Page-30 5 Hitendrasinh G Thakor — October 2000; J Indian Med Assoc Vol 98. No-10. Page 623-7. th

(Continued from page 100)

found the abundance of cattle ticks in Malaysian villages as cause for high incidence of human intra-aural ticks in the region. Also during the study unfed tick larvae in the surrounding forested habitats, suggest an extra domiciliary mode of infestation related to cattle rearing . 18

REFERENCES 1 Naude TW, Heyne H, van der Merwe IR, Benic MJ — Spinose ear tick, Otobius megnini (Duges, 1884) as the cause of an incident of painful otitis externa in humans. J S Afr Vet Assoc 2001; 72: 118-9. 2 Huchzermeyer HF — Another human ear tick case. J S Afr Vet Assoc 2002; 73: 2. 3 van der Merwe IR, Benic MJ, Naude TW, Heyne H — Spinose ear tick as the cause of an incident of painful otitis externa. S Afr Med J 2002; 92: 712-3. 4 Indudharan R, Ahamad M, Ho TM, Salim R, Htun YN — Human otocariasis. Ann Trop Med Parasitol 1999; 93: 1637. 5 Campbell NA — An unusual case of facial paralysis. Cent Afr J Med 1977; 23: 141-5. 6 Indudharan R, Dharap AS, Ho TM — Intra-aural tick causing facial palsy. Lancet 1996; 348: 613-4. 7 Somayaji KSG, Rajeshwari A — Human otoacariasis. Indian J Otolaryngol 2007: 59: 237-9. 8 Srinovianti N, Raja Ahmad RLA — Intra-aural tick infestation: the presentation and complications. Intern Med J 2003; 2: 21.

9 Spach DH, Liles WC, Campbell GL, Quick RE, Anderson DE, Fritsche TR — Tick-borne disease in the United States. N Engl J Med 1993, 329: 936-47. 10 Vedanarayanan V, Sorey WH, Subramony SH — Tick paralysis. Semin Neurol 2004; 24: 181-4. 11 Needham GR — Evaluation of five popular methods for tick removal. Pediatrics 1985; 75: 997-1002. 12 Zamzil AA, Baharudin A, Shahid H, Din Suhaimi S, Affendie MJ — Isolated facial palsy due to intra-aural tick (ixodoidea) infestation: Arch Orofac Sci 2007; 2: 51-3. 13 Fegan D, Glennon J — Intra-aural ticks in Nepal. Lancet 1996; 348: 1307-22. 14 Gammons M, Salam G — Tick removal. Am Fam Physician 2002; 66: 643-7. 15 Schultheis L — A novel technique to remove the common dog tick. Am Fam Physician 1998; 58: 354. 16 Sood SK, Salzman MB, Johnson BJ, Happ CM, Feig K and Carmody L — Duration of tick attachment as a predictor of the risk of Lyme disease in an area in which Lyme disease is endemic. J Infect Dis 1997; 175: 996-9. 17 Miller MK —. Massive tick (Ixodes holocyclus) infestation with delayed facial-nerve palsy. Med J Australia 2002; 176: 264-5. 18 Mariana A, Ho TM, Saleh I, Indudharan R — Species distribution of ticks in two localities in Kelantan. Trop Biomed 1996; 13: 185-7.

Case Note

EMPHYSEMATOUS PYELONEPHRITIS – IN A NON-DIABETIC YOUNG WOMEN — RAVIKUMAR ET AL

Emphysematous pyelonephritis – in a non-diabetic young women — a rare association

with high levels of glycosylated hemoglobin or high blood sugars. Rare cases have been reported in patients who are nondiabetic. Of these 22% had obstructed upper urinary tracts, 4% had polycystic kidney disease and 4% had end-stage renal disease. Renal cell adenocarcinoma complicated by emphysematous pyelonepritis has been reported. The left kidney is more commonly affected than the right. Bilateral cases of emphysematous pyelonephritis have been reported. The clinical manifestations of EPN appear to be similar to those encountered in classical cases of upper urinary tract infections. According to Huang and Tseng, fever was encountered in 79% of the patients, abdominal or back pain in 71%, nausea and vomiting in 17%, lethargy and confusion in 19%, dyspnea in 13% and shock in 29%. The most common organisms isolated are E.coli, klebsiella and proteus. Among the imaging studies, CT scan has been the most sensitive. In 2000, Huang et al proposed a staging system of emphysematous pyelonephritis. Class 1 – Gas confined to collecting system Class 2 – Gas confined to renal parenchyma alone Class 3A – Perinephric extension of gas or Abscess Class 3B – Extension of the gas beyond Gerota’s Fascia Class 4 – Bilateral EPN or EPN in a solitary kidney Our patient was not a diabetic and failed to show an features of obstruction of the urinary tract by imaging studies. E.Coli was isolated from the urine cultures which was consistent with the most common pathogens isolated. A rare case of Post-Partum renal failure due to emphysematous pyelonephritis has been reported. The success of treating the condition conservatively with flank drainage and percutaneous nephrostomy have been reported to be better than nephrectomy. Our patient with Huang Class II emphysematous pyelonephritis was treated conservatively and recovered completely. To the best of our knowledge Emphysematous pyelonephritis complicating IUD delivery in pregnancy has not been reported in literature. 2

Y S Ravikumar1, K M Srinath1, L S Adarsh2, Manjunath S Shetty3, Subrahmanyam Karuturi4, B Balaji Kirushnan5

Emphysematous Pyelonephritis is a life threatening infection that results from complicated pyelonephritis by gas producing organisms. It is an acute necrotizing infection of the kidney that occurs predominantly in diabetic patients. Patients frequently present with sepsis and ketoacidosis. Escherichia Coli appears to be the most frequent organism responsible for this infection. We present a case of emphysematous pyelonephritis in a women with intrauterine death of fetus at 20 weeks gestation who did not have features of obstruction of the urinary tract and a non diabetic, managed conservatively. [J Indian Med Assoc 2016; 114: 108-9]

Key words : Emphysematous pyelonephritis, Intrauterine death, non-diabetic patient, conservative management.

22 year old female patient who had PGE induced delivery of dead fetus 4 days back presented to us with severe, noncolicky pain in the right flank along with abdominal distension, fever and oliguria since 4 days. She had no history of vomiting, trauma, dysuria, hematuria, or bleeding per vaginum. She was not a known diabetic, hypertension, tuberculosis or renal disease in the past. Her general physical examination revealed pallor and bilateral pitting pedal edema. Pulse rate was 112/min, blood Pressure was 100/70 mm of Hg, Respiratory rate was 34/min and temperature was 100.F. Abdominal examination revealed distended abdomen with right renal angle tenderness. On Ausculation of the respiratory system patient had bilateral basal crepitations. Cardiac examination was unremarkable except for tachycardia. Per vaginum examination showed closed os and well contracted uterus.

CT abdomen showed diffuse enlargement of both kidneys with small pockets of air in the right kidney which is suggestive of emphysematous pyelonephritis on the right side. (Fig 1)

A diagnosis of Emphysematous Pyelonephritis of the right kidney Huang Class II was made. Patient was treated with intravenous antibiotics (Piperacillin+Tazobactum) and Clindamycin. Patient underwent percutaneous drainage for the collection in the perinephric space of the right kidney. In view of decreasing urine output and elevated renal parameters, patient was also initiated on hemodialysis through jugular intravenous catheter. Patient underwent 3 sessions of hemodialysis, continued on supportive management and percutanoeus drainage. Repeat renal functions were showing significant improvement.

Investigations — Blood investigations showed Hb-8.8 gm%, TLC – 14,300 with 79% neutrophils and a platelet count of 49,000 cells/dl. Renal parameters at admission were a Creatinine of 4.2 mg%, Urea of 103.9 mg%. Serum electrolytes at admission were normal. Urine routine showed 200-300 pus cells/Hpf, 40-60 RBC’s per hpf and albuminuria. Liver function test was normal except for low serum albumin of 2.6 gm/dl. Bleeding time and clotting time was within normal limits. PT INR was 1.18. Patient had a HbA1C of 5.5%. Fasting blood sugar was 89mg% and Post Prandial sugar was 119mg%

Urine culture showed E.Coli (>10 colonies) sensitive to the above antibiotics. Blood culture was sterile. Patient was continued with the above antibiotics for 3 weeks. 5

Two weeks after admission Patient became better with normal renal functions and good urine output. She was transferred out of the Intensive care unit and discharged from the hospital 3 weeks after admission. DISCUSSION

Emphysematous pyelonephritis is a severe necrotizing infection of the renal parenchyma caused by gas producing organisms. The clinical course can be devastating if not recognized early and treated .

Ultrasound abdomen and KUB revealed bilateral enlarged kidneys with emphysematous pyelonephritis of the right kidney with perinephric collection.

Emphysematous pyelonephritis is not a common condition. The reported incidence of the condition from India is not exactly known. The condition is classically described in diabetic women who present with pyelonephritis.

Department of Medicine, JSS Medical College & Hospital, Mysore 570015 MD, Associate Professor MD, Assistant Professor MD, DNB (Nephro), Professor of Nephrology MBBS, Junior Resident MBBS, Junior Resident 1

The most common predisposing condition is diabetes mellitus. 95% of the patients have diabetes which is uncontrolled

108

REFERENCES

1 Sean TG, Sheshadri S, Saravu K — Emphysematous pyelonephritis. J Assoc Physicians India 2002; 50: 1413-5. 2 Shokeir AA, El-Azab M, Mohsen T, El-Diasty T — Emphysematous pyelonephritis: a 15-year experience with 20 cases. Urology 1997; 49: 343-6. 3 Lin CH, Huang JJ, Liu HL, Lee SY, Hsieh RY, Tseng CC — Renal cell carcinoma complicated by emphysematous pyelonephritis in a non-diabetic patient with renal failure. Nephron 2002; 92: 227-9. 4 Huang JJ, Tseng CC — Emphysematous pyelonephritis: clinicoradiological classification, management, prognosis, and pathogenesis. Arch Intern Med 2000; 160: 797-805. 5 Lee IK, Hsieh CJ, Liu JW — Bilateral extensive emphysematous pyelonephritis. A case report. Med Princ Pract 2009; 18: 149-51. 6 Kumar N, Singh NP, Mittal A, Valson AT, Hira HS — An uncommon cause of postpartum renal failure—bilateral emphysematous pyelonephritis. Ren Fail 2009; 31: 171-4. 7 Aswathaman K, Gopalakrishnan G, Gnanaraj L, Chacko NK, Kekre NS, Devasia A — Emphysematous pyelonephritis: outcome of conservative management. Urology 2008; 71: 1007-9.

Fig 1 : CT abdomen showing diffuse enlargement of both kidneys with small pockets of air in the right kidney which is suggestive of emphysematous pyelonephritis on the right side

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Case Note

RHINOCEREBRAL MUCORMYCOSIS — MAKWANA ET AL

111

when spores reach the nasal cavity and/or nasopharynx . No patient to patient spread has been reported . In a predisposed host these spores are converted into fungal hyphae. 8,9

Rhinocerebral mucormycosis : report of two cases and review of literature

The principal predisposing factors are DM (especially with acidosis) and hematologic malignancies with neutropenia. Acidosis rather than hyperglycemia appear to be important predisposing factor. Other identified risk factors are chronic steroid treatment, organ transplant, chemotherapy, chronic renal insufficiency, ferrum intoxication (desferoxamine treatment in dialyzed patients), burns patient. However, it is not frequent in HIV patients as they suffer a lymphocitic immunity disorder .

Gopee E Makwana1, Vikash Jain2, Nandini Bahri3, Mala Sinha4, Manish Kumar Mathur5

Mucormycosis is an infection caused by fungi of the order Mucorales in the phylum Zygomycota. Rhinocerebral mucormycosis is the most common form of the disease and typically develops in diabetic or immunocompromised patients and presents as an acute fulminant infection, which is often lethal. Sinusitis, orbital cellulitis and rapidly progressing opthalmolplegia in the context of diabetes and immunosuppression should prompt the diagnosis. Early diagnosis and prompt treatment is the key. We herein present two patients with microbiologically proven rhinocerebral mucormycosis. A comprehensive review of the literature has been done to update the pathophysiology and the diagnosis.

Mucormysois is caused by one of the members of the mucoraceal family, including Absidia, Mucor, and Rhizopus.Histologic distinction of the Mucor fungi from the more common Aspergillus is based on the characteristically broad, ‘‘empty-appearing,’’ nonseptated hyphae of these fungi, which are readily visible after routine hematoxylin and eosin staining . .

Fig 1 : MRI of brain and sinuses showing left maxillary sinusitis. Rest of brain, sinuses & orbit were normal

[J Indian Med Assoc 2016; 114: 110-2 & 114]

11,12

In case of RCM, after inhalation the fungus causes necrotizing vasculitis of the nose and sinuses, and rapidly extend into the orbits, deep face, and cranial cavity . This results from perivascular, perineural , or direct soft-tissue invasion causing a suppurative arteritis, vascular thrombosis, and infarction of surrounding tissues. Patients often present acutely with headache, fever, facial swelling, sinusitis, and unilateral orbital apex syndrome. Neurologic deficits and obtundation may occur secondary to intracerebral abscess formation and septic thrombosis of major intracranial vessels . The necrotic nasal eschar is very suggestive but it only appears in 20-40% of the patients, and is considered a bad prognosis sign .

Key words : Mucormycosis, rhinocerebral, diabetes mellitus, opthalmoplegia.

ucormycosis (zygomycosis, phycomycosis) is one of the most common forms of the opportunistic fungal infections and the disease may present with pulmonary, rhinocerebral, gastrointestinal, cutaneous, haematogenous or mixed manifestations . Rhinocerebral mucormycosis (RCM) typically affect diabetic or immunocompromised patients disease with a high mortality rate . It usually begins in the nasal mucosa and paranasal sinuses, and extends towards the orbits and cranial cavity and causes necrotizing vasculitis . The most characteristic feature of mucormycosis is invasion of a blood vessel resulting in hemorrhage, thrombosis, infarction and necrosis of tissue. Generally, the infection is rapidly progressive, with local and perineural spread but, occasionally hematogenous dissemination with multiorgan involvement can be seen . We herein present two case of RCM who presented at our hospital with characteristic features and progression.

left 3 , 4 and 6 cranial nerves palsy. Local nasal examination by anterior rhinoscopy revealed no evidence of any eschar or suppuration. Laboratory findings showed neutrophilic leucocytosis with random blood glucose level 360 mg/dl. Renal function and electrolytes were normal. MRI was repeated (Fig 2) which revealed left sided sinusitis & premaxillary soft tissue swelling, left sided orbital cellulitis with proptosis. There was subtle asymmetry involving bilateral cavernous sinus with T2 hypointense non enhancing soft tissue on left side. On the basis of rapid progression of imaging findings over 3 days and the clinical profile, a possibility of mucormycosis was considered in spite of the patient being afebrile and non toxic. Nasal swab was taken and sent for microbiological examination which revealed broad, non-septate, ribbon like hyphae with wide angle branching at irregular intervals on KOH wet mount preparation suggestive of fungal etiology with likely diagnosis of mucormycosis. On emergency basis the patient was operated under general anesthesia and extended radical left maxillectomy and orbital exenteration was performed. Post operatively the patient was in altered sensorium with decreased gag and could not be extubated immediately. On examination he had left 7 , 9 and 11 cranial nerve palsy and right sided hemiplegia. MRI was done which showed presence of acute infarct involving left MCA territory with T2 hypointense non enhancing soft tissue involving left cavernous sinus with occlusion of left Internal carotid artery (Fig 3). The patient was treated with intravenous high-dose amphotericin B (15 mg/kg/day). Culture on Sabourad’s dextrose agar and lacto-phenol cotton blue preparation confirmed the diagnosis of mucormycosis (Fig 4). Clinical improvement was noted and the patient was discharged after 1 month. The patient remained clinically stable at the time of submission of this report. Case 2 : A 30 year old female patient with poorly controlled Type 1 DM presented with 5 days of worsening nasal discharge, left facial pain and erythema, headache and fever. Neutropenia was rd

2,3,4

[6]

Case 1 : A 40 years old male patient with diabetes mellitus (DM) presented to a local hospital with 5 days history of headache, left hemi facial pain and difficulty in deglutition since 3 days. MRI brain of the patient was done outside which showed mild left maxillary sinus mucosal thickening (Fig 1). Rest of the paranasal sinuses, orbit and brain were normal. He was symptomatically treated with NSAIDs on outpatient basis.

Subsequently three days later he presented to our hospital with inability to open left eye, diplopia and gradually progressive painful left sided vision loss and left hemi facial swelling and severe headache. There was no history of fever. On examination the patient was having left sided proptosis, opthalmoplegia with MP Shah Medical College & GG Hospital, Jamnagar 361008 MD, Tutor in Microbiology, Department of Microbiology MD, DNB, Senior Resident, Department of Radiodiagnosis MD, Head of the Department of Radiodiagnosis MD, Head of the Department of Microbiology MD (Microbiol) Senior Resident, Department of Microbiology 1

110

5,11,13

Fig 2 : (A) Axial T2WI shows soft tissue swelling involving left temporal and infratemporal region, masseteric, parotid, buccal and parapharyngeal space. (B) Axial T2WI shows left maxillary, bilateral ethmoidal sinusitis. T2 hyperintensity with swelling involving left extraocular muscle, stranding of orbital fat and proptosis. (C-F) [T2FS axial, T2FS coronal, T1 axial, post gadolinium (gd) T1 axial] Subtle asymmetry involving bilateral cavernous sinus with T2 hypointense non enhancing soft tissue on left side

In the appropriate clinical context, the imaging findings of RCM on CT and MR imaging are diagnostic. These include softtissue opacification of sinuses with hyperdense material, nodular mucosal thickening, and an absence of fluid levels in the maxillary, ethmoid, frontal, and sphenoid sinuses, in decreasing order of incidence . Sinus contents have a variety of MR signal characteristics, including T2 hyperintensity or marked hypointensity on all sequences, possibly secondary to the presence of iron and manganese in the fungal elements . Softtissue infiltration of the deep face and obliteration of the normal fat planes in the infratemporal fossa, pterygopalatine fossa, pterygomaxillary fissure, and periantral fat are often present . Typically, proptosis occurs because of enhancing soft-tissue masses crowding the orbital apex and the cavernous sinuses . Thickening and lateral displacement of the medial rectus muscle are characteristic of orbital invasion from disease in the ethmoid sinuses. Lack of enhancement of the superior ophthalmic vein or ophthalmic and internal carotid arteries may be seen and is related to vasculitis and thrombosis. Intracranial findings include infarcts related to vascular thrombosis, mycotic emboli, and frontal lobe abscesses . Mnif and colleagues suggested that the association between orbital cellulitis and sinusitis in the context of immunosuppression should prompt the diagnosis of mucormycosis . 14

detected in the blood count and blood glucose level was 435mg/dl. MRI was performed and demonstrated inflammatory changes involving paranasal sinuses, nasopharynx, face and neck spaces. T2 hypointense lesion causing a filling defect and lateral bulging of left cavernous sinus was seen with narrowing of cavernous ICA and resultant acute infarct involving left basal ganglia.The diagnosis was based on the microbiological evaluation of the biopsy specimen obtained via endoscopic examination of the paranasal sinuses. Urgent left sided extended radical maxillectomy and ethmoidectomy was performed. She was treated with amphotericin B. However the patient succumbed to cardio respiratory compromise 5 days after surgery. DISCUSSION

5,11,16

Mucormycosis (also known as zygomycosis or phycomycosis), was first described by Paulltauf in 1885 . Phycomycetes are ubiquitous fungi occurring in soil, air, skin, body orifices, manure, spoiled food and dust. Inoculation occurs by inhalation, 7

Management of chronic RCM is not well established. Widesurgical debridement where feasible, prolonged high-dose systemic liposomal amphotericin B, control of underlying

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Case Note

J INDIAN MED ASSOC, VOL 114, NO 6, JUNE 2016

comorbid factors, and hyperbaric oxygen are used . Survival rates range from 21% to 70%, with higher mortality among patients without DM and even higher in patient with intracranial extension . Surgical treatment is always necessary, with extended resection until bleeding tissue is found. Efforts to save the ocular globe with conservative resections usually lead to a delayed enucleation and worsening of the patient. Adequate paranasal sinuses drainage must be ensured. Liposomal amphotericin B, although more expensive has less renal toxicity, fewer adverse effects, and a better solubility in the CNS. Hence the dose can be safely increased. The initial dose is 1 mg /kg/day, which can be increased to 3 or even 5 mg /kg/day. Renal function as well as potassium and magnesium must be rigorously monitored during treatment, that usually lasts for 3 to 7 months . The fungistatic and angiogenic effects of hyperbaric oxygen could enhance the effect of amphotericin B and improve the vascularization. Its value is not well established but it is thought to improve prognosis in CNS cases, with the use of 100% oxygen for 90 to 180 minutes at pressures from 2 to 2.5 atmospheres with 1 or 2 exposures daily for a total of 40 treatments . Rhinocerebral mucormycosis should be suspected in the setting of rapidly progressive ophthalmoplegia and blindness in patients with DM. Computed tomography (CT) and the Magnetic resonance imaging (MRI) may play an important role from initial suspicion of the diagnosis to determining its extension. The treatment must focus in correcting the general status, appropriate antimicrobial treatment and surgical resection. Because of its rapid evolution and severe consequences which include a high mortality rate, a high index of suspicion should be maintained. Early diagnosis and aggressive treatment may be life saving. 2

Harlequin ichthyosis — a case report

2,3,4,11,18

Sendhil Coumary A1, Seethesh Ghose2

Harlequin ichthyosis is a potentially lethal congenital disorder of the skin characterized by an extremely thickened layer of keratin. Though primarily a skin disease, its manifestations compromise other systems as well. In undiagnosed cases (usually a rule) it comes as a shock to both the parents and the care provider. [J Indian Med Assoc 2016; 114: 113-4]

Key words : Congenital Ichthyosis, ABCA 12, Pre-natal sonogram.

Fig 3 : (A-C, axial T2WI, diffusion, ADC)Acute infarct involving left MCA territory with (D,E axial T2WI and Post gd T1WI)T2 hypointense non enhancing soft tissue involving left cavernous sinus with(F, TOF MR angiography) occlusion of left Internal carotid artery

REFERENCES

Fig : 4 (A) Culture on Sabourad’s dextrose agar incubated at 25 C and 37 C showed rapidly growing, fluffy, cottony colony which was white initially and turned greyish brown over a week. (B) Lactophenol cotton blue preparation of culture colony showing erect sporangiophores forming terminal spherical multispore sporangia o

3 Warwar RE, Bullock JD. Rhino-orbital-cerebral mucormycosis: a review. Orbit 1998; 17: 237-45 4 Yohai RA, Bullock JD, Aziz AA — Survival factors in rhinoorbital-cerebral mucormycosis. Surv Ophthalmol.1994; 39: 3-22. 5 Haliloglu NU, Yesilirmak Z, Erden A — Rhino-orbitocerebral mucormycosis: report of two cases and review of the literature. Dentomaxillofacial Radiology 2008; 37: 161-6. 6 McLean FM — Perineural spread of rhinocerebral mucormycosis. Am J Neuroradiol 1996; 17: 114-6

8 Naussbaum ES, Holl WA. Rhinocerebral mucormycosis: changing patterns of disease. Surg Neurol 1994; 41:152-6. 9 Hopkins MA, Treloar DM. Mucormycosis in diabetes. Am J Crit Care 1997; 6: 363-7. 10 Javier González Martín-Moro, Jose María López-Arcas Calleja, Miguel Burgueño García — Rhinoorbitocerebral

failure of desquamation. ABCA 12 is responsible for the development of epidermal barrier function and desquamation. Research has identified deletion of ABCA 12 gene in the families affected with HI . They also demonstrated recovery after corrective ABCA 12 gene transfer into patient keratinocytes. Histopathology of the skin showed marked compact orthohyperkeratosis, extending to the hair follicles and pilosebaceous units. Parakeratosis is also marked . 1

Clinically, the affected infant is usually pre-mature. The neonate appears to be encased in a yellow-brown rigid, thick hyperkeratotic coat, covering the whole body surface. This inflexible cast splits at sites of stress, producing deep red fissures, resembling a Harlequin’s costume. Facial features are distorted due to severe ectropion, conjunctival oedema, eclabium (everted lips). The nose and external ears are tethered and appear rudimentary. Hand and feet are oedematous and encased in mitten-like casts. Movement is restricted, so respiratory insufficiency results from limited chest expansion. They also have feeding difficulties, leading to hypoglycaemia, dehydration and renal failure. Temperature instability and infection commonly supervene leading to rapid demise. The distinctive clinical features of HI are unlikely to be confused, with less severe presentation of a colloidion baby or restrictive dermatopathy.

Twenty year old unbooked primigravida at 34 weeks gestational age presented to the casualty with draining per vagina of 6 hours duration. She conceived spontaneously two months after a second degree consanguinous marriage. There was no significant past, personal or family history especially in relevance to dermatological disorders. Her antenatal period was uneventful. At admission her general physical examination was unremarkable. Obstetric examination revealed a singleton live fetus with breech presentation in early labour. The CTG showed a distress pattern and a caesarean was planned and executed. A live preterm male fetus weighing 2100 grams with thick yellow plaques separated by deep red fissures and contractures of the extremities was born (Fig 1). An urgent dermatological opinion revealed the glaring diagnosis of HI. The new born was shifted to NICU where it succumbed to severe respiratory distress. She recovered well. The parents were counseled about the need for early amniotic fluid analysis and 3D ultrasound in the subsequent pregnancy.

2 Rumboldt Z, Castillo M — Indolent intracranial mucormycosis: case report. AJNR Am J Neuroradiol 2002; 23: 932-4.

7 Paulltauf A — Mycosis mucorina. Virchows Arch 1885; 102: 543

chthyosis describes a dry, rough skin with scaling over the body. There are several congenital or genetic, icthyosiform or ichthyotic syndromes and acquired ichthyoses which are a complication of several systemic and malignant diseases. They range from mild ichthyosis vulgaris to the often lethal harlequin ichthyosis. Harlequin ichthyosis (HI) is one of the first genodermatoses recorded with an incidence of 1: 300000 live births. Its mode of inheritance is autosomal recessive. It can be diagnosed prenatally by skin biopsy, amniotic fluid analysis and by ultrasound. Long term multidisciplinary approach can help these neonates survive to adulthood. CASE REPORT

1 Franquet T, Gimenez A, Hidalgo A. Imaging of opportunistic fungal infections in immunocompromised patient. Eur J Radiol 2004; 51: 130-8.

Detailed genetic counseling is required for affected families and pre-natal diagnostic testing should be offered in future pregnancies. Second trimester, fetal skin biopsy was the earliest and the only confirmatory investigation available. Hair canal keratinisation appears around 15 weeks. Electron microscopic studies can show abnormal vacuoles in keratinized cells and malformation of lamellar granules in the hair. However, the timing for foetal skin biopsy is very elusive . Amniotic fluid analysis revealed intra-cellular lipid vesicles in shed keratinocytes. Pre-natal sonographic features like a flat facial profile with absent nose, wide gaping mouth, dysplastic ears, abnormal fixed position of hands and IUGR . Three and four dimentional ultrasound shows extremely thickened keratin layer of skin, along with the above mentioned abnormalities . The successful identification of the specific ABCA 12 mutation in affected families has opened the way for early DNA based tests. Pre-natal chorionic villous sampling or amniocentesis can be done. Pre-implantation genetic diagnosis is also being studied. 3

DISCUSSION:

Fig 5 : (A-D: T2W FS axial, E: T1W axial post gd. F: TOF MR angiography) MRI showing inflammatory signal alteration in the paranasal sinuses, nasopharynx, left mastoid air cells, left mastigator space, infratemporal space, premaxillary space (A-C) with peripherally enhancing collection (E). T2 hypointense punctuate foci are seen in nasal cavity and ethmoid sinuses (B,C).T2 hypointense lesion causing a filling defect and lateral bulging of left cavernous sinus(B,C,E). Narrowing of left cavernous ICA with resultant acute infarct involving basal ganglia (F,D)

HI is a severe erythrodermic ichthyosis, with an incidence of one in three lakh births, which may be an under-estimate. It causes a distinctive and alarming appearance at birth.

HI cultured keratinocytes show excessive cornification and

Department of Obstetrics & Gynaecology, Mahatma Gandhi Medical College & Research Institute, Puducherry 607 402 MD, DNB (Obs & Gyn), Associate Professor MD (Obs & Gyn) Professor & Head 1

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long ichthyosis has to be explained gently to the parents. Care givers should be trained to cope with the predictable problems of hypothermia, feeding, respiratory problems, sepsis and dehydration. The benefit of retinoids is not very clear as not all survivors have received it. Early introduction of actiretin, probably accelerates shedding of plaques, within first few weeks. Survivors are at a high risk for osteopenia, vitamin-D deficiency, chronic ectropion, constrictive deformities of hand and feet. Gene therapy may eventually become possible . 1

REFERENCES:

Fig 1 : A live preterm male fetus

Outcome was poor, until in early 1980’s. Several babies have been reported to have long term survival. The dilemma of providing intensive neonatal care and accepting a severe life

1 Akiyama M, Sugiyama-Nakagiri Y, Sakai K — Mutation in lipid transporter ABCA 12 in HI and functional recovery by corrective gene transfer. J Clin Invest 2005; 115 : 1777-84. 2 Tapalwowicz K, Wygledowska G —Harlequin ichthyosis – difficulty in prenatal diagnosis. J Appl Genet 2006; 47: 195-7. 3 Shimizu A, Akiyama M, Ishiko A, Yosklke T — Prenatal exclusion of harlequin ichthyosis; Potential pitfalls in timing of skin biopsy. Br J Dermatology 2005; 153: 811-4. 4 Berg C, Geipel A, Kohl M — Prenatal sonographic features of harlequin ichthyosis. Arch Gynecol Obstet 2003; 268: 4851. 5 Vohra N, Rochelson B, Smith LM — Three dimensional sonographic findings in harlequin ichthyosis. J Ultrasound Med 2003; 22: 737-9.

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mucormycosis: A case report and literature review. Med Oral Patol Oral Cir Bucal 2008; 13: E792-5. Chan LL, Singh S, Jones D — Imaging of mucormycosis skull base osteomyelitis. AJNR Am J Neuroradiol 2000; 21: 828-31. Fotterpekar G, Mukherji S, Arbalez A — Fungal diseases of the paranasal sinuses. Semin Ultrasound CT MR 1999; 20: 391-401. Terk MR, Underwood DJ, Zee C — MR imaging in rhinocerebral and intracranial mucormycosis with CT and pathological correlation. MRI 1992; 10: 81-7 Gamba JL, Woodruff WW, Djang WT, Yeats AE —

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Craniofacial mucormycosis: assessment with CT. Radiology 1986; 160: 207-12 Press GA, Weindling SM, Hesselink JR — Rhinocerebral mucormycosis: MR manifestations. JCAT 1988; 12: 744-9 Jain KK, Mittal SK,Kumar S — Imaging features of central nervous sytem fungal infection. Neurology India 2007; 55: 241-50. Mnif N, Hmaied E, Oueslati S — Imaging of rhinocerebral mucormycosis. J Radiol 2005; 86: 1017-20. Horger M, Hebart H, Schimmel H — Disseminated mucormycosis in haematological patients: CT and MRI findings with pathological correlation. BJR 2006; 79: e88–e95.

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