Necrólisis cutánea - Casuística de 25 años / Cutaneous necrolysis - Casuistry of 25 years

Introducción: La Necrólisis Epidérmica es una reacción grave y potencialmente mortal, inducida sobre todo por fármacos. Incluye 2 cuadros que presentan similitudes histológicas, etio-patogénicas, pero difieren en el porcentaje de piel afectada: el Síndrome de Stevens-Johnson y la Necrólisis Epidérmica Tóxica. Existen cuadros intermedios entre ambas entidades. El objetivo del trabajo es comunicar las características clínico-epidemiológicas de los casos de Necrólisis Epidérmica registrados en el Hospital Nacional en un periodo de 25 años. Materiales y Métodos: Estudio retrospectivo, descriptivo de los casos de Necrólisis Epidérmica en sus variantes Síndrome de Stevens-Johnson, Necrólisis Epidérmica Tóxica y cuadros intermedios registrados en el Servicio de Dermatología del Hospital Nacional en el periodo 1992-2017. Resultados: Se registraron 46 casos, 27 de Stevens-Johnson, 15 de Necrólisis Epidérmica Tóxica y 4 intermedios. Los casos se observaron en ambos sexos por igual, con edad media de 26,7años (DE 20,69). Los fármacos involucrados con más frecuencia fueron los antibióticos en 16 casos (penicilina y derivados en primer lugar), los anticonvulsivantes (13 casos) predominando la difenilhidantoina y antiinflamatorios-analgésicos (11 casos). El tratamiento consistió en medidas generales en todos, corticoides sistémico en 21 casos y gammaglobulina en 3. La mortalidad global fue del 28%, llegando al 46% en la Necrólisis Epidérmica Tóxica. Conclusiones: La Necrólisis Epidérmica es un cuadro poco frecuente pero grave, con elevada mortalidad, causado principalmente por antibióticos y anticonvulsivantes en esta serie, al igual que en la mayoría de otras series

Introduction: Epidermal Necrolysis is a serious and potentially fatal reaction, induced mainly by drugs. It includes 2 clinical pictures that present histological, etio-pathogenic similarities, but differ in the percentage of affected skin: Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis. There are intermediate tables between both entities. The objective of the work is to communicate features epidemiological cases of Epidermal Necrolysis reported at a National Hospital in a period of 25 years. Materials and methods: Retrospective, descriptive study of the cases of Epidermal Necrolysis in its variants Stevens-Johnson Syndrome, Toxic Epidermal Necrolysis and intermediate tables registered in the Dermatology Service of the National Hospital in the period 1992-2017. Results: 46 cases were registered, 27 of Stevens-Johnson, 15 of Toxic Epidermal Necrolysis and 4 intermediate. Cases were observed in both sexes equally, with an average age of 26.7 years (SD 20.69). The drugs most frequently involved were antibiotics in 16 cases (penicillin and derivatives in the first place), anticonvulsants (13 cases), predominantly diphenylhydantoin and anti-inflammatoryanalgesics (11 cases). The treatment consisted of general measures in all, systemic corticoids in 21 cases and gamma globulin in 3. The overall mortality was 28%, reaching 46% in Toxic Epidermal Necrolysis. Conclusions: Epidermal necrolysis is a rare but serious condition, with high mortality, caused mainly by antibiotics and anticonvulsants in this series, as in most other series.

Guidelines for the management of Stevens–Johnson syndrome/toxic epidermal necrolysis: An Indian perspective.

Background: Stevens–Johnson syndrome and toxic epidermal necrolysis are severe, life‑threatening mucocutaneous adverse drug reactions with a high morbidity and mortality that require immediate medical care. The various immunomodulatory treatments include systemic corticosteroids, cyclosporine, intravenous immunoglobulin, cyclophosphamide, plasmapheresis and tumor necrosis factor‑α inhibitors. Aim: The ideal therapy of Stevens– Johnson syndrome/toxic epidermal necrolysis still remains a matter of debate as there are only a limited number of studies of good quality comparing the usefulness of different specific treatments. The aim of this article is to comprehensively review the published medical literature and frame management guidelines suitable in the Indian perspective. Methods: The Indian Association of Dermatologists, Venereologists and Leprologists (IADVL) assigned the task of preparing these guidelines to its special interest group on cutaneous adverse drug reactions. The group performed a comprehensive English language literature search for management options in Stevens–Johnson syndrome/toxic epidermal necrolysis across multiple databases (PubMed, EMBASE, MEDLINE and Cochrane) for keywords (alone and in combination) and MeSH items such as “guidelines,” “Stevens–Johnson syndrome,” “toxic epidermal necrolysis,” “corticosteroids,” “intravenous immunoglobulin,” “cyclosporine” and “management.” The available evidence was evaluated using the strength of recommendation taxonomy and graded using a three‑point scale. A draft of clinical recommendations was developed on the best available evidence which was also scrutinized and critically evaluated by the IADVL Academy of Dermatology. Based on the inputs received, this final consensus statement was prepared. Results: A total of 104 articles (meta‑analyses, prospective and retrospective studies, reviews [including chapters in books], previous guidelines [including Indian guidelines of 2006] and case series) were critically evaluated and the evidence thus gathered was used in the preparation of these guidelines. Recommendations: This expert group recommends prompt withdrawal of the culprit drug, meticulous supportive care, and judicious and early (preferably within 72 h) initiation of moderate to high doses of oral or parenteral corticosteroids (prednisolone 1‑2 mg/kg/day or equivalent), tapered rapidly within 7‑10 days. Cyclosporine (3‑5 mg/kg/day) for 10‑14 days may also be used either alone, or in combination with corticosteroids. Owing to the systemic nature of the disease, a multidisciplinary approach in the management of these patients is helpful.

Severe Cutaneous Adverse Reaction / 대한내과학회지

Severe adverse cutaneous reactions (SCARs) include Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS). Although recent advances in pharmacogenomics have revealed the association between specific human leukocyte antigens (HLAs) and certain drug-induced SCARs, such associations were found in a limited number of drug-associated SCARs and are not sufficient to explain many other drug-related SCARs. After introducing research on the HLA-restricted T cell response, the role of the T cell receptor in drug binding was emphasized and a new concept called "pharmacological interactions of drug with immune receptors" has been conceptualized over recent decades. Currently, many international and domestic collaborative consortia have been formed and should enable the phenotypic standardization of SCARs at the earliest practicable time to provide valuable insights into its pathogenesis and to find an ideal method to prevent patients from developing SCARs.

Lipid lowering drugs induced adverse cutaneous drug reactions

Background: Lipid lowering drugs (LLDs) are widely used. However, reports on its adverse cutaneous drug reactions (ACDRs) are scarce. Objectives: The study objective was to review the patterns of LLD induced ACDRs. Methods: We reviewed all LLDs induced ACDRs reported to MADRAC (Malaysian Adverse Drug Reaction Advisory Committee) from January 2005 till December 2009. Results: LLD induced ACDRs (124 patients) comprised of 2.07% of all ACDRs reported during the study period. Statins were responsible for most cases (81.5%), followed by fibrates (15.8%), selective cholesterol-absorption inhibitors (1.4%) and combination therapies (statin/selective cholesterol-absorption inhibitors and selective prostaglandin-2 receptor inhibitor/ niacin) in 1.4%. Majority were due to lovastatin (42.5%), simvastatin (28.1%) and gemfibrozil (8.9%). The three commonest ACDRs reported with statins usage were non-specific dermatitis (45.0%), pruritus/stinging (25.0%) and urticaria/angioedema (10.0%) while fibrates caused non-specific dermatitis (52.2%), urticaria/angioedema (13.0%) and photodermatitis (9.7%). There was no reported case of photodermatitis associated with statin usage. Interestingly, statins were the offending drugs resulting in all the five cases of vesiculobullous eruptions, two cases of Stevens-Johnson syndrome and one case of dermatomyositis. No mortalities were reported to be associated with LLD induced ACDRs. Conclusions: LLD induced ACDRs were not uncommon. Statins were the main putative drugs implicated in those reactions. Spectrum of ACDRs differed between statin and fibrate although non-specific dermatitis remained the main ACDRs in both classes. The unavailability of guided and classified ACDRs reporting accounted for the large number of non-specific dermatitis. Although most LLD induced ACDRs were mild, statins were reported to cause severe ACDRs.

Severe adverse cutaneous drug reactions: The 5 year Kuala Lumpur Hospital experience

Introduction: Stevens Johnson syndrome (SJS), Stevens Johnson Syndrome - toxic epidermal necrolysis overlap syndrome (SJS-TEN overlap), toxic epidermal necrolysis (TEN) and drug-induced hypersensitivity syndrome (DHS) are well known severe adverse cutaneous drug reactions (SACDRs). All clinicians are responsible for the diagnosis and management of SACDR. Objective: To retrospectively review the clinical patterns, management strategies and outcome of 134 patients with severe adverse cutaneous drug reactions managed at the Department of Dermatology, Kuala Lumpur Hospital between 2006 and 2010. Results: The mean age of presentation was 44.8 years (13-83). The male: female ratio was 1:1. There were 68 cases (50.7%) of SJS, 10 cases (7.5%) SJS-TEN overlap, 32 cases (23.9%) TEN and 24 cases (17.9%) DHS. The five commonest drugs associated with SACDRs were allopurinol (26.9%), carbamazepine (13.4%), phenytoin (9.7%), non-steroidal anti-inflammatory drugs (11.2%) and co-trimoxazole (7.5%). The mean duration of drug exposure before the onset of reaction was 2.8 weeks. A hundred and thirty patients (97%) were managed as in-patient. The mean duration of in-patient stay was 12.4 days. All identified culprit drugs were withheld. Systemic corticosteroids was given to 96% cases of DHS with mean duration of 9.7 weeks; 52.9% of SJS with mean duration of 2.8 weeks; 60% of SJS-TEN overlap with mean duration of 2.3 weeks; and 62.5% of TEN with mean duration of 3.3 weeks. Thirteen patients (42%) with TEN were treated with intravenous immunoglobulin. Eight patients (6%) died, of which 7 were TEN and one DHS. Conclusion: SACDRs are life-threatening emergencies which not only results in significant morbidity and mortality; but also potentially increases the health care cost and burden. Clinicians should recognize high risk medications and prescribe them with great caution.

Two Cases of HLA-B59(+) Stevens-Johnson Syndrome (SJS)-Toxic Epidermal Necrolysis (TEN) Associated with Methazolamide Treatment / 대한피부과학회지

Methazolamide is a sulfonamide derivative and carbonic anhydrase inhibitor used to lower intraocular pressure in glaucomatous eyes. Stevens-Johnson syndrome (SJS)-toxic epidermal necrolysis (TEN) associated with methazolamide treatment has been reported in Korean and Japanese patients. We report two cases of SJS-TEN associated with methazolamide treatment. The result of HLA typing of our two patients was a positive reaction for HLA-B59, which is specific to Koreans and Japanese. This suggests a possible relationship between genetic background and SJS-TEN associated with methazolamide treatment. Therefore, methazolamide should be prescribed with caution to Korean or Japanese patients.