HLA-B 15:13 Positive in an Indonesian Patient with PhenytoinInduced SJS/TEN

@#Steven-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are severe forms of delayed hypersensitivity reaction with an underlying immunologic mechanism involving the interaction between HLA and drug molecules. A-35-year-old Javanese-Indonesian-male, with a history of seizures, presented with skin peeling, mucosal erosions, and purulent eye discharges. He was clinically diagnosed as overlapping SJS/TEN, and both phenytoin and valproic acid became the suspected drugs. Unfortunately, the seizure relapsed and alternative antiepileptic drugs were urgently needed. HLA typing was then performed, revealing the presence of HLA-B*15:13, which has been proven to be correlated with phenytoin adverse reaction by previous study. Thus, phenytoin was totally discontinued and he only prescribed monotherapy valproic acid. Given the high prevalence and common use of phenytoin in clinical practice, HLA evaluation before phenytoin prescription in Indonesia is important. Further studies are recommended to provide more evidence regarding the role of HLA-B*15:13 in phenytoin-induced severe hypersensitivity reactions in Indonesia.

Stevens-Johnson syndrome induced by carbamazepine andamitriptyline in diabetic patient: a case report

Stevens-Johnson syndrome (SJS) is systemic immune reactions (type IV hypersensitivity) that are usually present by blistering and erosions of skin and mucous membranes with involvement of multiple organ systems. The incidence of SJS is rare, with the common comorbidities are diabetes mellitus, epilepsy, hypertension, and stroke. This condition is associated with systemic proinflammatory state. Diabetes mellitus is a metabolic disorder that is characterized by abnormally elevated levels of blood glucose due to glucose intolerance, hyperglycemia, and impaired insulin secretion. Nowadays, pathogenesis of diabetes is considered to be dysregulation of immune factors that are recognized as important etiological components in the development of insulin resistance. We report a case of a 30-years-old man with fever and sore throat, who had type 2 diabetes mellitus (T2DM) and used carbamazepine and amitriptyline for diabetic neuropathy, then followed by redness and blistering on his lips, palates, face, and trunk which subsequently diagnosed with SJS.

Ocular manifestations in Kindler syndrome

We aimed describe the chronic ocular sequelae of Kindler syndrome. All cases of Kindler syndrome with ocular involvement that presented to a tertiary eye care center were included. Three cases of Kindler syndrome with ocular changes were reviewed. Case 1 (10 years, female) had recurrent epithelial breakdown with severe dry eye and corneal opacity secondary to keratitis. Case 2 (28 years, male) had symblepharon , ocular surface keratinization , and severe dry eye. Case 3 (16 years , female ) had partial limbal stem cell deficiency with dry eye. All cases were treated with topical lubricants, short course of low?potency steroids and immuno?modulators. Attention must be paid to the eye in addition to the oro?an?genital mucosa to avoid longterm ocular sequelae

A pattern of serious adverse drug reactions reported in a tertiary care hospital, Rangaraya Medical College, Kakinada, Andhra Pradesh

Background: Serious adverse drug reactions (ADRs) constitute a major limitation in clinical development of a drug thus necessitating close monitoring. Studies regarding the pattern of serious ADRs are limited in southern India. The present study was conducted in tertiary care hospital in Andhra Pradesh with an objective to evaluate the pattern of severe cutaneous and non-cutaneous ADRs in our hospital and to assess the causality, severity, and preventability of these reactions.Methods: A retrospective observational study was conducted over two years, from January 2016 till January 2018 in our ADR monitoring center. The pattern of serious adverse drug reactions, the nature of ADR, suspected drug, the outcome and preventability were analyzed using Modified Hartwig and Siegel scale, and modified Schumock and Thorton scale.Results: Out of 734 ADRs reported, 42 were serious, while 692 were non-serious. Out of 42, 22 were dermatological in origin while the others were acute kidney injury, acute psychosis, febrile neutropenia, gynecomastia, and lipodystrophy. According to WHO causality assessment scale, 27 were probable while 15 were possible. The majority were reported in the age group of 16 to 65 years with female (34) preponderance. The most common drug category responsible was antimicrobials, followed by antiretrovirals, anti-epileptics, and analgesics.Conclusions: Antimicrobial, anti-epileptics, and analgesics contributed to serious ADRs. Although non-cutaneous ADRs did not result in hospitalization, they caused social inhibition and mental stress in the patient.

Bilateral panophthalmitis following toxic epidermal necrolysis: A case report

A 70 year old man presented with systemic signs of toxic epidermal necrolysis (TEN) following consumption of diclofenac tablets for a prodromal illness a week back. Ophthalmic evaluation showed no perception of light in both eyes along with lid edema, total corneal sloughing, and pus-filled anterior chamber. An amniotic membrane transplant was planned but within a few hours, both eyes developed panophthalmitis with restricted extraocular movements and mild proptosis and had to be eviscerated. This is perhaps the first case showing such devastating sequelae of TEN.

HLA-B*15:02 screening in epileptic patients using a high resolution melting-real time PCR (HRM-QPCR) method

Background: The HLA-B*15:02 polymorphism in epileptic patients is known to be associated with carbamazepine-induced Stevens-Johnson syndrome (SJS). The prevalence of HLA-B*15:02 polymorphism seemed to be ethnic-specific with a higher frequency of HLA-B*15:02 in Asian compared to the Europeans. This study was performed to determine the frequency of the HLA-B*15:02 polymorphism in epileptic patients at the Chancellor Tuanku Muhriz Hospital-UKM Medical Centre (HCTM-UKMMC) using high resolution melting-real time PCR (HRM-QPCR) method. Methods: We performed a fast and effective in-house high resolution melting-real time polymerase chain reaction method and compared it with the conventional multiplex-PCR method. The specificity and sensitivity of each test were also determined using DNA from saliva. Results: Using the conventional multiplex-PCR approach for screening, 25 out of 64 (39.1%) epileptic patients were positive for HLA-B*15:02. However, using the HRM-QPCR technique, 24/64 (37.5%) of the patients were positive. The one patient who tested positive by the multiplex-PCR but negative using the HRM-QPCR turned out to be negative by DNA sequencing. The HRM-QPCR and DNA sequencing showed 100% sensitivity and specificity. The multiplex-PCR showed 100% sensitivity and 98.4% specificity compared to both HRM-QPCR and DNA sequencing. The HRM-QPCR is also more cost-effective (<$16.40 USD/test) and less time-consuming when compared to the multiplex-PCR ($25.15 USD/test).Conclusion: Our result suggested that multiplex PCR, HRM-QPCR and Sanger sequencing can be used for detection of HLA-B*15:02. However, a qualitative method such as multiplex PCR should be confirmed with other quantitative methods such as HRM-QPCR and Sanger sequencing.

HLA-B*1502 and carbamazepine induced StevensJohnson syndrome/toxic epidermal necrolysis in Indonesia

Background & Objective: Association between HLA-B*1502 and carbamazepine-induced StevenJohnson syndrome/toxic epidermal necrolysis (CBZ-SJS/TEN) was reported in many Southeast Asian populations but not in Indonesian. The purpose of this study was to evaluate the association between HLA-B*1502 andCBZ-SJS/TEN in an Indonesian population. Methods: Patients with history of CBZ-SJS/TEN are recruited as cases and those who tolerated CBZ as controls. HLA-B typing was performed. Results: We recruited 14 cases with CBZ-SJS/TEN and 53 controls. Positive HLA-B*1502 was found in 8 (57.1%) cases and 14 (26.4%) controls (OR 3.7, 95% CI 1.09-12.61, p=0.035). Conclusion: HLA-B*1502 is associated with CBZ-SJS/TEN patients in Indonesian.

Steven Johnson Syndrome – A Triad of Mucosal Lesions, Cutaneous Involvement and History of Recent Drug Exposure

Steven Johnson Syndrome is relative a rare but yet an acute life-threatening condition. A middle aged lady presented to us in an emergency condition with high grade fever (104oF), oral mucosal ulcers, purulent discharge from both eyes, photophobia, generalized skin rashes, flank bruises, dyspnea, severe odynophagia along with dysphagia and blisters on both hands and feet. Because of extensive oral thrush, mouth ulcers and purulent discharge from eyes, the patient was initially suspected to be a case of oral candidiasis and bacterial conjunctivitis. However, due to wide spread muco-cutaneous involvement and after obtaining detailed drug history and getting opinion from dermatology and ophthalmology department, a diagnosis of Steven Johnson Syndrome was established. The treatment was started accordingly and the patient responded dramatically to the treatment, got improved and was subsequently discharged.

Vesiculobullous lesions of the oral cavity

Vesiculobullous lesions are a type of mucocutaneous disease that is characterized by vesicles and bullae or blisters. Both vesicles and bullae are fluid-filled lesions, and they are distinguished by size, vesicles being less than 5–10 mm and bulla being larger than 5–10 mm, In the case of vesiculobullous diseases which are also immune disorders the term immunobullous is sometimes used. This review will provide an overview of vesiculobullous lesions involving oral cavity, their characteristic features and recent developments in the diagnosis of these lesions.

A case of Stevens-Johnson syndrome due to rifampicin.

A 25 year old female known case of category II pulmonary Tuberculosis was on anti-coch’s treatment in the FDC of rifampicin, isoniazid, pyrazinamide, ethambutol and Streptomycin. Fifteen days after the commencement of Cat II anti TB treatment she developed diffuse erythematous rash on face, trunk and both extremities which turned into blisters. There were ulcers on oral and genital cavity. A diagnosis of Stevens Johnson’s syndrome was made. The patient had a history of cat I pulmonary TB and treated for 8 months and at the end of 8th month she was sputum smear negative. Four months later she had a relapse of sputum smear positive for pulmonary TB. She responded to the stoppage of drugs and oral/inj. Corticosteroids, antihistaminics and antibiotics.

Steven Johnson Syndrome / Síndrome de Steven Johnson

Ulcerative vesiculobullous disorders are common in Dermatology and Oral Medicine. Diagnosis of these conditions is pretty effortless if they give a classic appearance as described in the literature. Steven Johnson syndrome is one such condition which is a type of erythema multiforme. It is a disorder involving mucous membrane, skin and even the multiple organs in severe form. Multiple etiologies persist so be acquainted with the cause and prohibit the root is crucial. But still drugs are considered to be common cause. Early management is vital as complications are serious for this condition even leading to death. We hereby report a typical case with classic appearance of Steven Johnson syndrome.

Doenças ulcerativas vésicobolhosas são comuns em Dermatologia e Medicina Oral. O diagnóstico destas condições é bastante fácil se apresentar uma aparência clássica, tal como descrito na literatura. Steven Johnson é um tipo de eritema multiforme. É uma desordem envolvendo as mucosas, pele e até múltiplos órgãos de forma grave. Múltiplas etiologias são apontadas como causa. Mas ainda os medicamentos são considerados como causas comuns. O tratamento precoce é vital, pois complicações são graves para essa condição, podendo levar à morte. Vimos por meio deste relatar um caso típico, com aparência clássica de Síndrome de Steven Johnson.

Mucous membrane grafting for the post-Steven–Johnson syndrome symblepharon: A case report.

An 18-year-old woman was referred with late sequelae of chloroquine-induced Steven–Johnson syndrome. At the time of presentation, the symblepharon was involving the upper lids to almost the whole of the cornea, and part of the lower bulbar conjunctiva with the lower lid bilaterally. Other ocular examinations were not possible due to the symblepharon. B-scan ultrasonography revealed acoustically clear vitreous, normal chorioretinal thickness, and normal optic nerve head, with an attached retina. Conjunctivo-corneal adhesion released by superficial lamellar dissection of the cornea. Ocular surface reconstruction was carried out with a buccal mucous membrane. A bandage contact lens was placed over the cornea followed by the symblepharon ring to prevent further adhesion. The mucosal graft was well taken up along with corneal re-epithelization. Best corrected visual acuity of 20/120 in both sides after 1 month and 20/80 after 3 months was achieved and maintained till the 2.5-year follow-up.

Síndrome de Stevens-Johnson associada ao uso de antimicrobiano / Stevens-Johnson syndrome associated with antimicrobial agent

Dentre as reações medicamentosas graves, figuram como grandes representantes as doenças mucocutâneas imunologicamente mediadas. A síndrome de Stevens-Johnson, ou eritema multiforme maior, aparece como um distúrbio sistêmico com envolvimento de pele e membranas mucosas relacionado a diversos fatores, tais como infecções virais ou bacterianas e, principalmente, a administração de medicamentos, em geral analgésicos e antibióticos. O objetivo deste artigo é relatar o aparecimento de lesões vesículo-bolhosas ulcerativas em regiões de lábios, gengiva, língua e mucosa genital em um paciente de 26 anos, leucoderma, gênero masculino, em tratamento de infecção respiratória com sulfametoxazol-trimetropima, diagnosticado como síndrome de Stevens-Johnson

Among the severe reactions to medications, immune-mediated Mucocutaneous Disorders are widely represented. Steven-Johnson's syndrome, or great multiform erythema, appears as a systemic disturbance, involving the skin and mucous membranes, and is related to several factors, such as, viral or bacterial infections and particularly the administration of medicines, in general painkillers and antibiotics. The objective of this article is report the onset of ulcerative vesicle ûblister lesions in the regions of the lips, gums, tongue and genital mucosa membrane in a 26 year-old patient, a leukoderm man, being treated with sulfamethoxazole trimethoprim for a respiratory infection, after being diagnosed as having the Steven-Johnson syndrome.