An epidemiological and clinical analysis of cutaneous adverse drug reactions seen in a tertiary hospital in Johor, Malaysia.

BACKGROUND: The prevalence, clinical patterns, and causative drugs of cutaneous adverse drug reactions (cADR) vary among the different populations previously studied. AIM: To determine the prevalence, the clinical patterns of drug eruptions, and the common drugs implicated, particularly in severe cADR such as Stevens-Johnson Syndrome/Toxic epidermal necrolysis (SJS/TEN) and drug rash with eosinophilia and systemic symptoms (DRESS) in our population. METHODS: We analyzed the database established for all cADR seen by the department of Dermatology from January 2001 till December 2010. RESULTS: A total of 362 cADR were seen among 42 170 new clinic attendees, yielding an incidence rate of 0.86%. The most common reaction pattern seen was maculopapular eruption (153 cases) followed by SJS/TEN (110 cases) and DRESS (34 cases). Antibiotics was the most commonly implicated drug group (146 cases) followed by anticonvulsants (81 cases) and antigout drugs (50 cases). The most frequently implicated drug was allopurinol (50 cases). Carbamazepine, allopurinol, and cotrimoxazole were the three main causative drugs of SJS/TEN accounting for 21.8%, 20.9%, and 12.7%, respectively, of the 110 cases seen, whereas DRESS was mainly caused by allopurinol (15 cases). Mortality rates for TEN, SJS, and DRESS were 28.6%, 2.2%, and 5.9%, respectively. CONCLUSIONS: The low rate of cADR with a high proportion of severe reactions observed in this study was probably due to referral bias. Otherwise, the reaction patterns and drugs causing cADR in our population were similar to those seen in other countries. Carbamazepine, allopurinol, and cotrimoxazole were the three main causative drugs of SJS/TEN in our population.

Oxidative stress and leukocyte migration inhibition response in cutaneous adverse drug reactions.

BACKGROUND: Cutaneous adverse drug reactions (CADRs) may either be immunological or non-immunological. The precise mechanisms, however, are largely obscure. Other concomitant mechanisms may amplify and/or contribute to the severity and duration of a reaction. One such mechanism could be oxidative stress, a state of imbalance between reactive oxygen species, and their subsequent detoxification by antioxidants. AIMS: (a) to assess the oxidative stress status in the blood of cutaneous drug reaction patients by assaying for reduced glutathione (GSH) and malondialdehyde (MDA) levels, (b) to determine the leukocyte migration inhibition (LMI) response in these patients in response to the suspected drug (s), and (c) to look for the association between oxidative stress parameters and LMI. METHODS: Ethical committee approval was obtained for this study. Fresh venous blood samples were obtained from the patients of CADRs (group A) during the acute phase of reaction and healthy control subjects (group B). MDA levels, a measure of oxidative lipid damage, and reduced GSH levels, a measure of anti-oxidant capacity, were assayed in the blood samples of both groups using spectrophotometry. LMI response was measured by challenging the patients' peripheral blood mononuclear cells with the suspected drug to confirm immunological perturbation. RESULTS: Totally 66 participants, 33 cases in group A and equal number of controls in group B, were studied. The mean MDA levels were found to be raised (P < 0.001), but GSH levels were significantly reduced in group A when compared with group B (P = <0.001). LMI response against drug(s) was performed in 33 cases (group A), out of which 25 cases showed a positive LMI response as follows: fixed drug eruption (10/25), SJS (5/25), urticaria (3/25), exfoliative dermatitis (2/25), morbilliform rash (2/25), erythroderma (1/25), vasculitis (1/25), and dapsone syndrome (1/25). The mean MDA levels were found to be significantly higher in the LMI positive CADRs (P < 0.001) when compared with LMI-negative ones, while no significant difference was seen for GSH (P = 0.100). Furthermore, there was a significant positive correlation between MDA levels and LMI response (r = 0.831, P < 0.001). On the other hand, a negative but statistically insignificant correlation was found between GSH and LMI response (r = -0.248, P = 0.271). CONCLUSION: CADR patients were found to be under oxidative stress based on MDA and GSH levels in the peripheral blood. There is a significant positive correlation of LMI response (against the causative drug) with MDA levels, which strongly associates oxidative stress with the immunopathogenesis in CADRs.

Association of HLA-B*1502 allele and carbamazepine-induced Stevens-Johnson syndrome among Indians.

BACKGROUND: Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis are severe cutaneous reactions caused by certain drugs, including antiepileptic carbamazepine. A strong association has been reported between human leucocyte antigen (HLA)-B*1502 and carbamazepine-induced SJS in Han Chinese patients. European studies suggested that HLA-B*1502 is not a universal marker but is ethnicity-specific for Asians. AIM: To study the association between HLA-B*1502 and carbamazepine-induced SJS in Indian patients. METHODS: Eight individuals who fulfilled the diagnostic criteria of SJS induced by carbamazepine were identified and HLA-B molecular typing was performed. HLA-B genotyping was carried out by polymerase chain reaction using sequence-specific primers. RESULTS: Out of eight patients studied for genotype, six patients were found to have the HLA-B*1502 allele. CONCLUSION: This study suggests an association between HLA-B*1502 and carbamazepine-induced SJS in Indian patients.

Clinical study of cutaneous drug eruptions in 200 patients.

BACKGROUND: Cutaneous drug reactions are the most common adverse reactions attributed to drugs. Any skin disorder can be imitated, induced or aggravated by drugs. AIMS: The present study was carried out to determine the age, sex incidence and clinical pattern of drug eruptions, to recognize offending drugs (self medication or prescribed), to evaluate mortality and morbidity associated with drugs, to educate the patients, and to avoid self-administration of drugs and re-administration of the offending drugs. METHODS: The diagnosis of cutaneous drug reactions is mainly based on detailed history and correlation between drug intake and the onset of rash. Two hundred patients (112 males and 88 females) presenting with cutaneous drug reactions were studied. RESULTS: Fixed drug eruption was seen in 61 patients; others being urticaria and angioedema, morbilliform rash in 37, pruritus in 25, Stevens Johnson (SJ) syndrome in six, purpura in six, exfoliative dermatitis in five, photosensitivity in five, Toxic Epidermal Necrolysis in two, acneiform eruption in three, and erythema multiforme in two patients. The most frequently affected age group was 41-50 years, followed by the 21-30 and 31-40 years age groups. The youngest patient was one year old and the oldest was 80 years old. The period of development of lesions after the intake of drug(s) varies from 01-45 days. Cotrimoxazole was the offending drug in 26 cases, followed by Ibuprofen in 20 cases. CONCLUSIONS: Fixed drug eruption was the most common drug eruption seen. Cotrimoxazole was the most common cause of drug eruptions.

Stevens Johnson syndrome, toxic epidermal necrolysis and SJS-TEN overlap: a retrospective study of causative drugs and clinical outcome.

BACKGROUND AND AIMS: Stevens Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and SJS-TEN overlap are serious adverse cutaneous drug reactions. Drugs are often implicated in these reactions. METHODS: A retrospective analysis of inpatients' data with these dermatological diagnoses were carried out for three years, to study the causative drugs, clinical outcome, and mortality in these conditions. RESULTS: Thirty patients (15 TEN, nine SJS-TEN overlap, and six SJS) were admitted. In 21 cases, multiple drugs were implicated whereas single drugs were responsible in nine. Anticonvulsants (35.08%) were the most commonly implicated drugs followed by antibiotics (33.33%) and NSAIDS (24.56%). Twenty-five patients recovered whereas five died (four TEN, one SJS-TEN overlap). CONCLUSION: Anticonvulsants, antibiotics and NSAIDs were the most frequently implicated drugs. TEN causes higher mortality than both SJS and SJS-TEN overlap.

Carbamazepine--the commonest cause of toxic epidermal necrolysis and Stevens-Johnson syndrome: a study of 7 years.

BACKGROUND: Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are a group of severe life threatening drug reactions. The drugs commonly implicated as the cause of these drug reactions vary depending on host factors and the prescription pattern of drugs in that particular area. AIM: The aim of the study was to find the drugs implicated as the cause of SJS/TEN in the patients admitted in the dermatology ward at the Medical College, Thrissur and to find the clinical outcome. METHODS: It was a retrospective study of 7 years from 1997 to 2004. The case records of all patients with a clinical diagnosis of TEN or SJS were studied in detail regarding the drugs implicated as the cause, the management and the clinical outcome. RESULTS: During the study period, 41 patients in the age group ranging from 12 to 72 years were treated as inpatients, of which 20 were males and 21 were females. The commonest drug implicated as the cause of SJS/TEN was carbamazepine (44%). The indication for carbamazepine was control of pain in more than 50% of the cases. Presence of a major systemic disease before the onset of SJS/TEN was associated with a bad prognosis. CONCLUSION: The increased use of carbamazepine, especially for control of pain, may be the reason for the increased incidence of SJS/TEN due to the same drug. Awareness about the drugs implicated in life threatening drug reactions will help physicians in preventing them by judicious use of the drugs.

Reacoes dermatologica e hematologica graves durante o uso de sulfona: apresentacao de um caso / Dermatological and hematological reactions grave during the use of sulfones

A autora apresenta um caso clinico, caracterizado por graves reacoes dermatologica e hematologica - respectivamente: eritema polimorfo e bulhose e agranulocitose, desencadeadas durante o uso de sulfona para o tratamento de hanseniase, em paciente do sexo feminino, 51 anos, diagnosticada como portadora de MHV. O quadro clinico apresentou evolucao satisfatoria apos a suspensao da droga implicada - sulfona e a administracao de corticoterapia