Overview and Current Advances in Dapsone Hypersensitivity Syndrome.

PURPOSE OF REVIEW: As a sulfone antibacterial agent, dapsone has been widely used to treat leprosy. Moreover, dapsone is also used in many immune diseases such as herpetic dermatitis because of its anti-inflammatory and immunomodulatory effects. However, dapsone can cause several adverse effects, the most serious being dapsone hypersensitivity syndrome. Dapsone hypersensitivity syndrome is characterized by a triad of eruptions, fever, and organ involvement, which limits the application of dapsone to some extent. RECENT FINDINGS: In this article, we review current research about the interaction model between HLA-B*13:01, dapsone, and specific TCR in dapsone-induced drug hypersensitivity. In addition to the proposed mechanisms, we also discussed clinical features, treatment progress, prevalence, and prevention of dapsone hypersensitivity syndrome. These studies reveal the pathogenesis, clinical features, and prevalence from the perspectives of genetic susceptibility and innate and adaptive immunity in dapsone hypersensitivity syndrome, thereby guiding clinicians on how to diagnose, prevent, and treat dapsone hypersensitivity syndrome.

Dapsone Hypersensitivity Syndrome (DHS): A Detrimental Effect of Dapsone? A Case Report.

BACKGROUND: Dapsone is a sulfone derived drug used in the treatment of leprosy and several chronic inflammatory dermatological diseases. Dapsone Hypersensitivity Syndrome (DHS) is characterized by fever, hepatitis, generalized exfoliative dermatitis and lymphadenopathy. It is rare and potentially fatal. CASE REPORT: We present a case report of a 52 years old female with a recent history of antecedent dapsone exposure of 100 mg daily for 2 weeks. She developed fever 10 days after exposure to dapsone therapy and was treated in various primary and tertiary centers for features of sepsis. When she presented to us, clinical features of multi-organ dysfunction and intractable sepsis was evident. She was successfully managed with intravenous corticosteroids and other supportive therapy. This case of DHS is unique due to pulmonary, hepatic and colonic involvement in addition to secondary bacterial and fungal infection, which is associated with an increased risk of mortality. CONCLUSION: As dapsone is mainstay in the treatment several infections and inflammatory conditions, further research is needed to characterize markers to diagnose DHS and to develop screening policies prior to initiation of dapsone therapy.

A lethal case of the dapsone hypersensitivity syndrome involving the myocardium.

In the Netherlands dapsone is used for the treatment of dermatitis herpetiformis, leprosy and Pneumocystis jiroveci pneumonia and prophylaxis in case of cotrimoxazole allergy. An idiosyncratic drug reaction, known as the dapsone hypersensitivity syndrome (DHS), appears in about 0.5-3.6% of persons treated with dapsone. DHS can be associated with fever, rash and systemic involvement. We present a 35-year-old woman who developed severe DHS seven weeks after starting dapsone. Six weeks after being discharged in a good clinical condition she died from fulminant myocarditis, 11 weeks after the first DHS symptoms and the discontinuation of dapsone.

Drug reaction with eosinophilia and systemic symptoms (DRESS): A histopathology based analysis.

BACKGROUND: The data on the histology of cutaneous lesions of drug reaction with eosinophilia and systemic symptoms (DRESS) is limited. AIMS: To study the histopathology of cutaneous lesions of drug reaction with eosinophilia and systemic symptoms (DRESS) and to identify any features with diagnostic or prognostic significance. METHODS: All patients admitted to the dermatology ward of government medical college, Kozhikode from January 1, 2014 to December 31, 2014 with probable or definite DRESS as per the RegiSCAR scoring system and who were willing to undergo skin biopsy were included in this prospective study. RESULTS: The study population comprised of nine patients. The consistent histological finding documented was the predominantly lymphocytic dermal inflammatory infiltrate. Four of the five patients whose histology revealed focal interface dermatitis and keratinocyte vacuolation with or without apoptotic keratinocytes, had elevated liver transaminases. Tissue eosinophilia was associated with disease flares. The presence of atypical lymphocytes in peripheral smear and histological evidence of dense dermal inflammatory infiltrate showed an association with hepatic involvement. LIMITATIONS: The main limitations of our study were the small sample size and our inability to carry out a detailed immunohistochemistry work-up. CONCLUSIONS: In the appropriate setting, varying combinations of epidermal hyperplasia, spongiosis, parakeratosis and individually necrotic keratinocytes in the background of lymphocyte predominant dermal infiltrate (with some atypia) favor a diagnosis of drug reaction with eosinophilia and systemic symptoms. Female sex, the presence of atypical lymphocytes in peripheral smear, dense dermal inflammatory infiltrate, tissue eosinophilia and interface dermatitis with or without keratinocyte necrosis was associated with a poor prognosis.

Dapsone syndrome--first Malaysian paediatric case report.

Dapsone syndrome is a potentially fatal hypersensitivity reaction to sulphone. We report a 12-year-old girl who developed high grade fever associated with intense jaundice, exfoliative skin rash and hepatomegaly after five weeks of starting the multidrug regimen for the treatment of Hansen's disease. Laboratory investigations revealed presence of leucocytosis with eosinophilia, deranged liver enzymes and an abnormal coagulation profile. Immediate cessation of the offending drug and administration of steroid proved successful. A high level of clinical awareness is fundamental for early diagnosis of dapsone syndrome as initiation of a prompt treatment may lead to rapid recovery.

Drug hypersensitivity syndrome.

Drug hypersensitivity syndrome (DHS) is an adverse drug reaction commonly associated with the aromatic antiepileptic drugs (AEDs), viz., phenytoin (PHT), carbamazepine (CBZ), phenobarbital (PB), lamotrigine, primidone, etc. It can also be caused by other drugs, such as sulfonamides, dapsone, minocycline, gold derivatives, cyclosporine, captopril, diltiazem, terbinafine, azathioprine and allopurinol. Diagnosis of DHS may be difficult because of the variety of clinical and laboratory abnormalities and manifestations and because the syndrome may mimic infectious, neoplastic or collagen vascular disorders. The risk for developing hypersensitivity within 60 days of the first or second prescription in new users of PHT or CBZ was estimated to be 2.3-4.5 per 10,000 and 1-4.1 per 10,000, respectively. The syndrome is defined by the fever, skin rash, lymphadenopathy and internal organ involvement within the first 2-8 weeks after initiation of therapy. Internal manifestations include, among others, agranulocytosis, hepatitis, nephritis and myositis. Insufficient detoxification may lead to cell death or contribute to the formation of antigen that triggers an immune reaction. Cross-reactivity among PHT, CBZ and PB is as high as 70%-80%. Management mainly includes immediate withdrawal of the culprit drug, symptomatic treatment and systemic steroids or immunoglobulins.

Allergic to all medicines and red coloured urine.

Dermatitis artefacta is a disorder in which the skin is the target of self-inflicted injury. We report a case of dermatitis artefacta, in which the patient developed skin lesions, after taking each and every medication. Additionally he also had red coloured urine after taking certain group of medications, which, on further investigations, was found to be associated with glucose 6-phosphate dehydrogenase (G6PD) deficiency. This case illustrates the presence of factitious dermatitis and physical co-morbidity simultaneously, which was missed before psychiatric referral. Every symptom in a patient with a factitious disorder should not be labelled as feigned without a proper workup.

Severe dapsone hypersensitivity syndrome.

Dapsone, a potent antiparasitic and anti-inflammatory compound, is mainly used in the treatment of leprosy and a variety of blistering skin diseases. It may cause a severe adverse drug reaction with multiorgan involvement known as dapsone hypersensitivity syndrome. We report the case of a 21-year-old female patient with dapsone hypersensitivity syndrome. The clinical presentation mimicked a viral exanthema.

Eosinophilic leukemoid reaction associated with carbamazepine hypersensitivity.

Carbamazepine is widely used in the treatment of epilepsy, neuralgic pain, and bipolar affective disorders. Several adverse drug reactions have been described during the course of carbamazepine administration, including exanthemata and hematological reactions. Carbamazepine is one of the common drugs that have been implicated in the etiology of drug hypersensitivity syndrome. A 50-year-old male presented with generalized erythroderma following 10 weeks of ingestion of carbamazepine 200 mg daily for idiopathic epilepsy. His systemic examination was within normal limits. Blood counts revealed marked eosinophilia of 52% (absolute eosinophil count of 10,400 per mm3). Bone marrow aspiration revealed a moderate increase in the eosinophilic series with cells showing normal morphology. The eosinophil counts returned to normal after 2 weeks of oral prednisolone therapy. This case is reported because of its rarity in the Indian medical literature.

Dapsone hypersensitivity syndrome in an adolescent during treatment during of leprosy.

A 12 y old girl was admitted 24 days after start a WHO multidrug therapy scheme for multibacillary leprosy (dapsone, clofazimine and rifampicin) with intense jaundice, generalized lymphadenopathy, hepatoesplenomegaly, oral erosions, conjunctivitis, morbiliform rash and edema of face, ankles and hands. The main laboratory data on admission included: hemoglobin, 8.4 g/dL; WBC, 15,710 cells/mm3; platelet count, 100,000 cells/mm3; INR = 1.49; increased serum levels of aspartate and alanine aminotransferases, gamma-glutamyl transpeptidase, alkaline phosphatase, direct and indirect bilirubin. Following, the clinical conditions had deteriorated, developing exfoliative dermatitis, shock, generalized edema, acute renal and hepatic failure, pancytopenia, intestinal bleeding, pneumonia, urinary tract infection and bacteremia, needing adrenergic drugs, replacement of fluids and blood product components, and antibiotics. Ten days after admission she started to improve, and was discharged to home at day 39th, after start new supervised treatment for leprosy with clofazimine and rifampicin, without adverse effects. This presentation fulfils the criteria for the diagnosis of dapsone hypersensitivity syndrome (fever, generalized lymphadenopathy, exfoliative rash, anemia and liver involvement with mixed hepatocellular and cholestatic features). Physicians, mainly in geographical areas with high prevalence rates of leprosy, should be aware to this severe, and probably not so rare, hypersensitivity reaction to dapsone.

Síndrome de hipersensibilidad a la dapsona / Dapsone hypersensitivity syndrome

Las sulfonas han sido de gran ayuda en el tratamiento de la lepra. La dapsona (4,4' diaminofenilsulfona; DDS) es el derivado más utilizado. Su empleo se extiende a diversas dermatosis. Se describen variados efectos adversos con su administración, siendo los más severos: hemólisis, metahemoglobinemia, agranulocitosis, hepatitis, encefalopatía y raramente hipoalbuminemia. Una rara complicación la constituye el síndrome de hipersensibilidad a la dapsona (SHD) caracterizado por desarrollarse en las primeras semanas de iniciado el tratamiento con este fármaco. Dicha patología se presenta en su expresión más completa con hipertermia, dermatitis exfoliativa generalizada, poliadenopatías, anemia y hepatitis mixta. Dos datos son particularmente característicos de este cuadro: un síndrome mononucleosiforme y un recuento de eosinófilos elevado. Se presenta un paciente que recibiendo dapsona como parte del tratamiento de una lepra lepromatosa (LL) desarrolló un SHD

Síndrome de hipersensibilidad a la dapsona / Dapsone hypersensitivity syndrome

Las sulfonas han sido de gran ayuda en el tratamiento de la lepra. La dapsona (4,4 diaminofenilsulfona; DDS) es el derivado más utilizado. Su empleo se extiende a diversas dermatosis. Se describen variados efectos adversos con su administración, siendo los más severos: hemólisis, metahemoglobinemia, agranulocitosis, hepatitis, encefalopatía y raramente hipoalbuminemia. Una rara complicación la constituye el síndrome de hipersensibilidad a la dapsona (SHD) caracterizado por desarrollarse en las primeras semanas de iniciado el tratamiento con este fármaco. Dicha patología se presenta en su expresión más completa con hipertermia, dermatitis exfoliativa generalizada, poliadenopatías, anemia y hepatitis mixta. Dos datos son particularmente característicos de este cuadro: un síndrome mononucleosiforme y un recuento de eosinófilos elevado. Se presenta un paciente que recibiendo dapsona como parte del tratamiento de una lepra lepromatosa (LL) desarrolló un SHD (AU)

Reaçäo reversa macular pós-alta e poliquimioterapia multibacilar / Reversal macular reaction after discharge and multidrug therapy for multibacillary leprosy

Sao apresentados três casos de pacientes portadores de formas multibacilares de hanseníase que apresentaram máculas hipocrômicas, em média seis meses após o término da poliquimioterapia/OMS para multibacilares (MB). Baseados nos exames baciloscópico, histopatológico e na evoluçao clínica favorável, com ou sem corticoterapia, firmou-se o diagnóstico de reaçao reversa macular, atípica, para estes casos. Discute-se este diagnóstico, em oposiçao à hipótese de recidiva de forma PB em pacientes inicialmente MB. Enfatíza-se a necessidade de uma correta caracterizaçao das lesoes de reaçao reversa pós-alta medicamentosa, evitando a reintroduçao terapêutica desnecessária.