The Dapsone Hypersensitivity Syndrome revisited: a potentially fatal multisystem disorder with prominent hepatopulmonary manifestations

Abstract

4,4'-Diaminodiphenylsulphone (Dapsone) is widely used for a variety of infectious, immune and hypersensitivity disorders, with indications ranging from Hansen's disease, inflammatory disease and insect bites, all of which may be seen as manifestations in certain occupational diseases. However, the use of dapsone may be associated with a plethora of adverse effects, some of which may involve the pulmonary parenchyma. Methemoglobinemia with resultant cyanosis, bone marrow aplasia and/or hemolytic anemia, peripheral neuropathy and the potentially fatal dapsone hypersensitivity syndrome (DHS), the focus of this review, may all occur individually or in combination. DHS typically presents with a triad of fever, skin eruption, and internal organ (lung, liver, neurological and other systems) involvement, occurring several weeks to as late as 6 months after the initial administration of the drug. In this sense, it may resemble a DRESS syndrome (Drug Rash with Eosinophilia and Systemic Symptoms). DHS must be promptly identified, as untreated, the disorder could be fatal. Moreover, the pulmonary/systemic manifestations may be mistaken for other disorders. Eosinophilic infiltrates, pneumonitis, pleural effusions and interstitial lung disease may be seen. This syndrome is best approached with the immediate discontinuation of the offending drug and prompt administration of oral or intravenous glucocorticoids. An immunological-inflammatory basis of the syndrome can be envisaged, based on the pathological picture and excellent response to antiinflammatory therapy. Since dapsone is used for various indications, physicians from all specialties may encounter DHS and need to familiarize themselves with the salient features about the syndrome and its management.

Dapsone hypersensitivity syndrome: A rare life threatening complication of dapsone therapy

“…DHS can develop several weeks to as long as six months after treatment initiation and the reported incidence ranges from 0.5% to 3%. [1]…”

“…[1] Commonly encountered adverse effects of this drug include dose unrelated (idiosyncratic) skin hypersensitivity reactions and dose-related hemolytic anemia and methemoglobinemia. Other notable adverse effects include insomnia and psychosis.…”

Alternative Procedure to Allow Continuation of Dapsone Therapy despite Serious Adverse Reaction in a Case of Dapsone-Sensitive Erythema Elevatum Diutinum

“…Dapsone-induced DRESS was initially described in 1981 by Tomecki and Catalano [14], and the term ‘dapsone hypersensitivity syndrome’ was introduced and then generally used in the literature. The incidence of this condition ranges from 0.5 to 3% and symptoms usually consist of fever, skin eruption and internal organ involvement (pulmonary manifestations, hepatitis) [9] as presented by our patient. Other manifestations shared with DRESS can be observed such as eosinophilia, atypical lymphocytosis and adenopathy, suggesting that dapsone-induced DRESS is probably more appropriate to define this idiosyncratic reaction than ‘dapsone hypersensitivity syndrome’.…”

“…Dapsone is also used for a variety of dermatological conditions including autoimmune bullous diseases, leukocytoclastic disorders and other forms of vasculitides [8]. However dapsone, as others drugs including anticonvulsants, sulfonamides, allopurinol and minocycline, may cause DRESS, more recently termed drug-induced hypersensitivity syndrome (DIHS) [9,10]. This severe adverse drug-induced reaction usually occurs after 2–6 weeks of exposure to drugs.…”

Cervical Lymphadenopathy Mimicking Angioimmunoblastic T-Cell Lymphoma after Dapsone-Induced Hypersensitivity Syndrome

“…4,4'-Diaminodiphenyl sulfone (dapsone) is widely used to treat a variety of infectious, immune, and hypersensitivity disorders, with indications ranging from Hansen's disease to inflammatory diseases and insect bites 1. However, a potential severe side-effect, known as dapsone-induced hypersensitivity syndrome (DHS), may occur.…”