Hypersensitivity dapsone

Dapsone (Avlosulfon) is a member of a class of chemical agents known as the sulfones. Dapsone is especially effective against M. leprae and is used with rifampin as the primary method of treating leprosy. Dapsone appears to exert its antibacterial effects in a manner similar to that of the sulfonamide drugs that is, dapsone impairs folic acid synthesis by competing with PABA in bacterial cells. Primary adverse effects associated with dapsone include peripheral motor weakness, hypersensitivity reactions (skin rashes, itching), fever, and blood dyscrasias, such as hemolytic anemia. 

Serious cutaneous reactions, such as exfoliative dermatitis, toxic epidermal necrolysis, and erythema multiforme buUo-sum are extremely rare. Erythema nodosum leprosum has been described during dapsone therapy, mostly in the lepro-matous type of leprosy (10). If erythema nodosnm develops before the start of therapy, the drug should be withheld until the reaction has disappeared. Severe erythema nodosum can be controlled by short-term glucocorticoid therapy. Desensitization to dapsone in patients with hypersensitivity reactions has been proposed (29). 

Tomecki KJ, Catalano CJ. Dapsone hypersensitivity. The sulfone syndrome revisited. Arch Dermatol 1981 117(l) 38-9. 

Richardus JH, Smith TC. Increased incidence in leprosy of hypersensitivity reactions to dapsone after introduction of multidrug therapy. Lepr Rev 1989 60(4) 267-73. 

Three patients developed a hypersensitivity syndrome after taking pyrimethamine 12.5 mg + dapsone 100 mg weekly as malaria prophylaxis (16). The diagnosis was based on the presence of fever, lymphadenopathy, a maculopapular rash, and hepatitis. A mild Coombs -positive hemolytic anemia was also observed in one of the patients. All the clinical, hematological, and biochemical abnormalities normalized within 3 months of tapering regimens of moderate-dose prednisolone. 

Thong BY, Leong KP, Chug HH. Hypersensitivity syndrome associated with dapsone/pyrimethamine (Maloprim) antimalaria chemoprophylaxis. Ann Allergy Asthma Immunol 2002 88(5) 527-9. 

It appears that dapsone is a safe drug when used in standard dosage. Perhaps, renal involvement should be watched for when administering dapsone to patients with G6PD deficiency that could develop hemolytic complications [207] and in patients that present with dapsone hypersensitivity syndrome. 

Sener O, Doganci L, Safali M, Besirbellioglu B, Bulucu F, Pahsa A. Severe dapsone hypersensitivity syndrome. J Investig Allergol Clin Immunol. 2006 6(4) 268-70. 

Bucaretchi F, Vicente DC, Pereira RM, Tresoldi AT. Dapsone hypersensitivity syndrome in an adolescent during treatment during of leprosy. Revista do Institute de Medicina Tropical de Sao Paulo. 2004 Nov-Dec 46(6) 331-4. 

Alves-Rodrigues EN, Ribeiro LC, Silva MD,Takiuchi A, Rabel-Filho OC, Martini-Filho D, et al. Renal hypersensitivity vasculitis associated with dapsone. Am J Kidney Dis. 2005 Oct 46(4) e51-3. 

Note A hypersensitivity reaction - termed the sulfone syndrome or dapsone syndrome - may infrequently develop during the first six weeks of treatment. This syndrome consists of exfoliative dermatitis, fever, malaise, nausea, anorexia, hepatitis, jaundice, lymphadenopathy and hemolytic anemia. See (1982) Kromann NP +, Arch Dermatol I 18, 531... 

N-acetyltransferase (NAT2) Isoniazid, hydralazine, sulfonamides, amonafide, procainamide, dapsone, caffeine Hypersensitivity to sulfonamides, amonafide toxicity, hydralazine-induced lupus, isoniazid neurotoxicity... 

Resistance to sulfonamides is now common for N. meningitidiSy as well as in cases of bacillary dysentery. Antibiotics have generally replaced the sulfonamides for these purposes. Sulfonamides, particulady sulfisoxazole and sulfadiazine, are of value in treatment of infections due to Nocardia species, and sulfonamides are effective for trachoma. Inclusion conjunctivitis is also treated with sulfacetamide ointment. Oral administration of a sulfonamide, eg, sulfisoxazole, has been successful for treatment of lymphogranuloma venereum and chancroid Dapsone and sulfonamides have also been used for treatment of the skin disorder dermatitis herpetiformis. Sulfonamides have been used for long term prophylaxis of rheumatic fever, but are being replaced by penicillin for this purpose, except in cases of hypersensitivity to penicillin (19). 

Immunologic Ocular administration of dorzolamide and timolol (doses not stated) in a woman with glaucoma led to the development of a disseminated eruption associated with severe thrombocytopenia [4 ]. A skin biopsy showed hyperkeratosis, acanthosis, and perivascular and periadnexal infiltrates without vasculitis. The skin reaction resolved after withdrawal of dorzolamide and treatment with an antihistamine, but the thrombocytopenia persisted. Subsequent treatment with dapsone led to a recurrence of the skin changes this pattern is consistent with sulfonamide hypersensitivity syndrome [SEDA-30, 252]. 

Immunologic Dapsone has been used in the treatment of urticarial vasculitis, chronic idiopathic urticaria and angioedema, and delayed pressure urticaria, and in patients with poor responses to conventional therapy. Serious allergic reactions to dapsone have been described in under 5% of patients during long-term treatment and are known collectively as the dapsone hypersensitivity syndrome. 

A 35-year-old woman developed the dapsone hypersensitivity syndrome after taking dapsone for 13 days for delayed pressure urticaria [11 ]. She had an erythematous papular rash on the face, trunk, and limbs, multiple bilateral cervical and retroauricular tender lymph nodes, a hyperemic pharynx, and oral ulcers. There was an eosinophilia. Dapsone was withdrawn and she was given oral prednisone over 6 weeks with hydroxyzine and ranitidine. She recovered over 3 months. 

The internal organ most commonly involved in the dapsone hypersensitivity... 

Do Valle SO, Franca AT, Fires GV, Guimaraes P, Dias GA, Levy SA. Dapsone hypersensitivity syndrome during delayed pressure urticaria treatment. Ann Allergy Asthma Immunol 2010 104(2) 181-2. 

Cardiovascular Complete atrioventricular block has been reported in the context of dapsone hypersensitivity [44 ]. 

Sheen YS, Chu CY, Wang SH, Tsai TF. Dapsone hypersensitivity syndrome in non-leprosy patients a retrospective study of its incidence in a tertiary referral center in Taiwan. J Dermatolog Treat 2009 20 (6) 340-3. 

Hypersensitivity reaction With a prevalence rate of 1.4%, mucosal involvement, hepatitis and higher age were associated with an increased risk of fatal outcome following hypersensitivity reaction to dapsone [77 ]. 

---