Dapsone

Dapsone is a sulfone active against a wide range of bacteria but mainly employed for its actions against mycobacterium leprae. Target: Antibacterial Dapsone is an antibacterial most commonly used in combination with rifampicin and clofazimine as multidrug therapy (MDT) for the treatment of Mycobacterium leprae infections (leprosy). Dapsone antagonized all of the I/R end points measured, showing a remarkable ability to decrease markers of damage through antioxidant, antiinflammatory, and anti-apoptotic effects [1]. As an antibacterial, dapsone inhibits bacterial synthesis of dihydrofolic acid, via competition with para-aminobenzoate for the active site of dihydropteroate synthetase. Dapsone has anti-inflammatory and immunomodulatory effects [2].

References:
[1]. Diaz-Ruiz, A., et al., Antioxidant, antiinflammatory and antiapoptotic effects of dapsone in a model of brain ischemia/reperfusion in rats. J Neurosci Res, 2008. 86(15): p. 3410-9. [2]. Begon, E., O. Chosidow, and P. Wolkenstein, [Disulone]. Ann Dermatol Venereol, 2004. 131(12): p. 1062-73.

The Efficacy of Colchicine and Dapsone Combination Therapy in Relapsed Immune Thrombocytopenia.[Pubmed:28286634]

Hematol Rep. 2017 Feb 23;9(1):7034.

The aim of the present paper is to evaluate the efficacy and safety of colchicine and Dapsone combination therapy in cases of steroid-dependent, relapsed and refractory immune thrombocytopenia (ITP). This is a retrospective study of ITP patients who attended the Hematology Clinic at Chiang Mai University Hospital (Thailand) from 1 January 2008 to 30 September 2014. Medical records and clinical data were reviewed for efficacy and adverse effects. Sixty-four ITP patients received the combination therapy. The median age was 46 years and 70.3% were female. The majority (65.6%) were relapsed ITP patients. Median platelet count before starting treatment was 22.6x10(9)/L. The response rate was 82.8%, with 75.0% of patients having a complete response. Median time to response was 8 weeks. The response rate was higher in relapsed patients (90.4%) compared to refractory (61.5%) and steroid-dependent patients (77.8%). Steroid treatment was discontinued in 30 patients (50%) following combination therapy. The most common side effect was hemolysis due to Dapsone which was found in eight patients (12.5%). We can therefore conclude that combination therapy with colchicine and Dapsone is an alternative second-line therapy option in relapsed ITP cases with acceptable side effects.

Systemic Lupus Erythematosus and Bullous Pemphigoid with Dramatic Response to Dapsone.[Pubmed:28352068]

Am J Case Rep. 2017 Mar 29;18:317-319.

BACKGROUND Bullous pemphigoid is an autoimmune blistering disease, with relapses, isolated or associated with other autoimmune diseases such as systemic lupus erythematosus (SLE). Joint manifestations rapidly respond to small or moderate doses of corticosteroids, whereas skin manifestations usually respond to antimalarial drugs. CASE REPORT We describe the clinical case of an 11-year-old girl with SLE. She showed bullous skin lesions with arthralgia, mild proteinuria, resolved after steroid treatment. At the tapering of her prednisone dose, the patient had new skin lesions requiring an increased dose of prednisone. She started Dapsone at the dosage of 1 mg/kg/day, maintaining low dose prednisone; this treatment was successfully followed by the dramatic disappearance of skin lesions and limb pain. CONCLUSIONS Bullous skin lesions can represent the first clinical presentation of pediatric SLE and could influence the treatment and the outcome of these patients. This case showed an atypical course as both skin manifestations and arthritis promptly and persistently resolved with Dapsone without the use of high-dose glucocorticoids. Only a few cases of patients with SLE associated with bullous pemphigoid have been reported in the literature, and very few in the pediatric population.

Efficacy and Safety of Dapsone Versus Trimethoprim/Sulfamethoxazol for Pneumocystis Jiroveci Prophylaxis in Children With Acute Lymphoblastic Leukemia With a Background of Ethnic Neutropenia.[Pubmed:28234744]

J Pediatr Hematol Oncol. 2017 Apr;39(3):203-208.

STUDY OBJECTIVE: To study Dapsone in comparison with trimethoprim/sulfamethoxazole (TMP/SMX) for Pneumocystis jiroveci (PJP) prophylaxis in children with acute lymphoblastic leukemia (ALL). DESIGN: A retrospective study with a prospective follow-up. PATIENTS: Pediatric ALL patients diagnosed between May 2009 and May 2014, who are still receiving or have completed their maintenance chemotherapy. Patients who completed chemotherapy were prospectively followed up for neutropenia. METHODS: TMP/SMX was used as the initial PJP prophylaxis. An alternative drug was indicated if the patient remained cytopenic for >3 weeks. Average absolute neutrophilic count (ANC), average % of oral mercaptopurine (6-MP), and methotrexate doses were calculated over a period of 6 months before and after shifting to Dapsone. RESULTS: Sixty-two ALL patients were eligible for analysis. Twenty-four patients (38.7%) received TMP/SMX for PJP prophylaxis, whereas 34 patients received Dapsone (54.8%). Only 3 patients received IV pentamidine (4.8%), whereas 1 patient (1.6%) received atovaquone. The incidence of prophylaxis failure was 1/1041 months on TMP/SMX and 1/528 months on Dapsone. After shifting to Dapsone, patients maintained significantly higher ANC (1.46+/-0.46 vs. 1.17+/-0.40, P=0.0053), and received significantly higher doses of 6-MP (62.61%+/-11.45 vs. 57.45+/-10.14, P=0.0081) and methotrexate (64.9%+/-14.29 vs. 56.5%+/-9.9, P=0.0176), with a significantly shorter duration of chemotherapy interruption (1.94+/-1.2 vs. 3.25+/-1.29 wk, P=0.0002). CONCLUSIONS: Dapsone for PJP prophylaxis in ALL allowed patients to maintain higher ANC and to receive higher doses of chemotherapy, while maintaining a low incidence of PJP breakthrough infection.

Dapsone-induced agranulocytosis-possible involvement of low-activity N-acetyltransferase 2.[Pubmed:28322460]

Fundam Clin Pharmacol. 2017 Oct;31(5):580-586.

Dapsone-induced agranulocytosis is a rare but potentially fatal adverse drug reaction (ADR). A 45-year-old male Caucasian patient developed agranulocytosis caused by Dapsone (diamino-diphenyl sulfone), which he was prescribed for leukocytoclastic vasculitis. Patient's treatment consisted of termination of Dapsone, antibiotic therapy, and granulocyte colony-stimulating factor leading to prompt improvement of symptoms and normalization of laboratory blood values. Diagnostic evaluation revealed methemoglobinemia and excluded glucose-6-phosphate dehydrogenase deficiency. Pharmacogenetics testing showed that he was a carrier of NAT2 *5/*6 genotype, predisposing to low activity of the N-acetyltransferase 2 enzyme. This was the first and only ADR to Dapsone reported in Croatia. In total, there have been 73 ADR to Dapsone recorded worldwide, including only four cases of agranulocytosis.