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Specialist in Hospital Pharmacy Pharmacy Service Hospital General Universitario de Elche Camí de l'Almazara 11 03203 Elche (Alicante), Spain fax 34 966679162 jborrasb{at}sefh.es
Specialist in Hematology Hematology Service Hospital General Universitario de Elche
Specialist in Hospital Pharmacy Pharmacy Service Hospital General Universitario de Elche
Specialist in Dermatology Dermatology Section Hospital General Universitario de Elche
Specialist in Dermatology Dermatology Section Hospital General Universitario de Elche
Specialist in Hematology Hematology Service Hospital General Universitario de Elche
Published Online, May 3, 2005. www.theannals.com, DOI 10.1345/aph.1E349
Case Report. A 75-year-old man with type 2 diabetes mellitus had been treated with oral glyburide 5 mg twice daily during the last 2 years. He came to the Dermatology Service because of the appearance of skin lesions. A skin biopsy showed a granulomatous inflammation of mono- and multinucleated epithelioid histiocytes. He was diagnosed with granuloma annulare, and oral dapsone 100 mg/day was started. A complete blood cell count performed before initiation of dapsone showed normal values.
Four weeks after dapsone had been started, the patient presented to our hospital with asthenia. No abdominal pain, jaundice, vomiting, ulcers, or fever were present. He had no history of allergic drug reactions. Physical examination showed numerous annular, arcuate plaques with an erythematous border and central clearing. The results of laboratory tests were normal. There was no serologic evidence of acute infection by parvovirus B19, hepatitis B or C virus, herpes simplex, cytomegalovirus, and HIV antibody. Chest X-ray was normal, and thymoma was not found. Direct and indirect Coombs' tests, Ham, and saccharose tests were negative.
Further laboratory evaluation showed hemoglobin 3.6 g/dL, corrected reticulocyte count 0.54%, mean corpuscular volume 109 µm3, serum iron 270 µg/L, and ferritin 711 ng/mL. His vitamin B12 and folic acid levels were normal. Bone marrow aspiration revealed normocellular marrow, with profound erythroid hypoplasia (most cells were immature) and a high myeloid/erythroid ratio of 1/6. The morphology and maturation of the myeloid cells and megakaryocites were normal. A diagnosis of PRCA was made. We suspected that the causative agent was dapsone since this was the only drug added before the hematologic condition appeared. Consequently, dapsone was suspended, and the patient received blood transfusions until his condition improved considerably. The hematologic counts gradually returned to normal levels (Table 1). On day 8, the patient was asymptomatic.
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Discussion. PRCA is an uncommon hematologic disorder characterized by anemia, reticulocytopenia, and erythroid aplasia in bone marrow. It can be categorized as congenital or acquired. The secondary acquired form is associated with viral infections, thymoma, tumors, hemolytic anemia, pregnancy, severe nutritional deficiencies, and collagen vascular disease.1 Drug-induced PRCA is rare and has been reported predominantly in adults.2
The most common hematologic adverse reactions of dapsone are hemolysis in patients with glucose-6-phosphate dehydrogenase deficiency, agranulocytosis, and methemoglobinemia. In healthy individuals, hemolysis occurs in a dose-dependent manner, and a reduction in hemoglobin will be detectable at dapsone doses ranging from 50 to 300 mg/day. Aplastic anemia induced by dapsone is rare and its pathogenesis is unknown.3,4 In our patient, PRCA appears to have been an idiosyncratic reaction. A MEDLINE (1966-February 2005) search produced one other report of PRCA associated with dapsone and pyrimethamine.5
In our case, based on the Naranjo probability scale, the PRCA could be considered probable.6 Clinicians should be aware of this severe reaction. Therefore, close monitoring for anemia should be done in patients taking dapsone. If clinical evaluation leads to the suspicion of PRCA, dapsone should be discontinued.
References
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