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Year : 2016  |  Volume : 5  |  Issue : 3  |  Page : 215-218

Dapsone-induced pure red cell aplasia and cholestatic jaundice: A new experience for diagnosis and management

1 Department of Medicine, King George Medical University, Lucknow, Uttar Pradesh, India
2 Department of Clinical Hematology and Oncology, King George Medical University, Lucknow, Uttar Pradesh, India
3 Department of Pathology, King George Medical University, Lucknow, Uttar Pradesh, India

Date of Web Publication7-Jul-2016

Correspondence Address:
Jitendra Singh
Department of Medicine, King George Medical University, Lucknow, Uttar Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2279-042X.185743

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Dapsone (4,4'- diaminodiphenylsulfone) is the parent compound of the sulfones, and it has potent antiparasitic, anti-inflammatory, and immunomodulatory effects. It is used in the treatment of leprosy, dermatitis herpetiformis, and prophylactically to prevent Pneumocystis pneumonia and toxoplasmosis in patients unable to tolerate trimethoprim with sulfamethoxazole. We hereby report a case of dapsone toxicity who developed pure red cell aplasia and cholestatic jaundice in a suspected case of dermatitis herpetiformis. Patient had an excellent response to corticosteroids after withdrawal of dapsone.

Keywords: Cholestatic jaundice; Dapsone; dermatitis herpetiformis; pure red cell aplasia

How to cite this article:
Sawlani KK, Chaudhary SC, Singh J, Raja DC, Mishra S, Goel MM. Dapsone-induced pure red cell aplasia and cholestatic jaundice: A new experience for diagnosis and management. J Res Pharm Pract 2016;5:215-8

How to cite this URL:
Sawlani KK, Chaudhary SC, Singh J, Raja DC, Mishra S, Goel MM. Dapsone-induced pure red cell aplasia and cholestatic jaundice: A new experience for diagnosis and management. J Res Pharm Pract [serial online] 2016 [cited 2020 Jun 5];5:215-8. Available from: http://www.jrpp.net/text.asp?2016/5/3/215/185743

  Introduction Top

Dapsone is generally well tolerated. The common side effects of dapsone include hemolysis, methemoglobinemia, hypersensitivity syndrome, and toxic hepatitis. Dapsone-induced cholestatic jaundice and pure red cell aplasia are rare entities but have been reported separately. [1],[2] To the best of our knowledge, it is the first case of dapsone therapy who developed these two dangerous adverse effects in the same case.

  Case report Top

A 30-year-old female presented with generalized weakness, fever, jaundice, and pruritus all over the body for 7 days. On examination, she was febrile (temperature, 102°F), blood pressure was 110/70 mm Hg, and pulse rate was 112/min. She had icterus and pallor. Pruritic papulovesicular rashes and urticarial plaques were present all over the body with predominantly involvement of lower extremities without mucosal involvement. On systemic examination, hepatomegaly was present. Patient had a history of on and off pruritic skin lesions for the last 2 years. A general practitioner diagnosed her as a case of suspected dermatitis herpetiformis, and dapsone therapy was started. She was taking tablet dapsone 100 mg/day for the last 3 months. On inquiry, we found a normal report of complete blood count prior dapsone therapy.

On the day of admission, her hemoglobin was 2.6 g/dl, total leukocyte count 12,480/mm 3 , platelet count 310,000 cells/mm 3 , and reticulocyte count was 0.08%. Peripheral smear showed normocytic normochromic anemia. Liver function tests revealed bilirubin (total), 24.3 mg/dl (direct bilirubin - 17.7), aspartate aminotransferase - 365 U/L, alanine aminotransferase - 345 U/L, alkaline phosphatase - 2840 U/L, serum protein - 7.7 g/dl (serum albumin - 3.4 g/dl), and prothrombin time 13.0 s (INR 1.0). Her blood urea, creatinine, random blood sugar, uric acid, electrolytes, urine analysis, and stool examination were within normal limits. Significant complete blood counts and liver function tests are summarized in [Table 1].
Table 1: Significant laboratory parameters of patient

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Serologic tests for hepatitis A, B, C, E viruses and HIV screening were negative. Coombs test and polymerase chain reaction for parvo B19 virus were negative. Autoimmune hepatitis was ruled out by the absence of antinuclear (ANA), anti-mitochondrial (AMA), and anti-lysosomal kidney mitochondrial antibodies (anti-LKM. Serum assays for C 3, C 4 , haptoglobin, and glucose 6-phosphatase dehydrogenase were within normal limits. Urinary porphobilinogen excretion test was negative. Rapid malarial test was negative. X-ray chest was normal.

Repeated ultrasonography of abdomen showed hepatomegaly with normal echotexture without any evidence of extrahepatic biliary obstruction. Bone marrow aspiration showed cellular fragments with preponderance of myeloid cells with normal morphology and maturation [Figure 1]. Liver biopsy revealed ballooning of hepatocytes and canalicular cholestasis without any obvious inflammation suggestive of drug-induced cholestasis [Figure 2].
Figure 1: Bone marrow aspirate showing mainly myeloid precursors with very few erythroid precursors suggestive of pure red cell aplasia

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Figure 2: Liver parenchyma with ballooning of hepatocytes and canalicular cholestasis. No obvious inflammation. Findings suggestive of drug-induced cholestasis

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On the basis of clinical and laboratory findings, she was diagnosed as a case of dapsone-induced pure red cell aplasia and cholestatic jaundice. We stopped dapsone immediately and prednisolone 40 mg/day was started. Four units of packed red blood cells were transfused. She was also given antipyretics and oral antihistamines. Patient had fever and mild elevated leukocytes count which might be due to secondary infection, so broad spectrum antibiotics were given. Patient improved day by day and her laboratory parameters returned to normal after 3 weeks. During her 2-years follow-up, she was doing well.

  Discussion Top

Dapsone (4,4'-diaminodiphenylsulfone) has been in clinical use for almost 50 years. Dapsone is used in dermatology for its anti-inflammatory properties, particularly in sterile (noninfectious) pustular diseases of the skin. Dapsone is approved for the use in dermatitis herpetiformis and leprosy. It is particularly useful in the treatment of linear immunoglobulin A (IgA) dermatosis, bullous systemic lupus erythematosus, erythema elevatum diutinum, and subcorneal pustular dermatosis.

Potential side effects of dapsone are included in [Table 2]. [3],[4] Other adverse reactions of dapsone include dramatic generalized hypersensitivity syndrome termed as "dapsone syndrome." This syndrome has a frequency of 0.2-0.5% in patients on dapsone therapy. The constellation of features included in this syndrome is fever, exfoliative dermatitis, lymphadenopathy, lymphocytosis, methemoglobinemia, hemolytic anemia, and hepatotoxicity. Hyperbilirubinemia present in dapsone syndrome may partly be due to hemolysis in addition to hepatotoxicity. Both hepatocellular and cholestatic injury have been described. Cholestatic pattern may have less severe course and is characterized by high alkaline phosphatase level and modest increase of transaminases level. Rarely, dapsone can cause cholangitic liver injury. [1] The mechanism of injury, including hepatotoxicity in dapsone syndrome, seems to be hypersensitivity reaction. [5]
Table 2: Potential adverse effects of dapsone

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Pure red cell aplasia is the term now widely applied to isolated anemia secondary to failure of erythropoiesis. The cardinal findings are a low hemoglobin level, reticulocytopenia, and absent or extremely infrequent erythroid precursor cells in the marrow. Like other marrow failure syndromes, pure red cell aplasia can be inherited or acquired, and its pathophysiology is heterogeneous. Idiosyncratic drug reactions account for a far smaller proportion of red cell aplasia than for agranulocytosis. [6] The acquired form of pure red cell aplasia presents either as an acute self-limiting disease, predominantly seen in children or as a chronic illness that is more frequently seen in adults. It may present as a primary hematologic disorder in the absence of any other disease, or secondary to parvovirus infection, collagen vascular disease, leukemia, lymphoma, solid tumors, and treatment with recombinant human erythropoietin or other drugs. [7] Case reports have implicated various agents such as diphenylhydantoin, sulfa and sulfonamide drugs, azathioprine, allopurinol, isoniazid, procainamide, ticlopidine, ribavirin, and D-penicillamine. [6]

Pure red cell aplasia and cholestatic liver injury associated with dapsone therapy are life-threatening adverse reactions. Therefore, it is necessary for clinicians to confirm the diagnosis by histopathologic tests including skin biopsy before starting therapy. Furthermore, early diagnosis and aggressive management are necessary for a good outcome.

This case highlights an unusual and potentially fatal toxicity of dapsone therapy. Hence, treating physicians should have clear justification for diagnosis and use of dapsone therapy. Patient must also be counseled for any adverse reaction before starting dapsone therapy and should be advised to visit a respective doctor immediately.

  Authors Contribution Top

This manuscript is designed, studied, prepared and reviewed by all contributors. Beside this, Dr. Sanjay Mishra examined the bone Marrow and histopathological study was done by Dr. Madhu Mati Goel.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Itha S, Kumar A, Dhingra S, Choudhuri G. Dapsone induced cholangitis as a part of dapsone syndrome: A case report. BMC Gastroenterol 2003;3:21.  Back to cited text no. 1
Borrás-Blasco J, Conesa-García V, Navarro-Ruiz A, Devesa P, Matarredona J, Marín-Jiménez F. Pure red cell aplasia associated with dapsone therapy. Ann Pharmacother 2005;39:1137-8.  Back to cited text no. 2
Fox LP, Merk HF, Bickers DR. Dermatological pharmacology. In: Brunton LL, Lazo JS, Parker KL, editors. Goodman & Gilman′s The Pharmacological Basis of Therapeutics. 11 th ed. New York: McGraw-Hill; 2006. p. 1679-706.  Back to cited text no. 3
Zhu YI, Stiller MJ. Dapsone and sulfones in dermatology: Overview and update. J Am Acad Dermatol 2001;45:420-34.  Back to cited text no. 4
Johnson DA, Cattau EL Jr., Kuritsky JN, Zimmerman HJ. Liver involvement in the sulfone syndrome. Arch Intern Med 1986;146:875-7.  Back to cited text no. 5
Young NS. Pure red cell aplasia. In: Lichtman MA, Beutler E, Kipps TJ, Seligsohn U, Kaushansky K, Prchal JT, editors. Williams Hematology. 8 th ed. New York: McGraw-Hill; 2010. p. 485-95.  Back to cited text no. 6
Sawada K, Fujishima N, Hirokawa M. Acquired pure red cell aplasia: Updated review of treatment. Br J Haematol 2008;142:505-14.  Back to cited text no. 7


  [Figure 1], [Figure 2]

  [Table 1], [Table 2]

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