Journal of Postgraduate Medicine Medknow Publications and Staff Society of Seth GS Medical College and KEM Hospital, Mumbai, India ISSN: 0022-3859 EISSN: 0972-2823 Vol. 48, Num. 1, 2002, pp. 37-38

Journal of Postgraduate Medicine, Vol. 48, Issue 1, 2002 pp. 37-38

Acquired Pure Red Cell Aplasia in a Child

Sharma RA, Hiwarkar P, Manglani MV, Muralidhar HP

Division of Paediatric Haematology-Oncology, L.T.M.G. Hospital, Sion, Mumbai- 400022.
Address for Correspondence: Mamta Manglani, MD, 51, Sea Springs, B.J. Road, Band Stand, Bandra (w), Mumbai - 400 050. India. E-mail: mmanglani@hotmail.com 

Code Number: jp02011

Abstract:

Primary acquired pure red cell aplasia is a rare occurrence in childhood. An eleven-year old boy presented to us with pallor, which required multiple packed red cell transfusions. He did not have hepatosplenomegaly, jaundice or lymphadenopathy. Bone marrow examination revealed the diagnosis of pure red cell aplasia. All possible investigations were done to exclude secondary causes of pure red cell aplasia. No secondary cause was found on investigations. Rheumatoid factor and anti-nuclear antibodies were positive. He was started on oral steroids, to which he did not respond. He was then given cyclosporine A. Response to cyclosporine was dramatic and the child now does not require any transfusions.

Key Words: Anaemia, pure red cell aplasia, bone marrow failure.

Acquired pure red cell aplasia (PRCA) is a disease characterised by normocytic, normochromic anaemia, low haematocrit, reticulocytopaenia and selective erythroid hypoplasia. PRCA can occur as a chronic or acute form; the former is predominantly seen in adults and latter in children.¹ Pathogenesis involves immune dysfunction with antibodies directed against erythroid precursor cells or erythropoietin, or due to T-cell mediated suppression of erythropoiesis. Due to its rare occurrence in the paediatric age group, we report a case of chronic acquired PRCA who was treated with cyclosporine A. 

Case History

An eleven-year-old boy presented with a history of pallor, noticed two months prior to admission, and fever of four days duration, one month prior to admission. He was transfused four units of blood over a period of two months. There was no history of lump in abdomen, bleeding from any site, jaundice, bone pains, drug ingestion, joint swellings or rash. There was no history of blood transfusions received by him or his family members any time in the past. There was no history of tuberculosis or contact with tuberculosis.

Apart from pallor, his general examination findings were non-contributory. A functional systolic murmur was heard at the base of the heart. Other systemic examination did not reveal any abnormality.

On investigations, haemoglobin was 2.2gm%, haematocrit 8.8%, reticulocyte count 0%, total red cell count 0.94 million/cmm, mean corpuscular volume 93.3 fl, mean corpuscular haemoglobin 31.8 pg, mean corpuscular haemoglobin concentration 34.1%, and red cell distribution width 18.3%. The total white cell count was 4,800/cmm, with 57% polymorphs, 32% lymphocytes, 4% eosinophils and 7% monocytes, and the platelet count was 3,67,000/cmm. Peripheral blood smear showed normochromic, normocytic red cells with occasional macrocytes and tear drop cells. Stool for occult blood was negative. Serum bilirubin was 0.6mg%. Haemoglobin F was 0.40%. The direct and indirect antiglobulin tests were negative. Liver and renal function tests were normal. Chest X-ray was within normal limits and Mantoux test was negative. Bone marrow aspiration and trephine biopsy showed red cell hypoplasia, without giant pronormoblasts, with normal myeloid and megakaryocytic series. The M:E ratio was 11.2:1. A high resolution computed tomography of chest ruled out thymoma. Serum immunoglobulins revealed an IgG level of 2200 mg% (N - 565 to 1570 mg%), IgM and IgA of 87.5 mg% (N - 28 to 135 mg%) and 360 mg% (N - 102 to 545 mg%) respectively. Rheumatoid factor was positive (>128 IU/ml), anti-nuclear antibodies were also positive (1: 40) and anti-dsDNA was negative. Paul-Bunnel test, antibodies to HIV by ELISA, and HBsAg were negative. Parvovirus B19 DNA or IgM (ruled out on the basis of absence of giant pronormoblasts on bone marrow examination), and antibodies to erythroid precursors and erythropoietin could not be done, because these tests were not available. A diagnosis of primary acquired PRCA was made.

On diagnosis, the child was put on oral prednisolone in the dose of 2mg/kg/ day in four divided doses. A partial response was observed after a week, with an increase in reticulocytes (corrected reticulocyte count 1.8%). However, over the next three weeks, haemoglobin dropped from 9.2gm% to 6.1gm%, and hence he was started on cyclosporine A in the dose of 12 mg/kg/day in 2 divided doses and titrated to maintain blood trough levels of 100 to 250 ng/ml (done by radio-immunoassay). Steroids were tapered and omitted. After starting cyclosporine A he is maintaining haemoglobin between 8.5 and 10.5 gm% without blood transfusion during a period of nine months. 

Discussion

Pure red cell aplasia, first described by Kaznelson, more than 70 years ago,² may be congenital or acquired. Congenital PRCA is also known as Diamond-Blackfan syndrome. Acquired PRCA, rare in children, may be primary or secondary to conditions like Parvovirus B19 infection, thymoma, myelodysplatic diseases, drugs (including alpha-interferons, diphenylhydantoin, isoniazid, lamivudine), collagen vascular diseases and infections including tuberculosis.^1,3-6

Acquired primary PRCA commonly occurs at a mean age of 60 years. Rare familial cases have been reported. The male to female ratio is 2:1. It has been postulated that primary PRCA has an autoimmune basis, which has been confirmed by in-vivo and in-vitro studies.² It can be due to humoral or cellular mechanisms. Evidence of clonal rearrangement of the T-cell receptor beta chain gene has suggested it to be a clonal T-cell proliferative disorder, in which T cells suppress erythropoiesis.⁷ Since immune basis is commonly known to cause primary acquired PRCA, treatment includes immunosuppression and/or immunomodulation. Various drugs including immunosuppressive agents, such as corticosteroids, androgens, cytotoxic drugs like cyclophosphamide, azathioprine, 6-mercaptopurine, vincristine, daunorubicin etc. and immunomodulators like anti-thymocyte globulin/ anti-lymphocyte globulin, intravenous immunoglobulin G and cyclosporin have been tried with variable success.^8-10 Other modalities include splenectomy, plasmapheresis and stem cell transplantation.¹¹ Recently Anti-CD20 monoclonal antibody (Rituximab), which is highly effective for in-vivo B-cell depletion, has been tried with success in PRCA.¹²

Cyclosporin A (cyclic undecapeptide), a fungal metabolite, acts by inhibiting IL-2 production by T-lymphocytes, which, in turn, prevents cytotoxic T-cell activation. Amongst the various modalities tried, cyclosporin A has been the most successful drug.⁹ For patients on cyclosporine, monitoring is essential to prevent complications, especially, renal failure.

Acknowledgements

We are grateful to Dr. A. R. Fernandez, Dean of the institution for permitting to publish this article and Dr. Madhuri Kulkarni, Head of Department of Paediatrics for her encouragement towards the writing of this article. 

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