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Year : 2021  |  Volume : 1  |  Issue : 3  |  Page : 176-178

Aplastic Anemia Complicating Systemic Lupus Erythematosus

Department of Pediatrics, Lady Hardinge Medical College and Associated Kalawati Saran Children's Hospital, New Delhi, India

Date of Submission12-May-2021
Date of Decision15-Jun-2021
Date of Acceptance09-Aug-2021
Date of Web Publication31-Aug-2021

Correspondence Address:
Dr. Anu Maheshwari
Lady Hardinge Medical College and Kalawati Saran Children's Hospital, New Delhi - 110 001
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ipcares.ipcares_144_21

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Background: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder with a myriad of hematological manifestations. Pancytopenia occurs in 10%–50% of cases in these patients. Rare cases of aplastic anemia have been reported with SLE but mostly in adults. Clinical Description: A 6-year-old child presented with fever and painful multiple joint swelling for 6 months. Examination revealed pallor and polyarthritis involving small and large joints. Hemogram, bone marrow aspiration, and biopsy established the diagnosis of aplastic anemia. Since the clinical phenotype encompassed a childhood-onset multisystemic (musculoskeletal and hematological) chronic illness with constitutional symptoms, we considered included connective tissue disorders (CTDs), systemic-onset juvenile idiopathic arthritis with macrophage activation syndrome, hematological malignancy, and disseminated tuberculosis as differentials. Investigations confirmed the diagnosis of SLE. Management: The patient was treated with pulse doses of intravenous methylprednisolone for SLE and daily oral cyclosporine and supportive transfusions for aplastic anemia. She showed improvement in the constitutional symptoms and hematological parameters within 6 weeks. The arthritis resolved within 6 months of therapy, after which she was continued on low-dose steroids, hydroxychloroquine, and methotrexate. Conclusion: In cases of aplastic anemia with atypical features of CTDs such as arthritis, uveitis, oral ulcers, rash, and photosensitivity should be worked up for underlying autoimmune disorders.

Keywords: Aplastic anemia, cyclosporine, methylprednisolone, systemic lupus erythematosus

How to cite this article:
Maheshwari A, Nadri G, Meena R, Mahto D. Aplastic Anemia Complicating Systemic Lupus Erythematosus. Indian Pediatr Case Rep 2021;1:176-8

How to cite this URL:
Maheshwari A, Nadri G, Meena R, Mahto D. Aplastic Anemia Complicating Systemic Lupus Erythematosus. Indian Pediatr Case Rep [serial online] 2021 [cited 2021 Sep 26];1:176-8. Available from: http://www.ipcares.org/text.asp?2021/1/3/176/325082

Systemic lupus erythematosus (SLE) is a chronic, potentially fatal, autoimmune, inflammatory disease of unknown etiology that leads to tissue and cell damage by pathogenic autoantibodies and immune complexes. It is characterized by multiorgan involvement, an unpredictable course, and very high mortality in the pediatric age group. Hematological manifestations such as anemia, leukopenia, lymphopenia, thrombocytopenia, and antiphospholipid syndrome are commonly reported in SLE and are included in the diagnostic criteria for the disease. Anemia is seen in up to 50%–70% of patients of SLE.[1] Anemia of chronic disease is the most common cause. Other factors include inflammation, renal disease, blood loss, hemolysis, medications, dietary insufficiency, infection, hypersplenism, myelofibrosis, and myelodysplasia.

Aplastic anemia is a very unusual manifestation of SLE[1] that occurs due to an impaired erythropoietin response and formation of antibodies against erythropoietin.[2],[3] We report a girl with SLE and aplastic anemia. A literature search found 15 cases of previously published case reports of aplastic anemia with SLE. All of these were seen in adults, except for a single patient with neonatal lupus.

  Clinical Description Top

A 6-year-old girl presented with recurrent episodes of fever and painful swelling of multiple joints for 6 months. The joints involved were bilateral knees, ankles, elbows, and the small joints of both hands. These were accompanied with morning stiffness and severely decreased range of motion. The episodes of fever were high grade, occurred twice a month, had variable duration of 7–10 days, and were not associated with night sweats. There was no history of associated rash, eye redness, photosensitivity, or oral ulcers. There was a history of gradual onset of progressive pallor for a month that was accompanied by multiple petechial rashes. There was no history of bleeding from any site, recurrent episodes of sore throat, or appearance of nodular swellings. There was no history of decreased urine output or reddish discoloration of urine, jaundice, breathlessness, or palpitations. The child had decreased appetite and listlessness. The child was hospitalized 1 month after the onset of illness. On reviewing the documents, it was discovered that she had evidence of pleural and pericardial effusion, as well as ascites. There was no history of contact with tuberculosis.

On examination, she was undernourished. She was febrile and hemodynamically stable. The weight, height, and body mass index was 13.4 kg, 108 cm, and −2.49 Z score (thinness), respectively. General physical examination revealed pallor and generalized petechiae. Throat examination was normal. There was no icterus or lymphadenopathy. Bilateral knee, ankle, and elbow joints were swollen and tender with decreased range of movements. There were no deformities or contractures. Per-abdomen examination did not reveal any hepatosplenomegaly. Respiratory, cardiovascular, and central nervous system (CNS) examination was normal.

The clinical phenotype encompassed a childhood-onset multisystemic (musculoskeletal and hematological) chronic illness with constitutional symptoms. The differentials that were considered included a connective tissue disorder (CTD) (SLE, mixed CTD, or overlap syndromes) and systemic-onset juvenile idiopathic arthritis with macrophage activation syndrome [MAS] due to the presence of pallor and petechiae, a hematological malignancy, and disseminated tuberculosis.

Salient hematological findings were pancytopenia based on counts (hemoglobin 4.6 g/dL, total leukocyte count 900/μL, platelet count 3000/μL, and reticulocyte count 0.5%) and peripheral smear which did not reveal any atypical cells. Since this was suggestive of hypoproliferative marrow, a bone marrow aspiration (BMA) was performed. The report showed suppressed erythroid series with a predominant normoblastic reaction, with maturation arrest of myeloid series and absent megakaryocytes. Since bone marrow cellularity cannot be commented upon in a BMA, a bone marrow biopsy was done that revealed decreased cellularity of 30%. Since there were features of MAS, work-up for hemophagocytic lymphohistiocytosis (HLH) was planned (serum ferritin, fibrinogen, and triglycerides) although it was lower down in the list of differentials. The levels of these biomarkers were normal.

Results of the inflammatory parameters included an elevated erythrocyte sedimentation rate of 55 mm/1st h and raised C-reactive protein. The reports of investigation sent for the evaluation of CTDs were as follows: positive antinuclear antibody (ANA) by immunofluorescence, high titers (197.94 IU/ml) of anti-double-stranded DNA (dsDNA) and negative for phospholipid antibody (IgG, IgM), anticardiolipin antibody (IgG, IgM), lupus anticoagulant, and direct Coombs test. Slit lamp examination excluded uveitis. In view of the clinical phenotype (including the past history of polyserositis) and laboratory findings, a diagnosis of childhood SLE was made. Relevant clinical and laboratory evaluation for multisystemic involvement excluded renal, hepatic, and CNS involvement. The final diagnosis was childhood SLE with aplastic anemia.

The patient was treated with pulse doses of intravenous methylprednisolone for SLE. Daily oral cyclosporine was added to this standard protocol for the associated aplastic anemia, in addition to supportive treatment with multiple packed red blood cell and platelet concentrate transfusions. Within 6 weeks of therapy, she showed improvement in constitutional symptoms and hematological parameters. Her arthritis showed symptomatic resolution within 6 months of therapy, and she was continued on low-dose steroids, hydroxychloroquine, and methotrexate (which were started after resolution of pancytopenia). The child has been under follow-up for the last 10 years and has not shown any evidence of disease progression.

  Discussion Top

The etiology, pathogenesis, clinical manifestations, and laboratory findings of SLE in children are similar to that seen in adults. A diagnosis of SLE in childhood is based upon the American College of Rheumatology (ACR) criteria which requires the satisfaction of four out of 11 criteria for establishing diagnosis. In children, these criteria display sensitivity and specificity of 96% and 100%, respectively. Although these criteria are excellent guides, clinicians should use their clinical judgment in children if all these are not fulfilled, as many features evolve over time, and may not be found initially. The diagnosis of SLE was made in our patient in view of presence of arthritis, polyserositis, positive ANA, and anti-dsDNA, and hematological criteria (leukopenia and thrombocytopenia).

Pancytopenia is a rare hematological manifestation of SLE, the underlying mechanism of which is still unclear. Cytotoxic T cells are primarily responsible for immune-mediated destruction of bone marrow precursor cells.[4],[5],[6] Autoantibodies in SLE act against the pluripotent stem cells and lead to bone marrow suppression.[7] In addition, impaired apoptosis and defective clearance of these cells can also contribute to pancytopenia, similar to children with HLH. These apoptotic cells are likely to be a source of autoantigens in SLE as they express many of the nuclear autoantigens that are found in SLE. Impaired clearance of these particles can lead to dysregulated immune activation, causing disease activity. A high proportion of bone marrows obtained from patients with SLE contain apoptotic debris.[8] Overall hypocellularity, morphological dysplasia, increased fibrosis, and bone marrow necrosis were common findings in patients with SLE with pancytopenia, suggesting a primary bone marrow involvement in the tissue pathogeny of the disease, probably mediated by autoantibodies, immune complexes, and activated cytotoxic T cells.[9]

This case was unique in many aspects. This child was diagnosed as SLE despite the absence of classical features, such as malar rash, oral ulcers, photosensitivity, or renal disease. She did not have all features at presentation, and polyserositis was identified only after careful review of past history and documents. We did not administer antithymocyte globulin, which is usually used in severe aplastic anemia, as the etiology of the pancytopenia was autoimmune in nature. In cases of aplastic anemia with atypical features of CTDs such as arthritis, uveitis, oral ulcers, rash, and photosensitivity should be worked up for underlying autoimmune disorders.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Walport MJ, Hubbard WN, Hughes GR. Reversal of aplastic anaemia secondary to systemic lupus erythematosus by high-dose intravenous cyclophosphamide. Br Med J (Clin Res Ed) 1982;285:769-70.  Back to cited text no. 1
Stricker RB, Shuman MA. Aplastic anemia complicating systemic lupus erythematosus: Response to androgens in two patients. Am J Hematol 1984;17:193-201.  Back to cited text no. 2
Brooks BJ Jr., Broxmeyer HE, Bryan CF, et al. Serum inhibitor in systemic lupus erythematosus associated with aplastic anemia. Arch Intern Med 1984;144:1474-7.  Back to cited text no. 3
Wolach B, Choc L, Pomeranz A, et al. Aplastic anemia in neonatal lupus erythematosus. Am J Dis Child 1993;147:941-4.  Back to cited text no. 4
Marqués JA, Rhim H, Distenfeld A. Inhibition of hematopoiesis by a plasma factor in a case of aplastic anemia associated with systemic lupus erythematosus. P R Health Sci J 1995;14:293-6.  Back to cited text no. 5
Chute JP, Hoffmeister K, Cotelingam J, et al. Aplastic anemia as the sole presentation of systemic lupus erythematosus. Am J Hematol 1996;51:237-9.  Back to cited text no. 6
Morishita Y, Matsukawa Y, Kura Y, et al. Antithymocyte globulin for a patient with systemic lupus erythematosus complicated by severe pancytopenia. J Int Med Res 1997;25:219-23.  Back to cited text no. 7
Pavithran K, Raji NL, Thomas M. Aplastic anemia complicating systemic lupus erythematosus--Report of a case and review of the literature. Rheumatol Int 2002;22:253-5.  Back to cited text no. 8
Singh NP, Prakash A, Garg D, et al. Aplastic anemia complicating systemic lupus erythematosus: Successful management with cyclosporine. Rheumatol Int 2004;24:40-2.  Back to cited text no. 9


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