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 Table of Contents  
Year : 2018  |  Volume : 9  |  Issue : 3  |  Page : 101-103

Systemic-onset juvenile idiopathic arthritis in a child with thalassemia major

1 Department of Peadiatrics, Bangalore Baptist Hospital, Bengaluru, Karnataka, India
2 Department of Medicine and Rheumatology, Bangalore Baptist Hospital, Bengaluru, Karnataka, India

Date of Web Publication31-Oct-2018

Correspondence Address:
Dr. Pitta Mary Dayana
Department of Paediatrics, Bangalore Baptist Hospital, Bengaluru, Karnataka
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/joah.joah_8_18

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Patients with thalassemia are known to have an increased risk of immune-mediated illness. This increased risk may be due to a genetic predisposition or underlying immunological abnormalities. The clinical presentation of these immune-mediated illnesses may vary in these patients as compared to those without thalassemia. We report an 8-year-old boy with thalassemia major who presented to us with fever, arthritis, and hepatosplenomegaly. He was diagnosed to have systemic-onset juvenile idiopathic arthritis (SOJIA) and started on treatment. Although there have been reports of rheumatoid arthritis in patients with thalassemia, there are none on SOJIA in thalassemia. The possibility of systemic-onset juvenile arthritis should be considered in a child with thalassemia presenting with fever and arthritis, and the management should be instituted accordingly.

Keywords: Arthritis, rheumatoid arthritis, systemic-onset juvenile idiopathic arthritis, thalassemia

How to cite this article:
Dayana PM, Peterson RR, Maganthi M, Vahaneyil JM. Systemic-onset juvenile idiopathic arthritis in a child with thalassemia major. J Appl Hematol 2018;9:101-3

How to cite this URL:
Dayana PM, Peterson RR, Maganthi M, Vahaneyil JM. Systemic-onset juvenile idiopathic arthritis in a child with thalassemia major. J Appl Hematol [serial online] 2018 [cited 2023 Mar 24];9:101-3. Available from: https://www.jahjournal.org/text.asp?2018/9/3/101/244540

  Introduction Top

Beta-thalassemia is the most common single-gene disorder seen in the Indian population.[1] Immunological abnormalities such as the presence of autoantibodies and increased risk of autoimmune diseases are being increasingly reported in these patients.[2],[3] Rheumatoid arthritis is a common autoimmune disease that has been described in children with beta-thalassemia. The following is a report of a child with thalassemia major and systemic-onset juvenile idiopathic arthritis (SOJIA). SOJIA can be considered as a differential diagnosis in children with thalassemia major presenting with fever and arthritis.

  Case Report Top

An 8-year-old boy presented with complaints of fever, pain, and swelling of both knees and left ankle for 2 weeks. He also had painful movements of the neck. At 3 months of age, he was diagnosed to have thalassemia major and had been on transfusion and chelation therapy with deferasirox along with regular monitoring of serum ferritin levels since then. He had no history of swelling or pain in the joints. He was the first child born to third-degree consanguineous parents. He had a 6-year-old brother who was also diagnosed to have thalassemia major.

On examination, he was alert and febrile with a temperature of 102°F. He was noted to have pallor, but had no significant lymphadenopathy. Growth and development were appropriate for age. There were pain, tenderness, redness, swelling, local rise of temperature, and synovial thickening of both knees and left ankle. The range of movement was restricted in these joints as well as in the cervical spine. On abdominal examination, the liver was palpable 4 cm below the right costal margin, and the spleen was palpable 1 cm below the left costal margin. Examination of other systems was unremarkable.

Blood investigations revealed Hb – 8.8 gm/dl, white blood cell – 16,400/cu.mm, neutrophils – 68%, lymphocytes – 24%, eosinophils – 7%, platelet counts 540,000/cu.mm, erythrocyte sedimentation rate (ESR) – 140 mm/h, C-reactive protein – 152.3 mg/dl, and serum ferritin – 4030 ng/ml. Previous values of ferritin which were being regularly monitored had been normal. Serum iron-binding capacity and total iron-binding capacity were normal. Complements C3 and C4 were normal. Rheumatoid factor, antinuclear antibody, anti-cyclic citrullinated peptide antibody were negative. HIV antibody, hepatitis B surface antigen, and HCV antibody were negative. Bone marrow aspiration and biopsy showed active marrow with trilineage erythropoiesis. Two-dimensional echocardiogram was normal. Ophthalmic evaluation showed no evidence of uveitis. X-ray of the right knee joint showed widened intercondylar notch and prominent joint space, suggestive of joint effusion. X-ray of the cervical spine was normal. He was diagnosed to have SOJIA as he fulfilled the ILAR criteria for diagnosis, namely quotidian fever lasting for 2 weeks, arthritis involving four joints, and hepatosplenomegaly along with other laboratory evidence as mentioned earlier. DNA mutation analysis done using polymerase chain reaction and DNA sequencing revealed a homozygous mutation IVS 1 + 5 G > C in intron 1 of the HBB gene, indicative of beta-thalassemia major. This is a reported mutation and the Human Gene Mutation Database reference number is CS830004. Both parents had a heterozygous mutation IVS 1 + 5 G > C in intron 1 of the HBB gene, indicative of beta-thalassemia carrier state.

He was initially started on naproxen and after which fever subsided. Subsequently, prednisolone and methotrexate were added. After 4 months, in view of persistent arthritis of the knees, he was given intra-articular triamcinolone to both the knee joints. At follow-up, he was doing well and has resumed normal activity.

  Discussion Top

Rheumatoid arthritis has been reported with higher frequency in patients with hemoglobinopathies such as thalassemia as compared to the general population.[4] The clinical presentation of rheumatoid arthritis in this group of patients may show some variation as compared to the general population. In patients with thalassemia minor, rheumatoid arthritis has been described to be of lesser severity than the general population, and extra-articular manifestations were found to be less common. No significant differences were found with reference to clinical indices of disease activity, disease parameters, and joint erosions.[5] It has also been reported that in beta-thalassemia carriers, there has been a notable reduction in a number of systemic complications such as the presence of rheumatoid nodules along with severe osteoporosis and lower ESR value. Due to this variability in clinical presentation, it is suggested that beta-thalassemia may modify the immunological profile of circulating T cells in patients with rheumatoid arthritis through a different background immune reactivity.[5] Pliakou et al. reported four adult patients of thalassemia major who were diagnosed to have rheumatoid arthritis according to the American College of Rheumatology criteria in whom the arthritis was mild and extra-articular manifestations were rare; rheumatoid factor and ANA were positive in all these patients.[4] A case of thalassemia intermedia with rheumatoid arthritis has been described with highly increased rheumatoid factor and absence of particular radiologic findings.[6] There are no reports in the literature of SOJIA in patients with thalassemia major.

Although no definite evidence is available, the greater prevalence of rheumatoid arthritis in thalassemia could be due to genetic susceptibility or immunological abnormalities along with the presence of environmental triggers. It is a well-known fact that immune-regulating genes may be involved in the pathogenesis of autoimmune diseases including rheumatoid arthritis. Altinoz et al. proposed that the proximity of beta-globin gene locus to several important genes involved in regulating immune system may cause the haplotype association at 11p 15.5 of these immune-regulating genes with beta-globin chain gene.[2] In most of the studies, the genetic mutation of patients with thalassemia presenting with rheumatoid arthritis has not been studied. Our patient had a homozygous mutation IVS 1 + 5 G > C in intron 1 of the HBB gene, which is a common mutation in patients with thalassemia in India. It is not known whether any particular mutation predisposes these patients to develop rheumatoid arthritis.

Patients with hemoglobinopathies are known to have fewer T cells, decreased C4 levels, changes in CD8+/CD4+ lymphocyte ratio, increased levels of immunoglobulins and circulating immune complexes, and increased levels of autoantibodies which predispose them to increased expression of autoimmune diseases.[6] Persistent immunologic stimulation by frequent blood transfusions, iron overload, and iron chelators are believed to be responsible for these effects.[6] Apart from rheumatoid arthritis, other autoimmune diseases have also been described in patients with thalassemia trait.[2] While rheumatoid arthritis presents a milder form in patients with beta-thalassemia,[5] other autoimmune diseases such as systemic lupus erythematosus could present with more severe systemic symptoms.[2] In a large study done in Italy in the same geographical area, it was suggested that environmental triggers may not play a major role.[3]

Patients with beta-thalassemia are also known to suffer from other forms of arthritis which include thalassemic osteoarthropathy, arthritis due to iron overload, and use of iron chelators such as deferiprone. These causes were excluded in our child.

To the best of our knowledge, this is the first report of SOJIA in a child with thalassemia. Juvenile idiopathic arthritis is the most common rheumatic disease in children and represents a heterogeneous group of disorders, of which SOJIA is one.[7] It will be interesting to study the variations in clinical manifestations, disease severity, and disease progression of SOJIA in children with thalassemia major as compared to the general population. This article highlights the observation that SOJIA must be suspected in patients with thalassemia presenting with fever, arthritis, and hepatosplenomegaly.

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

Grow K, Vashist M, Abrol P, Sharma S, Yadav R. Beta thalassemia in India: Current status and the challenges ahead. Int J Pharm Pharm Sci 2014;6:28-33.  Back to cited text no. 1
Altinoz MA, Gedikoglu G, Deniz G. B-thalassemia trait association with autoimmune diseases: B-globin locus proximity to the immunity genes or role of hemorphins? Immunopharmacol Immunotoxicol 2012;34:181-90.  Back to cited text no. 2
Montecucco C, Caporali R, Rossi S, Epis O. Rheumatoid arthritis in beta-thalassaemia trait. Rheumatology (Oxford) 1999;38:1021-2.  Back to cited text no. 3
Pliakou XI, Koutsouka FP, Damigos D, Bourantas KL, Briasoulis EC, Voulgari PV, et al. Rheumatoid arthritis in patients with hemoglobinopathies. Rheumatol Int 2012;32:2889-92.  Back to cited text no. 4
Castellino G, Govoni M, Trotta F. Rheumatoid arthritis in beta-thalassaemia trait. Rheumatology (Oxford) 2000;39:1286-7.  Back to cited text no. 5
Giakoumi X, Tsironi M, Floudas C, Polymeropoylos E, Papalambros E, Aessopos A, et al. Rheumatoid arthritis in thalassemia intermedia: Coincidence or association? Isr Med Assoc J 2005;7:667-9.  Back to cited text no. 6
Kliegman R, Stanton B, St. Geme JW, Schor NF, Behrman RE. Nelson Textbook of Pediatrics. 20th ed. Phialdelphia, PA: Elsevier; 2016.  Back to cited text no. 7


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