A 24-year-old woman of Malay ethnicity presented to the thalassemia unit with a month history of prolonged fever, headache, and painful enlarged neck lymph nodes. She is known to have Hb H CS thalassemia, in which, she is on 3-monthly blood transfusion. She is on iron chelation subcutaneous deferoxamine 500 mg thrice weekly. She has a family history of Hb H disease. There is no history of parental consanguinity. She is a nonsmoker, a teetotaler, and works as a bank clerk.
Physical examination revealed a pale and jaundiced female with persistent pyrexia of 38 C. She was not septic looking and did not reveal any skin rash. She had bilateral palpable tender cervical lymphadenopathies with the largest measuring 4 x 4 cm. They were rubbery on palpation with no obvious nodal discharge or overlying skin colour changes. She had hepatosplenomegaly. Other systems were unremarkable.
The complete blood count revealed hypochromic microcytic anaemia, leucopenia, and a normal platelet count. She had hyperferritinemia of 3500 ng/mL. The other laboratory parameters are as tabulated in Table 1. Peripheral blood film (Figure 1) portrayed features consistent with hemoglobinopathy associated with chronic hemolysis. Capillary electrophoresis (Figure 2) showed Hb A of 69.1%, Hb A2 of 0.4%, Hb F of 0%, Hb H of 26.6%, Hb Barts of 1.5% and Hb CS of 2.4%. The agarose alkaline and acid gel electrophoresis (Figure 3A and B) revealed a faster-move band (Hb H band). The DNA analysis of alpha-globin gene showed heterozygosity for alpha zero thalassemia South East Asian (SEA) deletion with termination codon mutation (TAA-CAA) which was consistent with Hb H-Constant Spring thalassemia. The DNA analysis for Beta globin gene did not reveal any mutations.
Blood, fungal, and tuberculosis cultures were sterile. A complete autoimmune panel was negative. An abdominal ultrasonogram and transthoracic echocardiogram did not reveal any microabscesses or vegetations. Magnetic resonance imaging (MRI) T2* of the cardiac and liver showed moderate liver iron overload and normal myocardial iron load. A whole body computed tomography (CT) imaging showed diffuse cervical, axillary, and abdominal lymphadenopathies with the largest lymph node measuring 4 x 4 cm.
A decision was made to perform a cervical lymph node biopsy. It showed paracortical expansion by histiocytes, small lymphocytes, and tingible body macrophages. The histiocytes had pale and crescentic nuclei. Extensive apoptosis with large areas of necrosis were present. There were no neutrophils, granulomas, or multinucleated giant cells seen. Immunohistochemical studies showed histiocytes positive for CD68 and myeloperoxidase (MPO). Most small lymphocytes were CD8+ T-lymphocytes. Periodic acid Schiff (PAS), Grocott's methenamine silver (GMS), and Ziehl-Nielsen stains were negative for fungal bodies and acid-fast bacilli.
On the basis of these findings, a diagnosis of KFD was made. She was treated with oral prednisolone 1 mg/kg daily for a month followed by a gradual taper of 10 mg 2 weekly based on response. She responded clinically with complete resolution of symptoms. A repeat end-of-treatment whole body CT imaging showed complete resolution of lymphadenopathies. Currently, she is on a 3-monthly follow up at the thalassemia clinic.