Pediatric sarcoidosis presenting as huge splenomegaly

Childhood sarcoidosis is a rare chronic multisystem granulomatous disease with variable presentations. It has two distinct forms: the juvenile form and the early onset form. Early onset sarcoidosis is caused by nucleotide-binding oligomerization domain 2 (NOD2) mutation and is closely associated with dysfunction of the innate immunity. Symptomatic sarcoidosis is rare in children. The disease is more severe and extensive in African children. Splenic involvement in sarcoidosis is rare, with some sporadic cases reported in the literature. We herein present a rare case of splenic sarcoidosis in a 9-year-old Egyptian girl who had no pulmonary involvement. The patient presented with a 6 month history of abdominal pain and anorexia. Her past medical and family histories were irrelevant. On physical examination the patient had pallor and huge splenomegaly with no skin rash or lymphadenopathy. The pulmonary, cardiovascular, neurological, and other systems were normal. Initial laboratory tests indicated bicytopenia with hemoglobin 8.9 g/dL and platelet count 108 9 10 cells/lL. Total leukocyte count was 5.3 9 10 cells/lL. Reticulocyte count was 3%. Coagulation profile, serum electrolytes, liver and kidney function were all normal. A hemolytic cause was suggested, but hemoglobin electrophoresis, osmotic fragility, Coombs’ test and serum lactate dehydrogenase were all normal, excluding a hemolytic cause. The possibility of collagen vascular disorders was suggested. Erythrocyte sedimentation rate and C-reactive protein were mildly increased (32 mm/h and 12.4 mg/dL, respectively), but anti-nuclear-antibodies and rheumatoid factor were negative, ruling out this diagnosis. On bone marrow aspirate and biopsy to rule out serious malignant and chronic storage cause, bone marrow was hypercellular with normal morphology and maturation, and no abnormal cells. Abdominal ultrasonography and computed tomography (CT) showed a markedly enlarged spleen (19.5 cm in long dimension) with normal echopattern and no focal masses. Over a period of 1 month, pancytopenia developed with multiple transfusions. Although a cause was not identified, splenectomy was done due to evidence of hypersplenism. Histopathology of the splenic tissue indicated the unexpected diagnosis of sarcoidosis, with involvement of the spleen and the surrounding lymph nodes (Fig. 1a). Chest X-ray and CT of the lungs, along with pulmonary function, were all normal. Neck CT was also normal. Urinary calcium and serum calcium, vitamin D, and immunoglobulin levels were normal. Tuberculin test was negative. Angiotensinconverting enzyme and soluble interleukin-2 receptor were 800 and 90 U/L, respectively, which were slightly higher than normal. Due to financial issues, NOD2 mutation analysis and neutrophil sterilizing function investigation were not done. We consider this a limitation of this study. Although a definitive diagnostic test of sarcoidosis is generally lacking, diagnosis can be made on fulfillment of the following three criteria: (i) compatible clinical and radiological manifestations; (ii) exclusion of other diseases that may present similarly; and (iii) histopathologic detection of noncaseating granuloma. These three criteria were fulfilled in the present case, and the patient was diagnosed with juvenile sarcoidosis. On follow up, the patient’s general and blood elements had returned to normal. After 2 years of follow up, however, the patient developed significant enlargement of the cervical, axillary and supraclavicular lymph nodes. Again laboratory work up was done, together with neck, chest, and abdominal CT that showed enlargement of the cervical, axillary, supraclavicular, gastrohepatic, porta-hepatis, pericaval, and mesenteric groups of lymph nodes with no pulmonary involvement. Lymph node biopsy indicated sarcoidosis (Fig. 1b,c). Treatment was started with prednisone 2 mg/kg for 4 weeks, followed by marked improvement, after which the drug was gradually withdrawn over a period of 3 months. At the time of writing the patient had been in clinical remission for 11⁄2 years with no complications. The current case is unique in that the presentation of sarcoidosis did not involve the lungs (in contrast to 90% of cases). Splenic involvement is rare; huge splenomegaly even more so, and its occurrence as the initial presentation is extremely rare. Splenic sarcoidosis in the absence of clinical or radiographic pulmonary disease is also extremely rare, with only a few reports on mostly asymptomatic patients. These all occurred, however, in the present case. Correspondence: Laila M Sherief, MD, Department of Pediatrics and Pediatric Hematology and Oncology, Faculty of Medicine, Zagazig University, Zagazig, Egypt. Email: lamesh25@yahoo.com Received 22 June 2016; revised 6 November 2016; accepted 28 November 2016. doi: 10.1111/ped.13219 366 LM Sherief et al.