Rheumatology Advance Access originally published online on July 22, 2008
Rheumatology 2008 47(9):1435-1436; doi:10.1093/rheumatology/ken285
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Castleman's disease in childhood: a surgically curable mimic of autoimmune disease
1Department of Paediatric Rheumatology, Institute of Child Health, London, 2Department of Paediatric Rheumatology, Royal Hospital for Sick Children, Glasgow, 3Department of Histopathology, Great Ormond Street Hospital, London, 4Royal Aberdeen Children's Hospital, Aberdeen, 5Department of Radiology, Great Ormond Street Hospital and 6Infectious Diseases and Microbiology Unit, Institute of Child Health, London, UK
Correspondence to: D. Eleftheriou, Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK. E-mail: d.eleftheriou{at}ich.ucl.ac.uk
SIR, Castleman's disease (CD) is a rare, non-malignant, lymphoproliferative disorder of uncertain aetiology that is an important, surgically curable mimic of autoimmune disease. CD is classified clinically into two subtypes: unicentric and multicentric CD [1]. Pathologically, two major histological types are recognized: hyaline-vascular CD and plasma cell type. A mixed form, hyaline-vascular plasma cell CD is uncommon [2]. We present a case of unicentric plasma cell CD in a child presenting with a lupus-like phenotype where the lesion and extent of the disease was identified prior to surgery by 18-fluorine 2-fluoro-2-deoxy-D-glucose PET/CT (18F-FDG PET/CT).
A 3.5-yr-old boy presented with a 4-month history of pyrexia of unknown origin (PUO), abdominal pain, weight loss and lethargy. Examination revealed a cachectic child with 4 cm hepatomegaly. Investigations revealed a hypochromic microcytic anaemia and thrombocytosis. ESR and CRP were elevated at >150 mm/h and 144 mg/l, respectively. Extensive investigations for infective causes of the presenting clinical features were negative. Autoantibody screening was initially negative.
Abdominal USS and CT revealed two enlarged lymph nodes close to the pancreas. Biopsies of these at laparotomy revealed reactive hyperplasia only. Liver and gastric biopsies were unremarkable, and bone marrow examination demonstrated reactive inflammatory changes. Upper gastro-intestinal endoscopy revealed minor, non-specific inflammatory changes. A therapeutic trial of corticosteroids resulted in transient improvement of symptoms but no sustained disease control.
Nine months after the first presentation he developed multiple autoantibodies: anti-cardiolipin IgG elevated to 55.5 GPL U/ml (reference range <17 GPL U/ml), lupus anti-coagulant-positive, ANA 1/160 (speckled), positive Coomb's test and low C3 and low C4. Plasma cytokines revealed elevated IL-6 of 46.6 pg/ml (reference range 0.43–8.9 pg/ml), elevated IL-10 of 17.1 pg/ml (reference range 0–3.8 pg/ml), normal TNF-
of 12.4 pg/ml (reference range 0–15.6 pg/ml), elevated IL-1 receptor antagonist (IL1ra) of 3734 pg/ml (range 48–1168 pg/ml) and elevated TNF- receptor 1 (TNF-R1) of 1435 (reference range 484–1345 pg/ml).
Severe ongoing systemic inflammatory symptoms, with lupus-like features led to empiric sequential trial of treatment with monthly IV cyclophosphamide, rituximab (chimeric anti-CD20 monoclonal antibody) and AZA, but with no improvement. New development of microscopic haematuria and albuminuria of 154 mg/mmol creatinine led to renal biopsy that showed florid membranous nephropathy, deposition of mesangial IgM, IgG and C1q consistent with (but not pathognomonic of) a lupus Class V glomerulonephritis.
In view of ongoing symptomatology, whole body 18F-FDG PET/CT scanning was undertaken. This revealed a single 29-mm FDG avid soft-tissue mass in the left retroperitoneum, anterior to the left kidney and inferior to the tail of the pancreas, which coincided with a lymph node identified on abdominal ultrasound and CT scan (Fig. 1A). A second laparotomy with resection of the lesion was undertaken. Histology confirmed the diagnosis of plasma cell CD (Fig. 1B). Prompt recovery of symptoms and resolution of the acute-phase response followed. All pharmacological treatments were withdrawn and the patient remains well 9 months following surgery.
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CD is a rare and heterogeneous group of disorders that can mimic systemic CTDs [3]. In childhood, it is usually of the localized type [4]. Patients are frequently asymptomatic but can occasionally present with systemic symptoms [5]. Treatment of unicentric disease of either histological type involves resection, resulting in cure. One caveat to this may be malignant transformation of unicentric CD [6].
Multicentric CD is usually of the plasma cell type and commonly presents with lymphadenopathy, systemic symptoms, organomegaly and acute-phase response [1]. The prognosis of this variant in adults is poor. Moreover, some cases are associated with Kaposi sarcoma and lymphoma [5, 7]. Such malignancies are less commonly associated with CD of the young. Therapy of this form of CD includes immune modulators such as corticosteroids, IFN- and cytotoxic immunosuppression with or without radiotherapy [8]. Monoclonal antibody therapy including anti-CD20 or anti-Il-6 has been used with anecdotal efficacy [1].
A number of recent observations have cast light on the pathogenesis of CD. The levels of IL-6 and other pro-inflammatory cytokines are raised [1]. There also appears to be an association of multicentric CD and HHV-8 infection [1].
This is one of the few cases of paediatric CD with renal involvement described. Previous reports in adult patients describe various forms of glomerular and interstitial pathology and a few cases of nephrotic syndrome caused by renal amyloidosis [9].
In adult patients, there is an emerging experience of 18F-FDG PET for the diagnosis and subsequent follow-up of CD [10], but no such data in children. In our patient, initial abdominal lymph node biopsy identified only reactive inflammatory changes. Using 18F-FDG PET/CT we were able to precisely identify the most metabolically active node with confidence, thus guiding the successful surgical management of this case.
We conclude with the message that CD should be considered in children presenting with a lupus-like phenotype recalcitrant to cytotoxic immunosuppression.
Disclosure statement: The authors have declared no conflicts of interest.
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