1 Department of Nephrology 2 Department of Pathology Queen Elizabeth Medical Centre Birmingham UK
Sir,
Henoch-Schönlein nephritis (HSN) is occasionally associated with malignant disease. We report a case of vasculitic IgA nephropathy, cutaneous leukocytoclastic vasculitis, and non-Hodgkin's lymphoma (NHL). This is the first histologically proven report of this association.
Case.
A 66-year-old man presented with 2 weeks of diarrhoea and one episode of fresh blood per rectum. He also reported night sweats, malaise and anorexia, and one episode of frank haematuria. Clinical examination was normal. Investigations revealed abnormal renal function (urea of 16.1 mmol/l, creatinine of 214 µmol/l). Urine dipstick showed 3+ blood and 2+ protein and urine microscopy also demonstrated leukocyturia. The ESR was 79 mm/h, ANA was weakly positive at a titre of 1:40, ANCA was negative and complement and immunoglobulin levels were normal. A chest X-ray was normal. Shortly after he sustained a haematemesis. An upper GI endoscopy showed a small clot at the gastro-oesophageal junction. An abdominal ultrasound scan was normal. A renal biopsy was performed which showed heavy mesangial IgA deposition and evidence of a vasculitic glomerulonephritis (HSN).
Three weeks later he re-presented with fever and night sweats, an unproductive cough, anorexia and a rash. He had a swinging pyrexia, enlarged supraclavicular and posterior auricular lymph nodes, and palpable papules on the arms and trunk. The chest X-ray now showed bilateral hilar lymphadenopathy (Figure 1). A skin biopsy showed a leukocytoclastic vasculitis consistent with Henoch-Schönlein Purpura (HSP). A repeat upper GI endoscopy for further haematemesis showed abnormal and bleeding mucosa at 40 cm suspicious of malignant infiltration. This site was biopsied and injected with adrenaline. Subsequently the patient became hypoxic secondary to pulmonary aspiration and was transferred to ITU for ventilatory support. A CT scan of the chest showed left hilar and subcarinal lymphadenopathy and narrowing of the left main bronchus. Bronchoscopy showed irregular mucosa in the left main bronchus. The patient continued to deteriorate and died 3 days later. Post-mortem examination revealed a high grade, null cell, CD30+, NHL infiltrating through all layers of the jejunum. There were also deposits in the lower oesophagus, lungs, lymph nodes, and right kidney. The temporal relationship between the presentation with HSP and HSN and the post-mortem diagnosis of NHL suggests an association between these two diseases.
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There are two previous reports associating HSP and lymphoma. Vesole reported a large cell lymphoma expressing IgM in a patient with a 30 year history of relapsing HSP [1]. The patient had received Dapsone for 9 years of this illness and this use might have predisposed to the development of lymphoma. Ng and colleagues reported a 39-year-old man with a concurrence of Hodgkin's lymphoma and HSP [2]. In lymphoma and IgA disease without vasculitis there are three case reports of an association between mycosis fungoides and IgA GN [3,4] and several other reports of an association between other carcinomas and HSN.
Although the pathogenetic basis of this association is speculative there are several possible explanations. Firstly, the frequent association of HSP with mucosal infections and inflammatory diseases implicates mucosal-produced IgA2 in immune complexes deposited at distant sites. Secondly, tumour antigens may lead to systemic T-cell driven B-cell production of IgAl; this would be consistent with the presence of IgAl within the glomerulus in IgA GN [5]. Thirdly, abnormalities in the cellular immune system may skew T-cell subpopulations towards those promoting isotype switching from IgM to IgA. The trigger for vasculitis that develops subsequent to IgA deposition is unclear, although several mechanisms may apply including Fc receptor mediated cell cytotoxicity, complement activation, and T-cell mediated immune processes. Although the association reported here is unusual, it further illustrates the potential for renal involvement in disorders that affect systemic immunity.
References