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Editor,—We report a case of bilateral granulomatous uveitis, which prompted extensive diagnostic review in a 20 year old woman with a long history of recurrent infection and idiopathic thrombocytopenia. Investigations allowed the definitive diagnosis of common variable immunodeficiency with granulomas (granulomatous antibody deficiency syndrome.) To our knowledge this is the first reported case of granulomatous uveitis in association with granulomatous antibody deficiency (GAD). We discuss the features of GAD, and how it may be distinguished from sarcoidosis.
A 20 year old woman presented with sudden onset blurred vision. Examination revealed a bilateral granulomatous uveitis with mutton-fat keratic precipitates and anterior chamber cells. Two weeks later she developed bilateral optic disc swelling with multifocal areas of choroidal pallor in her left eye (Fig 1). There was no vitritis or evidence of retinal vascular changes. Her uveitis settled on topical steroids and she maintained vision of 6/6 in the right eye and 6/9 in the left. The working diagnosis was sarcoidosis.
However, serum angiotensin converting enzyme (ACE) was not elevated and magnetic resonance imaging (MRI) showed no evidence of neurosarcoid. Plain chest films and high resolution computed tomography of the thorax revealed bilateral hilar and paratracheal lymphadenopathy, with air space shadowing and ill defined nodular opacities in both lower zones. Bronchial biopsies, obtained at fibreoptic bronchoscopy, showed inflammation of the bronchial epithelium consistent with bronchial pneumonia. No granulomata were seen.
As a child she had suffered from recurrent chest infections, with severe neutropenia and thrombocytopenia. By 6 years of age she had developed splenomegaly and widespread lymph node enlargement. Kveim and Mantoux test were both negative. Investigations for lymphoma over several years were negative. At 13 she underwent splenectomy for idiopathic thrombocytopenia. No definitive diagnosis was established for her in childhood.
She suffered an episode of parotitis and then, at 18, infective discitis of the lumbar spine requiring intravenous antibiotics. This precipitated a drug induced hepatitis with ascites, which became infected, resulting in a chronic, low grade peritonitis. Epstein-Barr virus, cytomegalovirus, and parvovirus serology was normal. Histological review showed that the spleen had little white pulp and few germinal centres (Fig 2), while lymph nodes showed multiple, small, non-caseating granulomas and few germinal centres (Fig 2). Immunological investigation showed all immunoglobulin levels were reduced, with IgG 0.1 g/l (normal 5.4–16.1 g/l), IgA <0.1 g/l (normal 0.8–2.8 g/l), and IgM 1.0 g/l (normal 0.5–1.9 g/l). Lymphocyte subclasses and bone marrow biopsy were normal.
The diagnosis of common variable immunodeficiency syndrome (CVIS) with granulomas was made. Her exacerbations of idiopathic thrombocytopenia responded to immunoglobulin therapy.
CVIS is a primary immunodeficiency characterised by decreased or absent levels of immunoglobulins. Patients suffer from recurrent bacterial infections and respiratory failure is the principal cause of death.1 Autoimmune disease is seen in approximately 10% of cases, especially thromocytopenia, haemolytic anaemia, and rheumatoid arthritis; 25% have splenomegaly and approximately one third have non-caseating granulomata in sites such as the liver, lungs, spleen, and lymph nodes.2 This variant is called granulomatous antibody deficiency (GAD). A sarcoid-like syndrome may be seen in 7.5% of patients.3
To our knowledge this is the first reported case of bilateral granulomatous uveitis in association with GAD. As in sarcoidosis, serum ACE may be elevated if the granuloma burden is high4 and a Kveim test may be positive. The diagnosis of GAD hinges on the presence of hypogammaglobulinaemia, while in sarcoidosis immunoglobulin levels are normal or raised.5
Granulomatous uveitis is often an indicator of systemic disease. When there is a history of recurrent infection or of autoimmune disease, immunoglobulin levels should be measured to exclude the possibility of a treatable immunodeficiency.
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