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Chronic granulomatous disease (CGD) is characterized by recurrent infections and granuloma formation. In addition, we have observed a number of diverse autoimmune conditions in our CGD population, suggesting that patients with CGD are at an elevated risk for development of autoimmune (AI) disorders. In this report, we describe antiphospholipid syndrome (aPL), recurrent pericardial effusion, juvenile idiopathic arthritis (JIA), IgA nephropathy, cutaneous lupus erythematosus, and autoimmune pulmonary disease in the setting of CGD. The presence and type of autoimmune disease has important treatment implications for patients with CGD. KeywordsChronic granulomatous disease; autoimmune; antiphospholipid syndrome; IgA nephropathy; lupus; juvenile idiopathic nephropathy Chronic granulomatous disease (CGD) is a primary immunodeficiency (PID) resulting from a defect in the multicomponent nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex, which is responsible for production of bactericidal reactive oxygen species (ROS) in phagocytes. As a result, CGD patients are at increased susceptibility to certain catalasepositive bacteria and fungi, and Aspergillus species 1 . The primary clinical features of CGD are recurrent infections and granuloma formation. However, reports of sarcoidosis 2 , JIA 3 , IgA nephropathy 4 , pericardial effusion 5 , and severe Crohn's-like inflammatory bowel disease 6 suggest that the breadth of altered immune regulation extends beyond recurrent infections and granulomas. We propose, in addition, that CGD patients are at significant risk for development of autoimmune disease (AI), and provide a series of case reports and a review of the literature to support that hypothesis. Specifically we report here the following AI in our CGD patients; antiphospholipid syndrome (aPL), juvenile idiopathic arthritis (JIA), IgA nephropathy; steroidresponsive recurrent pericardial effusions, cutaneous lupus erythematosus, and lastly, a case with 'geographic pulmonary lesions', a finding we have observed in four other CGD patients. A 14.5 year-old Caucasian male was diagnosed with X-linked (gp91 phox -deficient) chronic granulomatous disease (CGD) following the development of Serratia marcescens abscesses of his neck and mesentery at 3 years of age. Long-term prophylaxis consisting of trimethoprimsulfamethoxazole, itraconazole and interferon-γ (IFN-γ) was commenced. Of interest, his mother (a CGD carrier) and maternal aunt (not a carrier) were both diagnosed with discoid lupus. At 10 years, he developed cellulitis of his arm following a minor skin abrasion. Treatment with intravenous antibiotics was complicated by venous thrombosis in his affected arm, which was treated with a 3-month course of warfarin. At age 14, he described acute swelling, pain and redness of the left thigh, with no other associated symptoms, fever, or history of trauma. His laboratory tests were unremarkable, other than an ESR of 50 mm/hr (NIH range 0-25mm/hr). Doppler ultrasound revealed a left femoral deep venous thromb...

Purpose Patients with Common Variable Immunodeficiency (CVID) are subject to the development of a liver disease syndrome known as nodular regenerative hyperplasia (NRH). The purpose of this study was to define the characteristics and course of this complication of CVID. Methods CVID patients were evaluated by retrospective and prospective clinical course review. Liver biopsy specimens were evaluated for evidence of NRH and studied via RT-PCR for cytokine analysis. Results NRH in our CVID patient population occurred in approximately 5% of the 261 patients in our total CVID study group, initially presenting in most cases with an elevated alkaline phosphatase level. While in some patients the disease remained static, in a larger proportion a more severe disease developed characterized by portal hypertension, the latter leading to hypersplenism with neutropenia and thrombocytopenia and, in some cases, to ascites. In addition, a substantial proportion of patients either developed or presented initially with an autoimmune hepatitis-like (AIH-like) liver disease that resulted in severe liver dysfunction and, in most cases to death due to infections. The liver histologic findings in these AIH-like patients were characterized by underlying NRH pattern with superimposed interface hepatitis, lymphocytic infiltration and fibrosis. Immunologic studies of biopsies of NRH patients demonstrated the presence of infiltrating T cells producing IFN-γ, suggesting that the NRH is due to an autoimmune process. Conclusion Overall, these studies provide evidence that NRH may not be benign but, can be a severe and potentially fatal disease complication of CVID that merits close monitoring and intervention.

To assess the relation between usual nutrient intake and subsequently diagnosed age-related nuclear lens opacities.Subjects: Four hundred seventy-eight nondiabetic women aged 53 to 73 years from the Boston, Mass, area without previously diagnosed cataracts sampled from the Nurses' Health Study cohort.Methods: Usual nutrient intake was calculated as the average intake from 5 food frequency questionnaires that were collected during a 13-to 15-year period before the evaluation of lens opacities. The duration of vitamin supplement use was determined from 7 questionnaires collected during this same period. We defined nuclear opacities as a nuclear opalescence grade of 2.5 or higher using the Lens Opacification Classification System III. Results:The prevalence of nuclear opacification was significantly lower in the highest nutrient intake quintile category relative to the lowest quintile category for vitamin C (PϽ.001), vitamin E (P = .02), riboflavin (P=.005), folate (P=.009), ␤-carotene (P=.04), and lutein/ zeaxanthin (P = .03). After adjustment for other nutrients, only vitamin C intake remained significantly associated (P=.003 for trend) with the prevalence of nuclear