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Collapsing glomerulopathy (CG) is a recently described form of glomerular injury. Characteristic histopathological changes of CG consist of segmental and global collapse of the glomerular capillaries, wrinkling and retraction of the glomerular basement membrane, and marked hypertrophy and hyperplasia of podocytes. The most common cause is HIV associated nephropathy, but a few other causes were found recently.1 CG has been reported during infections by parvovirus B19 (PVB19), cytomegalovirus, filariosis or tuberculosis and treatment with pamidronate.1 CG has been also reported in systemic autoimmune disorders.
We report a case of CG occurring as the initial manifestation of a well defined systemic lupus erythematosus (SLE). A 17 year old young African woman was referred in September 2003 to our Internal Medicine Department for fatigue and fever (40°C). Physical examination showed alopecia, typical discoid lupus, and non-deforming polyarthritis evolving for 2 months. Antinuclear antibodies (ANA, 1/1280 speckled and homogeneous), anti-DNA, anti-SSA, anti-SSB, and anti-Sm antibodies were positive, the C3 fraction was low (0.69 g/l, normal >0.85). Red and white cell counts displayed lymphopenia (1.2×109/l) and anaemia (haemoglobin 98 g/l) with 122 000 reticulocytes and a positive direct IgG Coombs test. Anticardiolipin antibodies and a search for lupus anticoagulant were negative. A lupus nephritis was suspected because of a nephrotic syndrome with hypoalbuminaemia (30 g/l), proteinuria (9 g/day; 70% albumin), and microscopic haematuria. The serum creatinine level was normal (75 μmol/l). SLE was diagnosed and a renal biopsy was performed. Renal biopsy found focal segmental collapse of glomerular capillaries. Immunofluorescence staining was negative for IgG, IgA, IgM, C1q, C3, fibrin, albumin, κ and λ chains. A diagnosis of CG was considered and lupus nephritis was ruled out.
Extensive searches for the main causes of CG were negative. PVB19 serology found IgG but no IgM, whereas PVB19 DNA polymerase chain reaction was negative in peripheral blood. The following serologies were negative: HIV, cytomegalovirus (CMV), hepatitis C virus, hepatitis B virus, Treponema pallidum haemagglutination-Venereal Disease Research Laboratory assay, Lyme borreliosis, Leishmania, and Loa loa. Blood HIV DNA polymerase chain reaction was negative at the time of diagnosis and 6 months later. The patient was not a drug misuser and had never received pamidronate, lithium, or interferon α before. The patient was treated with steroids (prednisone 0.5 mg/kg/day) and hydroxychloroquine (400 mg/day). Joint pain disappeared within 2 weeks. Three months later, her daily proteinuria had dropped to 0.6 g, albuminaemia was raised at 34 g/l, and there was no haematuria. One year later, there was no proteinuria, serum creatinine was 82 μmol/l. Prednisone was tapered to 15 mg/day.
We found 162 reported cases of HIV negative CG, at times called “idiopathic”.2–9 Among these, 18 (11%) were associated with either a connective tissue disease CTD) or positive ANA. CTD associated with CG were: SLE-like disorders (<4 SLE American College of Rheumatology criteria; n = 8),4,5 primary Sjögren’s syndrome (n = 1),6 mixed CTD (n = 1).4 Additionally, CG was reported in patients without clinical features of CTD but with positive ANA (n = 8)3,4,6 and/or positive anti-DNA test ( n = 1)6 and/or hypocomplementaemia (n = 1).6 CG associated with autoimmune conditions in 69% of patients evolved to end stage renal disease, an outcome, similar to that reported for patients with idiopathic CG, ranging from 50% to 100% in most series.5
Our patient with full blown SLE was promptly treated with steroids and hydroxychloroquine, and her renal disease improved with treatment. Because CG may relapse after an initial spontaneous remission,1,6,8 early improvement must be interpreted cautiously. Although there are no prospective treatment trials in CG, retrospective studies suggest that the best results have been obtained when treatment with steroids is started shortly after diagnosis.1 Association of CG with CTD is not restricted to systemic autoimmune disorders. Recently, two cases of CG occurring during adult’s Still’s disease were reported.10 This newly recognised entity should be considered when patients with SLE or SLE related disorders develop a severe nephrotic syndrome without SLE pathological changes on renal biopsy, especially negative immunofluorescence staining.
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