IGG4-RELATED DISEASE MIMICKING ANTI-NEUTROPHIL CYTOPLASMIC ANTIBODY-ASSOCIATED VASCULITIS(AAV): A DIAGNOSTIC CHALLENGE.

Background: Immunoglobulin G4-related disease (IgG4-RD) is now recognized as a systemic fibro-inflammatory disorder of unknown origin. Renal involvement occurs in approximately 15% of patients, mainly tubulointerstitial nephritis. Although IgG4-RD and AAV have different clinical and pathological features, it is sometimes difficult to distinguish between them. Case Report: A 70-year-old man presented with a 5-month history of asthenia, recurrent fever, anorexia, nauseas and weight loss. He had a previous diagnosis of AAV with renal involvement, 9 years ago, being in remission since then. His laboratory tests revealed normocytic normocromic anemia, hypereosinophilia (27,1%), hypoalbuminemia, ESR 102 mmh, C-RP 82.8 mg/L, renal function impairment (urea 70 mg/dl/creatinin 1.63 mg/dl) and active urinary sediment with markedly increased but intermittent erytrocituria (3914/ul), although red cell casts or dysmorphic erythrocytes were absent and with 0,25 g/l proteins in 24hurine sample. MPO-ANCA antibody was in normal range at this time. Nevertheless, he had polyclonal increase of gammaglobulins, particularly of IgG4 subclass (1940 mg/dl; normal range 8-140). Abdominal and renal scan were normal and abdomino-pelvic CT revealed mild and diffuse parenchymal heterogeneity of the kidneys and bilateral pyelectasis with thickening and hypercaptation of the urothelium in a probable relation with inflammatory manifestations, but with no evidence of abscesses or urolithiasis. PET and biopsy of minor salivary glands were unremarkable and fine needle biopsy of subcutaneous fat tissue was also negative for amyloide protein. Due to significant worsening of general condition with progressive weight loss, asthenia and anorexia, marked aggravation of anemia and renal function, associated with intermittent fever peaks, marked microscopic haematuria, sustained hypereosinophilia, increased IgG4 levels in blood samples and increased acute-phase reactants, renal biopsy was repeated. Histopathological analysis revealed presence of necrosis and tubular atrophy, interstitium with fibrosis and inflammatory infiltrate consisting of lymphocytes, plasmocytes and numerous eosinophils. Moreover, IgG4 immunoreactivity was observed in the plasma cells. The aspects described were compatible with the diagnosis of IgG4-related renal disease. The patient received 3 pulses of endovenous metylprednisolone 1g in consecutive days and then started oral prednisolone 30 mg/day (0,4 mg/Kg/day). He improved quickly after these treatment and at a 9-month follow-up he remained in sustained remission, apyretic and with progressive weight gain, maintaining progressive withdraw of prednisolone (15 mg/day). His laboratory tests further improved with hemoglobin 16.2 g/dL, hematocrit 45.2%, without hypereosinophilia, improvement of renal function and low acute phase reactants. Furthermore, serum IgG4 levels substantiatly decreased (153 mg/dl). Conclusion: Our case represents a description of an IgG4-related tubulointerstitial nephritis with concomitant positivity of cytoplasmic MPO-ANCA, mimicking AAV. The possibility that they have common immunopathogenetic mechanisms should be considered since it seems that they both are Th-2 mediated diseases, which may account for the enhanced IgG4 response observed for both syndromes. Nevertheless, distinction between these 2 conditions is crucial for treatment and prognostic purposes in order to be able to anticipate potential disease complications. [ABSTRACT FROM AUTHOR]