Evidence of immunopathological traces in mucormycosis: an autopsy case.

A 77-year-old diabetic man newly contracted pulmonary mucormycosis. A rapidly progressing clinical course including severe worsening of pneumonia and renal failure culminated in death. This patient presented with hypocomplementemia and dermal vasculitis. Autopsied organs were examined by histological technique. Lung tissues showed pulmonary artery thrombosis and extensive alveolar invasion by Mucor hyphae with depositions of immunoglobulins, mannose-binding lectin (MBL) and C1q. The right internal jugular vein was occluded by thrombi containing numerous hyphae. The glomerular change was a hallmark of extra-capillary proliferative glomerulonephritis, which was overlying diabetic nephropathy. Depositions of IgM, C3 and C4 on glomeruli were also detected. Electron microscopy showed electron-dense deposits in the mesangial area and the wall of the afferent arteriole. This report shows evidence of complement opsonization of Mucor hyphae and refers to mucormycosis that developed small-sized vasculitis with complement activation.

"Full house" proliferative glomerulonephritis: an unreported presentation of subacute infective endocarditis.

A severely ill 65-year-old man presented with symptoms of shortness of breath, edema and vasculitidic purpura over his lower extremities. He had severe mitral regurgitation which had not been surgically treated. Hematologic examination demonstrated leukocytosis with profound anemia. Other blood tests revealed impaired renal function, hypoalbuminemia, hypocomplementemia and mixed-type cryoglobulinemia. Urinalysis showed proteinuria, hematuria and pyuria, typical of a nephritic sediment. Renal biopsy indicated diffuse proliferative glomerulonephritis and a "full house" deposition in immunofluorescence study (positive for C3, C4, C1q, IgG, IgA and IgM), resembling the pathologic findings in class IV lupus nephritis. Although subacute bacterial endocarditis was initially suspected owing to a history of a predisposing valvular heart disease, probable vegetation shown by cardiac sonography and a clinical picture suggestive of a chronic infection, it was thought unlikely due to the entire afebrile course and initial sterile blood cultures. However, the blood cultures repeated 2 weeks after admission grew 3 sets of viridans streptococci. Following a course of penicillin and gentamicin treatment, his renal function, anemia and abnormal urine sediments improved gradually. Diffuse proliferative glomerulonephritis is well known to occur in infective endocarditis. However, the "full house" immunostaining in immunofluorescence study has never been reported. This case adds a new entity to the differential diagnosis of "full house" immune complex-related glomerulonephritis and exemplifies the need to maintain a high index of suspicion for underlying infectious disorders when facing glomerulonephritic or vasculitic syndrome.

Incidental healed postinfectious glomerulonephritis: a study of 1012 renal biopsy specimens examined by electron microscopy.

Glomerulonephritis (GN) characterized by immune complex deposits typical of postinfectious GN but with a paucity or absence of overt clinical symptoms and/or urinary abnormalities may occur after a group A streptococcus infection. The overall incidence of this type of subclinical GN is not known. To address this question, electron microscopy findings in 1012 consecutive renal biopsy specimens (952 native kidney, 60 transplant) examined by a single renal pathologist from August 1999 to April 2002 were retrospectively reviewed for the presence of distinct subepithelial and intramembranous deposits indicative of postinfectious GN. Such deposits were noted in 83 biopsy specimens, including 26 with a primary diagnosis of postinfectious GN (acute, persistent, or latent) and 57 in which these deposits were an incidental finding. In each of the latter 57 cases, some or all of the deposits showed partial or extensive loss of electron density typical of partially or largely resorbed deposits. A diagnosis of incidental postinfectious GN was not made in any biopsy specimen exhibiting another immune complex-related glomerular disease that could possibly account for the deposits, composing 443 of the 1012 biopsy specimens examined. Thirty of the 57 biopsy specimens with incidental postinfectious GN showed mesangial hypercellularity, although this was focal and segmental in all but 3 cases and was not accompanied by the endocapillary hypercellularity typical of acute postinfectious lesions. Immunofluorescence microscopy revealed glomerular deposits of C3 in >90% of these biopsy specimens and IgM deposits in 66%, but only rare IgG, IgA, and Cq deposits. Twenty-three (40%) of these 57 biopsy specimens exhibited diabetic nephropathy, either alone or in combination with another lesion; for perspective, only 128 (13%) of the 1012 biopsy specimens examined showed evidence of diabetic nephropathy. In summary, incidental evidence of resolving or largely healed postinfectious GN was noted in up to 10.5% of renal biopsy specimens (57 of 543, not including specimens with a primary diagnosis of an immune complex-related glomerular disease). The recognition of such lesions is potentially important in the interpretation of certain renal biopsy specimens.

[Association of nephrotic syndrome and Hodgkin's disease. Role of the Epstein-Barr virus]. / Association syndrome néphrotique -maladie de Hodgkin. Rôle du virus Epstein-Bar

The clinical association between glomerulonephrtis (GN) and malignant hematological disease is very rare. We report, in a 24 years old male, the occurrence of an apparently idiopathic nephrotic syndrome with minimal change glomerular lesions. This GN was in fact closely related to the progression of a stage 2A of Hodgkin's disease, following an infectious mononucleosis contracted one year ago. The nephrotic syndrome responded well to the therapy by Prednisone and Chlorambucil, and the complete remission persisted after eradication of Hodgkin's disease and despite early treatment discontinuation. Renal vein thrombosis, renal amyloidosis and renal interstitial infiltration with malignant cells were ruled out. Immunofluorescent and electron microscopy examination of the renal biopsies were consistent with, but not demonstrative of, an immune complex nephritis. Because of the chronological succession of infectious mononucleosis, Hodgkin's disease, and GN, we are stressing the possible oncogenic and immunogenic role of the Epstein-Barr virus.

[A protracted course in Cardiobacterium hominis endocarditis]. / Protrahierter Verlauf einer Cardiobacterium-hominis-Endokarditis.

A 69-year-old man without previous cardiac disease was found over the last 9 months to have a markedly elevated erythrocyte sedimentation rate (ESR: 120 mm/1. h), haemolytic anaemia (haemoglobin 8.2 g/dl, lactate dehydrogenase 304 U/l), markedly reduced exercise tolerance, backache and weight loss of 5 kg. Radiological, biochemical and endoscopic examinations failed to provide a diagnosis. Nine blood cultures grew, at normal body temperature, Cardiobacterium hominis, a rare Gram-negative organism which can cause endocarditis. Echocardiography revealed endocarditis of the aortic valve with regurgitation. Despite protracted and high-dosage antibiotics (4 times daily 10 million U penicillin G for 6 days, followed by four times 5 million U penicillin G for 6 days, followed by four times 5 million U daily for five weeks, and three times daily 60 mg gentamycin for 10 days), as well as treatment of extensive chronic parodontitis, anaemia, haemolysis and increased ESR have now persisted for over a year, with negative blood cultures. Immune-complex phenomena are thought to be the reason for the persistence of signs of infection.

Possible role for a polysaccharide antigen shared between Streptococcus pyogenes and S. mutans in the pathogenesis of poststreptococcal glomerulonephritis.

Streptococcus mutans has been shown to share a polysaccharide (PS) antigen with S. pyogenes strains isolated from patients with acute poststreptococcal glomerulonephritis (PSGN), using a monoclonal antibody f-77 reactive with the PS. To investigate the pathogenetic role of the shared PS in PSNG, experimental nephritis was induced in animals. Rats were immunized thrice with heat-killed cells of S. mutans or S. pyogenes, followed by an intravenous injection of live cells of S. pyogenes. Histologic examination showed that both animal groups had comparable degrees of diffuse proliferative nephritis characterized by immune deposits. The shared PS antigen was detected in glomeruli of all nephritic rats by immunofluorescence using monoclonal antibody f-77. Furthermore, all nephritic rats had an elevated antibody titer to the shared PS antigen. These results suggest that prior sensitization (infections such as dental caries) to S. mutans modulates immune responses to subsequent S. pyogenes infections and induces immune-complex disease (PSGN) through the shared PS antigen.

[HBs-antigen induced extrahepatic immune-complex disease (author's transl)]. / HBs-Antigen-induzierte passagere extrahepatische Immunkomplexkrankheit

A 62-year old patient was hospitalized with fever, polyarthritis and exanthema. All bacteriological, virological and biochemical findings were normal. The immunological analysis showed initially the HBs-antigen in the serum. No irregular antibody was found. Chemotherapy was failing, but application of corticosteroids was followed by a dramatic improvement. Nine weeks after the onset of the disease the patient was healthy again. Antibodies against HBs-antigen were found 3 months later. The data suggest an immune-complex disease like serum sickness based on an infection with hepatitis-B-virus without involvement of the liver.

Immune complex associated complications in the subacute phase of meningococcal disease: incidence and literature review.

AIM: To determine the incidence of immune complex associated complications (IAC) after severe meningococcal disease (SMD) in a group of Dutch children admitted to a paediatric intensive care unit (PICU). METHODS: Retrospective chart analysis and follow up of 130 survivors of SMD admitted to PICU. Signs of IAC, inflammatory parameters, and temperature profile were reviewed. RESULTS: Of 130 children with SMD, 20 (15.3%) showed one or more of the three manifestations of IAC: 18 (13.8%) developed arthritis (effusion, with or without erythema/arthralgia), 11 (8.4%) vasculitis, and five (3.8%) pleuritis. Eighteen of 20 (90%) patients with IAC had a secondary rise in temperature; in patients with no IAC this was 48 of 110 (43.6%). IAC was associated with leucocytosis in 82.3% versus 47.7% in patients without IAC, and with increased CRP in 86.6% versus 47.2% in patients without IAC. Leucocytes on admission were significantly lower in patients who would later develop IAC (mean 8.6 versus 13.8x10(9)/l). CONCLUSION: IAC is a common complication of SMD, mainly occurring 4-10 days after systemic disease. IAC presents clinically as arthritis or vasculitis, mostly accompanied by secondary fever and raised inflammatory parameters.

Effects of pulse cyclophosphamide on NZB/W disease.

Induced IgM anti-ss-DNA antibodies in NZB/W female mice did not alter the time of onset nor the course of nephritis. Monthly pulse doses of cyclophosphamide suppressed the mortality of these mice, and also prevented a switch of anti-ss-DNA from IgM to IgG class. The production of IgM anti-SRBC was markedly reduced in old NZB/W mice, but IgG anti-SRBC was only moderately reduced and this hyporesponsiveness towards SRBC could be reversed by CPA treatment. These observations are discussed in relation to cyclophosphamide as an effective therapeutic agent for the murine lupus syndrome.