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We report here two cases of mixed cryoglobulinemia showing renal involvement associated with hepatitis C virus (HCV) infection. The subjects were 62- and 63-year-old males. Both patients presented with purpura on the legs, which was diagnosed as allergic vasculitis by skin biopsy. Case 1 followed a clinical course of progressive nephrotic syndrome with mild hematuria. He also had diabetes mellitus and hypertension. In contrast, case 2 showed only mild hematuria without proteinuria at the time of the renal biopsy. Both cases had immunological disarrangements, such as severe hypocomplimentemia and seropositive rheumatic factor. Recently, it was reported that patients with type II mixed cryoglobulinemia had HCV seropositivity, and revealed membranoproliferative glomerulonephritis. These facts strongly suggested that renal lesions are the result of direct damage mediated by cryoglobulinemia and an activated complement pathway through an immune complex mechanism related to HCV.
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PMID:[Glomerular lesion in patients with type II mixed cryoglobulinemia having antibodies to hepatitis C virus]. 747 12

Since their initial description in 1957, the interferons (IFNs) have been increasingly used to treat a wide array of diseases. Acute adverse effects, i.e. 'flu-like' syndromes, hypo- or hypertension, tachycardia, headache, myalgias and gastrointestinal disorders, occur within the first hour or day after starting treatment. They are seldom treatment-limiting and are easily manageable. Sub-acute and chronic effects develop after several days, usually within 2 and 4 weeks of therapy. The most typical is neurological toxicity, including fatigue/asthenia, and behavioural and cognitive changes. Such symptoms may seriously impair quality of life and result in treatment discontinuation. Seizures have seldom been described. Other infrequent central nervous system adverse effects include vertigo, cramp and oculomotor nerve paralysis. Distal paraesthesias and peripheral neuropathy have been reported. IFN-associated autoimmunity is quite rare but a matter of concern. Biological or clinical manifestations usually require several months to become apparent. Autoantibodies have been shown to develop in most patients but have been inconsistently associated with clinical symptoms of systemic lupus erythematosus, rheumatoid-like arthritis and thyroiditis. Both hypo- and hyperthyroidism have been described but are usually reversible. Other infrequent autoimmune reactions include diabetes, pemphigus and worsening of multiple sclerosis. Although several patients present with a pre-existing autoimmune disorder, no predisposing factor has been clearly established. While hypotension and tachycardia are the most frequent acute cardiovascular complications, a few additional cases of cardiac arrhythmias and myocardial ischaemia have been reported after a short course or several weeks of treatment. These latter complications do not appear to be dose-dependent or age-related. Isolated cases of congestive heart failure have also been described. Mild proteinuria has been observed in 15 to 25% of patients, but acute renal toxicity is uncommon. A transient rise in serum aminotransferase levels is frequently noted during the first stage of therapy, especially in patients receiving the highest dosages. Direct hepatotoxicity is extremely rare. Autoimmune hepatitis, which is ill-diagnosed as chronic viral hepatitis, and de novo induction of autoimmune hepatitis, account for the majority of liver diseases. Haematotoxicity is relatively common but mild to moderate, and develops gradually during the first weeks of treatment. Neutropenia is the most common haematological toxicity, but is usually not dose-limiting and resolves rapidly upon drug discontinuation. Myelosuppression, autoimmune and immune allergic haemolytic anaemias and thrombocytopenias have seldom been described. Cutaneous adverse effects comprised nonspecific erythema and hair loss and, less frequently, vasculitis, local ulcerations at the site of injection and exacerbation of psoriasis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical toxicity of the interferons. 751 63

At some time in their lives one in a five persons is affected by urticaria and/or angioedema. The cause of urticaria may never be found in up to one quarter of patients with acute urticaria and in up to 90-95% with chronic urticaria. In this study we present results of our compounded approach (clinical follow up, laboratory findings, allergological testing) to patients with chronic urticaria and autoimmune diseases that progressed into chronic urticaria or started before the onset of the chronic urticaria. Our first case was a 56 year old woman with a 10 month history of chronic urticaria, angioedema and chronic gastritis before the diagnoses of insulin dependent Diabetes mellitus and Hypothyreoidismus primarius were established. Allergological testing reveals specific clinical significant immediate reaction to Balsam Peru. After adequate substitutional therapy was advocated and with specific clinical avoidance of offended allergen, remission was obtained. The second case was a 46 year old female suffering from chronic urticaria (with clinical features of urticaria like vasculitis) associated with hypocomplementemia (particularly C4 depressed) with negative antinuclear antibodies but positive circulating immune complexes after a 2 year follow up the patient developed Systemic lupus erythematosus. The third case was a 63 year old woman who developed chronic urticaria 3 years after total thyroidectomy, with pathological finding of Thyroiditis lymphocytaria-Hashimoto; after the allergological testing, positive lymphocyte transformation test revealed allergical sensitization to Vobenol was substituted with Thyvoral, complete remission was obtained.
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PMID:[Chronic urticaria from the aspect of autoimmune diseases]. 756 41

Fournier's gangrene represents an acute severe necrotizing inflammatory process affecting the scrotum and penis. It has an associated mortality of 30-50%. In most cases, aetiological factors can be identified, such as diabetes mellitus, chronic alcoholism and perianal, perirectal or periurethral infection. The disease is characterized by a polybacterial infection, and the classic treatment includes surgical removal of the necrotic tissue and the use of broad-spectrum antibiotics. We report a case of Fournier's gangrene, histologically characterized by a necrotizing vasculitis, in which surgical resection of the necrotic tissue and antibiotic treatment failed to halt progression of the disease, whereas complete remission was achieved by high-dose corticosteroid therapy. This suggests that Fournier's gangrene is related to some form of localized vasculitis, and represents a local Shwartzman phenomenon.
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PMID:Systemic corticosteroids are important in the treatment of Fournier's gangrene: a case report. 757 98

A 31-year-old woman with systemic lupus erythematosus (SLE), diabetes mellitus, and chronic renal failure developed digital ischemia, myocardial dysfunction, abnormal ECG, and elevated CPK levels. Radiographic studies revealed calcification of the peripheral vasculature although coronary angiography was unremarkable. An endomyocardial biopsy demonstrated intra and extracellular myocardial calcification without evidence of vasculitis or primary myocarditis. A diagnosis of calciphylaxis, as a result of secondary hyperparathyroidism, was made. This case demonstrates that calciphylaxis can mimic the cardiovascular manifestations of SLE. Early differentiation of these disparate diseases is important because treatment strategies employed in SLE may exacerbate calciphylaxis.
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PMID:Systemic lupus erythematosus: calciphylaxis induced cardiomyopathy. 769 81

Three typical cases of fibrous mastopathy associated with diabetes mellitus are described. The histological change is a connective-tissue overgrowth with vasculitis and some proliferation of duct epithelium. The clinical changes are indistinguishable by physical or radiographic findings from malignancy. In young patients with long-standing diabetes the presence of one or more suspicious clinical and imaging findings can suggest the presence of this lesion but a surgical biopsy or, at least, a close follow-up is required.
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PMID:Diabetic fibrous breast disease: a clinical entity that mimics cancer. 772 Sep 1

A small number of kidney transplant recipients abruptly lose function secondary to acute renal artery or vein thrombosis or more rarely a form of necrotizing vasculitis. We report a group of four kidney transplant recipients who lost renal function and share the following features: (1) diabetes (type I, insulin-dependent diabetes mellitus, type II or steroid-induced); (2) abrupt change/loss of renal function; (3) a concomitant clinical event (fever, viral symptoms, menometrorrhagia, viremia, bacteremia); (4) severe necrotizing vasculitis with hemorrhagic necrosis on histopathology; (5) patent renal artery and vein at time of transplant nephrectomy (i.e., no vascular thrombosis); and (6) high levels of peripheral serum gamma-IFN 1-5 days before transplant nephrectomy (467 +/- 175 pg/ml) compared with that of patients experiencing severe rejection (8.4 +/- 3.7 pg/ml) (P < 0.002). These data support the concept of a cytokine (IFN-gamma)-mediated accelerated inflammatory response resulting in graft loss from necrotizing vasculitis--the clinical equivalent of an organ-specific Shwartzman reaction.
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PMID:Acute graft loss secondary to necrotizing vasculitis. Evidence for cytokine-mediated Shwartzman reaction in clinical kidney transplantation. 773 54

In the randomized autopsy material of 161 patients with rheumatoid arthritis (RA), a letal, generalized septic infection (GSI) was observed in 22 cases (13.66%). The GSI was accompanied by a pyarthros in 12 (7.45%) and no pyarthros in 10 (6.21%) cases. The clinical parameters of 22 septic RA patients were compared with 139 age and sex matched RA patients without GSI. The average age of septic patients decreased (p < 0.02), with low serum electrophoretic b-globulin level (p < 0.04), and high Waaler-Rose (p < 0.02) and Latex level (p < 0.004). The clinical parameters of 22 septic patients were compared with 76 age and sex matched RA patients without sepsis, vasculitis, or generalized secondary amyloidosis (GSA), and/or miliary epitheloid granulomas of tuberculous type (mT). The differences between the two groups of patients were the same, with a statistically more pronounced age difference (p < 0.005). 29 out of 161 patients (18.01 %) suffered from a clinically manifest diabetes mellitus (in 6 patients accompanied by sepsis), and 11 (6.83 %) from a clinically latent diabetes mellitus (in 2 patients accompanied by sepsis). There was no significant relationship between sepsis and manifest diabetes mellitus. The controlled and treated diabetes mellitus does not influence the frequency of lethal sepsis. Significant correlations were found between sepsis and latent diabetes mellitus (based on the histological detection of amyloid deposition localized to the islets of Langerhans (p < 0.02). 34 out of 161 patients (21.12%) suffered from a generalized secondary amyloidosis (in 3 patients accompanied by sepsis). There was no significant relationship between sepsis and generalized secondary amyloidosis. The thickness of adrenal cortex represents the effect of steroid therapy. Critical random check, using the Mann-Whitney tests, supports significance relationship between the adrenal cortex atrophy and fatal sepsis (p < 0.010). The follicular lymphoid depletion in the spleen represents the effect of immunosuppressive therapy. The size of lympho-follicles decreased significantly in sepsis (p < 0.004). The long term corticosteroid therapy and immunosuppressive represent a potential danger for sepsis.
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PMID:[Generalized septic infections in rheumatoid arthritis. Study of autopsy material]. 782 86

A 49-year-old woman with diabetes mellitus rapidly developed necrotizing cellulitis with fat necrosis and vasculitis after minor trauma to the right arm. Zygomycosis was diagnosed histologically. The lesion responded to aggressive debridement, amphotericin B, and normalization of blood glucose. Cultures yielded structures characteristic of Saksenaea vasiformis only after transfer to saline agar.
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PMID:Cutaneous zygomycosis caused by Saksenaea vasiformis in a diabetic patient. 792 83

Neuromyositis defined as the association of dermatomyositis or polymyositis and a neuropathy without any found cause is a very controversial entity because of the possibility of, in one hand, muscular modifications caused by neurological involvement and, on the other hand, neurogenic type manifestations caused by polymyositis. The study of 4 cases seen in an Internal Medicine department and the review of the literature allowed us to show that the concept of neuromyositis corresponds to a clinico-pathological reality when the diagnosis is based on the association of definite criteria of both primary muscle and nerve involvement excluding muscular abnormalities that could be the consequence of nerve involvement and vice versa. The criteria, most relevant when associated are: a) for muscular involvement: high increase of muscular enzyme over 6 times the superior limit of the normal values, pseudomyotonic electrical discharges, perifascicular atrophy, intense inflammatory infiltrates and massive necrosis, b) for neurological involvement: early abolition of tendinous reflexes in a patient without notable muscular atrophy and with little or no myalgia, sensitive abnormalities in areas other than those of muscular involvement, especially when they are intense, early weakness of distal muscles, decrease of nerve conduction speed, target fibers and lesions of nerve trunks (and albuminocytological dissociation in the particular case of polyradiculoneuritis). Once the diagnosis of neuropathy settled, it is necessary to exclude an usual cause (alcoholism, diabetes...) before concluding to neuromyositis. When we apply these restrictive (but nevertheless necessary for the validity of diagnosis) criteria, only 6 cases of the literature respond to this entity. It is a peripheral neuropathy in 5 cases (like two of ours) and a polyradiculoneuritis in one case (like our two others). Among these 6 cases, there is a vasculitis in two, frequency much higher to what is observed in adult polymyositis, which suggest a possible causative role of vascular involvement in neuropathy arising. In the other cases we can just give pathogenic hypothesis making the neuropathy and the polymyositis the result of the same process (immunological disturbance, paraneoplastic origin, viral disease). In one of our four patients, who have shown an HTLV-I infection by polymerase chain reaction in situ hybridization was positive in muscle which suggest a direct pathogenic role of the virus. HTLV-I infection should be considered as a possible cause of neuromyositis especially in endemic areas.
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PMID:[Do neuromyosites exist?]. 802 85


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