IgG4-related disease in Italy: clinical features and outcomes of a large cohort of patients.

OBJECTIVES: To describe the clinical features, treatment response, and follow-up of a large cohort of Italian patients with immunoglobulin (Ig)G4-related disease (IgG4-RD) referred to a single tertiary care centre. METHOD: Clinical, laboratory, histological, and imaging features were retrospectively reviewed. IgG4-RD was classified as 'definite' or 'possible' according to international consensus guidelines and comprehensive diagnostic criteria for IgG4-RD. Disease activity was assessed by means of the IgG4-RD Responder Index (IgG4-RD RI). RESULTS: Forty-one patients (15 females, 26 males) were included in this study: 26 with 'definite' IgG4-RD and 15 with 'possible' IgG4-RD. The median age at diagnosis was 62 years. The median follow-up was 36 months (IQR 24-51). A history of atopy was present in 30% of patients. The pancreas, retroperitoneum, and major salivary glands were the most frequently involved organs. Serum IgG4 levels were elevated in 68% of cases. Thirty-six patients were initially treated with glucocorticoids (GCs) to induce remission. IgG4-RD RI decreased from a median of 7.8 at baseline to 2.9 after 1 month of therapy. Relapse occurred in 19/41 patients (46%) and required additional immunosuppressive drugs to maintain long-term remission. Multiple flares occurred in a minority of patients. A single case of orbital pseudotumour did not respond to medical therapy and underwent surgical debulking. CONCLUSIONS: IgG4-RD is an elusive inflammatory disease to be considered in the differential diagnosis of isolated or multiple tumefactive lesions. Long-term disease control can be achieved with corticosteroids and immunosuppressive drugs in the majority of cases.

Meningeal involvement in Wegener's granulomatosis is associated with localized disease.

Meningeal involvement is a rare occurrence in Wegener's Granulomatosis (WG). A Medline search uncovered only 48 previously reported cases. Here we describe the clinical features of meningeal involvement in WG and to evaluate the association with systemic disease extension. Through a systematic literature review of papers concerning meningeal involvement in WG, we collected and analysed data about sex, age, disease extension, symptoms, cerebrospinal fluid examination, imaging, ANCA and histology about previously reported patients. Headache is almost always the first symptom of meningeal involvement in WG. Later in the course of the disease other abnormalities may develop. Among them cranial nerve palsy, seizures and encephalopathy are the most frequent. Diagnosis is obtained by neuroimaging, which may disclose two distinct patterns of meningeal thickening: diffuse or focal. 62.9% of patients tests positive for ANCA. Histology typically shows necrotizing granulomatosis. Meningeal involvement is by far more frequent in the setting of localized WG. Meningitis is a rare complication of WG. It usually develops in patients with localized disease who are more likely to have destructive lesions of the upper airways. It may be recognized by a constellation of clinical and radiological findings and by histological signs of necrotizing granulomatosis, with little or no vasculitis.

[Wegener's granulomatosis: an analysis of 50 patients]. / Granulomatosi di Wegener: descrizione di una casistica di 50 pazienti.

OBJECTIVES: To evaluate the rate of different organs involvement in 50 patients with Wegener's Granulomatosis (GW), and to describe their clinical manifestations and their response to treatment. METHODS: We evaluated 50 consecutive patients with GW, come to our attention from January 1987 to May 2003. 43 patients met the 1990 American College of Rheumatology (ACR) criteria for classification of GW; 7 patients the 1993 ELK criteria. RESULTS: 82% of patients presented Ear/Nose/Throat (ENT) involvement, which is the most common site of inflammation. 22% of our patients had ENT-restricted disease; in 78% of cases disease extended to other organs. Lungs were involved in 72% of cases; kidney in 36%; eye in 24%; nervous system (NS) in 14% (central NS in 10% and peripheral NS in 4%); skin in 10%; heart in 8%; testis in 4%. Arthritis was present in 10% of patients. We discuss treatment of all patients and response to therapy of those 28 whose follow-up is available. CONCLUSIONS: Involvement of airways and kidney is by far the most common in GW, though potentially any other organ or system may be affected. The total rate of other organs involvement is 70%.

Tumores estromales gastrointestinales / Stromal tumors gastrointestinal

Introducción: los tumores estromales gastrointestinales (GISTs)son un grupo eterogéneo de neoplasias mesenquimáticas, controvertidas para muchos en cuanto a morfología, criterios diagnósticos y comportamiento. Datos clínicos: se revisaron todos los tumores mesenquimáticos gastrointestinales de archivo del período 1992-2002. Se hallaron 7 casos de GISTs (25 por ciento de los tumores mesenquimáticos): 4 mujeres y 3 hombres, de 53 a 89 años; 5 fueron de estámago, 1 de intestino delgado y 1 de trascavidad de los epiplones. Métodos disgnósticos: el material se procesó según técnicas de rutina y se coloreó con H.E. Se efectuó IHQ para Actina Músculo Liso (AML), Desmina, S 100, CD 117. Hallazgo macroscópicos: todos los casos correspondieron a piezas quirúrgicas (gastrectomía, resección segmentaria intestinal o tumorectomía). El tamaño tumoral osciló entre 4 y 25 cm. Hallazgos microscópicos: consistieron en proliferaciones fusiformes, con grado variable de celularidad, atipía y actividad mitótica (AM)...

PTX3 in small-vessel vasculitides: an independent indicator of disease activity produced at sites of inflammation.

OBJECTIVE: To verify whether the prototypical long pentraxin PTX3 represents an indicator of the activity of small-vessel vasculitis. METHODS: Concentrations of PTX3, a pentraxin induced in endothelium by cytokines, were measured by enzyme-linked immunosorbent assay in the sera of 43 patients with Churg-Strauss syndrome, Wegener's granulomatosis, and microscopic polyangiitis. PTX3 was also measured in the sera of 28 patients with systemic lupus erythematosus (SLE), 22 with rheumatoid arthritis, and 16 with CREST syndrome (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias). Serum concentrations of C-reactive protein (CRP) were measured by immunoturbidimetry. The cells involved in PTX3 production in vivo were identified in skin biopsy samples. RESULTS: Patients with active vasculitis had significantly higher concentrations of PTX3 than did those with quiescent disease (P < 0.001). PTX3 levels in the latter group were similar to those in healthy controls. PTX3 levels were higher in patients with untreated vasculitis and lower in patients who underwent immunosuppressive treatments (P < 0.005). In contrast, patients with active SLE had negligible levels of the pentraxin. PTX3 levels did not correlate with CRP levels in vasculitis patients. Endothelial cells produced PTX3 in active skin lesions. CONCLUSION: PTX3 represents a novel acute-phase reactant produced at sites of active vasculitis.

Acute echinococcosis: a case report.

We report the case of a 69-year-old man with acute pulmonary echinococcosis. A computed tomographic scan of the thorax revealed the presence of multiple nodules in both lungs, and laboratory tests showed eosinophilia and the presence of antibodies against Echinococcus granulosus. Therapy with albendazole led to resolution of the pulmonary nodules and a normalization of the white cell count. To our knowledge this is the first described case of acute echinococcosis, as the diagnosis of this disease is usually delayed to chronic phases. Therefore, finding unexplained eosinophilia, especially in association with pulmonary nodules, should lead one to suspect acute hydatid disease.

Carcinomas renales no convencionales / Carcinomas renal

Actualmente se reconocen carcinomas de células renales (CCR) convencionales y no convencionales. Se plantean técnicas diagnósticas diferenciales de tumores renales con características morfológicas similares, inmunofenotípicas particulares y pronósticas dispares. Se presentan cuatro casos de piezas de nefrectomía, tres correspondientes a pacientes de sexo masculino de 20, 66 y 79 años, y uno a una mujer de 22 años. Todos remitidos como MOR (masa ocupante renal). Se observaron formaciones tumorales de entre 15 y 20 cm de diámetro máximo, de aspecto heterogéneo. Las muestras se procesaron con técnicas histológicas de rutina y se colorearon con HE. Tras el exámen se realizaron técnicas de histo e inmunohistoquímica (PAS, Hale, Sudán, CK7, CK AEI-AE3 CD10, EMA, VIM). Se evidenciaron proliferaciones de células poligonales en playas, nidos, cordones, rosetas y túbulos, de contornos definidos cuyos citoplasmas variaban de claros a intensamente eosinófilos y otros de aspecto granular. Los núcleos mostraron grados II y III de Fuhrman. Focalmente se hallaron áreas de necrosis y hemorragias con compromiso capsular en dos de los casos. Ante variedades no convencionales de CCR adquieren relevancia diagnóstica la tinción con hierro coloidal de Hale (positiva en CCR cromófobo), inmunomarcación con VIM (negativa en CCR cromófobo y oncocitomas), CD10 (positivo en CCR de células claras) y CK 7 (positiva en CCR cromófobo y negativa en oncocitomas).

Budd-Chiari syndrome in a patient with ulcerative colitis: association with anticardiolipin antibodies.

This is the first reported case of a young patient with ulcerative colitis who developed acute Budd-Chiari syndrome and was found positive for anticardiolipin antibodies. Although an association between ulcerative colitis and Budd-Chiari syndrome, and between the latter and antiphospholipid antibodies, has been shown in the literature, the coexistence of these three conditions has never been reported. The patient we describe did poorly and was considered as a candidate for liver transplantation in spite of prompt heparin therapy, probably because of the presence of multiple risk factors.

Peripheral neuropathy in scleroderma.

Nervous system involvement is rare in progressive systemic sclerosis (PSS). We present a clinical pathological and immunological study of two patients with peripheral sensory motor neuropathy and PSS. In both, the sural nerve biopsies showed axonal degeneration with increased endoneurial connective tissue. There were also clusters of myelinated fibres indicating axonal regeneration. Only mild microangiopathic changes were evident in the endo, peri and epineurial vessels. By Western immunoblots, patients' sera contained a band of reactivity to a protein from peripheral nerve identified as collagen type I. Primary involvement of the peripheral nerves during PSS is very unusual. Abnormal production of collagen tissue and presence of microvascular disease are considered to be two possible causes of neuropathy. We think that our results suggest the important role of the connective tissue proliferation in the pathogenesis of PSS neuropathy.

Association of lupus anticoagulant with polyarteritis nodosa: report of a case.

A patient with a documented diagnosis of polyarteritis nodosa and laboratory evidence of a circulating lupus anticoagulant is described. Additional clinical features suggestive of the antiphospholipid antibody syndrome were found. The patient underwent amputation of the first two digits of the foot due to ischemic necrosis. Steroid and immunosuppressive treatment resulted in clinical improvement and disappearance of the circulating anticoagulant, without necessitating additional treatment with oral anticoagulants. The presence of the lupus anticoagulant might have worsened the vascular damage done by polyarteritis nodosa in this patient.

Electrophysiological and MRI evaluation of neurological involvement in Behçet's disease.

Eight patients with stable Behçet's disease were studied by means of multimodality evoked potentials and magnetic resonance imaging to evaluate the possibility of an earlier and objective demonstration of clinical and subclinical Central Nervous System (CNS) involvement. It was shown that both diagnostic techniques are useful for quantitative evaluation of neurological involvement in Behçet's disease; of particular interest was the demonstration of subclinical CNS changes.

Berger's disease with polyarteritis nodosa.

We describe a patient with Berger's disease and polyarteritis nodosa. This association has not been described previously in the literature. A causal relationship between the two diseases is suggested.

Essential mixed cryoglobulinemia: a report on 14 cases.

Fourteen cases of Essential Mixed Cryoglobulinemia (EMC) are described in this report. Clinical and laboratory manifestations in our patients were similar to those previously reported in literature, although involvement of the peripheral nervous system was much more prevalent in our series. We suggest that peripheral neuropathy should be systematically searched in EMC patients.