[Dendriform pulmonary ossification associated with idiopathic pulmonary fibrosis]. / Osificación pulmonar dendriforme asociada con fibrosis pulmonar idiopática.

Diffuse pulmonary ossification, a rare condition characterized by metaplastic ossification of the lung, is usually associated with diseases causing diffuse pulmonary lesions. Two types dendriform and nodular have been identified. In dendriform ossification, the less common type, osseous ramifications occur along the distal airways, with occasional islets of bone marrow. We report a case of diffuse dendriform pulmonary ossification associated with idiopathic pulmonary fibrosis. The diagnosis was based on histological examination, which demonstrated multiple nodules and ramified osseous spicules around the lung, mainly at the lower lobes, where the fibrotic lesions were also most evident.

Osificación pulmonar dendriforme asociada con fibrosis pulmonar idiopática / Dendriform pulmonary ossification associated with idiopathic pulmonary fibrosis

La osificación pulmonar difusa es una entidad poco frecuente en la que se produce una metaplasia ósea del pulmón y que suele asociarse con enfermedades que ocasionan lesiones pulmonares difusas. Existen dos tipos de osificación pulmonar: la dendriforme y la nodular. La forma dendriforme es la menos frecuente y se caracteriza por ramificaciones de estructura ósea a lo largo de las vías aéreas distales con islotes ocasionales de médula ósea. Se presenta un caso de osificación pulmonar difusa de tipo dendriforme asociada con fibrosis pulmonar idiopática. El diagnóstico se estableció mediante el examen histológico, que demostró la presencia de múltiples nódulos y espículas óseas ramificadas en la periferia del pulmón, principalmente en los lóbulos pulmonares inferiores, donde las lesiones fibróticas eran más evidentes. (AU)

Cryoglobulinemia in systemic lupus erythematosus: prevalence and clinical characteristics in a series of 122 patients.

OBJECTIVES: To determine the prevalence and nature of cryoglobulins in 122 patients with systemic lupus erythematosus (SLE) and identify the clinical and immunologic features related to their presence. METHODS: In a cross-sectional study, we investigated 122 consecutive patients (106 women and 16 men) with SLE who fulfilled the 1982 revised criteria of the American College of Rheumatology for the classification of SLE. All patients had documented medical histories and underwent a medical interview as well as a routine general physical examination by a qualified internist, and their clinical and serologic characteristics were collected on a protocol form. Serum samples were obtained at 37 degrees C, and cryoglobulinemia was estimated by centrifugation at 4 degrees C after incubation for 7 days in all patients. The type of cryoglobulinemia was identified by agarose gel electrophoresis and immunofixation. RESULTS: Cryoglobulins were detected in the sera of 31 SLE patients (25%): 20 patients (65%) had a cryocrit lower than 1%, 8 (26%) had percentages ranging between 1% and 5%, and only 3 patients (9%) had a cryocrit over 5%. Only cutaneous vasculitis (39% v 16%; P = .01) was more prevalent in patients with than in those without cryoglobulins. Rheumatoid factor (RF) (42% v 15%; P = .002) and low CH50 levels (84% v 49%; P <.001) were more prevalent in SLE patients with cryoglobulins. Hepatitis C virus (HCV) infection was investigated in 24 of the 31 cryoglobulinemic SLE patients and was detected in 5 (21%). In comparison, 4 (5%) of the 75 noncryoglobulinemic SLE patients studied were positive (P = 0.035; odds ratio, 4.67). Patients with a cryocrit greater than 1% showed a higher frequency of HCV infection than those with a cryocrit less than or equal to 1% (46% v 0%, P = .01). CONCLUSIONS: Cutaneous vasculitis, RF, hypocomplementemia, and HCV infection were associated with cryoglobulins in SLE patients. Testing for HCV infection is therefore recommended for patients with SLE and cryoglobulinemia to identify this subset of patients for prognostic and therapeutic reasons.

Hepatitis C virus infection mimicking primary Sjögren syndrome. A clinical and immunologic description of 35 cases.

Hepatitis C virus (HCV) infection is emerging as an extremely common and insidiously progressive liver disease that is often associated with several extrahepatic manifestations. In 1992, a possible relationship between Sjögren syndrome (SS) and patients with HCV infection was first postulated. Subsequently, several studies demonstrated that a "true" SS, with similar clinical and histologic features to those observed in primary SS, may occur in some patients with chronic HCV infection. We report the clinical and immunologic characteristics of 35 patients with chronic HCV infection and a well-documented diagnosis of SS. Compared with 60 patients with primary SS who tested negative for HCV antibodies, SS-HCV patients showed a higher mean age (65.9 yr versus 61.5 yr, p = 0.04), a lower prevalence of parotidomegaly (17% versus 47%, p = 0.004), and a higher prevalence of liver involvement (94% versus 3%, p < 0.001). Moreover, those patients with HCV-related SS showed a higher prevalence of anti-parietal cell gastric antibodies (31% versus 13%, p = 0.03), antimitochondrial antibodies (14% versus 2%, p = 0.02), cryoglobulinemia (60% versus 10%, p < 0.001), hypocomplementemia (60% versus 8%, p < 0.001), and a lower prevalence of anti-Ro/SS-A (17% versus 38%, p = 0.03). The "true" SS observed in some patients with HCV may be considered 1 of the extrahepatic manifestations of HCV, and we suggest that HCV infection can be considered as an exclusion criterion for the diagnosis of primary SS.

Cytopenia and past human parvovirus B19 infection in patients with primary Sjögren's syndrome.

OBJECTIVES: To determine the clinical significance of human parvovirus B19 infection in patients with primary Sjögren's syndrome (SS) and to investigate the immunologic and hematologic features related to B19 infection. METHODS: We included 80 consecutive patients with primary SS (74 women and 6 men), with a mean age of 62 years (range, 24 to 87 years) that were seen in our Unit. All patients fulfilled the European Community criteria for SS. As controls, we included 140 consecutive sera samples analyzed for B19 antibodies in our Microbiology Department and obtained from adult inpatients and outpatients of our Hospital. Serum from all patients and controls was tested for antibodies to B19 by enzyme-linked immunosorbent assay (ELISA). Additionally, the presence of B19 DNA in serum and in circulating leukocytes was investigated by nested polymerase chain reaction (PCR). RESULTS: Serological evidence of past B19 infection (positive IgG antibodies without IgM antibodies) was present in 28 (35%) patients with primary SS. None of these patients showed evidence for B19 viremia, and B19 virus DNA was not detected in the circulating leukocytes of IgG-B19(+) patients. Positivity for IgM antibodies to B19 was not detected in any patient. When compared with patients without evidence of past B19 infection, those with primary SS and past B19 infection showed a higher prevalence of cytopenia (57% v 15%; P < .001), and, specifically, of leukopenia (36% v 4%; P < .001). Additionally, when compared with controls positive for IgG-B19, SS patients with these antibodies had a higher prevalence of cytopenia (57% v 13%; P < .001), leukopenia (36% v 3%; P < .001) and thrombocytopenia (21% v 0%; P = .003). CONCLUSIONS: Serological evidence of past B19 infection is associated with the presence of cytopenia in our patients with primary SS. A possible relationship between B19 infection and the presence of cytopenia in primary SS may occur in some patients immunologically or genetically predisposed.

Mixed cryoglobulinemia: new concepts.

The most documented extrahepatic manifestation of hepatitis C virus (HCV) infection is mixed cryoglobulinemia (MC). MC is characterised by the presence of temperature-sensitive protein complexes: in type II MC, cryoglobulins are composed of a monoclonal rheumatoid factor (usually, IgMkappa) against polyclonal IgG. In type III MC, all components are polyclonal. The presence of microheterogeneity and other new types of cryoglobulins is a novel and recent observation. The production of different autoantibodies and circulating immune complexes, including the cryoglobulins, are responsible for systemic vasculitis and various organ damage. In a limited number of MC patients, a malignancy, that is B-cell non-Hodgkin's lymphoma or hepatocellular carcinoma, may also develop. Finally, results of interferon and/or ribavirin treatments in MC patients represent an indirect proof for the pathogenetic link between MC and HVC infection. The discovery of the relation between HCV infection and MC shows the striking association between a viral infection and an autoimmune disease and, thus, a potential link between the systemic autoimmune and lymphoproliferative disorders.

Hepatitis C virus infection mimicking systemic lupus erythematosus: study of hepatitis C virus infection in a series of 134 Spanish patients with systemic lupus erythematosus.

OBJECTIVE: To determine the prevalence and clinical significance of hepatitis C virus (HCV) infection in patients with systemic lupus erythematosus (SLE). METHODS: We investigated 134 consecutive SLE patients (121 women and 13 men; mean age 35 years) who fulfilled the 1982 revised criteria for SLE of the American College of Rheumatology. Two hundred consecutive volunteer blood donors were also studied. Serum from all patients and controls was tested for antibodies to HCV (by third generation enzyme-linked immunosorbent assay and confirmed by third generation recombinant immunoblot assay [RIBA-3]). RESULTS: Antibodies to HCV were present in 18 patients with SLE (13%) and in 2 (1%) of the blood donors studied. Among the anti-HCV-positive group, HCV infection was confirmed (by RIBA-3 and polymerase chain reaction) in 15 SLE patients (11%) and in the 2 blood donors (1%) (P < 0.001). We observed a lower frequency of cutaneous SLE features (40% versus 76%; P = 0.01) and positivity for anti-double-stranded DNA (anti-dsDNA) (33% versus 81%; P < 0.001), and a higher frequency of hepatic involvement (93% versus 2%; P < 0.001), low C4 levels (73% versus 39%; P = 0.002), low CH50 levels (73% versus 44%; P = 0.03), and cryoglobulins (60% versus 22%; P = 0.02) in SLE patients with HCV infection compared with SLE patients without infection. CONCLUSION: The prevalence of HCV infection in SLE patients was higher than in blood donors from the same geographic area. SLE HCV-positive patients showed a lower frequency of cutaneous SLE features and anti-dsDNA antibodies, and a higher prevalence of liver involvement, hypocomplementemia, and cryoglobulinemia. HCV testing should be considered in the diagnosis of SLE, especially in patients who lack the typical cutaneous features of SLE or who have low titers of autoantibodies, cryoglobulinemia, or liver involvement.

Suppression of total digoxin concentrations by digoxin-like immunoreactive substances in the MEIA digoxin assay. Elimination of negative interference by monitoring free digoxin concentrations.

Digoxin-like immunoreactive substances (DLIS) cross-react with antidigoxin antibody and falsely elevate immunoassay-measured total digoxin concentrations. The fluorescence polarization immunoassay (FPIA) for digoxin showed high cross-reactivity with DLIS, but a new microparticle enzyme immunoassay (MEIA) had low cross-reactivity. The concentration of digoxin in the presence of DLIS was falsely lowered (negative interference) when measured by MEIA. We prepared the following serum pools: 2 normal (no DLIS), 2 from patients with uremia, and 3 from patients with liver disease (high DLIS). No patients received digoxin or digitoxin. When normal pools were supplemented with known concentrations of digoxin, total and free concentrations measured by both assays were comparable, but when liver and uremic pools containing high DLIS were supplemented with digoxin, the measured total digoxin concentrations were lower by MEIA and higher by FPIA. However, by taking advantage of 25% protein binding of digoxin and high protein binding of DLIS, free digoxin levels were not affected by DLIS. In 2 patients receiving digoxin but without volume expansion, total and free digoxin concentrations measured by both assays were comparable; in the 2 volume-expanded patients, only free digoxin concentrations were comparable. Monitoring free digoxin concentration can eliminate negative interference of DLIS in the MEIA for digoxin.

Cryoglobulinemia in primary Sjögren's syndrome: prevalence and clinical characteristics in a series of 115 patients.

OBJECTIVES: To determine the prevalence and nature of cryoglobulins in a large series of patients with primary Sjögren's syndrome (SS) and identify the clinical and immunologic features related to their presence. METHODS: In a cross-sectional study, we investigated 115 consecutive patients (107 women and eight men) with primary SS. All patients fulfilled four or more of the preliminary diagnostic criteria for SS proposed by the European Community Study Group in 1993. Serum cryoglobulinemia was measured in all patients. Serum samples were obtained at 37 degrees C, and cryoglobulinemia was estimated by centrifugation after incubation at 4 degrees C for 7 days. The type of cryoglobulinemia was identified by agarose gel electrophoresis and immunofixation. RESULTS: Cryoglobulins were detected in the sera of 18 (16%) of our patients with primary SS; most were IgMkappa monoclonal/IgG polyclonal. When compared with patients without cryoglobulins, those with cryoglobulins presented a higher prevalence of leukocytoclastic cutaneous vasculitis (56% v8%, P < .001), hypocomplementemia (75% v 2%; P < 0.001) and antibodies to hepatitis C virus (HCV) (47% v8%, P < .001). Liver involvement (clinical signs, biochemical features, or ultrasound/histological data of liver disease) was present in all patients (100%) with cryoglobulins and HCV infection but in only 11% of patients with cryoglobulins without HCV infection (P < .001). CONCLUSIONS: Leukocytoclastic cutaneous vasculitis, hypocomplementemia, and HCV infection are associated with the presence of cryoglobulins in the sera of patients with primary SS. Testing for HCV infection is recommended for patients with SS and cryoglobulinemia because of its high prevalence and its strong association with liver disease.

Pleural effusion in patients infected with the human immunodeficiency virus.

In order to analyze the etiology, cytological and biochemical characteristics, and outcome of pleural disease in patients infected with HIV, the medical records of 86 HIV-positive patients with pleural effusion were reviewed. Controls were 106 HIV-negative patients with parapneumonic or tuberculous effusion. Most HIV-positive patients were intravenous drug abusers (95.3%). Pleural effusions in HIV-positive patients were caused by infections in 76 (89.4%) cases. Parapneumonic effusion was diagnosed in 59 patients and tuberculous pleuritis in 15 patients. Staphylococcus aureus was the most frequently isolated bacteria. Parameters for differentiating complicated cases of parapneumonic exudate from uncomplicated cases, such as pleural fluid pH < 7.20 (sensitivity 80% vs. 84.3%), pleural fluid glucose < 35 mg/dl (sensitivity 45% vs. 56.25%) pleural fluid LDH > 1600 UI/l (sensitivity 85% vs. 62.50%), showed similar sensitivity in HIV-positive and HIV-negative patients. Monocytes in pleural fluid were significantly decreased in tuberculous pleuritis in HIV-positive patients (506 +/- 425 vs. 1014 +/- 1196 monocytes/ml, p < 0.05). No significant differences were detected in the outcome of HIV-positive and HIV-negative patients with pleural disease. It can be concluded that the pleural effusion was of predominantly infectious etiology in HIV-positive patients from populations with a high prevalence of intravenous drug abuse. Neither the biochemical parameters in pleural fluid nor the outcome differed significantly between HIV-positive and HIV-negative patients.