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Objective: To describe the clinical and immunologic characteristics of a large series of patients with systemic autoimmune diseases (SAD) associated with chronic hepatitis C virus (HCV) infection., Methods: The HISPAMEC Registry is a multicenter international study group dedicated to collecting data on patients diagnosed with SAD with serological evidence of chronic HCV infection. The information sources are cases reported by physicians of the HISPAMEC Study Group and periodic surveillance of reported cases by a Medline search updated up to December 31, 2007., Results: One thousand twenty HCV patients with SAD were included in the registry. Patients were reported from Southern Europe (60%), North America (15%), Asia (14%), Northern Europe (9%), South America (1%), and Australia (1%). Countries reporting the most cases were Spain (236 cases), France (222 cases), Italy (144 cases), USA (120 cases), and Japan (95 cases). The most frequently reported SAD were Sjögren's syndrome (SS; 483 cases), rheumatoid arthritis (RA; 150 cases), systemic lupus erythematosus (SLE; 129 cases), polyarteritis nodosa (78 cases), antiphospholipid syndrome (59 cases), inflammatory myopathies (39 cases), and sarcoidosis (28 cases). Twenty patients had 2 or more SAD. Epidemiological data were available in 677 cases. Four hundred eighty-seven (72%) patients were female and 186 (28%) male, with a mean age of 49.5 +/- 1.0 years at SAD diagnosis and 50.5 +/- 1.1 years at diagnosis of HCV infection. The main immunologic features were antinuclear antibody (ANA) in 61% of patients, rheumatoid factor (RF) in 57%, hypocomplementemia in 52%, and cryoglobulins in 52%. The main differential aspect between primary and HCV-related SAD was the predominance of cryoglobulinemic-related markers (cryoglobulins, RF, hypocomplementemia) over specific SAD-related markers (anti-ENA antibodies, anti-dsDNA, anti-cyclic citrullinated peptide) in patients with HCV., Conclusion: In the selected cohort, the SAD most commonly reported in association with chronic HCV infection were SS (nearly half the cases), RA and SLE. Nearly two thirds of SAD-HCV cases were reported from the Mediterranean area. In these patients, ANA, RF and cryoglobulins are the predominant immunological features.

Objective: Hyperprolactinemia (HPRL) has been identified in more than half of patients with systemic sclerosis (SSc). However, the association with pituitary adenoma and the status of hypothalamic dopaminergic tone using metoclopramide (MTC) test has not been studied. We investigated the prevalence of prolactin (PRL)-secreting pituitary adenoma and evaluated production of PRL by dynamic testing with MTC in SSc., Methods: We studied 30 patients with SSc (mean age 38 +/- 10 yrs) and 20 healthy controls (mean age 37 +/- 11 yrs). Serum PRL concentrations were determined by radioimmunoassay in all subjects, and PRL response was measured 30, 60, 90, and 120 min after injection of 10 mg of MTC. Computed tomography (CT) of the sella turcica was performed., Results: The mean basal serum PRL levels before and after stimulation with MTC in SSc patients versus controls were: basal 18.2 +/- 5.4 versus 8.7 +/- 1.6 ng/ml, p = NS; 30 min: 175.0 +/- 5.4 versus 61.0 +/- 42 ng/ml, p < 0.001; 60 min: 160 +/- 64 versus 52 +/- 30 ng/ml, p < 0.001; 90 min: 125 +/- 57 versus 42 +/- 21.0 ng/ml, p < 0.05; 120 min: 108.0 +/- 57 versus 30.0 +/- 10 ng/ml, p < 0.005. CT scan showed microadenomas in 24/30 SSc patients and 1/20 controls (p = 0.001)., Conclusion: Our study suggests that a group of patients with SSc have a high prevalence of HPRL with increased central dopaminergic tone, and microadenomas. PRL may have a role in the pathogenesis of SSc. Further studies are necessary to confirm our results.

Objective: The role of prolactin (PRL) in the pathogenesis of systemic lupus erythematosus (SLE) is controversial. The effect of conventional treatment (steroids, antimalarials, immunosuppressor drugs) on PRL concentrations is unclear. We investigated correlation of PRL levels with lupus activity in patients at entry and after 6 months of conventional treatment., Methods: We studied 43 female patients with active SLE, who were divided in 2 groups; Group 1: 16 patients with minor organ involvement (cutaneous and articular involvement), and Group 2: 27 patients with major organ involvement (glomerulonephritis). Controls were 36 healthy individuals. PRL levels were determined by an immunoradiometric assay at entry and after 6 months of treatment. PRL levels were correlated with SLE Disease Activity Index (SLEDAI) score., Results: Mild hyperprolactinemia (HPRL, 20-40 ng/ml) was found in 30/43 (69.7%) SLE patients. After 6 months of treatment a reduction in PRL levels was found in both groups: Group 1: 24.3 +/- 10.8 to 16.96 +/- 10.87 ng/ml (p < 0.001); and Group 2: 23.6 +/- 5.7 to 12.07 +/- 11.13 ng/ml (p < 0.001). The SLEDAI score also decreased after treatment: Group 1: 16.5 +/- 5.9 to 2.1 +/- 1.3 (p < 0.001); Group 2: 16.8 +/- 5.4 to 1.6 +/- 1.4 (p < 0.001). At entry and after treatment, a significant correlation between PRL levels and SLEDAI score was found in all patients (r = 0.4946, p = 0.0007, and r = 0.9086, p = 0.0001, respectively)., Conclusion: HPRL was associated with SLE disease activity. Conventional immunosuppressive therapy decreased PRL levels in direct correlation with decreased SLE activity. This finding emphasizes that PRL may play a role in the pathogenesis and clinical expression of SLE.

Objective: To determine the efficacy of danazol for refractory autoimmune thrombocytopenia or Evans' syndrome complicating systemic lupus erythematosus (SLE)., Methods: We studied 16 consecutive patients with SLE and corticosteroid refractory autoimmune thrombocytopenia; 3 patients had coexisting autoimmune hemolysis (Evans' syndrome). Five patients had undergone splenectomy. Danazol was commenced at 200 mg/day, and increased stepwise (maximum 1200 mg/day) until benefit or toxicity was observed. After remission the danazol dose was gradually reduced to 200-400 mg/day., Results: All 16 patients achieved a complete remission (platelet count >100 x 10(9)/l, hematocrit >39%) 2 months after starting danazol (range 6 weeks-8 months). Remission persisted during continued danazol therapy (mean followup 18.2 months, range 2-49 months). One patient with Evans' syndrome required discontinuation of danazol because of jaundice and biopsy proven minimal hepatic necrosis: hemolysis recurred after discontinuation of danazol., Conclusion: Danazol is effective for the treatment of autoimmune thrombocytopenia or Evans' syndrome complicating SLE irrespective of splenectomy status. Longer followup will be needed to determine whether the remission persists after withdrawal of danazol.

Objective: Accumulated evidence suggests that certain immunoregulatory hormones including prolactin (PRL) may play a role in the pathogenesis and disease expression of certain autoimmune diseases. Our objective was to investigate the possible role of PRL in the pathogenesis and disease expression of the spondyloarthropathies, including Reiter's syndrome (RS)., Methods: Basal levels of PRL (serum) were determined by radioimmunoassay in patients with various types of spondyloarthropathies, patients with acute anterior uveitis (AAU), and healthy controls. Clinical manifestations at the time of serum collection were correlated with PRL levels., Results: Hyperprolactinemia (PRL > 20 ng/ml) was found in 9 of 25 (36%) patients with RS. In contrast, only 1 of 34 (2.9%) (p < 0.001) patients with ankylosing spondylitis and none of the patients with psoriatic arthritis, AAU or healthy controls had hyperprolactinemia. The frequency of conjunctivitis, urethritis, dysentery, and uveitis was higher in hyper than in normoprolactinemic patients with RS., Conclusion: Our results suggest a possible role for this immunoregulatory hormone in the pathogenesis and disease expression of RS.

Objective: Assess the impact of human immunodeficiency virus (HIV) infection on the onset of rheumatic manifestations in HIV+ patients, and to compare them with a control HIV- group with similar risk factors., Methods: We prospectively studied 74 consecutive HIV+ patients, looking for clinical and laboratory findings of rheumatic manifestations and compared them with 72 control subjects with similar risk factors for HIV who tested negative for HIV., Results: Rheumatic manifestations were more frequently observed in the HIV+ group than the HIV-group (p < 0.001): Arthralgias were found in 34 (45%), arthritis in 8 (10%), and Reiter's syndrome in 6 (8%). Laboratory findings revealed rheumatoid factor in 16 (21%) HIV+ vs 2 (2%) in HIV-, antinuclear antibodies in 13 (17%) HIV+ vs 0 in HIV-, IgG anticardiolipin antibodies in 70 (94%) HIV+ vs 7 (9%) in HIV- (p < 0.001). Hyperuricemia was found in 31 HIV+ patients (41%), and hypouricemia in 4 (5%), compared with none in the HIV- group (p < 0.0001). Neoplasia were identified in 13 HIV+ patients, in 7 associated with hyperuricemia and 3 with hypouricemia. Of interest, 2 patients had urate abnormalities before the diagnosis of neoplasia., Conclusions: Our study suggests that rheumatic manifestations are more prevalent in HIV+ patients. In advanced HIV infection, hypo and hyperuricemia may be considered markers of neoplasia.

In the last decade, methotrexate (MTX) has emerged as a useful second line agent for a variety of arthritides. However, there still exists some reluctance for its wider use mainly because of concerns about its liver side effects. We describe our clinical experience with this drug in psoriatic arthritis (PsA). The study group included 24 men and 16 women, with a mean age of 47 years (16-75), with oligoarticular (13) or polyarticular (27) involvement, with a mean disease duration of 12 years (1-36). Patients received a mean dose of 11.2 mg of MTX orally/week during a mean period of 34 months (6-132). Seven had been previously treated with other second line agents. Thirty-eight patients had an excellent or good response. In them, the erythrocyte sedimentation rate dropped in a mean of 38 mm/h. Only 2 patients had a rather poor response. Two patients discontinued the medication because of side effects: leukopenia in one and stomatitis in the other. Eleven patients presented with liver test abnormalities: 3 mild, 6 moderate and 2 severe. Seven patients had 11 liver biopsies. Except for one, none had evidence of cirrhosis or inflammation. Indeed, no changes were observed in the histopathology in those with repeated biopsies. The case reported as cirrhosis occurred very early in the course of MTX therapy. He continued taking MTX treatment without further deterioration of liver chemistry and/or histology. It is concluded that MTX is an effective and safe agent in PsA. Results also indicate that it is not necessary to perform liver biopsies on a routine basis.

We report the first case of systemic lupus erythematosus with hyperviscosity syndrome as the presenting manifestation. A polyclonal increase in all immunoglobulins was observed. Ultracentrifuge studies showed 17-19S intermediate immune complexes (IC) composed primarily of autoreactive IgG demonstrated at acid pH. This was confirmed by chromatographic fractionation of sera, since the intermediate IC eluted as did purified heat aggregated IgG. Small amounts of IgM and IgA in the intermediate IC were also demonstrated by more sensitive techniques, i.e., nephelometry, polyacrylamide gel electrophoresis, and electrophoretic blotting. The decrease of serum viscosity was associated with the decrease of circulating IC after plasmapheresis or combined treatment of prednisone and cyclophosphamide. Serum viscosity bore no relationship to the amount of dissociated immunoglobulins.