Search

Purpose: To evaluate comorbidity, complexity and poor outcomes in patients with sarcoidosis and to compare those scores with a control group., Methods: 218 consecutive patients were diagnosed with sarcoidosis according to the ATS/ERS/WASOG criteria; extrathoracic involvement was evaluated using the 2014 WASOG organ assessment instrument. Sarcoidosis patients were compared with an age- and gender-matched control group of primary care outpatients without sarcoidosis. Comorbidities were assessed retrospectively using the Charlson Comorbidity Index (CCI); complexity was evaluated according to the classification into Clinical Risk Groups (CRG) and severity levels., Results: The cohort included 142 women and 76 men; the mean age was 47.1 years at diagnosis of sarcoidosis and 55.9 years at the last visit. Patients with a CCI > 1 had a higher frequency of calcium/vitamin D abnormalities (p < 0.001), kidney involvement (p = 0.005) and a higher mortality rate (p < 0.001) compared with patients with a CCI ≤ 1. Patients with a CRG ≥ 6 had a higher frequency of extrathoracic involvement (p = 0.039), calcium/vitamin D abnormalities (p = 0.019) and treatment with glucocorticoids (p = 0.032) compared with patients with a CRG < 6. 11% patients died after a mean follow-up of 102.3 months. Country of birth, kidney involvement and extrathoracic disease were significantly associated with death. Patients with sarcoidosis had a higher frequency of liver (p < 0.001), pulmonary (p = 0.002) and autoimmune disease (p = 0.011) and cancer (p = 0.007) compared with the control group., Conclusion: We found higher rates of comorbidity and complexity in patients with sarcoidosis compared with a control group. Liver, pulmonary, autoimmune and neoplastic diseases were the main comorbidities found in patients with sarcoidosis.

Systemic sclerosis (SSc) is a rare, multisystem disease showing a large individual variability in disease progression and prognosis. In the present study, we assess survival, causes of death, and risk factors of mortality in a large series of Spanish SSc patients. Consecutive SSc patients fulfilling criteria of the classification by LeRoy were recruited in the survey. Kaplan-Meier and Cox proportional-hazards models were used to analyze survival and to identify predictors of mortality. Among 879 consecutive patients, 138 (15.7%) deaths were registered. Seventy-six out of 138 (55%) deceased patients were due to causes attributed to SSc, and pulmonary hypertension (PH) was the leading cause in 23 (16.6%) patients. Survival rates were 96%, 93%, 83%, and 73% at 5, 10, 20, and 30 years after the first symptom, respectively. Survival rates for diffuse cutaneous SSc (dcSSc) and limited cutaneous SSc were 91%, 86%, 64%, and 39%; and 97%, 95%, 85%, and 81% at 5, 10, 20, and 30 years, respectively (log-rank: 67.63, P < 0.0001). The dcSSc subset, male sex, age at disease onset older than 65 years, digital ulcers, interstitial lung disease (ILD), PH, heart involvement, scleroderma renal crisis (SRC), presence of antitopoisomerase I and absence of anticentromere antibodies, and active capillaroscopic pattern showed reduced survival rate. In a multivariate analysis, older age at disease onset, dcSSc, ILD, PH, and SRC were independent risk factors for mortality. In the present study involving a large cohort of SSc patients, a high prevalence of disease-related causes of death was demonstrated. Older age at disease onset, dcSSc, ILD, PH, and SRC were identified as independent prognostic factors.

Objective: To describe how systemic disease is treated in a large cohort of Spanish patients with primary Sjögren syndrome (pSS) in daily practice, focusing on the adequacy of therapies for the level of systemic activity measured by ESSDAI score., Patients and Methods: By December 2014, our database included 1120 consecutive patients who fulfilled the 2002 classification criteria for SS. Therapeutic schedules were classified into 4 categories: no systemic therapies, hydroxychloroquine (HCQ) and/or low dose glucocorticoids (GCS) (<20mg/day), high dose GCS (>20mg/day) and use of second-line therapies (immunosuppressive agents, intravenous immunoglobulins [IVIG] and/or rituximab [RTX])., Results: There were 1048 (94%) women and 72 (6%) men , with a mean age at diagnosis of 54 years. The main drug-based therapeutic approaches for systemic pSS during follow-up were HCQ in 282 (25%) patients, GCS in 475 (42%, at doses >20mg/day in 255-23%), immunosuppressive agents in 148 (13%), IVIG in 25 (2%) and RTX in 35 (3%) patients. HCQ was associated with a lower risk of death (adjusted HR of 0.57, 95% 0.34-0.95). We classified 16 (7%) of the 255 patients treated with >20mg GCS and 21/148 (14%) treated with immunosuppressive agents as patients inadequately treated, mainly associated with articular involvement of low/moderate activity., Conclusion: The management of pSS should be organ-specific, using low dose GCS in patients with moderate systemic activity, limiting the use of high dose GCS and second-line therapies to refractory or potentially severe scenarios. The use of systemic therapies for dryness, chronic pain or fatigue is not warranted., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The aim of this article is to study the evidence-based knowledge related to the use of biological therapies in patients diagnosed with idiopathic inflammatory myopathy (dermatomyositis, polymyositis and inclusion body myositis). In this review the leading published studies related to the use of biological therapy in patients with myositis are analysed; mainly those with high methodological standards, that means randomized and controlled studies. Methodological drawbacks due to the rarity and heterogeneity of these complex diseases are also addressed. Up to now is not possible to ascertain the biologics as a recommended therapy in patients with myositis, at least based in the current evidence-based knowledge, although it can not be neglected as a therapeutic option in some clinical situations, taking into account the scarce of effective treatments in those patients, especially in refractory myositis. Future studies probably will help to better define the role of biological therapies in patients with idiopathic inflammatory myopathy., (Copyright © 2013 Elsevier España, S.L.U. All rights reserved.)

Objective: To evaluate systemic involvement in primary SS in a large cohort of Spanish patients using the EULAR-SS disease activity index (ESSDAI) definitions., Methods: Systemic involvement was characterized using ESSDAI definitions for the 10 clinical domains (constitutional, lymphadenopathy, glandular, articular, cutaneous, pulmonary, renal, peripheral nervous system, central nervous system and muscular). ESSDAI scores at diagnosis, during follow-up and cumulated at the last visit were calculated., Results: The cohort consisted of 921 patients. After a mean follow-up of 75 months, 77 (8%) patients still had an ESSDAI score of zero at the last visit. Organ by organ, the percentage of patients who developed activity during the follow-up (ESSDAI score ≥ 1 at any time) ranged between 1.4% and 56%, with articular, pulmonary and peripheral neurological involvement being the most common. Logistic multivariate regression analysis showed the following features at diagnosis and had the closest association with systemic activity (statistically significant independent variables in at least two domains): cryoglobulinaemia in five domains; anaemia, lymphopenia and low C3 levels in three domains each and age <35 years in two domains. Sicca features, ANA and RF at diagnosis were not associated with a higher cumulated activity score in any clinical domain., Conclusion: Primary SS is undeniably a systemic disease, with the joints, lungs, skin and peripheral nerves being the most frequently involved organs. Cytopenias, hypocomplementaemia and cryoglobulinaemia at diagnosis strongly correlated with higher cumulated ESSDAI scores in the clinical domains. Clinically the ESSDAI provides a reliable picture of systemic involvement in primary SS.

Objective: The objective of this paper is to evaluate the prevalence and characterize the main epidemiological, clinical and immunological features of annular erythema (AE) in non-Asian patients with primary Sjögren's syndrome (SS)., Methods: We carried out a retrospective study searching for AE in 377 Spanish patients with primary SS fulfilling the 2002 American-European criteria. In addition, we searched PubMed (1994-2012) using the MeSH terms "annular erythema" and "primary Sjögren's syndrome" for additional cases. All cases with AE reported in patients with SS associated with systemic lupus erythematosus were excluded., Results: In our Spanish cohort, we found 35 (9%) patients diagnosed with AE. All were white females, with a mean age of 47 years at diagnosis of AE. AE preceded diagnosis of SS in 27 (77%) patients. Cutaneous AE lesions involved principally the face and upper extremities. All patients reported photosensitivity, with cutaneous flares being reported during the warmest months in 93% of patients. Immunological markers consisted of anti-Ro/La antibodies in 31 (89%) patients. In the literature search, we identified eight additional non-Asian patients with primary SS diagnosed with AE. In comparison with 52 Asian patients, the 43 non-Asian patients with AE related to primary SS were more frequently women (100% vs 78%, p=0.008), and cutaneous lesions were less frequently reported in the face (55% vs 81%, p=0.045) and more frequently in the neck (40% vs 14%, p=0.041). Immunologically, non-Asian patients had a lower frequency of anti-Ro antibodies and a higher frequency of negative Ro/La antibodies, although the differences were not statistically significant., Conclusion: AE is not an exclusive cutaneous feature of Asian patients with primary SS. In addition to the characteristic cutaneous expression, AE has a very specific clinical and immunological profile: often presenting before the fulfillment of SS criteria, overwhelmingly associated with anti-Ro antibodies but weakly associated with other immunological markers and the main systemic SS-related features.

Objectives: To characterise patients diagnosed with fibromyalgia (FM) who present a clinical profile suggestive of simulation., Methods: Observational case-control study of 218 patients who met the classification criteria for FM. The profile supporting simulation was based on the proposed criteria for evaluating disability related to the simulation of pain., Results: Compared with controls (n=105), patients with suspected simulation of FM (n=106) had a higher mean age (52.5 vs. 49.2 years, p=0.003), a higher frequency of primary education (88.7% vs. 58.1%; p<0.001), a higher percentage of separated/widowed persons (33.9% vs. 8.6%, p<0.001), a higher frequency of psychiatric disorders (100% vs. 67.6%, p<0.001), a higher mean number of positive 'control' tender points (4.5 vs. 1.3, p<0.001), a higher mean FIQ questionnaire score (89.8 vs. 68.8, p<0.001) and a lower mean LHS questionnaire score (41.0 vs. 59.9, p<0.001). Patients with suspected simulation were able to walk a shorter distance in the 6-minute walk test than controls (231.0 vs. 356.3 metres, p<0.001), while the appearance of allodynia was achieved with a significantly lower mmHg pressure (159.8 vs. 229.9 mm Hg, p<0.001)., Conclusions: Some physical/functional tests, together with the administration of specific questionnaires, may identify a subgroup of patients with FM with a profile consistent with simulation or malingering; these patients have a differentiated demographic and psychiatric profile in comparison with FM patients without a profile of simulation.

Objectives: This paper aims to analyse the etiology, characterisation and outcomes of the different types of peripheral neuropathy in patients with primary Sjögren's syndrome (SS) and their association with clinical and immunological disease expression., Methods: A total of 563 consecutive patients diagnosed with primary SS were evaluated. We retrospectively assessed the results of nerve conduction studies carried out in patients with suspected peripheral nervous system involvement. Peripheral neuropathies were classified into mononeuropathy, mononeuropathy multiplex, polyneuropathy and neuronopathy according to the patterns evidenced by electrodiagnostic studies., Results: Nerve conduction studies were carried out in 158/563 (28%) SS patients. The results were normal in 49 and abnormal in 109 patients, in whom peripheral neuropathy was diagnosed in 102. After excluding patients with neuropathy associated with other diseases and patients with entrapment mononeuropathies, 55/563 (10%) patients were classified as having SS-related peripheral neuropathy, including axonal sensorimotor polyneuropathy (n=24), pure sensory neuronopathy (n=15), mononeuropathy multiplex (n=15) and demyelinating polyradiculoneuropathy (n=1). In spite of therapy, clinical progression measured by the MOHS scale was observed in 12% of patients with axonal polyneuropathy, 13% of those with mononeuropathy multiplex and 47% of those with neuronopathy. Survival was significantly reduced in patients with peripheral neuropathy (especially in those with mononeuropathy multiplex and axonal polyneuropathy) in comparison with the control group (log rank =0.001)., Conclusions: We found a prevalence of SS-related peripheral neuropathy of 10%. Classification of neuropathy according to the clinical presentation and electrodiagnostic tests may be useful in determining the functional outcome, therapeutic response and survival.

Objective: To investigate the incidence of clinical and immunological characteristics of a large cohort of Spanish patients with scleroderma (SSc) and identifying factors associated with particular organ manifestations assessed by a nationwide cross-sectional analysis., Methods: We classified SSc patients in 4 subsets using a modification of LeRoy and Medsger classification that included: "prescleroderma" (pre-SSc), limited cutaneous SSc (lcSSc), diffuse cutaneous SSc (dcSSc), and SSc sine scleroderma (ssSSc). Fourteen Spanish centers participated in patient recruitment. On January 2008, the database included 916 consecutive Spanish SSc patients, 801 women (87.4%) and 115 men (12.6%), all of whom fulfilled the classification criteria proposed by LeRoy and Medsger. Epidemiological, clinical, and laboratory data were collected according to a standard protocol. Mean age at diagnosis was 51.2 ± 15.1 years and mean age at disease onset was 44.9.0 ± 15.8 years. lcSSc was the most frequent subset (61.8%) followed by dcSSc (26.5%), ssSSc (7.5%), and preSSc (4%) subsets. Gender ratios were as follows: dcSSc subset, 200 women and 43 men (4.7:1); lcSSc subset, 503 women and 63 men (ratio 7.9:1), and ssSSc subset, 62 women and 7 men (ratio 8.9:1). Digital ulcers, interstitial lung disease (ILD), musculoeskeletal and esophageal involvement, and scleroderma renal crisis were more frequent in dcSSc than lcSSc and ssSSc subsets. The incidence of pulmonary arterial hypertension assessed by echocardiography was similar in all subsets but mean estimated systolic pulmonary arterial pressure was higher in ssSSc than in lcSSc subset (47.3 ± 23.9 mm Hg vs 39.6 ± 19.2 mm Hg; P < 0.03). Cardiac involvement was identified more frequently in ssSSc than in dcSSc and lcSSc subsets (49.3% vs 32.5% and 31.1%, respectively; P = 0.015 and P = 0.004 for both comparisons). Acro-osteolysis (8.2% vs 2.4%, P = 0.049), calcinosis (19.8% vs 7.2%, P < 0.05), and sicca syndrome (37.5% vs 14.5%, P < 0.0001) were more frequent in lcSSc than in ssSSc subsets. The frequency of clinical manifestations related to the presence of anticentromere antibodies or antitopoisomerase I antibodies was very similar to that identified in patients categorized to lcSSc and dcSSc, respectively. However, in multivariate studies, the ranking of the variables according to their overall explanatory effect on the model showed that the contributory effect of the antibody status was not greater than that of the clinical categorization into lcSSc and dcSSc for the majority of disease manifestations, but, in important manifestations, as ILD, absence of anticentromere antibodies was an independent predictor factor., Conclusions: The classification of SSc into dcSSc, lcSSc, and ssSSc subsets is the one that most closely reflects the natural history of the disease, as they presented clear clinical differences. The immunological profile helps to define important visceral alteration as ILD. Finally, to improve early diagnosis of SSc, patients with preSSc should be considered both to trace the true evolution of the disease and to define which patients could benefit from therapeutic measures able to prevent the appearance of visceral involvements., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objectives: To analyse the safety and efficacy of the off-label use of rituximab in patients with severe, refractory systemic autoimmune diseases., Methods: In 2006, the Study Group on Autoimmune Diseases of the Spanish Society of Internal Medicine created the BIOGEAS project, a multicenter study devoted to collecting data on the use of biological agents in adult patients with systemic autoimmune diseases refractory to standard therapies (failure of at least two immunosuppressive agents)., Results: One hundred and ninety-six patients with systemic autoimmune diseases treated with rituximab have been included in the Registry (158 women and 38 men, mean age 43 years). Systemic autoimmune diseases included systemic lupus erythematosus (107 cases), inflammatory myopathies (20 cases), ANCA-related vasculitides (19 cases), Sjögren's syndrome (15 cases) and other diseases (35 cases). A therapeutic response was evaluable in 194 cases: 99 (51%) achieved a complete response, 51 (26%) a partial response and 44 (23%) were classified as non-responders. After a mean follow-up of 27.56+/-1.32 months, 44 (29%) out of the 150 responders patients relapsed. There were 40 adverse events reported in 33 (16%) of the 196 patients. The most frequent adverse events were infections, with 24 episodes being described in 19 patients. Thirteen (7%) patients died, mainly due to disease progression (7 cases) and infection (3 cases)., Conclusions: Although not yet licensed for this use, rituximab is currently used to treat severe, refractory systemic autoimmune diseases, with the most favourable results being observed in Sjögren's syndrome, inflammatory myopathies, systemic lupus erythematosus and cryoglobulinemia.

Biological agents are increasingly used for a rapidly-expanding number of rheumatic and systemic autoimmune diseases, with a growing number of reports of the paradoxical induction of autoimmune processes, overwhelmingly associated with anti-TNF agents. In this review, we analyze the clinical characteristics and outcomes of autoimmune diseases developing after biological therapies through a baseline Medline search as one of the objectives of the BIOGEAS project, created by the Spanish Society of Internal Medicine. The latest update of our registry (15 July 2009) included more than 800 cases of autoimmune diseases secondary to biological therapies, including a wide variety of both systemic (lupus, vasculitis, sarcoidosis and antiphospholipid syndrome) and organ-specific (interstitial lung disease, uveitis, optic neuritis, peripheral neuropathies, multiple sclerosis and autoimmune hepatitis) autoimmune processes. The majority of cases appeared between one month and one year after initiation of the biological agent and complete resolution was observed in nearly 75% of cases after cessation of therapy. The induced autoimmune diseases with the poorest outcomes were interstitial lung disease, inflammatory ocular disease and central nervous system demyelinating diseases., (Copyright 2009 Elsevier B.V. All rights reserved.)

Objective: To analyze the prevalence and clinical characteristics of chronic hepatitis B virus (HBV) infection in a large series of patients with Sjögren syndrome (SS)., Methods: We investigated the prevalence of chronic HBV infection in 603 consecutive patients with SS diagnosed in our department between 1994 and 2008. There were 517 patients with primary SS (482 women and 35 men, with a mean age at the time of fulfillment of the classification criteria of 57 years) and 86 patients with SS associated with chronic HCV infection (66 women and 20 men, with a mean age at the time of fulfillment of the classification criteria of 65 years). All patients fulfilled 4 or more of the 1993 European Community Study Group criteria for SS., Results: The presence of HBsAg+ was detected in five (0.83%) of the 603 patients with SS. All HBsAg+ patients had primary SS. No patient with HCV-related SS had HBV coinfection. There were 4 women and 1 man, with a mean age at diagnosis of primary SS of 65 years (range 31 to 89 years). All patients showed sicca and systemic involvement. The main extraglandular feature was articular involvement in 5 (100%) patients (including arthritis in two). The main immunologic features were RF in 4 (80%) patients and ANA in 3 (60%). No patient had hypocomplementemia, cryoglobulinemia, antimitochondrial or anti-LKM1 antibodies. Liver involvement was detected in two patients and consisted of slightly raised levels of transaminases. No patient showed clinical manifestations of liver disease such as hepatomegaly, splenomegaly, jaundice or clinical features of hepatic decompensation (ascites, encephalopathy or gastrointestinal bleeding)., Conclusions: We found a prevalence of chronic HBV infection of 0.83% in SS, very similar to the prevalence in general population in Spain (0.7%). In contrast to the close association between SS and HCV, chronic HBV infection is not associated with SS in our geographical area, with a ratio SS-HBV/SS-HCV cases of 1:10.

We conducted the current study to characterize the clinical presentation of primary Sjögren syndrome (SS) in a large cohort of Spanish patients and to determine whether epidemiologic, clinical, and analytical features modulate disease expression. Patients were from the GEMESS Study group, which was formed in 2005 and included 12 Spanish reference centers. By March 2007, the database included 1010 consecutive patients, recruited since 1994, both incident and prevalent cases. The cohort included 937 women and 73 men (ratio, 13:1), with a mean age of 53 years at diagnosis and 59 years at inclusion in the registry. Multivariate analysis showed that male patients had a lower frequency of thyroiditis, Raynaud phenomenon, and antinuclear antibodies. Young-onset patients had a low degree of sicca involvement (xerostomia and parotid enlargement) and a high frequency of immunologic markers (anti-Ro/SS-A and low C4 levels). Patients with disease duration of more than 10 years had a higher prevalence of xerophthalmia, parotid enlargement, lung involvement, and peripheral neuropathy in comparison with incident cases. The subset of patients with anti-Ro/La antibodies had the highest prevalence of most systemic, hematologic, and immunologic alterations (higher frequency of Raynaud phenomenon, altered parotid scintigraphy, positive salivary gland biopsy, peripheral neuropathy, thrombocytopenia, and rheumatoid factor). Hypocomplementemia was associated with a higher frequency of vasculitis and lymphoma, and cryoglobulins with a higher frequency of parotid enlargement, vasculitis, and leukopenia.Epidemiologic, clinical, and analytical features have a significant impact on the clinical presentation of primary SS, influencing the results of the main diagnostic tests, the prevalence and diversity of extraglandular involvement, and the frequency of the main immunologic markers. Primary SS should be considered as a systemic autoimmune disease that can express in many guises beyond sicca involvement.

The aim of this study was to analyze the effect of exposure to antimalarial drugs at diagnosis of lupus nephritis on the outcome of the disease, especially renal failure, comorbid processes, and survival. We analyzed a cohort of 206 consecutive patients with biopsy-proven lupus nephritis. Renal biopsies were categorized according to the classification proposed by the ISN/RPS in 2003. Exposure to antimalarial drugs (chloroquine and hydroxychloroquine) was defined as the use of these drugs before the diagnosis of lupus nephritis independent of dose and duration. Fifty-six (27%) patients had received antimalarials before the diagnosis of lupus nephritis. During the follow-up, these patients had a lower frequency of creatinine values >4 mg/dL (2% vs 11%, P = 0.029) and end-stage renal failure (2% vs 11%, P = 0.044) in comparison with those never treated with antimalarials. Patients exposed to antimalarials also had a lower frequency of hypertension (32% vs 50%, P = 0.027), infections (11% vs 29%, P = 0.006), and thrombotic events (5% vs 17%, P = 0.039). Twenty patients (10%) died during the study period. Patients exposed to antimalarials had a lower mortality rate at the end of the follow-up (2% vs 13% for those not exposed to antimalarials, P = 0.029). Multivariate analysis identified thrombosis and infections as statistically significant independent variables. Kaplan-Meier plots showed a lower rate of end-stage renal failure (log rank = 0.04) in patients exposed to antimalarials. In conclusion, exposure to antimalarials before the diagnosis of lupus nephritis was negatively associated with the development of renal failure, hypertension, thrombosis and infection, and with a better survival rate at the end of the follow-up. This, together with other published data, suggests that antimalarials should be considered a mandatory therapeutic option in all patients diagnosed with systemic lupus erythematosus.

To determine whether the clinical and immunological expression of patients with cryoglobulinaemia associated with chronic hepatitis C virus (HCV) infection varied according to HCV-RNA load, HCV genotype or human immunodeficiency virus (HIV) coinfection. We studied 340 HCV patients (188 women and 152 men, with a mean age of 49 years) consecutively diagnosed with cryoglobulinaemia between 1993 and 2003 in our hospital. HCV infection was confirmed by serum HCV-RNA determination in all patients. Two hundred and forty-eight (73%) patients had asymptomatic cryoglobulinaemia and 92 (27%) presented cryoglobulinaemic symptoms. Patients with genotype 1 had a higher mean age at diagnosis of cryoglobulinaemia (48.2 vs 40.2 yrs, P < 0.001) and a higher prevalence of cryoglobulinaemic symptoms (25%vs 10%, P = 0.02), especially of vasculitic features (19%vs 5%, P = 0.014). In comparison with monoinfected HCV patients, those with HIV coinfection had a lower mean age at diagnosis of cryoglobulinaemia (40.4 vs 52.8 years, P < 0.001), a lower prevalence of cryoglobulinaemic symptoms (15%vs 34%, P < 0.001), vasculitis (10%vs 28%, P < 0.001), associated systemic autoimmune disease (3%vs 14%, P = 0.001), rheumatoid factor (30%vs 70%, P = 0.001) and hypocomplementaemia (50%vs 78%, P = 0.01). In HCV-HIV patients, a high viral load was associated with a high frequency of symptomatic cryoglobulinaemia, especially in patients with a high viral load of the two viruses (50%vs 7%, P = 0.001) A higher frequency of cryoglobulinaemic symptoms (especially vasculitis) was found in patients with HCV monoinfection and in those carrying HCV genotype 1. In contrast, patients with HIV coinfection presented a threefold lower prevalence of vasculitis. Associated HIV infection significantly attenuated the clinical and immunological expression of cryoglobulinaemia, except in coinfected patients with high viral loads for the two viruses.

Objective: To analyze the prevalence and clinical significance of liver involvement in patients with Sjögren's syndrome (SS), focusing on the characterization and differentiation of autoimmune versus chronic viral liver disease., Methods: We investigated liver involvement (clinical signs, analytical data, chronic viral infections, and autoantibodies) in 475 consecutive patients with SS. All patients fulfilled 4 or more of the 1993 European Community Study Group criteria for SS., Results: Liver involvement was detected in 129 (27%) patients. After ruling out chronic illnesses or use of hepatotoxic drugs, the main etiologies were chronic viral liver disease in 64 (13%) cases [chronic hepatitis C virus (HCV) infection in 63 and HBV infection in one] and autoimmune liver diseases in 24 (5%; primary biliary cirrhosis in 16 patients and type-1 autoimmune hepatitis in 8). The analytical liver profile was not useful in differentiating between viral and autoimmune liver disease. In contrast, patients with SS and autoimmune liver disease presented higher mean values of erythrocyte sedimentation rate (p = 0.044), circulating gammaglobulins (p = 0.007), and a higher prevalence of antinuclear antibodies (p < 0.001), antimitochondrial antibodies (p < 0.001), anti-smooth muscle antibodies (p = 0.026), anti-Ro/SSA (p < 0.001), and anti-La/SSB (p = 0.01), while patients with chronic viral liver disease had a higher frequency of cryoglobulinemia (p < 0.001) and hypocomplementemia (p < 0.001)., Conclusion: Chronic viral liver disease (associated overwhelmingly with HCV) was the main cause of liver involvement in our patients with SS, with a prevalence of 13%, nearly 3-fold greater than that observed for autoimmune liver involvement. The immunological pattern played a key role in the differentiation of viral (predominance of cryoglobulins and low complement levels) and autoimmune (higher frequency of autoantibodies) liver involvement.

We decided to analyse the incidence and characteristics of infection in systemic lupus erythematosus (SLE) and determine the related risks factors. One-hundred and ten SLE patients and 220 controls were prospectively followed up over three years and all the infectious episodes were recorded. A case-control design was established to identify risk factors of infection. Thirty-nine SLE patients suffered at least one infection (36%) versus 53 controls (22%), RR = 1.63 (P < 0.05). The incidence of urinary infections, pneumonia and bacteraemia without known focus was significantly greater in SLE. E. coli was the chief isolated microorganism (21.3%). In the univariate analysis, nephritis, SLE activity, leucopenia, anti-dsDNA levels above 20 IU/mL, CH50 levels under 300 IU/mL, ever use of steroids, daily dose of prednisone higher than 10 mg and ever use of cyclophosphamide were significantly associated with infection. In the multivariate analysis, total serum complement levels below 300 UU/mL and a daily dose of prednisone above 20 mg during at least one month plus ever use of cyclophosphamide were found to be significant (P < 0.0001). We conclude that patients with SLE have an increased overall risk for infection and they are especially prone to develop urinary infection, pneumonia and bacteraemia without focus. Hypocomplementaemia represents an independent predictive factor for infection. It seems mandatory to closely follow up SLE patients with low complement levels and instruct them to report any suspicious sign of infection, especially in those receiving more than 20 mg/day of prednisone who have also been administered cyclophosphamide.

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.

The objective of our study was to determine the clinical and immunological characteristics of primary Sjögren's syndrome (SS) in patients with a young onset of the disease. We included 144 consecutive patients (134 female and 10 male; mean age at onset 53 y; range 20-87 y) visited in our Units. All patients were white and fulfilled four or more of the diagnostic criteria for SS, proposed by the European Community Study Group in 1993. Disease onset was determined on the basis of the appearance of symptoms strongly suggestive of SS. In 13 (9%) patients, disease onset occurred before the age of 35. All were female and the disease onset occurred between 20-34 y (mean, 28 y). When compared with patients with older onset, patients with a young onset of the primary SS presented a higher prevalence of lymphadenopathy (54% vs 6%, P < 0.001), rheumatoid factor (70% vs 39%, P=0.034), anti-Ro/SS-A antibodies (70% vs 28%, P=0.004) and monoclonal immunoglobulins (23% vs 4%, P=0.02) in their sera. From the initial diagnosis of SS, three patients with a young-onset of the primary SS have developed lymphoproliferative disease at the time of the study, compared with one patient of the older-onset group (23% vs 1%, P=0.002). Our study shows several differences between younger and older onset patients, including a higher incidence of lymphomas in the younger, thus conferring to the age at onset of the disease a prognostic value.