Non-typhi Salmonella infection in patients with rheumatic diseases on TNF-alpha antagonist therapy.

OBJECTIVES: The morbidity and mortality of patients with rheumatic diseases has improved considerably following the use of biologic therapies. However, an increase in the frequency of bacterial infections has been observed in patients receiving these drugs. In the present study we aimed to establish the incidence and clinical manifestations of non-typhi Salmonella infection in a large cohort of patients with rheumatic diseases undergoing TNF-alpha antagonist therapy due to severe rheumatic diseases refractory to conventional therapies. METHODS: The rate of non-typhi Salmonella infection found in the Spanish Registry of Adverse Events of Biological Therapies in Rheumatic Diseases (BIOBADASER) was compared with that observed in a cohort of rheumatoid arthritis (RA) patients from the EMECAR (Morbidity and Clinical Expression of Rheumatoid Arthritis) Study, who were not treated with TNF-alpha antagonists. The rate found in the BIOBADASER registry was also compared with that available in a non-RA historic control cohort reported in a population from Huesca (Northern Spain). RESULTS: Seventeen cases of non-typhi Salmonella infection were observed in the series of patients exposed to anti-TNF-alpha therapies. The incidence rate of non-typhi Salmonella in BIOBADASER was 0.73 per 1000 patient-years (95% confidence interval [CI]: 0.45-1.17). The incidence rate in the EMECAR cohort was 0.44 per 1000 patient-years. The relative risk for non-typhi salmonellosis in RA patients exposed to TNF-alpha inhibitors compared to those not treated with biological therapies was 2.07 (95% CI: 0.27-15.73) (p=0.480) whereas the relative risk of non-typhi Salmonella infections in patients with rheumatic diseases undergoing TNF-alpha antagonist therapy compared with the non-RA Spanish control cohort was 0.63 (95% CI: 0.38-1.04) (p=0.07). Nine of the 17 patients with non-typhi salmonellosis presented a severe systemic infection. CONCLUSION: Incidence of non-typhi Salmonella infection is not increased significantly in rheumatic patients undergoing anti-TNF-alpha therapy when compared with RA patients undergoing conventional DMARD therapy or with the general population. Nevertheless, at least 50% of patients on TNF-alpha have severe complications once they develop non-typhi Salmonella infection. This fact suggests that anti-TNF-alpha therapies may predispose to salmonella dissemination rather than to infection.

Listeria monocytogenes infection in patients with rheumatic diseases on TNF-alpha antagonist therapy: the Spanish Study Group experience.

OBJECTIVE: The prognosis of patients with rheumatic diseases has improved considerably following the use of biological therapies. However, an increase in the frequency of bacterial infections has been observed in patients receiving these therapies. In the present study we aimed to assess the frequency of Listeria monocytogenes infection in a large series of patients with rheumatic diseases on treatment with tumor necrosis factor (TNF)-alpha blockers because of active disease refractory to conventional therapy, included in the Spanish Registry of Adverse Events of Biological Therapies in Rheumatic Diseases (BIOBADASER) of the Spanish Society for Rheumatology. METHODS: Assessment of the incidence of infection due to Listeria monocytogenes in the Spanish Registry Study (BIOBADASER) per 1000 patient-years and 95% confidence intervals (95% CIs) was performed. Rate from this registry was compared with that from the general population in Europe and with the rate found in patients with rheumatoid arthritis (RA) from the Spanish Rheumatoid Arthritis Registry Cohort Study (EMECAR) that assessed morbidity and clinical expression of RA and included patients treated in most cases with conventional therapies. RESULTS: Six patients on treatment with TNF-alpha antagonists were diagnosed as having Listeria monocytogenes infection. The incidence of this infection per 1000 patient-year (95% CI) was 0.256 (95% CI: 0.115-0.570). This was greater than the incidence observed in the general population from Europe and in the EMECAR study. CONCLUSION: Despite the benefits associated to the use of TNF-alpha antagonists, a high level of surveillance is required to reduce the potential risk of infections related to the use of these drugs.

Implication of the age in the clinical spectrum of giant cell arteritis.

OBJECTIVE: To assess the potential influence of the age in the clinical spectrum of giant cell arteritis (GCA). METHODS: The case records of all patients diagnosed with biopsy-proven GCA at the Department of Medicine of the Hospital Xeral-Calde (Lugo, Northwest Spain) between 1981 and 2006 were reviewed. RESULTS: During the period of study, 273 Lugo residents were diagnosed with biopsy-proven GCA. The mean age +/- standard deviation at the time of disease diagnosis was 75.1+/-6.8 years (median: 75 years; interquartile range 71-80 years). A longer delay to the diagnosis was observed in patients younger than 70 years of age (13.2+/-12.8 weeks) compared to those 70 years and older (9.4+/-10.2 weeks) (p=0.03). Patients younger than 70 years presented more frequently polymyalgia rheumatica (p=0.02), cerebrovascular accidents (p=0.004), peripheral arteriopathy of recent onset due to large artery stenosis (p=0.03) and high alkaline phosphatase values (p=0.001) than those 70 years and older. Individuals 70-79 years of age at the time of disease diagnosis had ESR values (90.2+/-22.8 mm/1st hour) lower than those observed in patients younger than 70 years (98.3+/-22.2 mm/1st hour) or 80 years and older (99.5+/-20.6 mm/1st hour) (p=0.005). However, no significant differences in the frequency of visual ischemic complications according to the age at the time of disease diagnosis were observed. CONCLUSION: The results from this study display differences in the clinical spectrum of the disease according to the age of disease onset.

Generalized granuloma annulare and giant cell arteritis.

Granuloma annulare (Gan) and giant cell arteritis (GCA) share common histologic features. In Gan, a disease characterized by the presence of palisading granulomas usually in the dermis, the main alteration is the presence of elastic fiber degeneration and it strongly suggests that the primary target leading to the development of this disorder is the injury to the elastic tissue. On the other hand, in giant cell arteritis (GCA), a vasculitis involving large-and middle-sized blood vessels, the main histologic features are the disruption of the internal elastic lamina and the nonsuppurative granulomatous giant cell infiltrate, which seems to be focused around the disintegrated elastic fibers. Due to this, these two conditions appear to be related. However, to the best of our knowledge, only one case of association of generalized Gan and GCA is described in the literature. We herein report a new case of generalized Gan in a patient previously diagnosed with biopsy-proven GCA. Both diseases were successfully treated by oral prednisone. Although the etiology of generalized Gan and GCA remains still unknown, they seem to be immunologically mediated conditions showing predominance of T-cells in the inflammatory infiltrate.

Metastatic arthropathy report of two cases and review of the literature.

Metastatic arthropathy has been rarely reported as a manifestation of solid tumors. It is characterized by a monoarticular involvement and is frequently the first feature of the malignant process; therefore, it may pose a diagnostic challenge. We report two new cases of metastatic carcinomatous arthritis: a patient with right-knee monoarthritis as a presenting feature of pancreatic carcinoma and another one with right-elbow monoarthritis, preceded by constitutional and pulmonary symptoms, secondary to metastasis of undifferentiated carcinoma. We also review the literature for well documented cases of metastatic arthropathy secondary to solid tumors. Metastatic arthropathy indicates a poor prognosis because of a wide spread of the tumor when it is diagnosed. We emphasize the need for increasing awareness of cancer as a cause of monoarthritis.

[Primary Sjogren syndrome with involvement of the nervous system. Description of 4 cases]. / Síndrome de Sjögren primario con afectación del sistema nervioso. Descripción de 4 casos.

Four patients, 2 males and 2 females, with primary Sjögren's syndrome (PSS) and neurologic involvement are described. The first patient presented a progressive axonal polyneuropathy due to endo-epineural vasculitis. The second patient developed an acute and focal lymphocytic meningoencephalitis with increased IgG synthesis and excellent response to corticosteroids. The remaining 2 patients had previously been diagnosed as having definite multiple sclerosis (MS), but after a standardized study both fulfilled PSS diagnostic criteria. These cases illustrate the polymorphism of the neurological manifestations in PSS. Pathogenetic relationships between PSS and MS are briefly reviewed.

Prevalence of primary Sjögren's syndrome in patients with multiple sclerosis.

Sixty-four consecutive patients with clinically or laboratory-supported definite multiple sclerosis (MS) were evaluated prospectively for evidence of primary Sjögren's syndrome (SS). This diagnosis was established when a patient had objective keratoconjunctivitis sicca, xerostomia, or both together with positive labial salivary gland biopsy. We found 2 patients (3.1%) with clinical evidence of primary SS. Whether this association is fortuitous or whether there is pathogenetic linkage between MS and primary SS remains to be established.

[Anti-DNA determination using Crithidia luciliae. Specificity and clinical usefulness in systemic lupus erythematosus]. / Anti-DNA par Crithidia luciliae. Spécificité et utilité clinique dans le lupus érythémateux systémique.

The authors determined the existence of native anti-DNA antibodies by the crithidia lucilae (anti-DNA-CL) test in 44 patients suffering from systemic lupus erythematosus (SLE), 48 with rheumatoid arthritis (RA), 12 with scleroderma, 8 with polymyositis and/or dermatomyositis, 12 with mixed connective tissue disease, 53 with chronic liver disease and 100 blood donors in order to establish the specificity of the test in SLE, its possible correlation with the degree of clinical activity and the presence or absence of neuropathy, and its possible use in the therapeutic control of the disease. The presence of anti DNA-CL was specific to SLE. It was seen at significant titres only in patients with active disease. Anti DNA-CL antibodies capable of activating complement were seen more frequently and at higher titres in cases with active nephritis. In longitudinal studies it was seen that clinical activity or inactivity were associated with parallel oscillations in anti DNA-CL titres. These data confirmed the specificity of the method and its usefulness in the diagnosis and therapeutic control of the process.