Management of asymptomatic coccidioidomycosis in patients with rheumatic diseases.

Coccidioidomycosis is an endemic fungal infection common in the southwestern United States. Some rheumatology clinics periodically screen patients with coccidioidal serology, resulting in the identification of patients who are serologically positive but without clinical symptoms. The management of such patients is unclear. A retrospective study was conducted between 2007 and 2015 at two arthritis centers in Tucson, Arizona. The asymptomatic patients were identified who were receiving disease-modifying antirheumatic agents and had a positive coccidioidal serology. Serological testing including IgM and IgG was performed by enzyme immunoassay (EIA), immunodiffusion (IDTP and IDCF), or complement fixation. Out of 71 patients who were identified with positive coccidioidal serologies, 19 were asymptomatic. 18/19 patients continued antirheumatic therapy, 13 without interruption. 13/19 patients received no antifungal treatment, including 10 who remained on antirheumatic treatment. The other six were started on fluconazole, ranging from 8 to 73 months (median 30.5 months). After a median follow-up of 43 months, no patient developed clinically active coccidioidomycosis. Overall, 14 had only a positive EIA serological test. These results suggest that continued antirheumatic therapy is safe in asymptomatic patients with positive coccidioidal serological tests and that routine implementation of antifungal treatment may not always be warranted. The findings also raise concern regarding the utility of routine serological testing of asymptomatic patients residing in the coccidioidal endemic area, mainly using the EIA test.

Stroke Incidence and Survival in Ludwigshafen am Rhein, Germany: the Ludwigshafen Stroke Study (LuSSt).

BACKGROUND AND PURPOSE: Considerable locoregional differences in stroke incidence exist even within countries. Based on data from a statewide stroke care quality monitoring project, we hypothesized a high stroke incidence mainly among younger age groups in the industrial city of Ludwigshafen am Rhein, Germany. To test this hypothesis and to provide data on stroke incidence and case-fatality rates, a population-based stroke register was initiated. METHODS: The Ludwigshafen Stroke Study is a prospective ongoing population-based stroke register among the 167 906 inhabitants of Ludwigshafen am Rhein. Starting on January 1, 2006, standard definitions and multiple overlapping methods of case ascertainment were used to identify all patients with incident stroke or transient ischemic attack. RESULTS: In 2006 and 2007, 1231 cases with stroke or transient ischemic attack including 725 patients with first-ever stroke were identified. The crude annual incidence rate per 1000 for first-ever stroke was 2.16 (95% CI 2.10 to 2.32). After age adjustment to the European population, incidence for first-ever stroke was 1.46 (95% CI 1.35 to 1.57; men: 1.63; 95% CI 1.46 to 1.81; women: 1.29; 95% CI 1.15 to 1.43). Crude annual incidence rates per 1000 were 1.86 for ischemic stroke, 0.19 for intracerebral hemorrhage, 0.05 for subarachnoid hemorrhage, and 0.05 for undetermined stroke. Case-fatality rates for first-ever stroke were 13.6%, 16.4%, and 23.2% at Days 28, 90, and 365, respectively. CONCLUSIONS: High crude incidence rates in our study reflect the rising burden of stroke in our aging population. Age-adjusted incidence rates were somewhat higher than those reported by recent studies from Western Europe, mainly due to higher incidence in subjects <65 years.

Anticyclic citrullinated peptide antibody-positive paraneoplastic polyarthritis in a patient with metastatic pancreatic cancer.

Neoplasms may present as rheumatic disorders. Some of these rheumatologic manifestations may be paraneoplastic and can clinically and serologically mimic rheumatoid arthritis (RA). We report the case of a patient who initially presented with an asymmetrical, rapid onset polyarthritis. It resembled atypical RA with positive rheumatoid factor and anticyclic citrullinated peptide (CCP) antibodies. A good response to steroid therapy was noted. A few weeks later, he was diagnosed with metastatic pancreatic cancer that resulted in his mortality. His clinical course suggested that his rheumatic symptoms were a paraneoplastic manifestation of his underlying malignancy. Anticyclic citrullinated peptide antibodies have not been previously described in cancer polyarthritis. Awareness of this atypical, seropositive RA-like syndrome may prompt clinicians to investigate for an underlying malignancy.

Role of the toll-like receptor 4 in neuroinflammation in Alzheimer's disease.

Microglial activation is a key feature in Alzheimer's disease and is considered to contribute to progressive neuronal injury by release of neurotoxic products. The innate immune receptor Toll-like-receptor 4 (TLR4), localized on the surface of microglia, is a first-line host defense receptor against invading microorganisms. Here, we show that a spontaneous loss-of-function mutation in the Tlr4 gene strongly inhibits microglial and monocytic activation by aggregated Alzheimer amyloid peptide resulting in a significantly lower release of the inflammatory products IL-6, TNFalpha and nitric oxide. Treatment of primary murine neuronal cells with supernatant of amyloid peptide-stimulated microglia demonstrates that Tlr4 contributes to amyloid peptide-induced microglial neurotoxicity. In addition, stimulation experiments in transfected HEK293 cells allowed to define a tri-molecular receptor complex consisting of TLR4, MD-2 and CD14 necessary for full cellular activation by aggregated amyloid peptide. A clinical relevance of these findings is supported by a marked upregulation of Tlr4 mRNA in APP transgenic mice and by an increased expression of TLR4 in Alzheimer's disease brain tissue associated with amyloid plaque deposition. Together, these observations provide the first evidence for a role of the key innate immune receptor, TLR4, in neuroinflammation in Alzheimer's disease.