Diagnosis and treatment of Tropheryma whipplei infection in patients with inflammatory rheumatic disease: Data from the French Tw-IRD registry.

OBJECTIVES: Tropheryma whipplei infection can manifest as inflammatory joint symptoms, which can lead to misdiagnosis of inflammatory rheumatic disease and the use of disease-modifying antirheumatic drugs. We investigated the impact of diagnosis and treatment of Tropheryma whipplei infection in patients with inflammatory rheumatic disease. METHODS: We initiated a registry including patients with disease-modifying antirheumatic drugs-treated inflammatory rheumatic disease who were subsequently diagnosed with Tropheryma whipplei infection. We collected clinical, biological, treatment data of the inflammatory rheumatic disease, of Tropheryma whipplei infection, and impact of antibiotics on the evolution of inflammatory rheumatic disease. RESULTS: Among 73 inflammatory rheumatic disease patients, disease-modifying antirheumatic drugs initiation triggered extra-articular manifestations in 27% and resulted in stabilisation (51%), worsening (34%), or improvement (15%) of inflammatory rheumatic disease. At the diagnosis of Tropheryma whipplei infection, all patients had rheumatological symptoms (mean age 58 years, median inflammatory rheumatic disease duration 79 months), 84% had extra-rheumatological manifestations, 93% had elevated C-reactive protein, and 86% had hypoalbuminemia. Treatment of Tropheryma whipplei infection consisted mainly of doxycycline plus hydroxychloroquine, leading to remission of Tropheryma whipplei infection in 79% of cases. Antibiotic treatment of Tropheryma whipplei infection was associated with remission of inflammatory rheumatic disease in 93% of cases and enabled disease-modifying antirheumatic drugs and glucocorticoid discontinuation in most cases. CONCLUSIONS: Tropheryma whipplei infection should be considered in inflammatory rheumatic disease patients with extra-articular manifestations, elevated C-reactive protein, and/or hypoalbuminemia before disease-modifying antirheumatic drugs initiation or in inflammatory rheumatic disease patients with an inadequate response to one or more disease-modifying antirheumatic drugs. Positive results of screening and diagnostic tests for Tropheryma whipplei infection involve antibiotic treatment, which is associated with complete recovery of Tropheryma whipplei infection and rapid remission of inflammatory rheumatic disease, allowing disease-modifying antirheumatic drugs and glucocorticoid discontinuation.

Increased Cardiovascular Risk in Psoriatic Arthritis: Results From a Case-Control Monocentric Study.

Background: Psoriatic arthritis (PsA) is associated with increased cardiovascular morbidity and mortality. The aims of our real-life study were to compare the prevalence of cardiovascular risk factors (CVRFs) and cardiovascular events (CVEs) among patients with PsA with a control population, to evaluate the impact of correcting factors in equations that assess cardiovascular risk (CVR) in PsA, and to determine the percentage of patients who reach the LDLc target as indicated by the European guidelines. Methods: In this observational cross-sectional monocentric case-control study, we used a standardized procedure to systematically assess patients with PsA aged 25-85 years who met the Classification for Psoriatic Arthritis (CASPAR) criteria. Controls were extracted from the MOnitoring NAtionaL du rISque Artériel (MONALISA) study. We compared the prevalence of CVRFs, CVEs, the CVR, and the percentage of patients reaching recommended LDLc target in both populations. The CVR was first assessed using SCORE and QRISK2 equations. Then, the SCORE equation was corrected by applying a 1.5 multiplication factor, as recommended by EULAR for rheumatoid arthritis (SCORE-PsA), and the QRISK2 was corrected using the "rheumatoid arthritis" item (QRISK2-PsA). Results: A total of 207 PsA and 414 controls were included. CVRFs and CVEs were more frequent in the PsA group. After controlling for age and gender, atherothrombotic disease was increased in the PsA population (SCORE p = 0.002, QRISK2 p = 0.001). Using the SCORE-PsA increased the percentage of patients with a high or very high CVR from 39.3 to 45.3% in the PsA group. Similarly, using the QRISK2-PsA increased the percentage of patients with a CVR ≥ 10% from 44.9 to 53.2%. The percentages of patients with PsA with high LDLc in the high and very high CVR groups were not significantly different from controls, despite a trend in favor of patients with PsA. Of the 83 PsA with a QRISK2 ≥ 10%, only 22.9% were treated with statin vs. 35.8% of the 134 controls. The QRISK2-PsA score did not alter these results. Conclusion: In real-life, patients with PsA have a higher prevalence of CVRFs, as well as a higher prevalence of CVEs compared to the general population. The CVR is higher in the PsA population than in the controls either using the SCORE and QRISK2 equations or using the corrected SCORE- PsA and QRISK2-PsA equations.

Fcγ receptor profile of monocytes and macrophages from rheumatoid arthritis patients and their response to immune complexes formed with autoantibodies to citrullinated proteins.

OBJECTIVE: To analyse Fcγ receptor (FcγR) expression on monocytes and macrophages from rheumatoid arthritis (RA) patients versus healthy controls (HC), and to compare their responses to immune complexes containing RA-specific anti-citrullinated proteins auto antibodies (ACPA). METHODS: Monocytes and monocyte-derived macrophages were obtained from the peripheral blood of 34 RA patients and 69 HC. FcγR expression was studied by flow cytometry. Cells were stimulated with ACPA-containing immune complexes, and tumour necrosis factor alpha (TNFα) was assayed in culture supernatants. RESULTS: Variations distinguished RA from HC monocytes, corresponding to a 5% and 6% decrease in the percentages of monocytes expressing FcγRI and FcγRII, respectively, and a 7% increase in the proportion of FcγRIII-positive monocytes. Although in both HC and RA patients macrophage differentiation was accompanied by a dramatic increase in the percentage of FcγRIII-expressing cells (72% vs 74.5%), the parallel decline in the proportion of FcγRI-positive cells was markedly smaller in RA (7% vs 43%). Monocytes and macrophages from patients were responsive to ACPA-containing immune complexes but TNFα production in both cell types neither differed from that observed with the corresponding cells from HC, nor correlated with FcγR expression or clinical or biological data. In RA as in HC, ACPA-containing immune complexes induced secretions of more TNFα in macrophages than in paired monocytes (ninefold). Finally, the proinflammatory potential of ACPA-containing immune complexes was confirmed in CD14-positive monocyte macrophages from the synovial fluid of four RA patients. CONCLUSIONS: ACPA-containing immune complexes induce TNFα secretion by blood and synovial fluid-derived macrophages from RA patients, fitting with their probable involvement in RA pathophysiology.

Posttraumatic psoriatic osteitis of the frontal bone successfully treated with etanercept. Report of a case.

We report a case of aseptic osteomyelitis of the frontal bone that developed after a local injury in an 8-year-old girl with psoriasis of the scalp as a predisposing factor. Follow-up was 36 years (1972 to 2008). Enthesitis of the forehead muscles was a plausible pathophysiological mechanism. The symptoms responded to anti-inflammatory medications and resolved immediately after the introduction of etanercept therapy. The most interesting feature of this case of psoriatic osteomyelitis is the involvement of a skull bone.

Maffucci syndrome and adrenal cortex tumor.

We report the second known case of Maffucci syndrome associated with an adrenal cortex tumor. Endocrine tumors have been reported in patients with multiple enchondromas, although the underlying mechanism of this combination is unknown. Maffucci syndrome is characterized by abnormalities of several mesodermal derivates. Therefore, routine evaluation for involvement of the adrenal cortex may be warranted to improve our knowledge of this syndrome and of its pathophysiology.

Pneumomediastinum in interstitial lung disease associated with dermatomyositis and polymyositis.

OBJECTIVE: Spontaneous pneumomediastinum is a rare complication of dermatomyositis (DM) and polymyositis (PM). The aim of this study was to characterize this complication and determine its prognostic factors. METHODS: We retrospectively collected a multicenter series of PM/DM cases complicated by pneumomediastinum. We analyzed all published cases and combined those that were exploitable with ours for an investigation of the factors associated with poor survival. RESULTS: We collected 11 PM/DM cases complicated by interstitial lung disease and pneumomediastinum. Five of the 9 DM patients had clinically amyopathic DM without muscle weakness and high serum creatine kinase levels. The outcome was favorable in 7 of these patients and 6 had no sequelae. In total, approximately 25% of our patients of the 21 analyzable cases studied died within 1 month. With a median followup of 240 days, the cumulative estimated Kaplan-Meier survival rate was 64% at 1 year and 55% at 2 years. Poor survival was associated with absence of muscle weakness (P = 0.02), initial low vital capacity (P = 0.006), and initial low carbon monoxide diffusion capacity (P = 0.04). CONCLUSION: In this first large series of patients with connective tissue disease complicated by pneumomediastinum to be reported, most patients had DM and half amyopathic DM, as in previous reports. Pneumomediastinum may occur before DM diagnosis and may thus reveal DM with minimal or no muscle involvement. Death was associated with an absence of muscle weakness and severe pulmonary involvement before the onset of pneumomediastinum. Corticosteroids and immunosuppressive therapy can result in complete recovery, as in half our cases.

Aseptic osteomyelitis responding to TNFalpha antagonist therapy in a patient with Crohn's disease.

Aseptic osteomyelitis was diagnosed in a patient with Crohn's disease. This rarely reported manifestation responded to infliximab therapy.

Morquio syndrome: diagnosis in an adult.

Morquio syndrome or mucopolysaccharidosis (MPS) type IV is a rare autosomal recessive disease in which keratan sulfate builds up in cells. There are two variants, A and B, corresponding to deficiencies of two different enzymes. Type A is usually severe, although considerable clinical variability occurs due to the existence of attenuated phenotypes, which may escape diagnosis until adulthood. We illustrate this little known possibility by reporting a case of MPS IV A diagnosed in a 38-year-old woman. We review the clinical and radiological features of this disease, with which pediatricians are more familiar than other physicians. Our case provides an opportunity to emphasize the need for management by a rheumatologist in addition to the standard surgical treatment.

An unusual presentation of primary hyperparathyroidism: severe hypercalcemia and multiple brown tumors.

Primary hyperparathyroidism is common, particularly in postmenopausal women. Since the introduction of routine automated serum calcium assays and the development of assays for intact 1-84 parathyroid hormone, the diagnosis is usually made fortuitously in asymptomatic patients or during evaluation for osteoporosis. As a result, many physicians have no experience with the clinical manifestations. Here, we describe the case of a 70-year-old man with bone pain, multiple brown tumors, and severe hypercalcemia (4 mmol/L). The diagnostic pitfalls raised by these symptoms are illustrated.

Whipple disease revealed by musculocutaneous symptoms, with muscle biopsy cultures positive for Tropheryma whipplei.

A patient experienced sudden onset of musculocutaneous symptoms 3 years after being diagnosed with polyarthritis. Biopsies from the duodenum, skin, and muscle established the diagnosis of Whipple disease. Cultures of muscle biopsy specimens grew Tropheryma whipplei. Adequate antibiotic therapy ensured a favorable outcome. To our knowledge, this is the first case in which T. whipplei was recovered from muscle biopsy specimens, confirming the infectious nature of muscle involvement in Whipple disease.

Toxoplasmic chorioretinitis and antitumor necrosis factor treatment in rheumatoid arthritis.

OBJECTIVES: To present the data supporting the possible relationship of ocular toxoplasmosis to antitumor necrosis factor-alpha (TNF-alpha) therapy in patients with rheumatoid arthritis (RA). METHODS: A Medline search was performed using the words "toxoplasmosis, anti-TNF-alpha antagonists, chorioretinitis." We report 2 RA patients who developed ocular toxoplasmosis while receiving anti-TNF-alpha therapy. RESULTS: In addition to our patients with toxoplasmic chorioretinitis, there are 2 published cases of cerebral toxoplasmosis during treatment with anti-TNF-alpha agents. CONCLUSION: The risk of serious toxoplasmic infection during anti-TNF-alpha therapy for RA should be recognized.

Extrasynovial ultrasound abnormalities in the psoriatic finger. Prospective comparative power-doppler study versus rheumatoid arthritis.

We prospectively compared power Doppler ultrasound findings in 25 fingers with rheumatoid arthritis (RA) and 25 fingers with psoriatic arthritis (PsA). Erosive synovitis and tenosynovitis were seen in both groups. Extrasynovial changes were found in 21/24 (84%) fingers with PsA versus none of the fingers with RA. Of the 21 PsA fingers exhibiting extrasynovial changes, 15 (15/25, 60%) also had synovial changes. The extrasynovial changes reflected enthesitis or soft tissue inflammation, with the main patterns being capsular enthesophyte, juxtaarticular periosteal reaction, enthesopathy at the site of deep flexor tendon insertion on the distal phalanx, and subcutaneous soft tissue thickening of the finger pad or entire finger. In four fingers, ultrasonograhy showed pseudotenosynovitis, an underrecognized abnormality characterized by diffuse inflammation of the digital soft tissues. Pseudotenosynovitis may play a pivotal role in dactylitis (sausage digit), which is defined as diffuse uniform swelling of the entire finger. Our findings suggest that inflammation of the fibrous skeleton of the finger may lead to the clinical and radiological features that distinguish PsA from RA of the finger.

Acitretin-induced enthesitis in a patient with psoriatic arthritis.

A patient with psoriatic arthritis and cutaneous psoriasis took acitretin for 10 years to treat his skin lesions. Radiographs disclosed exuberant ossifications in several entheses. Their features were not typical for psoriatic arthritis but were consistent with acitretin-induced hyperostosis. Retinoids are known to induce hyperostosis, most notably when they are used in high dosages and over long periods. The concomitant presence of two conditions affecting the entheses may explain the exuberant nature of the ossifications in our patient.

Spondyloarthropathy with entheseal pain. A prospective study in 33 patients.

OBJECTIVES: To identify objective features individualizing spondyloarthropathy with isolated entheseal pain and distinguishing this condition from fibromyalgia. PATIENTS AND METHODS: Thirty-three patients presenting with entheseal pain were studied prospectively. The diagnoses were psoriatic arthritis in six patients and ankylosing spondylitis in seven patients; among the 20 remaining patients, in whom entheseal pain was the only symptom, 11 responded to nonsteroidal antiinflammatory drugs (NSAIDs) and were diagnosed with entheseal spondyloarthropathy whereas the nine unresponsive patients were diagnosed with fibromyalgia. A physical examination, laboratory tests, plain radiographs, and radionuclide scan and resonance imaging (MRI) scan of a painful enthesis were done in each patient. RESULTS: Among the 11 patients with entheseal spondyloarthropathy, two experienced inflammatory joint symptoms during the 4-6-month follow-up and three patients had radionuclide scanning and MRI evidence of entheseal inflammation similar to that in nine patients with definite spondyloarthropathy (ankylosing spondylitis or psoriatic arthritis). The feature that best discriminated between entheseal spondyloarthropathy and fibromyalgia was responsiveness to NSAIDs. CONCLUSION: These preliminary data suggest that isolated entheseal pain may indicate spondyloarthropathy in some patients. The imaging methods used in this study lacked sensitivity for enthesitis, which may therefore have been missed in some patients. The development of bone and joint ultrasonography may provide additional insights into the entheseal abnormalities present in patients with isolated entheseal pain.

Myeloma and monoclonal gammopathy of uncertain significance associated with acquired von Willebrand's syndrome. Seven new cases with a literature review.

OBJECTIVES: Acquired von Willebrand's syndrome (AvWS) is an uncommon complication of monoclonal gammopathy of uncertain significance (MGUS) or myeloma. We investigated clinical and laboratory test abnormalities, pathophysiological hypotheses, and treatment options in this poorly known condition. PATIENTS: Five patients with MGUS and two with myeloma who met classic criteria for acquired von Willebrand's syndrome were included in this retrospective study. RESULTS: Acquired von Willebrand's syndrome was diagnosed before the gammopathy in five of the seven patients. The severity of the bleeding events was chiefly dependent on the degree of von Willebrand's factor deficiency and on the presence or absence of gastrointestinal tract angiodysplasia. Bleeding event severity was similar in patients with nonmalignant and malignant disease. An antibody that inhibited von Willebrand's factor was detected in all seven patients. Clotting returned to normal after treatment of the malignancy in one of the two patients with myeloma. In patients with MGUS, treatment is warranted only when bleeding occurs or before surgery. Von Willebrand's factor concentrates were of limited efficacy because of their short half-life. Intravenous immunoglobulins had a longer-lasting effect (about 3 weeks); this treatment was used on a regular basis in two patients with recurrent bleeding. CONCLUSIONS: A diagnosis of von Willebrand's syndrome in adulthood should prompt a search for a monoclonal gammopathy. In patients with gammopathies, simple clotting tests ensure the diagnosis of acquired von Willebrand's syndrome.