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.

In inflammatory myopathies, dropped head/bent spine syndrome is associated with scleromyositis: an international case-control study.

BACKGROUND: Some myopathies can lead to dropped head or bent spine syndrome (DH/BS). The significance of this symptom has not been studied in inflammatory myopathies (IM). OBJECTIVES: To assess the significance of DH/BS in patients with IM. METHODS: Practitioners from five IM networks were invited to report patients with IM suffering from DH/BS (without other known cause than IM). IM patients without DH/BS, randomly selected in each participating centre, were included as controls at a ratio of 2 to 1. RESULTS: 49 DH/BS-IM patients (DH: 57.1%, BS: 42.9%) were compared with 98 control-IM patients. DH/BS-IM patients were older (65 years vs 53 years, p<0.0001) and the diagnosis of IM was delayed (6 months vs 3 months, p=0.009). Weakness prevailing in the upper limbs (42.9% vs 15.3%), dysphagia (57.1% vs 25.5%), muscle atrophy (65.3% vs 34.7%), weight loss (61.2% vs 23.5%) and loss of the ability to walk (24.5% vs 5.1%) were hallmarks of DH/BS-IM (p≤0.0005), for which the patients more frequently received intravenous immunoglobulins (65.3% vs 34.7%, p=0.0004). Moreover, DH/BS-IM patients frequently featured signs and/or complications of systemic sclerosis (SSc), fulfilling the American College of Rheumatology/European Alliance of Associations for Rheumatology criteria for this disease in 40.8% of the cases (vs 5.1%, p<0.0001). Distribution of the myopathy, its severity and its association with SSc were independently associated with DH/BS (p<0.05). Mortality was higher in the DH/BS-IM patients and loss of walking ability was independently associated with survival (p<0.05). CONCLUSION: In IM patients, DH/BS is a marker of severity and is associated with SSc (scleromyositis).

Performance of a diagnostic score for gouty arthritis: results from a cohort of acute arthritis suspected of being septic.

Septic arthritis (SA) and gout are the main suspected etiologies of acute monoarthritis. Differentiating them is essential because SA is an emergency. The performance of a gout diagnostic score developed by Janssens et al. was investigated in a cohort of patients with acute arthritis suspected of being septic. This was an ancillary study of a single-center cohort of patients with suspected SA. Patients were classified into three groups according to the final diagnosis (gout, SA or other diagnosis). We assessed the performance of the score (sensitivity [Se], specificity [Sp], positive and negative predictive value [PPV, NPV], area under the receiver operating characteristic [ROC] curve) for the diagnosis of gouty arthritis. In total, 138 patients were included: 28 (20.3%) had gout, 42 (30.4%) SA, and 68 (49.3%) another diagnosis. The median diagnostic score was 7.0 [4.5; 8.8] for patients with gout, 3.5 [2.5; 6.0] for those with SA and 3.0 [2.0-5.0] for those with another diagnosis. With a score threshold of ≥ 8, the Se for a diagnosis of gout was 28.6%, Sp 96.4%, PPV 66.7%, and NPV 84.1%. With a threshold of ≤ 4, the Se was 82.1%, Sp 64.5%, PPV 37.1%, and NPV 93.4%. The area under the ROC for the diagnostic score was 0.79. The performance of the clinico-biological score of Janssens et al. for a diagnosis of gout applied to a cohort of patients with acute arthritis and suspected of being septic was poor. Joint aspiration remains necessary to differentiate SA from another etiology.

Post-traumatic stress disorder prior to diagnosis is as rare in spondyloarthritis as in non-inflammatory rheumatic conditions and rheumatoid arthritis.

OBJECTIVE: Post-traumatic stress disorder (PTSD) may be a risk factor for the development of rheumatoid arthritis (RA). No data are available in spondyloarthritis (SpA). The aim of the present study was to investigate the frequency of traumatic events and PTSD in patients with SpA and its different phenotypes and to compare the results to patients with non inflammatory rheumatic disease and RA patients. METHODS: This was an observational, cross-sectional and bi-centric study. Participants were patients diagnosed with SpA, non-inflammatory rheumatic or autoimmune disease (controls), or RA. Traumatic events were identified by the brief trauma questionnaire (BTQ). PTSD was defined as the presence of a traumatic event and ≥4 symptoms on the short PTSD checklist scale. RESULTS: Among 1389 participants, 510 patients were diagnosed with SpA (167 ankylosing spondylitis, 140 psoriatic arthritis, 130 non-radiographic-axial SpA, and 51 peripheral SpA), 365 with non-inflammatory rheumatic disease and 514 patients with RA. The frequency of trauma in SPA patients was 33.7%, of which 30.5% in AS, 30.7% in PsA, 37.7% in nr-axSpA and 41.2% in peripheral SpA (P=NS). The prevalence of PTSD in SPA patients was 4.9%, (of which 3.6% in AS, 2.9% in PsA, 6.2% in nr-axSpA and 7.8% in peripheral SpA [P=NS]) and was not significantly different from the controls (after IPTW 4.8% vs. 6.7%). The frequency of trauma and PTSD was also comparable between RA and controls and between SPA and RA. CONCLUSION: Traumatic events and PTSD occurring prior to diagnosis is as rare in SpA as in non-inflammatory rheumatic diseases and RA.

Concomitant fibromyalgia in primary Sjögren's syndrome in the French ASSESS cohort: comparison of the ACR 1990 and ACR 2016 criteria, FiRST questionnaire and physician's opinion.

OBJECTIVES: Dryness, fatigue, and pain are classic symptoms in primary Sjögren's syndrome (pSS) but are also common in fibromyalgia (FM). We compared the characteristics of FM assessed by different criteria (American College of Rheumatology (ACR) 2016 and 1990 criteria), physician's opinion and Fibromyalgia Rapid Screening Tool (FiRST) questionnaire) in a cohort of patients with pSS. METHODS: Eight hospital departments tested 134 patients with pSS according to AECG criteria from the Assessment of Systemic Signs and Evolution in Sjögren's Syndrome (ASSESS) cohort. RESUKLTS: FM was present in 19%, 18%, 20%, and 29% of cases according to ACR 2016, ACR 1990 criteria, physician's opinion and the FiRST questionnaire, respectively. FM criteria-positive patients had higher EULAR SS Patient-Reported Index (ESSPRI) score, but not higher EULAR SS Disease Activity Index (ESSDAI) score. The objective measurements of dryness and the use of corticosteroids and immunosuppressive drugs did not differ between FM positive and negative patients. Regarding the ESSPRI dryness and fatigue subscale scores, depression and anxiety scores and the use of anxiolytics and antidepressants, the FiRST questionnaire exhibited a higher difference between positive and negative patients than ACR 2016 criteria. ACR 1990 and physician's opinion were somewhere in the middle. ACR 2016 exhibited moderate agreement with ACR 1990 (κ=0.52) and the physician's opinion (κ=0.60) and poor agreement with FiRST (κ=0.39). CONCLUSIONS: The FM criteria identified pSS patients with higher ESSPRI scores but not higher ESSDAI systemic disease scores. Agreement between the different FM criteria was moderate, and the characteristics they described did not fully coincide.

Lymphoma complicating rheumatoid arthritis: results from a French case-control study.

OBJECTIVES: To study the characteristics of B-cell non-Hodgkin's lymphoma (NHL) or Hodgkin lymphoma complicating rheumatoid arthritis (RA) and to identify RA-related factors associated with their occurrence. METHODS: A multicentre case-control study was performed in France. Cases were patients with RA fulfilling ACR-EULAR 2010 criteria in whom B-cell NHL or Hodgkin lymphoma developed after the diagnosis of RA. For each case, 2 controls were assigned at random from the ESPOIR cohort and were matched on age at lymphoma diagnosis (cases)/age at the 10-year follow-up visit in the cohort (controls). Case and control characteristics were compared to identify parameters associated with the occurrence of lymphoma. RESULTS: 54 cases were included and matched to 108 controls. Lymphomas were mostly diffuse large B-cell lymphoma (DLBCL, n=27, 50.0%). On immunochemistry, 4 of 27 (14.8%) lymphoma cases were positive for Epstein-Barr virus. On univariate analysis, factors associated with the occurrence of lymphoma were male sex (OR 3.3, 95% CI 1.7 to 6.7), positivity for ACPA (OR 5.1, 95% CI 2.0 to 15.7) and rheumatoid factor (OR 3.9, 95% CI 1.6 to 12.2), and erosions on radiographs (OR 3.8, 95% CI 1.7 to 8.3) and DAS28 (OR 2.0, 95% CI 1.5 to 2.7), both at the time of matching. Methotrexate, TNF blockers and a number of previous biologics were not associated with the occurrence of lymphoma. On multivariable analysis, erosions and DAS28 remained significantly associated with increased risk of lymphoma. CONCLUSION: Lymphomas complicating RA are mostly DLBCL. Risk of lymphoma in patients with RA was increased with markers of disease activity and severity, which supports the paradigm of a continuum between autoimmunity and lymphomagenesis in RA.

Therapeutic education improves rheumatoid arthritis patients' knowledge about methotrexate: a single center retrospective study.

To assess, by means of a questionnaire, the effectiveness of a therapeutic education session on rheumatoid arthritis patients' knowledge about methotrexate. Retrospective study of data collected in routine care. STROBE guidelines were used. Rheumatoid arthritis patients treated with methotrexate had a therapeutic education session conducted by a rheumatology nurse at time 0 and 6 months after. They completed a questionnaire to assess their knowledge about methotrexate before the first therapeutic education session and 6 and 12 months after. A score from 0 to 100 was calculated based on 20 questions. A total of 66 patients were enrolled (50 women), with a mean age of 57 years, median disease duration of 4 years, and methotrexate treatment duration of 2 years. The knowledge score improved 6 months after the first therapeutic education session and was unchanged at 12 months. Significant improvement was observed in knowledge about the need for contraception, the contraindication of trimethoprim, the maximum dose not to be exceeded, reduction in alcohol consumption, and the value of combining folic acid with methotrexate. Knowledge about the risk of hypersensitivity pneumonitis did not improve. Skills related to the need for and timing of laboratory testing and contraception were evaluated using two role-playing situations. None of the skills improved. A therapeutic education session improves patients' knowledge about methotrexate at 6 months.

Epidemiology of cutaneous involvement in Sjögren syndrome: Data from three French pSS populations (TEARS, ASSESS, diapSS).

OBJECTIVE: To determine the prevalence and significance of dermatological disorders in primary Sjögren syndrome (pSS). METHODS: We used 2 pSS French cohorts (ASSESS, in which prevalence of skin disorders in 395 patients was evaluated; and diapSS, in which 76 on 139 pSS patients had an examination by a dermatologist) and baseline data of the TEARS randomized trial (110 patients with recent or active pSS treated with rituximab or placebo and evaluated for skin dryness using a visual analogue scale (VAS) out of 100). RESULTS: Skin manifestations included in the EULAR Sjögren syndrome disease activity index (ESSDAI) were rare in the ASSESS cohort (n=16/395, 4.1%, mainly purpuras; only 3 had high activity), but they were associated with activity in the other ESSDAI domains (peripheral neurological (P<0.001), muscular (P<0.01), haematological (P<0.05), biological (P<0.05), history of arthritis (P<0.01), splenomegaly (P<0.05) and higher gamma globulin levels (P<0.01)). In the diapSS cohort, compared to pSS patients not receiving a dermatological consultation, the pSS patients who had a dermatological consultation had significantly more dermatological involvement outside the ESSDAI score [38.2% (29/76) versus 15.9% (10/63); P<0.01]. The TEARS study showed a high prevalence of cutaneous dryness (VAS>50; 48.2%) and found that patients with dry skin had higher VAS pain (P<0.01) and drought (P<0.01) scores. CONCLUSION: ESSDAI skin activity is rare and associated with hypergammaglobulinemia and ESSDAI activity. Systematic dermatological examination is informative for non-specific lesions. The most common skin disorder is skin dryness, which is associated with a higher pain and overall subjective dryness.

Refining myositis associated with primary Sjögren's syndrome: data from the prospective cohort ASSESS.

OBJECTIVES: To refine the prevalence, characteristics and response to treatment of myositis in primary SS (pSS). METHODS: The multicentre prospective Assessment of Systemic Signs and Evolution in Sjögren's Syndrome (ASSESS) cohort of 395 pSS patients with ≥60 months' follow-up was screened by the 2017 EULAR/ACR criteria for myositis. Extra-muscular complications, disease activity and patient-reported scores were analysed. RESULTS: Before enrolment and during the 5-year follow-up, myositis was suspected in 38 pSS patients and confirmed in 4 [1.0% (95% CI: 0.40, 2.6)]. Patients with suspected but not confirmed myositis had higher patient-reported scores and more frequent articular and peripheral nervous involvement than others. By contrast, disease duration in patients with confirmed myositis was 3-fold longer than without myositis. Two of the four myositis patients fulfilled criteria for sporadic IBM. Despite receiving three or more lines of treatment, they showed no muscle improvement, which further supported the sporadic IBM diagnosis. The two other patients did not feature characteristics of a myositis subtype, which suggested 'pure' pSS myositis. Steroids plus MTX was then efficient in achieving remission. CONCLUSIONS: Myositis, frequently suspected, occurs in 1% of pSS patients. Especially when there is resistance to treatment, sporadic IBM should be considered and might be regarded as a late complication of this disease.

Prevalence of Migraine and Neuropathic Pain in Rheumatic Diseases.

To investigate the physiopathology of pain in chronic inflammatory rheumatic diseases (CIRDs), we assessed the prevalence of migraine and neuropathic pain in 499 patients with CIRDs. We studied 238 patients with rheumatoid arthritis, 188 with spondyloarthritis (SpA), 72 with psoriatic arthritis (PsA), and 1 unclassified. Migraine was diagnosed according to IHS migraine diagnostic criteria. Neuropathic pain was diagnosed when patients scored at least 3 on the DN4 questionnaire. Participants completed a validated self-assessment questionnaire. Migraine prevalence was 34% (165/484), and it was highest in PsA. Risk factors for migraine were a high level of anxiety, female sex, young age, and TNF-alpha inhibitor treatment (OR = 1.90 (1.13-3.25)). Besides, high disease activity was a risk factor in SpA. Blood CRP level was not significantly associated with migraine. Of 493 patients with CIRDs, 21.5% had chronic pain with neuropathic characteristics. Compared to the French general population, these patients had significantly higher prevalences of migraine (two-fold) and neuropathic pain (three-fold). This study showed that migraine and neuropathic pain frequently occurred in patients with rheumatic diseases. Therefore, upon reporting residual pain, these patients should be checked for the presence of migraine or neuropathic pain, despite adequate clinical control of rheumatic disease.

Chronic bursitis and tenosynovitis revealing Whipple's disease.

Joint complaints, most commonly intermittent arthritis, are the initial manifestation in about three-fourths of Whipple's disease cases. We herein report on two cases wherein Whipple's disease manifested itself as chronic bursitis and tenosynovitis at several sites. A 42 year-old man had bilateral olecranon bursitis, a right patellar bursitis and an extensor tenosynovitis on the left wrist and a 54 year-old man had extensor tenosynovitis at both wrists and a bilateral tenosynovitis of the extensors at both ankle. Methotrexate in both patients and etanercept in one of them were not effective. Polymerase chain reaction testing revealed Tropheryma whipplei on feces, bursitis and articular fluid samples. Duodenal biopsy proved to be normal. Doxycycline and hydroxychloroquine were rapidly effective. Chronic bursitis and tenosynovitis must be added to the list of rheumatologic manifestations that may evoke the diagnosis of Whipple disease.