An add-on training program involving breathing exercises, cold exposure, and meditation attenuates inflammation and disease activity in axial spondyloarthritis - A proof of concept trial.

OBJECTIVES: The primary objective of this trial was to assess safety and anti-inflammatory effects of an add-on training program involving breathing exercises, cold exposure, and meditation in patients with axial spondyloarthritis. METHODS: This study was an open-label, randomised, one-way crossover clinical proof-of-concept trial. Twenty-four patients with moderately active axial spondyloarthritis(ASDAS >2.1) and hs-CRP ≥5mg/L were included and randomised to an intervention (n = 13) and control group (n = 11) group that additionally received the intervention after the control period. The intervention period lasted for 8 weeks. The primary endpoint was safety, secondary endpoints were change in hs-CRP, serum calprotectin levels and ESR over the 8-week period. Exploratory endpoints included disease activity measured by ASDAS-CRP and BASDAI, quality of life (SF-36, EQ-5D, EQ-5D VAS), and hospital anxiety and depression (HADS). RESULTS: We found no significant differences in adverse events between groups, with one serious adverse event occurring 8 weeks after end of the intervention and judged 'unrelated'. During the 8-week intervention period, there was a significant decline of ESR from (median [interquartile range] to 16 [9-26.5] to 9 [5-23] mm/hr, p = 0.040, whereas no effect was found in the control group (from 14 [8.3-27.3] to 16 [5-37] m/hr, p = 0.406). ASDAS-CRP declined from 3.1 [2.5-3.6] to 2.3 [1.9-3.2] in the intervention group (p = 0.044). A similar trend was observed for serum calprotectin (p = 0.064 in the intervention group versus p = 0.182 in the control group), but not for hs-CRP. CONCLUSIONS: This proof-of-concept study in axial spondyloarthritis met its primary endpoint with no safety signals during the intervention. There was a significant decrease in ESR levels and ASDAS-CRP upon the add-on training program in the intervention group. These findings warrant full-scale randomised controlled trials of this novel therapeutic approach in patients with inflammatory conditions. TRIAL REGISTRATION: ClinicalTrials.gov; NCT02744014.

Progressive disseminated histoplasmosis mimicking a flare of systemic lupus erythematosus: a European case report.

INTRODUCTION: Diagnosing progressive disseminated histoplasmosis (PDH) in patients with systemic lupus erythematosus (SLE) is diagnostically challenging. Since PDH is lethal when untreated, awareness of this infection in patients with SLE is of utmost importance. To the best of our knowledge, this is the first description of a case of PDH in a patient with SLE in Europe. CASE PRESENTATION: A 56-year-old woman of Surinamese descent with a history of SLE, presented with fever and polyarthritis. Although a flare of SLE was suspected initially, cultures of bone marrow and broncho-alveolar lavage fluid grew Histoplasma capsulatum. CONCLUSION: This case report highlights that physicians should be aware of progressive disseminated histoplasmosis in patients with SLE treated with immunosuppressive agents. The signs and symptoms can easily mimic a SLE flare, which would then be treated with more aggressive immunosuppression. Failure to recognize the infection will therefore invariably lead to death of the patient. Progressive disseminated histoplasmosis is usually not recognized by doctors in non-endemic areas such as Europe. However, globalisation and more frequent intercontinental traffic of immunocompromised patients currently increases the incidence of histoplasmosis in these areas. It is therefore of life-saving importance that doctors are aware of the features of the infection in areas where H. capsulatum is not endemic.

Results of a questionnaire on the treatment of patients with Behçet's syndrome: a trend for more intensive treatment.

OBJECTIVES: To determine the preferred treatment for patients with Behçet's syndrome. METHODS: A questionnaire was given to all participants of the 2010 meeting of the International Society for Behçet's Disease. RESULTS: Forty-one respondents from 6 different subspecialties. In the case of a patient with (severe) posterior uveitis or parenchymal central nervous system (CNS) disease no consensus was seen. A diffuse spectrum of different schedules were given. In both uveitis and CNS disease the majority of respondents preferred treatment options consisting of combination systemic therapy and systemic corticosteroids. TNF was preferred as first line drug in uveitis in 7.5% and in severe uveitis in 32.5% of respondents. In parenchymal CNS disease TNF blockage was given by 17% of the respondents. EULAR guidelines regarding uveitis were followed by 12/40 physicians. In patients with a new deep vein thrombosis, 90% of respondents would intensify immunosuppression. More than half would also anticoagulate. CONCLUSIONS: Although consensus about how to treat patients with Behçet syndrome in different clinical situations is far from present, treatment has become more intensive when compared to 10-20 years ago. More uniformity should be sought for in the decision process in individual patients with Behçet's syndrome, regarding their treatment, as well as adhering to evidence, as presented in the EULAR guidelines, when present.

Venous and arterial thromboembolic events in adalimumab-treated patients with antiadalimumab antibodies: a case series and cohort study.

OBJECTIVE: We observed 3 patients who developed severe venous and arterial thromboembolic events during treatment with adalimumab, 2 of whom had rheumatoid arthritis (RA) and 1 of whom had psoriatic arthritis. Antiadalimumab antibodies were detected in all 3 patients. We undertook this study to determine whether the development of antiadalimumab antibodies was associated with thromboembolic events during adalimumab treatment. METHODS: A retrospective search (with blinding with regard to antiadalimumab antibody status) for thromboembolic events was performed in a prospective cohort of 272 consecutively included adalimumab-treated RA patients. Incidence rates were calculated and hazard ratios (HRs) were estimated using Cox regression. None of the index patients were part of the cohort. RESULTS: Antiadalimumab antibodies were detected in 76 of 272 patients (28%). Eight thromboembolic events were found, 4 of which had occurred in patients with antiadalimumab antibodies. The incidence rate was 26.9/1,000 person-years for patients with antiadalimumab antibodies and 8.4/1,000 person-years for patients without those antibodies (HR 3.8 [95% confidence interval 0.9-15.3], P = 0.064). After adjustment for duration of followup, age, body mass index, erythrocyte sedimentation rate, and prior thromboembolic events, the HR was 7.6 (95% confidence interval 1.3-45.1) (P = 0.025). CONCLUSION: These findings suggest that the occurrence of venous and arterial thromboembolic events during adalimumab treatment is higher in patients with antiadalimumab antibodies than in those without antiadalimumab antibodies. Patient numbers were relatively small; therefore, validation in other cohorts is mandatory.

A 57-year-old man who developed arthritis during R-CHOP chemotherapy for non-Hodgkin lymphoma.

Rituximab is a chimeric human-mouse anti-CD20 monoclonal antibody, which is used in the treatment of both B-cell lymphomas and rheumatic diseases. We describe a case of a previously healthy 57-year-old man developing arthritis while being treated with rituximab-CHOP chemotherapy (R-CHOP) for a non-Hodgkin lymphoma. The remittant arthritis developed at successively shorter time-intervals after R-CHOP administration and only improved after rituximab was removed from the chemotherapy schedule, suggesting a rituximab-related phenomenon, as extensive diagnostic testing ruled out any other diagnosis.

[Ultrasonography in rheumatological practice]. / Echografie in de reumatologische praktijk.

Musculoskeletal ultrasonography of the rheumatologist can be useful as a supplement to physical diagnostic assessment or as an aid to diagnostic puncture or therapeutic injection. The essence of musculoskeletal ultrasonography includes visualisation of joints and periarticular structures, muscles, tendons, tendon-sheets and insertions. With ultrasound, punctures, biopsies, and injections can be performed more precisely. A specific ultrasound technique is (color and power) doppler; three-dimensional ultrasonography is a promising new imaging modality. The learning curve of musculoskeletal ultrasonography differs according to indication. Data regarding the validity, reproducibility, sensivity and specificity of ultrasonographic findings are scarce. Further development of guidelines for the use and indications of musculoskeletal ultrasonography is warranted.

The outcome of angiography in patients with Raynaud's phenomenon: an unexpected role for atherosclerosis and hypercholesterolemia.

OBJECTIVE: Upper extremity angiography can make an important contribution to the diagnosis in vasculopathy. The present study was designed to assess the diagnostic role of upper extremity angiography in patients with disturbed circulation of the hand, according to a standardised protocol. METHODS: The study was carried out in an outpatient setting in 103 patients suffering from bilateral Raynaud's phenomenon without any obvious underlying disease and who were unresponsive to nifedipine and aspirin. All patients had angiographies taken according to a standardized technique using vasodilating medication, and reviewed according to a standardised protocol that covered all the known characteristics of angiopathy such as diminished flow, stops, tortuosity, irregularity of the wall, tapering, collaterals and blushing. RESULTS: Standardised angiograms showed vasculopathy compatible with primary vasospasm in 42 patients [all women; mean age 35.1 years], atherosclerotic vascular disease in 44 patients [M/F 9/35; mean age 46.7 years], peripheral embolism in 8 patients [M/F 4/4; mean age 38.4 years], vasculitis in 3 patients [3 women; mean age 38 years] and Buerger's disease in 3 patients [3 men; mean age 47 years]. Inter-observer differences were present in 4 cases, but consensus could be reached through open discussion. An unexpected 47% of patients with atherosclerotic vascular disease had dyslipidemia, frequently of familial origin. CONCLUSIONS: The standardised angiography protocol proved to be helpful in the assessment of upper extremity angiography. Surprisingly, a high prevalence of angiographic abnormalities compatible with atherosclerotic vascular disease could already be diagnosed in relatively young patients with Raynaud's phenomenon, of whom 47% showed hypercholesterolemia.

Chronic wrist pain: diagnosis and management. Development and use of a new algorithm.

OBJECTIVE: Chronic wrist pain can be difficult to manage and the differential diagnosis is extensive. To provide guidelines for assessment of the painful wrist an algorithm was developed to encourage a structured approach to the diagnosis and management of these patients. METHODS: A review of the literature on causes of chronic wrist pain was undertaken; history taking, physical examination and imaging studies were evaluated systematically to determine which of the many potential conditions was the cause of the wrist pain. Chronic wrist pain was subdivided into pain of probable intra-articular or extra-articular origin. By means of this classification a clinical algorithm was developed to establish a diagnosis and its clinical usefulness was tested in a prospective study of 84 patients presenting to our outpatient clinic. RESULTS: A definite diagnosis could be established in 59% (49 of 84) of the cases by careful history taking, extensive physical examination, plain radiographs, ultrasound examination and bone scintigraphy. In 19% of the cases (16 of 84) a probable diagnosis was made resulting in a total figure 78% (65 of 84). Additional imaging studies (arthrography, magnetic resonance imaging and computed tomography) increased the definite diagnoses to 70% (59 of 84). CONCLUSION: The algorithm proved easy to use and by the use of careful history taking, thorough physical examination and simple imaging techniques (ultrasonography and scintigraphy) a diagnosis was made in 78% of cases.

Patterns of disease progression in the rheumatoid wrist: a long-term followup.

OBJECTIVE: To identify different patterns of disease manifestation and changes in the rate of progression of rheumatoid arthritis (RA) in the wrist. METHODS: Forty wrists, with normal baseline radiographs, of 20 patients with RA were evaluated by means of a retrospective radiographic review for a period of at least 15 years. RESULTS: Radiographical scores for damage (Larsen method) and malalignment (carpal collapse and ulnar translocation index; radial deviation of the wrist and ulnar shift of the fingers) showed progression with increasing disease duration for all patients. Women had higher Larsen scores than men (p < 0.05) and rheumatoid factor positive patients had higher Larsen scores than rheumatoid factor negative patients. For all 3 left-handed patients the dominant scores were somewhat higher than the right-handed scores, but the difference was not significant. For the 17 right-handed patients no differences were found between the dominant and the left hand. Early in the course of the disease 4 types of wrist involvement can be identified on the basis of the first localization of damage in the wrist (central, radial, ulnar, and diffuse type). Radial deviation of the wrist was increased in wrists with "central" involvement compared to wrists with "diffuse" involvement (p < 0.05). Furthermore, radial deviation of the wrist was positively correlated with ulnar drift of the fingers (p < 0.01). CONCLUSION: Wrist involvement was found to play an important role in the typical rheumatoid deformity of the hand. Early treatment of the wrist is proposed to prevent this deformity.

Deforming arthropathy or lupus and rhupus hands in systemic lupus erythematosus.

OBJECTIVE: Although deforming arthropathy in systemic lupus erythematosus (SLE) is characterised by a number of manifestations, definitive criteria for the different forms have not yet been established. To define deforming arthropathy and its different types a study was undertaken of 176 SLE patients. METHODS: Using as criterion any deviation from any of the metacarpus finger axes 17 patients (16 women, one man) were identified with clinical deforming arthropathy. These patients were evaluated according to a standardised protocol that covered all known characteristics of deforming arthropathy. By means of "Jaccoud's arthropathy index" three different forms were identified. RESULTS: Three patients had an erosive form of deforming arthropathy (or rhupus hand) such as those seen in frank rheumatoid arthritis (RA), eight patients were identified as having Jaccoud's arthropathy (or lupus hand), and the remaining six patients had mild deforming arthropathy. Jaccoud's arthropathy is characterised by severe deformation of the hands (ulnar deviation, swan neck deformities, and Z deformity of the thumb) and feet with multiple non-erosive subluxations, mild aching and little or no evidence of synovitis. All patients, but one, fulfilled just four criteria of the ACR classification and joint symptoms were always found to precede the diagnosis of SLE. Furthermore a remarkable association of Jaccoud's arthropathy with fetal loss, thrombosis--both venous and arterial--and the presence of antiphospholipid antibodies was found. CONCLUSIONS: These data suggest that Jaccoud's arthropathy represents a subset of SLE. Subdivision of deforming arthropathy into several clinical forms can facilitate the clinical management of this disorder.

The current role of high-resolution ultrasonography of the hand and wrist in rheumatic diseases.

OBJECTIVE: To assess the current role of ultrasound in the diagnosis and treatment of pathological changes in the wrist and hand. METHODS: 39 patients (14 male and 25 female, mean age 35 yrs.) with ill-defined pain and/or swelling of the wrist or hand were examined using a high-definition ultrasound (US) instrument. RESULTS: 18 patients had tenosynovitis, which in one patient was due to a previously unsuspected foreign body. 10 patients had arthritis involving the wrist and 5 the fingers; 2 patients had a ganglion; one had a neuroma of the median nerve and one patient with a previous tenorrhaphy suffered from the recurrent rupture of this tendon. Two patients had carpal tunnel syndrome, one due to tenosynovitis and one due to the formation of a post-operative fibrotic sheath around the median nerve. 7 patients with synovitis of the wrist underwent US-guided synovial biopsy. 12 patients with tenosynovitis and 6 with arthritis received injections of corticosteroids plus anaesthetic under US-guidance. The spreading of the steroid crystals around the tendon and throughout the joint could be easily monitored. No complications were encountered. CONCLUSION: High-definition ultrasound is a valuable technique for the imaging of pathologic changes of the wrist and hand and for injection therapy.

Ultrasound guided synovial biopsy of the wrist.

Seven patients (4 female and 3 male, mean age 46) with arthritis of the wrist (n = 7) without known etiology were evaluated. High-definition ultrasound equipment was used for localization of synovial hypertrophy, suitable for ultrasound guided biopsy without risk. A 18-gauge diameter Tru-cut biopsy needle was used in an automated gun. Two passes were performed with continuous guidance of the needle-tip. In all patients representative synovial tissue was obtained in adequate amount. No complications were encountered. Ultrasound guided biopsy is proposed as an effective technique which can be performed with low patient discomfort on an outpatient basis.

Changes in (markers of) bone metabolism during high dose corticosteroid pulse treatment in patients with rheumatoid arthritis.

OBJECTIVE: To examine the effect of high dose corticosteroid pulse treatment (three times 200 mg dexamethasone intravenously in eight days) on calcium and bone metabolism in 17 consecutive patients with active rheumatoid arthritis (RA). METHODS: Bone formation was quantified by measurement of serum alkaline phosphatase, osteocalcin, and carboxyterminal propeptide of type I procollagen (pro-I-CPP) concentrations. Bone resorption was measured by urinary excretion of calcium, hydroxyproline, (free and total) deoxypyridinoline (Dpyr), (free and total) pyridinoline (Pyr), and serum concentrations of the carboxyterminal cross linked telopeptide of type I collagen (I-CTP). Disease activity of RA was measured by erythrocyte sedimentation rate, C reactive protein, and Ritchie and Thompson joint scores. RESULTS: Disease activity was initially high, and decreased during corticosteroid pulse treatment and the following five weeks. Osteocalcin, alkaline phosphatase, and pro-I-CPP concentrations were initially within normal limits, while I-CTP, Dpyr, and Pyr were increased. Osteocalcin and pro-I-CPP concentrations decreased (p < 0.01) during corticosteroid pulse treatment, but rapidly returned to baseline after the treatment. No changes were observed in alkaline phosphatase and urinary excretion of calcium and hydroxyproline. Bone resorption measured by serum I-CTP and urinary excretion of Pyr and Dpyr was unchanged or decreased (p < 0.05-0.01), depending on the time of measurement and the parameter measured. CONCLUSIONS: In these patients with active RA, bone resorption was increased, while bone formation was within normal limits. During high dose corticosteroid pulse treatment, bone formation was only transiently decreased, while markers of bone resorption were unchanged or decreased. Because corticosteroid pulse treatment has only a short term negative effect on bone formation, and because it probably reduces bone resorption, at least partly as a result of the decreased disease activity, the effect of corticosteroid pulse treatment on bone may be assumed to be relatively mild.

Magnetic resonance imaging of the femoral head to detect avascular necrosis in active rheumatoid arthritis treated with methylprednisolone pulse therapy.

Efficacious management of patients with avascular necrosis of bone (AVN) necessitates the identification of patients with a high risk of collapse of the femoral head. In this prospective study we imaged both hips of 10 patients with active rheumatoid arthritis, who were treated with methylprednisolone pulse therapy. MRI and conventional radiography were performed before MP-pulse therapy and 6 and 12 months thereafter. Two patients showed unilateral changes, compatible with AVN. One patient became symptomatic and revealed characteristic radiographic abnormalities. The other patient remained asymptomatic and the MRI appearance returned to normal after 6 months.