ACE inhibitors in SSc patients display a risk factor for scleroderma renal crisis-a EUSTAR analysis.

OBJECTIVES: To investigate the effect of ACE inhibitors (ACEi) on the incidence of scleroderma renal crisis (SRC) when given prior to SRC in the prospectively collected cohort from the European Scleroderma Trial and Research Group (EUSTAR). METHODS: SSc patients without prior SRC and at least one follow-up visit were included and analyzed regarding SRC, arterial hypertension, and medication focusing on antihypertensive medication and glucocorticoids (GC). RESULTS: Out of 14,524 patients in the database, we identified 7648 patients with at least one follow-up. In 27,450 person-years (py), 102 patients developed SRC representing an incidence of 3.72 (3.06-4.51) per 1000 py. In a multivariable time-to-event analysis adjusted for age, sex, disease severity, and onset, 88 of 6521 patients developed SRC. The use of ACEi displayed an increased risk for the development of SRC with a hazard ratio (HR) of 2.55 (95% confidence interval (CI) 1.65-3.95). Adjusting for arterial hypertension resulted in a HR of 2.04 (95%CI 1.29-3.24). There was no evidence for an interaction of ACEi and arterial hypertension (HR 0.83, 95%CI 0.32-2.13, p = 0.69). Calcium channel blockers (CCB), angiotensin receptor blockers (ARB), endothelin receptor antagonists, and GC-mostly in daily dosages below 15 mg of prednisolone-did not influence the hazard for SRC. CONCLUSIONS: ACEi in SSc patients with concomitant arterial hypertension display an independent risk factor for the development of SRC but are still first choice in SRC treatment. ARBs might be a safe alternative, yet the overall safety of alternative antihypertensive drugs in SSc patients needs to be further studied.

Effect of rheumatoid arthritis and age on metacarpal bone shaft geometry and density: A longitudinal pQCT study in postmenopausal women.

OBJECTIVE: This study aimed to elucidate the effects of changes in the geometry and density of the metacarpal bone of patients with rheumatoid arthritis (RA). METHODS: This prospective study included consecutive postmenopausal RA patients who met the American College of Rheumatology Criteria and healthy controls (HC). Peripheral quantitative computed tomography scans at 50% of the total metacarpal shaft (third metacarpal bone) were obtained at baseline and follow-ups. Use of bisphosphonates (BP), glucocorticoids (GC), biologics, and disease-modifying anti-rheumatic drugs (DMARD) was monitored (baseline to follow-up). Total cross-sectional area (CSA), cortical-transitional zone and compact zone CSA, cortical volumetric bone mineral density, and compact cortex porosity were measured. A linear mixed-effects model was used to determine significant differences in the rate of change in the RA and control groups and in RA patient subgroups. RESULTS: Thirty-nine RA patients and 42 consecutive postmenopausal HC were followed for 63 months. RA and HC depicted a time-dependent increase of medullary CSA (+0.41 mm2/year, P < 0.0001), while total CSA remained stable (P = 0.2). RA status was associated with a loss of cortical bone mineral density (interaction: -3.08 mg/mm3; P = 0.014). In RA subgroup analysis, GC use ≥5 mg/day was positively correlated with a fourfold increase of medullary CSA (0.67 mm2/year P = 0.009), which resulted in a three- to fourfold loss of cortical density (-6.6 mg/mm3/year; P = 0.002) and cortical CSA (-0.57 mm2/year, P = 0.004). Patients with high disease activity and high GC dose at baseline demonstrated an increase in the total CSA (0.29 mm2/y; P = 0.049) and a loss of cortical BMD (-5.73 mg/mm3/y; P = 0.05) despite good clinical response. CONCLUSION: Increase in medullary metacarpal CSA and thinning of the cortical CSA are physiological and time dependent. RA status is associated with loss in cortical density. Even upon biological therapy, low glucocorticoid dose affects metacarpal bone shaft geometry and density over time.

[Large-vessel vasculitis-giant cell and Takayasu arteritis]. / Großgefäßvaskulitiden ­ Riesenzellarteriitis und Takayasu-Arteriitis.

Large-vessel vasculitis includes giant cell arteritis (GCA) and Takayasu arteritis (TA). GCA can affect persons from the age of 50 years and is more frequent among women. The disease course generally begins with an acute phase, with patients feeling very unwell and experiencing temporal headaches. Rapid diagnosis and treatment are necessary to reduce the risk of blindness. A suspected diagnosis must be confirmed by imaging, histology is optional. Initial treatment comprises oral prednisone. Recent studies have demonstrated inhibition of interleukin­6 with tocilizumab (TCZ) to be highly effective. Alternatively, methotrexate can be administered in a steroid-sparing approach. In contrast, TA onset is generally during childhood or adolescence, and begins with moderate systemic inflammation. The aorta and its main branches are affected. Treatment comprises steroids, disease-modifying antirheumatic drugs, and the tumor necrosis factor inhibitor infliximab or TCZ.

Paternal exposure to antirheumatic drugs-What physicians should know: Review of the literature.

Reproduction capacity and long-term preserved hormonal function are important aspects with big impacts on patients' quality of life. Updated information on the interaction between drug therapy and reproductive function is essential when discussing family planning with patients. Currently, limited data is published regarding paternal exposure to different medications. Thus, it may be a challenge for the practitioner to choose the right therapy for a young male patient. Therefore we reviewed the literature, for effects of antirheumatic drugs on male gonadal function with a focus on spermatogenesis and offspring.

[Large vessel vasculitis : Giant cell arteritis and Takayasu arteritis]. / Großgefäßvaskulitiden : Riesenzellarteriitis und Takayasu-Arteriitis.

According to the Chapel Hill Classification, large vessel vasculitides encompass giant cell arteritis (GCA) and the histologically related Takakaysu arteritis (TAK). The two diseases lack autoantibodies and present with a systemic inflammatory response. GCA typically shows a sudden onset with profound sickness, loss of appetite and of body weight, and temporal headache. Due to the substantial risk of sudden blindness, diagnostic work-up has to be performed immediately and treatment started without delay. A close association between polymyalgia rheumatica (PMR) and GCA is well established. Takayasu arteritis very often begins in adolescence. In contrast to GCA, the general symptoms are much less pronounced and aside from occasional carotidodynia there is a lack of diagnostic symptoms. TAK is often diagnosed in late stages due to exercise-induced claudication.

Home parenteral nutrition is beneficial in systemic sclerosis patients with gastrointestinal dysfunction.

OBJECTIVES: To assess 12-month changes in nutritional status and quality of life (QoL) in systemic sclerosis (SSc) patients requiring home parenteral nutrition (HPN). METHOD: We conducted a retrospective, single-centre database analysis of SSc patients regarding a 12-month period of HPN at an interdisciplinary University Unit/team for nutrition and rheumatic diseases. Nutritional status was analysed by nutritional risk screening (NRS) and body mass index (BMI). QoL was evaluated using Short-Form Health Survey (SF-36) questionnaires. RESULTS: Between 2008 and 2013, daily nocturnal HPN was initiated in five consecutive SSc patients (four females and one male, mean age 62.2 years) suffering severe malnutrition due to gastrointestinal tract (GIT) involvement. After 12 months of HPN, the mean NRS score decreased from 4.4 (range 4-5) to 1.4 (range 1-2), the mean BMI increased from 19.1 (range 17.4-20.3) to 21.0 kg/m2 (range 18.3-23.4). QoL improved in all patients, reflected by the summary of physical components with 33.92 points before vs. 67.72 points after 12 months of HPN, and the summary of mental components with 49.66 points before vs. 89.27 points after 12 months of HPN. Two patients suffered one catheter-related infection each with subsequent surgical removal and reinsertion. CONCLUSIONS: HPN is a feasible method for improving anthropometric parameters and QoL in SSc patients severely affected by GIT dysfunction. We recommend HPN in malnourished, catabolic SSc patients unable to otherwise maintain or improve their nutritional status.

Increased bone mineral density at the hypoxia prone site of the juxta-articular metacarpal bone in patients with limited systemic sclerosis: a cross-sectional study.

OBJECTIVES: Low levels of oxygen has been shown to be involved in the induction of osteogenesis, particularly in bone repair. It is unknown whether hypoxia leads to osteogenesis at the hypoxia prone skeletal sites in limited systemic sclerosis. This study determined the total and trabecular volumetric bone mineral density (vBMD) at the hypoxia prone site of the juxta-articular metacarpal bone. METHODS: In this cross-sectional study, female patients with limited systemic sclerosis were included and compared to healthy controls. Peripheral quantitative computed tomography was used to measure cross-sectional area, total vBMD, and trabecular vBMD at the radius, the tibia and the third metacarpal bone. Disease severity was assessed by the modified Rodnan Skin Score. RESULTS: Twenty consecutive patients were included in the sclerosis group and 20 in the control group. Mean age was 60 years (range 52-68 years), and mean disease duration was 45 months (range 4-156 months). Age, height, and weight were comparable between the groups. The mean modified Rodnan Skin Score was 1.78 (range 0 to 8). The sclerosis group showed both higher total and trabecular vBMD at the distal metacarpal bone (p=0.05 and 0.04, respectively). vBMD of the tibia and radius did not differ in both groups. CONCLUSIONS: vBMD at the juxta-articular metacarpal bone in patients with limited systemic sclerosis is increased, possibly due to an alteration in local bone metabolism and hypoxia induced local osteogenesis.

Changes in volumetric BMD of radius and tibia upon antidepressant drug administration in young depressive patients.

OBJECTIVES: To determine longitudinal changes in trabecular volumetric BMD (vBMD) at tibia and radius in young depressive patients under antidepressants using pQCT. METHODS: PQCT data on 26 patients (22 females, 4 males) on serotonin re-uptake inhibitors (SSRI), and 14 patients (12 females, 2 males) on non-SSRI (10 SNRI, 4 TCA) were obtained at 4% and 66% of radius and tibia at baseline and at 12-month. Depression was assessed by Beck Depression Inventory (BDI) at baseline and follow-up. Wilcoxon tests were performed to find longitudinal changes in bone parameters within each group, Mann-Whitney tests to detect differences between groups. RESULTS: The two groups were comparable with regard to age, height and BDI. None of the measured bone parameters changed in the SSRI group. In the non-SSRI group trabecular vBMD increased slightly but significantly from baseline to follow-up at radius and tibia (p<0.03). Between group differences were significant for trabecular BMD at the radius. BDI decreased significantly in both groups by the same amount. CONCLUSIONS: Bone properties were found to be stable over 12 months under therapy with SSRIs. Whether SNRI and TCA indeed increase trabecular vBMD need to be shown in larger cohort.

Current state of evidence on 'off-label' therapeutic options for systemic lupus erythematosus, including biological immunosuppressive agents, in Germany, Austria and Switzerland--a consensus report.

Systemic lupus erythematosus (SLE) can be a severe and potentially life-threatening disease that often represents a therapeutic challenge because of its heterogeneous organ manifestations. Only glucocorticoids, chloroquine and hydroxychloroquine, azathioprine, cyclophosphamide and very recently belimumab have been approved for SLE therapy in Germany, Austria and Switzerland. Dependence on glucocorticoids and resistance to the approved therapeutic agents, as well as substantial toxicity, are frequent. Therefore, treatment considerations will include 'off-label' use of medication approved for other indications. In this consensus approach, an effort has been undertaken to delineate the limits of the current evidence on therapeutic options for SLE organ disease, and to agree on common practice. This has been based on the best available evidence obtained by a rigorous literature review and the authors' own experience with available drugs derived under very similar health care conditions. Preparation of this consensus document included an initial meeting to agree upon the core agenda, a systematic literature review with subsequent formulation of a consensus and determination of the evidence level followed by collecting the level of agreement from the panel members. In addition to overarching principles, the panel have focused on the treatment of major SLE organ manifestations (lupus nephritis, arthritis, lung disease, neuropsychiatric and haematological manifestations, antiphospholipid syndrome and serositis). This consensus report is intended to support clinicians involved in the care of patients with difficult courses of SLE not responding to standard therapies by providing up-to-date information on the best available evidence.

[Musculoskeletal puncture, injection and infiltration: swiss rheumatologists' point of view]. / Muskuloskelettale Punktion, Injektion und Infiltration: Standpunkt von Schweizer Rheumatologen.

Arthrocentesis, injection and infiltration of joints and soft tissues belong to the basic procedures in rheumatology. The indications and the practical performance are based on experience and tradition. Nowadays, a crucial reappraisal and adaption of indications and technical aspects appear important in the light of new evidence and technical developments. The main indications for puncture remain the search of an infectious arthritis and reduction of intra-articular pressure due to effusion. Good indications for the injection of glucocorticoids are inflammation in sterile joints and activated osteoarthritis. The local infiltration with corticosteroids in mechanically induced enthesopathies at the lateral epicondyle of the humerus or at the plantar fascia have to be questioned in the light of recent publications which show that this common practice is associated with a poorer outcome than without injection.

[Hand and wrist surgery]. / Operative Eingriffe an Hand und Handgelenk.

Despite improved medical treatment of rheumatoid arthritis, carpal tunnel compression, caput ulnae syndrome and palmar and dorsal tenosynovitis with potential tendon rupture represent urgent surgical indications. While diagnostic and therapeutic synovectomy may guide medical treatment, it should be performed before joint instability and destructive arthritis are established. Swan-neck and Boutonniere deformities as well as ulnar or radial drift of metacarpophalangeal (MCP) joints or the wrist can only be corrected when the involved joints are supple and intact. In the presence of destructive arthritis, partial and total wrist fusion, arthroplasties of the MCP joints and arthrodeses of the distal interphalangeal joints are recommended.

Gender inequity in the provision of care for hip disease: population-based cross-sectional study.

OBJECTIVES: To examine gender differences along the care pathway to total hip replacement. METHODS: We conducted a population-based cross-sectional study of 26,046 individuals aged 35 years and over in Avon and Somerset. Participants completed a questionnaire asking about care provision at five milestones on the pathway to total hip replacement. Those reporting hip disease were invited to a clinical examination. We estimated odds ratios (ORs) [95% confidence intervals (CI)] for provision of care to women compared with men. RESULTS: 3169 people reported hip pain, 2018 were invited for clinical examination, and 1405 attended (69.6%). After adjustment for age and disease severity, women were less likely than men to have consulted their general practitioner (OR 0.78, 95%-CI 0.61-1.00), as likely as men to have received drug therapy for hip pain in the previous year (OR 0.96, 95%-CI 0.74-1.24), but less likely to have been referred to specialist care (OR 0.53, 95%-CI 0.40-0.70), to have consulted an orthopaedic surgeon (OR 0.50, 95%-CI 0.32-0.78), or to be on a waiting list for total hip replacement (OR 0.41, 95%-CI 0.20-0.87). Differences remained in the 746 people who had sought care from their general practitioner, and after adjustment for willingness and fitness for surgery. CONCLUSIONS: There are gender inequalities in provision of care for hip disease in England, which are not fully accounted for by gender differences in care seeking and treatment preferences. Differences in referral to specialist care by general practitioners might unwittingly contribute to this inequity. Accurate information about availability, benefits and risks of hip replacement for providers and patients, and continuing education to ensure that clinicians interpret and correct patients' assumptions could help reduce inequalities.

Short-term changes in magnetic resonance imaging and disease activity in response to infliximab.

OBJECTIVES: To characterise and quantify short-term changes in local inflammation using magnetic resonance imaging (MRI), and to correlate the findings with clinical disease activity in response to infliximab in patients with spondyloarthritis. METHODS: 28 consecutive patients with established spondyloarthritis under successful long-term treatment with infliximab underwent MRI immediately before and one week after re-administration of the TNF blocker. C-reactive protein and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) were assessed at both time points. The MRI protocol included coronal and sagittal turbo-short T1 inversion recovery (STIR) images as well as contrast-enhanced sagittal T1-weighted, fat-suppressed images. Images were assessed in independent sessions using the ASspiMRI-a score, the signal-difference-to-noise ratios (SDNR) and volumetry to assess oedematous and inflamed tissues. RESULTS: BASDAI values were expectedly low at study entry (3.3, SD 2.3). One week after administration of infliximab, 46% of patients reached a BASDAI 20, 39% a BASDAI 50. Kappa values for qualitative assessments and all measurements were excellent (range between 0.83 and 1.0) The ASspiMRI-a dropped most in the thoracic (3.3 points), less in the lumbar (1.21 points) and least in the cervical spine (0.38 points). The decrease of the ASspiMRI-a, the SDNR and the inflamed volumes in response to infliximab re-treatment was significant (p<0.01). The BASDAI showed a weak correlation with the ASspiMRI-a (r = 0.41). CONCLUSIONS: MRI proves to be a valid method to assess and quantify short-term effects of therapy in spondyloarthritis. Comparison between MRI and BASDAI changes show that the BASDAI may underestimate local inflammation. It suggests an explanation for the structural disease progression despite clinical remission.

Induction of complete and sustained remission of rheumatoid pachymeningitis by rituximab.

Aseptic pachymeningitis is a rare and serious complication of rheumatoid arthritis (RA). Herein, we describe a patient with rheumatoid factor-positive and anti-cyclic citrullinated peptide-positive RA who experienced a focal seizure, with aphasia and convulsions of the right side of the body. The findings of magnetic resonance imaging and histologic analysis led to a diagnosis of rheumatoid pachymeningitis. Because the patient had a large number of CD20-expressing B lymphocytes, therapy with rituximab was started and has resulted in complete and sustained remission of both the pachymeningitis and the RA for >2 years. Despite a decrease in immunoglobulins, the patient has remained free of infections, which illustrates the favorable outcome that can result from therapeutic B cell depletion in this potentially lethal manifestation of RA.

A randomised controlled trial of spinal manipulative therapy in acute low back pain.

OBJECTIVE: To determine whether treatment with spinal manipulative therapy (SMT) administered in addition to standard care is associated with clinically relevant early reductions in pain and analgesic consumption. METHODS: 104 patients with acute low back pain were randomly assigned to SMT in addition to standard care (n = 52) or standard care alone (n = 52). Standard care consisted of general advice and paracetamol, diclofenac or dihydrocodeine as required. Other analgesic drugs or non-pharmacological treatments were not allowed. Primary outcomes were pain intensity assessed on the 11-point box scale (BS-11) and analgesic use based on diclofenac equivalence doses during days 1-14. An extended follow-up was performed at 6 months. RESULTS: Pain reductions were similar in experimental and control groups, with the lower limit of the 95% CI excluding a relevant benefit of SMT (difference 0.5 on the BS-11, 95% CI -0.2 to 1.2, p = 0.13). Analgesic consumptions were also similar (difference -18 mg diclofenac equivalents, 95% CI -43 mg to 7 mg, p = 0.17), with small initial differences diminishing over time. There were no differences between groups in any of the secondary outcomes and stratified analyses provided no evidence for potential benefits of SMT in specific patient groups. The extended follow-up showed similar patterns. CONCLUSIONS: SMT is unlikely to result in relevant early pain reduction in patients with acute low back pain.