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.

Long-term immunogenicity after yellow fever vaccination in immunosuppressed and healthy individuals.

BACKGROUND: The live-attenuated yellow fever vaccine (YFV) is generally contraindicated in immunosuppressed patients. Our aim was to investigate if immunosuppressive therapy impairs the long-term protection against yellow fever virus in patients who had received YFV prior to the start of their immunosuppressive therapy. METHODS: Our study examined 35 healthy individuals and 40 immunosuppressed patients with autoimmune diseases or organ transplants. All individuals had received YFV prior to the onset of their immunosuppression. We analysed the long-term influence of the immunosuppressive therapy on the YFV protective immunity by measuring neutralising antibodies (NA) with the Plaque Reduction Neutralisation Test (PRNT). We assessed risk factors for a negative PRNT result (titre below 1: 10) and their influence on the magnitude of the NA. RESULTS: A median time interval of 21.1 years (interquartile range 14.4-31.3 years) after the YFV in all patients, a total of 35 immunosuppressed patients (88%) were seropositive (PRNT ≥ 1:10) compared to 31 patients (89%) in the control group. The geometric mean titres of NA did not differ between the groups. The duration of an underlying rheumatic disease was the only risk factor found for a lower magnitude of NA. An insufficient level of NA was found in nine subjects (12%) who had received a single dose of YFV (in one subject, the number of YFV doses was unknown). CONCLUSION: The use of an immunosuppressive drug started after the administration of the YFV did not affect long-term persistence of NA. A second dose of YFV may be necessary to secure long-term immunity.

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.

Rare Case of Large Bowel Injury due to Direct Blunt Trauma to a Preexisting Femoral Hernia.

We report a case of an 85-year-old man with a known asymptomatic left femoral hernia who was admitted to the emergency ward a few hours after falling from a bicycle and suffering from blunt trauma of the handlebar to the left inguinal region. The clinical findings and a computed tomography (CT) scan detecting free air in the femoral hernia sac suggested bowel perforation. Emergency laparotomy 6 hours after the incident confirmed a tear of the sigmoid colon accompanied by free blood and faeces in the left inguinal region of the abdomen. A segmental sigmoid resection and a primary end-to-end colorectal anastomosis were performed. The postoperative course was complicated by delayed oral feeding, a local infection, and a partial left testicle necrosis that led to secondary resection. The patient was discharged after 32 days of in-hospital care. Three months post trauma, we recorded a restitutio ad integrum. The case exemplifies that blunt trauma to preexisting femoral hernias may cause potentially lethal bowel perforation and that the time interval between time of injury and surgical treatment may be a prognostic factor. CT scans seem most suitable for ruling out bowel perforation. The scarce literature for blunt trauma to hernias is reviewed.

[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.

A Four-Year Hospital Journey for a Lost and Migrating Appendicolith.

We report a rare case of recurrent abscess formation, including being at a retroperitoneal site, due to a lost and migrating appendicolith. Over a four-year period and following an episode of perforated appendicitis, an otherwise healthy young man underwent two operations for abscess formation with eventual stone removal. Appendicoliths can pose a challenge during the diagnostic and therapeutic journey, and adequate attempts at removal need to be made to prevent avoidable complications. In patients suffering from recurrent flank pain and abscesses after appendectomy, the possibility of a lost or overlooked appendicolith should be considered.

Bilocal recurrence of a neuroendocrine carcinoma of the small intestine: A case report.

INTRODUCTION: Neuroendocrine tumors of the small intestine represent about half of all small intestine neoplasms. Recurrence after surgery with curative intention is frequently observed but recurrence rate has not yet been described or analyzed sufficiently. PRESENTATION OF CASE: In this case bilocal recurrence 4 years after curative surgery of an ileocoecal neuroendocrine carcinoma was observed in a 64 year old female. Diagnosis and follow-up was carried out as proposed in current ENETS guidelines using somatostatin receptor scintigraphy for primary diagnosis and Ga-DOTATOC-PET/CT in follow-up. DISCUSSION: We can confirm that PET/CT for somatostatin receptor imaging shows good sensitivity in detecting neuroendocrine neoplasms and should be preferred for diagnostic, if available. For individual adaptation of follow-up procedures, as far as time intervals and preferred imaging methods are concerned, research on recurrence rate and long term outcome after curative surgery should be extended. CONCLUSION: Livelong follow-up after surgical resection of neuroendocrine tumors is necessary and Ga-DOTA/TOC-PET/CT should be the method of choice, if available.

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.

Biological agents in monotherapy for the treatment of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory disease, which results in joint destruction and permanent disability. The advent of disease-modifying antirheumatic drugs (DMARDs) has made a profound impact on the outcome and prognosis of RA. Methotrexate (MTX) is a central agent in RA therapy, and is used either alone or in combination with biological DMARDs. However, a large proportion of RA patients (20%-40%) either do not respond to or are unable to tolerate MTX or the alternative agents used in place of MTX (including leflunomide, sulfasalazine, azathioprine, hydroxycholoquine and combination DMARDs). For these patients, monotherapy with biological DMARDs is a key treatment option that balances tolerability with improved clinical outcomes. This article reviews the data for four biological agents approved for use as monotherapy in Switzerland (adalimumab, certolizumab pegol, etanercept and tocilizumab) in order to formulate a consensus statement on their roles in biologic monotherapy of RA.

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.