Anti-tumour necrosis factor-induced skin rashes in inflammatory bowel disease: a systematic review and evidence-based management algorithm.

BACKGROUND: Anti-tumour necrosis factor alpha (anti-TNF) agents are a highly effective treatment for inflammatory bowel disease (IBD). Skin lesions, including psoriasiform, eczematous and lupoid eruptions, may paradoxically result from anti-TNF use and cause significant morbidity leading to discontinuation of therapy. There are no consensus guidelines on the management of these lesions. AIMS: This systematic review considers the existing evidence regarding cutaneous complications of anti-TNF therapy in IBD and the development of an algorithm for management. METHODS: A systematic review was performed by searching Medline (Pubmed) and Embase for articles published from inception to January 2021. The following search terms were used 'anti-tumour necrosis factor alpha', 'infliximab', 'adalimumab', 'certolizumab', 'golimumab', 'inflammatory bowel disease', 'Crohn disease', 'Ulcerative colitis', 'psoriasis', 'psoriasiform', 'dermatitis', 'lupus', 'skin lesion' and 'skin rash'. Reference lists of relevant studies were reviewed to identify additional suitable studies. RESULTS: Thirty-four studies were included in the review. Eczema can generally be managed with topical agents and the anti-TNF can be continued, while the development of lupus requires immediate cessation of the anti-TNF and consideration of alternative immunomodulators. Management of psoriasis and psoriasiform lesions may follow a step-wise algorithm where topical treatments will be trialled in less severe cases, with recourse to an alternative anti-TNF or a switch to an alternative class of biological agent. CONCLUSION: Assessment of anti-TNF skin lesions should be performed in conjunction with a dermatologist and rheumatologist in complex cases. High-quality prospective studies are needed to clarify the validity of these algorithms in the future.

A case series of suprascapular nerve block (with an historical comparator) for shoulder pain in motor neurone disease.

BACKGROUND: Shoulder pain is a distressing but under-reported and poorly managed symptom in people with motor neurone disease. OBJECTIVES: This study aimed to assess the efficacy of suprascapular nerve block for the management of shoulder pain in patients with motor neurone disease. METHODS: A total of 27 patients with motor neurone disease and shoulder pain were offered a suprascapular nerve block. Ten of these patients had bilateral shoulder pain and both were injected, making a total of 37 shoulders. The patients were followed up for a total of 3 months, or until death. Shoulder pain was measured using the pain scale (out of 100) of the shoulder pain and disability index and compared with baseline scores and a placebo control group from an earlier study using the same methodology (ACTRN12619000353190). RESULTS: Following the nerve block there was a significant improvement of pain scores from baseline (58.4) at week 1 (20.8, p < 0.000), week 6 (17.6, p < 0.000) and week 12 (30.4, p = 0.001) and a significant improvement compared with the control group across each time interval. CONCLUSION: Suprascapular nerve block is a safe, effective therapy for patients with chronic shoulder pain.

Update on the diagnosis and management of gout.

Gout is a common clinical problem encountered by both general and specialist clinicians. The key principles in gout management include establishing a definitive diagnosis, the swift treatment of acute attacks, and using urate-lowering therapies appropriately to prevent further attacks and joint damage. The gold standard diagnostic tool for gout remains the identification by polarised light microscopy of monosodium urate crystals in synovial fluid or in a tophus. Emerging diagnostic imaging techniques and novel therapies show promise in the diagnosis and treatment of gout. In most cases, using existing therapies judiciously remains the key determinant of success in managing gout.

Altered insulin response to an acute bout of exercise in pediatric obesity.

Pediatric obesity typically induces insulin resistance, often later evolving into type 2 diabetes. While exercise, enhancing insulin sensitivity, is broadly used to prevent this transition, it is unknown whether alterations in the exercise insulin response pattern occur in obese children. Therefore, we measured exercise insulin responses in 57 healthy weight (NW), 20 overweight (OW), and 56 obese (Ob) children. Blood samples were drawn before and after 30 min of intermittent (2 min on, 1 min off) cycling at ~80% VO2max. In a smaller group (14 NW, 6 OW, 15 Ob), a high-fat meal was ingested 45 min preexercise. Baseline glycemia was similar and increased slightly and similarly in all groups during exercise. Basal insulin (pmol/L) was significantly higher in Ob vs. other groups; postexercise, insulin increased in NW (+7± 3) and OW (+5 ± 8), but decreased in Ob (-15±5, p < .0167 vs. NW). This insulin drop in Ob was disproportionately more pronounced in the half of Ob children with higher basal insulin (Ob-H). In all groups, high-fat feeding caused a rapid rise in insulin, promptly corrected by exercise. In Ob, however, insulin rose again 30 min postexercise. Our data indicates a distinct pattern of exercise-induced insulin modulation in pediatric obesity, possibly modulated by basal insulin concentrations.

Hypergravity resistance exercise: the use of artificial gravity as potential countermeasure to microgravity.

The aims of this study were to 1) determine if hypergravity (HG) squats can produce foot forces similar to those measured during 10-repetition maximum (10RM) squats using weights under normal 1-G(z) condition, and 2) compare the kinematics (duration and goniometry) and EMG activities of selected joints and muscles between 10RM and HG squats of similar total foot forces. Eight men and six women [27 yr (SD 4), 66 kg (SD 10)] completed ten 10RM [83 kg (SD 23)] and 10 HG squats (2.25-3.75 G(z)). HG squats were performed on a human-powered short-arm centrifuge. Foot forces were measured using insole force sensors. Hip, knee, and ankle angles were measured using electrogoniometers. EMG activities of the erector spinae, biceps femoris, rectus femoris, and gastrocnemius were also recorded during both squats. All subjects were able to achieve similar or higher average total foot forces during HG squats compared with those obtained during 10RM squats. There were no differences in total duration per set, average duration per repetition, and goniometry and EMG activities of the selected joints and muscles, respectively, between 10RM and HG squats. These results demonstrate that HG squats can produce very high foot forces that are comparable to those produced during 10RM squats at 1 G(z). In addition, the technique and muscle activation are similar between the two types of squats. This observation supports the view that HG resistance training may represent an important countermeasure to microgravity.

Kinetic profiles of 18 systemic pro- and anti-inflammatory mediators during and following exercise in children.

While acute changes in systemic pro-/antiinflammatory cytokines occur with exercise, individual kinetics during and following exercise remain unclear; particularly, information is scarce regarding children. This study investigated the exercise-induced kinetic profiles of major pro-/anti-inflammatory mediators in 21 healthy children (13.9 +/- 0.8 yr, 7 M/14 F). Exercise was 30 min of intermittent cycling at approximately 80% VO2max. Multiple blood samples were drawn at baseline, during, and following exercise for cytokines assay. IL-1alpha, IL-6, IL-17, IL-8, IP-10, MIP-1alpha, and MIP-1beta initially decreased (nadir: 14-19 min into exercise) and subsequently exceeded baseline levels (peaks: 20-24 min into exercise). TNF-alpha, IL-12p70, IL-1RA, IL-4, EGF, TGF-alpha, GM-CSF, Eotaxin, and MCP-1 were moderately and persistently decreased throughout. VEGF was unchanged; sCD40L was elevated during exercise and recovery. Our results indicate that key immunomodulators display non-linear, biphasic kinetic profiles in response to exercise, suggesting that detection of exercise-induced changes over baseline may depend on exercise duration and sampling timing.

Australian and New Zealand recommendations for the diagnosis and management of gout: integrating systematic literature review and expert opinion in the 3e Initiative.

AIM: To develop evidence-based recommendations for the diagnosis and management of gout in Australia and New Zealand as part of the multi-national 3e Initiative. METHOD: Using a formal voting process, a panel of 78 international rheumatologists selected 10 key clinical questions pertinent to the diagnosis and management of gout. An additional question was also developed by participating Australian and New Zealand rheumatologists. Each question was investigated with a systematic literature review. MEDLINE, EMBASE, Cochrane CENTRAL and abstracts from 2010 to 2011 European League Against Rheumatism and American College of Rheumatology meetings were searched in each review. Relevant studies were independently reviewed by two individuals for data extraction and synthesis and risk of bias assessment. Using this evidence, 47 Australian and New Zealand rheumatologists developed national recommendations. For each recommendation the level of agreement was assessed and the level of evidence graded. RESULT: Eleven recommendations were produced relating to the diagnosis of gout, different aspects of the management of gout, cardiovascular and renal comorbidities and the management of asymptomatic hyperuricemia. The mean level of agreement with the recommendations was 9.1 on a 1-10 scale, with 10 representing full agreement. CONCLUSION: Eleven Australian and New Zealand recommendations on the diagnosis and management of gout were developed combining systematically reviewed evidence with local expertise, enhancing their utility in clinical practice.

Isotretinoin-induced skeletal hyperostosis.

We describe a case of skeletal hyperostosis in a 29 year old man presenting with non-inflammatory back pain with a past history of isotretinoin therapy for acne. The development of skeletal hyperostosis, predominantly of the spine, has been reported in association with isotretinoin use and has a radiographic picture similar to diffuse idiopathic skeletal hyperostosis. The prevalence and severity of this condition appears to correlate with duration of therapy. Isotretinoin is a well-established treatment for severe acne. It is important for the rheumatologist be aware of this phenomenon when assessing young patients with musculoskeletal symptoms and evidence of radiological abnormalities.

Low copy number of the FCGR3B gene and rheumatoid arthritis: a case-control study and meta-analysis.

INTRODUCTION: Low copy number (CN) of the Fc gamma receptor 3B (FCGR3B) gene has been associated with systemic autoimmune disease. This receptor for IgG is present almost exclusively on neutrophils and plays a role in their interaction with immune complexes. At present the relationship between FCGR3B and rheumatoid arthritis (RA) is unclear. The aim of the present study was to investigate whether low CN of the FCGR3B gene is associated with susceptibility to RA. METHOD: The FCGR3B CN was determined using a custom Taqman® CN assay (Hs04211858; Applied Biosystems, Foster City, CA, USA) in 197 RA patients, recruited from a tertiary setting, and in 162 population matched controls. Odds ratios for low CN (< 2) and high CN (> 2), both relative to the normal diploid 2CN, were estimated by logistic regression. RESULTS: A significant association between RA and low FCGR3B CN was observed, with frequencies of 13.7% in RA patients compared with 6.2% in controls (odds ratio 2.5, 95% confidence interval 1.2 to 5.4, P = 0.017). No association was observed between low CN and the presence of rheumatoid factor, anti-cyclic citrullinated peptide antibodies or radiographic erosions in RA patients. A meta-analysis including six previous studies confirmed an association between RA and low FCGR3B CN (odds ratio 1.47, 95% confidence interval 1.13 to 1.92, P = 0.004). CONCLUSIONS: The present study confirms that a low CN of the FCGR3B gene is associated with susceptibility to RA. The association may be stronger in patients recruited from a tertiary setting, which may relate to disease severity and/or complications. The mechanism of susceptibility remains unclear and further study is required.

South Australian Scleroderma Register: autoantibodies as predictive biomarkers of phenotype and outcome.

AIM: To investigate the relationship between scleroderma-specific autoantibodies and clinical phenotype and survival in South Australian patients with scleroderma. METHOD: Two cohorts of patients were studied from the South Australian Scleroderma Register (SASR). In the first, the sera of 129 consecutive patients were analyzed for anticentromere (ACA), anti-Scl70, anti-RNA polymerase III, anti-U1RNP, anti-Th/To, anti-Pm/Scl, anti-Ku and anti-fibrillarin antibodies using the Euroline immunoblot assay. Statistical analysis was performed to look for a significant association between specific antibodies and various clinical features. In the second cohort survival from first symptom onset was analyzed in 285 patients in whom the autoantibody profile was available, including ACA, Anti-Scl70, anti-U1RNP and anti-RNA polymerase III measured using multiple methods. Survival analysis compared mortality between different groups of patients with specific antibodies. RESULTS: ACA, Th/To and Ku antibodies were associated with limited scleroderma, Scl70 and RNA Pol III antibodies were associated with diffuse scleroderma and antibodies to U1RNP were associated with overlap syndrome. Significant associations between Scl70 and interstitial lung disease (P = 0.004), RNA Pol III and renal crisis (P = 0.002), U1RNP and pulmonary hypertension (P = 0.006) and Th/To and pulmonary hypertension (P = 0.034) were seen. Trends were observed with an increased frequency of lung disease with Pm/Scl and Th/To and an increased frequency of myositis with Ku. The presence of Scl70, RNA Pol III and U1RNP was associated with significantly reduced survival as compared with patients with ACA. CONCLUSIONS: Scleroderma-specific autoantibodies are associated with clinical phenotype and survival.