Association between weight gain and knee osteoarthritis: a systematic review.

OBJECTIVE: Although weight loss is recommended to manage knee osteoarthritis (KOA), adults tend to gain weight with age which may affect KOA symptoms and progression. We conducted a systematic review and data synthesis to investigate the association between weight gain and KOA, defined by clinical features, structural progression, and total knee replacement (TKR). DESIGN: MEDLINE and EMBASE were systematically searched for controlled trials and cohort studies of participants with (or at risk of) KOA examining the relationship between weight gain and KOA clinical features (pain, function, quality of life), structural progression, and TKR. Risk of bias was assessed using the ROBINS-I tool. Results were organised by outcome, with meta-analyses performed where appropriate. RESULTS: Twenty-three studies were included. Results showed significant detrimental effects of weight gain on pain (4 of 7 studies), stiffness (2 of 2 studies), function (5 of 6 studies), and the single studies examining quality of life, and clinical and radiographic KOA. Weight gain adversely affected cartilage (6 of 9 studies), bone marrow lesions (1 of 4 studies), meniscal damage (1 of 3 studies) and effusion/synovitis (1 of 1 study). Weight gain significantly increased TKR (3 of 6 studies): meta-analysis of 2 with available data demonstrated significant increases in TKR/5 kg weight gain in women, HR 1.34 (95% CI 1.18-1.51), and in men, HR 1.25 (95% CI 1.16-1.34). CONCLUSIONS: Weight gain in adults is associated with increased clinical and structural KOA and TKR. Prevention of weight gain should be considered to improve outcomes in KOA.

Management of cutaneous manifestations of lupus erythematosus: A systematic review.

BACKGROUND: Cutaneous lupus erythematosus (CLE), occurring with or without systemic lupus erythematosus (SLE), is a group of inflammatory skin diseases that can be very debilitating, causing significant psychological distress, and sometimes scarring. OBJECTIVES: We sought to comprehensively present the evidence for different treatment modalities in patients with cutaneous manifestations of lupus erythematosus (LE). METHODS: Medline, Embase, Scopus and Cochrane CENTRAL were searched electronically from 1990 to March 2019, using keywords related to cutaneous lupus and synonyms and treatment. Articles retrieved were screened for relevance, including reference lists of retrieved reviews. We included clinical trials, observational studies or case series with ≥5 patients focussing on treatment of CLE, with or without SLE. RESULTS: The search identified 6637 studies, of which 107 were included. Each study commonly included a heterogeneous mixture of CLE subtypes, with or without SLE. The 107 included studies investigated 11 different categories of treatment in 7343 patients. Treatments included topical calcineurin inhibitors (13 studies), sun protection (5 studies), R-salbutamol cream (2 studies), antimalarials (22 studies), synthetic DMARDs (10 studies), retinoids (2 studies), thalidomide/lenalidomide (22 studies), biologic therapies (15 studies), intravenous immune globulin (3 studies), laser (6 studies) and other therapies (7 studies). General measures to be considered include smoking cessation, sun protection measures and optimisation of vitamin D levels. Moderate evidence exists for benefit with topical CNIs, particularly as a steroid sparing agent in areas at high risk of steroid complications (e.g. facial skin). There is moderate evidence for hydroxychloroquine, which is first-line in SLE patients, limited evidence to support other synthetic DMARDs, and moderate evidence supporting thalidomide but with significant risk of toxicity. Of biologic therapies, there are moderate data to support belimumab. Limited evidence exists for other therapies. CONCLUSION: Many management options are available for CLE, including topical, systemic and biologic therapies, with a variable balance of efficacy and toxicity. There is a paucity of high-quality clinical trial data. Further trials are required to better understand optimal management of CLE, particularly in specific subgroups.

International Bullous Diseases Group: consensus on diagnostic criteria for epidermolysis bullosa acquisita.

BACKGROUND: Epidermolysis bullosa acquisita (EBA) is a complex autoimmune bullous disease disease with variable clinical presentations and multiple possible diagnostic tests, making an international consensus on the diagnosis of EBA essential. OBJECTIVES: To obtain an international consensus on the clinical and diagnostic criteria for EBA. METHODS: The International Bullous Diseases Group (IBDG) met three times to discuss the clinical and diagnostic criteria for EBA. For the final voting exercise, 22 experts from 14 different countries voted on 50 different items. When > 30% disagreed with a proposal, a discussion was held and re-voting carried out. RESULTS: In total, 48 of 50 proposals achieved consensus after discussion. This included nine diagnostic criteria, which are summarized in a flow chart. The IBDG was unable to determine one procedure that would be applicable worldwide. A limitation of the study is that differential diagnosis of bullous systemic lupus erythematosus has not been addressed. CONCLUSIONS: This first international consensus conference established generally agreed-upon clinical and laboratory criteria defining the clinical classification of and diagnostic testing for EBA. Holding these voting exercises in person with the possibility of discussion prior to voting has advantages in reaching consensus over Delphi exercises with remote voting.

Management options for femoroacetabular impingement: a systematic review of symptom and structural outcomes.

OBJECTIVE: The optimal therapy for femoroacetabular impingement (FAI) is unclear. The aim of this systematic review was to examine the evidence for surgical and non-surgical treatment of FAI on symptom and structural outcomes. DESIGN: MEDLINE and EMBASE were searched electronically. Surgical and non-surgical management strategies were searched with "FAI". Studies which included comparison groups and reported symptom or structural outcomes were included (Levels I-III evidence). A risk of bias assessment was performed. RESULTS: Eighteen studies comparing management strategies for FAI were identified. Most studies had high risk of bias. No study compared surgical and non-surgical treatment. When surgical approaches were compared there was evidence of superior symptom outcomes with arthroscopy compared to open surgery and with labral preservation. There was some evidence that surgical interventions are effective in reducing alpha angle (improved hip shape), but no data on whether this affects long-term outcomes. There was some weak evidence that surgery is associated with structural progression of hip osteoarthritis (OA). CONCLUSIONS: Although evidence supports improvement in symptoms after surgery in FAI, no studies have compared surgical and non-surgical treatment. Therefore no conclusion regarding the relative efficacy of one approach over the other can be made. Surgery improves alpha angle but whether this alters the risk of development or progression of hip OA is unknown. This review highlights the lack of evidence for use of surgery in FAI. Given that hip geometry may be modified by non-surgical factors, clarifying the role of non-surgical approaches vs surgery for the management of FAI is warranted.

A multicentre randomized trial of the treatment of patients with pemphigus vulgaris with infliximab and prednisone compared with prednisone alone.

BACKGROUND: Pemphigus vulgaris (PV) is a blistering disease and tumour necrosis factor-α has a role in its pathogenesis. OBJECTIVES: To evaluate the safety of infliximab (IFX) with prednisone compared with prednisone alone in the treatment of PV. In addition, treatment response was assessed and mechanistic studies were performed. METHODS: Subjects with PV who had ongoing disease activity while being maintained on prednisone were randomized to receive either IFX or placebo in addition to prednisone. Response status and immunoglobulin (Ig) G anti-desmoglein (Dsg)1 and Dsg3 antibodies were assessed at 18 and 26 weeks. RESULTS: Ten subjects were randomized to each group. There were no safety signals during the course of the study. At week 18, one subject in each group had responded. At week 26, three IFX-treated subjects vs. none in the placebo group had responded (P = 0·21). At weeks 18 and 26, the median IgG anti-Dsg1 and anti-Dsg3 levels were lower in the IFX-treated patients [IgG anti-Dsg-1 (week 18, P = 0·035; week 26, P = 0·022); IgG anti-Dsg3 (week 18, P = 0·035; week, 26 P = 0·05)]. CONCLUSIONS: This study is limited by the relatively small sample size. There was no significant difference between study arms in the proportion of subjects with treatment-related adverse events > grade 3. IFX therapy was not shown to be effective for the treatment of patients with PV in this randomized, placebo-controlled trial, although IFX treatment may be associated with a decrease in anti-Dsg1 and Dsg3 antibodies.

Unraveling the significance of IgE autoantibodies in organ-specific autoimmunity: lessons learned from bullous pemphigoid.

Bullous pemphigoid (BP), a cutaneous autoimmune blistering disease, has provided a useful model to elucidate a role for IgE in autoimmunity. IgE antibodies specific for the BP180 autoantigen are detected in sera and biopsy samples from the majority of BP patients. In BP biopsies, both IgE and BP180 antigen localize to the surface of mast cells, and incubation of circulating basophils from these patients with BP180 protein triggered degranulation. The in vivo pathogenicity of BP180-specific IgE was confirmed in mouse models, where injection of purified BP IgE into human skin grafted onto nu/nu mice replicated the early phase of lesion development, including mast cell degranulation, eosinophil infiltration and development of urticarial plaques. In addition, IgE antibodies from patient sera bind to BP180 on basal keratinocytes, resulting in internalization of BP180, production of inflammatory cytokines, IL-6 and IL-8, and a decrease in the number of hemidesmosomes at the basement membrane zone. These findings have led to therapeutic trials of the anti-IgE monoclonal antibody omalizumab in BP, resulting in substantial improvement in the patients' disease. Overall, the work in BP provides the first evidence for a pathogenic role for IgE in autoimmunity.

Topical imiquimod 5% as a treatment for localized genital Kaposi's sarcoma in an HIV-negative man: a case report.

We report a case of Kaposi's sarcoma (KS) in an HIV-negative man who has sex with men (MSM) that was successfully treated by topical application of imiquimod 5% cream (Aldara). Our case highlights a potentially effective and non-invasive method of treatment of Kaposi's sarcoma in the shortest timeframe yet recorded. The location of the lesions on the patient's penis also highlights the need for a non-invasive treatment.

Role of IgE in bullous pemphigoid: a review and rationale for IgE directed therapies.

Bullous pemphigoid (BP) is an autoimmune blistering disorder that is characterized by elevated total serum IgE and both IgG and IgE class autoantibodies directed against the hemidesmosomal proteins BP180 and BP230. In BP, IgE is found at the basement membrane zone and coating mast cells in lesional skin. IgE binding to immune cells is mediated through its high affinity receptor, FcεRI on the surface of mast cells, basophils and eosinophils. In BP lesions, IgE binding is thought to be a critical step in the activation of these cells. Models of the disease have demonstrated that BP IgE can replicate the early stages of BP lesion formation. These findings suggest that IgE inhibition may be a therapeutic approach for BP. Omalizumab is a humanized monoclonal antibody that inhibits IgE binding to FcεRI and is currently FDA-approved for the treatment of severe allergic asthma. To date, two case reports have each described the efficacy of omalizumab in a patient with severe recalcitrant BP. These studies are the first to provide clear evidence of the contribution of IgE autoantibodies in the pathogenesis of human BP and suggest that omalizumab may provide an additional therapeutic tool for treatment.

New and innovative interventions in the management of pemphigus.

Pemphigus is a rare autoimmune blistering disease usually treated with systemic glucocorticoids with adjuvant immunosuppressants or anti-inflammatories. However significant morbidity and mortality is associated with these treatments. This review discusses conventional therapeutic options, as well as new and emerging therapies that may be safer alternatives to broad-based immunosuppression.

The 14-item Paediatric Throat Disorders Outcome Test: a valid, sensitive, reliable, parent-reported outcome measure for paediatric throat disorders.

OBJECTIVES: We modified and abbreviated a pre-existing research questionnaire, the Tonsil and Adenoid Health Status Instrument, to make it suitable for rapid completion as a disease-specific, health-related quality of life research tool for children with tonsil and adenoid disease in the UK. We determined the main psychometric properties of the resulting 14-item Paediatric Throat Disorders Outcome Test. DESIGN, SETTING AND PARTICIPANTS: Pre- and post-operative questionnaires were completed by the parents of children with throat disorders referred to two large hospitals. We included children with recurrent tonsillitis and with obstructive sleep apnoea. A separate cohort of healthy children of comparable age range was also studied. MAIN OUTCOME MEASURES: The test's internal consistency and responsiveness were analysed and its construct validity documented via known-group differences. RESULTS: A total of 126 completed questionnaires were received from the hospital referral group. The children's mean age was 6.5 years (range one to 16). The 40 unaffected children were well matched in age to the study population (mean 6.1 years, range two to 15). Cronbach's alpha coefficient for the pre-operative assessment total score was 0.84. The test-retest reliability coefficient for the total score was 0.98, indicating very high reproducibility. The 14-item Paediatric Throat Disorders Outcome Test discriminated well between children known to suffer with throat problems and a group of healthy controls (p < 0.0001; t = 24.016). Six months after surgical intervention, parentally reported questionnaire scores had improved (i.e. were lower) (p < 0.0001; t = 7.01). The standard effect size (i.e. change in mean divided by baseline standard deviation) for children for whom post-operative questionnaires were completed was 1.53; this is very large. CONCLUSIONS: The 14-item Paediatric Throat Disorders Outcome Test is an appropriate, disease-specific, parent-reported outcome measure for children with throat disorders, for which we have demonstrated internal consistency, reliability, responsiveness to change and two forms of construct validity.

Autoimmunity in bullous pemphigoid.

Bullous pemphigoid (BP) is an autoimmune blistering disease primarily of the elderly, characterized by the development of urticarial plaques surmounted by subepidermal blisters and the deposition of immunoglobulins and complement at the basement membrane zone (BMZ). Immunologically, it is characterized by the development of autoantibodies targeting two structural proteins of the hemidesmosomes, BP180 (collagen XVII) and BP230. BP230 is intracellular protein of the hemidesmosomal plaque, while BP180 is a transmembrane protein with a collagenous extracellular domain. The weight of experimental evidence indicates that BP180 is the primary target of the pathogenic autoantibodies. Autoantibodies are of both the IgG or IgE class, and their binding in the skin triggers complement activation, mast cell degranulation and the accumulation of inflammatory cells, including eosinophils, mast cells, and neutrophils. Release of proteases from these inflammatory cells results in cleavage of the BMZ and blister formation. While the initial triggers of autoantibody production remain obscure, a better understanding of the pathomechanisms of blister formation will lead to the development of new therapeutic strategies.

Influenza immunisation uptake in carers.

In 2005 the United Kingdom departments of health added 'carers' to the list of people that should be offered seasonal influenza immunisation by their general practice. We surveyed a sample of carers registered for care assistance with the charity Crossroads Caring for Carers. Over half (58%) were not aware that they are eligible for free influenza immunisation. Young carers without a chronic disease, were least likely to be offered immunisation and least likely to be immunised.

Superficial temporal vein graft in stapedotomy: a functional and aesthetic alternative.

The Causse technique of performing stapedotomy with vein graft interposition is widely-employed, with the vein graft harvested from the dorsum of the hand/wrist. Donor site scarring may be of cosmetic concern, especially in female patients. A prospective series of 19 patients undergoing stapedotomy with vein graft harvested from the superficial temporal vein is evaluated from aesthetic and functional perspectives. Results show that vein interposition from this donor site is not only aesthically acceptable but just as successful in improving hearing outcome after stapedotomy. We suggest the use of the superficial temporal vein and/or its branches as an alternative vein graft in stapedotomy.