Serum Biomarkers in Bullous Pemphigoid: A Systematic Review.

INTRODUCTION: Bullous pemphigoid (BP) is the most common type of subepidermal blistering disease, usually observed in the elderly population, with a mean age of presentation between 66 and 83 years. BP is a psychosocially ladened disease, with many patients experiencing negative body image, social isolation, and depression. The identification and validation of biomarkers in BP may further the understanding of disease pathogenesis, provide objective measures in assessing efficacy in clinical trials, and identify new targets for targeted therapy. METHODS/RESULTS: Two databases (Medline and Embase) were searched from database inception to September 2023. All published articles reporting on biomarker levels of BP patients in serum compared to healthy controls were included. A total of 877 unique articles were identified, resulting in the inclusion of 62 case-control studies reporting on a total of 1837 patients and 140 unique biomarkers. Biomarkers were categorized into T-cell mediated, B-cell mediated, innate immune system, and coagulation cascade pathway. The most notable biomarkers identified include increases in anti-BP180/230 immunoglobulin (Ig)G/E, total IgE, TNF-α, B-cell activating factor, interleukin-31, eosinophil cationic protein, MMP-9, and coagulation cascade biomarker levels. The results of this review provide the greatest support for a role of anti-BP180/230 autoantibodies, Th2 cells, eosinophils, and the coagulation cascade in the pathogenesis of BP. CONCLUSIONS: The pathogenesis of BP has an underlying autoimmune etiology centred around the production of autoantibodies against BP180/230, but increased Th2, eosinophil and coagulation cascade activity may be contributory.

Biomarkers in Pemphigus Vulgaris: A Systematic Review.

INTRODUCTION: Pemphigus vulgaris (PV) is a rare intraepidermal blistering disease that is potentially life-threatening due to risk of infection and failure of skin barrier function. The identification of biomarkers has the potential to provide diagnostic utility and identify new therapeutic targets. The objective of this systematic review is to identify all potentially relevant PV biomarkers, categorize them, and identify trends to determine the involvement of T-cell-mediated, B-cell-1mediated, and innate immune-mediated pathways in PV pathogenesis. METHODS/RESULTS: Medline and Embase databases were searched according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, resulting in the inclusion of 66 studies that reported on a total of 2463 patients and 146 unique biomarkers. Biomarkers were categorized into T-cell-mediated, B-cell-mediated, and innate immune system pathways. The most notable biomarkers trends include elevations in IL-4, IL-6, IL-17A, anti-Dsg1/3 autoantibodies, and a reduction in Treg cells and FOXP3. CONCLUSION: The results of this review support current theories of PV pathogenesis, with increased Th2 activity, increased Th17 activity, decreased Treg activity, and production of anti-Dsg1/3 autoantibodies being observed. Targeting of IL-4 and IL-6 may provide therapeutic benefit. However, more research is required to validate biomarkers for clinical utility and assess viability as therapeutic targets.

Efficacy of Treatments in Reducing Inflammatory Lesion Count in Rosacea: A Systematic Review.

INTRODUCTION: Rosacea is a chronic inflammatory skin condition affecting approximately 5.5% of the global population. Patients present heterogeneously with a mix of features in the central facial region, of which papules and pustules are considered to be a major feature. The identification of effective treatments for reducing inflammatory lesions in rosacea can alleviate the psychosocial burden that many rosacea patients experience, including reduced self-esteem, anxiety, and social withdrawal. The objective of this systematic review is to determine the effectiveness of topical and systemic therapies in reducing lesion count in rosacea patients. METHODS/RESULTS: Medline, Embase, and Cochrane CENTRAL databases were searched, resulting in the inclusion of 43 clinical trials reporting on a total of 18,347 rosacea patients. The most well-studied treatments include ivermectin, metronidazole, azelaic acid, minocycline, and doxycycline. Oral isotretinoin was the most effective treatment in reducing inflammatory lesions and may be recommended for severe recalcitrant cases of rosacea. CONCLUSIONS: Several topical and systemic therapies have demonstrated efficacy in reducing inflammatory lesion count in rosacea patients, with mechanisms of action centred around suppressing inflammation and killing Demodex folliculorum mites. Additional research is required to determine effective combination therapies in rosacea.

The efficacy of trimethoprim in wound healing of patients with epidermolysis bullosa: a feasibility trial.

BACKGROUND: There are no systemic therapies known to facilitate wound healing in patients with recessive dystrophic epidermolysis bullosa (RDEB). OBJECTIVES: We sought to assess the feasibility of a trial to examine the efficacy of trimethoprim (TMP) in healing chronic wounds in patients with RDEB and to examine the effect of TMP on lesion counts, quality of life, and emergence of antibiotic resistance. METHODS: We conducted a feasibility study using a prospective, randomized, double-blinded, placebo-controlled, crossover design. The study took place between October 2006 and September 2007 in the epidermolysis bullosa clinic at the Hospital for Sick Children in Toronto, Ontario, Canada. Liquid TMP or placebo was given orally or via gastrostomy tube in two divided doses for 2 months; the main outcome measure was a decrease in surface area of selected chronic wounds. RESULTS: Ten subjects with RDEB were enrolled in the study; 7 completed both study arms (4 male, 3 female). Age at enrollment was 14 ± 5.4 years. Although all patients showed improved wound healing on TMP, the crossover analysis, TMP versus placebo, approached but did not reach statistical significance (P = .08). While receiving TMP, 6 of 7 patients had more than 50% reduction in chronic wound surface area; while receiving placebo, 2 of 6 patients had more than 50% reduction in wound surface area (P = .03). Secondary outcome measures did not achieve statistical significance. LIMITATIONS: Small sample size is a limitation. CONCLUSIONS: This proof-of-concept study demonstrates the potential efficacy of TMP in improving wound healing in RDEB, and provides useful information for further prospective studies.

Pretibial Myxedema: Case Presentation and Review of Treatment Options.

Pretibial myxedema (PM) is a rare autoimmune manifestation of Graves' disease, which commonly presents as diffuse, nonpitting edema of shins and less often as plaques, nodules, or elephantiasis lesions mimicking lymphedema. We present a 57-year-old woman with 12-month history of PM, which occurred a year after treatment of Graves' disease and improved with topical corticosteroids, support stockings, and intralesional steroid injections until recurrence with local erythema and woody edema. A literature review was undertaken of the evidence-based treatment modalities for symptomatic PM: although commonly asymptomatic and self-limited, severe cases of PM may be treated with topical corticosteroid, compressive therapy, and intralesional corticosteroid injections.