Localized Bullous Pemphigoid Following Orthopedic Surgery

Bullous pemphigoid is an autoimmune condition whereby the immune system forms antibodies that target the skin, resulting in the formation of blisters in a generalized and symmetric pattern. Localized bullous pemphigoid can occur in special circumstances. Here, we describe two patients that developed localized bullous pemphigoid in one lower extremity following orthopedic surgery. We propose that underlying edema following orthopedic surgery is a potential trigger for localized bullous pemphigoid.     

Self‐initiated use of topical cannabidiol oil for epidermolysis bullosa

Epidermolysis bullosa is a rare blistering skin disorder that is challenging to manage because skin fragility and repeated wound healing cause itching, pain, limited mobility, and recurrent infections. Cannabidiol, an active cannabinoid found in cannabis, is postulated to have antiinflammatory and analgesic effects. We report 3 cases of self‐initiated topical cannabidiol use in patients with epidermolysis bullosa in an observational study. One patient was weaned completely off oral opioid analgesics. All 3 reported faster wound healing, less blistering, and amelioration of pain with cannabidiol use. Although these results demonstrate promise, further randomized, double‐blind clinical trials are necessary to provide scientific evidence of our observed benefits of cannabidiol for the treatment of epidermolysis bullosa.     

Cicatricial Pemphigoid of the Oropharynx after Allogeneic Stem Cell Transplantation for Relapsed Follicular Lymphoma

A 44-year-old woman with refractory follicular lymphoma underwent allogeneic stem cell transplantation (SCT) and achieved complete remission. Grade III acute graft-versus-host disease (GVHD) developed on day 23, but no chronic GVHD occurred. The patient developed severe erosion with bullous lesions in the oral cavity 18 months after SCT. At that time, the lymphoma remained in complete remission, and she had no clinical or laboratory findings suggesting chronic GVHD. A biopsy of the oral mucosa showed moderate lymphoplasmacytic infiltration and subepidermal bullae, and direct immunofluorescence staining demonstrated linear deposition of C3 at the dermo-epidermal junction. An immunoblotting assay using human epidermal extracts confirmed the presence in her serum of an antibody against the 230-kd bullous pemphigoid antigen 1 (BPAG1). A diagnosis of cicatricial pemphigoid (CP) was made, and complete resolution of the CP was achieved with pred-nisolone therapy. The occurrence of autoimmune blistering diseases is rare after allogeneic SCT.     

Chronic colitis due to an epithelial barrier defect: the role of kindlin-1 isoforms

Kindlin-1 is an epithelium-specific phosphoprotein and focal adhesion adaptor component. Mutations in the corresponding gene (KIND1) cause Kindler syndrome (KS), which is manifested by skin blistering, poikiloderma, photosensitivity and carcinogenesis. Some patients also exhibit gastrointestinal symptoms, but it has remained unclear whether these represent a feature of Kindler syndrome or a coincidence. We examined kindlin-1 in human gastrointestinal epithelia and showed that it is involved in the aetiopathology of Kindler syndrome-associated colitis. Kindlin-1 expression was assessed by indirect immunofluorescence, western blot and RT-PCR. Kindlin-1 is expressed in oral mucosa, colon and rectum. Both the full-length 74 kDa kindlin-1 protein and a 43 kDa isoform were detected in CaCo2 cells, the latter resulting from alternative splicing. In the first months of life, patients (homozygous for null mutations) had severe intestinal involvement with haemorrhagic diarrhoea and showed morphological features of severe ulcerative colitis. Later in childhood, histopathology demonstrated focal detachment of the epithelium in all segments of the colon, chronic inflammation and mucosal atrophy. These findings define an intestinal phenotype for Kindler syndrome as a consequence of a primary epithelial barrier defect. The different clinical intestinal manifestations in Kindler syndrome patients may be explained by partial functional compensation of kindlin-1 deficiency by the intestinal isoform or by the presence of truncated mutant kindlin-1.     

Serum and blister fluid levels of cytokines and chemokines in pemphigus and bullous pemphigoid

Bullous pemphigoid and pemphigus constitute two major autoimmune blistering diseases (AIBD) with complicated disease pathomechanisms involving a multitude of cytokines and immunological pathways. The purpose of our literature review of the cytokines and chemokines involved in these AIBDs was to allow for a meta-analysis of studies detailing differential cytokine and chemokine changes in these conditions. Elucidation of inflammatory pathways could lead to more targeted therapies, several of which specific monoclonal antibodies already exist and are used safely for other autoimmune diseases. A systematic review of the Pubmed/Medline database was performed for articles characterizing cytokines/chemokines involved in BP and pemphigus. Further, a meta-analysis was carried out using standardized methods, including assessment for heterogeneity. The results of our analysis demonstrated numerous inflammatory alterations in these AIBDs. Significant alterations included serum levels of IL-5, IL-6, IL-8, IL-17, CCL-17, and CCL-26 in patients with BP, and increased blister fluids levels of IL-5, IL-6, IL-8, CCL11, and TNF-α. Blister fluid levels of IL-1α are decreased in BP. In pemphigus, we identified significantly increased serum levels of IL-10, IL-17, and CCL17. We have additionally summarized all studies excluded from meta-analysis to provide a comprehensive summary of cytokine/chemokine alterations in these two conditions.     

Congenital erosive and vesicular dermatosis with reticulated supple scarring

Congenital erosive and vesicular dermatosis with reticulated supple scarring is a rare cutaneous disorder of unknown aetiology first described by Cohen and colleagues in 1985. It classically presents in the neonate as erosions and vesicles that heal within the first months of life, with supple scarring of a reticulated pattern. Along with a review of the literature, this article presents two atypical cases of congenital erosive and vesicular dermatosis with reticulated supple scarring. Patient one presented with neither erosions nor vesicles at birth, yet continued to experience sporadic blistering at the age of 15 months and patient two is the second documented case to develop congenital erosive and vesicular dermatosis after birth.     

From the Cover: The macroscopic delamination of thin films from elastic substrates

The wrinkling and delamination of stiff thin films adhered to a polymer substrate have important applications in “flexible electronics.” The resulting periodic structures, when used for circuitry, have remarkable mechanical properties because stretching or twisting of the substrate is mostly accommodated through bending of the film, which minimizes fatigue or fracture. To date, applications in this context have used substrate patterning to create an anisotropic substrate-film adhesion energy, thereby producing a controlled array of delamination “blisters.” However, even in the absence of such patterning, blisters appear spontaneously, with a characteristic size. Here, we perform well-controlled experiments at macroscopic scales to study what sets the dimensions of these blisters in terms of the material properties and explain our results by using a combination of scaling and analytical methods. Besides pointing to a method for determining the interfacial toughness, our analysis suggests a number of design guidelines for the thin films used in flexible electronic applications. Crucially, we show that, to avoid the possibility that delamination may cause fatigue damage, the thin film thickness must be greater than a critical value, which we determine.     

Cicatricial pemphigoid and lichen sclerosus

Two patients with clinical and laboratory evidence of co-existing lichen sclerosus and eicatricial pemphigoid are reported. Autoimmune bullous diseases affecting the vulva may mimic lichen sclerosus but in these two patients both diseases were present. These two diseases have not previously been reported simultaneously to date.