Wound care in autoimmune bullous diseases

Medical treatment of autoimmune bullous diseases (AIBD) is focused on immunosuppression. In addition, proper wound care is equally important and can improve wound healing and recovery. Goals of wound care management include relieving pain, preventing infection, enhancing regeneration, and encouraging patient mobility and quality of life. Wound care in AIBD patients can be challenging as immunosuppressants may slow wound healing, large areas may be affected, skin fragility and wounds may occur on difficult to dress body sites, non-blistered skin may be fragile as well, and affected patients are often of higher age and less mobile. A personalized wound care plan is warranted, preferably established by experienced nurses.</p

The importance of accurate epidemiological data of epidermolysis bullosa

Linked article: Petrof et al. Br J Dermatol 2022; 186:843–848

Autoimmune bullous diseases in childhood

Autoimmune bullous diseases (AIBDs) rarely occur in childhood and in contrast to the chronic disease course in adults, often have a milder clinical course, a better treatment response and better prognosis. Although literature is scarce, several case reports and case series describe childhood cases of linear IgA disease, bullous pemphigoid, dermatitis herpetiformis, mucous membrane pemphigoid, epidermolysis bullosa acquisita, pemphigus vulgaris, pemphigus foliaceus and paraneoplastic pemphigus. Misdiagnosis and consequently delay in diagnosis is common in childhood AIBD with often initial diagnoses of infectious causes, such as hand-foot-mouth disease or impetigo bullosa. Clinical features of childhood AIBDs may overlap between subtypes, like adult cases, but the differential diagnosis is different in childhood. Another difference between the adult and childhood bullous pemphigoid is the mainly acral distribution of bullous lesions in children and the prognosis of the disease. Bullous pemphigoid and linear IgA disease might possibly be drug-induced or triggered by vaccination.</p

Structure of hemidesmosomes and the epidermal basement membrane zone

Hemidesmosomes are complex, multiprotein structures that mediate the attachment of epithelial cells to the underlying basement membrane. While providing mechanical attachment, these adhesion units are extremely dynamic. They play a significant role in signaling pathways involved in various important cell functions, such as differentiation, wound healing, and survival. Structurally, hemidesmosomes contain the following molecules: plectin (over 500 kDa protein), BP230 (230 kDa antigen, also known as BPAG1), integrin A6B4, BP180 (180 kDa protein, also known as BPAG2 or type XVII collagen, laminin 332 and CD151 (protein of tetraspan superfamily). The epidermal basement membrane zone can be viewed as a thin sheet of matrix underlying the basal epithelial cells. It consists of lamina lucida and lamina densa, mainly containing laminin and type IV collagen networks. Type VII collagen which enters the composition of semicircular anchoring fibrils provide the attachment to the papillary dermis underneath the lamina densa of the basement membrane. When molecules in hemidesmosomes or in the basement membrane zone become target of autoantibodies a particular acquired subepidermal autoimmune blistering disease (sAIBD) will develop.</p

Revertant Mosaicism in Genodermatoses:Natural Gene Therapy Right before Your Eyes

Revertant mosaicism (RM) is the intriguing phenomenon in which nature itself has successfully done what medical science is so eagerly trying to achieve: correcting the effect of disease-causing germline variants and thereby reversing the disease phenotype back to normal. RM was molecularly confirmed for the first time in a genodermatosis in 1997, the genetic skin condition junctional epidermolysis bullosa (EB). At that time, RM was considered an extraordinary phenomenon. However, several important discoveries have changed this conception in the past few decades. First, RM has now been identified in all major subtypes of EB. Second, RM has also been identified in many other genodermatoses. Third, a theoretical mathematical exercise concluded that reverse mutations should be expected in all patients with a recessive subtype of EB or any other genodermatosis. This has shifted the paradigm from RM being an extraordinary phenomenon to it being something that every physician working in the field of genodermatoses should be looking for in every patient. It has also raised hope for new treatment options in patients with genodermatoses. In this review, we summarize the current knowledge on RM and discuss the perspectives of RM for the future treatment of patients with genodermatoses

The C4EB study—Transvamix (10% THC / 5% CBD) to treat chronic pain in epidermolysis bullosa:A protocol for an explorative randomized, placebo controlled, and double blind intervention crossover study

Patients with the genetic blistering skin condition epidermolysis bullosa (EB) report severe pain as a consequence of skin and mucous membrane lesions including blisters, wounds, and scars. Adequate symptom alleviation is not often achieved using conventional pharmacologic interventions. Finding novel approaches to pain care in EB is imperative to improve the quality of life of patients living with EB. There are several anecdotal reports on the use of cannabinoid-based medicines (CBMs) by EB patients to reduce the burden of symptoms. However, controlled clinical investigations assessing these reported effects are lacking. As the pain quality “unpleasantness” delineates EB pain, we hypothesize the modulation of affective pain processing in the brain by way of intervention with CBMs comprising the cannabinoids Δ-9-tetrahydrocannabinol and cannabidiol—objectified by functional magnetic resonance imaging (fMRI). The C4EB study is an investigator-initiated, single-centre, randomized, double-blind, placebo-controlled and crossover trial. Adult patients with the diagnosis epidermolysis bullosa, reporting chronic pain will be eligible to participate. Following baseline measurements, participants will be randomized to receive the sublingually administered interventions placebo and Transvamix(®) in forward or reversed orders, each for two weeks and separated by a washout. The primary outcome is the difference in numeric rating scale pain scores between grouped interventions, using affective descriptors within the Short-form McGill Pain Questionnaire-2. Secondary outcomes include pain self-efficacy, concomitant analgesic medication-use and adverse events. Additionally, fMRI will be employed to assess brain connectivity related to neuroanatomic pain circuits at baseline, placebo and Transvamix(®) interventions. The study was approved by the ethical committee at the University Medical Center of Groningen in the Netherlands. Results will be submitted for publication in a peer-reviewed journal. Trial registration number: Netherlands Trial Register: NL9347 (Acronym: C4EB)

Identifying Epidermolysis Bullosa Patient Needs and Perceived Treatment Benefits:An Explorative Study Using the Patient Benefit Index

Epidermolysis bullosa (EB) is a genetic blistering skin condition for which no cure exists. Symptom alleviation and quality of life are therefore central to EB care. This study aimed to gain insight into EB patient needs and benefits from current clinical care. Two questionnaires were administered cross-sectionally to adult EB patients at the Dutch expertise centre for blistering diseases. Patient needs and benefits were analyzed using the patient benefit index survey (PBI-S). Ancillary data were compiled pertaining to self-reported EB severity, pain and pruritus, as well as current and previous treatments. In total, 104 participants were included (response rate 69.8%). Sixty-eight participants comprised the analyzed cohort (n = 36 omitted from analysis). The needs given the highest importance were to get better skin quickly (64.7%) and to be healed of all skin alterations (61.8%). A positive correlation between pain and EB severity and the importance of most needs was observed. Minimal clinically important differences within the PBI-S, relating to reported benefits from clinical care, were reported by 60.3% of the cohort. This study highlights a discrepancy between patient needs and feasible treatment outcomes. Utilizing the PBI-S in conjunction with well-established multidisciplinary care may catalyze the process of tailoring treatments to the needs of individual patients

Insights into clinical and diagnostic findings as well as treatment responses in patients with mucous membrane pemphigoid:A retrospective cohort study

Background: The variable clinical severity of mucous membrane pemphigoid (MMP) often leads to diagnostic and therapeutic delays. Objective: To describe the characteristics of a large cohort of patients with MMP. Methods: A retrospective review of clinical and diagnostic characteristics as well as treatment responses in 145 patients with MMP. Results: Monosite involvement was seen in 41.4% and multisite involvement in 58.6% of the patients. The oral mucosa was affected in 86.9% of the patients, followed by the ocular mucosa (30.3%), skin (26.2%), genital mucosa (25.5%), nasal mucosa (23.4%), and pharyngeal and/or laryngeal mucosa (17.2%). Ocular disease developed during the disease course in 41.7% of patients with initially other mucosal site involvement. The malignancy rate was significantly higher in patients with autoantibodies against laminin-332 than in patients with MMP without laminin-332 autoantibodies (35.3% vs 10.9%, respectively; P = .007). Systemic immunosuppressive or immunomodulatory therapy was administered to 77.1% of the patients, mainly to patients with multisite (P Limitations: Retrospective design. Conclusion: Patients with MMP present with a heterogeneous clinical presentation, and new symptoms may develop during the disease course. Cancer screening should be considered for patients with MMP and, in particular, for those with autoantibodies against laminin-332