Autoimmune subepidermal blistering diseases of the skin and mucosae constitute a large group of sometimes devastating diseases, encompassing bullous pemphigoid, gestational pemphigoid, mucous membrane pemphigoid, epidermolysis bullosa acquisita, and anti-p200 pemphigoid. Their clinical presentation is polymorphic. These autoimmune blistering diseases are associated with autoantibodies that target distinct components of the basement membrane zone of stratified epithelia. These autoantigens represent structural proteins important for maintenance of dermo-epidermal integrity. Bullous pemphigoid (BP) is the most common subepidermal autoimmune blistering disease of the skin and mucosae. Although the disease typically presents with a generalized blistering eruption associated with itch, atypical variants with either localized bullous lesions or "non-bullous" presentations are observed in approximately 20% of patients. A peculiar form of BP typically associated with pregnancy is pemphigoid gestationis. In anti-p200 pemphigoid, patients present with tense blisters on erythematosus or normal skin resembling BP, with a predilection for acral surfaces. These patients have antibodies targeting the 200-kDa basement membrane protein. Epidermolysis bullosa is a rare autoimmune blistering disease associated with autoantibodies against type VII collagen that can have several phenotypes including a classical form mimicking dystrophic epidermolysis bullosa, an inflammatory presentation mimicking BP, or mucous membrane pemphigoid-like lesions. Mucous membrane pemphigoid (MMP) is the term agreed upon by international consensus for an autoimmune blistering disorder, which affects one or more mucous membrane and may involve the skin. The condition involves a number of different autoantigens in the basement membrane zone. It may result in severe complications from scarring, such as blindness and strictures. Diagnosis of these diseases relies on direct immunofluorescence microscopy studies and immunoserological assays. Management of affected patients is often challenging. We will here review the clinical and immunopathological features as well as the pathophysiology of this group of organ-specific autoimmune diseases. Finally, we will discuss the diagnostic approach and the principles of management in clinical practice.

Autoimmune Subepidermal Bullous Diseases of the Skin and Mucosae: Clinical Features, Diagnosis, and Management.

Doxycycline, a tetracycline antibiotic, is widely used in the field of dermatology for its antibiotic properties, anti-inflammatory properties and good safety profile. Over the past decades, numerous studies have clarified some of the anti-inflammatory mechanisms of doxycycline. In this review article, we aimed to provide an update on recent data on the anti-inflammatory properties of doxycycline and its potential role in cutaneous inflammatory diseases. Better understanding of these mechanisms might offer the practicing clinicians a better use of this therapeutic tool. In addition, research in this field could help clarify pathogenic aspects of inflammatory dermatologic diseases responsive to this medication. Further research is needed to fully elucidate the potential of doxycycline as an anti-inflammatory agent, and the development of new topical vehicles could open ways to new therapeutic possibilities for dermatologists.

Doxycycline as an anti-inflammatory agent: updates in dermatology.

Epidermolysis bullosa acquisita (EBA) is an orphan autoimmune disease. Patients with EBA suffer from chronic inflammation as well as blistering and scarring of the skin and mucous membranes. Current treatment options rely on non-specific immunosuppression, which in many cases, does not lead to a remission of treatment. Hence, novel treatment options are urgently needed for the care of EBA patients. During the past decade, decisive clinical observations, and frequent use of pre-clinical model systems have tremendously increased our understanding of EBA pathogenesis. Herein, we review all of the aspects of EBA, starting with a detailed description of epidemiology, clinical presentation, diagnosis, and current treatment options. Of note, pattern analysis via direct immunofluorescence microscopy of a perilesional skin lesion and novel serological test systems have significantly facilitated diagnosis of the disease. Next, a state-of the art review of the current understanding of EBA pathogenesis, emerging treatments and future perspectives is provided. Based on pre-clinical model systems, cytokines and kinases are among the most promising therapeutic targets, whereas high doses of IgG (IVIG) and the anti-CD20 antibody rituximab are among the most promising "established" EBA therapeutics. We also aim to raise awareness of EBA, as well as initiate basic and clinical research in this field, to further improve the already improved but still unsatisfactory conditions for those diagnosed with this condition.

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Epidermolysis Bullosa Acquisita: The 2019 Update

IL-17A is functionally relevant and a potential therapeutic target in bullous pemphigoid.

Bullous pemphigoid (BP) is by far the most common autoimmune blistering dermatosis that mainly occurs in the elderly. The BP180 is a transmembrane glycoprotein, which is highly immunodominant in BP. The structure and location of BP180 indicate that it is a significant autoantigen and plays a key role in blister formation. Autoantibodies from BP patients react with BP180, which leads to its degradation and this has been regarded as the central event in BP pathogenesis. The consequent blister formation involves the activation of complement-dependent or -independent signals, as well as inflammatory pathways induced by BP180/anti-BP180 autoantibody interaction. As a multi-epitope molecule, BP180 can cause dermal-epidermal separation via combining each epitope with specific immunoglobulin, which also facilitates blister formation. In addition, some inflammatory factors can directly deplete BP180, thereby leading to fragility of the dermal-epidermal junction and blister formation. This review summarizes recent investigations on the role of BP180 in BP pathogenesis to determine the potential targets for the treatment of patients with BP.

/pdf/bp180-is-critical-in-the-autoimmunity-of-bullous-pemphigoid-2vycmkw1ra.pdf

BP180 Is Critical in the Autoimmunity of Bullous Pemphigoid

Doxycycline versus prednisolone as an initial treatment strategy for bullous pemphigoid: a pragmatic, non-inferiority, randomised controlled trial


 Phaeohyphomycosis is a group of multisystem mycoses owed to heterogeneous organisms called ‘dematiaceous’ or ‘melanized’ fungi. The presence of melanin in their cell walls is a distinguishing feature, likely to be acting as a virulence factor. Widely abundant in the environment, these organisms commonly infect humans through traumatic inoculation and have many clinical forms of presentation, including cutaneous, subcutaneous, systemic, and rarely disseminated. Both immunocompetent and immunocompromised hosts are affected. Diagnosis of the cutaneous infection is primarily reliant on histology and culture; treatment is not standardized and is based on clinical experience. We report a case of a 39-year-old man who presented to the dermatology clinic with ‘lumps’ on his lower limbs. His background included poorly controlled hypertension and diabetes mellitus type 2 leading to nephropathy and necessitating a renal transplant, which failed. A 5-year period of dialysis involving a sedentary lifestyle was followed by a repeat renal transplant during which time he developed multiple warty-looking nodules of varying size, with pseudomilia cysts on his lower limbs in addition to stasis changes. Histology reported a pigmented mould infection (probably phaeohyphomycosis), and there was no growth on culture. The patient was trialled on two azole antifungals at different times, but on both occasions, he dived into congestive cardiac failure needing intensive care unit admissions. Reducing immunosuppression therapy was difficult considering his previous failed renal transplant. Owing to the extent and multiplicity of the lesions on the background of immunosuppression, the surgical treatment option poses significant risks. Currently, he is managed on topical treatment with some stabilization of the lesions; however, it is unclear how these will progress in the future. Although uncommon, the number of patients with phaeohyphomycosis has increased due to awareness of melanized fungi on a background of the global COVID-19 pandemic, with SARS-CoV-2, and the use of immunosuppressive agents such as glucocorticoid therapy increasing the risk of infections of deep mycosis. Treatment for phaeohyphomycosis has largely been surgical excision for localized lesions in addition to oral antifungals. Our case highlights that, in transplant patients, therapeutics are difficult, with life-threatening complications from oral antifungals and the risks of surgical intervention including ulceration, bleeding and infections. In addition, the cosmetic appearance of the prevalent noticeable lesions for a relatively young patient is also significant and patient counselling is vital, especially when treatment options are minimal.

https://academic.oup.com/bjd/article-pdf/188/Supplement_4/ljad113.196/50699164/ljad113.196.pdf

Indre Verpetinske

Papers

Doxycycline versus prednisolone as an initial treatment strategy for bullous pemphigoid: a pragmatic, non-inferiority, randomised controlled trial

BI28 Phaeohyphomycosis in the immunosuppressed patients: the challenges of treatment