Recent Advances in Clinical Research on Rare Intractable Hereditary Skin Diseases in Japan.

Our Research Group for Rare and Intractable Skin Diseases operates within the Project for Research on Intractable Diseases of the Ministry of Health, Labour, and Welfare of Japan and is conducting research on eight rare intractable skin diseases. Five of these are monogenic disorders (epidermolysis bullosa, congenital ichthyoses, oculocutaneous albinism, pseudoxanthoma elasticum, and hereditary angioedema), and for a sixth [generalized pustular psoriasis (GPP)], genetic predisposing factors are important. This review introduces our activities for raising public awareness of these six intractable hereditary skin diseases and summarizes our recent achievements in clarifying the situation of medical treatments for these diseases in Japan.

Monogenic causes of pigmentary mosaicism.

Pigmentary mosaicism of the Ito type, also known as hypomelanosis of Ito, is a neurocutaneous syndrome considered to be predominantly caused by somatic chromosomal mosaicism. However, a few monogenic causes of pigmentary mosaicism have been recently reported. Eleven unrelated individuals with pigmentary mosaicism (mostly hypopigmented skin) were recruited for this study.

Current topics in Epidermolysis bullosa: Pathophysiology and therapeutic challenges.

Epidermolysis bullosa (EB) is a group of inherited skin and mucosal fragility disorders resulting from mutations in genes encoding basement membrane zone (BMZ) components or proteins that maintain the integrity of BMZ and adjacent keratinocytes. More than 30 years have passed since the first causative gene for EB was identified, and over 40 genes are now known to be responsible for the protean collection of mechanobullous diseases included under the umbrella term of EB. Through the elucidation of disease mechanisms using human skin samples, animal models, and cultured cells, we have now reached the stage of developing more effective therapeutics for EB.

A multicenter, open-label, uncontrolled, single-arm phase 2 study of tirabrutinib, an oral Bruton's tyrosine kinase inhibitor, in pemphigus.

Background: The treatment of pemphigus is based on systemic corticosteroid use and adjuvant therapies, but some patients are resistant to conventional therapy. Tirabrutinib is a highly selective oral Bruton's tyrosine kinase inhibitor that may be clinically effective in treating pemphigus by suppressing B-cell signaling.

Objective: We investigated the efficacy and safety of tirabrutinib in patients with refractory pemphigus.

Stratum corneum levels of calprotectin proteins S100A8/A9 correlate with disease activity in psoriasis patients.

Psoriasis is an intractable inflammatory skin disorder characterized by scaly erythema and plaques. The Psoriasis Area and Severity Index (PASI) is widely used to score disease severity, but evaluation is subjective, and an objective biomarker would be useful. The stratum corneum (SC), which can be non-invasively harvested, may reflect psoriasis-associated changes in epidermal keratinocytes, such as the upregulation of the calprotectin proteins S100A8 and S100A9.

Pemphigus Vulgaris and Foliaceus IgG Autoantibodies Directly Block Heterophilic Transinteraction between Desmoglein and Desmocollin.

Anti-desmoglein (Dsg) 1 and Dsg3 IgG autoantibodies in pemphigus foliaceus and pemphigus vulgaris cause blisters through loss of desmosomal adhesion. It is controversial whether blister formation is due to direct inhibition of Dsg, intracellular signaling events causing desmosome destabilization, or both. Recent studies show that heterophilic binding between Dsg and desmocollin (Dsc) is the fundamental adhesive unit of desmosomes.

Unusual Bone Lesions with Osteonecrosis Mimicking Bone Metastasis of Squamous Cell Carcinoma in Recessive Dystrophic Epidermolysis Bullosa.

Some bone lesions are reported to mimic bone metastasis on imaging tests. Herein, we report a case of a 55-year-old Japanese man who presented with a skin tumor on the left lower extremity. He also had a history of recurrent generalized cutaneous blister and erosion formation since childhood.

Histopathological and electron microscopic study in dogs with patellar luxation and skin hyperextensibility.

Patellar luxation is abnormal displacement of the patella from the femoral trochlear groove. It is seen primarily in small breed dogs and causes pain and limited mobility of the stifle joint. This study aimed to investigate the relationship among patellar luxation, skin extension, and skin collagen fibril diameter.

Splice site mutation in COL7A1 resulting in aberrant in-frame transcripts identified in a case of recessive dystrophic epidermolysis bullosa, pretibial.

Dystrophic epidermolysis bullosa (DEB), pretibial, a rare subtype of epidermolysis bullosa (EB), is characterized by recurrent blisters and erosions predominantly on the pretibial region. We report the case of a 60-year-old Japanese woman with persistent blistering eruptions and scar formation on the pretibial region and elbows. Mutational analysis revealed a previously reported c.

Skin lesions of Birt-Hogg-Dubé syndrome: Clinical and histopathological findings in 31 Japanese patients who presented with pneumothorax and/or multiple lung cysts.

Background: Birt-Hogg-Dubé syndrome (BHDS) (OMIM #135150) is an autosomal dominant disease, characterized by fibrofolliculomas (FFs) of the skin, pulmonary cysts with/without pneumothorax, and renal tumors. The prevalence of skin manifestations reported for Japanese BHDS patients is lower (<30%) compared with that of Western countries (75∼90%), which appear to be underestimated.

Objective: To precisely examine the prevalence of skin lesions with dermoscopy and histopathology with reference to genetic analyses.

Experimental Laminin 332 Mucous Membrane Pemphigoid Critically Involves C5aR1 and Reflects Clinical and Immunopathological Characteristics of the Human Disease.

Mucous membrane pemphigoid is an autoantibody-mediated disease predominantly affecting the oral cavity, pharynx, and conjunctiva. Conjunctival lesions may lead to impaired vision and, finally, blindness. About 25% of mucous membrane pemphigoid patients generate autoantibodies against the α3 chain of laminin 332 (LAMα3), a structural protein of epidermal/epithelial basement membranes.

Dermoscopic features of nail psoriasis treated with biologics.

Although psoriatic nail lesions are small, they cause considerable discomfort for patients and adversely affect quality of life. Few studies have evaluated the dermoscopic features of psoriatic nails. The aim of this study was to clarify the dermoscopic features of nail psoriasis and identify those that reflect psoriatic activity.

A scabies outbreak in a diabetic and collagen disease ward: Management and prevention.

Scabies is an infection caused by . In developed countries, scabies remains an important public health problem in hospitals and care facilities among elderly or immunocompromised patients. There are a number of medical providers who have not experienced scabies and there has been confusion surrounding its management and prevention.

Non-pathogenic pemphigus foliaceus (PF) IgG acts synergistically with a directly pathogenic PF IgG to increase blistering by p38MAPK-dependent desmoglein 1 clustering.

Background: Pemphigus foliaceus (PF) is an autoimmune blistering disease caused by autoantibodies (Abs) against desmoglein 1 (Dsg1). PF sera contain polyclonal Abs which are heterogeneous mixture of both pathogenic and non-pathogenic Abs, as shown by isolation of monoclonal Abs (mAbs).

Objective: To investigate how pathogenic and non-pathogenic anti-Dsg1 Abs contribute to blister formation in PF.