Midfacial Toddler Excoriation syndrome (MiTES): case series, diagnostic criteria and evidence for a pathogenic mechanism.

BACKGROUND: PRDM12 polyalanine tract expansions cause two different disorders; Midfacial Toddler Excoriation Syndrome (MiTES) - itch with normal pain sensation associated with homozygous 18 alanines (18A), and congenital insensitivity to pain (CIP) with normal itch with homozygous 19A. Knowledge of the phenotype, genotype, and disease mechanism of MiTES is incomplete. Why PRDM12 18A versus 19A can cause almost opposite phenotypes is unknown; no other poly-alanine or poly-glutamine tract expansion disease causes two such disparate phenotypes. METHODS: We assessed the genotype and phenotype of 9 new, 9 atypical, and 6 previously reported patients diagnosed with MiTES. Using cell lines with homozygous PRDM12 of 12A (normal), 18A (MiTES) and 19A (CIP) we examined PRDM12 aggregation and subcellular localisation by image separation confocal microscopy and sub-cellular fractionation western blotting. RESULTS: MiTES presents in the first year of life, and in all cases the condition regresses over the first decade leaving scarring. The MiTES phenotype is highly distinctive. Features overlapping with PRDM12-CIP are rarely found. The genotype-phenotype study of PRDM12 polyalanine tract shows that 7A -15A are normal; 16A -18A are associated with MiTES; 19A leads to CIP; and no clinically atypical MiTES cases had an expansion. PRDM12 aggregation and sub-cellular localisation differ significantly between 18A and normal 12A cell lines and between 18A and 19A cell lines. MiTES is a new protein aggregation disease. CONCLUSION: We provide diagnostic criteria for MiTES, and improved longitudinal data. MiTES and CIP are distinct phenotypes despite their genotypes varying by a single alanine in the PRDM12 polyalanine tract. We found clear distinctions between the cellular phenotypes of normal, MiTES and CIP cells.. We hypothesise that the developmental environment of the trigeminal ganglion is unique and critically sensitive to prenatal and postnatal levels of PRDM12.

Destructive Facial Plaque and Palatal Perforation in a Middle-Aged Woman.

A woman in her 30s had asymptomatic erythematous scaly plaques over the face and proximal extremities. The lesions started as a erythematous papule on the face, which had progressed to larger plaques within 10 years. What is your diagnosis?

Role of Cutaneous Microbiome in Dermatology.

The cutaneous microflora consists of various microorganisms which interact with host epithelial cells and innate and acquired immunity. This microbial milieu and its interaction with host cells prevent the growth of pathogenic organisms and educate host immunity to fight against harmful microorganisms. The microbial composition depends on various intrinsic and extrinsic factors and an imbalance in the cutaneous microflora predisposes the individual to both infectious and non-infectious diseases. Even though probiotics have been extensively studied in various diseases, their efficacy and safety profile are still unclear. A better understanding of the cutaneous microflora is required to develop newer therapeutic targets. In this review, we describe the commensal microbiome and its variation, the current role of the cutaneous microbiome in the pathogenesis of various dermatological diseases, and their therapeutic implications.

Biologicals in Treatment of Chronic Urticaria: A Narrative Review.

Chronic urticaria is a common inflammatory skin disease affecting around 0.5-1% of the world's population. The disease has a chronic indolent course which significantly affects the patient's quality of life. Urticaria pathogenesis involves cross-linking of immunoglobulin E (IgE) on mast cells causing degranulation which occurs by various pathways which leads to development of wheals and angioedema. The first-line treatment for chronic urticaria is non-sedating second-generation H1 antihistamines (AHs). After the advent of anti-IgE monoclonal antibody omalizumab, the response rate in resistant urticaria has improved significantly without any major adverse events. Other biologicals such as anti-IgE, anti-IL-5, anti-IL-1, anti-IL-17, and anti-CD20 monoclonal antibodies are under trial. These biologicals have better efficacy and safety profile as compared to conventional immunosuppressants. Even with the advances in the last decade, recurrence after stopping the therapy is common, and there is a need for better understanding of the pathogenesis and the drugs acting on the key pathways involved in urticaria. In this review, we provide the role of several biologicals in the treatment of chronic urticaria.