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 18 homozygous alanines (18A); and congenital insensitivity to pain (CIP) with normal itch associated with 19 homozygous alanines (19A). Knowledge of the phenotype, genotype and disease mechanism of MiTES is incomplete. Why 18A vs. 19A PRDM12 can cause almost opposite phenotypes is unknown; no other polyalanine or polyglutamine tract expansion disease causes two such disparate phenotypes. OBJECTIVES: To assess the genotype and phenotype of nine new, nine atypical and six previously reported patients diagnosed with MiTES. METHODS: Using cell lines with homozygous PR domain zinc finger protein 12 (PRDM12) containing 12 alanines (12A; normal), 18A (MiTES) and 19A (CIP), we examined PRDM12 aggregation and subcellular localization by image-separation confocal microscopy and subcellular fractionation Western blotting. RESULTS: MiTES presents in the first year of life; 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 the PRDM12 polyalanine tract shows that having 7-15 alanines is normal; 16-18 alanines is associated with MiTES; 19 alanines leads to CIP; and no clinically atypical cases of MiTES had a polyalanine tract expansion. PRDM12 aggregation and subcellular localization differed significantly between 18A and normal 12A cell lines and between 18A and 19A cell lines. MiTES is a new protein-aggregation disease. CONCLUSIONS: 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 hypothesize that the developmental environment of the trigeminal ganglion is unique and critically sensitive to pre- and postnatal levels of PRDM12.

Midfacial toddler excoriation syndrome (MiTES) causes facial itching and scratching in babies during their first year of life. MiTES tends to improve over the time period of approximately 10 years, but it can leave scars. Congenital insensitivity to pain (CIP) is a condition where a person cannot feel pain and is present from birth. This study looked at two conditions: MiTES and CIP. We specifically investigated changes in a gene called PRDM12, focusing on a part of the gene called the polyalanine tract ­ a sequence of many alanines (alanine is a type of amino acid). We discovered that the normal range for this sequence is between 7 and 15 alanines. If there are 16 to 18 alanines, it is associated with MiTES and causes the PRDM12 protein to clump together inside the cell. However, if there are 19 alanines, it leads to CIP, and the PRDM12 protein clumps together and moves to the cytoplasm, where it should not be. We found new evidence to suggest that MiTES is a disease where proteins clump together. Overall, our study findings show that despite there only being a small change in the same gene, MiTES and CIP are very different conditions.

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.