Impact of climate change on atopic dermatitis: A review by the International Eczema Council.

Atopic dermatitis (AD), the most burdensome skin condition worldwide, is influenced by climatic factors and air pollution; however, the impact of increasing climatic hazards on AD remains poorly characterized. Leveraging an existing framework for 10 climatic hazards related to greenhouse gas emissions, we identified 18 studies with evidence for an impact on AD through a systematic search. Most climatic hazards had evidence for aggravation of AD the impact ranged from direct effects like particulate matter-induced AD exacerbations from wildfires to the potential for indirect effects like drought-induced food insecurity and migration. We then created maps comparing the past, present, and future projected burden of climatic hazards to global AD prevalence data. Data are lacking, especially from those regions most likely to experience more climatic hazards. We highlight gaps important for future research: understanding the synergistic impacts of climatic hazards on AD, long-term disease activity, the differential impact on vulnerable populations, and how basic mechanisms explain population-level trends.

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.

Scrotal ulcers in an infant with multisystem inflammatory syndrome in children associated with severe acute respiratory syndrome coronavirus 2 infection.

The majority of cases of multisystem inflammatory syndrome in children (MIS-C) manifest non-specific mucocutaneous features. We report the case of a 3-month-old infant presenting with purpura, acral desquamation, and scrotal ulcers. Scrotal ulcers have not been previously reported in MIS-C and add to the spectrum of cutaneous findings associated with the disorder.

Disseminated cutaneous tuberculosis from BCG vaccination site in an immunocompetent child.

A healthy 4-month-old girl presented with widespread scaly papules and a nodule over the site of BCG immunization. A diagnosis of disseminated cutaneous tuberculosis in an immunocompetent child was confirmed with biopsy. The child was treated with antituberculosis therapy without recurrence.

Systemic mastocytosis associated with Hodgkin's lymphoma in a 4-year-old child.

Systemic mastocytosis with associated clonal hematologic non-mast cell lineage disease (SM-AHN) represents a specific subtype of mastocytosis and is extremely rare in children. We describe a 4-year-old child with systemic mastocytosis associated with Hodgkin's lymphoma. The child had cutaneous mastocytosis and lymphadenopathy without other clinical features of SM, which was diagnosed only by bone marrow examination.

Langerhans cell histiocytosis in children: A retrospective case series of 126 cases.

BACKGROUND/OBJECTIVES: Langerhans cell histiocytosis (LCH), a rare neoplasm of hematopoietic myeloid precursor cells, is clinically characterized by spontaneously resolving lesions to a progressive life-threatening multisystem disorder. Diagnosing LCH in children is challenging as it mimics other skin disorders. This study describes the varied clinical presentation and disease course in children less than 18 years diagnosed with LCH. METHODS: We performed a retrospective observational study of all cases diagnosed with LCH presenting to a children's hospital in the last 26 years. Data on history, cutaneous and systemic examination, and laboratory evaluation performed, were recorded. RESULTS: A total of 126 children diagnosed with LCH were included in the study. There were 68% cases limited only to skin, and 32% children with multisystem involvement at the initial presentation. Scaly papules were the most common morphologic finding in skin. The skeletal system was the second most common organ system to be affected. Failure to thrive was a common symptom. Progression of skin to systemic involvement was seen in 27.9%. In 76.7%, skin lesions cleared over a period of 2 to 4 years. Complete remission was seen in 56.9% of children over a period of 3 to 7 years, while 8.1% children died of complicationsand 31.8% were lost to follow-up. CONCLUSIONS: Long-term follow-up in this study has shown cutaneous LCH without systemic involvement has a good prognosis. Skin involvement,along with failure to thrive, was the most common clinical presentation in our study. The skeletal system was the second most common organ system involved.

Idiopathic Hypereosinophilic Syndrome Presenting with Recalcitrant Oral and Genital Ulcers Responding Well to Thalidomide.

Hypereosinophilic syndrome is a myeloproliferative disorder characterized by abnormal accumulation of eosinophils in the blood or peripheral tissues. It is uncommonly seen in children. We describe a 14-year-old girl diagnosed with idiopathic hypereosinophilic syndrome presenting with recurrent, painful oral and genital ulcers, hepatosplenomegaly along with consistently high eosinophil count and leucocytosis. Genetic studies showed negative for FIPIL-PDGFRA fusion gene. Mucosal ulcers were recalcitrant to conventional therapy and responded well to thalidomide.

KIT Gene Mutation Causing Piebaldism Associated with Multiple Café Au-Lait Like Macules and Freckling: Delineating a Cause of this Coexistence.

Piebaldism is a rare genetic disorder of congenital leukoderma caused by mutation in KIT proto-oncogene receptor tyrosine kinase. We present a 10-year-old boy with congenital depigmented macules suggestive of piebaldism associated with café au lait macules and skin fold freckling complicating the diagnosis. A diagnosis of piebaldism was made via exome sequencing that showed a pathogenic variant of KIT gene with no pathogenic variants of NF1 or SPRED1 gene. Our current understanding of the KIT tyrosine kinase function may provide a better explanation into this phenotypic coexistence and does not necessarily represent an overlap with Neurofibromatosis type 1.

Infantile Systemic Hyalinosis Presenting as Pseudo-Paralysis in Infancy: Study of Six Cases.

Infantile systemic hyalinosis is a very rare fatal autosomal recessive genetic disorder with a mutation in capillary morphogenesis gene-2- CMG2 /Human anthrax toxin-2 ANTXR2 resulting in spindle cell proliferation, altered collagen metabolism along with extensive deposition of hyaline material in the skin and several tissues. To date only a few cases have been reported in the literature, hence we reported this series. This study is a retrospective chart review of infants diagnosed with infantile systemic hyalinosis from January 2015 through December 2020 at a tertiary care children's hospital in South India. The mean age of presentation was 9.4 months, with a male to female ratio of 1:5. All children were born of consanguineous marriage except one child. All children had symptoms at birth, painful limb movements, multiple joint stiffness, gingival thickening, skin lesions around perianal, perioral areas, and frog-like position. Three (50%) children had stiff skin. Routine tests including complete blood count, liver function test, renal function test, creatine phosphokinase, nerve conduction studies, and metabolic tests were normal in all children. Skin biopsy showed hyalinized collagenous tissue in the dermis. Genetic study results of two cases revealed pathogenic variants in ANTXR2 gene. Infantile systemic hyalinosis should be considered in infants presenting with painful limb movements. The diagnosis helped in avoiding unnecessary investigations and prognostications. The genetic information from proband mutation helped in prenatal diagnosis in two families.

Filaggrin gene polymorphisms in Indian children with atopic dermatitis: A cross-sectional multicentre study.

Background Filaggrin (FLG) gene encoding the protein filaggrin plays an important role in barrier function of the skin and its alteration is a predisposing factor for atopic dermatitis. FLG gene variants result in absent or decreased filaggrin protein. Worldwide, the prevalence of FLG variants ranges from 14 to 56%. FLG null variants are distinct in each population. Objectives To study the FLG gene polymorphisms in Indian children and attempt a genotype-phenotype correlation in atopic dermatitis. Methods This was a cross-sectional, multicentre study conducted on 75 Indian children. Demographic details, clinical features and identified FLG null variants were recorded. We performed a whole gene sequencing of the entire FLG coding region using next-generation sequencing technology. Results The prevalence of FLG null variants was 34.7%. A total of 20 different FLG loss of function variants in 26 children were documented. Sixteen (80%) variants were novel and four (20%) were previously reported in Asian and European populations. We found a statistically significant association between FLG variants with early age of onset of atopic dermatitis (P = 0.016) and elevated serum IgE levels (P = 0.051). There was no significant difference between atopic dermatitis phenotypes in children having one variant as compared to children harbouring two or more null variants. Limitation Small sample size. Conclusion Our study reports a unique set of FLG variants different from Asian and European populations, with these variants being significantly associated with an early age of onset of atopic dermatitis and elevated serum IgE levels.

Recurrent Bilateral Lower Motor Neuron Type of Facial Palsy with Hearing Impairment: Hyperphosphatemic Familial Tumoral Calcinosis.

Hyperphosphatemic familial tumoral calcinosis (HFTC) presents with varied neurological manifestations that have been reported in the literature like facial palsy, vision and hearing impairment, stroke, and headache. In this article, we reported a 12-year-old girl child patient with recurrent facial weakness with bilateral hearing impairment and multiple ulcerative lesions on lower limbs and elbows. On examination, she had lower motor neuron (LMN) facial palsy with conductive hearing loss. The investigations showed hyperphosphatemia (9.3 mg/dL) with normal serum calcium (10.4 mg/dL), alkaline phosphatase (147.9 U/L), parathyroid hormone (23.12 pg/mL), and renal function tests. Elevated serum calcium and phosphorus product (96.72 mg 2 /mL 2 ) and elevated renal tubular reabsorption of phosphate (TMPxGFR) value (9.16) were noted. Skeletal survey showed hyperostosis in the long bone diaphysis, vertebrae, ribs, pelvic bone, skull, and facial bones with narrowing of cranial ostium, characteristically without any peri-articular soft tissue calcifications. An angiogram showed multiple intravascular calcifications. She was managed with a low-phosphate diet, sevelamer, niacinamide, acetazolamide, sucroferric oxyhydroxide to lower serum phosphate level, and topical sodium thiosulfate ectopic cutaneous calcification. Exome sequencing showed novel homozygous inframe deletion of ACG in FGF23 gene exon 3 at c.374_376 delins position (p. Asp125del) in the proband and a mutation in the heterozygous state in the mother and elder sibling, thus confirming a molecular diagnosis of HFTC. Our case had a unique neurological presentation of recurrent bilateral lower motor nerve facial palsy, hearing loss, multiple ectopic cutaneous calcifications without peri-articular deposits, multiple intravascular, intracranial, and vertebral endplate calcification, which has not been reported earlier. The proband showed a novel pathogenic variant suggesting an expanding phenotype of HFTC.

Psoriasis in Pediatric Age Group.

Psoriasis is a common, chronic, immune-mediated, multisystem, inflammatory disorder. It affects all age groups, including infancy. In one-third of the cases, the onset of the disease is in the first and second decades of life. Childhood psoriasis significantly affects the quality of life of the child as well as that of the entire family. Pediatric psoriasis has distinct clinical presentations and evolves with time. Like in adults, chronic plaque psoriasis has been found to be the most common type of childhood psoriasis. Psoriatic plaques in children are less pruritic, smaller and thinner with less prominent scaling. In pigmented skin, the erythema is less prominent and plaques appear violaceous or hyperpigmented. Pediatric psoriasis can be associated with arthritis, metabolic syndrome, depression and anxiety. Hence all children should be screened routinely for associated comorbidities. Management of pediatric psoriasis is challenging owing to the limitation of approved therapies. 'Proactive therapy' is a recent approach in childhood-onset psoriasis that would help to prevent the severity of flare-ups, thus improving the quality of life.

Real-World Effectiveness and Safety of Dupilumab for the Treatment of Moderate to Severe Atopic Dermatitis in Indian Patients: A Multi Centric Retrospective Study.

INTRODUCTION: Treatment of moderate to severe atopic dermatitis (AD) is a real challenge for the dermatologists. Dupilumab is the first targeted biologic therapy approved for the treatment of children and adults with moderate-to-severe AD. The efficacy and safety of dupilumab in Indian patients is limited to date, it is necessary to assess the performance of this treatment in real clinical practice in the Indian context. METHODOLOGY: Patients from three centers of India, two from Kolkata and one from Bangalore were included in the study for retrospective chart analysis. Efficacy was assessed by comparing the SCORAD and EASI and impact on quality of life was assessed by DLQI scores. All patients received standard doses of Dupilumab. Any side effect of the treatment was noted in the bi-weekly follow-up visit. RESULTS: Twenty-five patients who were treated with dupilumab for at least 6 months were retrospectively included to study. The mean EASI score improved from 19.48 at baseline to 4.84 at six months. Seventeen patients (68%) achieved EASI 75 (≥75% improvement from baseline) at the end of 6 months of treatment. All these patients were earlier treated with at least one systemic immunomodulator without any significant improvement. The mean SCORAD score also improved with dupilumab treatment from 37.32 at baseline to 8.04 at six months. The improvement were found to be statistically significant (P < 0.001). The quality of life also improved significantly (P < 0.001) from a baseline mean of 17.08 at baseline to 6.52 at 6 months. CONCLUSIONS: We observed significant efficacy, tolerability, and safety of dupilumab in Indian patients with AD in a real-world setting, which was similar to that shown in clinical trials in the western populations.

Association of Anti N-methyl-D-aspartate (NMDA) Receptor Encephalitis with Chediak-Higashi Syndrome.

BACKGROUND: Neurological manifestations of Chediak-Higashi syndrome mainly include peripheral neuropathy, ataxia, tremors, cranial nerve palsies, intellectual decline and seizures. CASE CHARACTERISTICS: A 2 years 10 month old girl with silvery hair syndrome presented with sub-acute onset behavioral issues, ataxia and multiple type abnormal movements. Cerebrospinal fluid examination was positive for Anti NMDA receptor antibodies. Hair shaft examination and peripheral blood film findings were suggestive of Chediak Higashi syndrome. MESSAGE: Anti NMDA receptor encephalitis may be associated with Chediak Higashi Syndrome.