Exacerbation of Hailey-Hailey Disease Following SARS-CoV-2 Vaccination.

is missing (Short communication).

[CHRONIC DERMATITIS OF THE DORSUM OF THE FEET AND SHINS, DUE TO ALLERGIC CONTACT DERMATITIS TO LEATHER PRODUCTS].

INTRODUCTION: A 40 year old woman presented with dermatitis mainly involving her dorsal feet and shins, a condition which was present for a prolonged period of time. The distribution was suggestive of allergic contact dermatitis, possibly to her shoes. Patch tests disclosed allergy to chromates, cobalt, colophony, all present in leather products, and allergy to myroxylon pereirae (Balsam of Peru). The patient was instructed to avoid wearing some of her shoes and sitting on her leather sofa. As a consequence, her symptoms ameliorated. This case demonstrates the importance of patch testing with correct interpretation and advice to improve quality of life in patients with dermatitis.

Valproic acid hypersensitivity and desensitization.

Rash, a hypersensitivity reaction, is a common cause of withdrawal from an effective antiepileptic drug (AED) in patients with epilepsy. We present a case of successful desensitization to valproic acid in a 12-year-old male with childhood absence epilepsy and a hypersensitivity reaction, whose epilepsy did not respond to other AEDs. Desensitization is a practical therapeutic solution for patients who develop a non-life-threatening hypersensitivity reaction to an AED for which there may be no substitute.

Cerebral Aneurysms and Recurrent TIAs in a 42-Year-Old Patient With DADA2 Mutation: A Case Report.

Objectives: Deficiency of adenosine deaminase 2 (DADA2) is a rare, recessively inherited autoinflammatory disease with a wide clinical spectrum of manifestations, including strokes and vasculitis. Methods: We report a case of a patient with DADA2 who presented with neurologic manifestations. Results: A 42-year-old woman with a known diagnosis of polyarteritis nodosa experienced several episodes of TIAs. Neuroimaging revealed 2 aneurysms in unusual locations. Her young age, ethnic origin, absent of cardiovascular risk factors, and skin involvement raised the suspicion of DADA2. Genetic testing confirmed the diagnosis, and a directed treatment with anti-TNF was initiated. Discussion: DADA2, although thought to be rare, needs to be borne in mind when evaluating patients with a combination of neurologic and systemic symptoms, as early diagnosis and treatment are imperative in preventing permanent disability.

Pediatric Contact Dermatitis: A 10-Year Multicenter Retrospective Study.

Background: Although allergic contact dermatitis (ACD) is relatively common in the adult and pediatric populations alike, few studies describe the special features of contact sensitization among the Israeli pediatric populations, none of them is multicenter. Our study aims to describe and analyze patch test results and trends in 4 tertiary care centers between 2012 and 2022. Methods: We assessed the results of 357 patch tests performed on children 0-18 years old between 2012 and 2022 in designated clinics in 4 tertiary medical centers. All patients were tested using the European baseline series and additional series as clinically indicated. We assessed the demographic features, atopic features, and influence, as well as the main allergens to cause sensitization and allergic contact dermatitis among the pediatric population. Results: In total 69% of the study population were females, mainly 12-18 years old, 35% of the study population were previously diagnosed with atopic dermatitis, and 57% had an atopic diathesis. Females were more commonly sensitized (P < 0.05). Patients without atopic dermatitis were more commonly diagnosed with ACD and had more reactions on patch test (P < 0.05). The most common allergens to cause ACD are preservatives and metals, as previously described, however, acrylate sensitivity is an emerging group that has not been described among the Israeli pediatric population in previous studies. Fragrance mix 2 and Mroxylon pereirae are relatively rare allergens among the Israeli pediatric population, whereas linalool hyperoxide might be considered an emerging allergen. Methylisothiazolinone causes ACD more frequently among patients without atopic dermatitis (P < 0.05). Conclusions: Among the Israeli pediatric population, ACD is more common in females without atopic dermatitis. Acrylates become a common culprit and should be included in baseline series. Patients with atopic dermatitis are less frequently sensitized by methylisothiazolinone.

Novel and recurrent FERMT1 gene mutations in Kindler syndrome.

Kindler syndrome (OMIM 173650) is an autosomal recessive condition characterized by skin blistering, skin atrophy, photosensitivity, colonic inflammation and mucosal stenosis. Fewer than 100 cases have been described in the literature. First reported in 1954, the molecular basis of Kindler syndrome was elucidated in 2003 with the discovery of FERMT1 (KIND1) loss-of-function mutations in affected individuals. The FERMT1 gene encodes kindlin-1 (also known as fermitin family homologue 1), a 77 kDa protein that localizes at focal adhesions, where it plays an important role in integrin signalling. In the current study, we describe five novel and three recurrent loss-of-function FERMT1 mutations in eight individuals with Kindler syndrome, and provide an overview of genotype-phenotype correlation in this disorder.

Marie Unna hereditary hypotrichosis caused by a novel mutation in the human hairless transcript.

Recently the causes for various forms of hypotrichosis and atrichia have been identified, increasing our understanding of the pathways involved in hair cycling and morphogenesis. Loss-of-function mutations of an inhibitory upstream ORF in the human hairless transcript were found as the cause for autosomal dominant Marie Unna hereditary hypotrichosis. At present, only two studies identified several pathogenic mutations. We ascertained a Jewish Ashkenazi family with hypotrichosis simplex of the Marie Unna type in a mother and her two children. Sequencing of the upstream ORF U2HR in the 5' UTR of the hairless gene resulted in the identification of a novel heterozygous missense mutation c.74C > T resulting in the amino acid change p.P25L. Functional assays confirmed that this mutation led to increased translation of the main HR ORF. This finding extends the mutations' spectrum of U2HR, and emphasizes its major role in hair growth.

Mutations in lipase H cause autosomal recessive hypotrichosis simplex with woolly hair.

BACKGROUND: Mutations in lipase H (LIPH) are a rare cause of autosomal recessive hypotrichosis (HT) simplex. OBJECTIVE: In this study, we investigated the clinical and molecular basis of HT simplex with woolly hair in 3 nonrelated families. METHODS: Three families of Jewish, Arab Muslim, and Italian origin that presented with HT with woolly hair were studied. The phenotype was confirmed by clinical, microscopic, and histologic examination. Polymorphic microsatellite genotyping and direct automated DNA sequencing of the LIPH gene were used to identify the mutations in our probands. RESULTS: All patients had woolly hair since birth. At presentation, scalp hair density was reduced or normal. Sequencing of the LIPH gene revealed two homozygous mutations: a large recurrent 90-base pair duplication mutation in exon 2 in the Jewish and Arab families, and a novel deletion/insertion mutation in exon 4 in the Italian family. LIMITATIONS: Only 3 families were studied. CONCLUSION: Mutations in LIPH result in variable degrees of HT. Woolly hair is an essential component of the clinical spectrum. A hot spot in the LIPH gene may be c.280_369dup in exon 2.

An autosomal recessive form of monilethrix is caused by mutations in DSG4: clinical overlap with localized autosomal recessive hypotrichosis.

Monilethrix is a structural defect of the hair shaft usually inherited in an autosomal dominant fashion and caused by mutations in the hHb1, hHb3, and hHb6 keratin genes. Autosomal recessive inheritance in this disease has been sporadically reported. We encountered 12 Jewish families from Iraq, Iran, and Morocco with microscopic findings of monilethrix, but with no evidence of vertical transmission. Since no mutations were found in these three hair keratin genes, we examined nine chromosomal regions containing gene clusters encoding skin and hair genes. On chromosome 18q, a common haplotype in the homozygous state was found among all seven Iraqi patients, but not in 20 controls (P<0.0001). Sequencing of the main candidate gene from this region revealed four different mutations in desmoglein 4 (DSG4). Mutations in DSG4 have been previously reported in localized autosomal recessive hypotrichosis, a disorder that shares the clinical features of monilethrix but lacks the characteristic microscopic appearance of the hair shaft. Our findings have important implications for genetic counseling to monilethrix patients and families, and suggest that DSG4-associated hair disorders may be more common than previously thought.

Germline fumarate hydratase mutations and evidence for a founder mutation underlying multiple cutaneous and uterine leiomyomata.

Multiple cutaneous and uterine leiomyomata syndrome (MCL) is an autosomal dominant disease characterized by the presence of concurrent benign tumors of smooth muscle origin (leiomyoma) in the skin and uterus of affected females, and in the skin of affected males. MCL can also be associated with type II papillary renal cell cancer (HLRCC). The genetic locus for MCL and HLRCC was recently mapped to chromosome 1q42.3-43 and subsequently, dominantly inherited mutations in the fumarate hydratase gene ( FH ) were identified. Importantly, analysis of the FH gene in tumors of MCL patients revealed a second mutation inactivating the wild-type allele in some tumors. Based on these findings, it has been suggested that FH may function as a tumor suppressor gene in MCL. Here, we report the analysis of the FH gene in a group of 11 MCL families, with the identification of 8 different mutations accounting for the disease in all families. One of the mutations, 905-1G>A, has been identified in 4 families of Iranian origin. The analysis of highly polymorphic markers in the vicinity of the FH gene showed a shared haplotype in these 4 families, suggesting that 905-1G>A represents a founder mutation. Collectively, identification of 5 novel and 3 recurrent mutations further supports the role of FH in the pathogenesis of MCL.

Yellow Feet in a Patient with Breast and Thyroid Carcinoma, Due to Oral Intake of Turmeric.

Yellow discoloration of the skin may be caused by several etiologies, including jaundice, hypervitaminosis, drug reaction or chemical exposure. Herein we describe a 68-year-old woman with a history of breast and thyroid carcinoma, presenting with a yellow discoloration of her soles, after ingestion of one capsule a day of turmeric root extract (Bluebonnet Turmeric Root, 500 mg, Vcap), taken for its anti-cancer properties, for 4 months. After drug cessation, the yellow hue disappeared completely. A Naranjo assessment score of 5 was obtained, indicating a probable relationship between the patient's symptom and her use of the drug. Curcumin, a mixture of diferuloymethane derivatives known as curcuminoids, is a yellow pigment present in the spice turmeric. Topical application of curcumin to the human skin is joined by orange-yellow discoloration. To the best of our knowledge, yellow skin discoloration after oral intake of turmeric is not mentioned in the medical literature.

Lymphatic Dissemination in Cutaneous Leishmaniasis Following Local Treatment.

Cutaneous leishmaniasis (CL) is diverse in its clinical presentation but usually demonstrates an erythematous, infiltrated, ulcerated, and crusted papule or nodule in exposed areas of the body. Rare clinical features have been reported including lymphatic dissemination, usually with subcutaneous nodules along lymphatic channels. Herein, we present six patients suffering from Old World CL with lymphatic dissemination characterized by sporotrichoid subcutaneous nodules along the lymphatic channels draining the primary lesion. Patients' history, clinical and laboratory findings were collected and summarized. Lymphatic dissemination of CL in our patients manifested as subcutaneous nodules without epidermal involvement within the axis of lymphatic drainage toward the regional lymph node, at times accompanied by regional lymphadenopathy. In all patients, the lymphatic dissemination was not present at initial diagnosis of CL, appearing only after local (topical or intralesional) treatment was initiated. In three patients, the subcutaneous nodules resolved without systemic treatment. Lymphatic dissemination of Old World CL is not uncommon and may possibly be triggered by local treatment. It should be recognized by dermatologists, especially those working in endemic areas. Systemic treatment may be not necessary since spontaneous resolution may occur.

Multiple cutaneous and uterine leiomyomas: refinement of the genetic locus for multiple cutaneous and uterine leiomyomas on chromosome 1q42.3-43.

Cutaneous leiomyomas, rare benign tumors originating from the arrector pili muscle of the hair follicle, can be associated with the common uterine fibroids in a syndrome called multiple cutaneous and uterine leiomyomas. Multiple cutaneous and uterine leiomyomas are inherited as an autosomal dominant trait, providing an excellent opportunity for the study of the common non-Mendelian manifestation of isolated uterine fibroids. This study reports the clinical and molecular characterization of an extended family with multiple cutaneous and uterine leiomyomas. Linkage analysis has shown that the disease in this family is linked to the recently reported genetic locus for multiple cutaneous and uterine leiomyomas, with a maximum two-point LOD score of 4.453 for markers D1S2670, D1S2785, D1S547, and D1S1609. The identification of key recombination events has allowed us to refine substantially the location of the genetic locus for multiple cutaneous and uterine leiomyomas, from 14 cM to an interval of 4.55 or 7.19 cM, depending on the final phenotype of a young family member in which one of the key recombination events has occurred. In addition, we provide a description of the interesting pattern and progression of the skin phenotype in this four-generation kindred. The refinement of the genetic locus for multiple cutaneous and uterine leiomyomas and the availability of an extended multigeneration pedigree will facilitate the identification of the mutated gene responsible for multiple cutaneous and uterine leiomyomas, which, in turn, may provide key information for the understanding of the molecular basis of the common uterine fibroids.

Germline fumarate hydratase mutations in families with multiple cutaneous and uterine leiomyomata.

Germline mutations in the fumarate hydratase gene (FH) predispose to multiple cutaneous and uterine leiomyoma syndrome (MCL) and MCL associated with renal cell cancer. MCL is inherited in an autosomal dominant pattern, manifesting as skin leiomyoma and uterine fibroids in affected individuals. Fumarate hydratase, a component of the tricarboxylic acid cycle, acts as a tumor suppressor gene in the development of cutaneous and uterine leiomyoma and renal cell cancer in this syndrome. Here we report the clinical and mutational analysis of five families with MCL, with the identification of five new mutations affecting highly conserved residues of the FH protein. These results provide further evidence for the role of the FH gene in the pathogenesis of MCL.