Lichen planus (LP) in children is a rare entity. We report 23 cases of childhood LP seen over a period of 7 years. Ninety-six percent of the children were of Arab ancestry. There were 52% boys and 48% girls. Classic LP was the most common clinical variant (70%), followed by eruptive generalized LP (13%). A majority of the patients had mild, localized disease. Oral involvement was seen in 39% of patients. Topical steroids were the mainstay of treatment in most of the cases. Children with chronic and recurrent disease responded to dapsone therapy, whereas in those with eruptive and widespread disease, UVB phototherapy was found to be safe and effective. The present report highlights the salient clinical features, treatment, and course of LP in children in Kuwait compared to those reported in children of other countries as well as those of adults.

Mycosis fungoides (MF) is rare in children and adolescents. This study was aimed to determine the clinicoepidemiologic features of juvenile onset (≤18 yrs) MF in Kuwait. Thirty-six children and adolescents (≤18 yrs) with MF registered in a referral photobiology unit for cutaneous lymphomas between July 1991 and June 2009 were included in this study. Children and adolescents were observed to constitute 16.6% of the total number of patients with MF, with 97% of patients of Arab ethnicity. The age-adjusted incidence rate of MF in children and adolescents among the total population was 0.29/100,000 persons/year. Among 36 Arab children and adolescents, boys outnumbered girls by 1.25:1. Mean and median age at onset of disease was 9 years, and age at diagnosis was 13 years. Patch stage disease was the most common clinical variant (75%) with 56% with pure hypopigmented MF-variant. The majority of patients (75%) had stage IB (TNM and B staging) disease. The study highlights a high prevalence and incidence of juvenile MF in Kuwait with a predominantly hypopigmented presentation.

Individuals with inherited skin diseases often pose one of the most difficult diagnostic challenges in dermatology. The hunt for the underlying molecular pathology may involve candidate gene screening or linkage analysis, which is usually determined by the initial history, the physical findings and laboratory tests. Recent technical advances in DNA sequencing, however, are shifting the diagnostic paradigm. Notably, next-generation sequencing allows a more comprehensive approach to diagnosing inherited diseases, with potential savings of both time and money. In the setting of a paediatric dermatology genetics clinic in Kuwait, we therefore performed whole-exome sequencing on seven individuals without a priori detailed knowledge of the patients' disorders: from these sequencing data, we diagnosed X-linked hypohidrotic ectodermal dysplasia (two cases), acrodermatitis enteropathica, recessive erythropoietic protoporphyria (two siblings) and localized recessive dystrophic epidermolysis bullosa (two siblings). All these groups of disorders are clinically and genetically heterogeneous, but the sequencing data proved inherently useful in improving patient care and avoiding unnecessary investigations. Our observations highlight the value of whole-exome sequencing, in combination with robust bioinformatics analysis, in determining the precise molecular pathology and clinical diagnosis in patients with genetic skin disorders, notably at an early stage in the clinical evaluation of these often complex disorders and thereby support a new paradigm for future diagnostics.

Grainyhead-like 2, encoded by GRHL2, is a member of a highly conserved family of transcription factors that play essential roles during epithelial development. Haploinsufficiency for GRHL2 has been implicated in autosomal-dominant deafness, but mutations have not yet been associated with any skin pathology. We investigated two unrelated Kuwaiti families in which a total of six individuals have had lifelong ectodermal defects. The clinical features comprised nail dystrophy or nail loss, marginal palmoplantar keratoderma, hypodontia, enamel hypoplasia, oral hyperpigmentation, and dysphagia. In addition, three individuals had sensorineural deafness, and three had bronchial asthma. Taken together, the features were consistent with an unusual autosomal-recessive ectodermal dysplasia syndrome. Because of consanguinity in both families, we used whole-exome sequencing to search for novel homozygous DNA variants and found GRHL2 mutations common to both families: affected subjects in one family were homozygous for c.1192T>C (p.Tyr398His) in exon 9, and subjects in the other family were homozygous for c.1445T>A (p.Ile482Lys) in exon 11. Immortalized keratinocytes (p.Ile482Lys) showed altered cell morphology, impaired tight junctions, adhesion defects, and cytoplasmic translocation of GRHL2. Whole-skin transcriptomic analysis (p.Ile482Lys) disclosed changes in genes implicated in networks of cell-cell and cell-matrix adhesion. Our clinical findings of an autosomal-recessive ectodermal dysplasia syndrome provide insight into the role of GRHL2 in skin development, homeostasis, and human disease.

Our patients with MF were observed to have a relatively younger age at diagnosis, with a high proportion of patients diagnosed by the age 20 years. Arabs were observed to have a higher annual IR of MF as compared to non-Arab Asians. Hypopigmented MF is prevalent in our population. The study highlights the ethnic and/or regional variations in the clinicoepidemiological characteristics of MF.

The protective role of epidermal melanin pigmentation against chronic exposure to ultraviolet radiation is widely accepted, although its photoprotective effect against acute exposure is less certain. In this study, the action spectra of erythema and melanogenesis in heavily pigmented individuals (skin type V) were determined at 295, 305, 315, and 365 nm, and compared with those of skin types I and II. When the erythema and melanogenesis action spectra for skin type V were normalized to 295 nm, they were identical to the corresponding action spectra for fair-skinned individuals, indicating that the photoprotection of epidermal melanin pigmentation is essentially independent of wavelength. The ratio of values for the minimum erythema dose (MED) between skin type V and skin types I and II was 2.29, which is close to the ratio of pigment in these skin types, as measured by diffuse reflectance spectroscopy in the visible range. The minimum immediate pigment darkening dose (IPD) and the minimum melanogenic dose (MMD) at 365 nm, and the MED and MMD at 315 nm were the same for all skin types, while the variation of MED for every skin type was maximum at 305 and 365 nm. The results provide circumstantial evidence that erythema and melanogenesis have the same mechanism at short-wavelength UVB (295 and 305 nm), and different mechanisms in UVA (365 nm). Furthermore, the 24 h MED at 305 nm appears to be a sensitive indicator of skin type.

Only two homozygous nonsense mutations in the epidermal isoform of the dystonin gene, DST-e, have been reported previously in autosomal recessive epidermolysis bullosa simplex (EBS); the affected pedigrees were Kuwaiti and Iranian. This subtype of EBS is therefore considered to be a rare clinicopathological entity. In this study, we identified four seemingly unrelated Kuwaiti families in which a total of seven individuals had predominantly acral trauma-induced blistering since infancy. All affected individuals were homozygous for the mutation p.Gln1124* in DST-e, the same mutation that was identified in the originally reported family from Kuwait. Haplotype analysis in the five pedigrees (including the previous case) revealed a shared block of ~60 kb of genomic DNA across the site of the mutation, consistent with a founder effect. Most heterozygotes had no clinical abnormalities although one subject had mild transient skin fragility during childhood, an observation noted in the previously reported Iranian pedigree, suggesting that the condition may also be semidominant in some pedigrees rather than purely autosomal recessive. Our study reveals propagation of a mutant ancestral allele in DST-e throughout Kuwait, indicating that this subtype of EBS may be more common in Kuwait, and perhaps other Middle Eastern countries, than is currently appreciated.

Data provided should improve the physicians' awareness of the importance of patients' QOL and enhance psychological evaluation of the psoriatic patient which will promote his/her positive outcome and compliance with treatment.