Mood symptoms, neurodevelopmental traits, and their contributory factors in X-linked ichthyosis, ichthyosis vulgaris and psoriasis.

BACKGROUND: High rates of adverse mood/neurodevelopmental traits are seen in multiple dermatological conditions, and can significantly affect patient quality of life. Understanding the sex-specific nature, magnitude, impact and basis of such traits in lesser-studied conditions like ichthyosis, is important for developing effective interventions. AIM: To quantify and compare relevant psychological traits in men with X-linked ichthyosis (XLI, n = 54) or in XLI carrier women (n = 83) and in patients with ichthyosis vulgaris (IV, men n = 23, women n = 59) or psoriasis (men n = 30, women n = 122), and to identify factors self-reported to contribute most towards depressive, anxious and irritable phenotypes. METHODS: Participants recruited via relevant charities or social media completed an online survey of established questionnaires. Data were analysed by sex and skin condition, and compared with general population data. RESULTS: Compared with the general population, there was a higher rate of lifetime prevalence of mood disorder diagnoses across all groups and of neurodevelopmental disorder diagnoses in the XLI groups. The groups exhibited similarly significant elevations in recent mood symptoms (Cohen d statistic 0.95-1.28, P < 0.001) and neurodevelopmental traits (d = 0.31-0.91, P < 0.05) compared with general population controls, and self-reported moderate effects on quality of life and stigmatization. There were strong positive associations between neurodevelopmental traits and recent mood symptoms (r > 0.47, P < 0.01), and between feelings of stigmatization and quality of life, particularly in men. Numerous factors were identified as contributing significantly to mood symptoms in a condition or sex-specific, or condition or sex-independent, manner. CONCLUSION: We found that individuals with XLI, IV or psoriasis show higher levels of mood disorder diagnoses and symptoms than matched general population controls, and that the prevalence and severity of these is similar across conditions. We also identified a number of factors potentially conferring either general or condition-specific risk of adverse mood symptoms in the three skin conditions, which could be targeted clinically and/or through education programmes. In clinical practice, recognizing mood/neurodevelopmental problems in ichthyosis and psoriasis, and addressing the predisposing factors identified by this study should benefit the mental health of affected individuals.

Filaggrin expression via immunohistochemistry in basal cell carcinoma and squamous cell carcinoma.

BACKGROUND: Filaggrin is a protein integral to the structure and function of the epidermis. Filaggrin (FLG) loss-of-function (LOF) mutations are common and increase the risk of developing atopic dermatitis (AD) and ichthyosis vulgaris (IV). Epidemiologic data suggest a link between skin cancer and AD. We examined if FLG staining pattern can be used to characterize cutaneous squamous cell carcinomas (SCC), basal cell carcinomas (BCC), and reactive squamous epithelium. METHODS: Tissue microarrays (TMAs) were created from 196 cases of formalin-fixed paraffin-embedded (FFPE) SCC and 144 BCC cases. TMAs and sections of reactive squamous epithelium were stained with optimized anti-FLG antibody and evaluated for FLG expression (normal, abnormal, or negative). RESULTS: FLG was absent in poorly differentiated (PD) compared to well-differentiated (WD) SCC (P < .0001) and moderately-differentiated (MD) (P = .0231) SCC, and in MD compared to WD SCC (P = .0099). Abnormal staining was significantly increased in PD compared to WD cases (P = .0039) and in MD compared to WD cases (P = .0006). Most BCC did not exhibit FLG expression (P < .05). Reactive squamous epithelium demonstrated normal, but exaggerated FLG expression. CONCLUSIONS: Our findings demonstrate the differences in FLG expression patterns in types of keratinocyte carcinomas and their mimickers.

Dermatological aspects of the S2k guidelines on Down syndrome in childhood and adolescence.

With an incidence of 1 in 700 births, Down syndrome (DS) is not an uncommon condition. It is associated with various disorders of different organ systems. Serious disorders include cardiac defects and leukemia. With an onset during the newborn period, the latter does not always progress to classic myeloid leukemia (transient myeloproliferative disorder). Skin manifestations in newborns include pustules/vesiculopustules. In individuals with DS, such lesions should not only prompt suspicion for typical neonatal rashes and infections but also for transient myeloproliferative disorder. However, most dermatoses are benign. They essentially comprise disorders of keratinization that present as xerosis, keratosis pilaris, lichenification, and ichthyosis vulgaris. Also typical but not specific is the four-finger palmar crease (simian crease). Patients frequently develop folliculitides, which - due to elastolysis - subsequently progress to anetoderma. The known immune disturbance in DS patients explains the occurrence of autoimmune diseases such as alopecia areata and vitiligo. Typical skin conditions associated with DS include elastosis perforans serpiginosa, syringomas, milia-like calcinosis cutis, and multiple eruptive dermatofibromas.

Skin diseases associated with atopic dermatitis.

Atopic dermatitis is a common chronic pruritic inflammatory skin disorder, characterized by an abnormal skin barrier, immune dysfunction, and an altered skin microbiome. Atopic dermatitis may be seen in conjunction with a variety of other skin disorders due to the complex pathogenesis of atopic dermatitis, involving genetic and environmental factors that are associated with immune dysfunction, barrier defects, and altered skin microbiomes. Skin disorders associated with atopic dermatitis include diseases sharing similar genetic origins like ichthyosis vulgaris, infectious diseases such as impetigo, and eczema herpeticum, in addition to the cutaneous autoimmune diseases, alopecia areata, and vitiligo. Atopic dermatitis is also often linked to such benign conditions as pityriasis alba and keratosis pilaris. This review discusses the cutaneous comorbidities of atopic dermatitis and their relationship via their occurrence in conjunction with atopic dermatitis.

[ANALYSIS OF ONE-CARBON METABOLISM GENES AND EPIDERMAL DIFFERENTIATION COMPLEX IN PATIENTS WITH ICHTHYOSIS VULGARIS].

The aim of the study was to evaluate the effects of allelic polymorphism of the FLG and MTHFR genes and their associations in gynecological patients with ichthyosis vulgaris. Gynecological disorders are observed in presence of some forms of ichtyosis. From the prospective of improving nation's healthcare, the greatest attention is drawn to reproductive disorders. Based on this, the research was also tasked with studying of the genetic nature of gynecological diseases, as well as the influence of geographical latitude on the frequencies of mutagenic alleles of the FLG gene and heterogeneous carriers of these mutations. The collection of clinical-gynecological history was carried out by the method of single registration of the proband on the basis of the Regional Clinical Dermatological and Venereological Health Center No. 1 and the Dermatovenerological Health Centers of the Kharkiv Region. The diagnosis and form of dermatosis is established on the basis of the analysis of clinical and gynecological data and the results of laboratory tests in accordance with ICD-10: ichthyosis vulgaris (Q 80.1.0, OMIM 146700). The data on 18 women and 20 men from 3 families, aged 26 to 76 years old, suffering from ichthyosis, were analyzed. As a result of the study, a direct correlation was determined between the latitude and frequencies of mutant alleles of the FLG gene, as well as between the geographical latitude and frequency of heterozygous carriers of these mutations. The frequencies of the T allele and the CT genotype according to polymorphic variant C677T of the MTHFR gene demonstrate feedback with the latitude indicators. The frequency distributions of the 2282del4 allele and the CT genotype, the N/2282del4 and CT genotypes, the 2282del4 and T alleles, the N/2282del4 genotype and the T allele have opposite latitudinal zonation. The established connections made it possible to predict the development of gynecological pathologies in women with ichthyosis vulgaris. The prevalence of endometriosis and endometrial cancer in women with ichthyosis vulgaris in the Kharkiv region was 33.3%, while the average for the female population in the region was 0.29-0.35%. The number of children born to women with ichthyosis vulgaris did not differ from the regional index.

Frequency of ear symptoms and hearing loss in ichthyosis: a pilot survey study.

Ichthyoses comprise a heterogeneous array of skin conditions resulting from impairment of cornification. Although ear structures can be affected, ear-related symptoms have never been investigated in patients with ichthyosis. In this pilot survey study, our aim was to determine the frequency of ear symptoms, hearing loss, and related medical interventions in patients with ichthyosis. Our secondary aim was to compare the frequency of these items according to age group. An online survey using Redcap was developed and posted online on the Foundation for Ichthyosis and Related Skin Types website for 6 months. Patients or parents of patients with ichthyosis were asked to complete the survey. Data analysis excluded patients with keratitis-ichthyosis-deafness syndrome and surveys that had fewer than two completed items. One hundred thirty-five unique surveys were used for data analysis. Of all participants, 80% reported ear pruritus, 66% reported trouble hearing, 29% reported frequent ear pain, 28% had abnormal hearing test results, and 16% had used hearing aids. Of the 88 participants who reported trouble hearing, 24 (27.3%) had never been to a hearing specialist. Significantly more participants older than 18 years of age (74%, 57/77) reported trouble hearing than participants age 18 years and younger (53%, 31/58; p = 0.02). The frequencies of other ear symptoms and hearing loss were not statistically significantly different between the age groups. Ear pruritus, ear pain, and hearing loss are important concerns in patients with all forms of ichthyosis in all age groups. Early diagnosis and intervention may improve the quality of life of patients with ichthyosis.

Symmetrical acrokeratoderma: A peculiar entity in China? Clinicopathologic and immunopathologic study of 34 new cases.

BACKGROUND: Symmetrical acrokeratoderma seems to be a new disorder in China, and 138 cases have been reported in the Chinese literature. OBJECTIVE: We sought to summarize the clinicopathologic features and immunophenotyping of inflammatory cells in 34 new cases. METHODS: Clinical data of 34 patients were prospectively collected over 4 years. Histopathology and immunostaining of infiltrated cells were performed in 27 and 9 patients, respectively. RESULTS: Brown to black hyperkeratotic patches were symmetrically distributed over the acral regions in 33 cases and on the scalp in 1 case, with a whitish change after water contact or sweating. The condition was aggravated in summer and alleviated in winter in 33 patients. History of ichthyosis vulgaris was seen in 23 cases. The typical histopathology included epidermal hyperkeratosis, acanthosis, and papillary dermal perivascular infiltrate of lymphohistiocytes. Number of CD3(+), CD4(+), and CD8(+) cells increased in lesional and perilesional skin compared with normal-appearing skin. The skin lesions developed slowly but were confined to the acral predilection sites after the mean follow-up of 25.4 ± 13.8 months. LIMITATIONS: The follow-up time was short. CONCLUSION: This disorder may represent a peculiar dermatosis that is frequently associated with ichthyosis vulgaris. No specific therapy is available for the disorder.

Ichthyosis vulgaris: the filaggrin mutation disease.

Ichthyosis vulgaris is caused by loss-of-function mutations in the filaggrin gene (FLG) and is characterized clinically by xerosis, scaling, keratosis pilaris, palmar and plantar hyperlinearity, and a strong association with atopic disorders. According to the published studies presented in this review article, FLG mutations are observed in approximately 7·7% of Europeans and 3·0% of Asians, but appear to be infrequent in darker-skinned populations. This clinical review article provides an overview of ichthyosis vulgaris epidemiology, related disorders and pathomechanisms. Not only does ichthyosis vulgaris possess a wide clinical spectrum, recent studies suggest that carriers of FLG mutations may have a generally altered risk of developing common diseases, even beyond atopic disorders. Mechanistic studies have shown increased penetration of allergens and chemicals in filaggrin-deficient skin, and epidemiological studies have found higher levels of hand eczema, irritant contact dermatitis, nickel sensitization and serum vitamin D levels. When relevant, individuals should be informed about an increased risk of developing dermatitis when repeatedly or continuously exposed to nickel or irritants. Moreover, with our current knowledge, individuals with ichthyosis vulgaris should be protected against neonatal exposure to cats to prevent atopic dermatitis and should abstain from smoking to prevent asthma. Finally, they should be advised against excessive exposure to factors that decrease skin barrier functions and increase the risk of atopic dermatitis.

Use of ceramides and related products for childhood-onset eczema.

Atopic eczema or dermatitis (AD) is a chronically relapsing dermatosis associated with pruritus, sleep disturbance and impaired quality of life. AD affects 10 to 20% of school-aged children. The prevalence has increased two to three folds over the past three decades in industrialized countries and there is evidence to suggest that this prevalence is increasing. AD is frustrating to both patients and caregivers and can impose considerable financial impact on the families. The pruritus and sleep disturbance can be intractable and the disease has important physical and psychological implications. Filaggrin (filament-aggregating protein) has an important function in epidermal differentiation and barrier function. Null mutations within the filaggrin gene cause ichthyosis vulgaris and are major risk factors for developing AD. The affected skin of atopic individuals is deficient in natural moisturizing factors (derived from deiminated filaggrin peptides filaggrin) or ceramides (a family of lipid molecules, composed of sphingosine and a fatty acid, found in high concentrations within the cell membrane of cells in the stratum corneum). Avoidance of triggering factors, optimal skin care and topical corticosteroids are the mainstay of therapy for AD. There are two important dermatologic facets to its management, namely, preventive and therapeutic measures. Preventive measures refer to the frequent and proper application of skin moisturizers. When these preventive measures fail to control the disease exacerbation, therapeutic measures such as topical/systemic corticosteroids, antibiotics and immunomodulating agents may be required to control the skin inflammation. Proper moisturizer therapy can reduce the frequency of flares and the demand of topical corticosteroids or topical calcineurin inhibitors. Regular topical application of a moisturizer is the key in the management of patients with AD. Moisturizer therapy of childhood-onset AD is significantly complicated by the diversity of disease manifestations and by a variety of complex immune abnormalities. Recent advances in the understanding of the pathophysiological process of AD leads to the production of new moisturizers and topical skin products targeted to correct reduced amount of ceramides in the skin with ceramide and pseudoceramide products. However, many cosmetic products claimed to have these ingredients have no or limited studies to document their clinical efficacy. Recent studies have shown the therapeutic efficacy of several new compounds. This review provides an update on recent patents that could develop into novel therapeutics available to the clinical armamentarium for the management of the disease.

One remarkable molecule: filaggrin.

The discovery, in 2006, that loss-of-function mutations in the filaggrin (FLG) gene are the cause of ichthyosis vulgaris-the most common disorder of keratinization-and also a strong genetic risk factor for atopic eczema, marked a significant breakthrough in the understanding of eczema pathogenesis. Subsequent investigations of the role of FLG-null mutations have identified a series of significant associations with atopic disease phenotypes, including atopic asthma, allergic rhinitis, and peanut allergy. However, many questions remain to be answered in relation to the precise mechanisms by which deficiency of an intracellular protein expressed primarily in the differentiating epidermis may contribute to the development of cutaneous and systemic pathology. This review aims to highlight the key milestones in filaggrin research over the past 25 years, to discuss the mechanistic, clinical, and therapeutic implications, and to consider possible future directions for ongoing investigation.

Detection of filaggrin gene mutation (2282del4) in Pakistani Ichthyosis vulgaris families.

The aim of this study was to detect an 811 bp filaggrin (FLG) gene fragment known to carry a mutation 2282del4 which causes ichthyosis vulgaris. Seven clinically examined ichthyosis vulgaris families were included in this study. An 811 bp FLG gene fragment was targeted in the genomic DNA of all the members of the seven families by PCR amplification using known primers RPT1P7 and RPT2P1. Successful amplification of an 811 bp FLG gene fragment in all the families suggested the possible role of the 2282del4 mutation in causing ichthyosis vulgaris in Pakistani population.

Clinical detection of ichthyosis vulgaris in an atopic dermatitis clinic: implications for allergic respiratory disease and prognosis.

BACKGROUND: Recent genetic studies have demonstrated that filaggrin mutations, shown to underlie ichthyosis vulgaris (IV), may also predispose patients with atopic dermatitis to allergic respiratory disease. OBJECTIVE: Our objective was to determine whether the clinical presence of IV influences the severity and age at onset of atopic dermatitis or the probability of having allergic respiratory disease. METHODS: We reviewed data collected from the initial visits of 1187 patients with atopic dermatitis. RESULTS: Asthma symptoms were more common in atopic dermatitis patients with IV than in those without (39.9% vs 32.9%, odds ratio [OR] = 1.35, P = .050) and were most associated with severe IV (OR = 2.52, P = .002). This relationship remained after controlling for the baseline severity of atopic dermatitis. Clinical IV was also associated with symptoms of allergic rhinoconjunctivitis, earlier onset of atopic dermatitis, severity of atopic dermatitis, hyperlinear palms, and keratosis pilaris. LIMITATIONS: Our limitations include subjective grading, few data points in some groups, and an inability to demonstrate causality. CONCLUSION: These results suggest that clinical evidence of IV, irrespective of filaggrin genotype, serves as a potential marker for those patients with atopic dermatitis who develop allergic respiratory disease and a more severe skin phenotype.

Prevalent and rare mutations in the gene encoding filaggrin cause ichthyosis vulgaris and predispose individuals to atopic dermatitis.

Mutations in the filament aggregating protein (filaggrin) gene have recently been identified as the cause of the common genetic skin disorder ichthyosis vulgaris (IV), the most prevalent inherited disorder of keratinization. The main characteristics of IV are fine-scale on the arms and legs, palmar hyperlinearity, and keratosis pilaris. Here, we have studied six Irish families with IV for mutations in filaggrin. We have identified a new mutation, 3702delG, in addition to further instances of the reported mutations R501X and 2282del4, which are common in people of European origin. A case of a 2282del4 homozygote was also identified. Mutation 3702delG terminates protein translation in filaggrin repeat domain 3, whereas both recurrent mutations occur in repeat 1. These mutations are semidominant: heterozygotes have an intermediate phenotype most readily identified by palmar hyperlinearity and in some cases fine-scale and/or keratosis pilaris, whereas homozygotes or compound heterozygotes generally have more marked ichthyosis. Interestingly, the phenotypes of individuals homozygous for R501X, 2282del4, or compound heterozygous for R501X and 3702delG, were comparable, suggesting that mutations located centrally in the filaggrin repeats are also pathogenic.

Association of atopic dermatitis with primary hereditary ichthyoses.

OBJECTIVE: The aim of this study is to find out the association of atopic dermatitis and other atopic features with primary hereditary ichthyosis (PHI) among Saudi patients in King Fahd Hospital of the University, Al-Khobar, Kingdom of Saudi Arabia. METHODS: From the out-patient Department of Dermatology logbooks, all Saudi patients with clinically and histopathologically confirmed PHI seen between January 1990 and December 1995 were included in this study. Clinical findings regarding the atopic manifestations of PHI were extracted into data collection forms and computer-analyzed, using Statistical Package for Social Sciences. RESULTS: Over a 6-year study period, 10,455 new patients were seen in our Dermatology Clinics. Of these, 61 had PHI, there were 37 males and 24 females with a ratio of 1.5:1. Atopic dermatitis (AD), diagnosed according to Hanifin and Rajka criteria, was found in 7 (11.5%) patients of PHI; 5 of which were ichthyosis vulgaris and 2 with x-linked recessive ichthyosis. Isolated features of atopy were observed in the form of pruritus 49 (80%), elevated immunoglobulin E 27 (44.3%), dandruff 24 (39%), keratosis pilaris (KP) 15 (25%) and asthma 3 (5%). CONCLUSION: In the present study, there was an 11.5% association between AD and PHI. However, isolated features of atopy were found in PHI in variable proportions ranging from 5-80%.

Scenario of chronic dermatophytosis: an Indian study.

Chronic dermatophytosis was observed in 2276 (10.02%) of 22,692 patients with dermatophytosis during a period of 5.5 years. Males were affected at least 3 times more frequently than females. The age group most commonly affected was between 20 and 40 years of age. Females were affected more between the ages of 30 to 40 years. Tinea cruris and tinea corporis were the most common clinical types and tinea pedis was the least common type observed. The most frequent isolate was Trichophyton rubrum followed by T. mentagrophytes and T. violaceum. Ichthyosis vulgaris was the most common cutaneous association whereas atopy and diabetes mellitus were the most common systemic associations.

Clinico-epidemiological profile of ichthyosis in south Indian patients.

A high frequency rate of hereditary ichthyosis (141.89 per 1000) was detected in a 1029 member South Indian study population selected at random from the skin outpatients of a teaching hospital. An age and sex matched control population screened from the medical and pediatric outpatients of the same institute recorded the incidence of ichthyosis vulgaris as 150 per 1000 population which is even higher.

Atopic dermatitis and ichthyosis vulgaris.

Atopic dermatitis remains a common skin problem in the pediatric age group. General approaches to management focus on reducing inflammation and pruritus as well as preventing xerosis. Ichthyosis vulgaris is the most common form of the ichthyoses and often is associated with atopic dermatitis. Recognition of these conditions is necessary to institute therapy that will alleviate the discomfort experienced by affected individuals.