Ichthyoses—A Clinical and Pathological Spectrum from Heterogeneous Cornification Disorders to Inflammation

Ichthyoses are inborn keratinization disorders affecting the skin only (non-syndromic) or are associated with diseases of internal organs (syndromic). In newborns, they can be life-threatening. The identification of the gene defects resulted in reclassification and a better understanding of the pathophysiology. Histopathologic patterns include orthohyperkeratosis with a reduced or well-developed stratum granulosum, hyperkeratosis with ortho- and parakeratosis with preserved or prominent stratum granulosum, and epidermolytic ichthyosis. Another pattern features “perinuclear vacuoles and binucleated keratinocytes”, which is associated with keratin mutations. Some ichthyoses are histologically defined by psoriasis-like features, and distinct subtypes show follicular hyperkeratosis. In addition to histological and immunohistochemical methods, these patterns allow a better histopathologic diagnosis.

CLINICALEVALUATION OF ORAL CAVITYSTATUS IN PATIENTS WITH KERATINIZATION D

Pathological processes associated with disturbed keratinization and risks of cancer tend to become more common and affect younger people. However, the currently available diagnostic methods are not always reliable, which explains the need to further study this. The aim of the study was to improve the efficiency of early diagnosis of keratoses of the oral cavity under autofluorescence spectroscopy incorporated into the proposed screening algorithm. The examination methods involved clinical, luminescent, analytical, statistical evaluation. The study allowed obtaining optical images through autofluorescence stomatoscopy in patients with keratinization disorders, identifying their color range within affected and healthy tissues, as well as confirming their reliability employing the Color Spatioplotter ver 2.46 software. The tested autofluorescent stomatoscopy method featured sufficient sensitivity (98%) against relative specificity (75%), with prediction of a positive outcome (100%).

Experimental Models for the Study of Hereditary Cornification Defects

Ichthyoses comprise a broad spectrum of keratinization disorders due to hereditary defects of cornification. Until now, mutations in more than 50 genes, mostly coding for structural proteins involved in epidermal barrier formation, have been identified as causes for different types of these keratinization disorders. However, due to the high heterogeneity and difficulties in the establishment of valid experimental models, research in this field remains challenging and translation of novel findings to clinical practice is difficult. In this review, we provide an overview of existing models to study hereditary cornification defects with focus on ichthyoses and palmoplantar keratodermas.

First Case of KRT2 Epidermolytic Nevus and Novel Clinical and Genetic Findings in 26 Italian Patients with Keratinopathic Ichthyoses

Keratinopathic ichthyoses (KI) are a clinically heterogeneous group of keratinization disorders due to mutations in KRT1, KTR10, or KRT2 genes encoding keratins of suprabasal epidermis. Characteristic clinical features include superficial blisters and erosions in infancy and progressive development of hyperkeratosis. Histopathology shows epidermolytic hyperkeratosis. We describe the clinical, histopathological, and molecular findings of a series of 26 Italian patients from 19 unrelated families affected with (i) epidermolytic ichthyosis due to KRT1 or KRT10 mutations (7 and 9 cases, respectively); (ii) KTR10-mutated ichthyosis with confetti (2 cases); (iii) KRT2-mutated superficial epidermolytic ichthyosis (5 cases); and (iv) KRT10-mutated epidermolytic nevus (2 cases). Of note, molecular genetic testing in a third case of extensive epidermolytic nevus revealed a somatic missense mutation (p.Asn186Asp) in the KRT2 gene, detected in DNA from lesional skin at an allelic frequency of 25% and, at very low frequency (1.5%), also in blood. Finally, we report three novel dominant mutations, including a frameshift mutation altering the C-terminal V2 domain of keratin 1 in three familiar cases presenting a mild phenotype. Overall, our findings expand the phenotypic and molecular spectrum of KI and show for the first time that epidermolytic nevus can be due to somatic KRT2 mutation.

A clinico-epidemiological study of various keratinization disorders

<p class="abstract"><strong>Background:</strong> There is a vast spectrum of disorders with basic defect in the process of keratinization. There are various associations (genetic, autoimmune and environmental) with different keratinization disorders. The aims and objectives of this study to study the epidemiology, clinical features and associations in various keratinization disorders. </p><p class="abstract"><strong>Methods:</strong> A retrospective observational study of 500 patients was done in a tertiary care center. Detailed history was taken and clinical examination was done. Investigations and skin biopsy were performed when needed.<strong></strong></p><p class="abstract"><strong>Results:</strong> In our study of 500 cases of keratinizing disorders, there were 269 (53.8%) cases of psoriasis, 132 (26.4%) cases of palmoplantar keratoderma, 22 (4%) cases of phrynoderma, 19 (3.8%) cases of ichthyosis, 13 (2.6%) cases of acanthosis nigricans, 11 (2.2%) cases of porokeratosis, 7 (1.4%) cases of Darier’s disease, 3 (0.6%) Cases of pityriasis rubra pilaris, 2 (0.4%) cases each of pachyonychia congenita and erythron keratoderma. The most common age group affected was 51-60 years (19.6%). Males to female ratio was 1.13:1. Chronic plaque psoriasis (43.51%) was the most common variant of psoriasis. Psoriasis vulgaris (75%) was the most common cause of erythroderma. Histopathological findings in all patients whose biopsy was taken was consistent with clinical diagnosis. Non trans gradient (97.75%) was the most common type of palmoplantar keratoderma. Ichthyosis vulgaris (47.38%) was the most common type of ichthyosis.</p><p class="abstract"><strong>Conclusions:</strong> Heredity plays an important role in keratinization disorders. Also, various comorbidities have been associated with different keratinization disorders. Hence, we need to look for these factors while evaluating the patients of keratinization disorders.</p>

Dermatology

This chapter in the Oxford Handbook of General Practice explores dermatology in general practice. It covers skin assessment, treatment of skin conditions, changes in skin colour and eruptions, itching and blistering of the skin, erythema, pigmentation disorder, hair and sweat gland problems, nail changes, and atopic and other eczemas. It discusses ulcers, urticaria, angio-oedema, acne, psoriasis, lichen planus, keratinization disorders, pityriasis, and seborrhoeic warts. It examines sunlight and the skin, benign skin tumours, and skin cancer. It also explores bacterial skin infection, viral skin infection, fungal infection, and infestation.