Palmoplantar keratodermas: clinical and genetic aspects

Abstract

Summary Palmoplantar keratodermas comprise a diverse group of acquired and hereditary disorders marked by excessive thickening of the epidermis of palms and soles. Early onset and positive family history suggest a genetic cause. While hereditary forms of palmoplantar keratoderma (PPK) may represent the sole or dominant clinical feature, they may also be associated with other ectodermal defects or extracutaneous manifestations. In recent years, much progress has been made in deciphering the genetic basis of PPK, which has led to the emergence of new disorders and syndromes. The elucidation of disease mechanisms has opened new avenues for specific therapies, increasingly sparking interest in this field. Given the high heterogeneity with respect to clinical features, genetic defects, and disease mechanisms, the classification of PPK is based on various criteria. These include extent of disease manifestations, morphology of palmoplantar skin involvement, inheritance patterns, and molecular pathogenesis. Though not always feasible, the clinical distinction of various PPK entities is based on fine‐tuned criteria or clues. Remarkably, apparently distinct disorders have been shown to be allelic, as they are caused by mutations in the same gene. By contrast, similar clinical pictures may result from mutations in different genes. Because of this complexity, mutation analysis is required to determine the precise type of PPK. The best‐defined entities are described in this review.

Hereditary palmoplantar keratodermas. Part I. Non‐syndromic palmoplantar keratodermas: classification, clinical and genetic features

“…Acquired PPKs are commonly caused by inflammatory dermatoses, such as psoriasis, eczema and chronic hand dermatitis, but can also be associated with systemic or infectious diseases, induced by chemicals or drugs, or be a sign of internal malignancy . Hereditary PPKs comprise an increasing number of entities with different prognoses, and a multitude of associated cutaneous and extracutaneous features . To date, the diagnosis of the different hereditary PPKs is based mainly on inheritance pattern, age at onset, morphology, distribution and severity of hyperkeratosis, pattern of additional dermatologic and systemic manifestations, and histopathological findings.…”

Autosomal Recessive Keratoderma-Ichthyosis-Deafness (ARKID) Syndrome Is Caused by VPS33B Mutations Affecting Rab Protein Interaction and Collagen Modification

“…The inheritance pattern, phenotype characteristics, and location of the hyperkeratosis as well as the presence of additional extracutaneous features form the basis of classification of different types of PPK (Has and Technau-Hafsi, 2016, Lucker et al., 1994, Schiller et al., 2014). Mutations in more than 20 genes have been associated with both isolated and syndromic forms of hereditary PPK.…”

Hereditary palmoplantar keratodermas. Part II: syndromic palmoplantar keratodermas – Diagnostic algorithm and principles of therapy

“…Systemic retinoids, in particular acitretin, may induce improvement in palmoplantar hyperkeratosis, although they are not recommended in epidermolytic PPK, due to a possible worsening of disease manifestations . Importantly, in women of childbearing age pregnancy must be excluded and contraception initiated before starting retinoid therapy .…”