Treatment of hereditary palmoplantar keratoderma: a review by analysis of the literature*

Abstract

Summary Background No specific or curative therapy exists for hereditary palmoplantar keratoderma (hPPK), which can profoundly alter patient quality of life, leading sometimes to severe functional impairment and pain. The rarity and the aetiological diversity of this group of disorders can explain the difficulty in comparing the efficacy of available treatments. Objectives To review the different treatments tried in patients with hPPK since 2008, their efficacy and safety, with an evaluation of the various therapeutic modalities that can be used to treat hPPK. Methods We undertook a comprehensive review of the literature data published since 2008. Results Only a few case series and individual case reports were identified. Topical (emollients, keratolytics, retinoids, steroids) and systemic treatments (mostly different retinoids), often combined, are used to relieve symptoms. Oral retinoids appear to be the most efficient treatment, but not in all PPK forms, and with variable tolerance. New targeted treatments, according to the specific mechanisms of hPPK, appear promising for the future. Conclusions More studies using robust methodology and involving larger cohorts of well‐characterized patients (phenotype–genotype) are necessary and should be prioritized by structured networks, such as the European Network for Rare Skin Diseases (ERN‐Skin), with the aim of better management of patients with rare skin diseases.

The Proteolytic Network in Palmoplantar Keratoderma: SERPINA12 Joins the Family

“…The natural suppression of premature terminations (readthrough) could be augmented using readthroughenhancing drugs such as gentamicin, which could increase the expression of SERPINA12. In a recent study of NPPK, topical gentamicin improved hyperkeratosis; however, there was no improvement in erythema (Bodemer et al, 2020).…”

“…Continued improvements in the understanding of hPPKs at a molecular level offer the promise of more targeted treatments (Figure 1). This is particularly important as the treatment of keratodermas is challenging and often unsatisfactory (Bodemer et al, 2020).…”

“…Treatments may be targeted at specific disease features. For example, hPPKs caused or exacerbated by water exposure may benefit from iontophoresis and botulinum toxin injections (Bodemer et al, 2020). In PPKs with inflammation and hyperkeratosis, such as SERPINA12 deficiency, topical rapamycin or JAK inhibitors may also be considered.…”

“…The molecular understanding of hPPKs has advanced significantly in recent years, with mutations in 45 genes now implicated in their etiologies (Bodemer et al, 2020). These include abnormalities in keratins, intercellular adhesion structures, and a variety of regulatory proteins, including proteases.…”

iRHOM2: A Regulator of Palmoplantar Biology, Inflammation, and Viral Susceptibility

“…PPKs can have a profound effect on an individual’s quality of life, with complications including: severe pain, blistering, difficulty in walking and infection. There is currently no effective therapy for PPK and existing treatments are largely palliative ( Bodemer et al, 2020 , Thomas and O’Toole, 2020 ).

Figure 1 Differential expression of Keratin 16 in palm epidermis.

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