Punctate palmoplantar keratoderma: Research & Drug Discovery Data

Drug discovery

drugs

With orphan designations

Overview

Punctate palmoplantar keratoderma (PPK) is a rare hereditary disorder characterized by hyperkeratotic papules on palms and soles, typically emerging in adolescence or early adulthood. Autosomal dominant mutations in AAGAB drive keratinocyte hyperproliferation, classified into three subtypes, with type 1 (Buschke-Fischer-Brauer) most common. Clinical features include "raindrop" keratoses, potential malignancy associations, and variable symptomatology. Management focuses on keratolytics (urea, salicylic acid), topical retinoids, and systemic acitretin in refractory cases [1][7][11].

Population

Affects 1.17–3.3 per 100,000 individuals, with onset typically between ages 12–30. Autosomal dominant inheritance with variable expressivity [4][11][14].

Burden

Chronic, uncurable condition causing pain, ambulatory impairment, and fungal infections. Linked to increased malignancy risk (renal, gastrointestinal, cutaneous) [1][7][12]. Quality-of-life impact correlates with lesion severity and mechanical stress [11][13].

Therapies

Topical: Emollients, urea (20–40%), salicylic acid, and corticosteroids [2][10][13].
Systemic: Low-dose oral retinoids (acitretin 10–30 mg/day) for severe cases [3][6][13].
Adjunctive: Mechanical debridement and light therapy (PUVA) [8][10].

Categories: rare genetic diseases, rare skin diseases

Research Papers

29 drug discovery papers about Punctate palmoplantar keratoderma, with 2 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:

categories:

Small molecules

small molecules

2022-02-05 | Resolution of acquired palmoplantar keratoderma and scurvy after treatment of multivitamin deficiencies

Palmoplantar keratodermas (PPK) are a diverse group of dermatologic conditions characterized by the thickening of palms and soles because of excessive keratinization.1 PPKs are classified as either hereditary or acquired depending on their onset. Hereditary PPKs are associated with genetic mutations, whereas acquired PPKs have numerous causes, including malignancy, medications, infection, inflammatory dermatoses, and systemic disease. PPK has also been reported in association with malnutrition2; however, the pathophysiology and prevalence of this etiology remains unclear.

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small molecules

2022-02-05 | Resolution of acquired palmoplantar keratoderma and scurvy after treatment of multivitamin deficiencies

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Drug Discovery Landscape

2 orphan drug designations for Punctate palmoplantar keratoderma.

Drug	Therapy type	Orphan designation	Clinical trial status	Sponsor
(R)-(3-(2'-cyclopropyl-3-(hydroxymethyl)-[1,1'-biphenyl]-4-yl) pyrrolidin-1-yl)(5-fluoropyridin-2-yl)methanone	small molecules	FDA 2025-05-12	Phase I Completed	Orvida Pharma Ltd.
(R)-(3-(2'-cyclopropyl-3-(hydroxymethyl)-[1,1'-biphenyl]-4-yl) pyrrolidin-1-yl)(5-fluoropyridin-2-yl)methanone	small molecules	EMA 2024-08-21	—	Granzer Regulatory Consulting & Services GmbH

Punctate palmoplantar keratoderma

Punctate palmoplantar keratoderma

Punctate palmoplantar keratoderma

Overview

Population

Burden

Therapies

Categories: rare genetic diseases, rare skin diseases

Research Papers

small molecules

2022-02-05 | Resolution of acquired palmoplantar keratoderma and scurvy after treatment of multivitamin deficiencies

small molecules

2022-02-05 | Resolution of acquired palmoplantar keratoderma and scurvy after treatment of multivitamin deficiencies

Drug Discovery Landscape

Updated: Nov 3, 2026