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Nagashima-type palmoplantar keratosis
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Nagashima-type palmoplantar keratosis

Contributors: Tyler Werbel MD, Susan Burgin MD
Other Resources UpToDate PubMed


Nagashima palmoplantar keratosis (NPPK) is a rare nonsyndromic genetic dermatosis that was first described in 1977. The disease affects both sexes equally and almost exclusively affects people of Asian ethnicity. There is an estimated prevalence of 1.2:10 000 in Japanese populations and 3.1:10 000 in Chinese populations.

This condition has been linked to loss of function mutations in the serine protease inhibitor (serpin), class B, member 7 (SERPINB7) gene. Most cases demonstrate an autosomal recessive inheritance pattern, but autosomal dominant cases have been reported. The pathophysiological mechanism of this disorder remains poorly understood. However, it is hypothesized that mutation of the SERPINB7 gene leads to serine protease overactivity in the stratum corneum. This results in structural degradation of the epidermis, enabling transepidermal water permeation.

NPPK typically presents within the first year of life with a nonprogressive, erythematous, well-demarcated palmoplantar hyperkeratosis that extends to the dorsal surfaces of the hands and feet and often involves the area of the Achilles tendon. Involvement of the elbows and knees is not uncommon. Affected areas frequently demonstrate hyperhidrosis. On exposure to water, patients may report a whitish, spongy change to the lesions.

NPPK is frequently complicated by malodorous maceration with recurrent tinea infections. However, unlike other palmoplantar keratodermas (PPKs), individuals with NPPK usually only have mild hyperkeratosis. Moreover, they do not develop flexion contractures or constricting bands.


Q82.8 – Other specified congenital malformations of skin

722205008 – Palmoplantar keratoderma Nagashima type

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Differential Diagnosis & Pitfalls

Inherited diffuse PPKs:
  • Mal de Meleda – progressive course, flexion contractures, SLURP1 mutation
  • Gamborg-Nielsen type PPK – hyperkeratosis is thicker, no hyperhidrosis, only localizes to knuckle pads
  • Acral keratoderma – hyperkeratosis is thicker, no hyperhidrosis
  • Vörner type PPK – autosomal dominant inheritance, no hyperhidrosis, epidermolytic hyperkeratosis, KRT1 mutation
  • Unna-Thost type PPK – autosomal dominant inheritance, no hyperhidrosis, KRT1 mutation
  • Greither type PPK – autosomal dominant inheritance, onset at age 8-10, KRT1 mutation
  • Sybert type PPK – autosomal dominant inheritance, hyperkeratosis is thicker, no hyperhidrosis
  • Bothnian type PPK – autosomal dominant inheritance, AQP5 mutation
  • Naxos disease – associated with hair defect and cardiomyopathy
Acquired diffuse PPKs:
  • Keratoderma climactericum – Seen in menopausal women, often associated with obesity or hypertension; pressure points on the soles of the feet are affected first.
  • Malnutrition-associated PPK
  • Paraneoplastic PPK – Acrokeratosis paraneoplastica of Bazex is associated with squamous cell carcinoma of the upper gastrointestinal tract, and "tripe palms" is associated with pulmonary or gastric malignancies. Other malignancies with associated paraneoplastic PPK include breast, bladder, and skin malignancies, myeloma, mycosis fungoides, and Sézary syndrome.

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Last Reviewed:06/11/2018
Last Updated:02/13/2022
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Nagashima-type palmoplantar keratosis
A medical illustration showing key findings of Nagashima-type palmoplantar keratosis : Hyperhidrosis, Knees
Copyright © 2023 VisualDx®. All rights reserved.