SciELO - Scientific Electronic Library Online

 
vol.28 número4Um Raro Caso de Hepatotoxicidade Induzida pela EmpagliflozinaOsteomielite Enfisematosa índice de autoresíndice de assuntosPesquisa de artigos
Home Pagelista alfabética de periódicos  

Serviços Personalizados

Journal

Artigo

Indicadores

Links relacionados

  • Não possue artigos similaresSimilares em SciELO

Compartilhar


Medicina Interna

versão impressa ISSN 0872-671X

Medicina Interna vol.28 no.4 Lisboa dez. 2021  Epub 01-Dez-2021

https://doi.org/10.24950.rspmi.cc.154.4.2021 

Casos Clínicos

Aquagenic Wrinkling of the Palms and Mutations in the Cystic Fibrosis Gene: A Diagnostic Clue

Acroqueratodermia Aquagénica e Mutações no Gene da Fibrose Quística: Uma Pista Diagnóstica

Marli Ferreira1 
http://orcid.org/0000-0001-8861-6085

Inês Henriques Ferreira1 
http://orcid.org/0000-0003-0202-2580

João Araújo Correia1 
http://orcid.org/0000-0002-6742-3900

1Serviço de Medicina Interna, Hospital de Braga, Braga, Portugal.


Abstract

Described for the first time in 1974, aquagenic wrinkling of the palms (AWP) is an entity characterized by pruritic wrinkling of the palms with associated oedema after brief contact with water. It was first noticed in children diagnosed with cystic fibrosis and in the last years the association between these conditions has been established. We report a case of a 21-year-old Caucasian woman with history of chronic rhinosinusitis and with a clinical diagnosis of AWP. The conducted study revealed a heterozygous mutation for p.Phe508del in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. AWP might represent a feature of CFTR mutation and its identifica-tion should lead to a full genetic test counselling.

Keywords: Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Keratoderma, Palmoplantar; Mutation

Resumo

Descrita pela primeira vez em 1974, a acroqueratodermia aquagénica (AA) é uma entidade caracterizada por um enru-gamento pruriginoso das palmas das mãos com edema associado após breve contacto com a água. Foi inicialmente reportado em crianças com diagnóstico de fibrose quística e, nos últimos anos, uma associação entre estas duas condições tem sido estabelecida. Descreve-se o caso de uma mulher caucasiana de 21 anos com história de rinossinusite crónica e diagnóstico clínico de AA. O estudo realizado revelou uma mutação F508del num dos alelos do gene da fibrose quística (CFTR). A AA pode constituir uma manifestação de mutações ao nível do gene CFTR e a sua identificação deve conduzir a um aconselhamento genético.

Palavras-chave: Queratodermia Palmar e Plantar; Fibrose Quística; Mutação; Regulador de Condutância Transmembrana em Fibrose Quística

Introduction

Aquagenic wrinkling of the palms (AWP) is a dermatolo-gical condition characterized by skin wrinkling of the palms with oedema and confluent whitish papules following brief contact with water.1,2It was first described in 1974 by the paediatrician R. B. Elliot in children with cystic fibrosis (CF), the most frequent severe autosomal inherited abnormality, caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.3 Since then, the association has been confirmed by several smaller studies and case reports and also in individuals where a single mutation of the CFTR gene has been reported, as well as in patients with non-classic CF.

Case Report

A 21-year-old Caucasian woman presented with a 12 months history of pruritic wrinkling of the palmar skin after brief contact with water. Symptoms were temporary and spontaneously regressed within a few minutes (15 minutes) after hands drying. On clinical examination, she developed substantial oedema and a whitish papillomatous appearance of the palms after immersion of the hands in water for about 5 to 7 minutes (Fig. 1). She had no history of hyperhidrosis or other skin condition, as well as no other concomitant diseases, except for chronic rhinosinusitis. She was not on any medication and had no family history of CF or upper airway pathology. A clinical diagnosis of AWP was made and a full medical routine was ordered, namely chest X-ray, chest computed tomography (CT) scan, sinus X-ray, sweat test and spirometry with no abnormality found. A complete CFTR gene sequencing was performed, leading to the identification of a heterozygous mutation for p.Phe508del. No specific treatment was applied; the patient and her family were referred to a genetic counselling consultation where global genetic counselling was made without family testing.

Figure 1: Aspect of the palmar area after exposure to water. 

Discussion

CF is an autosomal recessive disease in the CFTR gene leading to abnormal transport of chloride over epithelial membranes that results in reduced electrolyte reabsorption and raised concentrations of chloride in sweat and organ damage in the respiratory, pancreatic, biliary, reproductive and gastrointestinal systems.2,4 Currently, nearly 2 000 mutations have been identified and in recent years, with help from the field of genetics, the diagnosis of CF has been extended to include milder phenotypes regarded as non-classic CF or CFTR related disorders.2,5Some of these patients have mild or no lung disease with unusual clinical features such as chronic sinusitis or male infertility, and AWP could be another feature that may fall in this category.4

The link between CF and AWP was first established in 1974 but the exact physiological mechanism remains unknown. In the past decades, studies documented a prevalence of AWP between 78% and 84% in patients with CF and of 25% in CF carriers.3,5,6Nonetheless, in recent years, reports of AWP related to a carrier state of CF like the one in this article have exponentially increase.5

In conclusion, AWP is yet an unknown condition with a strong established connection with classic CF, non-classic CF and CF carriers. The identification of this phenomenon with a directed clinical history, physical examination and appropriate complementary study is mandatory and can be of great impact in individuals of childbearing age, knowing that the search for a mutation in the CFTR gene must be extended to the full gene sequencing and not only to the most common mutations associated with this disease.

REFERENCES

1. Grasemann H, Ratjen F, Solomon M. Aquagenic wrinkling of the palms in patient with cystic fibrosis. N Engl J Med. 2013; 369: 2362-3. doi: 10.1056/NEJMc1308349. [ Links ]

2. Cabrol C, Bienvenu T, Ruaud L, Girodon E, Noacco G, Delobeau M, et al. Aquagenic palmoplantar keratoderma as aCFTR-related disorder. Acta Derm Venereol. 2016; 96: 848-9. doi: 10.2340/00015555-2424. [ Links ]

3. Kaiser H, Brustad N, Pressler T, Bygum A. Aquagenic wrinkling of the palms in patients with cystic fibrosis. Br J of Dermatol. 2018; 179: 494-5. doi: 10.1111/bjd.16448. [ Links ]

4. Tchernev G, Semkova K, Cardoso JC, Ananiev J, Wollina U. Aquagenic ke-ratoderma. Two new case reports and a new hypothesis. Indian DermatolOnline J. 2014; 5:30-3. doi: 10.4103/2229-5178.126025. [ Links ]

5. Thomas JM, Durack A, Sterling A, Todd PM, Tomson N. Aquagenic wrinkling of the palms: a diagnostic clue to cystic fibrosis carrier status and non-classic disease. Lancet. 2017; 389:846. doi: 10.1016/S0140-6736(16)31636-1. [ Links ]

6. Gild R, Clay CD, Morey S. Aquagenic wrinkling of the palms in cystic fibro-sis and the cystic fibrosis carrier state: a cases-control study. Br J Derma-tol. 2010; 163: 1082-4. doi: 10.1111/j.1365-2133-2010.09914 [ Links ]

1Responsabilidades Éticas Conflitos de Interesse: Os autores declaram a inexistência de conflitos de interesse na realização do presente trabalho. Fontes de Financiamento: Não existiram fontes externas de financiamento para a realização deste artigo. Confidencialidade dos Dados: Os autores declaram ter seguido os pro-tocolos da sua instituição acerca da publicação dos dados de doentes. Consentimento: Consentimento do doente para publicação obtido. Proveniência e Revisão por Pares: Não comissionado; revisão externa por pares. Ethical Disclosures Conflicts of interest: The authors have no conflicts of interest to declare. Financing Support: This work has not received any contribution, grant or scholarship. Confidentiality of Data: The authors declare that they have followed the protocols of their work center on the publication of data from patients. Patient Consent: Consent for publication was obtained. Provenance and Peer Review: Not commissioned; externally peer re-viewed.

2© Autor (es) (ou seu (s) empregador (es)) e Revista SPMI 2021. Reutilização permitida de acordo com CC BY-NC. Nenhuma reutilização comercial. © Author(s) (or their employer(s)) and SPMI Journal 2021. Re-use permitted under CC BY-NC. No commercial re-use.

Received: May 03, 2021; Accepted: July 30, 2021

Correspondence / Correspondência: Marli Ferreira - marliferreira1992@gmail.com Serviço de Medicina Interna, Centro Hospitalar Universitário do Porto, Porto, Portugal Largo Prof. Abel Salazar, 4099-001 - PORTO

Creative Commons License This is an open-access article distributed under the terms of the Creative Commons Attribution License