LETTER TO THE EDITOR

Successful treatment ofmutilating palmoplantarkeratoderma with acitretincapsule and adapalene gel: acase report with review of theliteratureEditor

A 26-year-old man, who was born of a non-consanguineous

marriage and worked as a mason, was referred to our hospital

with multiple skin lesions on his palms and soles. Hyperkeratosis

had developed on his feet 7 years ago, and a few months later,

he experienced pain owing to verrucous hyperplasia in the kera-

tinized lesions. Gradually, similar lesions were noted on his

hands. During the course of these 7 years, he received several

treatments in other hospitals, such as cryotherapy, laser therapy,

local resection and medication. However, these treatments were

ineffective, as new lesions developed in close proximity to the

previous lesions once the treatments were discontinued. His

parents were healthy, and there was no family history of this

condition.

Physical examination revealed the following features: a

verrucous type of palmar keratoderma extending beyond the

wrists that was more severe on the right hand, and constric-

tion bands on the distal interphalangeal joints of the right

hand (Fig. 1a,b). The lesions varied in size, from 1 cm to

5 cm in diameter of the verrucous plaques, and extensive

superficial pitting was noted (Fig. 1a,b, and 2a,b). Apart from

these features, the nails, teeth and mucous membranes of the

patient appeared normal. The patient complained of pain in

the affected fingers and soles that was caused by compression.

He did not have symptoms of deafness or ichthyotic skin, and

the musculoskeletal features were normal. The tissue sample

taken from the skin lesion on the palm revealed dense hyper-

keratosis, spotty parakeratosis and hypergranulosis (Fig. 1c). A

radiograph of both hands showed no bone abnormality. Audi-

ometry revealed normal. Unfortunately, he and his family

refused to undergo genetic analyses. The skin lesions on our

patient did not improve after a 1-month administration of an

oral acitretin capsule (20 mg daily) and a topical emollient.

(a)

(c) (d)

(b)

Figure 1 Hand lesions (a, b) and outcomeof therapy (d), pathological feature of MPK(c).

© 2014 European Academy of Dermatology and VenereologyJEADV 2014

JEADV

(a)

(c) (d)

(b)

Figure 2 Foot lesions of MPK (a, b) andoutcome of treatment (c, d).

Table 1 Correlation between the genotype and phenotype of mutilating palmoplantar keratoderma (MPK)

Missensemutation

Age(years)

Sex Familyhistory

Clinical characteristics Treatment Reference Country

GJB2 p.D66H – M/F Yes Typical MPK with deafness,epilepsy, vitiligo, etc.

Acitretin 30 mg dailyand Chinese herbaldrugs

MaestriniQiuCastro

USAChinaSpain

GJB2 p.G59S 75 M No Mutilating keratoderma withgeneralized ichthyosis andcongenital deafness, and aproneness to skin cancer

Etretinate/acitretinfor over 20 years

Bondeson Sweden

GJB2 p.G130V – M/F Yes Mild palmoplantar keratodermawith hearing loss, sometimeswithout constrictions of thetoes or fingers.

Not mentioned SnoeckxIossa

EgyptItaly

GJB2 p.T65H 38 M Yes Severe atypical mutilatingkeratoderma

Acitretin 30 mg dailyfor 2 months

De Zwart –Storm UK

LOR 730 insG 2–92 M/F Yes Typical MPK, sometimes witha diffuse generalizedichthyosiform dermatosis

Not mentioned Maestrini USA

LOR 730 insG 2–76 M/F Yes Typical MPK, sometimes withichthyosis or deafness

Not mentioned Korge UK

LOR 730 insG 20 F No Typical MPK with mild ichthyosisand acoustic impairment

Not mentioned Takahashi Japan

LOR 730 insG – M/F Yes Typical MPK with mild ichthyosis;sometimes several skin markingson the knuckles

Not mentioned O’DriscollDrera

USAItaly

LOR 662 insT – M/F Yes Mutilating palmoplantarkeratoderma with ichthyosis

Not mentioned Armstrong UK

Negative forLOR

28 F Yes MPK without ichthyosisand deafness

Keratolytics Ali India

© 2014 European Academy of Dermatology and VenereologyJEADV 2014

2 Letter to the Editor

His symptoms and signs had improved significantly after

3 months of treatment that entailed administering oral acitre-

tin and a topical adapalene instead of the emollient. The

patient was followed up for 12 months with good outcomes

(Fig. 1d and 2c,d).

Mutilating palmoplantar keratoderma (MPK) or Vohwinkel

syndrome (VS) is a rare autosomal dominant palmoplantar ker-

atosis that occurs in infants, but is more evident in adulthood.

However, the etiopathogenesis remains unclear. Recently, Seirafi

et al.1 reported a new variant of VS that was noted in two sib-

lings with congenital hypotrichosis and the mode of inheritance

for the variant was likely autosomal recessive inheritance, which

imply that this variant could be consider as other kind of sub-

group. In our report, the patient presented with a sporadic case

with different clinical characteristics; on the basis of the

literature review, we suppose that our case is likely to be a new

subgroup.

In the cases reported thus far, genetic mutations have been

responsible for the epidermal alterations. One mutation

involves the GJB2 gene2–6 and the other involves the LOR

gene.7,8 Moreover, depending on the location of the gene muta-

tion, different types of mutations could cause various skin

problems9 with variable phenotypes (Table 1). Unfortunately,

our patient refused to undergo genetic analysis. Neither deaf-

ness nor ichthyosis was observed in our patient and no family

history of this condition, therefore, we consider this case to be

a new phenotype.

The treatment of keratoderma typically includes topical kera-

tolytics, topical or systemic retinoids, and sometimes, recon-

structive surgery.10 Fortunately, we successfully treated a patient

with MPK using an oral acitretin capsule and topical 0.1%

adapalene gel, as adapalene and acitretin may be synergistic

effective in the management of epidermal keratinization and dif-

ferentiation. However, the duration of treatment for preventing

keratoderma recurrence and the steps to be taken in the case of a

recurrence remain unclear.

B. Wang,1,2 Z. Zhang,3,* X. Huang,2 X. Lin,2 W. Qu,1

Y. Zhou21Department of Dermatology, 2Division of Regeneration Medicine and

Tissue Engineering, Huaihe Hospital, Henan University, Kaifeng,3Department of Plastic and Reconstructive Surgery, Shanghai First

People’s Hospital, School of Medicine, Shanghai Jiao Tong University,

Shanghai, China

*Correspondence: Z. Zhang. E-mail: zzf555@sina.com

References1 Seirafi H, Khezri S, Morowati S, Kamyabhesari K, Mirzaeipour M, Khezri

F. A new variant of Vohwinkel syndrome: a case report. Dermatol Online

J 2011; 17: 3.

2 Castro PJS, Fernandez CN, Subirana PQ, Ortiz MP. Vohwinkel

Syndrome secondary to missense mutation D66H in GJB2 gene (connex-

in 26) can include epileptic manifestations. Seizure 2010; 19: 129–131.3 Bondeson ML, Nystr€om AM, Gunnarsson U, Vahlquist A. Connexin 26

(GJB2) mutations in two Swedish patients with atypical Vohwinkel

(mutilating keratoderma plus deafness) and KID syndrome both exten-

sively treated with acitretin. Acta Derm Venereol 2006; 86: 503–508.4 Snoeckx RL, Hassan DM, Kamal NM, Van Den Bogaert K, Van Camp G.

Mutation analysis of the GJB2 (connexin 26) gene in Egypt. Hum Mutat

2005; 26: 60–61.5 Iossa S, Chinetti V, Auletta G et al. New evidence for the correlation of

the p. G130V mutation in the GJB2 gene and syndromic hearing loss with

palmoplantar keratoderma. Am J Med Genet A 2009; 149A: 685–688.6 de Zwart-Storm EA, van Geel M, Veysey E et al. A novel missense

mutation in GJB2, p.Tyr65His, causes severe Vohwinkel syndrome.

Br J Dermatol 2011; 164: 197–199.7 Maestrini E, Monaco AP, McGrath JA et al. A molecular defect in

loricrin, the major component of the cornified cell envelope, underlies

Vohwinkel’s syndrome. Nat Genet 1996; 13: 70–77.8 Drera B, Tadini G, Balbo F, Marchese L, barlati S, Colombi M. De novo

occurrence of the 730insG recurrent mutation in an Italian family with

the ichthyotic variant of Vohwinkel syndrome, loricrin keratoderma. Clin

Genet 2008; 73: 85–88.9 Ali MM, Upadya GM. Variant of Vohwinkel’s syndrome. Indian J Derma-

tol Venereol Leprol 2006; 72: 449–451.10 Bassetto F, Tiengo C, Sferrazza R, Belloni-Fortina A, Alaibac M. Vohwinkel

syndrome: treatment of pseudo-ainhum. Int J Dermatol 2010; 49: 79–82.

DOI: 10.1111/jdv.12672

Table 1 (Continued)

Missensemutation

Age(years)

Sex Familyhistory

Clinical characteristics Treatment Reference Country

Negative forGJB2, LOR

34/20 M/F No MPK in two siblings withcongenital hypotrichosis

Topical keratolyticswith emollients

Seirafi Iran

Without geneticanalyses

48 F Notmentioned

MPK with severe constrictingfibrous bands on the fifthdigit of both hands

Reconstructivesurgery

Bassetto Italy

26 M No MPK without ichthyosis,deafness, etc.

Acitretin capsule andadapalene gel 0.1%

Our case China

© 2014 European Academy of Dermatology and VenereologyJEADV 2014

Letter to the editor 3