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Table of Contents
CORRESPONDENCE
Year : 2019  |  Volume : 37  |  Issue : 3  |  Page : 170-171

Exertional plantar blistering as an easily overlooked clue for epidermolysis bullosa simplex


1 Department of Dermatology, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan
2 Department of Dermatology, College of Medicine, National Cheng Kung University Hospital; International Research Center for Wound Repair and Regeneration, National Cheng Kung University, Tainan, Taiwan

Date of Web Publication24-May-2019

Correspondence Address:
Dr. Wei-Ting Tu
Department of Dermatology, National Cheng Kung University Hospital, 138 Sheng-Li Road, Tainan 704
Taiwan
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ds.ds_19_18

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How to cite this article:
Yang HS, Yang CC, Hsu CK, Lee JY, Chao SC, Tu WT. Exertional plantar blistering as an easily overlooked clue for epidermolysis bullosa simplex. Dermatol Sin 2019;37:170-1

How to cite this URL:
Yang HS, Yang CC, Hsu CK, Lee JY, Chao SC, Tu WT. Exertional plantar blistering as an easily overlooked clue for epidermolysis bullosa simplex. Dermatol Sin [serial online] 2019 [cited 2019 Oct 16];37:170-1. Available from: http://www.dermsinica.org/text.asp?2019/37/3/170/259101



Dear Editor,

A 16-year-old man (IV-2) without underlying diseases presented recurrent painful blistering on the soles since childhood, especially after exercise [Figure 1]a[Figure 1]b [Figure 1]c. He was treated as a case of friction blisters, with topical antibiotics and emollients. However, the condition aggravated in the past 2 years with blisters occurring after every sports class at school. Multiple family members, including his mother (III-2), uncle (III-4), and grandmother (II-4), had similar recurrent blistering on the soles. The pedigree indicated an autosomal dominant inheritance [Figure 1]c.
Figure (1): Clinical pictures and genetic study results. (a) Multiple whitish, slightly edematous blisters developed over the bilateral soles, especially the pressure-bearing areas in the patient (IV-2). (b) A skin biopsy was done on a linear blister on the right sole in the patient (IV-2). (c) Multiple affected family members in the pedigree indicates an autosomal dominant inheritance. (d) A heterozygous mutation p.Glu411del (c.1231_1233delGAG) in the keratin 14 gene is identified in the patient (IV-2) and his mother (III-2) by Sanger sequencing

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Physical examination revealed multiple whitish blisters and dried-up scales on erythematous and edematous bases on the soles, especially the pressure-bearing areas [Figure 1]a. No such lesions were noted on his palms or other parts of the body. An incisional biopsy was taken from a bulla on the right sole [Figure 1]b. Histopathology showed cleft formation at the subepidermal level and occasionally at the basal layer of the epidermis [Figure 2]a [Figure 2]b [Figure 2]c. The underlying papillary dermis showed capillary proliferation with sparse lymphocytic infiltrate. Electron microscopy revealed subnuclear cytolysis of basal keratinocytes in the sections taken from the periphery of the blister [Figure 2]d.
Figure 2: (a and b) Histopathology of a blister from the right sole reveals a cleft formation at the level of basal layer and subepidermal level. (H and E, ×4 and ×20). (c) Close-up view showing cell-poor subepidermal cleavage (H and E, ×40). (d) Electron microscopic image showing an area of subnuclear cytoloysis of a basal cell (*), a finding typical of epidermolysis bullosa simplex

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The clinicopathological findings were consistent with epidermolysis bullosa simplex (EBS), localized (EBS-loc). With informed consent, Sanger sequencing was performed using peripheral blood from the patient and his mother, identifying a shared heterozygous mutation (c.1231_1233delGAG, p. Glu411del) in the keratin 14 (KRT14) gene in both the patient and his mother [Figure 1]d.

EBS is an inherited disease that is caused by mutations in the KRT5 and KRT14 genes in most cases.[1],[2]KRT5 and KRT14 are naturally dimerized by coiled-coil interactions, forming extensive intermediate filament network of the basal cell cytoskeleton, and connect to hemidesmosomes.[3] Mutations in either the KRT5 or KRT14 genes lead to functional impairment of intermediate filament and subsequent defect of attachment of basal keratinocytes to the underlying dermis. The same mutation (c.1231_1233delGAG, p. Glu411del in KRT 14) in this case was reported previously in two articles with similar clinical presentation.[2],[4]

The current classification of EB includes two major types and 17 minor subtypes of EBS.[5] The most common forms of EBS are subdivided into four clinical phenotypes: EBS, generalized severe (previously known as Dowling–Meara type); EBS with mottled pigmentation; EBS, generalized intermediate (previously known as Koebner type); EBS-loc (previously known as Weber-Cockayne type). Of all subtypes of EBS, EBS-loc presents localized blistering on the palms and soles and is the mildest in severity. Therefore, it is often overlooked despite it being a common genetic blistering disease with a prevalence of 8 per million live births.[6] Its main differential diagnosis is friction blister since both diseases are characterized by easy blistering on the soles after exercise and with hyperhidrosis. Unlike friction blister, which presents intraepidermal necrosis and cleft formation, EBS-loc presents subepidermal blister formation and is inherited in an autosomal dominant pattern.

To avoid misdiagnosis, EBS-loc should be considered for patients with recurrent blistering on soles after exercise. The family history should be traced; a skin biopsy for histopathology and ultrastructural studies is also recommended. To find the pathologic mutation, genetic studies are required. Herein, we report this case to highlight that exertional plantar blistering could be an easily overlooked clue for diagnosing EBS.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understand that his names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Bolling MC, Lemmink HH, Jansen GH, Jonkman MF. Mutations in KRT5 and KRT14 cause epidermolysis bullosa simplex in 75% of the patients. Br J Dermatol 2011;164:637-44.  Back to cited text no. 1
    
2.
Jerábková B, Marek J, Bucková H, Kopecková L, Veselý K, Valícková J, et al. Keratin mutations in patients with epidermolysis bullosa simplex: Correlations between phenotype severity and disturbance of intermediate filament molecular structure. Br J Dermatol 2010;162:1004-13.  Back to cited text no. 2
    
3.
Arin MJ. The molecular basis of human keratin disorders. Hum Genet 2009;125:355-73.  Back to cited text no. 3
    
4.
Müller FB, Küster W, Wodecki K, Almeida H Jr., Bruckner-Tuderman L, Krieg T, et al. Novel and recurrent mutations in keratin KRT5 and KRT14 genes in epidermolysis bullosa simplex: Implications for disease phenotype and keratin filament assembly. Hum Mutat 2006;27:719-20.  Back to cited text no. 4
    
5.
Pfendner GE, Bruckner LA. Epidermolysis bullosa simplex. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE. GeneReviews. Seattle: University of Washington; 2016.  Back to cited text no. 5
    
6.
Kelly-Mancuso G, Kopelan B, Azizkhan RG, Lucky AW. Junctional epidermolysis bullosa incidence and survival: 5-year experience of the Dystrophic Epidermolysis Bullosa Research Association of America (DebRA) nurse educator, 2007 to 2011. Pediatr Dermatol 2014;31:159-62.  Back to cited text no. 6
    


    Figures

  [Figure 1], [Figure 2]



 

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