investigating the effect of ustekinumab in the treatment ofPPP and PPPP are required.

Trine Bertelsen, MD

KnudKragballe , MD

Claus Johansen, MD

Lars Iversen, MD

Department of DermatologyAarhus University HospitalAarhusDenmarkE-mail: bertelsen.trine@gmail.com

References1 Christophers E, Mrowietz U. psoriasis. In: Burgdorf W,

Plewig G, Wolff HH, Landthaler M, eds. Braun-Falco’sDermatology (chapter 36), 3rd edn. Heidelberg: Springer,2009: 520.

2 Marsland AM, Chalmers RJG, Hollis S, et al.Interventions for chronic palmoplantar pustulosis.Cochrane Database Syst Rev 2006; 25: 1–51. CD001433.

3 Morales-M�unera C, Vilarrasa E, Puig L. Efficacy ofustekinumab in refractory palmoplantar pustularpsoriasis. Br J Dermatol 2013; 168: 820–824.

4 Gerdes S, Franke J, Domm S, et al. Ustekinumab in thetreatment of palmoplantar pustulosis. Br J Dermatol

2010; 163: 1116–1118.5 Mrowietz U, Van de Kerkhof PCM. Management of

palmoplantar pustulosis: do we need to change? Br J

Dermatol 2011; 164: 942–946.6 Di Cesare A, Di Meglio P, Nestle FO. The IL-23/Th17

axis in the immunopathogenesis of psoriasis. J InvestDermatol 2009; 129: 1339–1350.

7 Martin D, Towne J, Kricorian G, et al. The emerging roleof IL-17 in the pathogenesis of psoriasis: preclinical andclinical findings. J Invest Dermatol 2013; 133: 17–26.

8 Safa G, Martin A, Darrieux L. Exacerbation ofinfliximab-induced palmoplantar psoriasis underustekinumab therapy in a patient with ankylosingspondylitis. J Clin Rheumatol 2011; 17: 385–386.

9 Bulai Livideanu C, Lahfa M, Mazereeuw-Hautier J, et al.Efficacy of ustekinumab in palmoplantar psoriasis.Dermatology 2010; 221: 321–323.

10 Au S-C, Goldminz AM, Kim N, et al.Investigator-initiated, open-label trial of ustekinumab forthe treatment of moderate-to-severe palmoplantarpsoriasis. J Dermatolog Treat 2012; 24: 179–187.

Novel Ala94Thr mutation of keratin 14 in epidermolysis

bullosa simplex

Epidermolysis bullosa (EB) is a group of hereditarychronic dermatological conditions in which the proteinsnecessary for the cohesion of the skin are missing. Theprincipal clinical feature of EB is extremely fragile skinthat blisters very easily. Basal epidermolysis bullosa sim-plex (EBS) is generally considered to be the mildest formof EB, with an approximate prevalence of 6 to 30 per 1million live births.1 Blistering can either be localized tothe hands and feet or found in areas of friction. EBS ischaracterized by cleavage through basal keratinocytesupon minor trauma leading to skin blistering in a rangeof severity. Except for several rare EBS forms caused bymutations in the gene encoding plectin,2 75% of patientswith EBS are inherited in a dominant manner and resultfrom missense mutations in keratin 5 (K5) and keratin 14(K14).3–5 However, rare recessive keratin 14 mutationshave been reported, too.6 So far, more than 214 K5mutations and 223 K14 mutations have been reported inthe literature (http://www.interfil.org). K5 and K14 arenatural partners and form parallel coiled-coil heterodi-mers by means of their a-helical rod domains and furtherassemble into a dynamic tonofilament cytoskeleton toprovide strength and flexibility to basal keratinocytes. Ithas been noted previously that there is a close correlationbetween the position and nature of the mutation and the

severity of the disease,7 i.e., mutations at the highly con-served ends of the a-helical rod domain (helix initiationand termination peptides, HIP and HTP), which havebeen found to be crucial for keratin filament assembly,cause the most severe generalized EBS Dowling–Meara.Thus, based on the site of a mutation and the type ofamino acid substitution in K5 and K14, it is largely possi-ble to predict the resulting phenotype, which is useful inthe diagnosis of infants with EBS in whom the clinicaldifference between the subtypes is less obvious.8 Thepathogenic mutations of EBS are clustered in specificregions or hotspots in the protein molecule. Phenotype–genotype correlations for EBS-localized and EBS-general-ized are less specific, and the rate of novel mutationsdetected in patients is still high.Herein, we reported a Chinese girl who presents exten-

sive epidermal exfoliation at birth and developed blistersof various sizes over the body surface after scratching,trauma, or physical pressures. All fingernails or toenailswere thickening, cloudy or dark brown, and dystrophic.Multiple, 1–3 cm2 erosions were observed over the body,particularly obvious on hands, feet, back, and face (Fig. 1).No family history of this disease was observed. Histologi-cal examination revealed epidermal hyperkeratinization,subepidermal blister, and inflammatory cells. Clinical andhistological findings support a diagnosis of the Koebnerform of epidermolysis bullosa simplex (EBS-K). Mutation

International Journal of Dermatology 2014, 53, e461–e479 ª 2014 The International Society of Dermatology

Correspondencee466

screening for keratin 5 and keratin 14 was completed forcoding sequence and exon–intron boundary frames.Sequence analysis identified a missense mutation, desig-nated as c.280G>A, in exon 1 of K14 gene, leading tochange of the 94th amino acid from alanine to threonine inthe head domain of keratin 14 protein (Fig. 2a). The same

substitution mutation was not found in her parents and100 unrelated healthy controls (Fig. 2b). Up to the presenttime, four frameshift mutations were reported in the headdomain of keratin 14, respectively described as c.92delTfor reccesive epidermolysis bullosa simplex, c.129dupC forEBS-K,c.242_243insG for EBS Dowling–Meara, and

(a) (b)

(d)

(e)

(c)Figure 1 Clinical features of a 5-year-old female patient. Vesicles anderosions on the face (a), toenaildystrophy (b), bulla and erosions onthe legs (b) and back (d), Fingernaildystrophy and erosions on hands (c),Hematoxylin and eosin staining(9200) demonstrated epidermalhyperkeratinization, subepidermalblister, and inflammatory cells (e)

(a)

(b)

Figure 2 Direct sequencing. Aftersequence analysis for polymerasechain reaction products of eight exonsand exon–intron boundary of KRT14gene, a nucleotide acid substitution inexon 1 of K14 gene, designated asc.280G>A, was identified in thispatient (a), but not in 100 healthycontrols (b)

ª 2014 The International Society of Dermatology International Journal of Dermatology 2014, 53, e461–e479

Correspondence e467

c.313_314delGC for recessive epidermolysis bullosa sim-plex-K. Together with this present case, mutations in thehead domain seem to cause more severe clinical type ofEBS. More genotype–phenotype data are needed to reach aconclusive observation.Besides the chronic, painful, and visible skin condition,

the impact of EB on health-related quality of life is alsoconsiderable.9,10 This case was very irritable and self-iso-lated, not allowing others to touch her and reject commu-nications during physical examination. Furthermore, herparental relationship was also negatively affectedimpacted.10 Although gene therapy for skin diseases wasbest studied in EB, such as siRNAs and keratinocyte-based assays, spliceosome-mediated RNA trans-splicingtechnology, symptom controlling therapy is still currentlyavailable ways for the disease. A 2-month retrospectivereview demonstrated that the skin conditions were muchimproved by combined use of oral olopatadine with topi-cal vitamin E. However, the patient was dead due to thesudden onset of severe pneumonia. It is unknown if thepneumonia is secondary to the defect skin barrier, and/ora pulmonary manifestation of EB, or an EB-independentsymptom.

Kang Zeng, MD

Yan Duan, MD

Yan-Hua Liang, MD, PhD

Department of DermatologyNanfang HospitalSouthern Medical UniversityGuangzhouGuangdong, China

Yan-Hua Liang, MD, PhD

1838 North Guangzhou AvenueGuangzhou, Guangdong 510515, ChinaE-mail: liangdoctor@163.com

Conflicts of interest: None.

Funding: This work was supported by a grant fromZhujiang Science and Technology Star (2013J2200029)to Y-HL.

References1 Sprecher E. Epidermolysis bullosa simplex. Dermatol

Clin. 2010; 28:23–32.2 Rezniczek GA, Walko G, Wiche G. Plectin gene defects

lead to various forms of epidermolysis bullosa simplex.Dermatol Clin 2010; 28: 33–41.

3 Chan YM, Yu QC, Fine JD, et al. The genetic basis ofWeber-Cockayne epidermolysis bullosa simplex. ProcNatl Acad Sci USA 1993; 90: 7414–7418.

4 Chen MA, Bonifas JM, Matsumura K, et al. A novelthree-nucleotide deletion in the helix 2B region of keratin14 in epidermolysis bullosa simplex: delta E375. Hum

Mol Genet 1993; 2: 1971–1972.5 Bolling MC, Lemmink HH, Jansen GH, et al. Mutations in

KRT5 and KRT14 cause epidermolysis bullosa simplex in75% of the patients. Br J Dermatol 2011; 164: 637–644.

6 Hovnanian A, Pollack E, Hilal L, et al. A missensemutation in the rod domain of keratin 14 associated withrecessive epidermolysis bullosa simplex. Nat Genet 1993;3: 327–332.

7 Jerabkova B, Marek J, Buckova H, et al. Keratinmutations in patients with epidermolysisbullosa simplex: correlations between phenotypeseverity and disturbance of intermediate filamentmolecular structure. Br J Dermatol 2010; 162:1004–1013.

8 Arin MJ, Grimberg G, Schumann H, et al. Identificationof novel and known KRT5 and KRT14 mutations in 53patients with epidermolysis bullosa simplex: correlationbetween genotype and phenotype. Br J Dermatol 2010;162: 1365–1369.

9 Williams EF, Gannon K, Soon K. The experiences ofyoung people with epidermolysis bullosa simplex:a qualitative study. J Health Psychol 2011; 16:701–710.

10 Fine JD, Johnson LB, Weiner M, et al. Impact ofinherited epidermolysis bullosa on parental interpersonalrelationships, marital status and family size. BrJ Dermatol 2005; 152: 1009–1014.

Lichen planopilaris following whole brain irradiation

Editor,Lichen planus (LP) may occur in areas previously

subjected to trauma; this phenomenon has been termedthe Koebner phenomenon or isomorphic response. Agrowing body of literature suggests that radiation maybe an isomorphic trigger for LP. We present a womanwho developed lichen planopilaris (LPP) following brainirradiation.A 26-year-old woman, currently in remission for acute

lymphoblastic leukemia (ALL), was referred with a 3-

month history of hair loss associated with scalp pruritus.Previous treatment for ALL had included chemotherapy(Toronto Protocol C)1 and fractional central nervoussystem prophylaxis with 18 Gy of whole brain irradiationat the age of 15 years. Although the patient reported thathair loss had followed chemotherapy 10 years previously,her hair had regrown uneventfully without interveningalopecia. Examination revealed diffuse hair loss withsome remaining follicles showing perifollicular erythemaand scale (Fig. 1). There was no other body hair involve-ment. Blood work, including a complete blood count,

Correspondencee468

International Journal of Dermatology 2014, 53, e461–e479 ª 2014 The International Society of Dermatology