Fig 1. Loose anagen hair syndrome in a patient withepidermolysis bullosa simplex, Dowling-Meara type: Pa-tient 2 at age 4 years with fine, ‘‘sticky’’ blonde hair thatgrows very slowly.

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SEPTEMBER 2012e120 Letters

Joyeeta Bhattacharyya, MD, PhD,a KeichiroMihara, MD, PhD,a Ken’ichi Morimoto, MD,PhD,c Yoshihiro Takihara, MD, PhD,b andMichihiro Hide, MD, PhDd

Department of Hematology and Oncologya andDepartment of Stem Cell Biology,b Research In-stitute for Radiation Biology and Medicine,Hiroshima University; Department of Dermatol-ogy, Onomichi General Hospital, Onomichic;and Department of Dermatology, GraduateSchool of Biomedical Sciences,d Hiroshima Uni-versity, Hiroshima, Japan

Funding sources: Japanese grant-in-aid.

Conflicts of interest: None declared.

Correspondence to: Keichiro Mihara, MD, PhD, De-partment of Hematology and Oncology, ResearchInstitute for Radiation Biology and Medicine,Hiroshima University, 1-2-3 Kasumi, Minami-ku,Hiroshima, Japan 734-8553

E-mail: kmmihara@hiroshima-u.ac.jp

REFERENCES

1. Yoshimoto T, Mizutani H, Tsutsui H, Noben-Trauth N, Yamanaka

K, Tanaka M, et al. IL-18 induction of IgE: dependence on CD41T cells, IL-4 and STAT6. Nat Immunol 2000;1:132-7.

2. Migliorini P, Del Corso I, Tommasi C, Boraschi D. Free circulating

interleukin-18 is increased in Schnitzler syndrome: a new

autoinflammatory disease? Eur Cytokine Netw 2009;20:108-11.

3. Besada E, Nossent H. Dramatic response to IL1-RA treatment

in longstanding multidrug resistant Schnitzler’s syndrome: a

case report and literature review. Clin Rheumatol

2010;29:567-71.

4. Kluger N, Riviere S, Guillot B, Bessis D. Efficacy of interleukin

1 receptor antagonist (anakinra) on a refractory case of

Schnitzler’s syndrome. Acta Derm Venereol 2008;88:287-8.

5. Ryan JG, de Koning HD, Beck LA, Booty MG, Kastner DL, Simon

A. IL-1 blockade in Schnitzler syndrome: ex vivo findings

correlate with clinical remission. J Allergy Clin Immunol

2008;121:260-2.

http://dx.doi.org/10.1016/j.jaad.2011.10.002

Loose anagen hair syndrome in two patientswith epidermolysis bullosa simplex, Dowling-Meara type

To the Editor: We describe two patients with epider-molysis bullosa simplex, Dowling-Meara type (EBS-DM), who also have loose anagen hair syndrome(LAHS). EBS-DM is a severe form of EBS marked bywidespread herpetiform blistering, worse duringinfancy.1 LAHS is diagnosed by the ability to pain-lessly extract anagen hairs from the scalp that lack anexternal root sheath and demonstrate cuticle rufflingdistal to a misshapen bulb.2 The hair is typically

sparse and seldom requires cutting.2 An associationbetween these entities has not previously beenreported, to our knowledge.

The parents of a 7-year-old Portuguese girl diag-nosed with EBS-DM at birth observed that her hairwas thin and that she infrequently required haircuts.Her mother placed extensions in her hair, but thesefell out with the native hair attached. Examinationrevealed fine, lusterless, short brown hair with noblistering or dermatitis on the scalp. A hair pluckwithforceps of approximately 20 hairs caused no dis-comfort. Microscopic analysis demonstrated multi-ple dystrophic anagen hairs with misshapen hairbulbs, absent outer root sheaths, and ruffled cuticlescharacteristic of LAHS.2

A girl of Polish, Ukrainian, and French Canadiandescent was diagnosed with EBS-DM at birth. Whenshe was 32 months of age, her parents reported thather hair fell out easily and that clumps of hair couldbe pulled painlessly from her scalp by her youngersibling. She had fine, blonde hair that seldomrequired cutting (Fig 1). A hair pluck with forcepsrevealed multiple anagen hairs with ruffled cuticlesjust distal to the bulbs.

These two patients have the same keratin 14mutation, N123S, with an identical base pair muta-tion by genotype analysis. Keratins 5 and 14 arerequired for the formation of coiled heterodimersthat provide structural support to the epidermis, andblisters result when this epidermal attachment islost.1 Keratin 14 is also found in the medulla andouter root sheath of the hair follicle, providingsupport through intermediate filament formationand potentially contributing to the activation ofepithelial and hair-specific keratins.3 Abnormalhair findings have not been described previouslyin patients with EBS-DM and the N123Smutation.1,4,5

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The pathogenesis of LAHS is not fully under-stood but has been associated with structural ab-normalities in the inner root sheath.6 Given apossible role in trichocyte differentiation, it is con-ceivable that mutations in keratin 14 could contrib-ute to hair disorders such as LAHS. Mutations in thegene for keratin 6HF (keratin 75), found in themedulla and companion layer apposing the innerroot sheath, have been identified in some cases ofLAHS.3,7 Hair keratin mutations were not found inother LAHS cases.7 The authors postulated thatanother keratin may play a role. Interestingly,epithelial keratins, such as keratin 14, were notevaluated.7

The presence of EBS-DM and LAHS in twopatients with the same keratin 14 mutation raisesthe possibility that the common defect contributesto the pathogenesis of both disorders. Betterunderstanding of the pathogenesis of LAHS inthe future may help clarify this potentialrelationship.

Jennifer Crombie, BA,a Sheila Greenlaw, MD,b JulieFenner, MD,b Stephen Lyle, MD, PhD,c andKaren Wiss, MDb,d

University of Massachusetts Medical Schoola; Divi-sion of Dermatology, Department of Medicine,University of Massachusetts Medical School,UMass Memorial Healthcare,b Departments ofCancer Biology,c and Pediatrics,d University ofMassachusetts Medical School, Worcester

Funding sources: None.

Conflicts of interest: None declared.

Correspondence to: Karen Wiss, MD, UMass Memo-rial Medical Center e Hahnemann Campus, 281Lincoln St, Worcester, MA 01605

E-mail: karen.wiss@umassmemorial.org

REFERENCES

1. Pfendner EG, Sadowski SG, Uitto J. Epidermolysis bullosa

simplex: recurrent and de novo mutations in the KRT5 and

KRT14 genes, phenotype/genotype correlations, and implica-

tions for genetic counseling and prenatal diagnosis. J Invest

Dermatol 2005;125:239-43.

2. Price VH, Gummer CL. Loose anagen syndrome. J Am Acad

Dermatol 1989;20:249-56.

3. Langbein L, Yoshida H, Praetzel-Wunder S, Parry DA, Schweizer

J. The keratins of the human beard hair medulla: the riddle in

the middle. J Invest Dermatol 2010;130:55-73.

4. Sørensen CB, Ladekjær-Mikkelson A, Andresen BS, Brandrup F,

Veien NK, Buus SK, et al. Identification of novel and known

mutations in the genes for keratin 5 and 14 in Danish

patients with Epidermolysis Bullosa Simplex: correlation be-

tween genotype and phenotype. J Invest Dermatol

1999;112:184-90.

5. Bolling MC, Lemmink HH, Jansen GHL, Jonkman MF. Mutations

in KRT5 and KRT14 cause epidermolysis bullosa simplex in 75%

of the patients. Br J Dermatol 2011;164:637-44.

6. Mirmirani P, Uno H, Price V. Abnormal inner root sheath of the

hair follicle in the loose anagen hair syndrome: An ultrastruc-

tural study. J Am Acad Dermatol 2011;64:129-34.

7. Chapalain V, Winter H, Langbein L, Le Roy JM, Labr�eze C,

Nikolic M, et al. Is the loose anagen hair syndrome a keratin

disorder? A clinical and molecular study. Arch Dermatol

2002;138:501-6.

http://dx.doi.org/10.1016/j.jaad.2011.10.013

Hair regrowth in a male patient with extensiveandrogenetic alopecia on estrogen therapy

To the Editor: Androgenetic alopecia (AGA) is anonscarring pattern hair loss affecting both sexes.There have been no previous reports on very ad-vanced AGA responsive to medical treatment. Here,we present a sex reassignment patient on estrogentherapy who experienced full hair regrowth overcompletely alopecic scalp.

A 38-year-old Caucasian male-to-female transsex-ual candidate presented with AGA on August12, 1988. Physical examination showed alopeciainvolving the vertex, temporal, parietal, and frontalscalp with good occipital hair density (Table I). Perpatient, he developed vellus scalp hair after initiatingethynyl estradiol 0.5 mg daily 17 months ago, sub-sequently switching to estradiol 0.05 mg transdermaltwice weekly 9 months later. Minoxidil 3% solutiondaily was initiated, then changed to minoxidil 2%solution twice daily and estrone 20 mg/60 mL solu-tion every morning after 2 weeks, resulting in fineterminal hairs of the vertex (Table I and Fig 1, A).Estradiol was increased to 0.2 mg transdermalweekly. A hair replacement surgery consult exami-nation on October 5, 1988, showed extensive bald-ing with peripheral ‘‘fringe’’ and few terminal hairson vertex to occiput, Hamilton grade VI to VII,concluding he was a poor candidate because ofextensive baldness.

Aldactone 25 mg twice daily was started May1990, and increased 3 months later to 100 mg daily,while estrone solution was increased to 30 mg/60mL twice daily, with progress in further terminalhair growth (Table I and Fig 1, B). A follow-up visiton November 9, 1990, showed decreased facial andbody hair, with marked increase in permanentscalp hair growth on examination (Table I andFig 1, C ). Tretinoin 0.025% gel 3 times weekly wasinitiated April 1991, with continued excellentscalp hair growth (Table I and Fig 1, D and E ).He underwent sex reassignment surgery inSeptember 1992, and by February 1993, she was