Departments of Pathologyb and Infectious Diseasesc

Hopital L’Archet, Nice, France

REFERENCES

1. Khan Durani B, Jappe U. Drug-induced Sweet’s syndrome in

acne caused by different tetracyclines: case report and review

of the litterature. Br J Dermatol 2002;147:558-62.

2. Hetherington S, McGuirk A, Powell G, Cutrell A, Naderer O,

Spreen B, et al. Hypersensitivity reactions during therapy with

the nucleoside reverse transcriptase inhibitor abacavir. Clin

Therapeutics 2001;23:1603-14.

3. Hilliquin P, Marre JP, Cormier C, Renoux M, Menkes CJ, Puissant

A. Sweet’s syndrome and monarthritis in a human immunode-

ficiency virus-positive patient. Arthritis Rheum 1992;35:484-6.

4. Bevilacqua S, Hermans P, Van Laethem Y, Demaubeuge J,

Clumeck N. Sweet’s syndrome in an HIV-infected patient. AIDS

1999;13:728-9.

5. Brady RC, Morris J, Connelly BL, Boiko S. Sweet’s syndrome as

an initial manifestation of pediatric human immunodeficiency

virus infection. Pediatrics 1999;104:1142-4.

doi:10.1016/j.jaad.2003.09.033

J AM ACAD DERMATOL

VOLUME 51, NUMBER 3

Letters 475

Treatment of Hailey-Hailey disease withtopical calcitriol

To the Editor: Calcitriol, 1a25-dihydroxyvitamin D3,can induce differentiation of epidermal keratinocytesinto squamous and denucleated horny cells byregulating inter- and intra-cellular calcium concen-tration.1 Cytoplasmic calcium homeostasis is knownto be impaired in keratinocytes from Hailey-Haileydisease (HHD) and the normal epidermal calciumgradient is attenuated in HHD patients.2 Theseobservations and our previous study on the efficacyof systemic calcitriol in HHD,3 led us to use a topicalformulation of this compound in an HHD patient.

A 25-year-old woman with a 10-year history ofbiopsy-proven HHD, mostly involving the chest, wasreferred to our clinic because of substantial discomfortand ineffective response to several therapies. Herfather was also affected. She complained of a largeerythematous, superficial, crusted erosion on the an-terioraspectof thechest (Fig1).After informedconsenthad been obtained, she initiated twice-daily treatmentwith calcitriol 3 mg ge1 ointment (Silkis ointment,Galderma Laboratories) for one month. Local skinirritation was not reported. The patient experiencedcomplete clearing of the lesion (Fig 2). After 3 monthsof follow-up, the clinical result is still maintained.

Hailey-Hailey disease, or familial benign pemphi-gus, is an inherited suprabasal acantholytic disorderwith significant morbidity, transmitted as an irregularautosomal dominant trait, which affects in-tertriginous skin such as on the genital area, neck,axillae, and popliteal fossae. HHD has a chronic,relapsing-remitting course exacerbated by sweat,moisture, ultraviolet radiation, and friction, or bybacterial, fungal, and parasitic infections, and palli-

ated by several surgical and medical treatments. Ourprevious report3 has already documented the effi-cacy of systemic calcitriol on HHD at the daily dosageof 0.25 mg. More recently, another vitamin D3derivate, tacalcitol, was also topically effective onHHD lesions.4 Recent studies have revealed that theHHD region is localized to 3q21-q24 and that thedisorder is caused by mutations in the ATP2C1 geneencoding a Ca2+ pump.2 Ca2+ pumps are thought toplay important roles in maintaining cytoplasmic Ca2+

homeostasis. Extracellular calcium plays a criticalrole in regulating differentiation and adhesion ofcultured keratinocytes. Low levels of Ca2+ inducekeratinocyte proliferation, while physiological levelsof Ca2+ induce cell-to-cell adhesion and cell differ-entiation.2,5 HHD appears to represent a defect inkeratinocyte adhesion due to dysfunction of desmo-somal proteins.2,4,5 Experimental studies have dem-onstrated that HHD keratinocytes, ATP2C1 mutated,are deficient in intracellular Ca2+ regulation.2,4,5

Furthermore, the inhibitory effect of calcitriol on Tcells and on some inflammatory mediators could alsoparticipate in the healing process. Our experienceand the previous report with tacalcitol seem toindicate that topical vitamin D3 derivatives, mostly

Fig 1. Erosive crusted lesion on the anterior aspect of thechest.

Fig 2. Complete clearing of the lesion after one month ofcalcitriol application.

The skin graft healed well with the exception ofthe right upper corner of the graft site. Despitefourteen months of aggressive local wound care,a shallow erosion and erythematous, velvety tissuepersisted. Computed tomographic scan of uppergastrointestinal tissue confirmed the presence ofa large ventral hernia without evidence of a cutane-ous fistula.

Examination revealed a large, healed ventral

Fig 1. A large abdominal hernia covered with a split-thickness skin graft. On the upper right portion of the graftis a plaque of velvety red tissue.

Fig 2. Curettings of the tissue reveal small bowel mucosawith numerous villi and abundant goblet cells.

J AM ACAD DERMATOL

SEPTEMBER 2004

476 Letters

affecting the calcium gradient in differentiatingkeratinocytes, could regulate and preserve the des-mosome assembly and integrity, genetically alteredin HHD. One month, twice-daily, application clearedthe lesion and the remission has continued at threemonths observation.

In conclusion, we believe that calcitriol could beconsidered a therapeutic option for treating thisinherited disorder and for maintaining, with occa-sional application, a disease-free condition.

Luca Bianchi, MD a

Maria Sole Chimenti, MD b

Alessandro Giunta, MD a

Department of Dermatology, Tor VergataUniversity of Rome, Italya

Department of Reumathology, La SapienzaUniversity of Rome, Italyb

Correspondence to: Luca Bianchi, MD, Departmentof Dermatology, Tor Vergata University of Rome,Italy, Policlinico Tor Vergata, viale Oxford 81,

00133 Rome, ItalyE-mail: luca.bianchi@uniroma2.it

REFERENCES

1. Rizova E, Corroller M. Topical calcitriol studies on local tolerance

and systemic safety. Br J Dermatol 2001;144:3-10.

2. Hu Z, Bonifas JM, Beech J, Bench G, Shigihara T, Ogawa H, et al.

Mutations in ATP2C1, encoding a calcium pump, cause Hailey-

Hailey disease. Nat Genet 2000;24:61-5.

3. Carlesimo OA, Bottoni U, Bianchi L, Innocenzi D, Pala S, Ribuffo

D. Attivita terapeutica del calcitriolo nel morbo di Hailey-Hailey.

Dermatologia Clinica 1985;V:255-63.

4. Aoki T, Hashimoto H, Koseki S, Hozumi Y, Kondo S. 1alpha, 24-

dihydroxyvitamin D3 (tacalcitol) is effective against Hailey-

Hailey disease both in vivo and in vitro. Br J Dermatol 1998;

139:897-901.

5. Kitajima Y. Mechanism of desmosome assembly and disassem-

bly. Clin Exp Dermatol 2002;27:684-90.

doi:10.1016/j.jaad.2003.10.668

Cutaneous presentation of ectopic smallbowel mucosa

To the Editor: A 77-year-old man was referred todermatology with a chronic non-healing abdominalwound. Three years prior to presentation, he un-derwent a total colectomy for colon adenocarci-noma. During the following months, he developedseveral anastomotic leaks requiring an ileostomy anda low anterior resection anastomosis revision. Post-operative course was complicated by a retroperito-neal abscess. Following drainage of the abscess, hedeveloped an ileal fistula, a ‘BUD’ fistula, in the openwound. After two subsequent surgeries, the fistulawas successfully closed, and the resulting skin defectrepaired with a split thickness skin graft.

hernia with bowel visible just beneath the skin graft(Fig 1). On the right upper quadrant of the skin site,there was a 6 3 2.5 cm superficial ulcer with diffusebright red velvety tissue. The tissue was curettedresulting in brisk bleeding.

Histologic examination of the superficialcurettings of the tissue revealed small bowel mucosawith numerous villi and goblet cells (Fig 2).

Treatment initially consisted of gentle curettage ofthe ‘‘velvety’’ tissue with significant reduction of thebowel tissue. Monthly topical application of silvernitrate was added to the curettage for the remainingsmall area of persistent bowel tissue.

Ectopic gastrointestinal tissue in itself is not rare.In Meckel’s diverticulum, 50% of cases containectopic tissue, and 60-85% of those cases contain