J AM ACAD DERMATOL
Letters 679
VOLUME 65, NUMBER 3
Stomatology, Sichuan University,a and the Department of Dermatology, West China Hospital, Sichuan University,b Chengdu, China Funding sources: The National Natural Science Foundation of China (No. 30930100 and 30772424) and the Science Funds for Talented Professionals of Sichuan Province in China (No. 09ZQ026-037). Conflicts of interest: None declared. Correspondence to: Xin Zeng, PhD, DDS, State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, No. 14, Sec 3, Renminnan Road, Chengdu, Sichuan 610041, China
Fig 1. Eighty-year-old monozygotic twins, only one of whom shows extensive squamous dysplasia on the face.
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[email protected] REFERENCES 1. Lewis MAO, Yaqoob NA, Emanuel C, Potts AJC. Successful treatment of oral linear IgA disease using mycophenolate. Oral Surg Oral Med Oral Pathol Oral Radiol Endodontol 2007;103:483-6. 2. Guide SV, Marinkovich MP. Linear IgA bullous dermatosis. Clin Dermatol 2001;19:719-27. 3. Peters MS, Rogers MS. Clinical correlations of linear IgA deposition at the cutaneous basement membrane zone. J Am Acad Dermatol 1989;20:761-70. 4. Cozzani E, Drosera M, Parodi A, Carrozzo M, Gandolfo S, Rebora A. Frequency of IgA antibodies in pemphigus, bullous pemphigoid and mucous membrane pemphigoid. Acta Derm Venereol 2004;84:381-4. doi:10.1016/j.jaad.2010.07.007
Hydroxyurea-associated squamous dysplasia in a monozygotic twin To the Editor: The sudden onset of actinic keratoses (AKs), cutaneous squamous cell carcinomas (SCC), and squamous dysplasia in a photodistribution has been reported in mostly elderly patients taking hydroxyurea for hematologic conditions. Although there have also been case series reported, casecontrol studies are lacking, raising concerns as to the validity of the observed association. An 80-year-old woman presented with a 2-year history of multiple red scaly lesions on the face. On general skin examination her skin was noted to be hyperpigmented in a photodistribution. There were multiple large hyperkeratoses on sun-exposed sitesecheeks, forehead, lower lip, and templeeand on the backs of her hands (Fig 1). She was accompanied by her monozygotic twin who had no hyperkeratotic lesions, was not hyperpigmented, and looked 20 years younger. Both twins had lived in the same region, worked in comparable professions (housekeeper and sales clerk), and shared
daily hikes together. Their sun exposure was similar on history and they had the same skin phototype (Fitzpatrick II). The patient had essential thrombocytosis, treated with hydroxyurea for the previous 13 years (dose 750 mg/d, cumulative dose approximately 3500 g). This was her only medication and her twin sister took no medications. There was no history of skin cancer and neither twin had ever smoked. Excised lesions were reported as Bowenoid AK and Bowen disease. Since the first report in 1992, there have been an increasing number of case reports of SCC and AK developing in association with hydroxyurea use.1 Some of these cases have died from metastatic SCC.1 The majority of patients had Fitzpatrick type I or II skin, had been taking hydroxyurea for many years for myeloproliferative diseases or sickle cell anemia, and had other well-recognized skin side effects of hydroxyurea such as xerosis and hyperpigmentation. The AKs or SCCs were limited to sun-exposed skin, yet there had been no history of treatment required for AK or SCC before hydroxyurea use. The patient presented shares these same features and is therefore consistent with the diagnosis of hydroxyurea-associated squamous dysplasia. Two large case series of patients with hydroxyurea have been reported. A prospective study during a 2-year period observed 26 patients on hydroxyurea for more than 6 months: 8 patients developed AKs and two developed SCC.2 A retrospective study of 158 patients treated with hydroxyurea for chronic myeloid leukemia found 21 patients had severe cutaneous side effects including 5 with cutaneous SCC or keratoacanthomas on sun-exposed skin.3 A large twin study of skin pattern deterioration found the genetic influence on skin pattern decreases with age, from 86% at age 12 years, to 62% in adults
J AM ACAD DERMATOL
680 Letters
SEPTEMBER 2011
(mean age 42 years).4 In our presentation of monozygotic twins, genetic influences were identical and the environmental influences were very similar, except for the intake of hydroxyurea for essential thrombocytosis by the twin with squamous dysplasia. The patient presented is case-controlled by her monozygotic twin, with the one important difference between them being the long-term use of hydroxyurea. This therefore provides further evidence for hydroxyurea causing cutaneous squamous dysplasia. a
Thomas M. Schleußinger, MD, Delwyn Dyall-Smith, FACD,b,c and Lawrence M. Field, MD, FIACSd,e Private practice, Schongau, Germanya; the Department of Dermatology, University of Regensburg, Germanyb; the Department of Dermatology, Allergology, and the Environment, Klinikum Schwabing, K€ olner M€ unchen, Germanyc; the University of California, San Franciscod; and Stanford University School of Medicine, Stanford, Californiae Funding sources: None. Conflicts of interest: None declared. Correspondence to: Thomas M. Schleußinger, MD, Burggenerstrasse 13, 86956 Schongau, Germany REFERENCES 1. Sanchez-Palacios C, Guitart J. Hydroxyurea-associated squamous dysplasia. J Am Acad Dermatol 2004;51:293-300. 2. Salmon-Ehr V, Leborgne G, Vilque JP, Potron G, Bernard P. Secondary cutaneous effects of hydroxyurea: prospective study of 26 patients from a dermatologic consultation [in French]. Rev Med Interne 2000;21:30-4. 3. Vassallo C, Passamonti F, Merante S, Ardig o M, Nolli G, Mangiacavalli S, et al. Muco-cutaneous changes during longterm therapy with hydroxyurea in chronic myeloid leukemia. Clin Exp Dermatol 2001;26:141-8. 4. Shekar SN, Luciano M, Duffy DL, Martin NG. Genetic and environmental influences on skin pattern deterioration. J Invest Dermatol 2005;125:1119-29. doi:10.1016/j.jaad.2010.07.008
Adult-onset cutaneous mastocytosis in monozygotic twins To the Editor: A 36-year-old white man was evaluated for multiple pruritic skin lesions of 15 years duration. He had a history of symptomatic extrasystole during physical or emotional stress, sporadic flushing, anaphylaxis after an insect bite reaction, and endoscopic diagnosis of chronic gastritis with a positive culture for Helicobacter pylori. His monozygotic twin brother, who had suffered from asthma since early childhood, had developed similar cutaneous lesions
Fig 1. Cutaneous mastocytosis on chest: multiple, round, red-brown macules and papules, sharply defined and not confluent, with symmetric distribution.
on his trunk in the past few years. They had no siblings and their parents were unrelated. There was no history of skin or hematologic disease in the parents or other family members. Clinical examination of the patient revealed multiple, red-brown, sharply defined macules and papules in a symmetric distribution over the trunk and limbs; they varied in size up to 0.5 mm (Fig 1). There was no lymphadenopathy or hepatosplenomegaly. His brother had identical cutaneous lesions localized to the trunk. Darier sign was slightly positive in each case. Lesional skin biopsy specimens showed similar histopathological features. There was a diffuse inflammatory infiltrate in the superficial dermis composed of a moderate number of mast cells arranged around dilated vessels and in the interstitial spaces, lymphocytes, rare histiocytes, and sporadic eosinophils; there was mild hyperpigmentation of the basal layer of the epidermis. Mast cells showed the classic metachromatic reaction with a toluidine blue stain. Imaging studies (chest radiograph, bone scan, computed tomography of the abdomen), a bone marrow biopsy specimen, and endoscopy of the esophagus and stomach did not disclose evidence of systemic mastocytosis. Serum tryptase levels were 10 and 8 ng/mL in the two twins, respectively (reference value \20 ng/mL in healthy subjects). A diagnosis of urticaria pigmentosa (UP) was therefore established.1 Polymerase chain reaction (PCR) performed on cutaneous biopsy specimens from both patients using primers designed for exons 9, 11, and 17 of the c-kit proto-oncogene did not reveal any mutation. Urticaria pigmentosa is the most frequent form of cutaneous mastocytosis and typically appears as a sporadic disease in childhood. The occurrence of UP in twins has been rarely described, with a total of 20 cases reported in the literature.2,3 In every case the disease occurred during infancy or before 6 years of age and was characterized by the absence of
