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D Galimberti,* G Galimberti, A Ponto´n Montan˜o, LR Ja´come, R Galimberti Department of Dermatology and School of Medicine of the Hospital Italiano, Buenos Aires, Argentina *Correspondence: D Galimberti. E-mail:
[email protected]
References 1 Ackerman L. Verrucous carcinoma of the oral cavity. Surgery 1948; 23: 670–678. 2 Rock J, Fisher E. Florid papillomatosis of the oral cavity and larynx. Arch Otolaryngol 1960; 72: 593–598. 3 Koch B, Trask D, Hoffman H et al. National survey of head and neck verrucous carcinoma. Cancer 2001; 92: 110–120. 4 Kang C, Chang J, Chen T et al. Surgical treatment of oral verrucous carcinoma. Chang Gung Med J 2003; 26: 807–812. 5 Ferlito A, Recher G. Ackerman’s tumor (verrucous carcinoma) of the larynx: a clinicopathologic study of 77 cases. Cancer 1980; 46: 1617– 1630. 6 Spiro RH. Verrucous carcinoma, then and now. Am J Surg 1998; 176: 393–397. 7 Azevedo L, Galletta V, de Paula E. Treatment of oral verrucous carcinoma with carbo´n dioxide laser. J Oral Maxillofac Surg 2007; 65: 2361–236. 8 Shimizu A, Tamura O, Ishikawa O. Invasive squamous cel carcinoma arising from verrucous carcinoma. Eur J Dermatol. 2006; 16: 439–442.
Figure 1 Milia cysts, erosions and vesiculobullous lesions on the dorsum of the left hand.
DOI: 10.1111/j.1468-3083.2009.03541.x
Porphyria cutanea tarda induced by olmesartan Editor Porphyrias are a group of metabolic diseases that occur as a result of a deficiency of one enzyme in the haeme biosynthetic pathway. Porphyria cutanea tarda (PCT) is the most common and readily treated of the porphyrias. Most cases are sporadic, and some of them are caused by drugs. To the best of our knowledge, this is the first report of PCT induced by Olmesartan. A 62-year-old man diagnosed of essential hypertension was referred to our department because of a 2-year history of skin fragility on the hands. Lesions began 2 months after starting Olmesartan (20 mg ⁄ day). Clinical examination revealed vesiculobullous lesions and erosions coupled with atrophic scars and milia cysts involving the dorsum of the hands (Fig. 1). Slight hyperpigmentation could be seen in the photoexposed areas. No malar hypertrichosis was observed. There was no history of alcohol consumption. At diagnosis, laboratory findings showed elevated urinary porphyrins (1394 lg ⁄ 24 h; normal value 0–150). The ferritin level was normal, as was the full blood count and biochemistry, including hepatic and renal profile. Genetic study of haemochromatosis gene C282Y revealed a heterozygous mutation. HIV and hepatitis C serology were negative. A skin biopsy of the hand was performed, disclosing a subepidermal bulla with a lym-
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Figure 2 Subepidermal bulla with a lymphocytic perivascular infiltrate.
phocytic perivascular infiltrate (Fig. 2). As drug-induced PCT was suspected, olmesartan was discontinued, which led to a slow but progressive improvement in clinical and laboratory findings. Six months later, the urine porphyrins were found to be close to the normal value (195 lg ⁄ 24 h; normal value 0–150), and the patient was asymptomatic. Porphyria cutanea tarda is a blistering disorder caused by an inherited or acquired deficiency of uroporphyrinogen decarboxylase. Porphyria cutanea tarda is related to many acquired factors1 such as excessive alcohol consumption, exposure to halogenated aromatic chemicals, chronic viral hepatitis C, HIV infection, multiple myeloma, iron overload, dialysis, oestrogens, anticonvulsants, bortezomib2 and tamoxifen.3 Olmesartan is an angiotensin II receptor antagonist that is effective in the treatment of hypertension. Although olmesartan undergoes hepatic and renal metabolization,4 the hepatotoxicity is not related to cytochrome P-450.
ª 2009 The Authors Journal compilation ª 2009 European Academy of Dermatology and Venereology
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The most frequent adverse effects are related to flu-like symptoms, abdominal pain, constipation, hypotension and hyperkalaemia,4,5 but there is no PCT previously reported. The development of PCT while the patient was receiving olmesartan, which resolved when the drug was stopped, strongly suggests that olmesartan is an aetiological factor in the development of acquired deficiency of uroporphyrinogen decarboxylase. In our opinion, olmesartan should be added to the list of drugs that can cause PCT. A Mas-Vidal,†,* P Coto-Segura,† A Garcı´a-Varona,‡ J Santos-Juanes† Departments of †Dermatology and ‡Pathology, ‘Hospital Universitario Central de Asturias’ (HUCA), Oviedo, Spain *Correspondence: A Mas Vidal. E-mail:
[email protected]
References 1 Bulat V, Lugovic´ L, Situm M, Buljan M, Bradic´ L. Porphyria cutanea tarda as the most common porphyria. Acta Dermatovenerol Croat 2007; 15: 254–263. 2 Cabanillas M, Peteiro C, Toribio J. Multiple mieloma associated with porphyria cutanea tarda: a posible role of bortezomib. Dermatology 2006; 213: 246–247. 3 Agarwal R, Peters TJ, Coombes RC, Vigushin DM. Tamoxifen-related porphyria cutanea tarda. Med Oncol 2002; 19: 121–123. 4 Brunner HR. Olmesartan medoximil: current status of its use in monotherapy. Vasc Health Risk Manag 2006; 2: 327–340. 5 Warner GT, Javis B. Olmesartan medoxomil. Drugs 2002; 62: 1345–1353.
DOI: 10.1111/j.1468-3083.2009.03549.x
A novel mutation in the FERMT1 gene in a Spanish family with Kindler’s syndrome Editor Kindler syndrome (KS; OMIM 173650) is a rare autosomal recessive disorder characterized by congenital blistering in acral regions and photosensitivity followed by progressive diffuse poikiloderma and cutaneous atrophy. Other clinical features include hyperkeratosis of the palms and soles, sclerodermiform fingers, nail dystrophy and mucosal involvement with an increased risk of malignancy transformation. In the current report, a novel mutation involving the 11 exon in the FERMT1 gene in the patient affected by KS described by Mallo et al. is identified.1 These authors described a middle-aged man, born to consanguineous parents (Fig. 1), who developed traumainduced blistering during infancy, followed by photosensitivity and progressive skin atrophy with ‘cigarette-paper’-like wrinkling on the dorsa of the hands. Moreover, he developed oesophageal and urethral lesions leading to stenosis, unspecific digestive symp-
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Gen 38069 Kindler
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IV Figure 1 Consanguineous parents. In black, affected of Kindler syndrome.
toms and lost a half of his teeth because of periodontitis. Family history revealed two affected sisters; one of them had died a few months after birth as a consequence of a sepsis that originated in her blistering lesions. Currently, this patient leads an active life without medical treatment. He was referred to our department presenting whitish plaques on oral mucosa coupled with the known KS consisting of face and neck poikiloderma and severe skin atrophy, especially on the hands, webbed fingers, pseudosyndactyly and nail dystrophy (Fig. 2). We performed the genetic study for legal reasons. Blood samples were obtained from the patient following written informed consent. DNA was extracted from peripheral blood lymphocytes, showing a homozygous mutation spanning the last seven nucleotids of 11 exon and three nucleotids in previous intron (c1365_1371 + 3del10) of the FERMT1 gene. The consequence is the introduction of a frameshift mutation which generates a truncated kindlin-1 protein. Recently, Jobard et al.2 described an 834-kb interval localized in chromosome 20p12.3 identifying a new gene in four consanguineous families from North Africa and Senegal. Sieguel et al.3 reported further evidence localizing the gene responsible, KIND1 (now called FERMT1), in a Panamanian cohort, and then confirmed the locus in individuals with KS from diverse geographical backgrounds. The loss-function mutations in FERMT1 gen encodes kindlin-1, a protein, which is implicated in the organization and anchorage of the actin cytoskeleton to integrin-associated platforms and could explain some clinical findings.2,3 To our knowledge, there are 36 described mutations in FERMT1 gene.4 Furthermore, Zhou et al. had identified a new mutation spanning exons 7–9 in the FERMT1 gene in a Chinese family with KS.5 In this study, we identified a novel mutation, c1365_1371 + 3del10, in the 11 exon of FERMT1 gene which expanded the FERMT1 mutation repertoire and it is the first one described affecting the 11 exon. Although we present a novel mutation in KS, the clinical findings do not differ from the other mutations that have been reported previously. This could be interesting in cases were mutations in FERMT1 could not be disclosed with the routine mutation detection strategies used. This novel mutation is interesting because of wider geographical and mutational spectre of kindler syndrome.
ª 2009 The Authors Journal compilation ª 2009 European Academy of Dermatology and Venereology
