Letters to Editor OOsler-Weber-Rendusler-Weber-Rendu syndromesyndrome aassociatedssociated withwith vitiligovitiligo

Sir, A 60-year-old male patient presented to our outpatient department with a complaint of asymptomatic, depigmented lesions over his hands, feet, and lips of more than 10 years’ duration. The patient was a known diabetic on insulin. He had been evaluated and treated for the past 10 years for recurrent epistaxis. No apparent cause was found for the epistaxis. The patient also had a persistently low Figure 1: Plaque on left pinna with multiple open comedones and hemoglobin level, for which he had been on vitamin and erythematous papules iron supplements. Findings from all relevant investigations, including bone marrow biopsy, were normal. He gave no Face, neck, and chest are the common sites of NC.[4] Usually history of other bleeding tendencies. There was no history the lesions are localized and appear in groups and in linear of hematemesis, hemoptysis, bleeding from the gums, or pattern.[3] Involvement of an entire half of the body has been melena. reported.[4,5] In our patient, the lesions were limited to the pinna and adjacent parts. To the best of our knowledge, On examination he was found to have acral vitiligo. lesions limited to these areas have not been reported before. Interestingly we found multiple telangiectasias over the Usually NC is asymptomatic. Our patient had episodes hands, lips, tongue, and ear lobes [Figures 1-3]. The patient of inflammation of the lesions, which were self-limiting. had noticed these red lesions increasing in number over the Inflammatory episodes which worsen during puberty last few years but had attached no significance to the same. have been reported earlier.[4,5] In both of these patients,[4,5] Apparently all his brothers too had similar lesions over the the lesions were extensive. Occurrence of inflammatory extremities, but none had a history of epistaxis or other episodes in an infant with limited lesions was a peculiarity significant bleeding tendency. A skin biopsy confirmed the observed in our patient. lesions to be telangiectasia. Based on the history and clinical findings, the possibility of Osler-Weber-Rendu syndrome NN.. AAsokan,sokan, PP.. KK.. SSrideviridevi was considered. The patient was extensively investigated Department of Dermatology, Govt. Medical College, including abdominal, chest, and neurological imaging, Thrissur, Kerala, India to rule out other systemic involvement. All findings were within normal limits. AAddressddress fforor ccorrespondence:orrespondence: N. Asokan, Department of Dermatology, Govt. Medical College, Thrissur, Kerala, India. E-mail: [email protected] Osler-Weber-Rendu syndrome, or hereditary hemorrhagic telangiectasia (HHT), is easily recognized in individuals RREFERENCESEFERENCES displaying the classical triad of epistaxis, telangiectasia, and a suitable family history, but the disease is more difficult to 1. Manola I, Ljubojevic S, Lipozencic J, Pustisek N. Nevus diagnose in many patients. In our case, we assume that the comedonicus: Case report and review of therapeutical diagnosis was missed earlier probably because the lesions approach. Acta Dermatovenereol Croat 2003;11:221-4. 2. Kim SC, Kang WH. Nevus comedonicus associated with were few and not very evident initially. Serious consequences epidermal nevus. J Am Acad Dermatol 1989;21:1085. may have to be faced if visceral arteriovenous malformations 3. Patrzi A, Neri I, Fiorentini C, Marzaduri S. Nevus (AVM), particularly in the pulmonary circulation, are comedonicus syndrome: A new pediatric case. Pediatr unrecognized and left untreated.[1] The diagnosis of Osler- Dermatol 1998;15:304-6. Weber-Rendu syndrome is essentially clinical. The 4 criteria 4. Kirtak N, Inaloz HS, Karakok M, Erguven HG, Ozgoztasi O. (epistaxis, telangiectasia, visceral lesions, and an appropriate Extensive inflammatory nevus comedonicus involving half of family history) are carefully delineated. The HHT diagnosis the body. Int J Dermatol 2004;43:434-6. 5. Cestari TF, Rubim M, Valentini BC. Nevus comedonicus: Case is definite if 3 criteria are present (which was so in our report and brief review of the literature. Pediatr Dermatol case). A diagnosis of HHT cannot be established in patients 1991;8:300-5. with only 2 criteria, but should be recorded as ‘possible’ or

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Figure 1: Telangiectasia hands Figure 2: Telangiectasia tongue

recently independent studies have suggested a common chromosomal link (chromosome 7) for both vitiligo and HHT.[6,7] This case also highlights the importance of thinking of, and looking for, the possibility of Osler-Weber-Rendu syndrome in patients presenting with recurrent epistaxis without any other apparent cause.

FFerozeeroze KKaliyadanaliyadan Department of Dermatology, Amrita Institute of Medical Sciences, Kochi, Kerala, India

AAddressddress fforor ccorrespondence:orrespondence: Feroze Kaliyadan, Department of Dermatology, Amrita Institute of Medical Sciences, Kochi - 682 026, Kerala, India. E-mail: [email protected]

RREFERENCESEFERENCES Figure 3: Telangiectasia ears 1. Shovlin CL, Guttmacher AE, Buscarini E, Faughnan ME, ‘suspected’ to maintain a high index of clinical suspicion. If Hyland RH, Westermann CJ, et al. Diagnostic criteria for fewer than 2 criteria are present, HHT is unlikely, although hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber children of affected individuals should be considered at syndrome). Am J Med Genet 2000;91:66-7 risk in view of age-related penetration in this disorder.[1] 2. Bossler AD, Richards J, George C, Godmilow L, Ganguly A. Mutations in 2 genes, endoglin (ENG) and activin receptor– Novel mutations in ENG and ACVRL1 identified in a series like kinase 1 (ACVRL1 or ALK1), have been associated with of 200 individuals undergoing clinical genetic testing for hereditary hemorrhagic telangiectasia (HHT): Correlation of HHT,[2] HHT1 is caused by mutations in endoglin gene genotype with phenotype. Hum Mutat 2006;27:667-75. mapping on chromosome 9q, and HHT2 is caused by 3. Lenato GM, Guanti G. Hereditary Haemorrhagic [3] mutations in ALK1 located on chromosome 12q. In view Telangiectasia (HHT): Genetic and molecular aspects. Curr of the high prevalence of pulmonary and cerebral AVMs, all Pharm Des 2006;12:1173-93. patients with HHT should be screened for their presence, 4. Haitjema T, Westermann CJ, Overtoom TT, Timmer and relatives of patients with HHT should be investigated for R, Disch F, Mauser H, et al. Hereditary hemorrhagic presence of the disease.[4] This case is interesting because of telangiectasia (Osler-Weber-Rendu disease): New insights in pathogenesis, complications, and treatment. Arch Intern the association between Osler-Weber-Rendu syndrome and Med 1996;156:714-9. vitiligo. To the best of our knowledge, there has been only 5. Grapsa A, Farmakis D, Variami E, Polonifi A, Diamanti- [5] one previous report of a similar association. We assume Kandaraki E, Papalambros E. Hereditary haemorrhagic this to be a coincidental association as there seems to be no telangiectasia associated with vitiligo, autoimmune other definite basis to associate HHT with vitiligo, though thyroiditis, iridocyclitis and a myelodysplastic syndrome.

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Clin Exp Dermatol 2005;30:448-50. segmental type than in the segmental type.[3] Though rarely, 6. Fain PR, Gowan K, LaBerge GS, Alkhateeb A, Stetler GL, segmental vitiligo has been reported in association with Talbert JA, et al. Genomewide screen for generalized a few skin disorders like poliosis,[1] halo nevus,[1,3] nevoid vitiligo: Confirmation of AIS1 on chromosome 1p31 and basal cell carcinoma syndrome,[4] Parry-Romberg syndrome[5] evidence for additional susceptibility loci. Am J Hum Genet [6] 2003;72:1560-4. and linear scleroderma. 7. Bayrak-Toydemir P, McDonald J, Akarsu N, Toydemir RM, Calderon F, Tuncali T, et al. A fourth locus for hereditary The association of vitiligo and TND is very rare and has hemorrhagic telangiectasia maps to chromosome 7. Am J been sparsely reported,[7-10] and vitiligo in most of such Med Genet A 2006;140:2155-62. associations was of non-segmental type, like generalized vitiligo,[7] scalp vitiligo (localized),[8] and acrofacial vitiligo. [9] However, association of segmental vitiligo with TND has SSegmentalegmental vitiligovitiligo andand twenty-twenty- been described in 2 patients.[10] nnailail ddystrophy:ystrophy: AAnn uunusualnusual The association of segmental vitiligo with TND in the aassociationssociation present case can be explained by the autoimmune origin of these disorders. Although the etiology of segmental vitiligo is based primarily on the neurogenic theory of Sir, melanocyte destruction, an immune mechanism cannot be Localized depigmented patches in a dermatomal distribution completely ruled out, because autoimmune disorders have that do not cross the midline are called segmental vitiligo. been described in approximately 3.4% to 9.5% of cases of The course of the segmental type tends to be earlier in segmental vitiligo.[1,11] Further, systemic and topical steroids onset and more stable than generalized vitiligo and is not and psoralen with ultraviolet A (PUVA) therapy have shown familial.[1] encouraging responses in early lesions.[11] The strong association of TND with dermatoses which have autoimmune Twenty-nail dystrophy (TND) presents as rough surfaced etiopathogenesis has led some to speculate that the nail nail plates and involving up to 20 nails. Two types of nail changes are primarily due to an autoimmune process.[12,13] changes have been described. In the first type, the entire Thus our case emphasizes a common autoimmune insult to nail appears to have been sandpapered (sandpaper nails) the melanocytes and nail matrix as the logical explanation in a longitudinal direction and shows excessive ridging and for this rare association. roughness. In the second type, the nail plate is shiny (shiny nails).[2] Here we report a case of an unusual association of TT.. SS.. RRajashekar,ajashekar, GGurcharanurcharan SSingh,ingh, VV.. RRajkumarajkumar segmental vitiligo and twenty-nail dystrophy. Department of Dermatology, Sri Devaraj Urs Medical College, Kolar, Karnataka, India

A male patient aged 20 years presented with depigmented AAddressddress fforor ccorrespondence:orrespondence: Rajashekar T. S., Department of skin lesions since 5 years and also with nail changes of 2 Dermatology, R. L. Jalappa Hospital and Research Centre, Tamaka, Kolar - 563 101, Karnataka, India. E-mail: [email protected] years’ duration. RREFERENCESEFERENCES On cutaneous examination, localized, multiple, round-to- oval–shaped, achromic macules were seen in a segmental 1. Hann SK, Lee HJ. Segmental vitiligo: Clinical findings in 208 distribution over the abdomen (corresponding to T9,10 patients. J Am Acad Dermatol 1996;35:671-4. dermatome). Examination of the nails revealed longitudinal 2. Buran R. Twenty nail dystrophy of alopecia areata. Arch ridging and roughness over the nail plates (sandpaper Dermatol 1981;117:1. nails) in all the nails. Histopathology of an achromic macule 3. Koga M, Tango T. Clinical features and course of type A and showed marked absence of melanin granules, and Wood’s type B vitiligo. Br J Dermatol 1988;118:223-8. lamp examination revealed amelanotic macules. Nail biopsy 4. Muramatsu S, Suga Y, Mizuno Y, Haseeqawa T, Komuro S, Kubo Y, et al. A Japanese case of naevoid basal cell carcinoma showed spongiosis in the nail matrix with mononuclear syndrome associated with segmental vitiligo. Br J Dermatol inflammatory infiltrate. 2005;152:812-4. 5. Creus L, Sanchez-Regana M, Salleras M, Chaussade V, Umbert Association of cutaneous and systemic autoimmune P. Parry-Romberg syndrome associated with homolateral diseases with vitiligo occurs more significantly in the non- segmental vitiligo. Ann Dermatol Venereol 1994;121:710-1.

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