Boon Kee Goh

Developing core outcome set for vitiligo clinical trials: international e‐Delphi consensus

1 Centre of Evidence Based Dermatology, University of Nottingham, Nottingham,UK 2 Department of Dermatology, Ghent University Hospital, Ghent, Belgium3 Department of Dermatology, Henry Ford Hospital, Detroit, MI, USA4 Department of Dermatology, Yamagata University School of Medicine,Yamagata, Japan 5 Department of Dermatology, Osaka University, Osaka, Japan6 Dermatology Department, Al-Minya University, Al-Minya, Egypt 7 Departmentof Dermatology and Venereology, Ain Shams University, Cairo, Egypt8 Department of Dermatology, Ibn Sina University Hospital, Rabat, Morocco9 Mohammed V Souissi University, Rabat, Morocco 10 Department ofDermatology, University of Bordeaux National Reference Centre for Rare SkinDiseases H^opital St-Andr e, Bordeaux, France 11 Department of Medicine,Division of Dermatology, University of Massachusetts Medical School,Worcester, MA, USA 12 Department of Dermatology, Pontifcia UniversidadeCatœlica do Paranffi, Curitiba, Brazil 13 Department of Dermatology, University ofTexas Southwestern Medical Center, Dallas, TX, USA 14 National Skin Centre,Singapore City, Singapore 15 Department of Dermatology, Kaohsiung MedicalUniversity, Kaohsiung City, Taiwan 16 Department of Dermatology, KinkiUniversity Faculty of Medicine, Osaka-Sayama, Japan 17 Vitiligo Light Clinic,Riyadh, Saudi Arabia 18 Department of Dermatology, Cairo University, Kasr AlAiny Hospital, Cairo, Egypt 19 Departments of Pathology, Microbiology andImmunology/Oncology Institute, Loyola University Chicago, Chicago, IL, USA20 Department of Dermatology, Dongguk University Ilsan Hospital, Gyeonggi-do,Korea 21 Department of Dermatology, PGIMER, Chandigarh, India 22 Departmentof Dermatology, San Gallicano Dermatologic Institute IRCCS, Roma, ItalyCORRESPONDENCE Khaled Ezzedine and Viktoria Eleftheriadou, e-mails: khaled.ezzedine@chu-bordeaux.fr; viktoria.eleftheriadou@nottingham.ac.uk

Characteristics of basal cell carcinoma amongst Asians in Singapore and a comparison between completely and incompletely excised tumors

Background  Most published series of basal cell carcinomas (BCCs) are based on Caucasian populations. Very little is known about the characteristics of incompletely excised BCCs in Asians.

Genome-wide linkage, exome sequencing and functional analyses identify ABCB6 as the pathogenic gene of dyschromatosis universalis hereditaria

Background As a genetic disorder of abnormal pigmentation, the molecular basis of dyschromatosis universalis hereditaria (DUH) had remained unclear until recently when ABCB6 was reported as a causative gene of DUH. Methodology We performed genome-wide linkage scan using Illumina Human 660W-Quad BeadChip and exome sequencing analyses using Agilent SureSelect Human All Exon Kits in a multiplex Chinese DUH family to identify the pathogenic mutations and verified the candidate mutations using Sanger sequencing. Quantitative RT-PCR and Immunohistochemistry was performed to verify the expression of the pathogenic gene, Zebrafish was also used to confirm the functional role of ABCB6 in melanocytes and pigmentation. Results Genome-wide linkage (assuming autosomal dominant inheritance mode) and exome sequencing analyses identified ABCB6 as the disease candidate gene by discovering a coding mutation (c.1358C>T; p.Ala453Val) that co-segregates with the disease phenotype. Further mutation analysis of ABCB6 in four other DUH families and two sporadic cases by Sanger sequencing confirmed the mutation (c.1358C>T; p.Ala453Val) and discovered a second, co-segregating coding mutation (c.964A>C; p.Ser322Lys) in one of the four families. Both mutations were heterozygous in DUH patients and not present in the 1000 Genome Project and dbSNP database as well as 1,516 unrelated Chinese healthy controls. Expression analysis in human skin and mutagenesis interrogation in zebrafish confirmed the functional role of ABCB6 in melanocytes and pigmentation. Given the involvement of ABCB6 mutations in coloboma, we performed ophthalmological examination of the DUH carriers of ABCB6 mutations and found ocular abnormalities in them. Conclusion Our study has advanced our understanding of DUH pathogenesis and revealed the shared pathological mechanism between pigmentary DUH and ocular coloboma.

Periorbital Hyperpigmentation in Asians: An Epidemiologic Study and a Proposed Classification

BACKGROUND Periorbital hyperpigmentation (POH) presents with a dark area surrounding the eyelids. It is an ill‐defined condition, and the pathogenesis can be multifactorial. OBJECTIVE This epidemiologic study was conducted to assess the prevalence of periorbital hyperpigmentation in Singapore in an attempt to propose a classification. MATERIALS AND METHODS One thousand consecutive patients attending the general dermatology clinic at the National Skin Center were enrolled in the study to assess for POH, of whom 200 with POH were examined and investigated to define the cause of POH. The possible causes were determined according to a detailed history, clinical examination, and assessment by three dermatologists. The extent of the POH was measured using a mexameter. RESULTS The commonest form of POH was the vascular type (41.8%), followed by constitutional (38.6%), postinflammatory hyperpigmentation (12%), and shadow effects (11.4%). The vascular type was seen predominantly in Chinese, whereas as the constitutional type was most common in Indians and Malays. CONCLUSION The vascular form of POH was the predominant type. We propose a comprehensive classification for POH that we hope will influence the choice of treatment modalities used in managing POH in the future. Unilever R&D Trumbul, USA provided funding for this study.

A review of non-cultured epidermal cellular grafting in vitiligo

Non-cultured epidermal cellular grafting is an innovative surgical technique that can be used for the treatment of stabilized leucoderma, including vitiligo. Many reports have been published since its introduction in 1992, including several modifications and simplification of the original technique. This systematic review gives an overview of the literature.

Two Singaporean cases of guttate leucoderma in Darier's disease.

1 Laugier P, Hunziker N. Pigmentation melaniques lenticulare, essentielle, de la musqueuse jugale et des levres. Arch Bel 1971; 26: 391–9. 2 Mignogna MD, Muzio LL, Ruoppo E et al. Oral manifestations of idiopathic lenticular mucocutaneous pigmentation (Laugier–Hunziker syndrome): a clinical histopathological and ultrastructural review of 12 cases. Oral Dis 1999; 5: 80–6. 3 Lampe AK, Hampton PJ, Woodford-Richens K et al. Laugier–Hunziker syndrome: an important differential diagnosis for Peutz–Jeghers syndrome. J Med Genet 2003: 40: e77. 4 Velero A, Shert K. Pigmented nails in the Peutz–Jeghers syndrome. Am J Gastroenterol 1961; 42: 56–8. 5 Hanada K, Baba T, Sasaki C et al. Successful treatment of mucosal melanosis of the lip with normal pulsed ruby laser. J Dermatol 1996; 23: 263–6.

Investigating factors associated with depression of vitiligo patients in Singapore

AIMS To explore the depression level of a group of vitiligo patients in Singapore and to identify factors associated with depression. BACKGROUND Unlike most internal illness, skin disease is often immediately visible to others and therefore people suffers from dermatological conditions may suffer psychological consequences. DESIGN A descriptive survey was conducted during the period October 2009-August 2010 in Singapore; 145 vitiligo patients aged 21+  completed a structured questionnaire. METHODS Three main outcome variables were employed in the study: demographic characteristics, clinical and psychosocial outcomes. RESULTS Among the patients, 17·2% (n = 25) had been identified as depressed. Multiple logistic regression analyses were used to identify a model to predict vitiligo patients who will have depression. The results showed that females (p = 0·05), aged below 50 years old (p = 0·016), having 5+ years of illness (p = 0·021) and with low self-esteem (p = 0·002) and poor quality of life scores (p = 0·004) were significant risk factors for depression. CONCLUSION Providing a suitable health care consultation for vitiligo patients may reduces depressive symptoms and maintaining their psychological health may be crucial for preventing suffering from depressive symptoms. Apart from the findings, these conclusions resonate with recent Singapore guidance on managing depression in vitiligo patients. This stresses the importance of prevention, early detection and stepped care with a multifaceted approach to management. RELEVANCE TO CLINICAL PRACTICE It is important to regularly screen for depressive symptoms among vitiligo patients. Focusing on vitiligo patients with enhancing self-esteem and improving quality of life should help in both the prevention and recognition of onset of depression among vitiligo patients.

Prurigo pigmentosa: a report of two cases that responded to minocycline

Prurigo pigmentosa (PP) is an unusual pruriginous dermatosis of unknown aetiology and is often misdiagnosed. We report two people (a 16‐year‐old Chinese boy and a 21‐year‐old Chinese woman), who presented with clinicopathological features consistent with PP. Both patients were successfully treated with minocycline. Better knowledge of this disease will lead to early recognition and appropriate treatment.

Darier's disease in Singapore

Background  Dariers disease is a rare, dominantly inherited genodermatosis. Although it has been well studied in caucasians, very little is known about the clinical spectrum of this disorder among Asians.

Doxycycline in the treatment of acne agminata

Clinically, a pedunculated appearance is extremely rare in metastatic malignant melanoma. In addition, the histopathological finding of melanoma cell epidermotropism is also rare in metastatic malignant melanoma. Here, we describe a case of epidermotropic metastatic malignant melanoma (EMMM) that showed a pedunculated appearance. A 71-year-old man presented with a 3-month history of an asymptomatic flesh-coloured tumour within his oral cavity. Physical examination revealed a dome shaped brown–red tumour in his oral cavity (Fig. 1a). Histopathological examination of this tumour revealed the growth of atypical melanocytes throughout the mucous epithelium and into the dermis to a depth of 3.4 mm, which led us to diagnose this tumour as a malignant melanoma (Fig. 1b). He also had a 2-month history of asymptomatic skin coloured tumours on his right shoulder and back. On his right shoulder, there was a pedunculated flesh-coloured scaly ovoid tumour 10 mm in diameter (Fig. 2a). Histological studies of this tumour showed various sized and shaped nests of melanoma cells that pushed aside collagen fibres and spread from the epidermis into the dermis (Fig. 2b-1). Within the epidermis, tumour nests were located mainly within the basal layer. Marked epidermotropism of the melanoma cells in the upper epidermis, demonstrating a Pagetoid cell appearance, could also be seen (Fig. 2b-2). On his back, there was an 8–9-mm sized,