[Show abstract][Hide abstract] ABSTRACT: Eccrine syringofibroadenomatosis (ESFA) is a rare adnexal tumor with acrosyringeal differentiation. Clinically, it can be mistaken for granulomatous infections or malignancies such as squamous cell carcinoma. Despite the rarity of the condition, we recently encountered two cases of the reactive subtype, which occurred in patients with poorly controlled chronic psoriasis. Both patients presented with long-standing, thick verrucous lesions on the lower legs. The diagnosis was made after histological examination and exclusion of infectious and neoplastic disorders. As this is a reactive disorder, management is focused on treating the underlying condition. Unfortunately, psoriasis was difficult to manage in both our patients and they defaulted further treatment. It is important to recognize ESFA as it can be confused with infectious or malignant disorders.
Indian Journal of Dermatology Venereology and Leprology 11/2014; 80(6):534-6. DOI:10.4103/0378-6323.144172 · 1.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background/Objectives
Susceptibility to and clinical presentation of basal cell carcinoma (BCC) differ in Asian and Caucasian populations. This study aims to evaluate the epidemiological and clinicopathological characteristics of BCC in a multiracial Singaporean population, with a secondary comparative analysis between Chinese and Caucasian patients.Methods
We prospectively studied patients with newly diagnosed, histologically confirmed BCC at the National Skin Centre, Singapore from 2004 to 2008.ResultsIn total, 274 BCC from 260 patients were studied, with 19 patients having two or more tumours. Their mean age was 67.5 years and 54% were male. Chinese comprised 80% and Caucasians 14%. The Chinese were 1.8-fold as likely as Caucasians to be older than 60 years, and experienced itch thrice more frequently. Caucasians developed multiple BCC threefold and truncal or upper limb BCC 2.9-fold more frequently than the Chinese. In terms of tumour subtype, morphoeic BCC was 2.7-fold more common in Caucasians. Pigmented BCC occurred 2.7-fold more often in the Chinese, most frequently on the head and neck of elderly Chinese.Conclusions
Compared to the Chinese, BCC occurred more often in younger Caucasians, with a predilection for the trunk and upper limb, suggesting a greater role for recreational sun exposure as a risk factor. Pigmented BCC more commonly occurred on the head and neck of elderly Chinese and may be reflective of cumulative sun exposure as a risk factor. Aggressive morphoeic BCC was more common in Caucasians than in Singaporean Chinese patients.
Australasian Journal of Dermatology 09/2014; DOI:10.1111/ajd.12202 · 0.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Few studies have evaluated Asian children with mycosis fungoides (MF). We report a series of patients from a tertiary dermatologic institution in Singapore. A retrospective review was performed of patients younger than 16 years old diagnosed with MF between 2000 and 2008 at the National Skin Centre, Singapore. Forty-six patients were identified. At initial presentation, a provisional diagnosis of MF was made in 19 patients (41.3%), pityriasis lichenoides chronica (PLC) in 11 (23.9%) and postinflammatory hypopigmentation due to eczema or other causes in 11 (23.9%). After skin biopsy, the hypopigmented variant of MF was diagnosed in 42 patients (91.3%). There was one case each of PLC-like MF, pigmented purpuric dermatosis-like MF, classic MF, and solitary MF. Pityriasis lichenoides coexisted in three cases (6.5%). All except one patient presented with the early patch-plaque stage of disease (stage IA/B). The disease did not progress in any of our patients after a mean follow-up of 71.0 ± 52.5 months. Twenty-seven patients (58.7%) had complete disease clearance after a mean duration of 27.1 ± 28.1 months; 15 (49.7%) of 32 patients who received narrowband ultraviolet B treatment had complete clearance within an average of 8.9 ± 5.3 months, but 7 patients relapsed within 14.9 ± 14.8 months. One patient with solitary MF failed multiple treatment modalities before eventually achieving disease clearance with photodynamic therapy. Hypopigmented MF is the most common MF variant in Asian children. The diagnostic difficulty is in differentiating this from PLC, which may coexist with MF. Long-term prognosis is generally favorable.
[Show abstract][Hide abstract] ABSTRACT: We reviewed the clinical characteristics and therapeutic response in cases of newly diagnosed bullous pemphigoid at the National Skin Centre between June 2009 and December 2010. Most (76%, n = 68/90) achieved clinical remission within 6 months of commencement of therapy. Oral mucosal involvement was identified as a risk factor associated with a prolonged duration of treatment beyond 6 months.
[Show abstract][Hide abstract] ABSTRACT: To identify genetic risk factors underlying non-Hodgkin lymphomas (NHLs) from the B cell lineage, we conducted a genome-wide association study (GWAS) of 253 Chinese individuals with B cell NHL (cases) and 1,438 controls and further validation in 1,175 cases and 5,492 controls. We identified a new susceptibility locus, rs6773854, located between BCL6 (encoding B cell lymphoma protein 6) and LPP (encoding lipoma preferred partner) on oncogene-rich chromosome 3q27 that was significantly associated with increased risk of B cell NHL (meta-analysis P = 3.36 × 10(-13), per-allele odds ratio (OR) = 1.44) and with diffuse large B cell lymphoma (DLBCL) in particular (meta-analysis P = 1.14 × 10(-11), OR = 1.47). We found no evidence of association of rs6773854 with non-B cell NHLs (T cell and natural killer (NK) lineages) (P = 0.17, OR = 1.12) and observed significant heterogeneity between B cell and non-B cell subtypes (Phet = 0.01, I(2) = 84%). Our results provide insight that germline variation in the intergenic region between BCL6 and LPP has a role in risk of B cell lymphomagenesis.
[Show abstract][Hide abstract] ABSTRACT: The Flavivirus genus is composed of many medically important viruses that cause high morbidity and mortality, which include Dengue and West Nile viruses. Various molecular and biochemical techniques have been developed in the endeavour to study flaviviruses. However, microscopy techniques still have irreplaceable roles in the identification of novel virus pathogens and characterization of morphological changes in virus-infected cells. Fluorescence microscopy contributes greatly in understanding the fundamental viral protein localizations and virus-host protein interactions during infection. Electron microscopy remains the gold standard for visualizing ultra-structural features of virus particles and infected cells. New imaging techniques and combinatory applications are continuously being developed to push the limit of resolution and extract more quantitative data. Currently, correlative live cell imaging and high resolution three-dimensional imaging have already been achieved through the tandem use of optical and electron microscopy in analyzing biological specimens. Microscopy techniques are also used to measure protein binding affinities and determine the mobility pattern of proteins in cells. This chapter will consolidate on the applications of various well-established microscopy techniques in flavivirus research, and discuss how recently developed microscopy techniques can potentially help advance our understanding in these membrane viruses.
[Show abstract][Hide abstract] ABSTRACT: Extra-mammary Paget disease (EMPD) is a rare intra-epithelial carcinoma that is usually found on the apocrine-rich skin of the perineum. We report 2 cases in which EMPD was initially misdiagnosed on the initial punch biopsy as melanoma-in-situ and Bowen disease respectively. Reasons for the misdiagnoses included a rare pigmented axillary variant of EMPD in the first case and atypical bowenoid features on H&E in the second. The cases are described with a critical review of the histopathological findings, along with a review of the current literature. This highlights the necessity of a comprehensive immunohistochemical panel for the assessment of intra-epithelial pagetoid atypical cells.
[Show abstract][Hide abstract] ABSTRACT: Introduction: This study aims to analyse the clinico-epidemiological characteristics of Asian patients diagnosed with livedo vasculopathy (LV). Materials and Methods: We performed a retrospective analysis of all patients diagnosed with LV from 1997 to 2007 at our centre. Results: Seventy patients were diagnosed with LV with a mean age of 39 years, female: male ratio of 3:1 and no racial predilection. Most cases remained purely cutaneous, presenting with painful leg ulcers and atrophie blanche. Peripheral neuropathy was the only extra-cutaneous complication (9%). In patients who were screened, associations included hepatitis B (7%) and hepatitis C (4%), positive anti-nuclear antibody (14%), positive anti-myeloperoxidase antibody (5%), positive anti-cardiolipin antibodies (7%) and positive lupus anticoagulant (2%). In 49 patients who achieved remission, 55% required combination therapy, most commonly with colchicine, pentoxifylline and prednisolone. In those treated successfully with monotherapy, colchicine was effective in 59% followed by prednisolone (17.5%), pentoxifylline (17.5%) and aspirin (6%). Mean follow-up period was 50 months. Conclusion: LV in Asian patients is a high morbidity, chronic relapsing ulcerative skin condition. Most patients require induction combination therapy for remission. As further evidence emerges to support a procoagulant pathogenesis, a standardised protocol is needed to investigate for prothrombotic disorders during diagnosis.
Annals of the Academy of Medicine, Singapore 09/2012; 41(9):400-6. · 1.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: AimsArrhythmogenic right ventricular cardiomyopathy (ARVC) is a primary heart muscle disorder associated with sudden cardiac death. Its pathophysiology is still poorly understood. We aimed to produce an in vitro cellular model of ARVC using patient-specific induced pluripotent stem cell (iPSC)-derived cardiomyocytes and determine whether the model could recapitulate key features of the disease phenotype.Methods and resultsDermal fibroblasts were obtained from a 30-year-old man with a clinical diagnosis of ARVC, harbouring a plakophilin 2 (PKP2) gene mutation. Four stable iPSC lines were generated using retroviral reprogramming, and functional cardiomyocytes were derived. Gene expression levels of desmosomal proteins (PKP2 and plakoglobin) in cardiomyocytes from ARVC-iPSCs were significantly lower compared with cardiomyocytes from control iPSCs (P< 0.01); there were no significant differences in the expression of desmoplakin, N-cadherin, and connexin 43 between the two groups. Cardiomyocytes derived from ARVC-iPSCs exhibited markedly reduced immunofluorescence signals when stained for PKP2 and plakoglobin, but similar levels of staining for desmoplakin, N-cadherin, and connexin 43 compared with control cardiomyocytes. Transmission electron microscopy showed that ARVC-iPSC cardiomyocytes were larger and contained darker lipid droplets compared with control cardiomyocytes. After 2 weeks of cell exposure to adiopgenic differentiation medium, ARVC-iPSC cardiomyocytes were found to contain a significantly greater amount of lipid, calculated using Oil Red O staining, compared with controls (734 ± 35.6 vs. 8.1 ± 0.49 a.u., respectively; n = 7, P = 0.001).Conclusion
Patient-specific iPSC-derived cardiomyocytes display key features of ARVC, including reduced cell surface localization of desmosomal proteins and a more adipogenic phenotype.
European Heart Journal 07/2012; 34(15). DOI:10.1093/eurheartj/ehs226 · 14.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cutaneous melanoma is rare in Asia and the clinical presentation and outcome of melanoma is not well described in Southeast Asia. In addition, it is unclear if ethnic variations exist between the various racial groups. The objective of our study is to present the clinical characteristics of melanoma in Singapore and to highlight ethnical differences between Asians and Caucasians living in Singapore.
Data were retrospectively collected from 48 patients with histological confirmation of melanoma who were seen in both the National Skin Centre and National Cancer Centre of Singapore.
Acral lentiginous melanoma (ALM) was the most common subtype of melanoma in Singapore (50%). A higher proportion of non-ALM subtypes of melanoma compared to ALM were diagnosed at stage 1 (48% vs. 25%). The delay in diagnosis of ALM was 27 months compared to 12 months in other subtypes. Compared to Caucasians, there was a trend towards Asian patients being older, having a higher proportion of ALM and a longer delay to diagnosis.
Geographical and ethnic variations in the clinical presentation of melanoma exist. Specially adapted programmes are necessary to increase awareness of the different clinical presentation of melanoma in Asia and to encourage examination of the palms and soles in order to reduce the delay in diagnosis.
Annals of the Academy of Medicine, Singapore 01/2012; 41(1):17-20. · 1.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate the efficacy and safety of oral alendronate sodium therapy once daily in preventing glucocorticoid-induced bone loss in patients with immunobullous skin diseases treated with long-term glucocorticoid therapy.
A 12-month randomized, double-blind, placebo-controlled trial.
A tertiary referral dermatology center in Singapore.
Patients newly diagnosed as having an immunobullous disease and deemed to require at least 6 months of systemic glucocorticoid therapy.
The patients were randomized to receive either oral alendronate sodium (10 mg/d) or a matching placebo for 12 months. All patients also received concurrent calcium with vitamin D, 2 tablets daily.
Percent change in bone mineral density (BMD) at the lumbar spine and the femoral neck at 12 months.
A total of 29 patients (alendronate [n = 15], placebo [n = 14]) were evaluated. The percent change in BMD in the alendronate group was +3.7% and +3.5% at the lumbar spine and the femoral neck, respectively, whereas in the placebo group, it was -1.4% and -0.7% at the lumbar spine and the femoral neck, respectively. The increase in BMD observed in the alendronate group compared with the placebo group was statistically significant at both the lumbar spine (P = .01) and the femoral neck (P = .01). There was also a statistically significant decrease in serum heat-labile alkaline phosphatase levels after 12 months (-32.6%, P < .01) in the alendronate group but not in the placebo group. Adverse events were generally minor, and the frequency of occurrence did not differ significantly between both treatment groups (P = .59).
There were statistically significant increases in BMD at both the lumbar spine (P = .01) and the femoral neck (P = .01) with alendronate therapy. It is imperative to use bisphophonate therapy in patients with immunobullous disorders who are receiving oral corticosteroids because it largely prevents the morbidity associated with low BMD.
Archives of dermatology 11/2011; 148(3):307-14. DOI:10.1001/archdermatol.2011.354 · 4.31 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cutaneous plasmacytosis is a rare disease entity presenting with multiple extensive red-brown plaques, histopathology showing marked hyperplasia of mature polyclonal plasma cells, and polyclonal hypergammaglobulinemia on serum protein electrophoresis, in the absence of an underlying secondary cause. We report in this article the first case of cutaneous plasmacytosis from Singapore. A 33-year-old Chinese woman presented with mildly pruritic reddish brown papules and plaques over her trunk and arms for 2 years. Physical examination, laboratory investigations, and radiographic examination were negative for systemic involvement and lymphadenopathy. Serum immunoelectrophoresis showed polyclonal hypergammaglobulinemia with immunoglobulin G and immunoglobulin A. Two sets of skin biopsies performed 2 years apart essentially showed similar histopathological findings of a superficial and deep perivascular infiltrate with numerous mature plasma cells and small typical lymphocytes. There were lymphoid follicles with well-formed germinal centers and mantle zones, surrounded by mature lymphocytes. No light chain restriction was present on immunohistochemistry, and polymerase chain reaction for heavy chain gene rearrangement was negative for monoclonality. Despite potent topical corticosteroids and 8 months of phototherapy with narrow band ultraviolet light, there was no improvement. Intralesional triamcinolone injections to a few lesions afforded temporary relief of itch and flattening of lesions.
The American Journal of dermatopathology 07/2011; 33(5):498-503. DOI:10.1097/DAD.0b013e3181ea1198 · 1.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cancer is a leading cause of death worldwide. Tumor cells exploit various signaling pathways to promote their growth and metastasis. To our knowledge, the role of angiopoietin-like 4 protein (ANGPTL4) in cancer remains undefined. Here, we found that elevated ANGPTL4 expression is widespread in tumors, and its suppression impairs tumor growth associated with enhanced apoptosis. Tumor-derived ANGPTL4 interacts with integrins to stimulate NADPH oxidase-dependent production of O(2)(-). A high ratio of O(2)(-):H(2)O(2) oxidizes/activates Src, triggering the PI3K/PKBα and ERK prosurvival pathways to confer anoikis resistance, thus promoting tumor growth. ANGPTL4 deficiency results in diminished O(2)(-) production and a reduced O(2)(-):H(2)O(2) ratio, creating a cellular environment conducive to apoptosis. ANGPTL4 is an important redox player in cancer and a potential therapeutic target.
Cancer cell 03/2011; 19(3):401-15. DOI:10.1016/j.ccr.2011.01.018 · 23.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Dermatomyositis (DM) is a multisystem inflammatory disease with a strong association with malignancy. We aimed to describe a series of Asian patients with DM and identify any significant clinical factors associated with malignancy.
This was a retrospective review of a multi-racial cohort of 69 Asian patients diagnosed with DM over an 11-year period from 1996 to 2006.
Malignancy was detected in 15 out of 68 patients (22%), the most common of which was nasopharyngeal carcinoma (7 cases). Compared to the non-malignancy group, the malignancy-associated group was older and had more male patients. There were no statistically significant clinical, serological or laboratory factors associated with a higher risk of malignancy.
This study highlights the importance of ongoing malignancy screening especially for nasopharyngeal carcinoma in Asian patients with DM.
Annals of the Academy of Medicine, Singapore 11/2010; 39(11):843-7. · 1.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A 53-year-old Chinese man presented with a painless left upper eyelid lump of 2 weeks' duration. Histopathology was consistent with angiolymphoid hyperplasia with eosinophilia, and also revealed neutrophilic infiltrate secondary to ulceration. After incisional biopsy, the residual lesion, which was not treated, developed surface keratinization over the next 2 weeks and sloughed off, leaving intact epidermis and no scar. This case illustrates that observation awaiting spontaneous regression may be considered prior to surgical and other therapeutic interventions. The authors also briefly review the literature on angiolymphoid hyperplasia with eosinophilia and Kimura disease, with emphasis on ocular involvement.
Ophthalmic Plastic and Reconstructive Surgery 07/2008; 24(4):308-10. DOI:10.1097/IOP.0b013e31817d8765 · 0.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We report a case of B-cell post-transplant lymphoproliferative disorder in a 57-year-old female 19 years postrenal transplant patient who presented with multiple, progressive, painful ulcerated necrotic papules and nodules over the left leg. Histopathological examination showed diffuse infiltration of the dermis by large atypical B-lymphoid cells, with a negative in situ hybridization test for Epstein-Barr virus. Gastrointestinal involvement was evident by the presence of atypical lymphoid cells in the peritoneal fluid. She only had partial response to localized radiotherapy and intravenous rituximab and died 4 months later of septicaemia. Unusual features highlighted in this case include the very late onset of disease 19 years post-transplant, Epstein-Barr virus negativity and the aggressive course of disease that did not respond to the reduction of immunosuppression, localized electron beam therapy and intravenous rituximab.