Mortality of bullous pemphigoid in Singapore: risk factors and causes of death in 359 patients seen at the National Skin Centre.

BACKGROUND: Bullous pemphigoid (BP) is the most common autoimmune-mediated subepidermal blistering skin disease and is associated with significant morbidity and mortality. OBJECTIVES: To determine the 3-year mortality rate, risk factors and causes of death in patients with BP in Singapore, compared with the general population. METHODS: We conducted a retrospective cohort study of all newly diagnosed patients with BP seen at the National Skin Centre from 1 April 2004 to 31 December 2009. Demographic and clinical data on comorbidities and treatment were recorded. Mortality information was obtained from the National Registry of Diseases. RESULTS: In total 359 patients were included in our study. The 1-, 2-, 3-year mortality rates were 26·7%, 38·4% and 45·7%, respectively. The 3-year standardized mortality risk for patients with BP was 2·74 (95% confidence interval 2·34-3·19) times higher than for the age- and sex-matched general population. Parkinson disease, heart failure and chronic renal disease were associated with increased mortality, while combination treatment with low-to-moderate-dose corticoste-roids and immunomodulatory agents such as doxycycline and/or nicotinamide was associated with lower mortality. Overall, infections were the most common cause of death (59·8%), with the main causes of death being pneumonia (42·7%), cardiovascular disease (14·6%) and stroke (11·6%). CONCLUSIONS: This study confirms an increased 3-year mortality rate for patients with BP in Singapore. Risk factors for increased mortality include medical comorbidities, especially neurological, cardiac and renal diseases. Treatment with combination therapy, including the use of low-to-moderate-dose corticosteroid, appeared to decrease mortality risk in patients with BP.

Electronic e-isotretinoin prescription chart: improving physicians' adherence to isotretinoin prescription guidelines.

Oral isotretinoin is a highly effective treatment for refractory nodulocystic acne. However, it can be associated with serious adverse effects such as teratogenicity and hepatitis. Inadequate cumulative dosing may also result in reduced therapeutic efficacy and higher disease relapse. A preliminary audit had previously revealed a poor and inconsistent adherence to local isotretinoin prescribing guidelines by physicians. To achieve greater than 90% adherence to isotretinoin guidelines for all acne patients prescribed systemic isotretinoin at the National Skin Centre, Singapore, key areas and the reasons for non-adherence were identified. A specifically designed 'one-stop' electronic isotretinoin chart was launched within the electronic medical records (EMR) system to address important safety areas; namely, informed patient consent, pregnancy testing, baseline laboratory tests, and automatic calculation of cumulative and target doses of isotretinoin. Physician adherence to prescribing guidelines improved from a baseline of 50-60% to greater than 90% (range 95-100%) for 30 consecutive months post intervention. The e-isotretinoin chart has resulted in significant improvement in physicians' adherence to isotretinoin prescription guidelines and highlights the utility of EMR technology in influencing safe prescribing behaviour among doctors.

Scrotal pyoderma gangrenosum associated with Crohn's disease.

Scrotal pyoderma gangrenosum is uncommon. We present a 17-year-old Chinese male patient with newly diagnosed Crohn's disease presenting with scrotal pyoderma gangrenosum. Biopsy and other investigations were done to diagnose and look for associated diseases of pyoderma gangrenosum. Treatment with high-dose prednisolone failed. Subsequent treatment with oral cyclosporine was successful.

A case of recurrent erythema multiforme and its therapeutic complications.

INTRODUCTION: We report a patient with recurrent erythema multiforme (recurrent EM) who developed iatrogenic Cushing's syndrome due to prolonged corticosteroid use. CLINICAL PICTURE: The patient had been treated with multiple courses of oral and intramuscular prednisolone over a 10-year period to suppress his recurrent and episodic symptoms. This resulted in the development of iatrogenic Cushing's syndrome with secondary adrenal suppression and steroid-induced osteoporosis. TREATMENT: The patient was treated with continuous acyclovir therapy in addition to azathioprine. This combination controlled his disease and enabled us to stop his requirement for high-dose prednisolone. OUTCOME: The patient responded well to this treatment regimen and has been in remission to date. CONCLUSION: This represents a severe case of recurrent EM and the side effects associated with years of chronic high-dose steroid usage. We discuss the therapeutic options to aid physicians in treating this disabling condition.

Spectrum of subepidermal immunobullous disorders seen at the National Skin Centre, Singapore: a 2-year review.

BACKGROUND: The subepidermal immunobullous disorders (SEIBDs) comprise bullous pemphigoid (BP), cicatricial pemphigoid (CP), epidermolysis bullosa acquisita (EBA), linear IgA disease (LAD), dermatitis herpetiformis (DH), pemphigoid gestationis (PG) and bullous systemic lupus erythematosus (BSLE). They are thought to be rarer in the Far East than in western Europe. OBJECTIVE: This 2-year retrospective study investigates the spectrum seen at our centre and the minimum estimated incidence of each. PATIENTS AND METHODS: A total of 67 patients seen at the National Skin Centre (NSC), Singapore between January 1998 and December 1999 were diagnosed as having an SEIBD. Fifty-nine (88%) had BP, four (6%) had EBA, two (3%) LAD and two (3%) BSLE. There were no cases of CP, DH or PG diagnosed during this period. The minimum estimated incidence in our local population was 7.6, 0.5, 0.26 and 0.26 per million population per year, respectively. The mean age of onset was 77, 68, 65 and 31 years, respectively. RESULTS: BP is the commonest SEIBD seen locally, with an incidence at least equal to that in western Europe. It is diagnosed at our centre three times more frequently than pemphigus. There is a predilection for ethnic Chinese but not Indian. EBA is twice as common as in western Europe and shows a predilection for ethnic Indians. LAD is rare here compared to China, despite the predominant Chinese population. BSLE is also rare. In contrast to western Europe, CP, DH and PG are very rare in Singapore. CONCLUSIONS: This is the first study from this region to show that certain SEIBDs are not rarer in the Far East, as previously thought.

Bullous pemphigoid seen at the National Skin Centre: a 2-year retrospective review.

INTRODUCTION: Bullous pemphigoid (BP) is the most common immunobullous disorder in Western Europe, affecting mainly the elderly. Previous reports have suggested that it is rarer in the Far East. We report on the clinico-epidemiological features of BP seen at our centre. MATERIALS AND METHODS: This is a 2-year retrospective study of patients seen at the National Skin Centre who were diagnosed to have BP. RESULTS: Fifty-nine patients were newly diagnosed with BP over a 2-year period between January 1998 and December 1999. The minimum estimated incidence was 7.6 per million population per year, with mean age of onset of 77 years, and a male to female ratio of 1:2. There was a predilection for Chinese but not Indian. Localised disease was found in 34% and mucosal involvement in only 1.7%. Direct immunofluorescence was positive in almost all patients, and 94% of those tested had positive indirect immunofluorescence. 'Roof' pattern was present in 95.8% and 'roof and floor' pattern in 4.2%. Prednisolone was the treatment of choice in most patients (78%). Anti-inflammatory agents were more commonly used than a decade ago (13.5%). CONCLUSIONS: BP is the most common immunobullous disease locally, with an incidence at least equal to that in Western Europe. There was a predilection for ethnic Chinese rather than Indian. Apart from the rarity of mucosal involvement, the clinical features are similar to those of Western nations.

A case of generalised cutaneous granulocytic sarcoma in an elderly patient with myelodysplastic syndrome.

Granulocytic sarcoma is a rare extramedullary malignant mass composed of primitive cells of the granulocytic lineage. It can arise from any part of the body and is frequently associated with haematological diseases, commonly acute myeloid leukaemia. Rarely, it has been found in conjunction with myelodysplastic syndrome. We report a case of cutaneous granulocytic sarcoma in a 73-year-old lady. The patient presented with a two-month history of multiple skin nodules which were confirmed by skin biopsy to be granulocytic sarcoma. Bone marrow examination was consistent with myelodysplastic syndrome. Localised radiotherapy to the skin lesions were given. She died from septicaemia six months after presentation. The management of this condition presents a diagnostic and therapeutic dilemma for both the pathologist and physician. In cases which are poorly differentiated as in this case, histological diagnosis is particularly difficult. Its definitive diagnosis would then require the additional use of a broad panel of immunohistochemical and cytochemical stains.

Malignant melanoma seen in a tertiary dermatological centre, Singapore.

INTRODUCTION: Primary malignant melanoma is an uncommon skin tumour in Singapore compared with the Western countries. The clinical characteristics of melanoma have been rarely reported in Asians. OBJECTIVES: Our purpose was to study the incidence, clinical characteristics and risk factors of biopsy proven malignant melanoma seen in a tertiary referral skin hospital. METHODS: Case records of patients with histology proven malignant melanoma from January 1989 to December 1998 were retrieved. Patients were interviewed and a complete skin and systemic examination was performed. Data on demographics, histological types, clinical characteristics and risk factors were collated. RESULTS: Between 1989 and 1998, 27 patients were diagnosed with histology proven malignant melanoma. There was a predominance of Chinese with a female to male ratio of 1.3:1. There was a mean lag period of 1.6 years to diagnosing melanoma and there is a general lack of knowledge among the local patients. Most of the lesions (89%) occurred on the extremities. Acral lentiginous melanoma (41%) and nodular melanoma (41%) were the two commonest histologic types. Of the nodular melanomas, 64% were observed in patients below 50 years (64%) while majority of the acral lentiginous melanomas occurred in those above 50 years (91%). In terms of risk factors, we reported a high prevalence of diabetes mellitus with acral lentiginous melanoma. CONCLUSIONS: This study highlighted interesting aspects in terms of clinical characteristics and risk factors in our local patients. It also served as a remainder of the need to raise awareness among the public and medical community of skin cancers or melanomas as they are potentially treatable if detected early.

A case report of erythema induratum of Bazin's disease.

INTRODUCTION: Erythema induratum remains one of the rarely encountered tuberculid although tuberculosis is known to be endemic in the developing countries. We report a case of erythema induratum recently encountered in our centre. CLINICAL FEATURE: Clinically, erythema induratum typically manifests as ulcerative and indurated lesions on the lower limbs, especially the calves. TREATMENT OUTCOME: The patient responded well to a course of anti-tuberculous therapy with marked resolution of the lesions, suggesting the aetiological role of Mycobacterium tuberculosis in this condition. CONCLUSION: A short review of the distinguishing features of erythema induratum, the associated classical histological spectrum and the usefulness of polymerase chain reaction in the diagnosis of erythema induratum is given. A search for active foci of tuberculosis is advocated in all cases.

Classical and amyopathic dermatomyositis seen at the National Skin Centre of Singapore: a 3-year retrospective review of their clinical characteristics and association with malignancy.

INTRODUCTION: Dermatomyositis is a condition well-known to medical physicians, especially rheumatologists and dermatologists. Classically, patients present with typical cutaneous features and proximal muscle weakness. Amyopathic dermatomyositis has been reported in recent literature where patients present with skin changes without muscle involvement. MATERIALS AND METHODS: We reviewed 28 patients diagnosed with dermatomyositis at the National Skin Centre over a 3-year period from 1996 to 1998 to assess the prevalence of this amyopathic variant in our local population and its association with malignancy. RESULTS: Out of the 28 patients, 13 (46.4%) had no clinical or laboratory evidence of myositis at presentation. Nine patients (32.1%) had clinical muscle weakness and 6 patients (21.4%) had laboratory evidence of myositis. Malignancies were detected in 12 patients (42.8%), half of which were nasopharyngeal carcinomas. There was no significant difference in the prevalence of malignancy between those with detectable muscle weakness (33.3%) and those without (47.4%). However, there was a significant higher prevalence of malignancy in those with clinical and laboratory evidence of myositis (66.6%) than those without (15.4%). CONCLUSION: We conclude that amyopathic dermatomyositis is a common presentation in our population and may have a lower risk of malignancy than the classical variant. Screening for malignancy, especially nasopharyngeal carcinoma, is recommended for all dermatomyositis patients.

A case report: persistent acantholytic dermatosis in chronic renal failure.

INTRODUCTION: This is the second case of persistent acantholytic dermatosis in a patient with chronic renal failure, seen at the same institution in 2 years. CLINICAL PICTURE: A 70-year-old Chinese man with end-stage renal failure on continuous ambulatory peritoneal dialysis for 6 months presented with pruritic rashes over the scalp and chest for 3 months. Histologically, the lesions resembled Darier's disease. Differential diagnoses include Darier's disease, Grover's disease and perforating dermatosis in chronic renal failure. TREATMENT: The patient was treated with anti-histamines, topical steroids and emollients. OUTCOME: Resolution of pruritus was documented. However, the extensive hyperkeratotic papules remained persistent. CONCLUSION: A chronic non-remitting course is to be expected for this dermatoses in which the aetiology is unknown.

Retrospective study of Behcet's disease seen at the National Skin Centre, Singapore.

This retrospective study characterises the clinical manifestations and outcome of 34 patients diagnosed with Behcet's disease seen at the National Skin Centre from 1990 to 1997. The 2 diagnostic criteria used were the International Study Group and the O'Duffy criteria. Seventy-six per cent satisfied both criteria and the remaining 24% satisfied only the incomplete form of the O'Duffy criteria. We found that the male to female ratio was 1:1.8. The mean age of presentation was 33 years (range 21 to 63 years). The majority were Chinese (73%). In our series, patients had prominent mucocutaneous involvement. These findings may be attributed to patient selection to a tertiary dermatology clinic. Oral (100%) and genital (99%) ulceration were the 2 commonest symptoms. The other cutaneous features included papulo-pustular or acneiform eruption (26%), erythema nodosum (14.7%) and positive pathergy test. Five patients (15%) had arthritis, 1 patient had recurrent thrombophlebitis and 2 patients had eye complications. The outcome of our patients was generally good with minimal functional impairment and no mortality detected. Our patients were primarily outpatient referrals and this may explain why systemic complications were rare in our series.

Cutaneous vasculitis seen at a skin referral centre in Singapore.

OBJECTIVE: To study the clinical features and course of patients presenting to a skin referral centre with cutaneous vasculitis. METHOD: A retrospective review of patients presenting to the National Skin Centre from 1993 to 1995 with cutaneous vasculitis was done. All patients included in the study had histologically proven vasculitis on skin biopsy. The clinical manifestations and laboratory investigations of the patients were recorded. The response to the various drugs given as first line therapy and course of the disease 1 year after initial presentation was reviewed. RESULTS: Forty-seven patients were included in this study. Females outnumbered males in a ratio of approximately 2:1 (32 females versus 15 males). The age of the patients ranged from 14 to 78 years, with a mean of 36 years. The aetiology remained elusive in 70% of cases. Of the known secondary causes, drugs and streptococcal infections were the most frequently implicated. The lower limbs were involved in more than 90% of cases. Cutaneous lesions took the form of palpable purpura, ulcers, nodules and urticaria. Extracutaneous manifestations were present in 47% of patients. The main extracutaneous manifestations were arthralgia/arthritis (21%), microscopic haematuria (16%) and abdominal pain (8%). Direct immunofluorescence on lesional skin was positive in 65% of cases. A raised erythrocyte sedimentation rate was observed in 40% of patients. Positive antinuclear antibodies were detected in 30% of cases. Most patients who were given systemic corticosteroids responded predictably well. The response to other modalities of treatment was more variable. At 1 year follow-up, complete remission was recorded in 47% of the patients, while in 53% of the patients, the disease continued to run a chronic relapsing course.

Bullous dermatomyositis associated with nasopharyngeal carcinoma--a case report.

Cutaneous manifestations of dermatomyositis commonly include Gottron's papules, heliotrope rash, photosensitivity, poikiloderma and nailfold telangiectasia. Vesicles and bulla are rare. We report a patient with dermatomyositis who presented with blisters and oral ulcers. It is important to recognise this bullous variant in order to avoid a delay in diagnosis. Bullous dermatomyositis may also portend a poorer prognosis. Our patient was subsequently diagnosed to have undifferentiated nasopharyngeal carcinoma.

Topical squaric acid dibutylester therapy for alopecia areata: a double-sided patient-controlled study.

In this prospective, double-sided patient-controlled therapeutical trial involving 20 patients with alopecia areata, we investigated the efficacy of topical acid dibutylester (SADBE) in the treatment of alopecia areata. Sensitisation was achieved with 2% SADBE in acetone followed by weekly application of topical SADBE to designated alopecia sites for 20 weeks. Untreated alopecia sites on the same patient acted as controls. Nineteen of the twenty patients completed 20 weeks of treatment. On the SADBE treated sites, excellent response (> 75% hair regrowth) was observed in 68% (13/19) of patients at the end of 20 weeks of treatment. On the untreated control sites, the corresponding figure was 11% (2/19). The difference in response between SADBE treated and untreated sites was statistically significant (P < 0.001). Mean onset of hair regrowth was 6 weeks after starting treatment. Patients with duration of alopecia 12 months or longer fared poorer compared with patients with a shorter duration of the disease. The extent of involvement did not appear to influence treatment outcome. Side effects were mainly local and were mainly local and were well tolerated. At 6 months follow-up, 33% (2/6) of responders with alopecia totalis relapsed compared to 11% (19) of those with patchy alopecia areata. We conclude that topical immunotherapy with SADBE is effective in inducing hair regrowth in alopecia areata.

Systemic lupus erythematosus with erythema multiforme-like lesions and histiocytic necrotizing lymphadenitis--a case report.

A 9-year-old Chinese girl with systemic lupus erythematosus presented initially with persistent cervical lymphadenopathy without any constitutional symptoms. The histology of the involved lymph node showed histiocytic necrotizing lymphadenitis and the initial clinical diagnosis of Kikuchi-Fujimoto disease was made. The patient subsequently developed fever, oral ulcerations, epistaxis, generalised myalgia and erythema multiforme-like skin lesions over the face and upper arms. Investigations showed anaemia, leucopenia, hypocomplementemia, a positive antinuclear antibody and a positive anti-double-stranded DNA antibody test. The clinical diagnosis was revised to systemic lupus erythematosus. The histological picture of histiocytic necrotizing lymphadenitis can occur in systemic lupus erythematosus and may be indistinguishable from that seen in Kikuchi-Fujimoto disease. The diagnosis of Kikuchi-Fujimoto disease should be confined to a benign clinical subset of histiocytic necrotizing lymphadenitis which resolves spontaneously without treatment. The occurrence of erythema multiforme-like lesions in lupus erythematosus is unusual and together with the characteristic serologic abnormalities, fits Rowell's syndrome.

Genital ulcer disease in patients attending a public sexually transmitted disease clinic in Singapore: an epidemiologic study.

Genital ulcer disease forms about 10% of all sexually transmitted diseases (STDs) in Singapore. In this retrospective study of 531 cases of genital ulcer disease presenting at the Department of STD Control, 91.6% were due to venereal causes and 8.4% were due to non-venereal causes. The venereal causes of genital ulcers were found to be genital herpes (71.5%), chancroid (15.8%), primary syphilis (3.4%) and lymphogranuloma venereum (1%). The non-venereal causes were mainly trauma, drug eruptions or were non-specific in nature. The peak incidence in both sexes occurred in the 20-39 year age group. Males outnumbered females by a ratio of 5.8:1. The ethnic distribution showed an under-representation of Malays relative to the racial makeup of the general population, reflecting perhaps a protective effect conferred by circumcision from genital ulcer diseases or a lower health-risk sexual behaviour in this ethnic group. The accuracy of initial clinical diagnosis was low indicating the need for laboratory investigations to establish accurate aetiologic diagnosis. Commercial sex workers were the main source of infection in males, highlighting the continued need to educate, screen and effectively treat this high risk group.