HLA-B*58: 01 association in allopurinol-induced severe cutaneous adverse reactions: the implication of ethnicity and clinical phenotypes in multiethnic Malaysia.

OBJECTIVE: The association between human leukocyte antigen (HLA)-B*58:01 and risk of allopurinol-induced severe cutaneous adverse reactions (AIS) was observed across different populations. We explore the association between HLA-B*58:01 and AIS risk in multiethnic Malaysian population. The HLA-B*58:01 risk for different AIS clinical phenotypes and ethnicity was determined. METHODS: We performed a case-control association study by genotyping the HLA-B alleles of 55 patients with AIS [11 toxic epidermal necrolysis (TEN), 21 Steven Johnson syndrome (SJS) 22 drug reaction wit eosinophilia and systemic symptoms (DRESS) and one acute generalized exanthematous pustulosis (AGEP)] and 42 allopurinol-tolerant controls (ATC). RESULTS: HLA-B*58:01 was positive in 89.1 and 14.3% of the AIS and ATC study groups [odds ratio (OR) = 49.0, 95% confidence interval (CI) = 14.6-164.4, P < 0.0001)], respectively. Our data showed that 93.8% of the AIS-SJS/TEN patients and 86.4% of the AIS-DRESS patients were HLA-B*58:01 positive (AIS-SJS/TEN, OR = 90, 95% CI = 16.9-470.1, P < 0.0001 and AIS-DRESS OR = 38, 95% CI = 8.5-169.2, P < 0.0001). Stratification by ethnicity and clinical phenotypes revealed a significant increased risk between HLA-B*58:01 and Chinese-AIS patients (OR = 137.5, 95% CI = 11.3-1680.2, P < 0.0001), in particular Chinese patients with AIS-SJS/TEN phenotype (100% HLA-B*58:01 positive). HLA-B*58:01 was positive in 90.9% Chinese AIS-DRESS (P < 0.0001). Highly significant associations of HLA-B*58:01 were observed in Malay AIS-SJS/TEN (OR = 78, 95% CI = 9.8-619.9, P < 0.0001) and Malay AIS-DRESS (OR = 54, 95% CI = 6.6-442.9, P < 0.0001). Although the number of Indian-AIS patients was relatively small (n = 2), both were HLA-B*58:01 positive. CONCLUSION: Our data suggest strong associations between HLA-B*58:01 and AIS in Malaysian population with Chinese and Malays ethnicity. The strong association was also observed in three different clinical phenotypes of AIS, mainly the AIS-SJS/TEN.

Quality of life and cost of illness in patients with psoriasis in Malaysia: a multicenter study.

BACKGROUND: Psoriasis is an immune-mediated, chronic, inflammatory skin disease which affects approximately 2% of the world's population. It has a major impact on the patient's quality of life (QoL), influencing career, social activities, family relationships, and all other aspects of life. Many studies have described the various ways in which psoriasis can affect a patient's life. Very little is known, however, about the impact of psoriasis on the QoL of patients treated in Malaysia and the cost of illness in this region. OBJECTIVES: This study aims to describe the extent to which psoriasis affects the QoL of patients treated in government-run dermatology clinics in Malaysia and to estimate the cost of illness. METHODS: A total of 250 psoriasis patients treated at eight dermatology clinics in government-run hospitals in Malaysia were studied. The severity of psoriasis was assessed by dermatologists. Quality of life was evaluated using the Dermatology Life Quality Index (DLQI) and Version 2 of the 12-Item Short-Form Health Survey (SF-12v2). Scores on the SF-12v2 of healthy subjects and of patients with other medical conditions, such as depression, diabetes mellitus, hypertension, and ischemic heart disease, were also assessed for comparison. The costs of dermatology outpatient consultant fees, medications, investigations, procedures, transportation, over-the-counter medications, and hospitalization were retrospectively estimated using questionnaires. RESULTS: The cohort studied had a median Psoriasis Area Severity Index (PASI) score of 9.9 and a median DLQI score of 10.0. The average SF-12v2 scores were 43.68 (standard deviation [SD] 9.23) and 42.25 (SD 10.7) on the Physical Health Summary and Mental Health Summary, respectively. The impact of disease on QoL was found to be greater in those with more extensive psoriatic lesion involvement, in younger patients, and in those with psoriatic arthropathy. Psoriasis was found to affect QoL in both genders equally. Body mass index had no effect on the severity of psoriasis or QoL. Patients with psoriasis had a significantly lower SF-12v2 score than healthy subjects. Comparisons with data for patients with other chronic medical conditions demonstrated that psoriasis has a negative effect on health-related QoL similar to the impact of other chronic conditions. The estimated cost of illness for psoriasis in the current cohort was ringgit Malaysia (RM) 1307.47 per person per year excluding costs of hospitalization. Patients were noted to spend a large amount of money on over-the-counter products obtained without doctors' prescriptions. CONCLUSIONS: The QoL of patients with psoriasis was significantly impaired compared with that of healthy subjects and was comparable with that of patients with other chronic medical illnesses. The estimated cost of illness of psoriasis in the current study was lower than in other countries, mainly because healthcare costs in public hospitals are heavily subsidized by government and because usage of newer but more expensive treatment options is low in Malaysia.

Fingerprint changes and verification failure among patients with hand dermatitis.

OBJECTIVES: To determine the prevalence of fingerprint verification failure and to define and quantify the fingerprint changes associated with fingerprint verification failure. DESIGN: Case-control study. SETTING: Referral public dermatology center. PATIENTS: The study included 100 consecutive patients with clinical hand dermatitis involving the palmar distal phalanx of either thumb and 100 age-, sex-, and ethnicity-matched controls. Patients with an altered thumb print due to other causes and palmar hyperhidrosis were excluded. MAIN OUTCOME MEASURES: Fingerprint verification(pass/fail) and hand eczema severity index score. RESULTS: Twenty-seven percent of patients failed fingerprint verification compared with 2% of controls. Fingerprint verification failure was associated with a higher hand eczema severity index score (P.001). The main fingerprint abnormalities were fingerprint dystrophy (42.0%) and abnormal white lines (79.5%). The number of abnormal white lines was significantly higher among the patients with hand dermatitis compared with controls(P=.001). Among the patients with hand dermatitis, theodds of failing fingerprint verification with fingerprint dystrophy was 4.01. The presence of broad lines and long lines was associated with a greater odds of fingerprint verification failure (odds ratio [OR], 8.04; 95% CI, 3.56-18.17 and OR, 2.37; 95% CI, 1.31-4.27, respectively),while the presence of thin lines was protective of verification failure (OR, 0.45; 95% CI, 0.23-0.89). CONCLUSIONS: Fingerprint verification failure is a significant problem among patients with more severe hand dermatitis. It is mainly due to fingerprint dystrophy and abnormal white lines. TRIAL REGISTRATION: Malaysian National Medical Research Register Identifier: NMRR-11-30-8226

Diffuse large B-cell lymphoma presenting with extensive cutaneous infiltration.

We report a case of systemic diffuse large B-cell lymphoma presenting with extensive infiltration of the skin. A 56-year-old woman presented with a two-month history of pruritic erythematous plaques and nodules over the neck, trunk and upper limbs. She also had night sweats, weight loss, lethargy and reduced effort tolerance. Systemic examination revealed a pale, ill appearance with hepatosplenomegaly and lymphadenopathy. Blood investigations showed pancytopenia (haemoglobin 6.3 g/dL, total white cell count 3.0 × 10(9)/L, platelet count 138 × 10(9)/L) with a few suspicious mononuclear cells and a mildly elevated lactate dehydrogenase level (478 U/L). Skin biopsy demonstrated diffuse sheets and nodular infiltrates of CD20 and CD79a positive neoplastic cells in the dermis and subcutis. Computed tomography revealed multiple cervical, axillary, mediastinal, para-aortic and mesenteric lymph nodes. Bone marrow aspiration and trephine biopsy confirmed marrow involvement by non-Hodgkin's lymphoma. The patient was treated with chemotherapy, which resulted in resolution of the skin lesions.

Cutaneous sporotrichosis: a six-year review of 19 cases in a tertiary referral center in Malaysia.

BACKGROUND: Sporotrichosis is a subcutaneous fungal infection caused by a thermally dimorphic aerobic fungus, Sporothrix schenckii. It results from traumatic inoculation or contact with animals. Most cases were reported mainly in the tropics and subtropics. OBJECTIVE: The objective of our study is to assess the clinical characteristic of cutaneous sporotrichosis among our patients. METHODOLOGY: We performed a retrospective review of all cases diagnosed with cutaneous sporotrichosis from July 2004 to June 2010. Patients' medical records were retrieved and analyzed according to demography, preceding trauma, sites of lesions, clinical subtypes, treatment, and clinical response. RESULTS: Nineteen cases were diagnosed with cutaneous sporotrichosis with a male/female ratio of 9:10. Thirteen cases (68.4%) were able to recall preceding trauma, and seven of them reported cat scratches or cat bites. Lymphocutaneous sporotrichosis was observed in 13 cases (68.4%) followed by four cases of fixed cutaneous sporotrichosis and two cases of disseminated sporotrichosis. Histologically, 11 cases (57.8%) demonstrated a granulomatous reaction. Sporothrix schenckii was cultured in 12 cases (63.2%). Thirteen cases (68.4%) were successfully treated with oral itraconazole alone for a mean duration of 15.6 weeks. Two cases with disseminated cutaneous sporotrichosis were treated with intravenous amphotericin B. CONCLUSION: Lymphocutaneous sporotrichosis was the most common subtype of cutaneous sporotrichosis in our series, with cat scratches or bites being the most common preceding trauma. Oral itraconazole was highly effective for the localized subtypes, whereas intravenous amphotericin B was required in disseminated cutaneous sporotrichosis.

Association of HLA-B*1502 allele with carbamazepine-induced toxic epidermal necrolysis and Stevens-Johnson syndrome in the multi-ethnic Malaysian population.

BACKGROUND: Carbamazepine (CBZ), a frequently used anticonvulsant drug, is one of the most common causes of life-threatening cutaneous adverse drug reactions such as toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS). Recent studies have revealed a strong association between HLA-B*1502 and CBZ-induced TEN/SJS in the Taiwan Han Chinese population. OBJECTIVES: This study is aimed to investigate the association between human leucocyte antigens (HLA) and CBZ-induced TEN/SJS in the multi-ethnic Malaysian population. METHODS: A sample of 21 unrelated patients with CBZ-induced TEN/SJS and 300 race-matched, healthy controls were genotyped for HLA-A, -B and -DR using polymerase chain reaction (PCR). Allele frequencies were compared. RESULTS: HLA-B*1502 was present in 75.0% (12/16) of Malay patients with CBZ-induced TEN/SJS but in only 15.7% (47/300) of normal controls (odds ratio 16.15, 95% confidence interval 4.57-62.4; corrected P-value = 7.87 × 10(-6) ), which suggests a strong association between HLA and CBZ-induced TEN/SJS. Additionally, HLA-B*1502 was found in all three Chinese and two Indian patients. Existing data show that frequencies of the HLA-B*1502 allele are generally much higher in Asian populations than in White European populations, which explains the higher incidences of SJS and TEN in Asian countries. CONCLUSIONS: HLA-B*1502 is strongly associated with CBZ-induced TEN/SJS in the Malay population in Malaysia, as has been seen in Han Chinese in Taiwan. This indicates that the genetic association apparent in the incidence of CBZ-induced TEN/SJS is linked with the presence of HLA-B*1502, irrespective of racial origin. Screening of patients for this genetic marker can help to prevent the occurrence of TEN/SJS.