HLA-A*24:07 as a potential biomarker for carbamazepine-induced Stevens-Johnson syndrome/toxic epidermal necrolysis in Filipino patients.

Aim: A case-control study was conducted in Filipino patients to determine the association between HLA alleles and carbamazepine-induced Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). Materials & methods: A retrospective review of medical records and data collection were performed. A total of 10 carbamazepine-induced SJS/TEN cases and 40 tolerant controls were recruited. Genomic DNA extracted from saliva samples was genotyped. Statistical analysis was done. Results: The HLA-B75 serotype (p = 0.003; odds ratio [OR] = 13.8; 95% CI = 2.5-76.8), HLA-B*15:21 (p = 0.041; OR = 4.7; 95% CI = 1.1-20.8) and HLA-A*24:07 (p = 0.032; OR = 6; 95% CI = 1.2-30.7) were significantly associated with carbamazepine-induced SJS/TEN. Conclusion: The HLA-B75 serotype, HLA-B*15:21 or HLA-A*24:07 may be used for pharmacogenetic screening prior to prescribing carbamazepine in Filipinos.

Association of carbamazepine-induced Stevens-Johnson syndrome/toxic epidermal necrolysis with the HLA-B75 serotype or HLA-B*15:21 allele in Filipino patients.

A case-control study was conducted to investigate the association of HLA-A alleles, HLA-B alleles including HLA-B*15:02 and HLA-B75 serotype with carbamazepine-induced SJS/TEN in Filipino patients. A retrospective review of medical records was performed. Pertinent clinical data were collected. Eight (8) carbamazepine-induced SJS/TEN cases and 32 tolerant controls were recruited. Genomic DNA was extracted from the saliva samples and genotyping was performed by employing allele-specific polymerase chain reaction. Data were analyzed using the Fisher's exact test, Mann-Whitney U test, univariate logistic regression, and multivariate logistic regression. Single allele association analysis was done. The strength of association was expressed as odds ratio with 95% confidence interval. Positive predictive value, negative predictive value, sensitivity, and specificity were computed. Of all the alleles tested, the HLA-B75 serotype (p = 0.007, OR = 23.25, 95% CI = 2.33-232.21) and HLA-B*15:21 (p = 0.026, OR = 7.53, 95% CI = 1.27-44.79) were significantly associated with carbamazepine-induced SJS/TEN. The HLA-B75 serotype or HLA-B*15:21 allele may be used as a genetic risk assessment prior to prescription for prevention of carbamazepine-induced SJS/TEN in Filipino patients.

The Medication Risk of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in Asians: The Major Drug Causality and Comparison With the US FDA Label.

Specific ethnic genetic backgrounds are associated with the risk of Stevens-Johnson syndrome / toxic epidermal necrolysis (SJS/TEN) especially in Asians. However, there have been no large cohort, multiple-country epidemiological studies of medication risk related to SJS/TEN in Asian populations. Thus, we analyzed the registration databases from multiple Asian countries who were treated during 1998-2017. A total 1,028 SJS/TEN cases were identified with the algorithm of drug causality for epidermal necrolysis. Furthermore, those medications labeled by the US Food and Drug Administration (FDA) as carrying a risk of SJS/TEN were also compared with the common causes of SJS/TEN in Asian countries. Oxcarbazepine, sulfasalazine, COX-II inhibitors, and strontium ranelate were identified as new potential causes. In addition to sulfa drugs and beta-lactam antibiotics, quinolones were also a common cause. Only one acetaminophen-induced SJS was identified, while several medications (e.g., oseltamivir, terbinafine, isotretinoin, and sorafenib) labeled as carrying a risk of SJS/TEN by the FDA were not found to have caused any of the cases in the Asian countries investigated in this study.

Carbamazepine-induced Stevens-Johnson syndrome/toxic epidermal necrolysis overlap in a Filipino with positive HLA-B75 serotype.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are two related mucocutaneous disorders with different severities. Although the incidence is low, SJS and TEN are life-threatening and predominantly drug-induced conditions. There is a strong relationship between the HLA-B*1502 allele and carbamazepine-induced SJS and TEN in different Southeast Asian populations. Here, we report a case of Filipino with SJS/TEN overlap probably induced by carbamazepine. The condition was treated with hydrocortisone followed by prednisone. The HLA-B*1502 allele was not found in this case. The patient tested positive for the HLA-B75 serotype, suggesting that carbamazepine-induced SJS/TEN may be serotype specific. Establishing the genotype before initiation of the drug may be advantageous for some patients and will aid physicians in determining the optimal drug therapy. Prevention of adverse drug reactions (ADR) may be done if pharmacists and other healthcare professionals work as a multidisciplinary ADR team to ensure that safe medication practices are realised.

A multi-center retrospective study on atopic dermatitis at the outpatient departments of Philippine Dermatological Society-accredited training institutions from 2007-2011

BACKGROUND: To date, no multicenter studies have been conducted on the prevalence and clinical profile of AD in the Philippines. Since AD is one of the top 10 skin diseases seen in the outpatients departments of all the Philippine Dermatologic Society (PDS)- accredited institutions, conducting a multicenter study provides important epidemiological information about this disease and serve as a valuable reference for future studies. OBJECTIVES: To determine the prevalence and clinical profile of patients with atopic dermatitis (AD) seen at the outpatient departments (OPD) of Philippine Dermatological Society (PDS) - accredited training institutions from 2007 to 2011. METHODS: Records of patients with a diagnosis of AD seen from January 1, 2007 to December 31, 2011 were retrieved and clinical data were collected. RESULTS: There were 744,673 dermatological consults in the 10 PDS-accredited outpatient clinics from 2007-2011. A total of 4,275 records of atopic dermatitis were reviewed for this study. The prevalence of atopic dermatitis was determined to be 0.57%. Most institutions reported a prevalence rate of less than 1% except for St. Luke's Medical Center (3.36%), and Research Institute for Tropical Medicine (7.07%). More than half of the patients (65.1%) were children between 1 to 12 years old. Twenty-four percent (24%) were infants less than one year. The average age was seven years old while the youngest was one month and the oldest was 94 years old. There were more females (56.1%) than males (42.75%). Bronchial asthma was the most prevalent co-morbid medical condition. Majority of AD patients seen in institutions were newly diagnosed. Those with previous consultations were mostly seen by dermatologists and pediatricians. Moisturizers and topical corticosteroids were the most commonly used topical preparation while antihistamines followed by oral antibiotics were the commonly prescribed oral medications. Follow-up rate was low. CONCLUSION: The prevalence of atopic dermatitis among the 10 PDS-accredited institutions is low except for SLMC and RITM. The clinical profile of patients is consistent with published literature. However, this study revealed the patient follow-up is low. This practice needs to be addressed since optimal management of this chronic disease requires close and regular follow-up to prevent complications and irrational drug use.

Ostraceous and inverse psoriasis with psoriatic arthritis as the presenting features of advanced HIV infection.

Knowledge of both the common and atypical presentations of human immunodeficiency virus (HIV)-associated dermatoses may be helpful in arousing suspicion of HIV, especially in patients with no reported risk factors. Herein, we report the case of an otherwise healthy, nonpromiscuous 29-year-old man who presented to our institution with an eight-week history of plaques with oyster shell-like scales on the trunk, extremities and genital area. The plaques were associated with fever, and intermittent knee pain and swelling. Initial diagnostic tests were suggestive of drug hypersensitivity syndrome, and the patient's condition improved with treatment using oral prednisone. However, the lesions recurred when the dose of prednisone was tapered, even after the culprit drug had long been discontinued. Repeat skin punch biopsy and arthrocentesis revealed a diagnosis of psoriasis vulgaris with psoriatic arthritis. Due to the atypical presentation of psoriasis, the patient was counselled to undergo HIV testing, which came back positive. Clinicians should be attuned to the skin signs heralding HIV/acquired immunodeficiency syndrome, in order to facilitate early diagnosis and treatment.

Topical corticosteroid therapy for the prevention of acute radiation dermatitis: a systematic review of randomized controlled trials.

Acute radiation dermatitis (ARD) is a common side effect of radiation therapy and is characterized by erythema, dry desquamation or moist desquamation. This wet desquamation is a very painful condition for the patient and often leads to interruption of radiotherapy. The objective of this article is to assess the efficacy of topical corticosteroids in the prevention of ARD compared with placebo, other topical medication or no treatment. The prophylactic application of topical corticosteroid among patients undergoing radiotherapy appears to significantly reduce the incidence of ARD, specifically moist desquamation, compared with other treatments. Future trials with a more standardized measure of radiation dermatitis grading are recommended. Further research may also be conducted to determine if a mildly potent, midpotent or super potent topical steroid will be more effective in preventing ARD.

Ustekinumab for adult Filipino patients with moderate to severe chronic plaque psoriasis: A clinical series

BACKGROUND: Psoriasis is a chronic inflammatory disease occurs worldwide. At the Philippine General Hospital dermatology clinic, psoriasis accounted for 2.2% -2.4 % of new consults seen in 2004-2010. Its pathogenesis remains obscure but current studies indicate that activated Thai and Thai response mechanisms mediate inflammation and are implicated as key players in psoriasis genesis. Ustekinumab is a fully human monoclonal antibody that targets two interleukins (IL): IL-12 and IL-23 which influence T-cell differentiation into Thi and Thai, respectively. These naturally occurring proteins help regulate the immune system secondary to their role in linking innate and adaptive immune responses.CASE SERIES: This is a retrospective chart review on the use of ustekinumab in 22 adult Filipinos (10 males and 12 females) conducted at six (6) dermatologists' clinics in 2010. Included were patients enrolled in the Named Patient Program (NPP) of Janssen Pharmaceutical Companies of Johnson & Johnson Philippines, diagnosed with moderate to severe long-standing plaque psoriasis and contraindicated for, or with inadequate response to, conventional systemic treatment. Patients received ustekinumab subcutaneously at loading doses of 45mg during the initial visit and at four weeks. Subsequently, it was given every twelve weeks. For patients who weighed 100 kg or more, 90mg of ustekinumab was administered. Clinical responses to the drug were assessed using Psoriasis Area and Severity Index (PASI) at initial visit and at the end of the program (52 weeks). At the end of the one-year program period, the median (range) PASI score of patients was 1.50 (0-29.2). Sixteen of the twenty-two subjects (72.73%) were able to achieve ±75% improvement from baseline (PASI 75). There was a significant (94.52%) reduction in median PASI scores of the patients from baseline to end visit (p CONCLUSION: Ustekinumab was shown to significantly reduce the median PASI scores of 22 adult Filipino patients with moderate to severe plaque psoriasis. It was also shown to be well tolerated, with relatively mild adverse events.

Stevens-Johnson syndrome and toxic epidermal necrolysis at the Philippine General Hospital: A seven-year retrospective study

BACKGROUND: Stevens Johnson syndrome (SJS), Stevens Johnson Syndrome-Toxic Epidermal Necrolysis (SJS-TEN) and Toxic Epidermal Necrolysis (TEN) are dermatologic emergency that necessitate early recognition and management to prevent fatal outcome.OBJECTIVES: To identify the demographic, etiologic and clinical features, management, outcomes and complications commonly seen in patients diagnosed with SJS-TEN and admitted at the Philippine General Hospital.METHODS: Available records of all patients with the diagnosis of SJS, SJS-TEN and TEN admitted to the Philippine General Hospital from January 2004 to December 2010 were reviewed.RESULTS: A total of 31 cases of SJS/TEN were seen. This accounted for 0.01% of the total admissions. Mean age was 45 years with 1: 1.07 female-to-male ratio. Etiologic drugs were mostly anticonvulsants (38.7%), allopurinol (19.4%) and antibiotics (16.20%). The mean time interval between drug intake and onset of symptoms was 15.36 days. Antibiotics had the shortest mean interval (7 days), while phenytoin had the longest (26.8 days). Systemic steroids were given as treatment intervention in majority of cases (98.9%). Average hospital stay was 10 days. Secondary infection was the most common complication seen (41.90%). Resolution was observed in 93.5% of the cases. High SCORTEN score (SCORTEN = 4) corresponded with increased mortality (6.45%).CONCLUSION: SJS, SJS-TEN and TEN are rare and potentially fatal conditions commonly affecting the middle age group as seen in this study. Anticonvulsant was the most common group of drug implicated in our review. These findings were similar with studies done in other Asian countries. Systemic corticosteroid was the mainstay of treatment at our institution due to its low cost, availability and efficacy when given early on in the disease.

A study on the knowledge, attitudes and practices of Southeast Asian dermatologists in the management of atopic dermatitis.

INTRODUCTION: This study evaluated the knowledge, attitudes and practices of Southeast Asian dermatologists in the management of atopic dermatitis (AD). MATERIALS AND METHODS: A questionnaire survey of 255 dermatologists in Indonesia, Malaysia, the Philippines, Singapore, Thailand and Vietnam. RESULTS: Familiarity with diagnostic criteria varied considerably. The usage of moisturisers by the respondents from Vietnam and Indonesia was significantly less frequent than the other countries. Most respondents (91% to 100%) used topical corticosteroids in children with mild-to-moderately severe dermatitis. Some respondents in the Philippines (17% to 19%) and Vietnam (11% to 25%) only used topical corticosteroids for severe disease. For infected eczema, most respondents would prescribe systemic antibiotics for mild-to-moderate infection. A minority in the Philippines (14%) and Vietnam (11%) did so only for severe infection. The top 4 systemic antibiotics prescribed most frequently were: erythromycin, cloxacillin, cephalosporin and amoxicillin/clavulanic acid. In Indonesia, a large proportion of the respondents (47%) prescribed amoxicillin most frequently. The majority of respondents (60% to 100%) prescribed both sedating and non-sedating oral antihistamines. Most respondents used oral corticosteroids to treat severe AD. Some in Malaysia, Singapore and Vietnam used cyclosporin (7% to 58%), azathioprine (5% to 31%) and methotrexate (5% to 14%). With the exception of those in Singapore, the majority of respondents (71% to 97%) did not use phototherapy. CONCLUSION: Familiarity with diagnostic criteria, the early and judicious use of moisturisers and topical corticosteroids, as well as the treatment of Staphylococcus aureus superinfection with penicillinase-stable antibiotics should be emphasised in this region.