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Fulltext Two years review of cutaneous adverse drug reaction from first line anti-tuberculous drugs

Tan WC, Ong CK, Kang SC, Razak MA

Med J Malaysia, 2007 Jun;62(2):143-6.
PMID: 18705448 MyJurnal

First line Anti-TB therapy with rifampicin, isoniazid, pyrazinamide, and ethambutol/streptomycin is very effective. However, major adverse reactions to antituberculous drugs can cause significant morbidity and mortality. Cutaneous adverse drug reaction (CADR) is one of the commonly observed major adverse events. This retrospective study looked at the cases of TB treated in Respiratory Unit, Penang Hospital from January 2004 to December 2005. Of 820 patients treated for active TB, 47 patients (25 females; 22 males) developed CADR (5.7%). CADRs observed include morbiliform rash (72.3%), erythema multiforme syndrome (8.5%), urticaria (8.5%) and others (which include exfoliative dermatitis and lichenoid eruption). Ninety-seven percent of events occurred within two months after the initial dose. Incidence rate of CADR among the first line anti-TB drugs, pyrazinamide was the commonest offending drug (2.38%), followed by streptomycin (1.45%), ethambutol (1.44%), rifampicin (1.23%) and isoniazid (0.98%). Various clinical characteristics of patients with CADR identified include Human Immunodeficiency Virus (HIV) infection (27.7%), polypharmacy (21.3%), elderly (19.1%), autoimmune disorders (6.4%), pre-existing renal impairment (4.3%), pre-existing liver disorders (4.3%). In conclusion, CADR is common and majority of cases occurred within two months after initiation of anti-TB treatment, particularly in HIV infected patients. Pyrazinamide is the commonest offending drug.

Matched MeSH terms: Skin Diseases/chemically induced*
Risk factors of allopurinol-induced severe cutaneous adverse reactions in a Thai population

Saksit N, Tassaneeyakul W, Nakkam N, Konyoung P, Khunarkornsiri U, Chumworathayi P, et al.

Pharmacogenet Genomics, 2017 07;27(7):255-263.
PMID: 28509689 DOI: 10.1097/FPC.0000000000000285

BACKGROUND: Allopurinol is one of the most common causes of severe cutaneous adverse drug reactions (SCARs) including drug reactions with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). This study identified the risk factors associated with the development of allopurinol-induced SCARs in a Thai population.
PATIENTS AND METHODS: Eighty-six allopurinol-induced SCARs (i.e. 19 DRESS and 67 SJS/TEN) and 182 allopurinol-tolerant patients were enrolled in the study. The HLA-B*58:01 allele was determined. Clinical and medicinal data were collected.
RESULTS: Results from multivariate analysis showed that only the HLA-B*58:01 and female sex were identified as risk factors of allopurinol-induced SCARs in this Thai population. Patients who carried the HLA-B*58:01 allele were at a higher risk of allopurinol-induced DRESS [odds ratio (OR)=149.2, 95% confidence interval (CI)=24.0-∞, P<1.00×10]. Similar results were observed in allopurinol-induced SJS/TEN (OR=175.0, 95% CI=44.3-690.9, P=1.69×10). The risk of allopurinol-induced SCARs in women was higher than that in men (OR=4.6, 95% CI=1.4-15.6, P=1.44×10). The overall mortality rate of allopurinol-induced SCARs was 11.39% and a higher mortality rate was observed in elderly women.
CONCLUSION: Among the risk factors identified, the HLA-B*58:01 allele had the greatest impact on the development of both phenotypes of allopurinol-induced SCARs in this studied Thai population. In case HLA-B*58:01 genotyping cannot be accessed, close monitoring of allopurinol usage, especially in elderly women with impaired renal function, is necessary to reduce the mortality rate of these life-threatening SCARs.

Matched MeSH terms: Skin Diseases/chemically induced*
Safety and efficacy of fixed-dose 10 mg daily isotretinoin treatment for acne vulgaris in Malaysia

Yap FB

J Cosmet Dermatol, 2017 Sep;16(3):348-352.
PMID: 27539948 DOI: 10.1111/jocd.12268

INTRODUCTION: Low-dose isotretinoin is used to reduce side effects albeit higher relapse. This study aimed to determine the efficacy and safety of fixed-dose 10 mg daily isotretinoin for the treatment of acne.
METHODS: This prospective study was performed between 2011 and 2015. All 150 patients were given 10 mg daily isotretinoin until a cumulative dose of 90-110 mg/kg.
RESULTS: The mean age was 26.6 years with 64.7% moderate acne, 29.3% severe, and 6% very severe. The mean cumulative dose was 98.8 ± 6.05 mg/kg. All 150 patients had total clearance with a mean time to clearance of 24.0 weeks. Patients with severe/very severe acne had higher cumulative dosage (102.1 vs. 97.0, P

Matched MeSH terms: Skin Diseases/chemically induced
Minimization of Local and Systemic Adverse Effects of Topical Glucocorticoids by Nanoencapsulation: In Vivo Safety of Hydrocortisone-Hydroxytyrosol Loaded Chitosan Nanoparticles

Siddique MI, Katas H, Amin MCIM, Ng SF, Zulfakar MH, Buang F, et al.

J Pharm Sci, 2015 Dec;104(12):4276-4286.
PMID: 26447747 DOI: 10.1002/jps.24666

Hydrocortisone (HC) is a topical glucocorticoid for the treatment of atopic dermatitis (AD); the local as well as systemic side effects limit its use. Hydroxytyrosol (HT) is a polyphenol present in olive oil that has strong antimicrobial and antioxidant activities. HC-HT coloaded chitosan nanoparticles (HC-HT CSNPs) were therefore developed to improve the efficacy against AD. In this study, HC-HT CSNPs of 235 ± 9 nm in size and with zeta potential +39.2 ± 1.6 mV were incorporated into aqueous cream (vehicle) and investigated for acute dermal toxicity, dermal irritation, and repeated dose toxicity using albino Wistar rats. HC-HT CSNPs exhibited LD50 > 125 mg/body surface area of active, which is 100-fold higher than the normal human dose of HC. Compared with the commercial formulation, 0.5 g of HC-HT CSNPs did not cause skin irritation, as measured by Tewameter®, Mexameter®, and as observed visually. Moreover, no-observed-adverse-effect level was observed with respect to body weight, organ weight, feed consumption, blood hematological and biochemical, urinalysis, and histopathological parameters at a dose of 1000 mg/body surface area per day of HC-HT CSNPs for 28 days. This in vivo study demonstrated that nanoencapsulation significantly reduced the toxic effects of HC and this should allow further clinical investigations.

Matched MeSH terms: Skin Diseases/chemically induced