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1.
J Eur Acad Dermatol Venereol ; 35(3): 712-720, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32896010

RESUMO

BACKGROUND: There is increasing use of anti-osteoporotic agents (AOA) worldwide for prevention or management of patients with osteoporosis. However, there have been reports of severe cutaneous adverse reactions (SCAR) induced by AOA. A recent study showed weak association between HLA and strontium ranelate (SR)-SCAR. OBJECTIVE: To characterize patients with AOA-SCAR and investigate the HLA association and utility of in vitro diagnostic methods. METHODS: We enrolled 16 cases with AOA-cutaneous adverse drug reactions (cADR), including SCAR (n = 10: 8 with Stevens-Johnson syndrome [SJS] and 2 with drug rash with eosinophilia and systemic symptoms [DRESS]) and maculopapular exanthema (MPE) (n = 6) from Taiwan and Hong Kong. We analysed the clinical characteristics, outcomes, HLA alleles and in vitro testing of AOA-SCAR, and tolerability to alternative drugs. We further performed literature review and meta-analysis on the HLA association of AOA-SCAR. RESULTS: Our data showed strontium ranelate is the most common causality of AOA-SCAR in Asian populations. There was no cross-hypersensitivity of SR-SCAR with other AOA. HLA genotyping showed that SR-SJS was most significantly associated with HLA-A*33:03 (Pc = 5.17 × 10-3 , OR: 25.97, 95% CI: 3.08-219.33). Meta-analysis showed that HLA-A*33:03 was associated with SR-SJS (P = 5.01 × 10-5 ; sensitivity: 85.7%) in Asians. The sensitivity of lymphocyte activation test (LAT) for identifying the culprit drug of SR-SJS was 83.3%. CONCLUSIONS: Strontium ranelate is identified as the most notorious AOA associated with SCAR. The HLA-A*33:03 genetic allele and LAT testing may add benefits to the diagnosis of SR-SCAR in patients whose reaction developed while taking multiple drugs.


Assuntos
Síndrome de Stevens-Johnson , Alelos , Anticonvulsivantes , Povo Asiático , Antígenos HLA-B/genética , Hong Kong , Humanos , Taiwan
2.
Br J Dermatol ; 178(1): 124-131, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28815560

RESUMO

BACKGROUND: Indigo naturalis and its refined formulation, Lindioil, are effective in treating psoriatic symptoms topically. Indirubin is the active ingredient in indigo naturalis. OBJECTIVES: To determine the efficacy and safety of different concentrations of indirubin in Lindioil ointment for treating psoriasis. METHODS: In this randomized, double-blind trial, adult patients presenting with chronic plaque psoriasis for > 1 year and with < 20% of the body surface area (BSA) affected were randomized to apply Lindioil ointment containing 200, 100, 50 or 10 µg g-1 of indirubin twice daily for 8 weeks followed by an additional 12-week safety/extension period. The primary end point was the mean percentage change in Psoriasis Area and Severity Index (PASI) score along with the proportion of participants achieving 75% and 90% reductions in PASI scores (PASI 75 and PASI 90, respectively) from baseline to week 8. RESULTS: The results from week 8 revealed that the 200 µg g-1 group had the greatest reduction in PASI score [69·2%, 95% confidence interval (CI) 55·5-82·8], followed by the 100 µg g-1 group (63·1%, 95% CI 52·8-73·5), the 10 µg g-1 group (53·4%, 95% CI 42·8-64·0) and the 50 µg g-1 group (50·3%, 95% CI 37·4-63·2), with a between-group comparison of P = 0·0445. The group with the highest proportion of the patients achieving PASI 75 (57%, P = 0·0474) and PASI 90 (30%, P = 0·0098) was the 200 µg g-1 group. No severe treatment-related adverse events were reported during the 20-week evaluation. CONCLUSIONS: An amount of 200 µg g-1 of indirubin in Lindioil ointment is the most effective concentration studied so far for treating psoriasis topically, and is safe.


Assuntos
Fármacos Dermatológicos/administração & dosagem , Medicamentos de Ervas Chinesas/administração & dosagem , Psoríase/tratamento farmacológico , Adulto , Fármacos Dermatológicos/efeitos adversos , Fármacos Dermatológicos/análise , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Medicamentos de Ervas Chinesas/química , Feminino , Humanos , Indóis/administração & dosagem , Indóis/efeitos adversos , Indóis/análise , Masculino , Pomadas , Resultado do Tratamento
3.
Br J Dermatol ; 170(4): 866-73, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24329105

RESUMO

BACKGROUND: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe cutaneous adverse drug reaction. However, its histopathological features have not been well defined. OBJECTIVES: To identify the clinicohistopathological findings of DRESS, and analyse the cutaneous histopathological changes observed in DRESS compared with those observed in maculopapular exanthema (MPE). METHODS: In a retrospective study, conducted at Chang Gung Memorial Hospital (Taiwan) between 2001 and 2011, we compared the clinicohistopathological features of 32 patients with probable/definite DRESS (defined by the RegiSCAR scoring system) with those of 17 patients with MPE. RESULTS: The major pathological changes observed in patients with DRESS included dyskeratosis (97%), epidermal spongiosis (78%), interface vacuolization (91%), perivascular lymphocytic infiltration (97%) and eosinophilic infiltration (72%). Many pathological features were common to both MPE and DRESS. However, severe dyskeratosis, epidermal spongiosis and severe interface vacuolization were significantly more prominent in cases of DRESS (P < 0·05). The presence of severe dyskeratosis was significantly associated with the clinical severity of renal impairment (P = 0·01). CONCLUSIONS: The severe dyskeratosis detected in patients with DRESS may correlate with a greater extent of systemic involvement compared with that noted in MPE. However, the histopathological changes associated with DRESS are not entirely specific.


Assuntos
Síndrome de Hipersensibilidade a Medicamentos/patologia , Pele/patologia , Biópsia , Diagnóstico Diferencial , Humanos , Ceratose/etiologia , Ceratose/patologia , Nefropatias/etiologia , Hepatopatias/etiologia , Estudos Retrospectivos
4.
J Eur Acad Dermatol Venereol ; 27(3): 356-64, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22211830

RESUMO

BACKGROUND: The usefulness of the drug patch testing for Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) is still controversial. Recent studies have shown that HLA-B*1502 is strongly associated with CBZ-SJS/TEN in Chinese and Southeast Asian populations. OBJECTIVE: To evaluate the usefulness of patch tests for patients with carbamazepine (CBZ)-induced SJS, TEN and drug reaction with eosinophilia and systemic symptoms (DRESS) and the cross-reactivity in patch tests among the aromatic antiepileptic drugs. METHODS: We measure the frequency of positive patch test reactions and cross-sensitivity to structure-related aromatic anti-epileptic drugs (AEDs) for patients after SJS/TEN or DRESS episodes caused by CBZ. CBZ and other structure-related AEDs used for patch testing were prepared in 10% and 30% petrolatum. Secondary measures included the association of HLA-B*1502 genotype and frequency of possible side effects from the patch tests. RESULTS: Positive patch test reactions to 30% CBZ in the CBZ-SJS/TEN were 62.5% (10/16), and 70% (7/10) in the CBZ-DRESS. None of the 10 healthy controls displayed a positive reaction to tested agents. Cross-sensitivity to other aromatic AEDs was observed in both the CBZ-SJS/TEN and the CBZ-DRESS. Only the HLA-B*1502 genotype was present and strongly associated with the CBZ-SJS/TEN, but not with the CBZ-DRESS. CONCLUSION: Drug patch testing is a safe and useful method for the identification of CBZ as the culprit drug of SJS/TEN as well as DRESS. Testing of chemically or pharmacologically related AEDs may provide information on cross-reactivity for these patients.


Assuntos
Carbamazepina/efeitos adversos , Testes do Emplastro , Pele/efeitos dos fármacos , Estudos de Casos e Controles , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos
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