Ya-Ching Chang

Hand‐foot skin reaction in patients treated with sorafenib: a clinicopathological study of cutaneous manifestations due to multitargeted kinase inhibitor therapy

Background  Hand‐foot skin reaction is a distinctive cutaneous side‐effect of antineoplastic kinase inhibitor‐targeted therapy. Severe hand‐foot skin reaction requires postponement of treatment or dose reduction. Histopathological studies of skin toxicity associated with kinase inhibitors are currently unavailable.

Clinicopathlogical features and prognosis of drug rash with eosinophilia and systemic symptoms : a study of 30 cases in Taiwan

Background  Drug rash with eosinophilia and systemic symptoms (DRESS), a group of non‐blistering severe cutaneous adverse drug reactions (SCADRs), is characterized by skin rash and multiorgan involvement. Details of this reaction have not been reported in the literature so far.

Clinical Assessment of Patients With Recalcitrant Psoriasis in a Randomized, Observer-Blind, Vehicle-Controlled Trial Using Indigo Naturalis

OBJECTIVE To evaluate the efficacy and safety of treatment with indigo naturalis in patients with recalcitrant plaque-type psoriasis. DESIGN Randomized, observer-blind, vehicle-controlled, intrapatient comparison study. SETTING Ambulatory department of a hospital. PARTICIPANTS Forty-two outpatients with chronic plaque psoriasis were enrolled in the study from May 1, 2004, to April 30, 2005. INTERVENTION The patients applied either indigo naturalis ointment or vehicle ointment topically to each of 2 bilaterally symmetrical psoriatic plaque lesions for 12 weeks (depending on the date of enrollment in the study). MAIN OUTCOME MEASURES The outcomes were assessed using the following criteria: the sum of erythema, scaling, and induration scores and the clearing percentage of the target plaque lesion assessed by 2 blinded observers. RESULTS Significant reductions in the sum of scaling, erythema, and induration scores (P < .001) (mean score, 6.3 after indigo naturalis treatment vs 12.8 in control subjects) and plaque area percentage (P < .001) (mean percentage, 38.5% after indigo naturalis treatment vs 90% in controls) were achieved with topical application of indigo naturalis ointment. Approximately 31 of 42 patients (74%) experienced clearance or near clearance of their psoriasis in the indigo ointment-treated lesion. CONCLUSION Topical indigo naturalis ointment was a novel, safe, and effective therapy for plaque-type psoriasis.

The Efficacy and Safety of Topically Applied Indigo Naturalis Ointment in Patients with Plaque-Type Psoriasis

Background: It has been reported in the Chinese literature that indigo naturalis exhibits potential antipsoriatic effects in systemic therapy. Objective: To evaluate the efficacy and safety of topically applied indigo naturalis on treating plaque-type psoriasis and to analyze the histological change in skin tissues. Methods: Fourteen patients with chronic plaque psoriasis were enrolled. The patients were topically applied with either indigo naturalis ointment or vehicle ointment on contralateral skin lesions daily for 8 weeks. Efficacy was evaluated on the basis of the clinical scores, including induration, scaling, erythema and clearing percentage. At the end of treatment, skin punch biopsies were taken and prepared for the immunohistochemical analysis. Results: A significant reduction in clinical scores was achieved with topically applied indigo naturalis ointment. Analysis of biopsies showed a marked improvement of skin histology. The expressions of proliferating marker Ki-67 and inflammatory marker CD3 were decreased, but the differentiation marker such as filaggrin was increased in the epidermis after indigo naturalis ointment treatment. Conclusions: The results suggest that topical application of indigo naturalis ointment may be a novel, safe and effective therapy for psoriasis that is mediated, at least in part, by modulating the proliferation and differentiation of keratinocytes in epidermis, as well as by inhibiting the infiltration of T lymphocytes and therefore the subsequent inflammatory reactions in psoriatic lesions.

A patch testing and cross‐sensitivity study of carbamazepine‐induced severe cutaneous adverse drug reactions

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.

Relationships between obesity and the clinical severity of psoriasis in Taiwan

Background  Obesity has been found to be associated with an increased risk of psoriasis in general population. However, studies addressing the relationship between obesity and clinical severity of psoriasis are still scarce, especially in Asian people.

Risk and association of HLA with oxcarbazepine-induced cutaneous adverse reactions in Asians

Objective: To investigate the risk and genetic association of oxcarbazepine-induced cutaneous adverse reactions (OXC-cADRs), including Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), in Asian populations (Chinese and Thai). Methods: We prospectively enrolled patients with OXC-cADRs in Taiwan and Thailand from 2006 to 2014, and analyzed the clinical course, latent period, drug dosage, organ involvement, complications, and mortality. We also investigated the carrier rate of HLA-B*15:02 and HLA-A*31:01 of patients with OXC-cADRs and compared to OXC-tolerant controls. The incidence of OXC-SJS/TEN was compared with carbamazepine (CBZ)–induced SJS/TEN according to the nationwide population dataset from the Taiwan National Health Insurance Research Database. Results: We enrolled 50 patients with OXC-cADRs, including 20 OXC-SJS/TEN and 6  drug reaction with eosinophilia and systemic symptoms, of Chinese patients from Taiwan and Thai patients from Thailand. OXC-cADRs presented with less clinical severity including limited skin detachment (all ≦5%) and no mortality. There was a significant association between HLA-B*15:02 and OXC-SJS (p = 1.87 × 10−10; odds ratio 27.90; 95% confidence interval [CI] 7.84–99.23) in Chinese and this significant association was also observed in Thai patients. The positive and negative predictive values of HLA-B*15:02 for OXC-SJS/TEN were 0.73% and 99.97%, respectively. HLA-A*31:01 was not associated with OXC-cADRs. The incidence and mortality of OXC-SJS/TEN was lower than CBZ-STS/TEN in new users (p = 0.003; relative risk 0.212; 95% CI 0.077–0.584). Conclusions: Our findings suggest that HLA-B*15:02 is significantly associated with OXC-SJS in Asian populations (Chinese and Thai). However, the severity and incidence of OXC-SJS/TEN are less than that of CBZ-SJS/TEN. The need for preemptive HLA-B*15:02 screening should be evaluated further.

Association between the insertion/deletion polymorphism of the angiotensin I-converting enzyme gene and risk for psoriasis in a Chinese population in Taiwan

Background  Genetic factors play an important role in susceptibility for psoriasis. The angiotensin I‐converting enzyme (ACE) is expressed by keratinocytes. Administration of ACE inhibitors may induce or exacerbate psoriasis in clinical practice. Thus, ACE gene variants may contribute to the genetic background of psoriasis.

Comparison of Refined and Crude Indigo Naturalis Ointment in Treating Psoriasis: Randomized, Observer-Blind, Controlled, Intrapatient Trial

individual cycles in secondary analyses. Cox proportional hazards regression models were used to estimate relative risks (RRs) and 95% CIs. Analyses were updated because the main exposure, outcome, and covariates were all time varying. We had multivariate models with or without smoking. Analyses were conducted using SAS software, version 9.2 (SAS Institute Inc). The study was approved by the institutional review board of Brigham and Women’s Hospital. Our receipt of each completed questionnaire implied participant’s informed consent of the present study.

Fatal Toxic Epidermal Necrolysis Associated With Cetuximab in a Patient With Colon Cancer

In August 2006, a 74-year-old man was admitted to our hospital for toxic epidermal necrolysis (TEN). He had been diagnosed with moderately differentiated adenocarcinoma of the proximal sigmoid colon, with hepatic metastases, in November 2004. He had received a regimen of bevacizimab 5 mg/kg, oxaliplatin 65 mg/m, leucovorin 200 mg/m, and fluorouracil 300 mg/m from November 2004 to October 2005. In March 2006, he received three cycles of irinotecan 125 mg/m, leucovorin 20 mg/m, and fluorouracil 500 mg/m treatment. There were no adverse reactions during the previous treatment course. Because of advanced hepatic metastases, he received additional cetuximab (250 mg/m) weekly, from May 30 to July 19, 2006. Progressive paronychia and acneiform papules on the four limbs developed after the eighth course (mid-July). These cutaneous reactions continued to progress, turning into large blisters with extensive epidermal shedding on the trunk; he was sent to our emergency department on July 31. On physical examination, there were generalized confluent purpuric maculopapular lesions with blisters and large epidermal detachment. Severe oral ulcers were also present. StevensJohnson syndrome was diagnosed through clinical morphology. However, this case rapidly progressed to toxic epidermal necrolysis the next day (more than 70% epidermal detachment of the total body surface; Fig 1). Analysis of blister cells collected from skin lesions revealed a predominance of CD8 cytotoxic T lymphocytes (83%) and natural killer cells (10%), which is in line with previous StevensJohnson syndrome/TEN studies. Serum antibodies for herpes simplex virus and Mycoplasma pneumoniae were all negative. Intravenous immunoglobulin 0.5 g/kg/d was prescribed for 4 days for his skin condition. Systemic antibiotics (imipenem and teicoplanin) were used for his complications of pneumonia (Staphylococcus aureus) and systemic fluconazole was also given for his cutaneous Candida albicans infection. However, acute renal and respiratory failure developed rapidly, and this patient died on August 13, 2006. Cetuximab is a recombinant human and mouse chimeric monoclonal antibody that competitively inhibits the epidermal growth factor receptor (EGFR). It was the first antibody targeting EGFR approved by the US Food and Drug Administration for cancer therapy. Cetuximab monotherapy, with or without irinotecan, is increasingly used for metastatic colorectal cancer. Several types of adverse cutaneous reactions (such as acneiform skin reactions and periungual inflammation) to EGFR inhibitors have been reported. However, there is no documented fatal toxic epidermal necrolysis. The most common etiology of TEN is medication. Mucocutaneous TEN lesions usually develop 2 to 8 weeks after starting the culprit drug. Cytotoxic T lymphocytes are sensitized during this period. Although this is the first report of antibody-drug–induced TEN, a delayed allergic reaction associated with monoclonal antibody drug has been reported. Moreover, the underlying mechanism of EGFR inhibitors, which can enhance inflammatory responses and decrease survival of epithelial cells, may also contribute to the development of toxic epidermal necrolysis. To the best of our knowledge, this is the first case report of fatal TEN associated with cetuximab and anticancer agents. This report is all the more important because of the increasing use of cetuximab in patients with colorectal cancer. Clinical physicians should be aware of these possible complications so that early interventions can be made.