Analysis of Individual Case Safety Reports of Severe Cutaneous Adverse Reactions in Korea

PURPOSE: Despite morbidities and fatalities, nationwide epidemiologic data for severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS), are not widely available. We aimed to investigate SCAR epidemiology over the last two decades in Korea. MATERIALS AND METHODS: We analyzed individual case safety reports (ICSRs) of SCARs in the Korea Adverse Event Reporting System from 1988 to 2013. Administered drugs, demographic profiles, and causality assessment according to the World Health Organization-Uppsala Monitoring Center system were analyzed. RESULTS: A total of 755 SCAR cases (508 SJS/TEN, 247 DRESS) were reported. The number of SCAR ICSRs has been increasing with increasing ICSRs for overall adverse drug events. Since 2010, the number of SCAR ICSRs has increased up to 100 cases/year. Allopurinol was the most common causative drug (SJS/TEN: 10.2%; DRESS: 11.3%; SCAR ICSRs: 10.6%), followed by carbamazepine (SJS/TEN: 8.7%; DRESS: 9.7%; SCAR ICSRs: 8.6%). Regarding drug groups, antiepileptics (19.5%) and antibiotics for systemic use (12.7%) were common causative drug groups. Twenty SCAR-related deaths were recorded. Antibacterials were the most common causes of deaths (8 cases), followed by antiepileptics (5 cases). The potential risk of SCARs was not specified in the drug information leaflet for 40.2% of drugs causing SJS/TEN and 82.5% causing DRESS syndrome in Korea. CONCLUSION: The number of SCAR ICSRs has increased rapidly with recent active pharmacovigilance programs in Korea. Allopurinol and antiepileptics are the most common individual and categorical causative agents, respectively.

Optimal methods to detect DRESS (drug reaction with eosinophilia and systemic symptoms) syndrome by electronic medical records

PURPOSE: Since drug reaction with eosinophilia and systemic symptom (DRESS) syndrome is very rare and difficult to diagnose, its exact epidemiology is still unknown. If screening tools based on laboratory results or electronic medical records are available, the occurrence of DRESS syndrome can be monitored in real time. METHODS: To screen cases with DRESS syndrome, all the results of both eosinophil and alanine transaminase (ALT) level from July 2014 to June 2015 were analyzed by 36 searching conditions for the signal detection of 7 definite DRESS cases among 199,924 patients during the study period. Those searching conditions were diverse combinations of different cutoff levels of eosinophil and ALT with or without nursing records presenting skin symptoms. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value were calculated for individual searching conditions. RESULTS: As cutoff levels of eosinophil and ALT for screening DRESS increased from 3% to 5% and 40 U/L to 300 U/L, respectively, the sensitivity decreased from 100% to 42.9% and the PPV increased from 0.06% to 13.0%. A combination of eosinophil >10% and ALT >300 U/L which had the highest PPV among 36 search conditions could detect DRESS syndrome by sensitivity 42.9% and PPV 13.0%. When nursing records for skin symptoms were added, PPV was augmented to 21.4%. CONCLUSION: A combination of eosinophil and ALT levels is a useful search condition for the screening of DRESS syndrome. Nursing records can provide an additional increment in PPV.

A case of oral desensitization for hypersensitivity to exogenous progesterone

Hypersensitivity reaction to progesterone is a rare pathologic condition which consists of autoimmune response to endogenous progesterone, known as autoimmune progesterone dermatitis, and hypersensitivity reaction to exogenous progestogen. We report the case of a 31-year-old woman with a history of whole body urticaria during exogenous progesterone supplementation for in vitro fertilization (IVF). She was admitted to the hospital for the diagnosis and management of progestogen hypersensitivity. An intradermal test with progesterone revealed positivity to 5 mg/mL of progesterone. For her next IVF, progesterone desensitization was performed in a method combining oral and intramuscular progesterone administration. After successfully achieving a target dose of 100 mg per day, the route of progesterone administration was converted to intravaginal tablet (90 mg twice a day) without any hypersensitivity reactions.

ERRATUM: Corrections of Figure 1 and Dose Information of Methylprednisolone: DRESS (drug reaction with eosinophilia and systemic symptom) syndrome caused by both first-line and second-line antitubercular medications: A case report with a brief literature

In this paper, some parts of Fig. 1 and dose information of methylprednisolone on page 113 were misprinted.

DRESS (drug reaction with eosinophilia and systemic symptom) syndrome caused by both first-line and second-line antitubercular medications: A case report with a brief literature review

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare but potentially fatal drug-induced systemic hypersensitivity response characterized by erythematous eruption, fever, leukocytosis with eosinophilia, and internal organ involvement. Antitubercular agents are potential causative agents for DRESS syndrome but difficult to verify as a culprit drug, since antitubercular agents are coadministered as a combination regimen. A 42-year-old female with endobronchial tuberculosis was diagnosed with DRESS syndrome after 4-week treatment of isoniazid, rifampicin, ethambutol, and pyrazinamide with prednisolone 50 mg. All the antitubercular agents were stopped and replaced with levofloxacin, cycloserine, p-aminosalicylic acid, and kanamycin. However, severe exacerbation of DRESS syndrome compelled the patient to discontinue the administration of the second-line antitubercular agents. Two months later, the patient underwent a patch test for all the antitubercular agents which had been used, and the results showed positivity to isoniazid and cycloserine. We report a rare case of DRESS syndrome that reacted to cycloserine as well as isoniazid. Development of coreactivity to other drugs should be differentiated with a flare-up reaction in the management of DRESS syndrome.

Polybrominated Diphenyl Ethers Orally Administration to Mice Were Tansferred to Offspring during Gestation and Lactation with Disruptions on the Immune System

BACKGROUND: The present study was undertaken to examine the immunological effects of pentabrominated diphenyl ether (penta-BDE) and decabrominated diphenyl ether (deca-BDE) on the immune system of the dams and the developmental immune system of the offsprings. METHODS: In this study, mated female C57BL/6J mice were orally administered penta-BDE, deca-BDE or corn oil for 5 weeks, from gestational day 6 to lactational day 21. RESULTS: The body weight of PND21 exposed to penta-BDE was significantly decreased relative to control mice, but that of post-natal day 63 (PND63) were recovered. Orally dosed dams with penta-BDE had significantly smaller absolute and relative spleen masses than control mice. Absolute and relative spleen and thymus masses of PND21 exposed to penta-BDE were significantly decreased over control. The exposure of dams and PND21 with penta-BDE reduced the number of splenocytes and thymocytes. As results of hematologic analysis, percentage WBC and percentage neutrophils increased in dams with deca-BDE. Splenic T cell proliferation in dams and PND21 exposed to penta-BDE was increased, and there were no significant difference in splenic B cell proliferation in all treatment groups. As results of flow cytometric analysis of splenocyte, percentage total T cell, Th cell and Tc cell in PND21 exposed to penta-BDE was slightly increased, and percentage macrophage in dams and PND21 exposed to deca-BDE was decreased. The ELISA results of antibody production show no significant difference in all treatment groups relative to controls. CONCLUSION: These results imply that PBDEs given to the dam were transferred to the offspring during gestation and lactation, and PBDEs transferred from the dam affect immune system of offspring.

Clinical Efficacy for 1% Zinc Pyrithione Shampoo for the Treatment of Dandruff / 대한피부과학회지

BACKGROUND: Dandruff is a common complaint, and is suffered by up to 50% of the population at some time. Malassezia yeasts, which comprise part of the normal skin flora, might be a critical factor in this disease, as they have been found in higher proportions in patients with seborrheic dermatitis or dandruff, its milder form. OBJECTIVE: The aim of this study was to evaluate the clinical efficacy of 4 weeks of treatment with 1% zinc pyrithione (ZP) shampoo. METHODS: A randomized, double-blind, 4-week treatment period was preceded by a 1-week run-in period. A total of 30 patients were enrolled in this study. Assessments included the patient's subjective score (PSS) and the investigator's assessment score (IAS), images of the affected scalp area, the severity of sebum production, and the erythema and moisturizing effect of the shampoo. RESULTS: 1% ZP shampoo significantly reduced the extent and severity of scaling, as measured by folliscope imaging on visit 2 (p=0.0391) and visit 3 (p=0.0381), as well as pruritus related to the disease as measured by the grading systems, PSS (p=0.0352) and IAS (p=0.0142). Additionally, the results of this study show that a treatment regimen with 1% ZP shampoo significantly reduced scalp sebum production as measured by a sebumeter. Erythema measured by the chromameter was not as meaningful. The corneometric values were slightly increased in the group treated with 1% ZP shampoo but not in the group treated with ZP-free shampoo. Side effects of the ZP shampoo were quite mild and tolerable, and were observed only in a small group of patients. CONCLUSION: 1% ZP shampoo appears to be both effective and well-tolerated when used for the treatment of dandruff.

Biodistribution of Adenovirus p53 Following Intraperitoneal Administration in Mice

Reproductive toxicology is relatively new to the field of gene therapy, and is a very important issue for the safety. An important safety concern of gene therapy products is the distribution of vector beyond target organs. This is particularly important if vector distributes to gonads, raising the possibility of inadvertent germ-line transmission. In addition, for indications such as prostate cancer and ovarian cancer, the proximity of the point of viral administration to organs of the reproductive system raises concerns regarding inadvertent germ-line transmission of genes carried by the virus. To evaluate the reproductive toxicity of in vivo E1-deleted replication-incompetent adenoviral vector encoding p53 or lacZ, we studied the biodistribution and potential germ-line transmission of the vector. Both male and female Balb/c mice were injected with 1x10(8) pfu of Ad-CMV-LacZ or Ad-CMV-p53. DNA and RNA extracted from major organs including gonadal tissues were analyzed for vector sequences and expression. The PCR analysis showed that there were detectable vector sequences in liver, kidney, spleen, seminal vesicle, epididymis, prostate, ovary, and uterus. The RT-PCR analysis showed that Ad-CMV-LacZ or Ad-CMV-p53 viral RNA were present in spleen, prostate and ovary. Vectoradministered female and male mice were mated and their offspring were evaluated for germ-line transmission of the adenoviral vector. The PCR analysis showed no evidence of germ-line transmission, although vector sequences were detected in DNA extracted from gonadal tissues. Together, we conclude that the risk of the inadvertent germ-line transmission of vector sequences following intraperitoneal injection of adenovirus is extremely low, although vector distributed to gonadal tissues.