Humans ; Dapsone/adverse effects* ; Drug Hypersensitivity/etiology* ; Hypersensitivity ; Syndrome

Stevens-Johnson syndrome (SJS), also known as the multifactorial erythematous drug eruption, is a class of adverse reactions of the skin and mucous membranes primarily caused by drug allergy often involving the oral cavity, eyes, and external genital mucosa, generally accompanied by fever, and can be life-threatening in severe cases. In February 2022, the Department of Stomatology, the First Affiliated Hospital of Zhengzhou University admitted a patient with huge inflammatory hyperplasia of bilateral lingual margins secondary to SJS. Upon admission, no other obvious symptoms were observed except for tongue hyperplasia. The patient suffered from a severe adverse drug reaction caused by acetaminophen 2 months ago and was complicated by liver dysfunction and pulmonary infection. After 1 month of treatment and rehabilitation, he developed a secondary tongue mass and was subsequently admitted to Dept. of Oral and Maxillofacial Surgery Ward 2, the First Affiliated Hospital of Zhengzhou University. After completing the examination, the tongue mass was surgically removed. After a follow-up of 11 months, the patient's condition was satisfactory and no temporary discomfort was observed. The case of tongue mass secondary to SJS is extremely rare. If a stomatologist encounters a similar case, we should carefully inquire about the drug allergy history and recent medication history, and be alert to whether or not they had adverse drug reactions recently.
Male ; Humans ; Stevens-Johnson Syndrome/drug therapy* ; Hyperplasia/pathology* ; Skin ; Drug Hypersensitivity/pathology* ; Tongue

Summary We describe nine cases of anti-tuberculosis DRESS (drug reaction with eosinophilia and systemic symptoms) syndrome, a potentially serious complication of treatment that led to interruption of treatment, systemic corticosteroid usage and the resumption of treatment with different regimens. All patients had skin rash, six out of nine patients with hepatitis, two out of nine patients had acute kidney injury, five out of nine patients died. All-cause mortality is high in our cohort.
Drug Hypersensitivity Syndrome

drug eruptions include drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). One class of medications that has been highly associated with such drug eruptions is antiepileptic drugs (AEDs). We attempt to investigate drug eruptions associated with AEDs as a class, as well as with individual AEDs, in Korea.METHODS: We used the Korea Institute of Drug Safety and Risk Management - Korea Adverse Event Reporting System (KIDS-KAERS) database, a nationwide database of adverse events reports, between January 2008 and December 2017 to investigate the reporting count of all drug eruptions and calculated the ratio of DRESS/SJS/TEN reports for each AED.RESULTS: Among a total of 2,942 reports, most were of rash/urticaria (2,702, 91.8%), followed by those of DRESS (109, 3.7%), SJS (106, 3.6%), and TEN (25, 0.85%). The common causative AEDs were lamotrigine (699, 23.8%), valproic acid (677, 23%), carbamazepine (512, 17.4%), oxcarbazepine (320, 10.9%), levetiracetam (181, 6.2%), and phenytoin (158, 5.4%). In limited to severe drug eruptions (DRESS, SJS, and TEN; total 241 reports), the causative AEDs were carbamazepine (117, 48.8%), lamotrigine (57, 23.8%), valproic acid (20, 8.3%), phenytoin (15, 6.3%), and oxcarbazepine (10, 4.2%). When comparing aromatic AED with non-aromatic AED, aromatic AEDs were more likely to be associated with severe drug eruption (aromatic AEDs: 204/1,793 versus non-aromatic AEDs: 37/1,149; OR, 3.86; 95% CI, 2.7–5.5). Death was reported in 7 cases; DRESS was the most commonly reported adverse event (n = 5), and lamotrigine was the most common causative AED (n = 5).CONCLUSION: Although most cutaneous drug eruptions in this study were rash or urticaria, approximately 8% of reports were of severe or life-threatening adverse drug reactions, such as SJS, TEN, or DRESS. When hypersensitivity skin reactions occurred, aromatic AEDs were associated with 4 fold the risk of SJS/TEN/DRESS compared with non-aromatic AEDs. Our findings further emphasize that high risk AEDs should be prescribed under careful monitoring, and early detection and prompt interventions are needed to prevent severe complications.]]>
Anticonvulsants ; Carbamazepine ; Drug Eruptions ; Drug Hypersensitivity Syndrome ; Drug-Related Side Effects and Adverse Reactions ; Exanthema ; Hypersensitivity ; Korea ; Pharmacovigilance ; Phenytoin ; Risk Management ; Skin ; Stevens-Johnson Syndrome ; Urticaria ; Valproic Acid

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome and toxic epidermal necrolysis (TEN) are severe cutaneous adverse reactions. Although viral reactivation is associated with DRESS syndrome, its role in TEN remains unclear. An 80-year-old woman visited our hospital because of fever and skin eruption. DRESS syndrome was diagnosed and was thought to caused by the use of the drug allopurinol. She was treated by discontinuation of the drug and administration of systemic steroids. She recovered from DRESS syndrome and was discharged from the hospital with tapering doses of steroids prescribed. One week after discharge, she visited our hospital again as the skin rash recurred and oral pain as well as oral and ocular mucosal lesions developed. In addition to the skin rash, blisters and Nikolsky's sign that were different from the skin lesions present in the previous DRESS syndrome were observed. Unlike those in DRESS syndrome, the viral serological test results were positive for anti-cytomegalovirus (CMV) IgM and CMV polymerase chain reaction. Therefore, it was thought that TEN was due to reactivation of CMV and she was treated this with ganciclovir and intravenous immunoglobulin. Here, we report a case of TEN caused by viral reactivation after DRESS syndrome developed after use of allopurinol which recovered after steroid treatment.
Aged, 80 and over ; Allopurinol ; Blister ; Cytomegalovirus Infections ; Cytomegalovirus ; Drug Hypersensitivity Syndrome ; Eosinophilia ; Exanthema ; Female ; Fever ; Ganciclovir ; Humans ; Immunoglobulin M ; Immunoglobulins ; Polymerase Chain Reaction ; Serologic Tests ; Skin ; Steroids ; Stevens-Johnson Syndrome

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe cutaneous adverse reaction involving various internal organs. Flare-ups after recovery from the initial presentation of DRESS are caused by relapse of drug-induced T-cell-mediated reactions. However, the specific underlying mechanism is unclear. Here, we report a case of a 60-year-old man with allopurinol-induced DRESS who suffered recurrent episodes of generalized rash with eosinophilia, which mimicked immune reconstitution inflammatory syndrome. Analysis of immunological profiles revealed that the percentages of T lymphocytes and regulatory T cells in the patient with DRESS were higher than those in healthy controls. In addition, there was a notable change in the subtype of monocytes in the patient with DRESS; the percentage of nonclassical monocytes increased, whereas that of classical monocytes decreased. Upon viral infection, nonclassical monocytes exhibited strong pro-inflammatory properties that skewed the immune response toward a Th2 profile, which was associated with persistent flare-ups of DRESS. Taken together, the results increase our understanding of the pathogenesis of DRESS as they suggest that expansion of nonclassical monocytes and Th2 cells drives disease pathogenesis.
Allopurinol ; Drug Hypersensitivity Syndrome ; Eosinophilia ; Exanthema ; Herpesviridae ; Humans ; Immune Reconstitution Inflammatory Syndrome ; Middle Aged ; Monocytes ; Recurrence ; T-Lymphocytes ; T-Lymphocytes, Regulatory ; Th2 Cells

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.
Allopurinol ; Anti-Bacterial Agents ; Anticonvulsants ; Carbamazepine ; Cause of Death ; Cicatrix ; Drug Hypersensitivity Syndrome ; Drug-Related Side Effects and Adverse Reactions ; Epidemiology ; Global Health ; Korea ; Pharmacovigilance ; Stevens-Johnson Syndrome

BACKGROUND/AIMS: There are only a few reports on the direct costs of severe cutaneous adverse reactions (SCARs), including drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), despite the tremendous negative impact these reactions can have on patients. We estimated the direct costs of treating SCARs. METHODS: Patients admitted to a tertiary teaching hospital for the treatment of SCARs from January 1, 2005 to December 31, 2010 were included. Patients who had experienced SCARs during their admission for other medical conditions were excluded. The direct costs of hospitalization and outpatient department visits were collected. Inpatient and outpatient care costs were calculated, and factors affecting inpatient care costs were analyzed. RESULTS: The total healthcare cost for the management of 73 SCAR patients (36 with DRESS, 21 with SJS, and 16 with TEN) was 752,067 US dollars (USD). Most of the costs were spent on inpatient care (703,832 USD). The median inpatient care cost per person was 3,720 (range, 1,133 to 107,490) USD for DRESS, 4,457 (range, 1,224 to 21,428) USD for SJS, and 8,061 (range, 1,127 to 52,220) USD for TEN. Longer hospitalization significantly increased the inpatient care costs of the patients with DRESS (by 428 USD [range, 395 to 461] per day). Longer hospitalization and death significantly increased the inpatient care costs of the patients with SJS/TEN (179 USD [range, 148 to 210] per day and an additional 14,425 USD [range, 9,513 to 19,337] for the deceased). CONCLUSIONS: The management of SCARs required considerable direct medical costs. SCARs are not only a health problem but also a significant financial burden for the affected individuals.
Ambulatory Care ; Cicatrix ; Drug Hypersensitivity Syndrome ; Health Care Costs ; Hospitalization ; Hospitals, Teaching ; Humans ; Inpatients ; Korea* ; Outpatients ; Stevens-Johnson Syndrome ; Tertiary Care Centers*

PURPOSE: Although there have been reported cases of drug reactions with eosinophilia and systemic symptoms (DRESS) syndrome caused by antituberculosis drugs, there has been no research to examine its prevalence. This study assessed the prevalence and clinical characteristics of DRESS syndrome caused by antituberculosis drugs. METHODS: The electronic medical records of a cohort consisting of adult patients diagnosed with tuberculosis between July 2006 and June 2010 were reviewed and retrospectively inspected. We searched the surveillance system for adverse drug reactions and the electronic medical records to identify patients who reported severe cutaneous adverse reactions to antituberculosis drugs. These patients were then re-assessed using a European Registry of Severe Cutaneous Adverse Reactions to Drugs and Collection of Biological Samples (RegiSCAR) scoring system. Clinical characteristics, including the symptoms and latency of DRESS syndrome, the therapeutic dosage and period of steroids, and the final duration of tuberculosis therapy, were examined. RESULTS: Of the 1,253 adult patients with tuberculosis receiving antituberculosis drugs, 15 were identified as potential cases of DRESS syndrome (prevalence of 1.2%). Ethambutol was the most frequently used drug (53.5%), followed by rifampicin (26.7%), pyrazinamide (20.0%), streptomycin (13.3%), and isoniazid (6.7%). The median latency after day 1 of antituberculosis medication was 42 days. The median daily dose of steroids, expressed in prednisone-equivalent units, was 33-mg/day, and the median dosing period was 14 days. The duration of tuberculosis treatment was 76 days longer than the standard treatment period of 180 days. There was a significant difference in the peak eosinophil counts of DRESS syndrome patients according to RegiSCAR scores. Moreover, there was a significant quantitative correlation between the RegiSCAR score and peak eosinophil count. A negative correlation was also found between the RegiSCAR score and latency. CONCLUSIONS: This study confirmed the prevalence of DRESS syndrome in a cohort of adult patients with tuberculosis.
Adult ; Cohort Studies* ; Drug Hypersensitivity Syndrome ; Drug-Related Side Effects and Adverse Reactions ; Electronic Health Records ; Eosinophilia* ; Eosinophils ; Ethambutol ; Humans ; Isoniazid ; Prevalence* ; Pyrazinamide ; Retrospective Studies* ; Rifampin ; Steroids ; Streptomycin ; Tuberculosis

PURPOSE: Although severe cutaneous adverse drug reactions (SCARs) are rare, they are associated with high morbidity and mortality, and thus early diagnosis and treatment are critical for improving prognoses. However, few studies have reported the characteristics of SCARs in children. Thus, we aimed to evaluate the clinical characteristics, current management and prognosis of pediatric SCARs. METHODS: We analyzed pediatric data in the Korean SCARs registry, which was built retrospectively in 2016 with SCAR cases treated in 34 tertiary referral university hospitals during 2010–2015. Using these cases, we descriptively analyzed detailed data regarding etiology, clinical and laboratory features, treatment strategies, and prognosis. RESULTS: Forty-seven pediatric SCAR cases from 15 tertiary referral hospitals were included. The median patient age was 10 (interquartile range, 3-15.5) years and 68.1% (n = 32) were males. The culprit drug was identified in 95.7% (n = 45) of the patients; antibiotics (44.7%) and antiepileptic drugs (19.1%) were the most common and second most common culprits, respectively. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) cases presented with the largest area of skin involvement without permanent sequelae. Stevens-Johnson syndrome (SJS) cases involved relatively small areas of skin but serious sequelae in two children. Of 4 patients with toxic epidermal necrolysis (TEN), 1 died. Of all patients assessed, 36 (76.6%) received systemic steroids and 21 (44.7%) received intravenous immunoglobulin (IVIG). Thirteen (27.7%) received both systemic steroids and IVIG. Cyclosporine was administered to only 1 patient along with a systemic steroid. CONCLUSIONS: In patients with pediatric SCARs, including those with DRESS, SJS and TEN, clinical presentations were variable. Thus, there was no clear continuous disease spectrum. Although the mortality rate was low (2.1%), clinical suspicion may be the best tool for proactive SCAR management.
Anti-Bacterial Agents ; Anticonvulsants ; Child ; Cicatrix ; Cyclosporine ; Drug Eruptions ; Drug Hypersensitivity Syndrome ; Drug-Related Side Effects and Adverse Reactions ; Early Diagnosis ; Hospitals, University ; Humans ; Immunoglobulins ; Immunoglobulins, Intravenous ; Korea ; Male ; Mortality ; Prognosis ; Referral and Consultation ; Retrospective Studies ; Skin ; Steroids ; Stevens-Johnson Syndrome ; Tertiary Care Centers