Toxic epidermal necrolysis (TEN) is a rare, life-threatening dermatological emergency characterized by extensive epidermal necrosis and detachment, along with significant mucous membrane erosions and systemic symptoms. While conventional medications such as sulfonamides and anticonvulsants are known triggers, recent reports suggest that herbal medications can also induce TEN. This case report highlights the development of TEN in a patient with invasive cervical cancer following the use of an herbal supplement.

A 48-year-old Filipino woman with newly diagnosed invasive cervical cancer developed TEN after taking an herbal supplement containing 23 botanical extracts. Despite discontinuing the supplement, her condition rapidly worsened, with vesicles and bullae progressing to epidermal detachment over 90% of her body surface area. A histopathological examination confirmed the diagnosis of TEN. The patient was treated with systemic corticosteroids and supportive care, achieving full recovery within 14 days.

This case underscores the potential risks associated with herbal medications, particularly in vulnerable patients such as those with cancer. Although conventional pharmaceuticals are the primary culprits for TEN, this report highlights the need for greater awareness of herbal medicine-induced adverse drug reactions. Underreporting of such events, due to lack of awareness among patients and healthcare providers, further complicates the issue. This case emphasizes the need for strengthened regulatory policies and enhanced education to safeguard public health amidst the increasing use of herbal remedies worldwide.

Acute generalized exanthematous pustulosis (AGEP) and Stevens-Johnson Syndrome (SJS) are uncommon, severe cutaneous drug eruptions with distinct clinical and histopathological features. AGEP-SJS overlap is a rare and complicated cutaneous drug eruption. Neutrophilia, leukocytosis, and elevated liver enzymes can be seen in these patients. Currently, there are no available dermoscopic studies on AGEP overlapping SJS. The pathophysiology of overlapping drug reaction are mediated by T cells and delayed-type hypersensitivity. Management includes removal of offending drug and giving supportive measures like pain management, moist dressing and fluids.

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

Child ; Family ; Humans ; Necrosis ; Skin Diseases ; Stevens-Johnson Syndrome/etiology*

Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a rare adverse cutaneous reaction with a low incidence and high mortality. Despite posing a serious threat to patients' health and lives, there is no high-quality evidence for a standard treatment regimen. Here we report the case of a 62-year-old man with stage IV pancreatic cancer who experienced immunotherapy-induced SJS/TEN. After consensus-based regular treatments at a local hospital, his symptoms became worse. Thus, he consented to receive Chinese herbal medicine (CHM) therapy. The affected parts of the patient were treated with the CHM Pi-Yan-Ning which was applied externally for 20 min twice a day. After 7 days of treatment, the dead skin began peeling away from the former lesions that had covered his hands, feet, and lips, indicating that skin had regenerated. After 12 days of treatment, the patient's skin was completely recovered. In this case, SJS/TEN was successfully treated with Pi-Yan-Ning, suggesting that there might be tremendous potential for the use of Pi-Yan-Ning in the treatment of severe skin reactions to drug treatments. Further basic investigations and clinical trials to explore the mechanism and efficacy are needed.
Drugs, Chinese Herbal/therapeutic use* ; Humans ; Immunologic Factors ; Incidence ; Male ; Middle Aged ; Skin ; Stevens-Johnson Syndrome/etiology*

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but severe diseases. This study aimed to validate the predictive ability of risk models in patients with SJS/TEN and propose possible refinement in China. Patients in the Department of Dermatology of Huashan Hospital from January 2008 to January 2019 were included. Results showed that the severity-of-illness score for TEN (SCORTEN) had a good discrimination (area under the receiver operating characteristic curve (AUC), 0.78), and it was superior to auxiliary score (AS) and ABCD-10, which indicates age, bicarbonate level, cancer, dialysis, and 10% involved body surface area (AUC, 0.69 and 0.68, respectively). The calibration of SCORTEN (Hosmer-Lemeshow goodness-of-fit test, P = 0.69) was also better than that of AS (P = 0.25) and ABCD-10 (P = 0.55). SCORTEN and ABCD-10 were similar (Brier score (BS), 0.04 and 0.04) in terms of accuracy of predictions. In addition, the imaging appearance of pulmonary consolidation on computed tomography was associated with high mortality. Refined models were formed using the variables and this imaging appearance. The refined AS and ABCD-10 models were similar in discrimination compared with the original SCORTEN (0.74 vs. 0.78, P = 0.23; 0.74 vs. 0.78, P = 0.30, respectively). Therefore, SCORTEN showed good discrimination performance, calibration, and accuracy, and refined AS or ABCD-10 model may be an option when SCORTEN variables are not available.
Cohort Studies ; Humans ; Retrospective Studies ; Severity of Illness Index ; Stevens-Johnson Syndrome/diagnostic imaging* ; Tomography

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

Antiepileptic drugs (AEDs) can induce severe cutaneous adverse reactions (SCARs) such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome. We performed HLA genotyping and lymphocyte activation tests (LATs) for five AED-induced SCAR patients (three males and two females; aged 40–66 years old). Three patients were treated with carbamazepine (CBZ) for pain control, one was treated with phenytoin (PHT) for seizure prevention, and one was treated with valproic acid (VPA) for seizure prevention. One patient was diagnosed with CBZ-induced DRESS syndrome and the remaining patients were diagnosed with SJS. All patients recovered from SCARs after stopping suspicious drugs and supportive care. LATs were conducted to confirm the culprit drug responsible for inducing SCARs; and LAT results were positive for the suspected culprit drugs, in all except in one case. HLA-A,
Alleles ; Anticonvulsants ; Carbamazepine ; Cicatrix ; Drug Hypersensitivity Syndrome ; Female ; HLA-A Antigens ; Humans ; Long-Acting Thyroid Stimulator ; Lymphocyte Activation ; Lymphocytes ; Male ; Methods ; Phenytoin ; Seizures ; Stevens-Johnson Syndrome ; Valproic Acid

PURPOSE: Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) to antiepileptic drug (AED), are rare, but result in significant morbidity and mortality. We investigated the major culprit drugs, clinical characteristics, and clinical course and outcomes of AED-induced SCARs using a nationwide registry in Korea. METHODS: A total of 161 patients with AED-induced SCARs from 28 referral hospitals were analyzed. The causative AEDs, clinical characteristics, organ involvements, details of treatment, and outcomes were evaluated. We compared the clinical and laboratory parameters between SJS/TEN and DRESS according to the leading causative drugs. We further determined risk factors for prolonged hospitalization in AED-induced SCARs. RESULTS: Carbamazepine and lamotrigine were the most common culprit drugs causing SCARs. Valproic acid and levetiracetam also emerged as the major causative agents. The disease duration and hospital stay in carbamazepine-induced SJS/TEN were shorter than those in other AEDs (P< 0.05, respectively). In younger patients, lamotrigine caused higher incidences of DRESS than other drugs (P= 0.045). Carbamazepine, the most common culprit drug for SCARs, was associated with a favorable outcome related with prolonged hospitalization in SJS (odds ratio, 0.12; 95% confidence interval, 0.02-0.63, P= 0.12), and thrombocytopenia was found to be a risk factor for prolonged hospitalization in DRESS. CONCLUSION: This was the first large-scale epidemiological study of AED-induced SCARs in Korea. Valproic acid and levetiracetam were the significant emerging AEDs causing SCARs in addition to the well-known offending AEDs such as carbamazepine and lamotrigine. Carbamazepine was associated with reduced hospitalization, but thrombocytopenia was a risk factor for prolonged hospitalization. Our results suggest that the clinical characteristics and clinical courses of AED-induced SCARs might vary according to the individual AEDs.
Anticonvulsants ; Carbamazepine ; Cicatrix ; Drug Hypersensitivity Syndrome ; Epidemiologic Studies ; Hospitalization ; Humans ; Incidence ; Korea ; Length of Stay ; Mortality ; Referral and Consultation ; Risk Factors ; Stevens-Johnson Syndrome ; Thrombocytopenia ; Valproic Acid