Combination of vulgar pemphigus and toxic epidermal necrolysis: a case report

Toxic epidermal necrolysis (TEN) is a rare, life-threatening mucocutaneous condition, most commonly triggered by drugs, with particularly high mortality in elderly populations. The medications most frequently associated with TEN include antibiotics such as sulfamethoxazole-trimethoprim (sulfonamides), penicillins, cephalosporins, and quinolones (e.g., ciprofloxacin); anticonvulsants such as phenytoin, carbamazepine, and lamotrigine; nonsteroidal anti-inflammatory drugs (NSAIDs), especially oxicam derivatives (e.g., piroxicam), and, less commonly, ibuprofen; allopurinol; nevirapine; and other agents such as paracetamol, celecoxib, tyrosine kinase inhibitors, and immunobiological therapies like infliximab.We describe a 71-year-old, functionally dependent male who developed fever and progressive skin detachment after self-medicating with paracetamol and ibuprofen. Examination revealed widespread bullae and skin sloughing involving approximately 70% of his total body surface area (TBSA). Despite supportive measures, the patient rapidly deteriorated and died on the second day of hospitalization. TEN was assumed as the primary cause of death.The prognosis in TEN is strongly influenced by age, comorbidities, and the extent of skin involvement. Genetic predispositions, such as HLA-B15:02 (associated with carbamazepine-induced TEN, particularly in Southeast Asian populations), HLA-A31:01 (carbamazepine hypersensitivity in European, Japanese, and Latin American populations), and HLA-B*58:01 (allopurinol-induced TEN in Asian populations), are important risk factors that guide genetic screening recommendations before prescribing certain high-risk drugs.Supportive care remains the mainstay of treatment for TEN, focusing on meticulous wound care, fluid and electrolyte management, infection prevention, and pain control. However, the use of immunomodulatory therapies, such as corticosteroids, cyclosporine, and biologics, remains a subject of ongoing debate, with inconsistent evidence regarding their efficacy.Timely recognition of TEN and immediate cessation of the offending drug are paramount to improving patient outcomes and reducing mortality.This case highlights the potential role of ibuprofen, a commonly used over-the-counter NSAID, as a trigger for TEN, particularly in frail elderly individuals. Although ibuprofen is generally considered a low-risk medication, its capacity to induce severe cutaneous adverse reactions should not be underestimated. The prognosis in TEN is heavily influenced by factors such as advanced age, existing comorbidities, and the extent of skin involvement.Given the high fatality rates associated with TEN, especially in older adults, clinicians should maintain a high index of suspicion in patients presenting with acute mucocutaneous symptoms following recent drug exposure, including over-the-counter medications like ibuprofen, and emphasize the importance of public education on the dangers of unsupervised self-medication.

Toxic epidermal necrolysis and paraneoplastic pemphigus

Toxic epidermal necrolysis caused by etonogestrel implantation: A rare presentation

Toxic Epidermal Necrolysis vs Lupus Flare?

Toxic epidermal necrolysis in a mother and fetus

BackgroundSoluble CD200 (sCD200) is a novel immuno-effective molecule, which acts to regulate inflammatory and acquired immune responses. Recently, our study group showed that sCD200 was present in serum and blister fluid in a patient with bullous pemphigoid and a patient with toxic epidermal necrolysis. We therefore planned this study to evaluate the sCD200 levels of autoimmune and inflammatory skin disorder patients and to compare them with that of healthy controls.Maleral/MethodsOur study included 30 consecutive patients with psoriasis vulgaris, 15 with pemphigus vulgaris, and 15 healthy controls. Clinical examination and laboratory tests were performed on the same day. Psoriasis patients were also assessed with the Psoriasis Area and Severity Index (PASI) and pemphigus patients were assessed using the Pemphigus Disease Area Index (PDAI). Levels of sCD200 in the serum samples were quantified using ELISA kits.ResultsThe serum sCD200 level was observed to be statistically significantly higher in patients with psoriasis vulgaris (96.7±15.8) compared to patients with pemphigus vulgaris (76.2±14.6), (p<0.001) and healthy controls (26.8±7.0) (p<0.001). The serum sCD200 levels were observed to be statistically significantly higher in patients with pemphigus vulgaris compared with that in healthy controls (p<0.001). In addition, there was a statistically significant correlation between serum sCD200 levels and PDAI (r=0.987, p=0.001). Nevertheless, there was no statistically significant correlation between serum sCD200 levels and PASI (r=0.154, p=0.407).ConclusionssCD200 might play a role in immune response in the pathogenesis of autoimmune and inflammatory skin disorders. However, it remains to be fully elucidated how sCD200 can orchestrate inflammatory response in psoriasis and pemphigus.

Acrodermatitis enteropathica-like eruption

Toxic epidermal necrolysis (TEN) and Stevens-Johnson Syndrome (SJS) are drug-induced diseases with no well-established treatments. The application of corticosteroid therapy is controversial. Intravenous immunoglobulin (IVIG) therapy is emerging as a promising new method for the treatment of these two diseases. The efficacy of combination therapy of IVIG and corticosteroid in the treatment of TEN/SJS has seldom been reported. Sixty-five consecutive patients with either TEN or SJS, admitted over a 14-year period from January 1993 to October 2007, were treated with corticosteroid and analyzed retrospectively using SCORTEN, a severity-of-illness scoring system for TEN/SJS prognosis, to evaluate efficacy. For patients admitted after January 2001, additional therapy with a dose of 0.4 g/kg/day of IVIG for 5 days was applied. In the 45 patients with TEN treated without IVIG, 8.63 patients were expected to die based on the SCORTEN system, but 10 deaths were observed. Standardized mortality ratio (SMR) analysis [(Sigmaobserved deaths/Sigmaexpected deaths) x 100] suggested that patients with TEN treated with systemic corticosteroid were 16% more likely to die than those treated with routine therapy (SMR = 1.16; 95% confidence interval, 0.56-2.13). In the further study of combination therapy, 12 patients with TEN and eight patients with SJS were admitted. There were two deaths in the TEN group and one death in the SJS group, with 3.51 deaths expected on the basis of the SCORTEN system. SMR analysis showed that combination therapy had a tendency to reduce the mortality rate of TEN (SMR = 0.85; 95% confidence interval, 0.18-2.50). Nevertheless, in both the TEN and SJS groups, the difference in mortality rate between the two therapies was not statistically significant (P = 0.651 and P = 1, respectively). In patients with TEN, combination therapy also reduced significantly the time of arrested progression (P = 0.019) and the total hospitalization time (P = 0.043), but could not reduce the time to the tapering of corticosteroid (P = 0.96). In SJS patients, the times of arrested progression and hospitalization were also reduced significantly (P = 0.019 and P = 0.0475, respectively). Likewise, the time to the tapering of corticosteroid was not reduced (P = 0.122). Combination therapy with corticosteroid and IVIG exhibited a tendency to reduce the mortality rate in comparison with the solo administration of corticosteroid. The decrease in the mortality rate, however, was not statistically significant. Combination therapy also arrested progression earlier and decreased the hospitalization time, meaning that the total dose of corticosteroid may be reduced. Combination therapy, however, did not lead to earlier tapering of corticosteroid. No severe adverse effects of IVIG were found during treatment.

Objective To compare the efficacy of combination therapy of intravenous immunoglobulin (IVIG) and corticosteroids versus corticosteroids alone in the treatment of toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS). Methods A retrospective study was conducted. Totally, 65 consecutive patients diagnosed as either TEN or SJS from January 1993 to October 2007 were included in this study. For 45 patients collected from 1993 to 2000, including 35 cases of TEN and 10 cases of SJS, methylprednisolone of 1 - i.5 mg per kilogram bodyweight per day or equivalent hydrocortisone or dexamethasone was given; for the remaining 20 patients collected from 2001 to 2007, including 12 cases of based on SCORTEN, a severity-of-illness-score system for TEN/SJS prognosis. Results Among the 45 patients treated with corticosteroids alone, 8.63 patients were expected to die based on SCORTEN system, while 10 deaths were observed. Standardized mortality ratio (SMR) analysis revealed that the patients treated with corticosteroids alone were 16% more likely to die than those treated with routine therapy (SMR = 1.16; 95% confidence interval, 0.56 - 2.13). In the remaining 20 patients who received combination therapy, 3 deaths occurred, while 3.51 deaths were expected based on the SCORTEN system. SMR analysis showed that the combination therapy had a trend to reduce the mortality rate of TEN/SJS (SMR = 0.85; 95% confidence interval, 0.18 - 2.50). No significant difference was noted in the mortality rate of TEN/SJS between the combination therapy and corticosteroid monotherapy (16.7% vs 22.8% in TEN, 12.5% vs 20% in SJS, respectively, both P > 0.05). In patients with TEN, the combination therapy significantly reduced the time to arrest disease progression (4.30 ± 2.36 days vs 7.15 ± 3.35 days, t = 2.46, P 0.05) compared with the corticosteroid monotherapy did; so was the case for SJS. Conelusious Compared withsolo administration of corticosteroids, the combination therapy with corticosteroid and IVIG seems to reducethe mortality rate of TEN/SJS. Also, the combination therapy could arrest the progression of TEN/SJS earlier accompanied by a decrease in hospitalization time. However, the time period of corticosteroid tapering is not shortened by the combination therapy. Key words: Toxic epidermal necrolysis; Stevens-Johnson syndrome; Corticosteroid; gamma-Globulins; Drug therapy, combination

Validation of two predictive models designed to aid clinicians in identifying Stevens-Johnson syndrome/toxic epidermal necrolysis: A single institution retrospective review

Purpose: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), potentially life-threatening skin diseases with organ failures caused by drugs, require specialized intensive care. However, SJS and TEN have usually been managed in general wards and intensive care units by most doctors. This study describes the efficacy of treatment in the burn intensive care unit (BICU) compared to previous general treatments. Methods: To investigate the clinical features, outcomes and benefits of 11 patients with SJS and TEN treated in our burn intensive care unit. Data on 11 patients who were treated between January 2004 and December 2008 were collected via a retrospective chart review. Also, the data were reviewed with previous literatures on SJS and TEN treatments. Results: Patients were classified with overlap SJS/TEN (n=4, 36.36%) or TEN (n=7, 63.64%). Nonsteroidal anti-inflammatory drugs (NSAIDs) were the most common causative agents. Hepatitis was the most common organ involvement in both overlap SJS/TEN (n=1, 9.1%) and TEN (n=4, 36.36%). Renal dysfunction (n=4, 36.36%) and respiratory disorders (n=3, 27.27%) were seen in some cases. Mean time of total reepithelization was 9 days and mean hospital day was 14.66 days. Two patients with TEN died from sepsis with multi-organ failure, and the mortality rate was 18.18%. Conclusion: Adequate treatment of SJS and TEN in the BICU supports efficacy with a low mortality rate, short healing time, short hospitalization and fewer complications.

Performance of the SCORTEN in Taiwanese patients with Stevens-Johnson syndrome and toxic epidermal necrolysis

BackgroundStevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but severe adverse drug reactions with high mortality. MethodsTo present the clinical characteristics of SJS and TEN in Japan and evaluate the efficacy of treatments, we retrospectively analyzed cases of SJS and TEN treated in 2 university hospitals during 2000–2013. ResultsFifty-two cases of SJS (21 males and 31 females; average age, 55.1 years) and 35 cases of TEN (17 males and 18 females; average age, 56.6 years) were included in this study. Twenty-eight cases of SJS (53.8%) and all cases of TEN were caused by drugs. Hepatitis was the most common organ involvement in both SJS and TEN. Renal dysfunction, intestinal disorder, and respiratory disorder were also involved in some cases. The major complication was pneumonia and sepsis. All cases except for 3 cases were treated systemically with corticosteroids. Steroid pulse therapy was performed in 88.6% of TEN. Plasmapheresis and/or immunoglobulin therapy was combined with steroid therapy mainly in TEN after 2007. The mortality rate was 6.9% and the rates for SJS and TEN were 1.9% and 14.3%, respectively. These were much lower than predicted mortality according to a severity-of-illness scoring system for TEN prognosis (SCORTEN) score. When comparing the mortality rate between 2000–2006 and 2007–2013, it was decreased from 4.5% to 0.0% in SJS and from 22.2% to 5.3% in TEN. ConclusionsTreatment with steroid pulse therapy in combination with plasmapheresis and/or immunoglobulin therapy seems to have contributed to prognostic improvement in SJS/TEN.

Toxic epidermal necrolysis (TEN) represents the most severe drug-related skin condition that is potentially life-threatening with no well-established treatments. The application of corticosteroid therapy is controversial, whereas recently intravenous immunoglobulin (IVIG) therapy is emerging as a promising new method. A severity-of-illness score for TEN (SCORTEN) has gained acceptance in some western countries. In this study, our objectives were to assess the applicability of SCORTEN in Chinese patients with TEN and to evaluate the efficacy of the combination therapy of IVIG and corticosteroid in these patients. We performed a retrospective review of data from 61 patients with TEN treated at our intensive care unit from 2000 to 2010 to assess the performance of SCORTEN. In particular, 55 patients between 2002 and 2010 were grouped as a series to compare the therapeutic effects of corticosteroid therapy and IVIG combined therapy contemporaneously. During this period, 16 patients were administered with corticosteroid therapy and 39 were treated with the combination therapy. An initial dose of 1.5 mg/kg/day of methylprednisolone was given to all TEN patients. The combination therapy was combined with a total dose of 2 g/kg IVIG within 5 days. Areas under receiver operating characteristic curves and Hosmer-Lemeshow statistic were analyzed to illustrate the performance of SCORTEN. The comparison of the efficacy of the two therapies was conducted on the basis of clinical outcomes, standardized mortality ratio (SMR), and survival analysis. The overall actual mortality of patients between 2000 and 2010 was 16% (10/61), statistically insignificantly lower than predicted (24%, SMR = 67.98). Excellent discriminatory power (the areas under the receiver operating characteristic curves: 88.9, 88.2, 90.6%) and good calibration (P = .637, .833, .530) were found in all the groups. In patients admitted between 2002 and 2010, IVIG combined therapy showed a trend toward reducing the mortality rate (13%, SMR = 52.35), whereas corticosteroid monotherapy suggested no such difference (31%, SMR = 123.92). Besides, the cumulative survival rates of the combination therapy were higher at almost all the levels of SCORTEN (P = .002), especially at the score of 5 (P = 3.10 × 10⁻⁷). Compared with corticosteroid alone, the combination therapy arrested progression earlier (P = .013), although it did not significantly lead to a tapering of corticosteroid or a reduction of the time of hospitalization. We concluded that SCORTEN was generally applicable to Chinese patients with TEN. The comparison of the effect indicated that the combination therapy might achieve a better therapeutic effect than the administration of corticosteroid alone, especially in severe TEN patients.

Pemphigus or pemphigus-related autoantibodies have been found in sera of patients with diverse diseases, such as toxic epidermal necrolysis, thermal burns, and penicillin reactions. Here we report a patient with a typical cutaneous necrotizing vasculitis in whom immunofluorescence studies revealed the presence of circulating and tissue-bound pemphigus autoantibodies.