High risk and low prevalence diseases: Stevens Johnson syndrome and toxic epidermal necrolysis.

INTRODUCTION: Stevens Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are serious conditions that carry a high rate of morbidity and mortality. OBJECTIVE: This review highlights the pearls and pitfalls of SJS/TEN, including presentation, diagnosis, and management in the emergency department (ED) based on current evidence. DISCUSSION: SJS/TEN is a rare, delayed hypersensitivity reaction resulting in de-epithelialization of the skin and mucous membranes. The majority of cases are associated with medication or infection. Clinicians should consider SJS/TEN in any patient presenting with a blistering mucocutaneous eruption. Evaluation of the skin, mucosal, pulmonary, renal, genital, and ocular systems are essential in the diagnosis of SJS/TEN, as well as in the identification of complications (e.g., sepsis). Laboratory and radiological testing cannot confirm the diagnosis in the ED setting, but they may assist in the identification of complications. ED management includes stabilization of airway and breathing, fluid resuscitation, and treatment of any superimposed infections with broad-spectrum antibiotic therapy. All patients with suspected SJS/TEN should be transferred and admitted to a center with burn surgery, critical care, dermatology, and broad specialist availability. CONCLUSIONS: An understanding of SJS/TEN can assist emergency clinicians in diagnosing and managing this potentially deadly disease.

Anesthesia management in a child with mucopolysaccharidosis and toxic epidermal necrolysis: A case report.

Toxic epidermal necrolysis and mucopolysaccharidosis are both rare diseases that pose significant airway maintenance challenges to anesthesiologists. In this report, we describe the anesthesia management in a 4-year-old male with mucopolysaccharidosis type II who developed toxic epidermal necrolysis and presented for ophthalmic surgical procedures. Combined use of propofol and ketamine with the support of high-flow nasal oxygen enabled adequate analgesia and sedation while maintaining spontaneous ventilation and airway patency. The strategy presented in this report may contribute to enhancing the safety of sedation in spontaneously breathing children with abnormal airways.

An individual patient data meta-analysis of wound care in patients with toxic epidermal necrolysis.

Toxic epidermal necrolysis (TEN) involves extensive mucocutaneous loss, and care is supportive. The approach to wound care includes surgical debridement or using dressings while leaving the epidermis intact. Robust evidence for either approach is lacking. We compared surgical debridement to the use of dressings while leaving the epidermis in situ (referred to hereon as dressings) in adult patients with TEN. The primary outcome assessed was mortality. The secondary outcome was time to re-epithelialisation. The impact of medications was evaluated. An individual patient data (IPD) systematic review and meta-analysis was undertaken. A random effects meta-analysis and survival analysis for IPD data examined mortality, re-epithelisation time and the effect of systemic medications. The quality of evidence was rated per the Grading of Recommendations Assessment, Development and Evaluation (GRADE). PROSPERO: CRD42021266611 Fifty-four studies involving 227 patients were included in the systematic review and meta-analysis, with a GRADE from very low to moderate. There was no difference in survival in patients who had surgical debridement or dressings (univariate: p = 0.91, multivariate: p = 0.31). Patients who received dressings re-epithelialised faster than patients who underwent debridement (multivariate HR: 1.96 [1.09-3.51], p = 0.023). Intravenous immunoglobulin (univariate HR: 0.21 [0.09-0.45], p < 0.001; multivariate HR: 0.22 [0.09-0.53], p < 0.001) and cyclosporin significantly reduced mortality (univariate HR: 0.09 [0.01-0.96], p = 0.046; multivariate HR: 0.06 [0.01-0.73], p = 0.028) irrespective of the wound care. This study supports the expert consensus of the dermatology hospitalists, that wound care in patients with TEN should be supportive with the epidermis left intact and supported with dressings, which leads to faster re-epithelialisation.

Stevens-Johnson syndrome and toxic epidermal necrolysis in Hong Kong.

INTRODUCTION: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) [hereafter, SJS/TEN] are uncommon but severe mucocutaneous reactions. Although they have been described in many populations worldwide, data from Hong Kong are limited. Here, we explored the epidemiology, disease characteristics, aetiology, morbidity, and mortality of SJS/TEN in Hong Kong. METHODS: This retrospective cohort study included all hospitalised patients who had been diagnosed with SJS/TEN in Prince of Wales Hospital from 1 January 2004 to 31 December 2020. RESULTS: There were 125 cases of SJS/TEN during the 17-year study period. The annual incidence was 5.07 cases per million. The mean age at onset was 51.4 years. The mean maximal body surface area of epidermal detachment was 23%. Overall, patients in 32% of cases required burns unit or intensive care unit admission. Half of the cases involved concomitant sepsis, and 23.2% of cases resulted in multiorgan failure or disseminated intravascular coagulation. The mean length of stay was 23.9 days. The cause of SJS/TEN was attributed to a drug in 91.9% of cases, including 84.2% that involved anticonvulsants, allopurinol, antibiotics, or analgesics. In most cases, patients received treatment comprising either best supportive care alone (35.2%) or combined with intravenous immunoglobulin (43.2%). The in-hospital mortality rate was 21.6%. Major causes of death were multiorgan failure and/or fulminant sepsis (81.5%). CONCLUSION: This study showed that SJS/TEN are uncommon in Hong Kong but can cause substantial morbidity and mortality. Early recognition, prompt withdrawal of offending agents, and multidisciplinary supportive management are essential for improving clinical outcomes.

[Chinese expert consensus on diagnosis and treatment of immune checkpoint inhibitor-related skin adverse reactions (2024 edition)].

Immune checkpoint inhibitors (ICIs) have emerged as crucial therapeutic agents for various malignancies by activating the host immune system against tumor cells. However, many different types of skin adverse reactions may occur during its use, including eruption, pruritus, blistering, hypopigmentation, alopecia, and even severe cases, Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). These cutaneous immune-related adverse events (cirAEs) had a high incidence, which seriously affected patients' quality of life and antitumor treatment decisions. Some severe cutaneous adverse reactions (SCARs) even endanger patients' lives. Therefore, the Chinese Society of Dermatology, the Chinese Dermatologist Association of the Chinese Medical Doctor Association, the Dermatology Division of the Chinese Geriatrics Society, and other relevant experts jointly discussed and formulated the 'Chinese Expert Consensus on the Diagnosis and Treatment of Immune Checkpoint Inhibitor-Related Cutaneous Adverse Reactions'. This consensus covers the name, epidemiology, pathogenesis, clinical features, classification and grading of cirAEs, principles of management and the re-initiation of ICIs. It aims to provide a more scientific and authoritative reference for the diagnosis and treatment of cirAEs in China in the future.

Cutaneous Immune-Related Adverse Events Secondary to Immune Checkpoint Inhibitors and Their Management.

Immune checkpoint inhibitors (CPIs) are highly effective in the treatment of various cancers. Immunotherapy enhances antitumor activity by relieving inhibition of T cells responsible for immune surveillance. However, overactivation of T cells leads to immune-related adverse events (irAE), of which cutaneous adverse events are the most common. Examples include pruritus and maculopapular eruption most commonly, psoriasis and bullous dermatoses less commonly, and, rarely, severe, life-threatening eruptions such as Stevens-Johnson Syndrome or Toxic Epidermal Necrolysis. Many of these are autoimmune in nature, and these may present de novo or as recurrence of pre-existing disease. In order to maximize the therapeutic potential of CPIs, it is essential to recognize and effectively manage cutaneous irAE, which can otherwise lead to treatment interruption or discontinuation. This review summarizes the presentation and management of dermatologic adverse events secondary to immune dysregulation as a result of immune checkpoint inhibitor therapy, including the most common (maculopapular eruption, pruritus, lichenoid dermatitis, and vitiligo), less common (psoriasis, bullous pemphigoid, erythema multiforme, eczematous dermatitis, alopecia areata, and granulo-matous and neutrophilic dermatoses), and severe (acute generalized exanthematous pustulosis [AGEP], drug reaction with eosinophilia and systemic symptoms [DRESS], and Stevens-Johnson syndrome or toxic epidermal necrolysis [SJS/TEN]), as well as exacerbation of pre-existing cutaneous autoimmune disease (subacute cutaneous lupus erythematosus, dermatomyositis, eosinophilic fasciitis, leukocytoclastic vasculitis, and scleroderma-like reaction).

Exosomal microRNAs from PBMCs stimulated with culprit drugs enhanced keratinocyte cell death in Stevens-Johnson syndrome/toxic epidermal necrolysis.

BACKGROUND: Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and drug reactions with eosinophilia and systemic symptoms (DRESS) are both severe cutaneous adverse reactions. Keratinocyte death is much more prominent in SJS/TEN compared to DRESS. OBJECTIVE: This study aimed to investigate the role of exosomal miRNAs on keratinocyte death in SJS/TEN. METHODS: Peripheral blood mononuclear cells (PBMCs) from SJS/TEN and DRESS patients were stimulated with the culprit drugs. The exosomes released in cell supernatants were co-incubated with HaCaT cells to study the cytotoxic effects on keratinocytes. Exosomal miRNA sequencing analysis was performed to compare the expression patterns between SJS/TEN and DRESS subjects. HaCaT cells were then transfected with miRNA mimics and inhibitors to explore the functions of miRNAs on keratinocyte cell death. RESULTS: Cytotoxic effects of PBMC-derived exosomes on keratinocytes were demonstrated in SJS/TEN and could be neutralized with exosome inhibitors. Cytotoxic effects of PBMC-derived exosomes from SJS/TEN subjects were higher after incubating PBMCs with the culprit drugs than those incubating with irrelevant drugs and unstimulated controls. The sequencing data revealed differential expressions of 61 exosomal miRNAs between SJS/TEN and DRESS. Exosomal miR-4488 was upregulated while miR-486-5p, miR-96-5p and miR-132-3p were downregulated in SJS/TEN compared to DRESS as determined by quantitative real-time PCR. The increased percentage of apoptotic cells upon transfection of HaCat cells was 36.3% and 34.9% with miR-4488 mimic and miR-96-5p inhibitor, respectively. CONCLUSION: This study illustrated the regulatory functions of exosomal miRNAs in controlling keratinocyte death in SJS/TEN. Exosome inhibitors might have a therapeutic role in SJS/TEN.

Long-Term Benefits of Tear Exchangeable Limbal-Rigid Contact Lens Wear Therapy in Stevens-Johnson Syndrome Cases.

OBJECTIVES: To evaluate the long-term benefits of tear-exchangeable, limbal-rigid contact lens (CL) wear therapy in patients with Stevens-Johnson syndrome (SJS)-associated ocular sequelae. METHODS: This retrospective study evaluated 50 eyes of 41 SJS patients (15 men and 26 women) who underwent limbal-rigid CL wear therapy for more than 2 years post fitting. Ocular sequelae (i.e., conjunctival hyperemia, corneal neovascularization, and upper tarsus scarring) before fitting and at 3 months, 6 months, 12 months, and annually after initiating CL wear therapy were evaluated and then graded on a severity score (range: 0-3, maximum score: 3). Moreover, visual acuity (VA) at immediately post initiating CL wear therapy was evaluated. RESULTS: The mean follow-up period was 4.3±1.1 years. Compared with before fitting, the mean conjunctival hyperemia score improved from 1.14 to 0.86 at 3 months of CL wear therapy ( P <0.01) and was maintained thereafter; the mean corneal neovascularization score improved from 2.10 to 1.98 at 3 months of CL wear therapy, with no deterioration of the score observed in all cases at the final follow-up examination, and mean VA (log of minimum angle of resolution) improved from 1.60 to 1.04 at immediately post initiating CL wear therapy ( P <0.01). CONCLUSIONS: Limbal-rigid CL wear therapy can provide long-term ocular surface stabilization and improved VA in SJS patients.

Stevens-Johnson syndrome in children.

PURPOSE OF REVIEW: The concept of Stevens-Johnson syndrome (SJS) in children is evolving. This manuscript reviews recent advances with the lens of new terminology namely infection-triggered reactive infectious mucocutaneous eruption and drug-induced epidermal necrolysis, with the objective of integrating this novel terminology practically. RECENT FINDINGS: Traditionally considered to exist on a spectrum with toxic epidermal necrolysis, SJS in children is more often caused or triggered by infections instead of medications. Proposed pediatric-specific terminology can be applied to literature to gain further insights into blistering severe cutaneous adverse reactions. SUMMARY: Distinguishing infection-triggered from drug-triggered blistering reactions is useful for 3 main reasons: (1) early clinically recognizable different features such as isolated or predominant mucositis, (2) different initial management depending on trigger, (3) avoiding the label of a drug reaction on cases triggered by infection.

The role of treatment with plasma exchange therapy in two pediatric toxic epidermal necrolysis cases related to COVID-19.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening mucocutaneous reactions characterized by necrosis and detachment of the epidermis. Drugs and bacterial or viral infections are the most common causes of SJS/TEN. Although cases of SJS/TEN have been reported after hydroxychloroquine, vaccine (mRNA [Biontech], and inactivated vaccine [Sinovac]) administration and during the clinical course of active Coronavirus disease 2019 (COVID-19), limited data is indicating the COVID-19 disease as a triggering factor. Also, there are no pediatric cases of SJS/TEN associated with COVID-19 in the literature. Herein we reported two pediatric cases with a diagnosis of TEN related to COVID-19. Therapeutic plasma exchange therapy was applied to both of our patients. Although there are a few adult cases in the literature, our article is the first pediatric case report about patients diagnosed with TEN related to COVID-19 and successfully treated with plasma exchange.

Infantile Stevens Johnson syndrome and toxic epidermal necrolysis: A systematic review of clinical features and outcomes in children ages 12 months and under.

BACKGROUND/OBJECTIVES: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening mucocutaneous hypersensitivity reactions that carry significant morbidity and mortality. While clinical features are well documented in adult and pediatric patients, infantile cases are rarely reported. Our objective was to synthesize clinical features and outcomes in this population. METHODS: A literature search was performed from three large databases (PubMed, EMBASE, and Web of Science) to systematically identify reports of SJS/TEN in the infantile period (defined as less than 12 months of age) between 1962 and 2019. Cases determined to represent SJS/TEN based on defined criteria were included. Each case was scored based on Quality Rating Scheme for Studies and Other Evidence. The initial search yielded 4856 publications, of which 19 (n = 26) met final inclusion criteria. RESULTS: All cases for which body surface area (BSA) involvement was available or able to be approximated (n = 18/26) met criteria for TEN. All cases (n = 26) had mucous membrane involvement, with the oral mucosa most commonly affected (85.7%). Mortality was high within our population with 39.1% of infants expiring, 77.8% secondary to bacterial sepsis. The most common triggers were medications (52.4%), infections (33.3%), and vaccinations (14.3%). CONCLUSIONS: This review highlights several unique clinical findings amongst infants with SJS/TEN, including increased BSA involvement, higher rates of bacterial sepsis, and higher mortality rates compared to older children and adults. Infants are more likely to present as TEN over SJS. More research is needed to identify triggers, successful treatments, and specific outcomes in this population.

Toxic epidermal necrolysis-like acute graft-versus-host disease in pediatric bone marrow transplant patients: Case series and review of the literature.

BACKGROUND/OBJECTIVES: Complications of hematopoietic stem cell transplant (HSCT) include acute graft-versus-host disease (aGVHD). Severe cutaneous aGVHD can present with generalized erythroderma, desquamation, and bullae which can mimic toxic epidermal necrolysis (TEN). TEN occurs in response to a culprit medication. Transplant patients are often on many medications, making it difficult to distinguish between the two conditions. Given that TEN-like aGVHD is rare, we describe a case series of pediatric patients and review the literature. METHODS: This is a multi-institutional case series of children who developed TEN-like aGVHD following bone marrow transplantation. Demographic, clinical, and treatment information was collected. RESULTS: Ten patients were identified. Median age at transplantation was 8.5 years (range 0.12-17 years). Median time from transplant to first skin symptoms was 35 days (range 6-110 days) and to first TEN-like symptoms was 40 days (range 16-116 days). 7/10 had other organ GVHD involvement. All patients were on concurrent medications at time of first skin symptoms including immunosuppression for GVHD prophylaxis, infection prophylaxis or treatment, and pain medication. Treatments for TEN-like aGVHD included immunosuppression. CONCLUSIONS: We observe that patients with > or equal to 50% BSA involvement of their skin with TEN-like aGVHD, extracutaneous GVHD, and lack of reepithelization tend to have poor outcomes. Given the rarity of this condition, multidisciplinary care of these patients is important for accurate and timely diagnosis and treatment.

Accuracy of SCORTEN in predicting mortality in toxic epidermal necrolysis.

BACKGROUND: Toxic epidermal necrolysis (TEN) patients require multi-directional and multi-disciplinary treatment. In most cases, they are hospitalised at intensive care units and require multi-directional, burn-complication preventive care. Choosing the most appropriate treatment option might be troublesome even when predicting scores are used. SCORTEN is the most renowned prognostic score for TEN patients, however, there are some data indicating that the accuracy of this test may be limited. The credibility of not just the predicted mortality risk, but also componential laboratory results and clinical features subject to debate. The aim of this study was to evaluate the efficacy and credibility of SCORTEN in clinical practice, on proprietary material. METHODS: A retrospective analysis of 35 patients with diagnosed in histopathology TEN was performed. The inclusion criteria were as follows: day of submission before 5th day from the onset of the symptoms, full protocol of plasmaphereses and IVIGs according to our scheme. Our protocol includes cycle of plasmapheresis with frozen fresh plasma twice daily for the first 2 days following admission, and once daily for the subsequent 5 to 7 days. IVIGs were administered after the first two sessions of plasmapheresis, for 4 to 7 days. The dosage was calculated according to body weight, at 0.4 to 0.5 g/kg per dose. RESULTS: The sensitivity of SCORTEN for the analysed cohort was 100%, with a specificity of 24%. The estimated death was 41,9%, while the actual death rates were 12,5%. Our protocol improved the survival, OR = 26,57, RR = 6,34, p = 0,022. Decrease in mortality was caused by a combined treatment protocol we use- plasmaphereses with IVIGs. No independent risk factor was significant in death evaluation. CONCLUSION: Our data suggest that the scoring system for predicting death among TEN patients are reliable when they are high. New prognostic factors should be found to improve the evaluation of patients with low SCORTEN.

Supportive care in the acute phase of Stevens-Johnson syndrome and toxic epidermal necrolysis: an international, multidisciplinary Delphi-based consensus.

BACKGROUND: Supportive care is the cornerstone of management of adult and paediatric Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). However, consensus on the modalities of supportive care is lacking. OBJECTIVES: Our aim in this international multicentric Delphi exercise was to establish a multidisciplinary expert consensus to standardize recommendations regarding supportive care in the acute phase of SJS/TEN. METHODS: Participants were sent a survey via the online tool SurveyMonkey, consisting of 103 statements organized into 11 topics: multidisciplinary team composition, suspect drug management, infection prevention, fluid resuscitation and prevention of hypothermia, nutritional support, pain and psychological distress management, management of acute respiratory failure, local skincare, ophthalmological management, management of other mucosa, and additional measures. Participants evaluated the level of appropriateness of each statement on a scale of 1 (extremely inappropriate) to 9 (extremely appropriate). The results were analysed according to the RAND/UCLA Appropriateness Method. RESULTS: Forty-five participants from 13 countries (on three continents) participated. After the first round, a consensus was obtained for 82.5% of the 103 initially proposed statements. After the second round, a final consensus was obtained for 102 statements. CONCLUSIONS: We have reached an international Delphi-based consensus on best supportive care practice for SJS/TEN. Our expert consensus should help guide physicians in treating patients with SJS/TEN and thereby improve short-term prognosis and the risk of sequelae.

Treating toxic epidermal necrolysis with systemic immunomodulating therapies: A systematic review and network meta-analysis.

BACKGROUND: Various systemic immunomodulating therapies have been used to treat toxic epidermal necrolysis (TEN), but their efficacy remains unclear. OBJECTIVE: To perform a systematic review and network meta-analysis (NMA) evaluating the effects of systemic immunomodulating therapies on mortality for Stevens-Johnson syndrome (SJS)/TEN overlap and TEN. METHODS: A literature search was performed in online databases (from inception to October 31, 2019). Outcomes were mortality rates and Score of Toxic Epidermal Necrolysis (SCORTEN)-based standardized mortality ratio (SMR). A frequentist random-effects model was adopted. RESULTS: Sixty-seven studies involving 2079 patients were included. An NMA of 10 treatments showed that none was superior to supportive care in reducing mortality rates and that thalidomide was associated with a significantly higher mortality rate (odds ratio, 11.67; 95% confidence interval [CI], 1.42-95.96). For SMR, an NMA of 11 treatment arms showed that corticosteroids and intravenous immunoglobulin combination therapy was the only treatment with significant survival benefits (SMR, 0.53; 95% CI, 0.31-0.93). LIMITATIONS: Heterogeneity and a paucity of eligible randomized controlled trials. CONCLUSIONS: Combination therapy with corticosteroids and IVIg may reduce mortality risks in patients with SJS/TEN overlap and TEN. Cyclosporine and etanercept are promising therapies, but more studies are required to provide clearer evidence.

Severe cutaneous adverse reaction associated with antiseizure medications: Diagnosis, management, and prevention.

Severe cutaneous adverse reactions (SCARs) are potentially life-threatening, with considerable morbidity and mortality. They are nonimmediate hypersensitivity reactions that occur in specifically predisposed patients with delayed T-cell-mediated hypersensitivity reaction. Antiseizure medications (ASMs) are among the drugs that can induce SCAR. Increased awareness of SCAR among clinicians treating patients with ASMs is critically important for early recognition of symptoms, prompt identification and removal of the causal drug, and early intervention to reduce SCAR-related acute and long-term morbidity and mortality. The diagnosis, management, and prevention of Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) are reviewed, along with the current understanding of the pathomechanisms and role of genetics in SCAR development. Supportive care and immunomodulating treatments for SCAR are discussed.

Retrospective Study of Patients With SJS/TEN Treated at a Tertiary Burn Unit in Canada: Overview of 17 Years of Treatment.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are adverse drug reactions. OBJECTIVES: To learn about the clinical characteristics of patients with SJS/TEN including treatments provided, outcomes, and mortality. METHODS: We conducted a retrospective chart review of patients who were hospitalized with the diagnosis of SJS/TEN at the Ross Tilley Burn Center between the years 1999 and 2015. RESULTS: A total of 43 patients were identified with a mean age of 54 ± 19 (58, 18-85). The most common offending medications were allopurinol and carbamazepine. The overall mortality rate in our study is 21% with the most common causes of death being multiorgan failure and sepsis. The majority of our patients had oral (84%), ocular (79%), and genital (60%) involvement during hospitalization. Our data revealed that combination treatment involving oral corticosteroids with intravenous immunoglobulin (IVIG) had the highest mortality rate in our study since 55% (6/11) of patients who were treated in this manner passed away compared to 11% (2/18) of patients passing away who were treated with solely IVIG and 33% (1/3) who were treated with only supportive care. Our study also demonstrates the addition of etanercept and cyclosporine treatment in the second time period we studied: 2008-2015 versus the earlier time period of 1999-2007. None of the patients in our study who were treated with therapies including cyclosporine and/or etanercept passed away. CONCLUSIONS: Our study sheds light on a possible beneficial role of cyclosporine and etanercept for the treatment of SJS and TEN and reinforces the necessity of a multidisciplinary care team for patients.

Cutaneous Immune-Related Adverse Events (irAEs) to Immune Checkpoint Inhibitors: A Dermatology Perspective on Management [Formula: see text].

Immune checkpoint inhibitors have proven to be efficacious for a broad spectrum of solid organ malignancies. These monoclonal antibodies lead to cytotoxic T-cell activation and subsequent elimination of cancer cells. However, they can also lead to immune intolerance and immune-related adverse event (irAEs) that are new and specific to these therapies. Cutaneous irAEs are the most common, arising in up to 34% of patients on PD-1 inhibitors and 43% to 45% on CTLA-4 inhibitors. The most common skin manifestations include maculopapular eruption, pruritus, and vitiligo-like lesions. A grading system has been proposed, which guides management of cutaneous manifestations based on the percent body surface area (BSA) involved. Cutaneous irAEs may prompt clinicians to reduce drug doses, add systemic steroids to the regiment, and/or discontinue lifesaving immunotherapy. Thus, the goal is for early identification and concurrent management to minimize treatment interruptions. We emphasize here that the severity of the reaction should not be graded based on BSA involvement alone, but rather on the nature of the primary cutaneous pathology. For instance, maculopapular eruptions rarely affect <30% BSA and can often be managed conservatively with skin-directed therapies, while Stevens-Johnson syndrome (SJS) affecting even 5% BSA should be managed aggressively and the immunotherapy should be discontinued at once. There is limited literature available on the management of the cutaneous irAEs and most studies present anecdotal evidence. We review the management strategies and provide recommendations for psoriatic, immunobullous, maculopapular, lichenoid, acantholytic eruptions, vitiligo, alopecias, vasculitides, SJS/toxic epidermal necrolysis, and other related skin toxicities.

A progressive and severe rash - Answers.

A 73-year-old female patient with epilepsy presented to hospital with a progressive, diffuse macular rash over the trunk and limbs with associated mucosal blistering and discharge. Ocular symptoms initially predominated and she was treated for presumed bacterial conjunctivitis by her General Practitioner the previous day. On the acute medical unit supportive management was initiated for suspected adverse drug reaction (ADR) to a recent lamotrigine dose increase. Skin biopsy confirmed a diagnosis of toxic epidermal necrolysis. We present this case to highlight the importance of medication history taking and raise awareness of indolent presentations of life-threatening ADRs. Caution should be applied following dose changes to anti-epileptics, even if previously stable.

Aetiopathogenesis of severe cutaneous adverse reactions (SCARs) in children: A 9-year experience in a tertiary care paediatric hospital setting.

BACKGROUND: Severe cutaneous adverse reactions (SCARs) are delayed-type hypersensitivity reactions to drugs including as follows: Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), Stevens-Johnson syndrome (SJS), Toxic Epidermal Necrolysis (TEN) and Acute Generalized Exanthematous Pustulosis (AGEP). Incidence, triggers and management of SCARs have not been investigated in large-scale epidemiological studies on children. OBJECTIVE: The aim of our study was to collect epidemiological, clinical and aetiological data from children with SCARs referred to our tertiary care paediatric hospital of Florence. METHODS: From 2010 to 2018 charts of children with diagnosis of SCAR were reviewed, and data collected during the acute phase and/or the subsequent allergy evaluation. Patients underwent patch tests, intradermal tests and lymphocyte transformation tests. All children were investigated for infectious diseases. RESULTS: Incidence of SCARs in hospitalized children was 0.32% over a 9-year period. Fifty-four children were enrolled (31 M; 23 F; median age 6.5 years): 17 cases of DRESS, 30 SJS, 3 TEN, 2 AGEP, 1 linear immunoglobulin A bullous disease (LABD) and 1 pemphigus. Twenty-eight out of 54 patients underwent drug allergy investigations, and 50% of them resulted positive. Combining clinical history and results of allergy work-up, 74% SCARs seem to be caused by drugs, 18.6% by both drugs and infections, 3.7% by infections, and 3.7% remained idiopathic. No deaths occurred. CONCLUSIONS: In this study, SCARs incidence is in line with literature data. Drugs were most commonly the leading cause. Management of SCARs requires cooperation among professional figures for an early diagnosis and a prompt treatment. Mortality rate seems to be lower in children.