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PURPOSE: This study aims to elucidate the tear proteome and understand the underlying molecular mechanisms involved in the ocular complications following Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). METHODS: Mass spectrometry (MS) was performed to quantify the tear fluid proteins from chronic SJS/TEN patients (n = 22 eyes) and age- and gender-matched controls (n = 22 eyes). The candidate proteins were validated using ELISA (n = 80 eyes) in tear samples and immunohistochemistry (IHC; n = 12) in eyelid margin specimens. These proteins were compared for significant differences based on age, gender, disease duration, and ocular severity. RESULTS: A total of 1692 tear fluid proteins were identified, of which 470 were significantly differentially regulated in chronic SJS/TEN. The top 10 significantly upregulated proteins were neutrophil secretions including neutrophil elastase (p < .0001), defensin (p < .0001), and matrix metalloproteinase 8 (p < .0001). The presence of neutrophils was confirmed by the upregulation of IL-8 (p < .001) in tears, a key cytokine known for recruiting neutrophils. Additionally, positive expression of myeloperoxidase was observed in the keratinized eyelid margins of SJS/TEN to validate the presence of neutrophils. Among 41 unique proteins identified by MS, IL-36γ (p < .01) was expressed in three SJS/TEN patients and was confirmed in SJS/TEN tears and eyelid margins by ELISA and IHC, respectively. IL-36γ was specifically expressed in the superficial layers of eyelid margin keratinized conjunctiva. The majority of the significantly downregulated proteins were lacrimal gland secretions such as lacritin (p < .0001) and opiorphin (p < .002). Neutrophil elastase (p < .02) was significantly elevated in patients with severe eyelid margin keratinization. CONCLUSION: Our observations indicate a clear correlation between eyelid margin keratinization and the expression of IL-36γ, potentially mediated by neutrophils recruited via IL-8. Future experimental studies are needed to test the role of therapies targeting IL-8 and/or IL-36γ in reducing eyelid margin keratinization and its associated ocular complications in SJS/TEN.
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Interleucina-1 , Neutrófilos , Síndrome de Stevens-Johnson , Lágrimas , Humanos , Feminino , Masculino , Neutrófilos/metabolismo , Neutrófilos/imunologia , Interleucina-1/metabolismo , Síndrome de Stevens-Johnson/metabolismo , Síndrome de Stevens-Johnson/patologia , Adulto , Lágrimas/metabolismo , Pessoa de Meia-Idade , Doença Crônica , Inflamação/metabolismo , Idoso , Adulto JovemRESUMO
Cutaneous graft versus host disease (cGVHD) has substantial clinical and histopathologic overlap with erythema multiforme (EM), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). This overlap can make it difficult to distinguish these disorders in patients who have received hematopoietic transplants. We sought to evaluate the utility of Dp I/II immunohistochemical stain in differentiating EM/SJS/TEN and cGVHD in a large cohort. Skin biopsy specimens from patients with cGVHD (n = 58) and EM/SJS/TEN (n = 60) were evaluated for Dp I/II expression by immunohistochemistry. We found a statistically significant difference in Dp I/II staining between cGVHD (all grades) and EM/SJS/TEN (mean scores 1.62 and 2.14, respectively; p < 0.005), as well as between Grades 2 + 3 cGVHD and EM/SJS/TEN (mean scores 2.26 and 1.62, respectively; p < 0.005), while we did not find a significant difference between Grade 4 cGVHD and EM/SJS/TEN (mean scores 1.69 and 1.62, respectively; p = 0.71). Dp I/II immunostain may be useful for differentiating EM/SJS/TEN from Grade 2 and Grade 3 cGVHD, especially in clinically ambiguous cases without extracutaneous GVHD.
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Eritema Multiforme , Doença Enxerto-Hospedeiro , Síndrome de Stevens-Johnson , Humanos , Síndrome de Stevens-Johnson/diagnóstico , Síndrome de Stevens-Johnson/patologia , Desmoplaquinas , Eritema Multiforme/diagnóstico , Eritema Multiforme/patologia , Doença Enxerto-Hospedeiro/diagnóstico , Coloração e RotulagemRESUMO
Chimeric antigen receptor (CAR) T-cell therapy has demonstrated remarkable success in treating various B-cell malignancies, redirecting T-cell cytotoxicity toward cancer cells. Despite its efficacy, CAR-T therapy is associated with potential risks, including cytokine release syndrome (CRS) and cytopenia. We present a case of a 69-year-old man with diffuse large B-cell lymphoma treated with axicabtagene-ciloleucel CAR-T therapy, who developed a rare and severe cutaneous toxicity resembling toxic epidermal necrolysis (TEN). The patient exhibited persistent fevers, CRS, and subsequent development of a widespread erythematous macular eruption, progressing to vesiculation with bullae. Notably, allopurinol-induced TEN was considered with the patient's recent exposure to allopurinol, although the onset and minimal mucosal involvement did not align with typical presentations of allopurinol-induced cases. The cutaneous reaction, distinct from typical SJS/TEN, showed minimal mucosal involvement and coincided with the cytokine release storm, differing from allopurinol-induced TEN. Despite the absence of guidelines, the patient was managed with systemic steroids, achieving significant improvement. This case expands the spectrum of CAR-T therapy-related cutaneous toxicities, highlighting the need for early recognition of histopathology and tailored management by dermatologists. Further understanding of these reactions is crucial for optimizing the safety profile of this groundbreaking immunotherapy.
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Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are potentially life-threatening severe cutaneous adverse drug reactions. These diseases are rare, and their onset is difficult to predict because of their idiosyncratic reactivity. The Japan Severe Adverse Reactions Research Group, led by the National Institute of Health Sciences, has operated a nationwide to collect clinical information and genomic samples from patients with SJS/TEN since 2006. This study evaluated the associations of clinical symptoms with sequelae and specific causative drugs/drug groups in Japanese patients with SJS/TEN to identify clinical clues for SJS/TEN treatment and prognosis. Acetaminophen, antibiotics, and carbocisteine were linked to high frequencies of severe ocular symptoms and ocular sequelae (p < 0.05). For erythema and erosion areas, antipyretic analgesics had higher rates of skin symptom affecting <10% of the skin than the other drugs, suggesting narrower lesions (p < 0.004). Hepatic dysfunction, was common in both SJS and TEN, and antiepileptic drugs carried higher risks of hepatic dysfunction than the other drug groups (p = 0.0032). This study revealed that the clinical manifestations of SJS/TEN vary according to the causative drugs.
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Síndrome de Stevens-Johnson , Humanos , Síndrome de Stevens-Johnson/etiologia , Síndrome de Stevens-Johnson/complicações , Japão/epidemiologia , Pele/patologia , Acetaminofen/efeitos adversos , OlhoRESUMO
PURPOSE: To summarize the outcomes of corneal sight rehabilitating surgery in Stevens-Johnson syndrome (SJS). METHODS: This is a retrospective analysis of a consecutive case series. Twenty-four eyes of 18 SJS patients were included in this study. The ocular parameters, surgical procedures, postoperative complications, and additional treatments of the cases were reviewed. RESULTS: A total of 29 corneal sight rehabilitating surgeries, which consists of 9 keratoplasties, 8 Keratolimbal allograft (KLAL) and 12 combined surgeries (keratoplasty and KLAL simultaneously) were performed on the 24 eyes. All patients were treated with glucocorticoid eyedrops and tacrolimus eyedrops for anti-rejection treatment without combining systemic immunosuppression, except two patients who were prescribed prednisone tablets for the management of systemic conditions. The mean follow-up period was 50.6 ± 28.1 months. The optimal visual acuity (VA) (0.74 ± 0.60 logarithm of the minimum angle of resolution [logMAR]) and endpoint VA (1.06 ± 0.82 logMAR) were both significantly better than the preoperative VA (1.96 ± 0.43 logMAR) (95% CI, p = 0.000). 57.1% patients (8/14) were no longer in the low vision spectrum, and 88.9% patients (8/9) were no longer blind. The mean epithelialization time was 7.1 ± 7.6 weeks. The success rate was 86.7%. Additional treatments for improving epithelialization included administration of serum eyedrops (n = 10), contact lens (n = 15), amniotic membrane transplantation (n = 6), and tarsorrhaphy (n = 8). Complications included delayed epithelialization (n = 4, over 12 weeks), glaucoma (n = 11), and severe allograft opacity (n = 4). Only one graft rejection was observed. CONCLUSIONS: Keratoplasty and KLAL can remarkably enhance VA and improve low vision or even eliminate blindness for ocular complications of SJS. The outcome of the surgeries was correlated with the preoperative ocular situation and choice of operative methods.
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Doenças da Córnea , Síndrome de Stevens-Johnson , Acuidade Visual , Humanos , Síndrome de Stevens-Johnson/cirurgia , Síndrome de Stevens-Johnson/fisiopatologia , Estudos Retrospectivos , Feminino , Masculino , Adulto , Acuidade Visual/fisiologia , Pessoa de Meia-Idade , Adulto Jovem , Adolescente , Doenças da Córnea/cirurgia , Doenças da Córnea/fisiopatologia , Resultado do Tratamento , Criança , Transplante de Córnea/métodos , Seguimentos , Ceratoplastia Penetrante/métodos , Complicações Pós-Operatórias , Limbo da Córnea/cirurgiaRESUMO
This study aims to characterize the timeline and clinical features of onset, progression, and management of drug-induced epidermal necrolysis in pediatric patients. Sixteen pediatric patients were retrospectively identified and selected if under age 18 years at admission with one identified culprit drug exposure. Culprit drugs were antiepileptics (12/16, 75%) and antibiotics (4/16, 25%). Notably, anti-epileptic drugs (AED) had delayed onset and reported dose escalations that precipitated symptom onset; thus, patients prescribed AED with or without planned dose escalations should be monitored for prodromal symptoms longer than the typical onset window.
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BACKGROUND/OBJECTIVES: The immune checkpoint inhibitors (ICIs) have been increasingly associated with severe cutaneous adverse reactions (SCARs). These reactions, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalized exanthematous pustulosis (AGEP) are uncommon but potentially lethal. Despite the severity of these reactions and growing association with the ICIs, their specific risk and mortality rates have been largely unexplored. METHODS: A case/non-case analysis was performed using data from the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) to examine the reporting odds ratios (RORs) for ICI-associated SCARs cases under two conditions: (1) ICIs compared with all drugs in FAERS and (2) ICIs compared with a reference group of pooled anticancer drugs to control for underlying malignancy. RESULTS: A statistically significant ROR for SJS (ROR: 5.44), TEN (ROR: 5.81) and DRESS (ROR: 1.38) were identified under Condition 1. Under Condition 2, this significance was maintained for SJS (ROR: 7.31), TEN (ROR: 7.40) and DRESS (ROR: 3.90), and mild significance was identified for AGEP (ROR: 1.89). Mortality rates for the ICIs were increased compared with the anticancer medications (28.5% vs. 24.5% for SJS, 55.3% vs. 46% for TEN, 3.0% vs. 2.1% for AGEP and 7.1% vs. 6.1% for DRESS). CONCLUSIONS: Our results suggest an association between SCARs and the ICIs independent of cancer status.
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Sistemas de Notificação de Reações Adversas a Medicamentos , Inibidores de Checkpoint Imunológico , Síndrome de Stevens-Johnson , United States Food and Drug Administration , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Estados Unidos , Síndrome de Stevens-Johnson/etiologia , Toxidermias/etiologia , Feminino , Masculino , Síndrome de Hipersensibilidade a Medicamentos/etiologia , Pessoa de Meia-Idade , Pustulose Exantematosa Aguda Generalizada/etiologia , IdosoRESUMO
Stevens Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse reactions characterised by keratinocyte apoptosis, necroptosis and epidermal detachment. Several cytokines and cytotoxic proteins have been shown to be elevated in the blood and skin of SJS/TEN sufferers and biologics such as intravenous immune globulin and tumour necrosis factor (TNF)-alpha inhibitors have demonstrated good therapeutic potential. The exact pathogenic model of SJS/TEN however remains elusive. This systematic review aimed to evaluate the case-control studies of cytokines and cytotoxic proteins in the blister fluid and skin of adults with Stevens Johnson syndrome and/or toxic epidermal necrolysis. This review was registered with INPLASY and conducted in accordance with the PRISMA reporting guidelines. Potential bias was assessed using the NIH criteria. Eleven articles describing results from 96 cases and 170 controls were included. Fas, Fas ligand, Interleukin (IL)-8 and B-cell lymphoma (Bcl)-2 were elevated in SJS/TEN blister fluid and skin tissue, compared with healthy controls. IL-2, IL-6, TNF-alpha, tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), interferon-gamma and matrix metalloproteinase-2 were elevated in SJS/TEN blister fluid compared with fluid sampled from lesional controls. Granulysin, IL-33, TGF-beta-1 and IL-13 were elevated in SJS/TEN skin tissue compared with lesional lichen planus tissue, as was IL-13, IFN-gamma, IL-2 and IL-5, when compared with erythema multiforme tissue. A wide array of cytokines and cytotoxic proteins are present at higher concentrations in the blister fluid and skin tissue of SJS/TEN patients compared with healthy and lesional controls. Our findings suggest that these proteins may be pathogenic, as well as possibly markers for diagnosis, disease severity and course. They may also prove to be useful therapeutic targets. More research is needed.
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INTRODUCTION: Severe cutaneous adverse reactions (SCARs) arising from drug interactions can carry life-threatening implications and result in lasting effects. SCARs can be triggered by various factors, with trimethoprim/sulfamethoxazole identified as a primary culprit. Anticonvulsants and antineoplastic agents have been noted as secondary triggers. Notably, antineoplastics linked to SCARs include immunomodulatory agents. The higher mortality rates among cancer patients with SCARs underscore the significance of comprehending cancer--specific risk factors. Our objective is to present the case of a boy with acute lymphocytic leukemia (ALL) who developed Stevens-Johnson syndrome (SJS) following MTX treatment. CASE REPORT: We present the case of a three-year-old male patient diagnosed with ALL who developed Stevens-Johnson syndrome (SJS) subsequent to the administration of MTX, following the "BFM 2009" protocol. He had undergone intrathecal MTX administration on six previous occasions. Our patient received IVIG at a dose of 2g/kg along with steroids, resulting in partial clinical improvement after 21 days. An innovative protocol was developed, involving IVIG before MTX infusion and dexamethasone before MTXi, with folinic acid rescue. Intravenous immunoglobulin (IVIG) mitigates SJS/TEN via type IV hypersensitivity down-regulation and apoptosis curbing. CONCLUSION: As far as we know, the prophylactic use of IVIG to counteract SCARs in a pediatric leukemia patient represents uncharted territory. Moreover, research into the immune system dynamics within these patients and the preservation of indispensable treatments should involve allergist-immunologists as part of the multidisciplinary team attending to neoplastic conditions.
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Metotrexato , Leucemia-Linfoma Linfoblástico de Células Precursoras , Síndrome de Stevens-Johnson , Humanos , Masculino , Síndrome de Stevens-Johnson/tratamento farmacológico , Síndrome de Stevens-Johnson/etiologia , Síndrome de Stevens-Johnson/diagnóstico , Pré-Escolar , Metotrexato/uso terapêutico , Metotrexato/efeitos adversos , Metotrexato/administração & dosagem , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Imunoglobulinas Intravenosas/uso terapêutico , Imunoglobulinas Intravenosas/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Antimetabólitos Antineoplásicos/uso terapêutico , Dexametasona/administração & dosagem , Dexametasona/uso terapêuticoRESUMO
BACKGROUND: Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) are potentially life-threatening severe cutaneous adverse reactions (SCARs). Although the classical causal agents of SCARs (antibiotics, anticonvulsants, nonsteroidal anti-inflammatory drugs, and allopurinol) are well characterized, there has been little update to this list to account for newly marketed medications. OBJECTIVE: To provide an updated and stratified list of medications with significant reporting odds ratios (RORs) of SCARs. METHODS: A case/non-case analysis using the United States FDA Adverse Event Reporting System was performed. RESULTS: As expected, the prototypical medication classes made up the majority of reported cases of SJS, TEN, AGEP, and DRESS (77%, 64%, 75%, and 72%, respectively). In addition, several infrequently or previously undescribed classes/medications implicated in SCARs were identified to have significant ROR signals, including acetylcysteine, anticoagulants, diuretics, immunotherapies, proton pump inhibitors, antivirals, and antifungals. Among these reported for SJS were acetylcysteine (ROR: 64.38) and fluconazole (ROR: 17.13). For TEN, we identified furosemide (ROR: 26.32), spironolactone (ROR: 14.45), fluconazole (ROR: 30.21), amphotericin B (39.06), and acetylcysteine (ROR: 93.12). For AGEP, we identified acyclovir (ROR: 61.72), valacyclovir (ROR: 30.76), and enoxaparin (ROR: 27.37). For DRESS, we identified vemurafenib (ROR: 17.35), acyclovir (ROR: 30.63), abacavir (ROR: 26.62), raltegravir (ROR: 23.27), and valacyclovir (ROR: 21.77) to have strong reporting odds. CONCLUSION: Our analysis provides an updated tool for physicians to reference when identifying suspected SCARs and a basis for future studies to investigate atypical medication causality.
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Pustulose Exantematosa Aguda Generalizada , Síndrome de Stevens-Johnson , Humanos , Estados Unidos , Acetilcisteína , Cicatriz , Fluconazol , Valaciclovir , Síndrome de Stevens-Johnson/etiologia , Pustulose Exantematosa Aguda Generalizada/etiologiaRESUMO
Intravenous immune globulin (IVIG) is a manufactured blood product commonly used to treat immunodeficiency syndromes, inflammatory disorders, and autoimmune diseases of the skin. The use of IVIG in dermatology has evolved and expanded over time, serving as a useful therapeutic intervention for several inflammatory skin disorders. In addition to demonstrating efficacy in treating several cutaneous pathologies, IVIG also mitigates the need for steroids or other immunosuppressant medications in many dermatologic diseases. This review highlights the evidence for IVIG use across several dermatologic conditions, emphasizing the dosing regimens and safety considerations.
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Imunoglobulinas Intravenosas , Dermatopatias , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Imunoglobulinas Intravenosas/administração & dosagem , Dermatopatias/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Fatores Imunológicos/administração & dosagemRESUMO
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.
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Síndrome de Stevens-Johnson , Humanos , Síndrome de Stevens-Johnson/epidemiologia , Síndrome de Stevens-Johnson/terapia , Síndrome de Stevens-Johnson/mortalidade , Síndrome de Stevens-Johnson/etiologia , Hong Kong/epidemiologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Masculino , Feminino , Adulto , Incidência , Idoso , Tempo de Internação/estatística & dados numéricos , Alopurinol/efeitos adversos , Anticonvulsivantes/efeitos adversos , Anticonvulsivantes/uso terapêutico , Sepse/epidemiologia , Insuficiência de Múltiplos Órgãos/epidemiologia , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/mortalidadeRESUMO
PURPOSE: To evaluate the outcomes of trichiasis (excluding entropion) management in non-trachomatous cicatricial ocular surface diseases. METHODS: This is a multicenter, retrospective study of 59 patients with trichiasis who were managed using two different techniques: electroepilation using radiofrequency (RF) cautery and eyelash resection. The assessed outcomes were residual trichiasis at 6 weeks, 6, and 12 months of follow-up and the number of procedures needed. RESULTS: 41 patients (90 eyelids) underwent electroepilation, and 18 (41 eyelids) were managed with eyelash resection. All patients belonged to either Indian or Japanese ethnicity. Most patients in both groups had Stevens-Johnson Syndrome (63.4% vs. 88.9%). The mean age (43.2 vs. 46 years), disease duration (122 vs. 192.4 months), median trichiasis grade (2 vs. 2), and involvement of upper eyelids (53/90 vs. 23/41) were similar in the two groups. At six weeks, 48.9% of eyelids that underwent electroepilation had no trichiasis, and recurrences were managed with repeat electroepilation (6 eyelids) and mucous membrane grafting (10 eyelids), and 35 eyelids opted for manual epilation, giving 67.8% success at a mean follow-up of 20 months. The eyelash resection group had 75.6% success at 6 months, and recurrences were managed using lid splitting and eyelash resection, resulting in 100% success at a mean follow-up of 79 months. More interventions were needed in the electroepilation group compared to eyelash resection. CONCLUSION: Eyelash resection of the trichiatic eyelashes achieves a better success rate than electroepilation in cicatricial ocular surface disorders. Following electroepilation, one needs multiple interventions to resolve trichiasis.
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Advanced clinical practitioners (ACPs) encounter patients with acute dermatological presentations ranging from minor to life-threatening conditions in both primary and secondary care settings. However, ACPs often feel unprepared to assess and treat patients with dermatological emergencies. This article aims to provide guidance to trainee and qualified ACPs, whether in acute hospital settings or primary care, in understanding the essential aspects to consider when consulting with patients presenting with acute dermatological emergencies. It also emphasises appropriate referrals to relevant specialties for necessary inpatient or outpatient investigations and ensure prompt treatment.
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Emergências , Dermatopatias , Humanos , Dermatopatias/terapia , Doença Aguda , Encaminhamento e Consulta , EmpoderamentoRESUMO
Background: The term severe cutaneous adverse reactions to drugs (SCAR) comprises of acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms complex (DRESS), Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS-TEN) and drug-induced erythroderma or exfoliative dermatitis (ED). The present study aims at describing the epidemiological and clinical profile, probable cause and the extent of morbidity and mortality in patients with severe cutaneous adverse drug reactions. Methods: An observational study of all cases of SCAR presenting to our centre during the period from Jun 2018 to July 2019 was carried out. Results: A total of 24 SCAR patients were studied. Most of the patients were in the age group of 11-20 years. The commonest reactions observed were SJS-TEN (54.2%) followed by DRESS (42%). Antibiotics are the most common cause of SJS-TEN, whereas almost all the drug groups were implicated equally in DRESS. No causative drug could be found in two of the SJS-TEN patients. These patients had raised atypical targetoid lesions as well as evidence of viral reactivation which could have been the probable trigger for the SCAR. A total of five patients (20.8%) died during treatment in hospital, and the percentage mortality was highest in SJS-TEN. Conclusion: Nondrug aetiologies for SJS-TEN are on the rise, and this was observed in this study too. Viral reactivation may be the commonest aetiology in such cases, and the morphology of the rash can give a clue to such cases.