Severe cutaneous adverse reactions in a tertiary care center in Jamaica.

Background: Severe cutaneous adverse reactions (SCARs) are associated with morbidity and mortality. Objective: The aim was to determine the different types of SCARs, their morphology, common offending drugs, interventions, and outcomes. Methods: A retrospective cohort study was conducted of all patients admitted to the dermatology service at the University Hospital of the West Indies with Stevens-Johnson syndrome (SJS), SJS/toxic epidermal necrolysis overlap (TEN), TEN, drug reaction with eosinophilia and systemic symptoms and acute generalized exanthematous pustulosis between January 1, 2012 to June 1, 2022. Results: Fifty-one cases (51) met the inclusion criteria for SCAR. SJS, SJS/TEN overlap and TEN together accounted for 71.2% of cases. SCARs were most frequent in the fourth, fifth and 6th decades of life and there was a female preponderance. Antibiotics (31%) and anticonvulsants (29%) were the most common causative agents for SCARs. Most patients had at least 1 complication. The liver was the most common extracutaneous organ affected. Mortality was 7.8%. The main cause of death was sepsis. Limitations: Results were not generalizable. There were missing data and loss to follow-up. Conclusion: Judicious use of antimicrobials and corticosteroids may be beneficial in treatment of severe cutaneous drug reactions.

Recent findings on drug hypersensitivity in children.

Drug hypersensitivity reactions (DHR) in children have a significant impact on clinical practice and public health. Both under-diagnosis (due to under-reporting) and over-diagnosis (due to the overuse of the term "allergy") are potential issues. The aim of this narrative review is to describe the most recent findings of DHR in children/adolescents and gaps regarding epidemiology, antibiotic allergy, antiepileptic hypersensitivity, vaccine allergy, and severe cutaneous adverse reactions (SCAR) in this age group.

Necrólisis epidérmica tóxica debido a un fármaco a base de caléndula más acetilcisteína: presentación de caso / Toxic Epidermal Necrolysis Induced by a Drug Combination of Calendula and Acetylcysteine: A Case Report / Necrólise epidermal tóxica por medicamento à base de calêndula mais acetilcisteína: relato de caso

Introducción: la hipersensibilidad por fármacos es inducida por una respuesta aberrante del sistema inmune; por lo general, impredecible, dosis independiente y amenazante para la vida del paciente. Las reacciones de hipersensibilidad por fármacos con compromiso mucocutáneo se dan en alrededor del 2 %-3 % de los pacientes hospitalizados. Objetivo: describir un caso de necrólisis tóxica epidérmica por un fármaco a base de caléndula y acetilcisteína como los presuntos desencadenantes. Presentación del caso: hombre de 39 años, quien asistió a emergencias, por malestar general, artralgias, mialgias, astenia y adinamia de un día de evolución. Tres días después refirió la aparición de lesiones purpúricas progre-sivas que se extendieron por cara, extremidades y glúteos; delimitadas; no dolorosas, y sin desaparecer a la digitopresión, asociado con disnea, inestabilidad hemodinámica y cardiovascular. Al sexto día de hos-pitalización, se interrogó al paciente, quien se había automedicado un fármaco de origen desconocido, presuntamente de extracto herbal a base de caléndula más acetilcisteína para artralgias, osteomialgias y disfagia. A la mañana siguiente, presentó lesiones purpúricas y ulcerativas extensas. Se observaron lesiones purpúricas progresivas y ulcerativas en cara extremidades y glúteos. Mediante la sospecha clínica y la evaluación histopatológica, se confirmó la necrólisis tóxica epidérmica. Conclusiones: las reacciones adversas medicamentosas severas que amenazan la vida del paciente son relativamente raras, pero representan un verdadero desafío diagnóstico y terapéutico. Es necesario profundizar en la investigación para esclarecer la causa de este tipo de reacción medicamentosa.

Introduction: Drug hypersensitivity is induced by an aberrant response from the immune system. It is usually unpredictable, dose-independent, and can be life-threatening to the patient. Drug-induced hypersensitivity reactions with mucocutaneous involvement occur in approximately 2­3% of hospitalized patients. However, Toxic Epidermal Necrolysis is a rare case. Aim: To describe a case of drug-induced toxic epidermal necrolysis triggered by Calendula officinalis and acetylcysteine. Case report: A 39-year-old male was pre-sented to the emergency room with malaise, arthralgia, myalgia, asthenia, and adynamia since day one. Three days later, he developed progressive purpuric lesions that spread to the face, extremities, and buttocks. These lesions were painless, not delineate, and did not blanch under pressure. They were asso-ciated with dyspnea and hemodynamic and cardiovascular instability. On the sixth day of hospitaliza-tion, the patient admitted to self-medicating with an unknown drug, presumably a herbal extract based on calendula and acetylcysteine, for arthralgia, myalgia, and dysphagia. The morning after the drug consumption, the patient developed extensive purpuric and ulcerative lesions. A diagnosis of toxic epi-dermal necrolysis was made based on clinical suspicion and histopathological confirmation. Conclusion:Severe adverse drug reactions that threaten a patient's life are relatively rare. However, they represent a real diagnostic and therapeutic challenge when they do occur

Introdução: a hipersensibilidade a drogas é induzida por uma resposta aberrante do sistema imunoló-gico; geralmente imprevisível, independente da dose e com risco de vida para o paciente. As reações de hipersensibilidade a drogas com comprometimento mucocutâneo estão em torno dos 2-3% dos pacien-tes hospitalizados. Objetivo: descrever um caso de necrólise epidérmica tóxica causada por uma droga à base de Calendula officinalis e acetilcisteína como os supostos desencadeantes. Apresentação do caso:homem, 39 anos, deu entrada no pronto-socorro manifestando mal-estar, artralgia, mialgia, astenia e adinamia há um dia. Posteriormente, três dias depois, relatou o aparecimento de lesões purpúricas pro-gressivas que se espalharam para a face, extremidades e nádegas; que são delimitadas, não dolorosas e não desaparecem com a acupressão associada a dispnéia, instabilidade hemodinâmica e cardiovascular. No sexto dia de internação, o paciente foi questionado, y disse que tinha se automedicado com uma droga de origem desconhecida, presumivelmente extrato de ervas à base de calêndula mais acetilcis-teína para artralgia, osteomialgia e disfagia. Na manhã seguinte, apresentou extensas lesões purpúricas e ulcerativas. Observam-se lesões purpúricas progressivas e ulcerativas que se estendem à face, extre-midades e nádegas. Pela suspeita clínica e confirmação histopatológica, confirma-se a necrólise epidér-mica tóxica. Conclusões: reações adversas graves a medicamentos que ameaçam a vida do paciente são relativamente raras, mas quando ocorrem representam um verdadeiro desafio a nível diagnóstico e terapêutico. São precisas mais pesquisas para esclarecer a causa desse tipo de reação medicamentosa.

Role of Silver Nitrate Spray for Skin Wound Care in Patients with Toxic Epidermal Necrolysis: Our Experience in 4 Patients.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are examples of severe cutaneous adverse reactions to drugs (SCARs) with several international recommendations for global medical management, ranging from pharmacological systemic therapy to skin wound care. There is no defined best management of the skin wounds in SJS/TEN. The care of wounds is essential to initiate re-epithelialization. Our objective is to improve the cicatrization process, avoiding scarring due to deepening of the wounds, as well as prevent infections, achieve pain control, and avoid loss of serum proteins, fluids, and electrolytes. In this retrospective case series, we highlight the value of systemic therapy and the use of silver nitrate for wound management in four patients with TEN.

[Stevens-Johnson syndrome in a patient with positive lymphocyte transformation test]. / Síndrome de Stevens-Johnson en una paciente con prueba positiva de transformación linfocitaria.

BACKGROUND: Stevens-Johnson syndrome is a severe drug reaction. Sulfonamides have been associated with drug reactions, complications, sequelae, even death. CASE REPORT: A 40-year-old female patient with a medical history of endometriosis and recently diagnosed chronic inflammatory ulcerative colitis. She was treated at the Allergology service of the San Juan de Dios Hospital of the Costa Rican Social Security Fund, and after 20 days of treatment with sulfasalazine she had a severe drug reaction on the skin, compatible with Stevens-Johnson syndrome. The lymphocyte transformation test was positive, confirming sulfasalazine as the causative agent. CONCLUSION: The lymphocyte transformation test is a useful method that can confirm the causative agent and prevent important complications in the future.

ANTECEDENTES: El síndrome de Stevens-Johnson es una reacción medicamentosa severa. Las sulfamidas se han asociado con reacciones medicamentosas, complicaciones, secuelas, incluso la muerte. REPORTE DE CASO: Paciente femenina de 40 años, con antecedentes médicos de endometriosis y colitis ulcerativa crónica inflamatoria de reciente diagnóstico. Fue atendida en el servicio de Alergología del Hospital San Juan de Dios de la Caja Costarricense del Seguro Social, y luego de 20 días de tratamiento con sulfasalazina tuvo una reacción medicamentosa severa en la piel, compatible con síndrome de Stevens-Johnson. La prueba de transformación linfocitaria resultó positiva, con lo que se confirmó la sulfasalazina como el agente causal. CONCLUSIÓN: La prueba de transformación linfocitaria es un método útil que puede confirmar el agente causal y prevenir complicaciones importantes a futuro.

[ABCD-10 scale as a predict of mortality in children with severe pharmacodermias. Case report]. / Escala ABCD-10 como predictor de mortalidad en niños con farmacodermias graves. Reporte de caso.

BACKGROUND: The severe pharmacodermias (SF) are associated with high morbidity and mortality. Chronic kidney failure (CKD) related with dialysis is one of the main factors associated with higher mortality. ABCD-10 is a predictive mortality scale that includes the history of dialysis. CASE REPORT: Male 2 years old with a history of CKD on peritoneal dialysis and Lennox-Gastaut syndrome, admitted to the hospital due to acute peritonitis and developed SJS-NET secondary to phenytoin administration. He was treated with immunoglobulin and systemic steroid without improvement. Septic shock was added, presenting a fatal outcome. CONCLUSIONS: In the case presented, the ABCD-10 scale was applied, reporting a greater prediction of mortality compared to SCORTEN due to a history of dialysis. In children with SF there are no validated predictive mortality. Future initiatives should search for risk factors for mortality in children who develop SF for the creation of a predictive mortality scale.

ANTECEDENTES: Las farmacodermias graves se asocian con alta morbilidad y mortalidad. La insuficiencia renal crónica relacionada con diálisis es uno de los principales factores asociados con mortalidad. REPORTE DE CASO: Paciente pediátrico masculino de 2 años, con antecedente de insuficiencia renal crónica (en tratamiento con diálisis peritoneal) y síndrome de Lennox-Gastaut, que ingresó al hospital por peritonitis aguda y evolucion a síndrome de Stevens-Johnson-necrólisis epidérmica tóxica, debido a la administración de fenitoína. Recibió tratamiento con inmunoglobulina y corticosteroide sistémico sin mejoría; se agregó choque séptico y posteriormente falleció. CONCLUSIONES: La escala ABCD-10 versus SCORTEN es más efectiva para predecir la mortalidad por antecedente de diálisis. En niños con farmacodermias graves no existen escalas predictoras de mortalidad validadas. Las futuras iniciativas deben buscar factores de riesgo de mortalidad en niños con farmacodermias graves para la creación de una escala predictora de mortalidad.

Oral involvement by Stevens-Johnson Syndrome associated with carbamazepine in an immunosuppressed patient: Case report

Introduction: Stevens-Johnson syndrome (SJS) is caused by a delayed immune response triggered by the association of genetic and environmental factors. This reaction can be mediated mainly by some drugs. Objective: The purpose of this article is to report the case of a patient with SJS associated with carbamazepine. Case report: A man was hospitalized complaining of odynophagia, whitish plaques in the mouth and swelling of the lips. Clinical examination revealed ulcerated and erosive lesions involving the buccal mucosa, lips, tongue and hard palate. The lips were swollen and with hemorrhagic crusts. Papular and purplish-colored lesions were observed on the skin. The patient reported that the lesions started 10 days ago, coinciding with the start of carbamazepine use. The diagnosis of SJS was established based on clinical information and the patient treated with support therapy. Conclusion: SJS is a clinical condition that affects the oral mucosa and can be triggered by the use of carbamazepine. (AU)

Eritema multiforme, una rara presentación de exantema en población pediátrica: a propósito de un caso / Erythema multiforme, a rare occurrence of exanthema in the pediatric population: on the subject of a case

El Eritema multiforme (EM) o eritema polimorfo es una enfermedad aguda de la piel de naturaleza inmunológica con o sin compromiso de mucosas, que puede comportarse como crónica recurrente. Se presenta con lesiones cutáneas en diana distintivas, a menudo acompañado de úlceras o bullas en mucosas (oral, genital u ocular). Entre sus formas clínicas se distingue: una forma menor caracterizado por un síndrome cutáneo leve y su forma mayor que se manifiesta como una afectación cutánea con daño mucoso marcado. Entre sus principales diagnósticos diferenciales se encuentran el Síndrome de Stevens-Johnson (SSJ) y Síndrome de Lyell (Necrólisis epidérmica tóxica (NET)). Tiene una incidencia estimada < 1%, siendo su forma mayor levemente más frecuente que su forma menor (0.8-6 por millón/año). Puede darse a cualquier edad, presentando un peak de incidencia entre los 20 y 30 años, predominando ligeramente el sexo masculino con una proporción 3:2, sin predilección racial. Su presentación en edad pediátrica es rara, más aún en la primera infancia. En esta población es más frecuente el EM menor recurrente. En el presente texto se reporta un caso de EM en población pediátrica como una rara forma de presentación exantemática, abordado en el Servicio de Pediatría del Complejo Asistencial Dr Victor Rios Ruiz (CAVRR)en la ciudad de Los Ángeles, Chile en el presente año.

Erythema multiforme (EM) also known as polymorph erythema is an acute skin disease of immunological nature with or without mucous membrane involvement, which may behave as chronic recurrent. It presents with distinctive targets like skin lesions, often together with ulcers or bullae in mucous membranes (oral, genital or ocular). Among its clinical forms are: a minor form characterized by a mild skin syndrome and its major form that manifests as a skin disease with marked mucosal damage. Among its main differential diagnoses are Stevens-Johnson Syndrome (SJS) and Lyell Syndrome (Toxic Epidermal Necrolysis (TEC)). It has an estimated incidence < 1%, with its major form being slightly more frequent than its minor form (0. 8-6 per million/year). It can occur at any age, presenting a peak incidence at the age between 20 and 30 years, with a slight predominance of males with a 3:2 ratio, without racial predilection. Its presentation in pediatric age is rare, even more so in early childhood. Minor recurrent EM is more common in this population. This paper reports a case of EM in the pediatric population as a rare form of exanthematic presentation, addressed at the Department of Pediatrics of the Complejo Asistencial Victor Rios Ruiz (CAVRR) in the city of Los Angeles, Chile this year.

Síndrome de stevens johnson, a propósito de un caso / Stevens Johnson syndrome: about a case

El síndrome de Stevens Jonson y la Necrolisis Epidérmica Toxica forman parte de un mismo espectro clínico caracterizado por lesiones cutáneas y mucosas con necrosis y desprendimiento de la piel, se diferencian por la extensión y la gravedad de las lesiones, aunque existen casos traslapados como en este caso, donde la paciente presentaba lesiones en más del 30% del cuerpo pero, solo fueron lesiones cutáneas y no así mucosas, lo que favoreció a su recuperación exitosa sin necesidad de ingresar a un servicio de terapia intensiva.

The Stevens Johnson syndrome and Toxic Epidermal Necrolysis are part of the same clinical spectrum characterized by cutaneous lesions and mucous membranes with necrosis and detachment of the skin. They differ by the extent and severity of the lesions. Although, there are overlapping cases as in this case, where the patient had lesions in more than 30% of the body. But they were only skin lesions and not mucous membranes, which favored her successful recovery without the need to enter and ITS (intensive therapy service).

The evolution of the modified osteo-odonto-keratoprosthesis, its reliability, and long-term visual rehabilitation prognosis: An analytical review.

An exhaustive search of the world's literature was performed to analyze all case reports and series on the modified osteo-odonto-keratoprosthesis (MOOKP) published up to January 2022. The demographic profile, the primary indication for surgery, surgical technique variations, postoperative medical management, long-term functional and anatomical outcomes, and intra- and postoperative complications were analyzed and compared. Additionally, some of the authors' (GI, VP, and GA) unpublished MOOKP cases were studied. An extensive literature search yielded 37 case series and case reports. Overall, 958 patients were analyzed. The most common indication for surgery was autoimmune disease (39.1%), closely followed by chemical injury (38.8%). The most common intraoperative complications (21.67%) included maxillofacial, vitreous hemorrhage/vitritis, and mucosal. The most common postoperative complications (78.4%) were lamina and oral mucosa-associated, secondary glaucoma, and choroid/retinal detachment. Follow-up periods ranged from one to 364 months (median: 36.7 months). Altogether, 78% of patients achieved a visual acuity of 20/400 or better at the end of the follow-up period, and 91.2% improved at least temporarily after MOOKP surgery. Mean anatomic success at the end-of-follow-up for all patients was 88.25% (range, 50-100%). The long-term anatomic and functional success of the MOOKP makes it a reliable option for visual rehabilitation in patients with bilateral corneal blindness and end-stage ocular surface disease. This review aims to describe the evolution of the MOOKP procedure, analyzing all published case series for its long-term reliability, visual and anatomical outcomes, complications, and future directions.

Dental management in the Intensive Care Unit in the treatment of toxic epidermal necrolysis associated with phenytoin: case report / Manejo odontológico na Unidade de Terapia Intensiva no tratamento da necrólise epidérmica tóxica associada a fenitoína: relato de caso

ABSTRACT Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are adverse reactions, usually medicine-related, in which extensive and painful mucocutaneous lesions are formed. Oral lesions are characterized by the presence of erosions and ulcers. The treatment usually requires intensive care in a hospital setting, where the Dentist is essential in the multidisciplinary team, as he will act in the treatment of oral lesions. In this article, a 26-year-old female patient was reported, who presented TEN-compatible mucocutaneous lesions associated with the drug Phenytoin and required admission to a Teaching Hospital. The treatment consisted of the immediate suspension of the Phenytoin use and systemic therapy with corticosteroids and immunosuppressants. Oral lesions were monitored by the hospital dentistry team. The procedures adopted were: oral hygiene with 0.12% non-alcoholic Chlorhexidine Digluconate solution, hydration of the oral tissue with an essential fatty acid, application of frozen chamomile tea, and prescription of topical Triamcinolone Acetonide. Also, low-level laser therapy sessions (red and infrared) were performed. Oral lesions evolved with significant improvement. In this case, the importance of the Dentist in the multi-professional team is demonstrated. Although there is no protocol, the procedures used in the present case can be an alternative to therapies used in SSJ and TEN oral lesions.

RESUMO A Síndrome de Stevens Johnson (SSJ) e a Necrólise Epidérmica Tóxica (NET) são reações adversas, geralmente medicamentosas. Na pele, formam-se máculas que se tornam pápulas, vesículas e bolhas, além de eritema extenso e desprendimento da epiderme. As lesões bucais caracterizam-se pela presença de erosões e úlceras dolorosas. O tratamento geralmente é realizado em âmbito hospitalar, com necessidade de cuidados intensivos, onde o Cirurgião-dentista é fundamental na equipe multiprofissional, pois atuará na terapêutica das lesões bucais. Neste artigo foi relatado o caso de uma paciente do sexo feminino, de 26 anos, a qual apresentou lesões mucocutâneas compatíveis com NET associadas ao medicamento Fenitoína e necessitou de internamento em um Hospital Universitário. O tratamento realizado foi a suspensão imediata do fármaco desencadeador, além de terapia sistêmica com corticóide e imunossupressor. As lesões bucais foram acompanhadas pela equipe de odontologia hospitalar. As condutas adotadas foram: higiene bucal com solução de Digluconato de Clorexidina 0,12% não alcoólica, hidratação da mucosa bucal com Ácido Graxo Essencial, aplicação de raspas de chá de gelo de camomila e prescrição de Triancinolona Acetonida tópica. Além disso, foram realizadas sessões de laserterapia de baixa intensidade (vermelho e infravermelho). As lesões bucais evoluíram com melhora significativa. A paciente permaneceu internada durante 22 dias, sendo 12 em Unidade de Terapia Intensiva. Este caso demonstra a importância do Cirurgião-dentista na equipe multiprofissional. Apesar de não haver um protocolo para as lesões bucais, as condutas utilizadas no presente caso podem ser uma alternativa de terapêuticas utilizadas em lesões de SSJ e NET.

Stevens-Johnson syndrome and herpes simplex reactivation associated with paracetamol use. Case report / Síndrome de Stevens-Johnson con reactivación de herpes simple asociado a la ingesta de paracetamol. Reporte de caso

Abstract Introduction: Stevens-Johnson syndrome (SJS) is a rare disease that affects the skin, as well as the oral, ocular, and urogenital mucous membranes. This condition is caused by drug reactions in more than 50% of cases. Case presentation: A 20-year-old male visited the emergency service of a tertiary care hospital of Popayán due to a 10-day history of asthenia, adynamia, fever (without objective measurement records), cough with scarce whitish sputum, and headache that improved with paracetamol treatment. However, his condition worsened in the last two days, and he developed hyporexia, pharyngeal pruritus, vesicles, and blisters on the corners of the mouth, the oral mucosa, the trunk, and limbs, as well as breathing difficulty and odynophagia, prompting him to seek medical treatment at the ER. At first, disseminated herpes simplex, systemic lupus erythematosus and SJS were suspected, but based on clinical and laboratory findings, the patient was finally diagnosed with SJS with herpes simplex reactivation associated with the use paracetamol. Consequently, the administration of this drug was stopped and management with acyclovir and methylprednisolone was started. The patient progressed satisfactorily and was discharged 10 days after beginning the new treatment, and his general condition was optimal during follow-up appointments. Conclusion: The occurrence of SJS may be associated with the oral administration of paracetamol; nevertheless, its use is not discouraged due to its great overall benefits. In this sense, given that paracetamol is an over-the-counter drug widely used in Colombia, recognizing the clinical manifestations of SJS is essential to provide adequate management and avoid complications in cases such as the one reported here.

Resumen Introducción. El síndrome de Stevens-Johnson (SJS) es una enfermedad poco común que afecta la piel y las mucosas oral, ocular y urogenital; además, en más del 50% de los casos es producida por reacciones a medicamentos. Presentación del caso. Hombre de 20 años quien asistió al servicio de urgencias de un hospital de tercer nivel de Popayán (Colombia) por un cuadro clínico de 10 días de evolución consistente en astenia, adinamia, fiebre no cuantificada, tos con escasa expectoración blanquecina y cefalea, sintomatologia que mejoraba con el uso de paracetamol; sin embargo, la condición del paciente empeoró en los últimos dos días, presentando hiporexia, prurito en faringe, vesículas y ampollas en comisuras labiales, mucosa oral, tronco y extremidades, además de dificultad respiratoria y odinofagia, razón por la cual acudió al servicio. En principio de sospechó de herpes simple diseminado, lupus eritema-toso sistêmico, y SJS; sin embargo, con base en los hallazgos clínicos y de laboratorio se confirmó el diagnóstico de SJS con reactivación de herpes simple asociado a la ingesta de paracetamol, por lo que se suspendió este medicamento y se inició manejo con aciclovir y metilprednisolona. El paciente tuvo una evolución satisfactoria y fue dado de alta a los 10 días del inicio del nuevo tratamiento y en las citas de control su condición general era óptima. Conclusiones. El desarrollo de SJS puede estar asociado al consumo de paracetamol; sin embargo, su uso no se desaconseja gracias a sus grandes bondades y beneficios generales. En este sentido, dado que el paracetamol es un medicamento de venta libre y uso extenso en Colombia, es indispensable reconocer las manifestaciones clínicas del SJS para poder dar un manejo adecuado y evitar complicaciones en casos como el aquí reportado.

Reacciones cutáneas adversas graves en la infancia / Severe adverse skin reactions in the childhood

RESUMEN Las reacciones cutáneas a drogas son cada vez más frecuentes en edades pediátricas, con un alto impacto en la salud de los niños. Pueden manifestarse en formas muy disímiles, desde un exantema transitorio hasta cuadros graves con afectación multisistémica potencialmente fatales. En la presente revisión se hace énfasis en las farmacodermias graves en la infancia, con el objetivo de promover el conocimiento por parte del personal médico para facilitar su diagnóstico y tratamiento oportuno. Se desarrolló una búsqueda en la Biblioteca Virtual de Salud de Infomed y en Google: se revisaron 28 trabajos científicos sin limitación de año y país, 24 de ellos pertenecen a los últimos cinco años y de estos 17 a los últimos tres. El dominio de los elementos para el diagnóstico precoz y las opciones terapéuticas son indispensables para elegir la conducta adecuada frente a estas reacciones cutáneas graves y disminuir la morbimortalidad por estas afecciones (AU).

ABSTRACT Skin reactions to drugs are increasingly common at pediatric ages, with a high impact on children's health. They can appear in very dissimilar forms, from a transient rash to serious pictures with potentially fatal multisystem involvement. This review focuses on severe pharmacodermies in the childhood, with the aim of promoting medical staff knowledge to facilitate their timely diagnosis and treatment. A search was led in the Infomed Virtual Health Library and in Google: 28 scientific papers were reviewed without limitation of year and country, 24 of them belong to the last five years and from these 17 to the last three. Mastery of the elements for early diagnosis and therapeutic options are indispensable to choose the appropriate behavior against these serious skin reactions and to decrease morbidity and mortality due to these conditions (AU).

Toxic epidermal necrolysis associated with anticonvulsants / Necrólisis epidérmica tóxica asociada a anticonvulsivantes

ABSTRACT Background and Objectives: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are considered as a continuum of the same process. TEN or Lyell Syndrome is the most severe form. Both entities involve an acute mucocutaneous blistering reaction associated with systemic inflammation. Materials and Methods: We present a case of a young woman who developed TEN following concomitant treatment with valproate, lamotrigine, and phenobarbital. Despite the extensive mucocutaneous detachment (over 90%), prognostic evaluation was favorable (SCORTEN score 2; probability of survival 88%), and this patient evolved satisfactorily. Five days after admission, valproate was reinitiated without any subsequent adverse reaction. Results: Causality evaluation identified both lamotrigine and phenobarbital as "very probable" (ALDEN score = 6) causes and valproate as "very unlikely" (ALDEN score = 0) cause of TEN. Conclusions: SJS and TEN are true life-threatening medical emergencies. This case emphasizes the importance of early diagnosis and treatment, including the discontinuation of the causative agent, which can be lifesaving.

RESUMEN Antecedentes y objetivos: El síndrome de Stevens-Johnson (SSJ) y la necrólisis epidérmica tóxica (NET) se consideran un continuum del mismo proceso. La NET o síndrome de Lyell es la forma más grave. Ambas entidades implican una reacción ampollosa mucocutánea aguda asociada con inflamación sistémica. Materiales y métodos: Presentamos el caso de una mujer joven que desarrolló NET posterior al tratamiento concomitante con valproato, lamotrigina y fenobarbital. A pesar del extenso desprendimiento mucocutáneo (más del 90%), la evaluación pronóstica fue favorable (puntuación SCORTEN 2; probabilidad de supervivencia 88%), y esta paciente evolucionó satisfactoriamente. Cinco días después de su ingreso, se reinició el valproato sin ninguna reacción adversa posterior. Resultados: La evaluación de causalidad identificó tanto la lamotrigina como el fenobarbital como causas "muy probables" (puntuación ALDEN = 6) y el valproato como causas "muy improbables" (puntuación ALDEN = 0) de NET. Conclusiones: El SJS y la NET son verdaderas emergencias médicas potencialmente letales. Este caso enfatiza la importancia del diagnóstico y tratamiento tempranos, incluida la interrupción del agente causal, lo cual puede salvar la vida del paciente.

Clinical Aspects of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis With Severe Ocular Complications in Brazil.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are acute and potentially fatal inflammatory vesiculobullous reactions that affect the skin and mucous membranes, and which are most often triggered by particular medications and infections. In Brazil, the drugs most frequently associated with TEN and SJS include cold medicine such as dipyrone and NSAIDs, followed by carbamazepine, phenobarbital, penicillin, and allopurinol. Genetic variations have been found to increase the risk of SJS/TEN in response to triggering factors such as medications. The most closely associated genes found in Brazilian cold-medicine-related SJS/TEN patients with severe ocular complications are HLA-A*66:01 in those of mixed African and European ancestry and HLA-B*44:03 and HLA-C*12:03 in those of solely European ancestry. Our classification system for grading ocular surface complication severity in SJS/TEN patients revealed the most severe complications to be limbal stem cell deficiency and dry eye. Changes to the conjunctival flora have also been observed in SJS/TEN patients. Our group identified bacterial colonization in 95% of the eyes (55.5% of which were gram-positive cocci, 25.5% of which were gram-negative bacilli, and 19% of which were gram-positive bacilli). Several new treatment options in the acute and chronic ocular management of the SJS/TEN patients have been described. This article highlights some Brazilian institutions' contributions to ocular surface care in both the acute phase (including the use of amniotic membrane transplantation) and the chronic phase (such as eyelid margin and fornix reconstruction, minor salivary gland transplantation, amniotic membrane and limbal transplantation, scleral contact lenses, anti-angiogenic eyedrops for corneal neovascularization, ex-vivo cultivated limbal epithelium transplantation, conjunctival-limbal autografting, oral mucosa transplantation, and keratoprosthesis).

Reações cutâneas graves em crianças: como se comportam? / Severe cutaneous adverse reactions in children: how do they behave?

Introdução: As reações cutâneas graves a medicamentos (RCGM) compreendem um grupo de doenças caracterizadas por hipersensibilidade tardia a um ou vários tipos de fármacos. Por ser uma doença potencialmente fatal, o diagnóstico precoce, bem como o início do tratamento, são de suma importância. Objetivo: Analisar a evolução das RCGM em pacientes pediátricos acompanhados em dois hospitais da cidade de São Paulo, SP. Método: Trata-se de um estudo retrospectivo baseado na análise de prontuários de pacientes atendidos no período de 2002 a 2018 em dois hospitais da capital paulista. Resultados: Não houve diferença entre os sexos, prevaleceu a faixa etária dos adolescentes, e os medicamentos mais implicados com o desenvolvimento das lesões cutâneas foram os anticonvulsivantes, sendo os principais a carbamazepina e fenitoína, sem diferença entre eles, seguidos dos antibióticos betalactâmicos. No tratamento, todos os pacientes fizeram uso de corticoides sistêmicos e anti-histamínicos, sendo que oito pacientes também receberam imunoglobulina intravenosa e um recebeu ciclosporina. A taxa de mortalidade foi baixa e, em relação às complicações e sequelas, a autoimunidade foi a mais encontrada. Conclusão: Os casos de RCGM são eventos raros na faixa etária pediátrica, todavia de alta morbimortalidade e risco de sequelas. O diagnóstico e tratamento precoces contribuem para um melhor prognóstico, sendo de suma importância a identificação da medicação associada, bem como a retirada da mesma.

Background: Severe cutaneous adverse reactions (SCARs) comprise a group of diseases characterized by late hypersensitivity to one or more types of drugs. Because they are potentially fatal, early diagnosis and initiation of treatment are of paramount importance. Objective: To analyze the evolution of SCARs in pediatric patients followed up in two hospitals in São Paulo, SP, Brazil. Methods: This is a retrospective study based on the analysis of medical records of patients treated between 2002 and 2018 in two hospitals in the state capital. Results: There was no difference between sexes, and the age group of adolescents prevailed. Anticonvulsants were the drugs most implicated in the development of skin lesions, especially carbamazepine and phenytoin, with no difference between them, followed by betalactam antibiotics. During treatment, all patients used systemic corticosteroids and antihistamines; eight patients also received intravenous immunoglobulin and one received cyclosporine. The mortality rate was low, and regarding complications and sequelae, autoimmunity was the most commonly found. Conclusion: Cases of SCAR are rare events in the pediatric age group, but morbidity, mortality, and risk of sequelae are high. Early diagnosis and treatment contribute to a better prognosis, and identification of the associated medication as well as its withdrawal are extremely important.

Necrólisis epidérmica tóxica en una adolescente diagnosticada de trastorno bipolar II y tratada con lamotrigina / Toxic epidermal necrolysis in an adolescent with Bipolar Disorder II and treated with Lamotrigine

Resumen La necrólisis epidérmica tóxica es una enfermedad cutánea severa, la mayoría de las veces desencadenada como reacción adversa a medicamentos, con alta morbilidad y mortalidad. La lamotrigina, junto a otros medicamentos estabilizadores del ánimo, constituye la causa medicamentosa más frecuente de esta complicación, consistente en necrosis y esfacelo de la epidermis y mucosas en más del 30 % de la superficie corporal, con la consecuente pérdida de líquidos y electrolitos, respuesta inflamatoria sistémica, susceptibilidad a infecciones y hasta sepsis, además de posibles secuelas ominosas. En la actualidad, el diagnóstico de trastorno bipolar se hace con mayor frecuencia, incluyendo al grupo etario de niños y adolescentes, pero tal proceso diagnóstico se caracteriza por dificultades y controversias en mayor cuantía que otros diagnósticos psiquiátricos. Ello obliga a una meticulosa elucubración diagnóstica y selección farmacológica, con pleno conocimiento de las moléculas del arsenal medicamentoso para, en caso de prescripción de lamotrigina, establecer una escrupulosa psicoeducación al paciente y sus familiares además de un seguimiento estricto y cercano. A propósito del caso de una adolescente diagnosticada de trastorno bipolar II, que recibió lamotrigina durante un episodio depresivo pero con un esquema posológico inadecuado, y desarrolló necrólisis epidérmica tóxica, revisamos y comentamos la literatura correspondiente. Concluimos en que es preciso extremar las precauciones al decidir el uso de lamotrigina para minimizar el riesgo de este severo efecto adverso.

Toxic epidermal necrolysis is a severe skin disease, most often triggered as an adverse drug reaction, with high morbidity and mortality. Lamotrigine, together with other mood stabilizer drugs, constitutes the most frequent drug that causes this complication, which consists of necrosis and detachment of the epidermis and mucosa in more than 30% of the body surface, with the consequent loss of water and electrolytes, systemic inflammatory response, susceptibility to infections and even sepsis, in addition to other possible ominous sequelae. Currently, the diagnosis of bipolar disorder is made more frequently, including the age group of children and adolescents, but such a diagnostic process is characterized by difficulties and controversies to a greater extent than other psychiatric diagnoses. This requires meticulous diagnostic process and pharmacological selection, with full knowledge of the molecules in the drug arsenal so, in case of lamotrigine prescription, it should be established scrupulous psychoeducation to the patient and their family members, as well as strict and close follow-up. A propos of the case of an adolescent girl diagnosed with bipolar II disorder, who received lamotrigine during a depressive episode but with an inappropriate posology, and developed toxic epidermal necrolysis, we reviewed and commented on the corresponding literature. We conclude that extreme caution is necessary when deciding the use of lamotrigine to minimize the risk of this severe adverse effect.

Cese en el desarrollo radicular. Secuelas orales del Síndrome de Stevens-Johnson: Reporte de un caso / Cesse no desenvolvimento radicular. Sequelas orais da síndrome de Stevens-Johnson: relato de caso / Cease in root development. Oral sequelae of Stevens-Johnson Syndrome: A case report

Resumen El Síndrome de Stevens-Johnson (SSJ) y la Necrólisis Epidérmica Tóxica (NET) son enfermedades que se encuentran dentro del espectro de las reacciones adversas cutáneas severas. Estas enfermedades comprometen cavidad oral entre el 25% y 50% de los casos. Se presenta el caso de un paciente de 10 años de edad que sufrió unataque agudo de SSJ a la edad de 6 años. Con implicación de la cavidad oral debido a las secuelas que presenta mucosa oral, raíces cortas y poco desarrolladas en todos los órganos dentario sin otra causa atribuible en su historial médico, diferente al SSJ. La edad a la que se presentó la enfermedad y el estadio de desarrollo dental señalan como causa probable el ataque agudo de SSJ, lo que permite concluir que durante su curso ocurrió un daño en la vaina epitelial de Hertwig, provocando apoptosis y, en consecuencia, un cese en el desarrollo radicular.

Abstract Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are diseases that are within the spectrum of severe cutaneous adverse reactions. These diseases compromise the oral cavity in 25% to 50% of the cases. We present a case of a 10-year-old patient who suffered an acute attack of SJS at the age of 6 years. In the oral cavity, he presented sequelae in the oral mucosa, delayed root developed in all teeth, with no other cause attributable in its medical history, different to the SJS. The age at which the disease occurred and the stage of dental development point to that the acute SJS as a probable cause, which allows us to conclude that damage occurred in the Hertwig epithelial sheath during its course, causing apoptosis and, consequently, a cessation in root development.

Resumo A síndrome de Stevens-Johnson (SJS) e a Necrólise Epidérmica Tóxica (NET) são doenças que estão dentro do espectro de reações adversas cutâneas graves. Essas doenças comprometem a cavidade oral em 25% a 50% dos casos. É apresentado um caso de um paciente de 10 anos de idade que sofreu um ataque agudo de SJS aos 6 anos de idade. Na cavidade oral, apresentava sequelas na mucosa oral, raízes curtas e pouco desenvolvidas em todos os dentes, sem outra causa atribuível no seu histórico médico, diferente da SJS. A idade em que a doença ocorreu e o estágio do desenvolvimento dentário apontam o ataque agudo da SJS como causa provável, o que permite concluir que o dano ocorreu na bainha epitelial de Hertwig durante o seu curso, causando apoptose e, consequentemente, cesse no desenvolvimento radicular.

Whole-Exome Sequencing in Patients Affected by Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Reveals New Variants Potentially Contributing to the Phenotype.

BACKGROUND: Adverse drug reactions (ADRs) are frequent occurring events that can essentially be defined as harmful or unpleasant symptoms secondary to the use of a medicinal product. ADRs involve a wide spectrum of clinical manifestations ranging from minor itching and rash to life-threatening reactions. Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare ADRs. SJS-TEN may be considered a polygenic pathology due to additive/epistatic effects caused by sequence variants in numerous genes. Next-generation sequencing (NGS) represents a potentially interesting exploration tool in such scenario as it facilitates the simultaneous analysis of large genomic regions and genes at affordable cost. METHODS: The present study has involved using whole-exome sequencing (WES) for the first time on SJS-TEN patients. It involved robust and innovative multistep bioinformatics analysis focusing on 313 candidate genes potentially participating in the disease's aetiology, specific drugs' metabolism and gene regulation. RESULTS: We identified combinations of frequently occurring and rare variants that may contribute to the disease's pathogenesis. Depending on the specific drug being taken, different variants (and alleles) in NAT2, CYP2D8, CYP2B6, ABCC2, UGT2B7 and TCF3 were identified as coherent candidates representing potential future markers for SJS-TEN. CONCLUSION: The present study proposed and has described (for the first time) a large-scale genomic analysis of patients affected by SJS-TEN. The genes and variants identified represent relevant candidates potentially participating in the disease's pathogenesis. Corroborating that proposed by others, we found that complex combinations of frequently occurring and rare variants participating in particular drug metabolism molecular cascades could be associated with the phenotype. TCF3 TF may be considered a coherent candidate for SJS-TEN that should be analysed in new cohorts of patients having ADRs.

Síndrome de Steven Johnson: Caso clínico / Steven Johnson syndrome: Clinical case

Resumen El síndrome de Stevens-Johnson (SJS) y la necrosis epidérmica tóxica (TEN) son consideradas como un espectro de enfermedades cutáneas raras pero potencialmente fatales. Se presenta el caso de una mujer de 55 años, con antecedente de epilepsia secundario a angiomas cavernosos en manejo con fenitoína. Asistió por cuadro clínico de dos días de evolución consistente en edema facial asociado a rash pruriginoso en región toracocervical, disfagia y picos febriles no cuantificados. A la exploración física conhiperemia e inyección conjuntival, edema de labios superior e inferior con lesiones tipo aftas blanquecinas y dolorosas. En piel, exantema maculopapular, confluente y eritematoso que desaparece a la digitopresión, de predominio en tronco y extremidades superiores. Ante estos resultados se sugirió que la paciente estuviera cursando con un síndrome de Steven Johnson. Esta es una patología de baja prevalencia, generalmente secundaria a una reacción idiosincrática que en la mayoría de los casos se produce por medio de medicamentos como los antibióticos, anticonvulsivantes, antiinflamatorios no esteroideos, entre otros. El manejo se basa en un diagnóstico temprano, retiro de las sustancias causales, realizar una vigilancia estricta de líquidos corporales, temperatura, aislamiento y un adecuado cuidado de la piel. Dentro de las medidas farmacológicas se puede usar la inmunoglobulina intravenosa.

Summary Stevens-Johnson syndrome (SJS) and toxic epidermal necrosis (TEN) are considered as a spectrum of rare but potentially fatal skin diseases. The case of a 55-year-old woman with a history of epilepsy secondary to cavernous angiomas under management with phenytoin is presented. She attended for a clinical picture of two days of evolution consisting of facial edema associated with pruritic skin eruption in the thoracocervical region, dysphagia and unquantified feverish peaks. On physical examination with hyperemia and conjunctival injection, upper and lower lip edema with whitish and painful thrush-like lesions. In the skin, a maculopapular, confluent and erythematous rash that disappears when digitopressured, predominantly in the trunk and upper extremities. Given these results, it was suggested that the patient be studying with Steven Johnson syndrome. This is a pathology of low prevalence, generally secondary to an idiosyncratic reaction that in most cases occurs through medications such as antibiotics, anticonvulsants, non-steroidal anti-inflammatory drugs, among others. Management is based on early diagnosis, removal of causal substances, strict monitoring of body fluids, temperature, isolation and proper skin care. Within pharmacological measures, intravenous immunoglobulin can be used.