Moderate and serious adverse reactions to antimicrobials among hospitalized children: A systematic review.

AIMS: This systematic review aimed to investigate the occurrence of moderate and severe adverse drug reactions (ADRs) to antimicrobials among hospitalized children. METHODS: The PubMed/Medline, Cochrane Library, Embase, Web of Science, Scopus, Lilacs and CINAHL databases were searched in April 2023 to systematically review the published data describing the characteristics of moderate and severe ADRs to antimicrobials among hospitalized children. The search was carried out without date restrictions, up to the search date (April, 2023). RESULTS: At the end of the selection process, 30 articles met the inclusion criteria. Cutaneous reactions were the primary serious clinical manifestations in most articles (19/30), followed by erythema multiforme (71 cases), Stevens-Johnson syndrome (72 cases), and toxic epidermal necrolysis (22 cases). The main antimicrobials involved in moderate and severe ADRs were penicillins, cephalosporins and sulfonamides. Regarding the primary outcomes, 30% (9/30) of the articles reported deaths, and 46.7% (14/30) of studies reported increased lengths of hospital stay, need for intensive care, and transfer to another hospital. Regarding the main interventions, 10% (3/30) of the articles mentioned greater monitoring, suspension, medication substitution or prescription of specific medications for the symptomatology. CONCLUSIONS: The findings of this review could be used to identify areas for improvement and help health professionals and policymakers develop strategies. In addition, we emphasize the importance of knowing about ADRs so that there is adequate management to avoid undesirable consequences.

[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.

Investigation of Four Cases of Stevens-Johnson Syndrome among Participants in a Mass Drug Administration Campaign with Sulfadoxine-Pyrimethamine and Primaquine in Haiti, 2020.

In 2018, a mass drug administration (MDA) campaign for malaria elimination was piloted in Haiti. The pilot treated 36,338 people with sulfadoxine-pyrimethamine (SP) and primaquine; no severe adverse events were detected. In 2020, another MDA campaign using the same medications was implemented to mitigate an upsurge in malaria cases during the COVID-19 pandemic. Four cases of Stevens-Johnson syndrome (SJS) were identified among the 42,249 people who took the medications. Three of these individuals required hospitalization; all survived. In addition to SP ingestion, an investigation of potential causes for increased SJS cases identified that all four cases had human leukocyte antigens A*29 and/or B*44:03, another known risk factor for SJS. Additionally, three of the four case individuals had antibodies to SARS-CoV-2, and the fourth may have been exposed around the same time. These findings raise the possibility that recent SARS-CoV-2 infection may have contributed to the increased risk for SJS associated with SP exposure during the 2020 campaign.

Use of Intravenous Immunoglobulins and Systemic Corticosteroids in Patients with Toxic Epidermal Necrolysis: Experience of a Hospital in Mexico City. / Tratamiento con inmunoglobulina intravenosa y esteroides sistémicos en pacientes con necrólisis epidérmica tóxica: Experiencia en un hospital en Ciudad de México.

Toxic epidermal necrolysis is the most serious mucocutaneous adverse drug reaction. Multidisciplinary treatment and withdrawal of the causative drug are key to reducing mortality. Few studies have analyzed the use of systemic corticosteroids and intravenous immunoglobulins (IVIG) in patients with toxic epidermal necrolysis in Latin America. We describe our experience with 6 cases treated at a dermatology referral hospital in Mexico City. None of the patients died or developed complications in the short or medium term. The most widely used regimen was a combination of IVIG 1 g/kg for 3 to 5 days and methylprednisolone 1 g for 3 to 5 days. Mean hospital stay was 14.8 days. The combined use of systemic corticosteroids and IVIG seems to be a safe treatment option for patients with toxic epidermal necrolysis.

[Toxic epidermal necrolysis: idiosyncratic reaction to drugs]. / Necrólisis epidérmica tóxica: reacción idiosincrática a neurofármacos.

Toxic epidermal necrolysis (NET) and Steven Johnson syndrome (SJS) are infrequent mucocutaneous hypersensitivity reactions with systemic involvement. They are predominantly caused by drugs. We report the case of a patient over 60 years of age who presented with extensive mucocutaneous and ophthalmic injury with hemodynamic failure, associated with the rapid onset of lamotrigine in a short period of time. Although the incidence is low, the mortality rate is high. It requires early suspicious and diagnosis in addition to an interdisciplinary therapeutic approach.

Cutaneous adverse reactions associated with antiseizure medication: clinical characteristics and implications in epilepsy treatment.

OBJECTIVE: To describe the clinical characteristics of cutaneous adverse reactions and cross-sensitivity induced by antiseizure medications and compare the pattern of use of antiseizure medications in patients with epilepsy according to skin rash history. METHODS: We analysed patients with a history of skin rash presenting for up to 12 weeks after initiating antiseizure medication. The history of skin rash was verified by medical charts, interviews, and identification of skin lesions by patients based on illustrative images. The minimum follow-up period was eight months. The control group comprised epilepsy patients with regular antiseizure medication use for at least 12 weeks without skin rash. We included 109 cases and 99 controls. RESULTS: The median (interquartile range) period from the index rash was six years (2-11). Carbamazepine was the trigger medication in 48% of cases and induced skin rashes in all patients with cross-sensitivity and carbamazepine exposure. Stevens-Johnson syndrome, toxic epidermal necrolysis, or drug reactions with eosinophilia and systemic symptoms affected 36% of cases. Carbamazepine- or oxcarbazepine-induced maculopapular exanthema occurred earlier (median: one week) than that induced by other antiseizure medications (median: three weeks) (p=0.006). Cross-sensitivity was more common in patients with at least one episode of Stevens-Johnson syndrome (29%) and Stevens-Johnson/toxic epidermal necrolysis overlap (50%) than in patients with maculopapular exanthema (8%) (p=0.01). Although most cases were mild, the pattern of antiseizure medication use differed from that of controls, with a lower proportion of antiseizure medication typically associated with severe cutaneous adverse reactions (carbamazepine, phenytoin, phenobarbital, primidone, oxcarbazepine, and lamotrigine) (p<0.001). Most cases exposed to high-risk medication, however, did not develop cross-sensitivity. SIGNIFICANCE: Cutaneous adverse reaction history may influence antiseizure medication use. Cross-sensitivity is more common in severe cases and most patients are affected by mild, self-limited skin rashes. Further research should consider the relevance of mild skin rashes in lifelong epilepsy treatment.

Toxic epidermal necrolysis in HIV-infected patients: are intravenous immunoglobulins really necessary in this subgroup?

The spectrum of Stevens-Johnson syndrome/toxic epidermal necrolysis (TEN) is the most severe form of cutaneous adverse reactions to drugs. We report a case of a HIV-positive man with TEN who presented a very good response to a single dose of intravenous immunoglobulins and a short pulse of corticosteroids, together with intensive supportive care. Although the largest study on the management of this type of patients reported to date suggests a scheme of three doses of intravenous immunoglobulins together with glucocorticoids, we implemented a single dose of immunoglobulins due to lack of availability.

[Drug provocation tests to identify analgesic alternatives for an infant with Stevens-Johnson syndrome caused by ibuprofen-acetaminophen]. / Provocación farmacológica para identificar alternativas analgésicas en infante con síndrome de Stevens-Johnson por ibuprofeno-acetaminofén.

BACKGROUND: The Stevens-Johnson syndrome is a serious skin reaction to drugs, and it is potentially life-threatening. Its handling involves the strict restriction of the drug involved, as well as of the drugs that are similar or structurally related. CASE REPORT: A two-year and eight-month old girl with Stevens-Jonson syndrome that was caused by acetaminophen and ibuprofen. Due to the total restriction of non-steroidal anti-inflammatory drugs, and with the purpose of establishing antipyretic alternatives, an oral provocation test was carried out with the usual dose of oral nimesulide, which was negative for both immediate and late reactions. In order to offer a parenteral alternative, a provocation test was carried out with intravenous dipyrone, with in-hospital monitoring for 48 hours in an administration protocol of 10, 30 and 60 %; one dose per hour, for a total of 400 mg. The provocation test was negative for both immediate and late reactions. Oral nimesulide or parenteral dipyrone were prescribed upon requiring analgesic, anti-inflammatory, or antipyretic medication. CONCLUSION: At a pediatric age, febrile symptoms are common and controlling them is fundamental; such that if an allergy to non-steroidal anti-inflammatory drugs and acetaminophen is identified in an infant, an affectation on the quality of life will be entailed.

Antecedentes: El síndrome de Stevens-Johnson es una reacción farmacológica cutánea grave, potencialmente mortal. Su manejo incluye estricta restricción del medicamento implicado y de los fármacos estructuralmente relacionados o similares. Caso clínico: Niña de dos años y ocho meses quien presentó síndrome de Stevens-Johnson desencadenado por acetaminofén e ibuprofeno. Debido a la restricción total de antiinflamatorios no esteroideos y con el fin de establecer alternativas antipiréticas, se realizó provocación oral con dosis usual de nimesulida oral, la cual fue negativa para reacciones inmediatas y tardías. Para ofrecer una alternativa parenteral, se efectuó prueba de provocación con dipirona intravenosa, con vigilancia intrahospitalaria por 48 horas en un protocolo de administración de 10, 30 y 60 %, una dosis cada hora, para un total de 400 mg. La prueba de provocación fue negativa para reacciones inmediatas y tardías. Se indicó nimesulida oral o dipirona oral o parenteral en caso de requerir medicación analgésica, antiinflamatoria o antipirética. Conclusión: En la infancia, los cuadros febriles son comunes y el control de este síntoma es fundamental, de tal forma que si en un infante se identifica alergia a los antiinflamatorios no esteroideos y al acetaminofén, eso supondrá afectación en la calidad de vida.

Stevens-Johnson syndrome and toxic epidermal necrolysis - retrospective review of cases in a high complexity hospital in Brazil.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare conditions characterized by epidermal necrosis, mostly caused by drugs. Despite the rarity of these conditions, morbidity and mortality are high (even in previously healthy patients), and they may be associated with permanent sequelae. METHODS: A retrospective study conducted at a quaternary hospital in Brazil in a period of 10 years. RESULTS: The sample was composed by 41 patients with SJS, SJS/TEN, and TEN confirmed by skin biopsy. Antibiotics and anticonvulsants were the most frequently implied drug classes, and phenytoin was the most important individual culprit drug. In this study, 12.2% of the patients had sequelae, being ophthalmological lesions the most common and one case of a newly described hearing loss. The mortality rate was 16.7% in patients with TEN. CONCLUSIONS: This study describes the largest Latin American case series of SJS and TEN with the diagnosis proven by skin biopsy and adds important data regarding the profile of the disease in Brazil. It also describes a novel sequelae of hearing loss.

Lamotrigine and its relationship with Stevens-Johnson syndrome and toxic epidermal necrolysis / Lamotrigina y su relación con el síndrome de Stevens-Johnson y la necrólisis epidérmica tóxica

Lamotrigine is an antiepileptic drug that has been widely used for epilepsy, as a mood stabilizer (for type 1 bipolar disorder) and in the management of neuropathic pain, it is used both in monotherapy and in complementary therapy. Considered relatively new, approved by the Food and Drug Administration in 1994, its benefits include a greater margin of safety compared to other anticonvulsants. However, although in a lower percentage, it causes severe adverse skin reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis. A review is made about the probable pathways that trigger this delayed hypersensitivity immune response.

La lamotrigina es un fármaco anticonvulsivo que ha sido utilizado ampliamente para tratar la epilepsia, como estabilizador del ánimo (en casos de trastorno bipolar tipo 1) y en el manejo del dolor neuropático; se usa tanto en monoterapia como en terapia complementaria. Considerado como un medicamento relativamente nuevo, aprobado por la Food and Drug Administration en 1994, dentro de sus beneficios se encuentra un mayor margen de seguridad en comparación con otros anticonvulsivos; sin embargo, aunque en menor porcentaje, es causa de reacciones cutáneas adversas graves, como el síndrome de Stevens-Johnson y la necrólisis epidérmica tóxica. En el presente estudio se realiza una revisión de las probables vías que desencadenan esta respuesta inmunitaria de hipersensibilidad tardía.

Unusual oral findings of the toxic epidermal necrolysis in an HIV-infected patient: a case report.

Erythema multiforme (EM), Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis (TEN) have been reported as possible adverse effects of some classes of first-line antiretroviral drugs (ART) for HIV treatment. Herein we report an unusual presentation of TEN lesions associated with ART in an HIV-infected patient. The patient presented disseminated cutaneous eruption and oral lesions from the lips to the oropharynx region, causing odynophagia and dysphagia. In the tongue, circular, atypical erythematous lesions appeared, increasing in diameter over seven days and coalescing since then to complete remission. TEN treatment included efavirenz interruption, use of methylprednisolone, prophylactic antibiotic, and daily laser therapy with low-intensity red light. The circular oral lesions have not been described yet. Reporting our findings and clinical management may help diagnosing other similar cases and guide the clinical conduct. Analgesia and acceleration of oral ulcer repair with red laser therapy are recommended.

Stevens-Johnson syndrome and toxic epidermal necrolysis: a retrospective descriptive study.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare and potentially life-threatening mucocutaneous reactions. Given their rarity, limited cohort studies have been done. The aim of this study is to evaluate and compare the demographics, etiology, management, clinical and laboratory characteristics, complications, and outcome of SJS/TEN patients seen by the inpatient dermatology service at the University of Puerto Rico. METHODS: A retrospective review of 30 cases with identified diagnosis of SJS, overlap SJS/TEN, or TEN who were consulted to the Dermatology Department of the University of Puerto Rico from 2006 to 2017. RESULTS: A total of 24 adult and six pediatric cases were reviewed. Females were predominant with a female to male ratio of 1.3 : 1. The most frequent offending drugs identified were antibiotics (56.7%), anticonvulsants (23.3%), and nonsteroidal anti-inflammatory drugs (NSAIDs) (16.7%) with the most frequent antibiotic identified being trimethoprim/sulfamethoxazole (23.3%). Seventy percent of patients experienced at least one complication, most often of infectious etiology (80.1%). During hospital course, 73% received pharmacologic therapy (23% received IVIG alone, 17% received steroids alone, and 33% both) versus 27% which received only supportive care. Mortality rate in this study was 13.8%. When comparing SCORTEN at day one of admission, deceased cases had a mean SCORTEN at day 1 of 4.0, while survivors had an average of 1.54 (P < 0.001). CONCLUSION: Antibiotics followed by anticonvulsants were the most frequently offending drugs identified within this study.

Fulvestrant-induced toxic epidermal necrolysis.

Toxic epidermal necrolysis is a condition with massive keratinocyte apoptosis, and it is associated with high mortality rates. Fulvestrant, an estrogen receptor antagonist, is indicated in the treatment of estrogen receptor-positive metastatic breast cancer in postmenopausal women. To our knowledge, this is the first described case of toxic epidermal necrolysis due to fulvestrant. A 56-year-old woman received 500 mg of intramuscular fulvestrant monthly for metastatic ductal carcinoma of the breast. Five days after the first dose, the patient presented with a maculopapular rash that evolved to blisters, and a detachment of the epidermis in over 30% of the total body surface area. Histological analysis was compatible with toxic epidermal necrolysis. Fulvestrant was discontinued, topical management and supportive care were initiated.

Fulvestrant-induced toxic epidermal necrolysis

Abstract Toxic epidermal necrolysis is a condition with massive keratinocyte apoptosis, and it is associated with high mortality rates. Fulvestrant, an estrogen receptor antagonist, is indicated in the treatment of estrogen receptor-positive metastatic breast cancer in postmenopausal women. To our knowledge, this is the first described case of toxic epidermal necrolysis due to fulvestrant. A 56-year-old woman received 500 mg of intramuscular fulvestrant monthly for metastatic ductal carcinoma of the breast. Five days after the first dose, the patient presented with a maculopapular rash that evolved to blisters, and a detachment of the epidermis in over 30% of the total body surface area. Histological analysis was compatible with toxic epidermal necrolysis. Fulvestrant was discontinued, topical management and supportive care were initiated.