RESUMEN
ABSTRACT: The novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is rapidly spreading throughout the world. The study describes 12 patients with SARS-CoV-2 pneumonia, who developed an acute erythematous rash with nonfollicular pinhead-sized pustules, without mucosal involvement. The clinical differential diagnosis was viral rash, acute generalized exanthematous pustulosis (AGEP), or multiform erythema. computed tomography with a diagnosis of interstitial pneumonia and a respiratory tract sample positive for SARS-CoV-2 in a reverse transcriptase polymerase chain reaction assay. Patients had signs of respiratory distress and were treated with hydroxychloroquine, darunavir, ritonavir, heparin, ceftriaxone, and azithromycin. Punch biopsies showed subcorneal pustules typical of AGEP. Dermal microvascular injury and thrombosis as described in skin damage by SARS-CoV-2 infection was not observed. The direct immunofluorescence for IgG, IgA, IgM, and C3 was negative in 8 patients investigated. A polymerase chain reaction for RNA SARS-CoV-2 performed on frozen skin was negative in 5 of 6 patients. Most of our patients were treated with systemic corticosteroids. After some days (4-10), the diffuse erythema and pustules had improved. AGEP is classified as a severe cutaneous adverse reaction, provoked by drugs and acute infections. Characteristically, removal of the offending agent leads to spontaneous resolution typically in less than 15 days. The recognition of AGEP is important, in order to avoid confusion with a systemic infection and consequently to avoid incorrect treatment. Cutaneous adverse reactions to drugs are common and are major health problems worldwide causing considerable costs for health care systems. We suggest that in the patients with AGEP during SARS-CoV-2 pneumonia, viral infection is a risk factor for developing drug reaction.
Asunto(s)
Pustulosis Exantematosa Generalizada Aguda/etiología , Antivirales/efectos adversos , Tratamiento Farmacológico de COVID-19 , Piel/efectos de los fármacos , Pustulosis Exantematosa Generalizada Aguda/tratamiento farmacológico , Pustulosis Exantematosa Generalizada Aguda/inmunología , Pustulosis Exantematosa Generalizada Aguda/virología , Corticoesteroides/uso terapéutico , Anciano , Anciano de 80 o más Años , Biopsia , COVID-19/diagnóstico , COVID-19/inmunología , COVID-19/virología , Prueba de Ácido Nucleico para COVID-19 , Diagnóstico Diferencial , Femenino , Interacciones Huésped-Patógeno , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Factores de Riesgo , SARS-CoV-2/efectos de los fármacos , SARS-CoV-2/inmunología , Piel/inmunología , Piel/patología , Piel/virología , Resultado del TratamientoAsunto(s)
Pustulosis Exantematosa Generalizada Aguda/genética , Azatioprina/efectos adversos , Proteínas Adaptadoras de Señalización CARD/genética , Síndrome de Hipersensibilidad a Medicamentos/genética , Guanilato Ciclasa/genética , Proteínas de la Membrana/genética , Pirofosfatasas/genética , Pustulosis Exantematosa Generalizada Aguda/diagnóstico , Pustulosis Exantematosa Generalizada Aguda/inmunología , Pustulosis Exantematosa Generalizada Aguda/patología , Adulto , Azatioprina/farmacocinética , Proteínas Adaptadoras de Señalización CARD/inmunología , Análisis Mutacional de ADN , Síndrome de Hipersensibilidad a Medicamentos/diagnóstico , Síndrome de Hipersensibilidad a Medicamentos/inmunología , Síndrome de Hipersensibilidad a Medicamentos/patología , Femenino , Guanilato Ciclasa/inmunología , Humanos , Proteínas de la Membrana/inmunología , Mutación , Pirofosfatasas/metabolismo , Piel/inmunología , Piel/patologíaAsunto(s)
Pustulosis Exantematosa Generalizada Aguda/microbiología , Infecciones por Mycobacterium no Tuberculosas/complicaciones , Pustulosis Exantematosa Generalizada Aguda/sangre , Pustulosis Exantematosa Generalizada Aguda/inmunología , Anciano de 80 o más Años , Anticuerpos Neutralizantes/sangre , Autoanticuerpos/sangre , Humanos , Interferón gamma/inmunología , Masculino , Infecciones por Mycobacterium no Tuberculosas/sangre , Infecciones por Mycobacterium no Tuberculosas/inmunologíaAsunto(s)
Pustulosis Exantematosa Generalizada Aguda/inmunología , Citocinas/inmunología , Inmunidad Innata , Síndrome de Stevens-Johnson/inmunología , Pustulosis Exantematosa Generalizada Aguda/patología , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Síndrome de Stevens-Johnson/patologíaRESUMEN
Cutaneous adverse drug reactions are unpredictable and include various different skin conditions of varying degrees of severity. The most concerning are usually referred to as severe cutaneous adverse reactions (SCARs) and include acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS), also known as drug-induced hypersensitivity syndrome (DiHS) or hypersensitivity syndrome (HSS), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). All are delayed type IV hypersensitivity reactions in which a T-cell-mediated drug-specific immune response is responsible for causing the disease. Nonetheless, specific T-cell subpopulations develop in response to certain environmental conditions and produce cytokines that orchestrate the various phenotypes. Cytotoxic T lymphocytes (CTLs), T-helper type 1 (Th1), Th2, Th17, and regulatory T cells (Treg), among other T-cell subpopulations, participate in the development of SCAR phenotypes. Cell subpopulations belonging to the innate immune system, comprising natural killer cells, innate lymphoid cells, monocytes, macrophages and dendritic cells, can also participate in shaping specific immune responses in various clinical conditions. Additionally, tissue-resident cells, including keratinocytes, can contribute to epidermal damage by secreting chemokines that attract pro-inflammatory immunocytes. The final phenotypes in each clinical entity result from the complex interactions between a variety of cell lineages, their products, soluble mediators and genetic and environmental factors. Although the pathophysiology of these reactions is not fully understood, intensive research in recent years has led to major progress in our understanding of the contribution of certain cell types and soluble mediators to the variability of SCAR phenotypes.
Asunto(s)
Erupciones por Medicamentos/inmunología , Síndrome de Hipersensibilidad a Medicamentos/inmunología , Pustulosis Exantematosa Generalizada Aguda/inmunología , Pustulosis Exantematosa Generalizada Aguda/patología , Animales , Erupciones por Medicamentos/patología , Síndrome de Hipersensibilidad a Medicamentos/patología , Humanos , Inmunidad InnataRESUMEN
IL-17E (IL-25) is a member of the IL-17 cytokine family involved in the promotion of type 2 immune responses. Recently, IL-17E has been reported to be up-regulated in distinct skin inflammatory diseases such as psoriasis and atopic and contact dermatitis. We assessed the role played by IL-17E in skin inflammation. Here, we show that IL-17E induces skin inflammation in vivo, characterized by the expression of innate immune response genes and the recruitment of innate immune cells, particularly neutrophils. Genetic deletion or IL-17E neutralization ameliorated skin inflammation induced by imiquimod application or tape stripping, with reductions in neutrophil and macrophage infiltration as assessed by t-distributed stochastic neighbor embedding-guided multiparameter flow cytometry analysis, in mice. In humans, IL-17E promotes the recruitment of neutrophils via activation of macrophages in a p38-dependent mechanism. In addition, IL-17E is up-regulated in neutrophil-rich inflammatory skin diseases, such as pyoderma gangrenosum and acute generalized exanthematous pustulosis. Our data show a role for IL-17E in skin inflammation that is unrelated to the development of type 2 immune reactions. We propose that IL-17E is an important common denominator of chronic skin inflammation, promoting innate immune cell recruitment and activation.
Asunto(s)
Pustulosis Exantematosa Generalizada Aguda/inmunología , Dermatitis/inmunología , Interleucina-17/metabolismo , Interleucinas/metabolismo , Piodermia Gangrenosa/inmunología , Pustulosis Exantematosa Generalizada Aguda/patología , Adyuvantes Inmunológicos/administración & dosificación , Animales , Dermatitis/patología , Modelos Animales de Enfermedad , Femenino , Humanos , Imiquimod/administración & dosificación , Inmunidad Innata , Interleucina-17/inmunología , Interleucinas/genética , Interleucinas/inmunología , Macrófagos/inmunología , Macrófagos/metabolismo , Ratones , Ratones Noqueados , Neutrófilos/inmunología , Neutrófilos/metabolismo , Piodermia Gangrenosa/patología , Piel/citología , Piel/inmunología , Piel/patología , Regulación hacia Arriba , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoAsunto(s)
Pustulosis Exantematosa Generalizada Aguda/genética , Anticonvulsivantes/efectos adversos , Epilepsia/tratamiento farmacológico , Antígenos HLA-B/sangre , Pustulosis Exantematosa Generalizada Aguda/sangre , Pustulosis Exantematosa Generalizada Aguda/etiología , Pustulosis Exantematosa Generalizada Aguda/inmunología , Alelos , Carbamazepina/efectos adversos , Epilepsia/diagnóstico , Predisposición Genética a la Enfermedad , Antígenos HLA-B/inmunología , Humanos , India , Masculino , Persona de Mediana Edad , Fenitoína/efectos adversosRESUMEN
BACKGROUND: Distinguishing acute generalized exanthematous pustulosis (AGEP) and pustular psoriasis (PS) can be challenging. Staining for plasmacytoid dendritic cells, or PDCs (producer of IFN-α/ß), and MxA (an IFN-α/ß inducible protein) may help discriminate these entities. METHODS: Forty-three cases of AGEP and PS were compiled from two academic institutions. All cases were examined for CD123+ PDCs, eosinophils, acanthosis, papillomatosis, suprapapillary plate thinning, tortuous dilated capillaries, single necrotic keratinocytes, papillary dermal edema, vasculitis, eosinophil exocytosis, intraepidermal pustules, and subcorneal pustules. A subset of cases (n = 26) was stained for MxA. RESULTS: Perivascular and intraepidermal PDCs, dilated tortuous vessels, and MxA expression in the dermal inflammatory infiltrate were significantly (P < 0.05) in favor of a diagnosis of PS. The absence of PDCs and presence of eosinophils favored a diagnosis of AGEP (P < 0.05). CONCLUSIONS: We found compelling evidence for the use of CD123 to highlight PDCs in these cases. The presence of PDCs and expression of MxA in dermal inflammatory infiltrate, as well as absence of eosinophils and presence of tortuous dilated capillaries favored a diagnosis of PS. Expression of MxA in the dermal infiltrate corresponds with a Th1 pathway in PS and may indicate a Th1 component in the early initial phase of AGEP.
Asunto(s)
Pustulosis Exantematosa Generalizada Aguda , Células Dendríticas , Proteínas de Resistencia a Mixovirus/inmunología , Psoriasis , Enfermedades Cutáneas Vesiculoampollosas , Pustulosis Exantematosa Generalizada Aguda/diagnóstico , Pustulosis Exantematosa Generalizada Aguda/inmunología , Pustulosis Exantematosa Generalizada Aguda/patología , Células Dendríticas/inmunología , Células Dendríticas/patología , Femenino , Humanos , Masculino , Psoriasis/diagnóstico , Psoriasis/inmunología , Psoriasis/patología , Enfermedades Cutáneas Vesiculoampollosas/diagnóstico , Enfermedades Cutáneas Vesiculoampollosas/inmunología , Enfermedades Cutáneas Vesiculoampollosas/patología , Células TH1/inmunología , Células TH1/patologíaRESUMEN
BACKGROUND: Acute Generalized Exanthematous Pustulosis (AGEP) is a rare dermatologic reaction characterized by an erythematous rash with pustular erosions, fever and leukocytosis. Although most often secondary to antibiotic use, AGEP has also been associated with many drugs. A thorough literature search showed only four previously documented cases of ibuprofen-associated AGEP, and one case of dog bite-associated AGEP. CASE REPORT: We present the case of a 46â¯year old Caucasian female who developed AGEP after self-treating with ibuprofen for a dog bite. CONCLUSION: In the clinical setting this rash is often dramatic and illuminating the causative agent can be a diagnostic challenge. Our case represents a rare cause of AGEP and an important finding for current practitioners.
Asunto(s)
Pustulosis Exantematosa Generalizada Aguda/patología , Analgésicos no Narcóticos/efectos adversos , Analgésicos no Narcóticos/uso terapéutico , Mordeduras y Picaduras/patología , Ibuprofeno/efectos adversos , Dolor/tratamiento farmacológico , Pustulosis Exantematosa Generalizada Aguda/etiología , Pustulosis Exantematosa Generalizada Aguda/inmunología , Analgésicos no Narcóticos/administración & dosificación , Animales , Antibacterianos , Mordeduras y Picaduras/tratamiento farmacológico , Mordeduras y Picaduras/inmunología , Perros , Femenino , Fiebre , Humanos , Ibuprofeno/administración & dosificación , Persona de Mediana Edad , Resultado del TratamientoAsunto(s)
Pustulosis Exantematosa Generalizada Aguda/etiología , Antifúngicos/efectos adversos , Candidiasis Cutánea/tratamiento farmacológico , Psoriasis/patología , Terbinafina/efectos adversos , Pustulosis Exantematosa Generalizada Aguda/inmunología , Pustulosis Exantematosa Generalizada Aguda/patología , Anciano de 80 o más Años , Candida/inmunología , Candida/aislamiento & purificación , Candidiasis Cutánea/inmunología , Candidiasis Cutánea/microbiología , Progresión de la Enfermedad , Humanos , Masculino , Psoriasis/inmunología , Piel/efectos de los fármacos , Piel/patologíaAsunto(s)
Pustulosis Exantematosa Generalizada Aguda/etiología , Antibacterianos/efectos adversos , Erupciones por Medicamentos/etiología , Interleucina-23/inmunología , Piel/efectos de los fármacos , beta-Lactamas/efectos adversos , Pustulosis Exantematosa Generalizada Aguda/diagnóstico , Pustulosis Exantematosa Generalizada Aguda/tratamiento farmacológico , Pustulosis Exantematosa Generalizada Aguda/inmunología , Anciano , Biopsia , Erupciones por Medicamentos/diagnóstico , Erupciones por Medicamentos/tratamiento farmacológico , Erupciones por Medicamentos/inmunología , Femenino , Humanos , Piel/inmunología , Piel/patología , Esteroides/uso terapéutico , Resultado del TratamientoAsunto(s)
Pustulosis Exantematosa Generalizada Aguda/etiología , Antagonistas Adrenérgicos/efectos adversos , Antihipertensivos/efectos adversos , Hipertensión Inducida en el Embarazo/tratamiento farmacológico , Labetalol/efectos adversos , Pustulosis Exantematosa Generalizada Aguda/diagnóstico , Pustulosis Exantematosa Generalizada Aguda/inmunología , Antagonistas Adrenérgicos/inmunología , Adulto , Antihipertensivos/inmunología , Atenolol/efectos adversos , Atenolol/inmunología , Reacciones Cruzadas , Sustitución de Medicamentos , Femenino , Humanos , Hipertensión Inducida en el Embarazo/diagnóstico , Labetalol/inmunología , Pruebas del Parche , Valor Predictivo de las Pruebas , Embarazo , Tercer Trimestre del EmbarazoRESUMEN
Pharmacogenomics is gradually becoming more and more indispensable in modern medicine. In several cases, a pharmacogenomics test may alleviate serious drug-induced adverse reactions, if it precedes drug prescription. In this article, we provide an overview of the well-established HLA-based carbamazepine- and allopurinol-induced adverse reactions, as one of the most characteristic examples of the clinical application of pharmacogenomics, highlighting its regional impact in Southeast Asian populations in preventing adverse reactions of certain drug/allele pairs. This example provides useful insights towards evidence generation for policy implementation, including economic evaluation analysis, the implementation of pharmacogenomics testing procedures and monitoring of policy effectiveness, hence serving, per se or in the context of international collaborative efforts, as a model for similar cases in several national healthcare systems worldwide.
Asunto(s)
Alopurinol/efectos adversos , Anticonvulsivantes/efectos adversos , Antimetabolitos/efectos adversos , Carbamazepina/efectos adversos , Antígenos de Histocompatibilidad Clase II/genética , Antígenos de Histocompatibilidad Clase I/genética , Pustulosis Exantematosa Generalizada Aguda/genética , Pustulosis Exantematosa Generalizada Aguda/inmunología , Alelos , Pueblo Asiatico/genética , Síndrome de Hipersensibilidad a Medicamentos/genética , Síndrome de Hipersensibilidad a Medicamentos/inmunología , Humanos , Farmacogenética , Polimorfismo Genético , Síndrome de Stevens-Johnson/genética , Síndrome de Stevens-Johnson/inmunologíaRESUMEN
Acute generalized exanthematous pustulosis (AGEP) and generalized pustular psoriasis (GPP) are rare pustular skin disorders with systemic involvement. IL-17A/F is a proinflammatory cytokine involved in various neutrophilic inflammatory disorders. Here we show that IL-17A/F is highly expressed by innate immune cells such as neutrophils and mast cells in both AGEP and GPP.