Asunto(s)
Síndrome de Hipersensibilidad a Medicamentos , Herpesvirus Humano 6 , Linfadenitis , Linfoma , Infecciones por Roseolovirus , Humanos , Herpesvirus Humano 6/aislamiento & purificación , Linfadenitis/virología , Linfadenitis/diagnóstico , Linfadenitis/etiología , Infecciones por Roseolovirus/complicaciones , Infecciones por Roseolovirus/diagnóstico , Síndrome de Hipersensibilidad a Medicamentos/diagnóstico , Síndrome de Hipersensibilidad a Medicamentos/etiología , Síndrome de Hipersensibilidad a Medicamentos/patología , Linfoma/complicaciones , Diagnóstico Diferencial , Masculino , Femenino , Persona de Mediana EdadRESUMEN
IMPORTANCE: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe cutaneous adverse reaction occurring 2 to 8 weeks after medication initiation. Diagnosis is clinical; RegiSCAR scoring includes biopsy "suggestive of DRESS," undefined in the literature. OBJECTIVE: This study correlates DRESS dermatopathology, culprit drugs, disease course, and outcome severity compared with maculopapular drug reactions (MDR). METHODS: Between 2014 and 2023, a retrospective cohort study at a tertiary care institute reviewed 55 patients with DRESS, assessing demographics, culprit drug, illness course, and histopathology. Biopsies of 15 patients with DRESS and 15 MDR patients were graded by a predefined histopathological scoring system. Statistical analysis (significant P -value<0.05) included the Fisher exact probability, ANOVA, and correlation tests. RESULTS: Among 55 patients with DRESS (mean age 50.13, 28 female/27 male), 15 (mean age 50.4, 7 female/8 male) had diagnostic biopsies. Compared with MDR patients, patients with DRESS exhibited significantly more interface dermatitis ( P = 0.04), lichenoid dermatitis ( P = 0.0007), pigment incontinence ( P = 0.04), and periadnexal interface dermatitis ( P = 0.002). MDR biopsies displayed perivascular inflammation and higher eosinophils than DRESS, trending toward significance. CONCLUSIONS: Key histopathologic features are interface dermatitis, periadnexal interface dermatitis, lichenoid dermatitis, pigment incontinence, and neutrophils dominance over eosinophils indicate DRESS clinically.
Asunto(s)
Síndrome de Hipersensibilidad a Medicamentos , Humanos , Femenino , Masculino , Síndrome de Hipersensibilidad a Medicamentos/patología , Estudios Retrospectivos , Persona de Mediana Edad , Adulto , Anciano , BiopsiaAsunto(s)
Síndrome de Hipersensibilidad a Medicamentos , Hipersensibilidad , Pancitopenia , Humanos , Pancitopenia/inducido químicamente , Pancitopenia/patología , Eosinófilos/patología , Piel/patología , Síndrome de Hipersensibilidad a Medicamentos/diagnóstico , Síndrome de Hipersensibilidad a Medicamentos/etiología , Síndrome de Hipersensibilidad a Medicamentos/patología , Biopsia , Hipersensibilidad/patologíaRESUMEN
BACKGROUND: Drug-induced hypersensitivity syndrome (DIHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is an important adverse reaction caused by a few drugs. Reactivation of human herpesvirus 6 (HHV-6) is known to be associated with its pathogenesis. DIHS occasionally manifests as pulmonary lesions with a variety of imaging findings. CASE PRESENTATION: An 83-year-old woman started taking minodronic acid hydrate 5 years before admission. She noticed a generalized skin rash 44 days before admission and started oral betamethasone-d-chlorpheniramine maleate combination tablets for allergic dermatitis. She developed a fever and cough in addition to the rash, and was referred to our hospital. Laboratory data showed a high level of eosinophils and liver and biliary enzymes. Computed tomography (CT) studies revealed bilateral diffuse ground-glass opacities with ill-defined centrilobular nodules from the central to peripheral regions of the lungs. Transbronchial lung cryobiopsy specimens showed that lymphocyte infiltration was observed in the alveolar walls and fibrinous exudates and floating macrophages in the alveolar lumina. Immunohistochemistry of biopsy specimens showed more CD4+ lymphocytes than CD8+ lymphocytes, while few Foxp3+ lymphocytes were recognized. The serum anti-HHV-6 immunoglobulin G titer increased at 3 weeks after the first test. Based on these findings, we diagnosed her with DIHS. We continued care without using corticosteroids since there was no worsening of breathing or skin condition. Eventually, her clinical symptoms chest CT had improved. Minodronic acid hydrate was identified as the culprit drug based on the positive results of the patch test and drug-induced lymphocyte stimulation test. CONCLUSIONS: We described the first case of DIHS caused by minodronic acid hydrate. Lung lesions in DIHS can present with bilateral diffuse ground-glass opacities and ill-defined centrilobular nodules on a CT scan during the recovery phase. Clinicians should be aware of DIHS, even if patients are not involved with typical DIHS/DRESS-causing drugs.
Asunto(s)
Difosfonatos/efectos adversos , Síndrome de Hipersensibilidad a Medicamentos/etiología , Imidazoles/efectos adversos , Anciano de 80 o más Años , Síndrome de Hipersensibilidad a Medicamentos/patología , Femenino , Humanos , Pulmón/diagnóstico por imagen , Pulmón/patología , Pruebas CutáneasRESUMEN
Glucocorticoids are the final products of the neuroendocrine hypothalamic-pituitary-adrenal axis, and play an important role in the stress response to re-establish homeostasis when it is threatened, or perceived as threatened. These steroid hormones have pleiotropic actions through binding to their cognate receptor, the human glucocorticoid receptor, which functions as a ligand-bound transcription factor inducing or repressing the expression of a large number of target genes. To achieve homeostasis, glucocorticoid signaling should have an optimal effect on all tissues. Indeed, any inappropriate glucocorticoid effect in terms of quantity or quality has been associated with pathologic conditions, which are characterized by short-term or long-lasting detrimental effects. Two such conditions, the primary generalized glucocorticoid resistance and hypersensitivity syndromes, are discussed in this review article. Undoubtedly, the tremendous progress of structural, molecular, and cellular biology, in association with the continued progress of biotechnology, has led to a better and more in-depth understanding of these rare endocrinologic conditions, as well as more effective therapeutic management.
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Síndrome de Hipersensibilidad a Medicamentos/patología , Resistencia a Medicamentos/genética , Glucocorticoides/farmacología , Errores Innatos del Metabolismo/patología , Receptores de Glucocorticoides/deficiencia , Receptores de Glucocorticoides/genética , Animales , Síndrome de Hipersensibilidad a Medicamentos/etiología , Síndrome de Hipersensibilidad a Medicamentos/metabolismo , Humanos , Errores Innatos del Metabolismo/genéticaAsunto(s)
Ciclosporina/uso terapéutico , Síndrome de Hipersensibilidad a Medicamentos/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Metotrexato/uso terapéutico , Corticoesteroides/uso terapéutico , Síndrome de Hipersensibilidad a Medicamentos/patología , Quimioterapia Combinada , Femenino , Humanos , Resultado del TratamientoAsunto(s)
Anticonvulsivantes/efectos adversos , Carbamazepina/efectos adversos , Síndrome de Hipersensibilidad a Medicamentos/etiología , Síndrome de Hipersensibilidad a Medicamentos/patología , Humanos , Masculino , Persona de Mediana Edad , Convulsiones/tratamiento farmacológico , Convulsiones/patología , Piel/efectos de los fármacos , Piel/patologíaAsunto(s)
Benzaldehídos/efectos adversos , Síndrome de Hipersensibilidad a Medicamentos/etiología , Eosinofilia/inducido químicamente , Fármacos Hematológicos/efectos adversos , Pirazinas/efectos adversos , Pirazoles/efectos adversos , Síndrome de Hipersensibilidad a Medicamentos/patología , Eosinofilia/patología , Femenino , Humanos , Persona de Mediana EdadRESUMEN
Although the incidence of severe cutaneous adverse reactions (SCARs) to medications is very low, SCARs can result in disability or even death if they are not diagnosed and treated properly. As the rapid recognition of SCARs is essential, it is necessary to develop diagnostic markers for them that can also be used to assess severity and predict outcomes in the early phase. In addition, it is important to identify novel therapeutic targets for SCARs. Chemokines are chemotactic cytokines that control the migratory patterns and locations of immune cells and usually exhibit markedly specific associations with certain human diseases. In Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), the Th1-associated chemokines chemokine (C-X-C motif) ligand 9 (CXCL9) and CXCL10 predominate, while in drug-induced hypersensitivity syndrome (DIHS)/drug reaction with eosinophilia and systemic symptoms (DRESS), the levels of the Th2-associated chemokines chemokine (C-C motif) ligand 17 (CCL17) and CCL22 are markedly elevated. We suggest that the distinct chemokine profiles of SJS/TEN and DIHS/DRESS can be used to aid their differential diagnosis. CXCL10 has also been reported to be associated with the development of long-term sequelae in DIHS/DRESS. This review focuses on the chemokines involved in the pathogenesis and adjuvant diagnosis of SCARs, particularly SJS/TEN and DIHS/DRESS, but also provides a brief overview of SCARs and the chemokine superfamily. As it is being increasingly recognized that an association exists between human herpesvirus 6 (HHV-6) and DIHS/DRESS, the possible roles of the chemokine/chemokine receptor homologs encoded by HHV-6 in the pathogenesis of DIHS/DRESS are also discussed.
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Quimiocinas/metabolismo , Cicatriz/metabolismo , Cicatriz/patología , Piel/metabolismo , Piel/patología , Animales , Síndrome de Hipersensibilidad a Medicamentos/metabolismo , Síndrome de Hipersensibilidad a Medicamentos/patología , Humanos , Síndrome de Stevens-Johnson/metabolismo , Síndrome de Stevens-Johnson/patologíaRESUMEN
Azathioprine is an immunosuppressant drug used in many dermatological and nondermatological pathologies. Azathioprine hypersensitivity syndrome (AHS) is a rare idiosyncratic reaction that is not related to dose or thiopurine methyltransferase activity. Up to half of cases of AHS can present with variable cutaneous manifestations besides fever, malaise and other systemic symptoms. It is important to be aware of AHS, as continuance or reintroduction of the drug can led to multiorgan failure and cardiovascular collapse.
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Azatioprina/efectos adversos , Síndrome de Hipersensibilidad a Medicamentos/etiología , Síndrome de Hipersensibilidad a Medicamentos/patología , Inmunosupresores/efectos adversos , Piel/patología , Diagnóstico Diferencial , Edema/patología , Humanos , Masculino , Persona de Mediana Edad , Neutrófilos/patologíaRESUMEN
Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS) is a severe type of adverse drug eruption associated with multiorgan involvement and the reactivation of human herpesvirus 6, which arises after prolonged exposure to certain drugs. Typically, two waves of disease activity occur during the course of DIHS/DRESS; however, some patients experience multiple waves of exacerbation and remission of the disease. Severe complications, some of which are related to cytomegalovirus reactivation, can be fatal. DIHS/DRESS is distinct from other drug reactions, as it involves herpes virus reactivation and can lead to the subsequent development of autoimmune diseases. The association between herpesviruses and DIHS/DRESS is now well established, and DIHS/DRESS is considered to arise as a result of complex interactions between several herpesviruses and comprehensive immune responses, including drug-specific immune responses and antiviral immune responses, each of which may be mediated by distinct types of immune cells. It appears that both CD4 and CD8 T cells are involved in the pathogenesis of DIHS/DRESS but play distinct roles. CD4 T cells mainly initiate drug allergies in response to drug antigens, and then herpesvirus-specific CD8 T cells that target virus-infected cells emerge, resulting in tissue damage. Regulatory T-cell dynamics are also suggested to contribute to the diverse symptoms of DIHS/DRESS. However, the pathomechanisms of this complex disease remain largely unknown. In particular, how viral infections contribute to the pathogenesis of DIHS/DRESS and why autoimmune sequelae arise in DIHS/DRESS are yet to be elucidated. This review describes the clinical features of DIHS/DRESS, including the associated complications and sequelae, and discusses recent advances in our understanding of the immunopathogenic mechanisms of DIHS/DRESS.
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Síndrome de Hipersensibilidad a Medicamentos/inmunología , Síndrome de Hipersensibilidad a Medicamentos/patología , Eosinofilia/complicaciones , Presentación de Antígeno/inmunología , Síndrome de Hipersensibilidad a Medicamentos/diagnóstico , Síndrome de Hipersensibilidad a Medicamentos/virología , Antígenos HLA/metabolismo , Humanos , Linfocitos T/inmunologíaAsunto(s)
Antibacterianos/efectos adversos , Síndrome de Hipersensibilidad a Medicamentos/diagnóstico , Síndrome de Hipersensibilidad a Medicamentos/genética , Predisposición Genética a la Enfermedad , Vancomicina/efectos adversos , Síndrome de Hipersensibilidad a Medicamentos/etiología , Síndrome de Hipersensibilidad a Medicamentos/patología , Femenino , Humanos , Persona de Mediana EdadAsunto(s)
Antibacterianos/efectos adversos , Síndrome de Hipersensibilidad a Medicamentos/diagnóstico , Linfohistiocitosis Hemofagocítica/inducido químicamente , Osteomielitis/microbiología , Combinación Piperacilina y Tazobactam/efectos adversos , Antibacterianos/uso terapéutico , Antifúngicos/uso terapéutico , Candida albicans/efectos de los fármacos , Candida albicans/aislamiento & purificación , Síndrome de Hipersensibilidad a Medicamentos/patología , Síndrome de Hipersensibilidad a Medicamentos/terapia , Eosinofilia/inducido químicamente , Eosinofilia/patología , Fluconazol/uso terapéutico , Humanos , Linfohistiocitosis Hemofagocítica/patología , Osteomielitis/tratamiento farmacológico , Combinación Piperacilina y Tazobactam/uso terapéutico , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/aislamiento & purificación , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/aislamiento & purificación , Inhibidores de beta-Lactamasas/uso terapéuticoAsunto(s)
Alveolitis Alérgica Extrínseca/complicaciones , Síndrome de Hipersensibilidad a Medicamentos/complicaciones , Disnea/etiología , Exantema/etiología , Isocianatos/efectos adversos , Exposición Profesional/efectos adversos , Adulto , Alveolitis Alérgica Extrínseca/inducido químicamente , Alveolitis Alérgica Extrínseca/tratamiento farmacológico , Alveolitis Alérgica Extrínseca/patología , Síndrome de Hipersensibilidad a Medicamentos/tratamiento farmacológico , Síndrome de Hipersensibilidad a Medicamentos/etiología , Síndrome de Hipersensibilidad a Medicamentos/patología , Glucocorticoides/uso terapéutico , Humanos , Masculino , Prednisolona/uso terapéuticoAsunto(s)
Síndrome de Hipersensibilidad a Medicamentos/diagnóstico , Predisposición Genética a la Enfermedad , Infecciones por VIH/tratamiento farmacológico , VIH-1 , Antígenos HLA-B/genética , Raltegravir Potásico/uso terapéutico , Alelos , Población Negra , Síndrome de Hipersensibilidad a Medicamentos/patología , Femenino , Humanos , Masculino , Raltegravir Potásico/efectos adversosRESUMEN
Drug rash with eosinophilia and systemic symptoms (DRESS) is a rare delayed drug reaction that often occurs 2-6 weeks after initiation of therapy and may develop into a life-threatening systemic reaction. Besides immediate discontinuation of the suspected inciting drug, initiation of high dose systemic corticosteroids has long been the mainstay of treatment for severe cases. Nevertheless, significant drawbacks associated with systemic corticosteroid therapy, such as the requirement of a long tapering period post resolution and extensive adverse side effects profile, have motivated clinicians to seek alternative treatment options. Over the past decade, an undisputed increasing number of favorable case reports has highlighted cyclosporine as an emerging, safe, and effective alternative despite inconsistent dosing regimens reported. Herein, we report a severe case of vancomycin-induced DRESS syndrome in which the patient failed initial intervention with cyclosporine and needed rescue with methylprednisolone. To the best of our knowledge, this constitutes the first unsuccessful report of cyclosporine treatment for DRESS syndrome.
Asunto(s)
Ciclosporina/uso terapéutico , Síndrome de Hipersensibilidad a Medicamentos/etiología , Vancomicina/efectos adversos , Síndrome de Hipersensibilidad a Medicamentos/tratamiento farmacológico , Síndrome de Hipersensibilidad a Medicamentos/patología , Resistencia a Medicamentos , Eosinofilia/inducido químicamente , Eosinofilia/patología , Exantema/inducido químicamente , Femenino , Antebrazo/patología , HumanosRESUMEN
BACKGROUND: There are conflicting reports on the association between interface dermatitis and hepatic involvement in DRESS. METHODS: A cross-sectional analysis of the clinical and the histopathologic features of DRESS was performed to study the association between the histopathology of the skin rash and hepatic involvement. RESULTS: The clinical and the histopathologic findings were evaluated in 40 cases of DRESS. Thirty patients (75%) had a hepatic involvement. Thirty (75%) biopsy specimens showed a combination of different inflammatory patterns. The interface dermatitis was noted in 24 specimens (60%). Twenty-one patients with the interface dermatitis had a hepatic involvement (P = .04). CONCLUSIONS: The skin rash of DRESS often shows the coexistence of different inflammatory patterns. The interface dermatitis showed a statistically significant association with the hepatic involvement in DRESS.
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Dermatitis/patología , Síndrome de Hipersensibilidad a Medicamentos/patología , Eosinofilia/inducido químicamente , Exantema/inducido químicamente , Hígado/efectos de los fármacos , Adulto , Biopsia , Estudios Transversales , Dermatitis/inmunología , Síndrome de Hipersensibilidad a Medicamentos/diagnóstico , Exantema/patología , Femenino , Humanos , Hiperbilirrubinemia/inducido químicamente , Hígado/enzimología , Hígado/patología , Masculino , Persona de Mediana Edad , Transaminasas/sangre , Transaminasas/efectos de los fármacosAsunto(s)
Síndrome de Hipersensibilidad a Medicamentos/diagnóstico , Eosinofilia/inducido químicamente , Exantema/inducido químicamente , Vacunas contra la Influenza/efectos adversos , Anciano de 80 o más Años , Síndrome de Hipersensibilidad a Medicamentos/patología , Eosinofilia/patología , Exantema/patología , Humanos , MasculinoAsunto(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/patologíaRESUMEN
Drug-induced hypersensitivity syndrome (DIHS), also referred to as drug reaction with eosinophilia and systemic symptoms (DRESS), is a severe hypersensitivity drug reaction affecting the skin and multiple internal organ systems. We report a 47-year-old man with DIHS/DRESS and comorbidities (fulminant type 1 diabetes mellitus, valsartan-induced photosensitivity, vitiligo and acute interstitial nephritis). Although acute interstitial nephritis usually appears in the early phase, his is a rare case of acute interstitial nephritis more than 2 years after the onset of DIHS/DRESS.