RESUMEN
Skin rash is a well-known predictive marker of the response to cetuximab (Cmab) in metastatic colorectal cancer (mCRC). However, the mechanism of skin rash development is not well understood. Following exposure to EGFR-targeted therapies, changes in IL-8 levels have been reported. The aim of this study was to evaluate the association between skin rash and inflammatory cytokine levels, including IL-8. Between 2014 and 2017, we prospectively enrolled 38 mCRC patients who underwent chemotherapy with either Cmab or bevacizumab (Bmab) at two hospitals. We performed multiplex cytokine ELISA with 20 inflammatory cytokines including E-selectin, GM-CSF, IFN-alpha, IFN-γ, IL-1 alpha, IL-1 beta, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-17A, IP-10, MCP-1, MIP-1 alpha, MIP-1 beta, P-selectin, sICAM-1, and TNF-alpha at baseline before cycle 1, 24 h after cycle 1, before cycle 2 (= 14 d), and before cycle 3 (= 28 d). Cytokine levels were compared using ANOVA after log-transformation. IL-8 genotypes in 30 patients treated with Cmab were determined using the polymerase chain reaction restriction fragment length polymorphism technique. Depending on the RAS mutational status, 30 and eight patients were treated with Cmab and Bmab-based chemotherapy, respectively. Skin rash developed in 23 (76.6%) of the 30 patients treated with Cmab plus FOLFIRI, after cycle 1. Only the mean log-transformed serum IL-8 level in patients with skin toxicity was statistically lower (2.83 ± 0.15) than in patients who did not experience skin toxicity (3.65 ± 0.27) and received Bmab (3.10 ± 0.26) (ANOVA test, p value = 0.0341). In addition, IL-8 polymorphism did not affect IL-8 levels, skin toxicity, or tumor response in Cmab treated patients. This study suggests that the inflammatory cytokine levels might be affected by Cmab exposure and are associated with the development of skin rash in mCRC patients. Further studies are warranted to evaluate this interaction in Cmab treated patients.
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Cetuximab , Neoplasias Colorrectales , Exantema , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bevacizumab/uso terapéutico , Cetuximab/efectos adversos , Quimiocina CXCL10 , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Selectina E , Receptores ErbB/efectos de los fármacos , Receptores ErbB/metabolismo , Exantema/etiología , Exantema/inmunología , Factor Estimulante de Colonias de Granulocitos y Macrófagos/uso terapéutico , Interleucina-10 , Interleucina-13 , Interleucina-17 , Interleucina-1alfa , Interleucina-1beta , Interleucina-4 , Interleucina-6 , Interleucina-8 , Selectina-P , Factor de Necrosis Tumoral alfa/uso terapéuticoRESUMEN
INTRODUCTION: A new entity, which occurs a few weeks after SARS-CoV-2 infection and resembling incomplete Kawasaki disease or toxic shock syndrome, has been defined and named multisystem inflammatory syndrome (MIS-C) associated with COVID-19 in children. The aim of our study was to describe histopathological characteristics of skin lesions of MIS-C patients to reveal whether there is a relationship between histopathological features and clinical manifestations. MATERIALS AND METHODS: Seventeen who had skin involvement of 57 patients who were diagnosed with MIS-C between December 2020 and February 2021 were included in this prospective study. Demographic information, laboratory findings, and patients' managements were recorded. Skin biopsies were taken simultaneously of each patient. Formalin-fixed, paraffin-embedded skin samples were examined microscopically. RESULTS: The rate of skin rash was 30% in patients with MIS-C and was predominantly the maculopapular type. The anatomical distribution of the rash was evaluated as localized in 10 and generalized in 7 patients. In patients with myocarditis, C-reactive protein and fibrinogen were found to be significantly higher, and lymphocyte and albumin values were found to be low. Herpes-like inclusions were found in the microscopic examination of 2 patients with a history of zona zoster in themselves or in their mother. There was a significant difference between keratinocyte necrosis and some clinical parameters. DISCUSSION: Localized skin lesions appear to be associated with a more severe inflammatory.
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COVID-19/complicaciones , Exantema/etiología , Piel/patología , Síndrome de Respuesta Inflamatoria Sistémica/complicaciones , Adolescente , Biopsia , COVID-19/inmunología , COVID-19/virología , Niño , Preescolar , Exantema/inmunología , Exantema/patología , Femenino , Humanos , Masculino , Estudios Prospectivos , Piel/inmunología , Síndrome de Respuesta Inflamatoria Sistémica/inmunología , Síndrome de Respuesta Inflamatoria Sistémica/virologíaAsunto(s)
Vacunas contra la COVID-19/efectos adversos , COVID-19/prevención & control , Erupciones por Medicamentos/diagnóstico , Exantema/diagnóstico , SARS-CoV-2/inmunología , Administración Oral , Vacuna BNT162 , Biopsia , COVID-19/complicaciones , COVID-19/diagnóstico , COVID-19/virología , Diagnóstico Diferencial , Erupciones por Medicamentos/tratamiento farmacológico , Erupciones por Medicamentos/inmunología , Erupciones por Medicamentos/patología , Exantema/tratamiento farmacológico , Exantema/inmunología , Exantema/patología , Femenino , Humanos , Persona de Mediana Edad , Prednisolona/administración & dosificación , SARS-CoV-2/genética , Piel/inmunología , Piel/patologíaRESUMEN
Introduction: Immune checkpoint inhibitors (ICIs) achieved response rates around 20% in advanced non-small cell lung cancer (NSCLC) with 8% of patients becoming long-term survivors. Outcomes have improved with the addition of chemotherapy to immunotherapy or the combination of anti-PD(L)1 with anti-CTLA-4 agents.Areas covered: The incidence of immune-related adverse events (irAEs) in patients with NSCLC treated with ICIs varied across clinical trials and real-life studies. The onset of irAEs was 10 weeks. Toxic deaths from irAEs following anti-PD(L)1 administration resulted mainly from pneumonitis. Some irAEs such as rash and thyroiditis were probably associated with better clinical outcomes, though confounding biases exist. Investigations are on-going to determine ideal biomarkers to predict the occurrence, to screen for and to diagnose irAEs.Expert opinion: Prevention, anticipation, detection, treatment and careful monitoring are the five principles that characterize our management of irAEs. Distinguishing immune-induced pneumonitis from progression, pseudo progression, hyper progression, or other etiologies (COVID-19) can be particularly challenging in lung cancer due to the baseline vulnerable pulmonary function and thus requires caution and teamwork. We treat patients according to institutional and international guidelines and we only rechallenge them with ICIs after resolution of the AE and corticosteroid tapering.
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Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Exantema/inducido químicamente , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Neoplasias Pulmonares/tratamiento farmacológico , Neumonía/inducido químicamente , Tiroiditis/inducido químicamente , Corticoesteroides/uso terapéutico , COVID-19/diagnóstico , Diagnóstico Diferencial , Progresión de la Enfermedad , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Exantema/tratamiento farmacológico , Exantema/inmunología , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neumonía/diagnóstico , Neumonía/tratamiento farmacológico , Neumonía/inmunología , Guías de Práctica Clínica como Asunto , SARS-CoV-2 , Tiroiditis/tratamiento farmacológico , Tiroiditis/inmunologíaRESUMEN
INTRODUCTION: Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) is a clinically very well-defined drug eruption, but the histopathological findings are still considered to be nonspecific. OBJECTIVES: To characterize the histopathological and immunophenotypical features of SDRIFE. MATERIAL AND METHODS: We performed a retrospective study that identified 11 biopsies from 9 patients with SDRIFE. The histopathological features were analyzed in conjunction with the immunohistochemical findings. RESULTS: The most common histopathological feature was basal cell vacuolization, which was often associated with necrotic keratinocytes and focal spongiosis. TIA1+ T cells and neutrophils were frequently detected in the epidermis and at the dermoepidermal junction. The dermal inflammatory infiltrate was mixed, consisting of CD3+ T cells, macrophages, granulocytes, low numbers of CD20+ B cells, and plasma cells. A combination of histopathological patterns was observed in 5 cases. The most frequent combined histopathological patterns were interface dermatitis, spongiotic dermatitis, and psoriasiform dermatitis. Other histopathological patterns found in different combinations were pustular dermatitis, perivascular and interstitial neutrophilic dermatitis, and interstitial granulomatous dermatitis. In the other 4 cases, a single histopathological pattern predominated, such as psoriasiform dermatitis, vacuolar interface dermatitis of erythema multiforme-like type, or superficial and deep perivascular and interstitial dermatitis with eosinophils and neutrophils. CONCLUSIONS: SDRIFE is characterized histologically by a vacuolar interface dermatitis induced by cytotoxic T lymphocytes and neutrophilic granulocytes. This pattern may be obscured by accompanying spongiotic, psoriasiform, or pustular features combined with a mixed superficial and sometimes deep dermal infiltrate.
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Erupciones por Medicamentos/inmunología , Exantema/inmunología , Inmunohistoquímica , Inmunofenotipificación , Neutrófilos/inmunología , Piel/inmunología , Linfocitos T Citotóxicos/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/análisis , Biopsia , Erupciones por Medicamentos/patología , Exantema/inducido químicamente , Exantema/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fenotipo , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Piel/efectos de los fármacos , Piel/patologíaAsunto(s)
Eosinofilia/diagnóstico , Exantema/diagnóstico , Leucemia Mieloide Aguda/complicaciones , Síndromes Paraneoplásicos/diagnóstico , Prurito/diagnóstico , Administración Cutánea , Administración Oral , Biopsia , Eosinofilia/tratamiento farmacológico , Eosinofilia/inmunología , Eosinofilia/patología , Exantema/tratamiento farmacológico , Exantema/inmunología , Exantema/patología , Femenino , Glucocorticoides/administración & dosificación , Humanos , Leucemia Mieloide Aguda/inmunología , Persona de Mediana Edad , Síndromes Paraneoplásicos/tratamiento farmacológico , Síndromes Paraneoplásicos/inmunología , Síndromes Paraneoplásicos/patología , Prurito/tratamiento farmacológico , Prurito/inmunología , Prurito/patología , Piel/inmunología , Piel/patología , Resultado del TratamientoRESUMEN
Rash is one of the most common adverse events observed with mogamulizumab, an anti-C-C chemokine receptor 4 monoclonal antibody approved for previously treated mycosis fungoides (MF) and Sezary syndrome (SS). Given the nonspecific clinical presentations of this rash, histopathologic distinction from MF/SS is critical for informing clinical management. We performed a comprehensive characterization of the histopathologic findings in mogamulizumab-associated rash (MAR) with the integration of high-throughput sequencing of T-cell receptor (TCR) genes. Fifty-two biopsy specimens from 19 patients were evaluated retrospectively. Three major histologic reaction patterns were identified: spongiotic/psoriasiform dermatitis (33/52), interface dermatitis (11/52), and granulomatous dermatitis (8/52). Almost half of the specimens (21/52) showed at least 2 of these reaction patterns concurrently. Dermal eosinophils were not a consistent feature, being present in only half (27/52) of specimens and prominent in only 3. Features mimicking MF/SS, including lymphocyte exocytosis, lamellar fibroplasia, and adnexal involvement, were commonly seen but tended to be focal and mild. In 38/43 specimens with available immunohistochemistry, intraepidermal lymphocytes demonstrated a CD4:CD8 ratio ≤1 : 1. Low background levels of the patient's previously identified MF/SS-associated TCR sequence(s) were demonstrated in 20/46 specimens analyzed by high-throughput sequencing of TCR. We conclude that MAR may demonstrate diverse histologic features. Findings that may distinguish MAR from MF/SS include the inverted or normalized CD4:CD8 ratio within intraepidermal lymphocytes and demonstration of absent or nondominant levels of disease-associated TCR sequences. Correlation with the clinical findings and immunohistochemical and molecular characterization of the patient's MF/SS before mogamulizumab, when possible, may facilitate recognition of MAR.
Asunto(s)
Anticuerpos Monoclonales Humanizados/efectos adversos , Antineoplásicos/efectos adversos , Erupciones por Medicamentos/etiología , Exantema/inducido químicamente , Piel/efectos de los fármacos , Linfocitos T/efectos de los fármacos , Relación CD4-CD8 , Erupciones por Medicamentos/genética , Erupciones por Medicamentos/inmunología , Erupciones por Medicamentos/patología , Exantema/genética , Exantema/inmunología , Exantema/patología , Femenino , Genes Codificadores de los Receptores de Linfocitos T , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Piel/inmunología , Piel/patología , Linfocitos T/inmunologíaRESUMEN
RATIONALE: The clinical manifestations of the SARS-CoV-2 infection are mainly respiratory but the virus can cause a variety of symptoms. Dermatological findings are less well-characterized. Data is scarce on their timing, type and correlation with the immune response. PATIENT CONCERNS: We present the case of SARS-CoV-2 infection in a previously healthy woman who presented with respiratory symptoms and developed anosmia, diarrhea, and an erythematous maculo-papular rash on day 15 from symptom onset. DIAGNOSIS: The nasopharyngeal swab tested by real time PCR for COVID-19 was positive. We interpreted this as a viral exanthema likely caused by an immune response to SARS-CoV-2 nucleotides. INTERVENTIONS: She was treated with Hydroxychloroquine, Azithromycin and Lopinavir/Ritonavir, and the rash with topical corticosteroids. OUTCOMES: All symptoms resolved except for anosmia which persisted for 6 weeks. At the 4- and 6-weeks follow-up the IgG titers for SARS-CoV-2 were high. LESSONS: We must consider that SARS-CoV-2 has a multi-organ tropism. In our case, the SARS-CoV-2 infection had lung, nasopharyngeal, neurological, digestive, and skin manifestations. Identifying the different manifestations is useful for understanding the extent of SARS-CoV-2 infection. We not only present a rare manifestation but also suggest that cutaneous manifestations may correlate with immunity.
Asunto(s)
Azitromicina/administración & dosificación , Betacoronavirus , Infecciones por Coronavirus , Exantema , Glucocorticoides/administración & dosificación , Hidroxicloroquina/administración & dosificación , Lopinavir/administración & dosificación , Pandemias , Neumonía Viral , Ritonavir/administración & dosificación , Administración Tópica , Adulto , Antivirales/administración & dosificación , Betacoronavirus/inmunología , Betacoronavirus/aislamiento & purificación , COVID-19 , Prueba de COVID-19 , Técnicas de Laboratorio Clínico/métodos , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/fisiopatología , Infecciones por Coronavirus/terapia , Combinación de Medicamentos , Exantema/diagnóstico , Exantema/tratamiento farmacológico , Exantema/etiología , Exantema/inmunología , Femenino , Humanos , Neumonía Viral/diagnóstico , Neumonía Viral/fisiopatología , Neumonía Viral/terapia , SARS-CoV-2 , Evaluación de Síntomas/métodos , Resultado del TratamientoAsunto(s)
Betacoronavirus/aislamiento & purificación , Infecciones por Coronavirus/complicaciones , Exantema/etiología , Neumonía Viral/complicaciones , COVID-19 , Niño , Infecciones por Coronavirus/inmunología , Diagnóstico Diferencial , Exantema/inmunología , Exantema/virología , Humanos , Masculino , Pandemias , Neumonía Viral/inmunología , SARS-CoV-2 , TiempoRESUMEN
The new coronavirus, severe acute respiratory syndrome coronavirus 2, is associated with a wide variety of cutaneous manifestations. Although new skin manifestations caused by COVID-19 are continuously being described, other cutaneous entities should also be considered in the differential diagnosis, including adverse cutaneous reactions to drugs used in the treatment of COVID-19 infections. The aim of this review is to provide dermatologists with an overview of the cutaneous adverse effects associated with the most frequently prescribed drugs in patients with COVID-19. The skin reactions of antimalarials (chloroquine and hydroxychloroquine), antivirals (lopinavir/ritonavir, ribavirin with or without interferon, oseltamivir, remdesivir, favipiravir, and darunavir), and treatments for complications (imatinib, tocilizumab, anakinra, immunoglobulins, corticosteroids, colchicine and low molecular weight heparins) are analyzed. Information regarding possible skin reactions, their frequency, management, and key points for differential diagnosis are presented.
Asunto(s)
Infecciones por Coronavirus/tratamiento farmacológico , Erupciones por Medicamentos/diagnóstico , Neumonía Viral/tratamiento farmacológico , Antimaláricos/efectos adversos , Antivirales/efectos adversos , Betacoronavirus/inmunología , Betacoronavirus/patogenicidad , COVID-19 , Colchicina/efectos adversos , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/virología , Diagnóstico Diferencial , Erupciones por Medicamentos/etiología , Quimioterapia Combinada/efectos adversos , Quimioterapia Combinada/métodos , Exantema/diagnóstico , Exantema/inmunología , Exantema/virología , Glucocorticoides/efectos adversos , Humanos , Pandemias , Neumonía Viral/complicaciones , Neumonía Viral/inmunología , Neumonía Viral/virología , SARS-CoV-2 , Urticaria/diagnóstico , Urticaria/inmunología , Urticaria/virología , Tratamiento Farmacológico de COVID-19RESUMEN
Cutaneous involvement by leukemia, or leukemia cutis, is a rare manifestation of leukemic disorders, most frequently occurring in children. The skin findings, which usually include multiple violaceous or erythematous nodules on the face, most often follow the classic presenting signs and symptoms of leukemia and occur in patients with an established primary diagnosis. Patients with T-cell acute lymphoblastic leukemia and associated leukemia cutis typically present with a solitary firm red to bluish nodule, often with an accompanying mediastinal mass, that can produce respiratory symptoms. In this article, we report a case of a patient with primary T-cell acute lymphoblastic leukemia/lymphoma presenting with a diffuse exanthem mimicking a viral illness with an associated SET-NUP214 translocation.
Asunto(s)
Exantema/patología , Infiltración Leucémica/patología , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patología , Piel/patología , Adolescente , Biomarcadores de Tumor/análisis , Biopsia , Exantema/inmunología , Humanos , Inmunohistoquímica , Infiltración Leucémica/inmunología , Masculino , Leucemia-Linfoma Linfoblástico de Células T Precursoras/inmunología , Piel/inmunologíaRESUMEN
The SARS-Cov-2 is a single-stranded RNA virus composed of 16 non-structural proteins (NSP 1-16) with specific roles in the replication of coronaviruses. NSP3 has the property to block host innate immune response and to promote cytokine expression. NSP5 can inhibit interferon (IFN) signalling and NSP16 prevents MAD5 recognition, depressing the innate immunity. Dendritic cells, monocytes, and macrophages are the first cell lineage against viruses' infections. The IFN type I is the danger signal for the human body during this clinical setting. Protective immune responses to viral infection are initiated by innate immune sensors that survey extracellular and intracellular space for foreign nucleic acids. In Covid-19 the pathogenesis is not yet fully understood, but viral and host factors seem to play a key role. Important points in severe Covid-19 are characterized by an upregulated innate immune response, hypercoagulopathy state, pulmonary tissue damage, neurological and/or gastrointestinal tract involvement, and fatal outcome in severe cases of macrophage activation syndrome, which produce a 'cytokine storm'. These systemic conditions share polymorphous cutaneous lesions where innate immune system is involved in the histopathological findings with acute respiratory distress syndrome, hypercoagulability, hyperferritinemia, increased serum levels of D-dimer, lactic dehydrogenase, reactive-C-protein and serum A amyloid. It is described that several polymorphous cutaneous lesions similar to erythema pernio, urticarial rashes, diffuse or disseminated erythema, livedo racemosa, blue toe syndrome, retiform purpura, vesicles lesions, and purpuric exanthema or exanthema with clinical aspects of symmetrical drug-related intertriginous and flexural exanthema. This review describes the complexity of Covid-19, its pathophysiological and clinical aspects.
Asunto(s)
Infecciones por Coronavirus/inmunología , Síndrome de Liberación de Citoquinas/inmunología , Coagulación Intravascular Diseminada/inmunología , Eritema/inmunología , Exantema/inmunología , Interacciones Huésped-Patógeno/inmunología , Neumonía Viral/inmunología , Enzima Convertidora de Angiotensina 2 , Betacoronavirus/inmunología , Betacoronavirus/patogenicidad , COVID-19 , Infecciones por Coronavirus/patología , Infecciones por Coronavirus/virología , Síndrome de Liberación de Citoquinas/patología , Síndrome de Liberación de Citoquinas/virología , Progresión de la Enfermedad , Coagulación Intravascular Diseminada/patología , Coagulación Intravascular Diseminada/virología , Eritema/patología , Eritema/virología , Exantema/patología , Exantema/virología , Regulación de la Expresión Génica , Interacciones Huésped-Patógeno/genética , Humanos , Inmunidad Innata , Linfocitos/inmunología , Linfocitos/patología , Linfocitos/virología , Macrófagos/inmunología , Macrófagos/patología , Macrófagos/virología , Pandemias , Peptidil-Dipeptidasa A/genética , Peptidil-Dipeptidasa A/inmunología , Neumonía Viral/patología , Neumonía Viral/virología , Receptores Virales/genética , Receptores Virales/inmunología , SARS-CoV-2 , Serina Endopeptidasas/genética , Serina Endopeptidasas/inmunología , Índice de Severidad de la Enfermedad , Glicoproteína de la Espiga del Coronavirus/genética , Glicoproteína de la Espiga del Coronavirus/inmunologíaAsunto(s)
Anticuerpos Monoclonales Humanizados/administración & dosificación , COVID-19/virología , Fármacos Dermatológicos/administración & dosificación , Exantema/inmunología , Psoriasis/tratamiento farmacológico , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/patogenicidad , Anciano , Anticuerpos Monoclonales Humanizados/efectos adversos , COVID-19/diagnóstico , COVID-19/inmunología , Fármacos Dermatológicos/efectos adversos , Esquema de Medicación , Exantema/diagnóstico , Exantema/virología , Interacciones Huésped-Patógeno , Humanos , Masculino , Psoriasis/diagnóstico , Psoriasis/inmunología , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/inmunologíaAsunto(s)
Síndrome de Liberación de Citoquinas/diagnóstico , Exantema/inmunología , Inmunoterapia Adoptiva/efectos adversos , Linfoma de Células B Grandes Difuso/terapia , Receptores Quiméricos de Antígenos/inmunología , Enfermedades Cutáneas Vesiculoampollosas/inmunología , Adulto , Anticuerpos Monoclonales Humanizados/uso terapéutico , Biopsia , Síndrome de Liberación de Citoquinas/complicaciones , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Síndrome de Liberación de Citoquinas/inmunología , Exantema/diagnóstico , Exantema/tratamiento farmacológico , Exantema/patología , Humanos , Inmunoterapia Adoptiva/métodos , Linfoma de Células B Grandes Difuso/inmunología , Masculino , Piel/inmunología , Piel/patología , Enfermedades Cutáneas Vesiculoampollosas/diagnóstico , Enfermedades Cutáneas Vesiculoampollosas/tratamiento farmacológico , Enfermedades Cutáneas Vesiculoampollosas/patologíaAsunto(s)
Antivirales/efectos adversos , Betacoronavirus/inmunología , Infecciones por Coronavirus/complicaciones , Erupciones por Medicamentos/diagnóstico , Exantema/diagnóstico , Neumonía Viral/complicaciones , Urticaria/diagnóstico , Betacoronavirus/aislamiento & purificación , COVID-19 , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/inmunología , Diagnóstico Diferencial , Exantema/inmunología , Exantema/virología , Humanos , Pandemias , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/epidemiología , Neumonía Viral/inmunología , SARS-CoV-2 , Urticaria/inmunología , Urticaria/virologíaAsunto(s)
Autoanticuerpos/sangre , Dermatomiositis/inmunología , Exantema/inmunología , Complejo Desacetilasa y Remodelación del Nucleosoma Mi-2/inmunología , Neoplasias/epidemiología , Adulto , Anciano , Autoanticuerpos/inmunología , Dermatomiositis/sangre , Dermatomiositis/complicaciones , Dermatomiositis/mortalidad , Exantema/sangre , Exantema/patología , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Músculo Esquelético/inmunología , Músculo Esquelético/patología , Necrosis/inmunología , Neoplasias/inmunología , Pronóstico , Estudios Retrospectivos , Medición de Riesgo/estadística & datos numéricos , Factores de Riesgo , Piel/inmunología , Piel/patologíaRESUMEN
BACKGROUND: Several cases of folliculotropic mycosis fungoides, associated with immunosuppressive therapy, including calcineurin inhibitors, have been reported in solid organ transplant patients. We have encountered 3 patients on immunosuppressive therapy who developed follicular eruptions with folliculocentric infiltrates of nonatypical lymphocytes. OBJECTIVE: To characterize these follicular eruptions and review the literature. METHODS: Three patients, aged 7-15 years, who were treated with systemic immunosuppressive therapy developed follicular eruptions characterized histopathologically by folliculocentric lymphocytic infiltrates. These were studied clinically, histopathologically, immunophenotypically, and molecularly for T-cell receptor (TCR) gene rearrangement. RESULTS: All 3 cases were characterized histopathologically by folliculocentric infiltrates of nonatypical CD3 T lymphocytes with variable follicular exocytosis. Two cases also showed follicular mucinosis. Marked reduction in CD7 staining, and marked predominance of CD4 cells over CD8 cells was observed in all 3 cases. The TCR gene rearrangement studies were monoclonal in 2 cases. Oral calcineurin inhibitors (2 cyclosporine A and 1 tacrolimus) were part of the therapeutic regimen in all 3 patients. Their cessation along with local corticosteroid creams in 2 patients, and phototherapy with oral acitretin in one patient, was associated with complete clinical remission. CONCLUSIONS: Patients undergoing systemic immunosuppressive therapy that includes calcineurin inhibitors might develop follicular eruption with some immunophenotypical variations and a monoclonal TCR gene rearrangement but lack sufficient cytomorphological features of folliculotropic mycosis fungoides. Altering the immunosuppressive agent including calcineurin inhibitors may result in regression of the eruptions.
Asunto(s)
Exantema/inmunología , Huésped Inmunocomprometido , Inmunosupresores/efectos adversos , Adolescente , Niño , Humanos , Enfermedad Iatrogénica , MasculinoRESUMEN
Papulopustular rash, an acneiform rash, appears on the seborrheic region during the first to second week of treatment with an epidermal growth factor receptor inhibitor (EGFRi). The rash gradually disappears after the fourth week; however, it persists or newly develops in other regions during EGFRi treatment. Because Staphylococcus aureus is frequently isolated from late-phase papulopustular rash, we assessed the incidence of bacterial infection and treatment outcomes of patients with late-phase papulopustular rash. Sixty-four cases treated with an EGFRi over 4 weeks who presented with papulopustular rash were assessed retrospectively. The median duration of EGFR inhibitor treatment was 5 months. Grade 2 and 3 papulopustular rash was observed in 47 and eight cases, respectively. Bacterial culture was performed in 51 cases, 50 of which yielded positive results: methicillin-sensitive S. aureus in 29, methicillin-resistant S. aureus in 14, Staphylococcus species in five, Pseudomonas aeruginosa in three, and other in four cases. Of the S. aureus isolates, 42% were resistant to minocycline and 40% to levofloxacin. After treatment with topical and/or oral antibiotics without topical corticosteroids, the papulopustular rash rapidly improved by an average of 2.9 ± 3.4 weeks. However, use of a combination of antibiotics and a topical corticosteroid prolonged the recovery period to an average of 18.9 ± 11.4 weeks. In conclusion, folliculitis that develops over 4 weeks after the initiation of EGFRi treatment is typically caused by staphylococcal infection. Bacterial culture is necessary due to the high rate of antibiotic resistance. It is important to distinguish late- from early-phase papulopustular rash and to treat using different approaches.