RESUMO
We report 3 complicated and prolonged cases of mpox in people with advanced human immunodeficiency virus (HIV) not on antiretroviral therapy (ART) at mpox diagnosis. Multiple medical countermeasures were used, including prolonged tecovirimat treatment and immune optimization with ART initiation. Immunofluorescence of skin biopsies demonstrated a dense immune infiltrate of predominantly myeloid and CD8+ T cells, with a strong type I interferon local response. RNAscope detected abundant replication of monkeypox virus (MPXV) in epithelial cells and dendritic cells. These data suggest that prolonged mpox in people with advanced HIV may be due to ongoing MPXV replication, warranting aggressive medical countermeasures and immune optimization.
Assuntos
Infecções por HIV , Mpox , Dermatopatias , Humanos , HIV , BenzamidasRESUMO
BRAF/MEK inhibition remains standard of care for treatment of BRAF-mutated non-small cell lung cancer (NSCLC). Although common adverse events (AEs) have been reported through clinical trials and ongoing clinical practice, only a handful of reports have detailed unusual adverse events associated with these medications. This report presents a patient with BRAF-mutated NSCLC treated with dabrafenib and trametinib who experienced 2 unusual AEs-Sweet syndrome and MEK-associated retinopathy-that responded to steroid treatment. The patient was able to continue BRAF/MEK inhibition through a coordinated multidisciplinary approach. This case highlights the importance for all clinicians to recognize unusual AEs associated with BRAF/MEK inhibition, particularly in the setting of expanded use for all BRAF V600E-mutated solid tumors.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias Pulmonares/tratamento farmacológico , Quinases de Proteína Quinase Ativadas por Mitógeno/uso terapêutico , Oximas/uso terapêutico , MutaçãoAssuntos
Dermatose Linear Bolhosa por IgA , Síndrome de Stevens-Johnson , Humanos , Dermatose Linear Bolhosa por IgA/induzido quimicamente , Dermatose Linear Bolhosa por IgA/diagnóstico , Síndrome de Stevens-Johnson/diagnóstico , Síndrome de Stevens-Johnson/etiologia , Etanercepte/efeitos adversos , Antibacterianos/efeitos adversos , Vancomicina/efeitos adversos , Imunoglobulina ARESUMO
IMPORTANCE: We describe the first report to our knowledge of cutaneous and systemic pathogenicity of human polyomavirus 9 in solid organ transplant recipients. OBJECTIVE: Three solid organ transplant recipients developed a widespread, progressive, violaceous, and hyperkeratotic skin eruption. All died from pulmonary and multiorgan failure around 1 year from onset of the rash. Routine clinical diagnostic testing could not identify any causative agent; therefore, samples and autopsies were investigated for novel pathogens using high-throughput sequencing. DESIGN, SETTING, AND PARTICIPANTS: This case series, including 3 solid organ transplant recipients who developed characteristic pink, violaceous, or brown hyperkeratotic papules and plaques throughout the body, was conducted at the Columbia University Medical Center. Lesional skin biopsies were collected from all 3 patients and subjected to high-throughput illumina sequencing for identification of microbial pathogens. Human polyomavirus 9 was identified in lesional skin biopsies. We subsequently collected ocular swabs, oral swabs, urine samples, and blood samples from patients, and organ tissues at autopsy in 1 patient. We investigated these samples for the presence of human polyomavirus 9 using in situ hybridization and quantitative polymerase chain reaction (PCR) assays. MAIN OUTCOMES AND MEASURES: A description of the clinical and pathologic findings of 3 patients. RESULTS: This case series study found that human polyomavirus 9 was detected in the skin biopsies of all 3 patients by a capture-based high-throughput sequencing method platform (VirCapSeq-VERT). Human polyomavirus 9 was also detected in blood, oral, ocular swabs, and urine by real-time polymerase chain reaction (PCR) assay. In situ hybridization and quantitative PCR assays were performed on the skin biopsies from 3 patients and lung autopsy of 1 patient, which showed the presence of human polyomavirus 9 messenger RNA transcripts, indicating active viral replication and pathogenesis in the skin and lungs. CONCLUSIONS AND RELEVANCE: Human polyomavirus 9 was associated with the widespread cutaneous eruption. All 3 patients had progression of cutaneous disease, accompanied by clinical deterioration, pulmonary failure, and death. One patient underwent autopsy and human polyomavirus 9 was identified in the lungs and paratracheal soft tissue. These findings suggest that human polyomavirus 9 may be associated with cutaneous and possibly pulmonary infection and death in solid organ transplant recipients.
Assuntos
Exantema , Transplante de Órgãos , Infecções por Polyomavirus , Polyomavirus , Dermatopatias , DNA Viral/análise , Humanos , Pulmão , Transplante de Órgãos/efeitos adversos , Polyomaviridae , Polyomavirus/genética , Reação em Cadeia da Polimerase em Tempo Real , TransplantadosAssuntos
Antineoplásicos/uso terapêutico , Compostos de Boro/uso terapêutico , Glicina/análogos & derivados , Pioderma Gangrenoso/tratamento farmacológico , Mieloma Múltiplo Latente/tratamento farmacológico , Idoso , Glicina/uso terapêutico , Humanos , Imunoglobulina A/análise , Masculino , Pioderma Gangrenoso/complicações , Mieloma Múltiplo Latente/complicaçõesAssuntos
Erupções Acneiformes/induzido quimicamente , Aminofenóis/efeitos adversos , Benzodioxóis/efeitos adversos , Agonistas dos Canais de Cloreto/efeitos adversos , Fibrose Cística/tratamento farmacológico , Toxidermias/etiologia , Indóis/efeitos adversos , Pirazóis/efeitos adversos , Piridinas/efeitos adversos , Pirrolidinas/efeitos adversos , Quinolonas/efeitos adversos , Erupções Acneiformes/patologia , Adulto , Combinação de Medicamentos , Toxidermias/patologia , Humanos , MasculinoAssuntos
COVID-19/complicações , Dermatopatias/etiologia , Estado Terminal , Hospitalização , HumanosRESUMO
Neutrophilic drug reactions are unique eruptions that can affect hospitalized patients and share a common pathophysiology with neutrophils as the key mediators of inflammation. They range in clinical presentation from papules and plaques to bullae and erosions to pustules. Although there is some overlap in presentation, each has distinguishing features that aid the clinician in differentiation from one another and from other drug hypersensitivity reactions. Much of the data on these reactions are from case reports and series or retrospective review studies. There are limited prospective observational studies dedicated to these adverse drug reactions. We review the more common and life-threatening neutrophilic drug reactions, their proposed mechanism of action, and their management.