RESUMO
Globally, vaccination against COVID-19 has prevented countless infections, hospitalisations and death and represents the most successful intervention in combating the pandemic caused by SARS-CoV-2 infection. Utilisation of existing mRNA vaccine technology has allowed for rapid development of highly immunogenic and effective vaccines. Myopericarditis can occur as an adverse effect of COVID-19 mRNA vaccination, albeit at significantly lower rates than those that occur during SARS-CoV-2 infection. Higher rates are seen in adolescent males, usually within 1-5 days of receiving the second vaccine dose. Although most cases are self-limited and respond to first-line treatment, refractory cases can occur, with a limited evidence base on which to guide management. Here, we present a brief review of COVID-19 mRNA vaccines and associated myopericarditis including risk factors, proposed mechanism, and treatment including management strategies for refractory disease.
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COVID-19 , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Miocardite , Adolescente , Masculino , Humanos , Vacinas contra COVID-19 , SARS-CoV-2 , Vacinação , Vacinas de mRNARESUMO
There is ample evidence that doctors frequently miss meals at work, which negatively impacts concentration, decision-making and overall patient care. Junior doctors are particularly vulnerable given their heavy workload. We report on the impact of a pilot programme supporting home-based meal preparation on the dietary habits and energy levels of interns at a tertiary hospital and demonstrate this is one strategy healthcare organisations can adopt to promote a healthier workforce.
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Almoço , Desempenho Profissional , Humanos , Centros de Atenção Terciária , Refeições , HábitosRESUMO
PURPOSE OF REVIEW: Recipients of allogeneic hematopoietic stem cell transplantation (HSCT) are at increased risk for inflammatory myositis; histological subsets reported include dermatomyositis, necrotising myopathy and chronic graft-versus-host disease (cGVHD)-related myositis. Though corticosteroids and various immunosuppressive therapies have been used, there is a lack of consensus guidelines dictating therapy. RECENT FINDINGS: Recent evidence suggests the fascia as a preferential target in cGVHD myositis, with conditioning regimens promoting fascial microtrauma. Positron emission tomography (PET) can be a useful diagnostic tool, and case reports suggest that the Bruton's tyrosine kinase inhibitor ibrutinib may have therapeutic potential. Emerging therapies include targeted B cell depletion with rituximab, and extracorporeal photophoresis. Clinicians need to be vigilant for the development of inflammatory myositis post-allogeneic HSCT as most patients respond to treatment. Advances in immunohistochemistry to determine the dominant cell type and cytokine profile may enable targeted and individualised therapies.
Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Miosite , Adenina/análogos & derivados , Adenina/uso terapêutico , Doença Crônica , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Miosite/etiologia , Piperidinas/uso terapêutico , Pirimidinas , Rituximab/uso terapêuticoRESUMO
Idiopathic granulomatous mastitis is a chronic inflammatory breast disorder that typically affects young, parous women, often following lactation. Patients present with tender, erythematous breast lesions with histological evidence of non-caseating granulomata and an inflammatory cell infiltrate. An immune-mediated pathophysiology is hypothesised and an association with lipophilic Corynebacterium species is observed. Initial diagnosis is often delayed due to lack of awareness of the condition and management of refractory disease can be challenging. We present an extensive case series of patients collaboratively managed by subspecialty physicians and surgeons at a single centre in Sydney, Australia. The accompanying review expands on features of this condition and supports the utility of a multidisciplinary approach.
Assuntos
Mastite Granulomatosa , Austrália , Aleitamento Materno , Feminino , Granuloma/diagnóstico , Mastite Granulomatosa/diagnóstico por imagem , Mastite Granulomatosa/terapia , Humanos , LactaçãoRESUMO
BACKGROUND: Caspase activation and recruitment domain 11 (CARD11) encodes a scaffold protein in lymphocytes that links antigen receptor engagement with downstream signaling to nuclear factor κB, c-Jun N-terminal kinase, and mechanistic target of rapamycin complex 1. Germline CARD11 mutations cause several distinct primary immune disorders in human subjects, including severe combined immune deficiency (biallelic null mutations), B-cell expansion with nuclear factor κB and T-cell anergy (heterozygous, gain-of-function mutations), and severe atopic disease (loss-of-function, heterozygous, dominant interfering mutations), which has focused attention on CARD11 mutations discovered by using whole-exome sequencing. OBJECTIVES: We sought to determine the molecular actions of an extended allelic series of CARD11 and to characterize the expanding range of clinical phenotypes associated with heterozygous CARD11 loss-of-function alleles. METHODS: Cell transfections and primary T-cell assays were used to evaluate signaling and function of CARD11 variants. RESULTS: Here we report on an expanded cohort of patients harboring novel heterozygous CARD11 mutations that extend beyond atopy to include other immunologic phenotypes not previously associated with CARD11 mutations. In addition to (and sometimes excluding) severe atopy, heterozygous missense and indel mutations in CARD11 presented with immunologic phenotypes similar to those observed in signal transducer and activator of transcription 3 loss of function, dedicator of cytokinesis 8 deficiency, common variable immunodeficiency, neutropenia, and immune dysregulation, polyendocrinopathy, enteropathy, X-linked-like syndrome. Pathogenic variants exhibited dominant negative activity and were largely confined to the CARD or coiled-coil domains of the CARD11 protein. CONCLUSION: These results illuminate a broader phenotypic spectrum associated with CARD11 mutations in human subjects and underscore the need for functional studies to demonstrate that rare gene variants encountered in expected and unexpected phenotypes must nonetheless be validated for pathogenic activity.
Assuntos
Proteínas Adaptadoras de Sinalização CARD/genética , Proteínas Adaptadoras de Sinalização CARD/imunologia , Guanilato Ciclase/genética , Guanilato Ciclase/imunologia , Doenças do Sistema Imunitário/genética , Doenças do Sistema Imunitário/imunologia , Adulto , Feminino , Humanos , Masculino , Mutação , FenótipoRESUMO
Individuals with common variable immunodeficiency (CVID) have an increased risk of gastric cancer, and gastrointestinal lymphoma, yet screening for premalignant gastric lesions is rarely offered routinely to these patients. Proposed screening protocols are not widely accepted and are based on gastric cancer risk factors that are not applicable to all CVID patients. Fifty-two CVID patients were recruited for screening gastroscopy irrespective of symptoms or blood results and were compared to 40 controls presenting for gastroscopy for other clinical indications. Overall, 34% of CVID patients had intestinal metaplasia (IM), atrophic gastritis or moderate to severe non-atrophic gastritis, which can increase the risk of gastric cancer, compared to 7.5% of controls (p < 0.01). Focal nodular lymphoid hyperplasia, a precursor lesion for gastrointestinal lymphoma, was seen in eight CVID patients (16%), one of whom was diagnosed with gastrointestinal lymphoma on the same endoscopy. High-risk gastric pathology was associated with increased time since diagnosis of CVID, smoking, Helicobacter pylori, a low-serum pepsinogen I concentration, and diarrhea, but not pepsinogen I/II ratio, iron studies, vitamin B12 levels or upper gastrointestinal symptoms. There was a lower rate of detection of IM when fewer biopsies were taken, and IM and gastric atrophy were rarely predicted by the endoscopist macroscopically, highlighting the need for standardized biopsy protocols. The prevalence of premalignant gastric lesions in patients with CVID highlights the need for routine gastric screening. We propose a novel gastric screening protocol to detect early premalignant lesions and reduce the risk of gastric cancer and gastric lymphoma in these patients.
Assuntos
Imunodeficiência de Variável Comum/complicações , Imunodeficiência de Variável Comum/epidemiologia , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Biópsia , Imunodeficiência de Variável Comum/etiologia , Detecção Precoce de Câncer , Feminino , Gastrite Atrófica/complicações , Gastroscopia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/microbiologia , Humanos , Masculino , Programas de Rastreamento , Metaplasia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Lesões Pré-Cancerosas , Prevalência , Vigilância em Saúde Pública , Medição de Risco , Fatores de Risco , Neoplasias Gástricas/diagnóstico , Inquéritos e Questionários , Adulto JovemRESUMO
Dual antiplatelet therapy, consisting of aspirin and a P2Y12 receptor antagonist, has been the cornerstone of management in those undergoing percutaneous coronary intervention, reducing stent thromboses and cardiovascular events. Given the pivotal role of aspirin in cardiovascular disease management, patients with aspirin hypersensitivity pose complex clinical challenges. Allergy to aspirin is reported in 1.5-2.6% of patients presenting with cardiac disease. Identification of the subtype of aspirin hypersensitivity will determine suitability for aspirin desensitization, dictate choice of desensitization protocol and inform risk management. Aspirin desensitization is an effective and viable clinical strategy, although it remains underutilised in clinical practice. Collaboration between cardiologists and immunologists should be strongly encouraged to facilitate optimal management of such patients. This review describes the complexity of managing patients with aspirin hypersensitivity in cardiac disease, the indications and risks of aspirin desensitization, and the approach to management of the minority of patients who are unsuitable for desensitization.
Assuntos
Aspirina/uso terapêutico , Doença da Artéria Coronariana/tratamento farmacológico , Dessensibilização Imunológica/métodos , Hipersensibilidade a Drogas , Tolerância a Medicamentos , Hipersensibilidade a Drogas/epidemiologia , Hipersensibilidade a Drogas/etiologia , Hipersensibilidade a Drogas/terapia , Humanos , Inibidores da Agregação Plaquetária/uso terapêuticoRESUMO
Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome belong to a family of severe cutaneous adverse reactions that can be life-threatening and carry a risk of significant morbidity and potential mortality in the event of re-exposure. Lifelong avoidance of the culprit agent is mandated, which can lead to the exclusion of multiple medications if the trigger is unclear. This can result in adverse health outcomes analogous to that of a penicillin allergy label. We present a case in which the patient would progress to fatal myeloma in the absence of treatment, however, multiple medications were administered prior to the occurrence of TEN following previous chemotherapy. Available risk stratification tools including human leucocyte antigen assessment and the algorithm of drug causality for epidermal necrolysis scoring system were utilized followed by patch testing which identified a lesser-suspected agent as possibly causative. Further evidence-based in vivo testing and subsequent challenges allowed for the reintroduction of life-saving chemotherapy.
RESUMO
B cells require signals delivered through B-cell activating factor of the TNF family receptor (BAFF-R) and CD40 to survive and produce antibody responses in vivo. In vitro data indicate that these signals are controlled by the homologous RING finger proteins cIAP1 and cIAP2, in collaboration with TRAF2 and TRAF3. There is also mounting evidence that all 4 of these signaling molecules can act as tumor suppressors in human B-lineage malignancies. However, it has not been possible to identify the roles of cIAP1 and cIAP2 in controlling B-cell physiology because of the absence of an appropriate in vivo model. Here we describe a unique genetically modified mouse in which the linked cIap1 and cIap2 genes can be independently inactivated. Deletion of cIAP1 plus cIAP2 (but not either protein alone) rendered primary B cells independent of BAFF-R for their survival and led to their uncontrolled accumulation in vivo. B cells deficient in cIAP1 and cIAP2 were also incapable of forming germinal centers, a key step in antibody-mediated immunity. These data define a fundamental role for cIAP1/cIAP2 in regulating B-cell survival and responsiveness, show this requires direct binding to TRAF2, and suggest how mutations of TRAF2, TRAF3, and cIAP1/cIAP2 contribute to B-lineage malignancies, such as multiple myeloma.
Assuntos
Linfócitos B/citologia , Linfócitos B/fisiologia , Centro Germinativo/citologia , Proteínas Inibidoras de Apoptose/genética , Animais , Fator Ativador de Células B/metabolismo , Receptor do Fator Ativador de Células B/metabolismo , Proteína 3 com Repetições IAP de Baculovírus , Antígenos CD40/metabolismo , Diferenciação Celular/imunologia , Linhagem da Célula/imunologia , Sobrevivência Celular/imunologia , Deleção de Genes , Centro Germinativo/fisiologia , Humanos , Proteínas Inibidoras de Apoptose/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mieloma Múltiplo/genética , Mieloma Múltiplo/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais/imunologia , Fator 2 Associado a Receptor de TNF/genética , Fator 2 Associado a Receptor de TNF/metabolismo , Fator 3 Associado a Receptor de TNF/genética , Fator 3 Associado a Receptor de TNF/metabolismo , Ubiquitina-Proteína LigasesRESUMO
Hemophagocytic lymphohistiocytosis (HLH) is a rare and often fatal condition characterized by inappropriate immune system activation leading to a "cytokine storm", and ultimately resulting in end-organ damage. Causes include primary defects in genes involved in immune-mediated cytolytic pathways, or secondary triggers such as infection or malignancy. We describe a case of HLH precipitated by fungal infection which occurred as a consequence of immunosuppression for management of systemic lupus erythematosus (SLE) and necrotizing myopathy. The patient presented with immune-mediated disease of the muscles and lung which was treated with high-dose corticosteroids and aggressive immunosuppression. HLH emerged in the context of confirmed candidiasis and features of severe sepsis. The patient responded rapidly to antifungal therapy and high-dose anakinra, which was administered subcutaneously and progressively weaned over 4 weeks. She completed HLH treatment as an outpatient and remains well at 12 months with controlled SLE and no recurrence of HLH.
Assuntos
Candidíase , Lúpus Eritematoso Sistêmico , Linfo-Histiocitose Hemofagocítica , Feminino , Humanos , Proteína Antagonista do Receptor de Interleucina 1/efeitos adversos , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Corticosteroides/uso terapêuticoRESUMO
Background: Male breast cancer (MBC) is a rare disease and differs from female breast cancer (FBC) in clinicopathological and immune tissue types. Given the limited research on MBC due to its rarity, an understanding of the shared and distinct features of MBC and FBC is vital for formulating efficacious treatment strategies. Methods: Data of patients diagnosed with metastatic breast cancer in the Surveillance, Epidemiology, and End Results (SEER) database from 2012 to 2017 were analysed. Chi-square test was used to compare clinicopathological characteristics between male and female patients. Kaplan-Meier analysis was utilized to compare differences in overall survival (OS). Results: A total of 2,858 patients with MBC were studied, 134 of whom had distant metastasis. Compared with 8,698 patients with metastatic FBC, a higher proportion of metastatic MBC patients had tumors located in the center of the breast, received surgical treatment, and had bone + lung metastasis. Survival analysis revealed no difference in OS between metastatic MBC and FBC patients (P=0.27), but there was a significant difference in OS between metastatic and nonmetastatic MBC (P=0.004). Compared with metastatic FBC, MBC patients with bone metastasis alone, lung metastasis alone, liver metastasis alone, and bone + lung metastasis also had worse prognosis (P=0.021, 0.019, 0.024, 0.011, respectively). Conclusions: Metastatic MBC has unique clinicopathological disease features and patterns of metastasis. No significant difference between the survival of metastatic MBC and FBC patients was observed. Distant metastasis was an independent risk factor impacting the prognosis of MBC patients.
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BACKGROUND: Myotonic dystrophy type 1 is an autosomal dominant disorder characterized by muscle weakness, myotonia, cataracts, and cardiac conduction defects; it is associated with expansions of cytosine-thymine-guanine repeats in the myotonic dystrophy protein kinase. Hypogammaglobulinemia is a lesser known association of myotonic dystrophy type 1 and the underlying pathogenesis of immunoglobulin G depletion remains unclear. CASE PRESENTATION: Here we report a kindred of two members (a 62-year-old white woman and a 30-year-old white man; mother and son) with myotonic dystrophy type 1-associated hypogammaglobulinemia associated with altered intravenous immunoglobulin elimination kinetics and reduced half-life. There was no history of systemic immunosuppression or renal or gastrointestinal protein loss in either patient, and no underlying case for a secondary immunodeficiency could be found. One patient required fortnightly intravenous immunoglobulin to maintain adequate trough immunoglobulin G levels. CONCLUSIONS: Ongoing study of myotonic dystrophy type 1-associated hypogammaglobulinemia using contemporary tools of genomic medicine may help to further delineate the pathogenesis of this entity.
Assuntos
Agamaglobulinemia/diagnóstico , Imunoglobulina G/sangue , Imunoglobulinas Intravenosas/uso terapêutico , Mães , Distrofia Miotônica/diagnóstico , Núcleo Familiar , Adulto , Agamaglobulinemia/imunologia , Agamaglobulinemia/terapia , Feminino , Predisposição Genética para Doença , Humanos , Hospedeiro Imunocomprometido , Masculino , Pessoa de Meia-Idade , Distrofia Miotônica/imunologia , Distrofia Miotônica/terapiaRESUMO
A 58-year-old man was referred for review due to the finding of splinter haemorrhages and digital infarcts. Further questioning revealed a history of unintentional weight loss and calf pain. There were no other clinical features of endocarditis, and no clear cause for the splinter haemorrhages on initial investigations. The discovery of widespread thromboembolic disease prompted a search for malignancy and an eventual diagnosis of oesophageal adenocarcinoma. Splinter haemorrhages resolved with anticoagulation and directed treatment of the underlying malignancy. This case report reminds clinicians of the potentially broad differential diagnosis associated with this clinical sign.
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Adenocarcinoma , Neoplasias Esofágicas , Hemorragia , Unhas , Adenocarcinoma/complicações , Adenocarcinoma/diagnóstico , Adenocarcinoma/tratamento farmacológico , Anticoagulantes/uso terapêutico , Antineoplásicos/uso terapêutico , Diagnóstico Diferencial , Neoplasias Esofágicas/complicações , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/tratamento farmacológico , Hemorragia/tratamento farmacológico , Hemorragia/etiologia , Hemorragia/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Unhas/irrigação sanguínea , Unhas/patologiaAssuntos
Amoxicilina/efeitos adversos , Anafilaxia/etiologia , Antibacterianos/efeitos adversos , Administração Oral , Amoxicilina/administração & dosagem , Anafilaxia/tratamento farmacológico , Antibacterianos/administração & dosagem , Hipersensibilidade a Drogas/etiologia , Feminino , Humanos , Pessoa de Meia-Idade , Penicilina G , Penicilinas/efeitos adversos , Testes Cutâneos/efeitos adversosRESUMO
BACKGROUND: Flow cytometric techniques are increasingly used in pretransplant crossmatching, although there remains debate regarding the clinical significance and predictive value of donor-specific antibodies detected by flow cytometry. At least some of the discrepancies between published studies may arise from differences in cutoffs used and lack of standardization of the test. METHODS: We selected cut-off values for pretransplant flow cytometric crossmatching (FCXM) based on the correlation of retrospective results with the occurrence of antibody-mediated rejection. The impact on long-term renal graft survival of prospective FCXM was determined by comparing graft survival between patients crossmatched with complement-dependent cytotoxicity (CDC) only with those prospectively crossmatched with both CDC and FCXM. RESULTS: Chosen cut-off values gave a positive predictive value of FCXM for antibody-mediated rejection of 83%, and a negative predictive value of 90%. After the introduction of prospective B- and T-cell crossmatching by flow cytometry in addition to CDC in our center, there was a significant improvement in renal graft survival in highly sensitized patients (P=0.017). Four-year graft survival in highly sensitized patients after the introduction of FCXM was 89%, which did not differ significantly from that seen in nonsensitized patients (93%; P=0.638). CONCLUSIONS: Our data demonstrate that prospective FCXM improves renal transplant outcome in highly sensitized patients, provided that cut-off values are carefully validated and results interpreted in the context of sensitization history and antibody screening results.
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Sobrevivência de Enxerto/imunologia , Teste de Histocompatibilidade , Imunização , Transplante de Rim/imunologia , Linfócitos B/imunologia , Citometria de Fluxo/métodos , Humanos , Isoanticorpos/imunologia , Transplante de Rim/mortalidade , Valor Preditivo dos Testes , Análise de Sobrevida , Sobreviventes , Linfócitos T/imunologiaRESUMO
The following case reports are of two patients who have developed hypersensitivity reactions to the red cell growth hormones, darbepoietin and erythropoietin. The subsequent skin testing and clinical course suggested that the cause of these reactions was due to the excipient polysorbate 80. This finding might have implications in the recent increase in the incidence of pure red cell aplasia.
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Anemia/tratamento farmacológico , Hipersensibilidade a Drogas/etiologia , Eritropoetina/análogos & derivados , Eritropoetina/administração & dosagem , Excipientes/efeitos adversos , Polissorbatos/efeitos adversos , Adulto , Idoso , Anemia/etiologia , Darbepoetina alfa , Eritropoetina/efeitos adversos , Feminino , Humanos , Falência Renal Crônica/complicações , Proteínas RecombinantesRESUMO
BACKGROUND: Early diagnosis of rheumatoid arthritis allows prompt initiation of antirheumatic therapy, which is associated with improved outcome. The use of IgM rheumatoid factor, the most widely used serologic test in assisting the diagnosis of rheumatoid arthritis, is limited by low specificity. An enzyme-linked immunosorbent assay test detecting antibodies to cyclic citrullinated peptide (CCP) has been developed with apparently higher specificity for rheumatoid arthritis. AIM: We aimed to evaluate an assay for anti-CCP antibodies by determining the prevalence and titer of antibodies to CCP in a group of patients with chronic arthritis. METHOD: Thirty-four sera were collected from outpatients attending an arthritis-monitoring clinic and tested for anti-CCP and IgM rheumatoid factor. RESULTS: Anti-CCP and rheumatoid factor were detected in 86% and 72% of patients with rheumatoid arthritis, respectively. Six patients negative for rheumatoid factor were positive for anti-CCP. CONCLUSION: Anti-CCP antibodies are frequently detectable in high titer in patients with longstanding rheumatoid arthritis. This assay may be especially helpful in such cases when positive in rheumatoid factor-negative patients.