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Despite progress, the molecular mechanisms underlying Kawasaki Disease (KD) and intravenous immunoglobulin's (IVIG) ability to mitigate the inflammatory process remain poorly understood. To characterize this condition, plasma proteomic profiles, flow cytometry, and gene expression of T cell subsets were investigated in longitudinal samples from KD patients and compared with two control groups. Systems-level analysis of samples in the acute phase revealed distinctive inflammatory features of KD, involving mainly Th-1 and Th-17 mediators and unveiled a potential disease severity signature. APBB1IP demonstrated an association with coronary artery involvement (CAI) and was significantly higher in CAI+ compared to CAI- patients. Integrative analysis revealed a transient reduction in CD4+ EM T cells and a comprehensive immune activation and exhaustion. Following treatment, Tregs at both frequency and gene expression levels revealed immune dynamics of recovery. Overall, our data provide insights into KD, which may offer valuable information on prognostic indicators and possible targets for novel treatments.
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Vaccine challenge responses are an integral component in the diagnostic evaluation of patients with primary antibody deficiency, including Common Variable Immunodeficiency Disorders (CVID). There are no studies of vaccine challenge responses in primary hypogammaglobulinemia patients not accepted for subcutaneous/intravenous immunoglobulin (SCIG/IVIG) replacement compared to those accepted for such treatment. Vaccine challenge responses in patients enrolled in two long-term prospective cohorts, the New Zealand Hypogammaglobulinemia Study (NZHS) and the New Zealand CVID study (NZCS), were compared in this analysis. Almost all patients in the more severely affected SCIG/IVIG treatment group achieved protective antibody levels to tetanus toxoid and H. influenzae type B (HIB). Although there was a highly significant statistical difference in vaccine responses to HIB, tetanus and diphtheria toxoids, there was substantial overlap in both groups. In contrast, there was no significant difference in Pneumococcal Polysaccharide antibody responses to Pneumovax® (PPV23). This analysis illustrates the limitations of evaluating vaccine challenge responses in patients with primary hypogammaglobulinemia to establish the diagnosis of CVID and in making decisions to treat with SCIG/IVIG. The conclusion from this study is that patients with symptoms attributable to primary hypogammaglobulinemia with reduced IgG should not be denied SCIG/IVIG if they have normal vaccine responses.
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Imunodeficiência de Variável Comum , Vacinas Anti-Haemophilus , Vacinas Pneumocócicas , Humanos , Imunodeficiência de Variável Comum/imunologia , Feminino , Masculino , Vacinas Pneumocócicas/imunologia , Vacinas Pneumocócicas/uso terapêutico , Pessoa de Meia-Idade , Adulto , Vacinas Anti-Haemophilus/imunologia , Vacinas Anti-Haemophilus/uso terapêutico , Vacinas Anti-Haemophilus/administração & dosagem , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Agamaglobulinemia/imunologia , Agamaglobulinemia/diagnóstico , Imunoglobulinas Intravenosas/uso terapêutico , Estudos Prospectivos , Toxoide Tetânico/imunologia , Idoso , Adulto Jovem , Adolescente , Nova Zelândia , Criança , Haemophilus influenzae tipo b/imunologiaRESUMO
BACKGROUND: Immunoglobulin G replacement therapy (IgRT), intravenous (IV) and subcutaneous (SC) routes, is pivotal in treatment of primary immunodeficiencies (PID). In recent years, facilitated subcutaneous immunoglobulin (fSCIG), a combination of rHuPH20 and 10% IgG has emerged as a delivery method to combine advantages of both IV and SC. METHOD: In an observational prospective cohort, we investigated patient experience with fSCIG in PID patients from 5 PID centers for up to 12 months. We assessed the efficacy and safety of this treatment with patient/caregiver- and physician-reported indicators. Additionally, we analyzed patient treatment satisfaction (TSQM-9) and quality of life (QoL). RESULTS: We enrolled 29 patients (22 pediatric and 7 adults; 14 females and 15 males; (median: 15, min-max: 2-40.9 years) who initiated fSCIG as IgRT-naive (n = 1), switched from conventional rapid-push 10% SCIG (n = 6) or IVIG (n = 22). Among the participants, 19 (65%) exhibited antibody deficiencies, 8 (27%) combined immunodeficiencies, and 2 (7%) immune dysregulations. Remarkably, targeted trough immunoglobulin G levels were achieved under all previous IgRTs as well as fSCIG. No severe systemic adverse drug reactions were documented, despite prevalent local (%86.45) and mild systemic (%26.45) adverse reactions were noted with fSCIG. Due to mild systemic symptoms, 2 patients switched from fSCIG to 10% SCIG. The patient satisfaction survey revealed a notable increase at 2-4th (p = 0.102); 5-8th (p = 0.006) and 9-12th (p < 0.001) months compared to the baseline. No significant trends were observed in QoL surveys. CONCLUSION: fSCIG demonstrates admissable tolerability and efficacy in managing PIDs in addition to notable increase of patients' drug satisfaction with IgRT. The identified benefits support the continuation of this therapy despite the local reactions.
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Imunoglobulina G , Imunoglobulinas Intravenosas , Satisfação do Paciente , Qualidade de Vida , Humanos , Masculino , Feminino , Criança , Estudos Prospectivos , Adulto , Pré-Escolar , Adolescente , Adulto Jovem , Imunoglobulinas Intravenosas/uso terapêutico , Imunoglobulina G/uso terapêutico , Doenças da Imunodeficiência Primária/terapia , Resultado do Tratamento , Injeções Subcutâneas , Infusões Subcutâneas , Síndromes de Imunodeficiência/terapia , Síndromes de Imunodeficiência/tratamento farmacológicoRESUMO
BACKGROUND: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a distinct demyelinating disease of the central nervous system. Immunoglobulin (Ig) has been used as a maintenance therapy to prevent relapses in MOGAD, but the impact of Ig on serum MOG-IgG titers is unclear. OBJECTIVE: To characterize the variation in serum MOG-IgG titers after initiation of Ig treatment in people with MOGAD. METHODS: We conducted a retrospective study of 10 patients with a diagnosis of MOGAD and available serum MOG-IgG titers before and after initiation of maintenance Ig treatment. RESULTS: We found that most of the patients remained MOG-IgG seropositive while on Ig treatment with a reduced or unchanged titer, despite a lack of disease activity. CONCLUSIONS: This case series suggests that the mechanism of action of Ig therapy in MOGAD is not exclusively dependent on MOG-IgG titer reduction.
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Cognição , Pesquisa , Humanos , Estudos Retrospectivos , Sistema Nervoso Central , Imunoglobulina G , Glicoproteína Mielina-Oligodendrócito , AutoanticorposRESUMO
BACKGROUND: Intravenous immunoglobulins (IVIgs) derived from the pooled plasma of thousands of donors contain numerous types of IgG molecules, including autoantibodies commonly used to diagnose autoimmunity. While these autoantibodies can cause misinterpretation of serological tests for IVIg recipients, their profiles in IVIg preparations are not fully understood. STUDY DESIGN AND METHODS: Using binding-capability based immune assays, we measured 18 varieties of clinically relevant autoantibodies in domestic blood donor-derived IVIg products. In addition, we analyzed an IVIg product from a US brand to evaluate the influence of regional and racial differences. Based on the determined autoantibody titers, pharmacokinetics of passively acquired autoantibodies and their possible detection period in serum were estimated. RESULTS: Anti-thyroglobulin (Tg), anti-thyroidperoxidase (TPO), and anti-Sjögren's-syndrome-related antigen A (SS-A) antibodies were present in considerable amounts in IVIg products. Notably, these three autoantibodies can be detected in IVIg recipients' sera for up to 3 months after infusion. DISCUSSION: To the best of our knowledge, this is the first study that analyzed multiple autoantibody profiles in both pooled plasma and IVIg products and that further evaluated their potential influences on diagnosis of autoimmunity. Clinicians should keep in mind that IVIgs contain several autoantibodies and that their infusion can produce false-positive serology results. To establish an accurate diagnosis, serological tests must be carefully interpreted and clinical symptoms should be more purposefully considered if patients are receiving IVIg therapy.
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Autoimunidade , Imunoglobulinas Intravenosas , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Autoanticorpos , Doadores de TecidosRESUMO
Three large multi-center studies have identified the clinical utility of intravenous immunoglobulin (IVIg) in the treatment of Down syndrome regression disorder (DSRD). Yet the tolerability of infusions in individuals with DS and the safety of IVIg remains unknown in this population. This study sought to evaluate the safety and tolerability of IVIg in individuals with DSRD compared to a real-world cohort of individuals with pediatric onset neuroimmunologic disorders. A single-center, retrospective chart review evaluating clinically documented infusion reactions was performed for individuals meeting international consensus criteria for DSRD and having IVIg infusions between 2019 and 2023. Infusion reactions were evaluated for severity and need for alterations in infusion plan. This cohort was compared against an age and sex matched cohort of children with neuroimmunologic conditions who had also received IVIg infusions. In total, 127 individuals with DSRD and 186 individuals with other neuroimmunologic disorders were enrolled. There was no difference in the overall rate of adverse reactions (AEs) between the DSRD and general neuroimmunology cohorts (p = 0.31, 95% CI: 0.80-2.00), but cardiac-related AEs specifically were more common among the DSRD group (p = 0.02, 95% CI: 1.23-17.54). When AEs did occur, there was no difference in frequency of pharmacologic intervention (p = 0.12, 95% CI: 0.34-1.13) or discontinuation of therapy (p = 0.74, 95% CI: 0.06-7.44). There was a higher incidence of lab abnormalities on IVIG among the general neuroimmunology cohort (p = 0.03, 95% CI: 0.24-0.94) compared to the DSRD cohort. Transaminitis was the most common laboratory abnormality in the DSRD group. In a large cohort of individuals with DSRD, there were no significant differences in the safety and tolerability of IVIg compared to a cohort of children and young adults with neuroimmunologic conditions.
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Síndrome de Down , Imunoglobulinas Intravenosas , Criança , Adulto Jovem , Humanos , Imunoglobulinas Intravenosas/efeitos adversos , Estudos Retrospectivos , Síndrome de Down/complicações , Síndrome de Down/tratamento farmacológicoRESUMO
INTRODUCTION/AIMS: Objective outcome measures in children undergoing treatment for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) are lacking. The aim of the study was to record serial grip strength and motor nerve conduction studies to assess interval change. METHODS: This was a retrospective review of 16 children (8 females and 8 males; median age, 9.7 years; interquartile range, 6-13 years) with CIDP followed at a tertiary children's hospital from 2013 to 2021. Subjects were treated with intravenous immunoglobulin (IVIG). Right and left grip strength measurements were obtained at each clinic visit using a handheld dynamometer. Annual right median motor nerve conduction study data were recorded during the study period. RESULTS: Mean duration of follow-up was 2.9 years. Grip strength (right: 0.19 kg/month, p < 0.001; left 0.23 kg/month, p < 0.001) and median F-wave latencies (-0.23/month, p = 0.015) showed significant improvement over time. Akaike information criterion showed time + IVIG frequency <21 days as best fit for grip strength and distal compound muscle action potential amplitude. DISCUSSION: Our study results indicate serial grip strength measurements are a feasible and objective way to assess motor strength improvement in children with CIDP receiving immunotherapy.
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Polirradiculoneuropatia Desmielinizante Inflamatória Crônica , Masculino , Feminino , Humanos , Criança , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/diagnóstico , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/tratamento farmacológico , Imunoglobulinas Intravenosas/uso terapêutico , Avaliação de Resultados em Cuidados de Saúde , Estudos Retrospectivos , Força da Mão/fisiologia , Resultado do TratamentoRESUMO
INTRODUCTION/AIMS: Not all patients with chronic inflammatory demyelinating polyneuropathy (CIDP) have evidence of demyelination on nerve conduction studies (NCS). Patients with "supportive" evidence of CIDP on cerebrospinal fluid (CSF), magnetic resonance imaging (MRI), ultrasound (US), or nerve biopsy but not on NCS, often receive immunomodulating therapy. We evaluated the treatment response of patients with clinical and supportive features of CIDP lacking NCS evidence of demyelination. METHODS: Retrospective chart review was conducted on 232 patients who met CIDP clinical criteria and were treated with disease-modifying therapy. Patients included did not have NCS criteria of demyelination, but did have supportive CSF, MRI, or US findings consistent with CIDP. A positive treatment response was defined as at least a one-point improvement in the modified Rankin scale (mRS), or a four-point increase in the Medical Research Council sum score (MRCSS). RESULTS: Twenty patients met criteria: 17 of the 18 (94%) patients with CSF protein >45 mg/dL, 6 of the 14 (43%) with MRI lumbosacral root or plexus enhancement, and 4 of the 6 (67%) with enlarged proximal nerves on US. Eighteen patients received intravenous immunoglobulin, 10 corticosteroids, one plasma exchange, and six other immunomodulatory therapies. Twelve patients had a positive treatment response on the MRCSS or mRS. The presence of MRI lumbosacral root or plexus enhancement was associated with a positive treatment response. DISCUSSION: A trial of immunomodulating treatment should be considered for patients with clinical features of CIDP in the absence of NCS evidence of demyelination, particularly when there is MRI lumbosacral root or plexus enhancement.
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INTRODUCTION/AIMS: If myasthenia gravis (MG) symptoms are inadequately controlled, patients may experience exacerbations or life-threatening myasthenic crises. Patients with inadequately controlled MG symptoms tend to be treated with chronic intravenous immunoglobulin (IVIg) therapy and/or multiple immunosuppressant therapies (ISTs). This study aimed to examine disease burden, healthcare resource utilization, and associated costs in these patients. METHODS: This was a retrospective observational study using a claims database. Patients with MG were classified into three cohorts based on treatment over a 1-y follow-up period: (a) treated with four or more IVIg episodes (chronic IVIg cohort); (b) received two or more non-steroidal ISTs (NSISTs) sequentially (multiple NSIST cohort); (c) received neither chronic IVIg nor multiple NSISTs (reference cohort). Incidences of crises and exacerbations and annual healthcare costs in each cohort were estimated. RESULTS: In total, 3516 patients with MG were included in the analysis. Compared with the reference cohort (n = 2992), the MG crisis rate was approximately twice as high in both the chronic IVIg (n = 324) and multiple NSIST (n = 291) cohorts (p < 0.001); and the MG exacerbation rate was approximately four-fold higher in the chronic IVIg cohort (p < 0.001) and three-fold higher in the multiple NSIST cohort (p < 0.001). Median annual MG-related inflation-adjusted total healthcare costs were higher in the chronic IVIg ($81,900) and multiple NSIST ($30,300) cohorts than in the reference cohort ($2540). DISCUSSION: The burden of crises/exacerbations was substantially higher and healthcare costs were considerably greater in patients with MG treated with chronic IVIg or multiple NSISTs than in patients not receiving these treatments.
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Imunoglobulinas Intravenosas , Miastenia Gravis , Humanos , Estados Unidos/epidemiologia , Imunoglobulinas Intravenosas/uso terapêutico , Miastenia Gravis/tratamento farmacológico , Troca Plasmática , Custos de Cuidados de Saúde , Imunossupressores , Efeitos Psicossociais da DoençaRESUMO
BACKGROUND AND OBJECTIVES: In May 2022, the United Kingdom reported the first case of chained transmission of the monkeypox (mpox) virus without any known epidemiological links to west or central Africa. The monthly number of mpox patients currently has passed a peak and is declining globally, and infected patients include both non-vaccinated and vaccinated individuals. Herein, the virus-neutralizing (VN) activity against vaccinia viruses, which are considered to cross-react with the mpox virus, in the intravenous immunoglobulin (IVIG) lots derived from donors, including vaccinated Japanese populations, was evaluated to clarify the status of the Japanese blood donor population. MATERIALS AND METHODS: VN titres against vaccinia and human mpox viruses in IVIG lots derived from donors in Japan and the United States manufactured between 1999 and 2021 and 1995 and 2001, respectively, were evaluated by neutralization testing. RESULTS: VN titres of IVIG derived from donors in Japan and the United States against vaccinia and mpox viruses showed a slowly decreasing trend between 1999 and 2021. CONCLUSION: VN titres are expected to decrease in the future since the percentage of vaccinated donors in the donor population seems to have decreased. Therefore, continuous monitoring of VN titres is required.
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Doadores de Sangue , Imunoglobulinas Intravenosas , Monkeypox virus , Humanos , Japão , Estados Unidos , Imunoglobulinas Intravenosas/uso terapêutico , Anticorpos Neutralizantes/sangue , Vaccinia virus/imunologia , Anticorpos Antivirais/sangue , Mpox/prevenção & controle , Mpox/epidemiologia , Testes de Neutralização , Feminino , MasculinoRESUMO
BACKGROUND AND PURPOSE: It is not known whether the route of administration affects the mechanisms of action of therapeutic immunoglobulin in chronic inflammatory demyelinating polyneuropathy (CIDP). The aim of this study, therefore, was to compare the immunomodulatory effects of intravenous (IVIg) and subcutaneous immunoglobulin (SCIg) in patients with CIDP and in IVIg-treated common variable immunodeficiency (CVID) patients. METHODS: Serum and peripheral blood mononuclear cell samples were obtained from 30 CIDP patients receiving IVIg, 10 CIDP patients receiving SCIg, and 15 patients with CVID receiving IVIg. Samples and clinical data were obtained prior to IVIg/SCIg and at 3 days, 7 days, and, in CIDP patients receiving IVIg, 21 days post-administration. Serum cytokines were assessed by Luminex-based multiplex assay and enzyme-linked immunosorbent assay. Immune cells were characterized by flow cytometry. RESULTS: Immune cell profiles of CIDP and CVID patients differed in frequencies of myeloid dendritic cells and cytotoxic natural killer cells. During treatment with IVIg or SCIg in CIDP patients, cellular immunomarkers were largely similar. CIDP patients receiving IVIg had higher macrophage inflammatory protein (MIP)-1α (p = 0.01), interleukin (IL)-4 (p = 0.04), and IL-33 (p = 0.04) levels than SCIg recipients. IVIg treatment more broadly modulated cytokines in CIDP than SCIg treatment. CONCLUSIONS: Our study demonstrates that the modulation of cellular immunomarkers in CIDP is independent of the application route of therapeutic immunoglobulin. Minor differences were observed between CIDP and CVID patients. In contrast, cytokines were differentially modulated by IVIg and SCIg in CIDP.
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Polirradiculoneuropatia Desmielinizante Inflamatória Crônica , Humanos , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/tratamento farmacológico , Imunoglobulinas Intravenosas/uso terapêutico , Leucócitos Mononucleares , Administração Intravenosa , CitocinasRESUMO
Cytomegalovirus (CMV) reactivation remains one of the major and life-threatening complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Yet, there is still a lack of safe and effective ways to prevent CMV reactivation in allo-HSCT patients. Here, we retrospectively analyzed a cohort of patients who underwent HSCT at our transplant center between 2018 and 2022 to evaluate the efficacy of prophylactic CMV-specific intravenous immunoglobulin (CMV-IVIg) against CMV reactivation. After Propensity Score Matching, the CMV reactivation rate was significantly decreased in the CMV-IVIg group (HR, 2.952; 95% CI,1.492-5.841; P = .002) compared with the control group. Additionally, the time duration of CMV reactivation (P = .001) and bacterial infection rate (P = .013) were significantly lower in the CMV-IVIg group. Moreover, prophylactic CMV-IVIg was more effective in CMV seropositive patients who received ATG as part of GVHD prevention (HR, 8.225; 95% CI,1.809-37.39; P = .006). In conclusion, CMV-IVIg is considered an effective and safe way to prevent CMV reactivation in HSCT recipients, which may be related to the acceleration of immune reconstitution in the early stage after transplantation.
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Infecções por Citomegalovirus , Transplante de Células-Tronco Hematopoéticas , Humanos , Citomegalovirus , Imunoglobulinas Intravenosas/uso terapêutico , Infecções por Citomegalovirus/etiologia , Infecções por Citomegalovirus/prevenção & controle , Infecções por Citomegalovirus/tratamento farmacológico , Estudos Retrospectivos , Transplante Homólogo , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Anticorpos AntiviraisRESUMO
BACKGROUND: Drug shortages are a common issue that healthcare systems face and can result in adverse health outcomes for patients requiring inferior alternate treatment. The United States recently experienced a national drug shortage of intravenous immunoglobulin (IVIG). Several reported strategies to address the IVIG and other drug shortages have been proposed; however, there is a lack of evidence-based methods for protocol development and implementation. OBJECTIVE: To evaluate the efficacy of introducing a multidisciplinary task force and tier system of indications and to minimize adverse effects during a shortage of IVIG. METHODS: Faculty members across disciplines with expertise in IVIG use were invited to participate in a task force to address the shortage and ensure adequate supply for emergent indications. A tier system of IVIG indications was established according to the severity of diagnosis, urgency of indication, and quality of supporting evidence. Based on inventory, indications in selected tiers were auto-approved. Orders that could not be automatically approved were escalated for task force review. RESULTS: Overall, there were 342 distinct requests for IVIG during the study period (August 1, 2019 to December 31, 2019). All Tier 1 indications were approved. Of all requests, only 2.6% (9) of requests were denied, none of which resulted in adverse effects based on retrospective chart review. Seven patients who regularly receive IVIG had possible adverse effects due to dose reduction or spacing of treatment; however, each complication was multifactorial and not attributed to the shortage or tier system implementation alone. CONCLUSION: Implementation of a multidisciplinary task force and tier system to appropriately triage high-priority indications for limited pharmaceutical agents should be considered in health institutions faced with a drug shortage.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Imunoglobulinas Intravenosas , Criança , Humanos , Imunoglobulinas Intravenosas/efeitos adversos , Estudos Retrospectivos , Atenção Terciária à Saúde , Centros de Atenção Terciária , Injeções Intravenosas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/tratamento farmacológicoRESUMO
OBJECTIVE: This study assesses response to intravenous immunoglobulin (IVIG) in presumed autoimmune postural orthostatic tachycardia syndrome (POTS). BACKGROUND: POTS may be associated with autoimmune disorders, serum autoantibodies, or recent infection. Uncontrolled case studies suggest that IVIG is beneficial for treating autoimmune POTS. No previous randomized controlled trials have been conducted. METHODS: This single-site randomized controlled trial compared IVIG with intravenous albumin infusions. Albumin comparator ensured blinding and control for effects of volume expansion. Eligible patients with POTS had COMPASS-31 total weighted score ≥ 40 and met predetermined criteria suggesting autoimmunity. Over 12 weeks, participants received eight infusions (0.4 gm/kg each). Four infusions were given weekly followed by four infusions every other week. Primary outcome measure was improvement in COMPASS-31 2 weeks after final infusion. RESULTS: A total of 50 participants consented; 30 met inclusion criteria and received study drug (16 IVIG and 14 albumin; 29 female). Group baseline characteristics were well matched; 27 participants completed treatment protocol. Change in COMPASS-31 did not differ between groups (median change [IQR]; IVIG: -5.5 [-23.3, 2.5] versus albumin: -10.6 [-14.1, -4.7]; p-value = 0.629). The IVIG group had a higher response rate (46.7% versus 38.5%), but this was not statistically significant. Adverse events were common but usually mild and did not differ between treatment groups. CONCLUSIONS: This small randomized controlled trial of IVIG in POTS found no statistical difference in response compared with albumin infusion. Both groups showed improvement possibly related to volume expansion or other effects obscuring group differences. These findings inform development of future immunomodulatory clinical trials in POTS.
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Doenças Autoimunes , Síndrome da Taquicardia Postural Ortostática , Humanos , Feminino , Imunoglobulinas Intravenosas/uso terapêutico , Síndrome da Taquicardia Postural Ortostática/tratamento farmacológico , Autoimunidade , Albuminas , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
INTRODUCTION: Guillain-Barré syndrome (GBS) is a rare but serious condition that carries with it a high rate of morbidity and mortality. OBJECTIVE: This review highlights the pearls and pitfalls of GBS, including presentation, diagnosis, and management in the emergency department (ED) based on current evidence. DISCUSSION: GBS is a rare immune-mediated neurologic disorder with peripheral nerve injury. It most commonly presents weeks after a bacterial or viral infection, though there are a variety of associated inciting events. The diagnosis is challenging and often subtle, as only 25-30% of patients are diagnosed on their initial healthcare visit. Clinicians should consider GBS in patients with progressive ascending weakness involving the lower extremities associated with hyporeflexia, but the cranial nerves, respiratory system, and autonomic system may be involved. While the ED diagnosis should be based on clinical assessment, further evaluation includes laboratory testing, cerebrospinal fluid (CSF) analysis, and potentially neuroimaging. Not all patients demonstrate albumino-cytological dissociation on CSF testing. Several criteria exist to assist with diagnosis, including the National Institute of Neurological Disorders and Stroke criteria and the Brighton criteria. Management focuses first on assessment of the patient's hemodynamic and respiratory status, which may require emergent intervention. Significant fluctuations in heart rate and blood pressure may occur, and respiratory muscle weakness may result in the need for airway protection. Neurology consultation is recommended, and definitive treatment includes PLEX or IVIG. CONCLUSIONS: An understanding of GBS can assist emergency clinicians in diagnosing and managing this potentially deadly disease.
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Síndrome de Guillain-Barré , Humanos , Síndrome de Guillain-Barré/diagnóstico , Síndrome de Guillain-Barré/epidemiologia , Síndrome de Guillain-Barré/terapia , Prevalência , Debilidade MuscularRESUMO
OBJECTIVE: The study aimed to characterize serum immunoglobulin (Ig) concentrations and their relationship with clinical and paraclinical features in patients with COPD group E in the stable stage. Additionally, the study focused on evaluating the relationship between serum Ig levels and the risk of exacerbations over the next 12 months, thereby clarifying the role of serum Ig deficiency in affecting the future risk for these patients. METHODS: A prospective observational study assessed IgG, IgA, IgM, and IgE levels in 67 COPD patients and 30 healthy controls at Military Hospital 103 from October 2017 to August 2020. Primary outcomes included Ig isotype levels in COPD patients, with secondary outcomes exploring differences compared to controls and associations with clinical variables. RESULTS: COPD patients showed significantly lower IgG concentrations and higher IgA levels than controls. IgM and IgE levels did not differ significantly. Subgroup analysis revealed notable decreases in IgG1 and IgG3 concentrations, with 10.4% of patients exhibiting reduced IgG levels and 0.3% diagnosed with common variable immunodeficiency. No significant associations were found between Ig levels and exacerbation risk or clinical variables. CONCLUSIONS: Serum IgG and IgM concentrations were significantly reduced in COPD patients compared to normal individuals, with IgG1 and IgG3 concentrations notably low. Serum IgA levels were significantly higher in COPD patients compared with normal controls. However, no significant association was found between Ig concentrations, particularly serum IgG deficiency and its subclasses, with the frequency and risk of exacerbations during 12 months of longitudinal follow-up. Caution is warranted in the use of immunoglobulin therapy in the treatment of COPD patients. TRIAL REGISTRATION: An independent ethics committee approved the study (Ethics Committee of Military Hospital 103 (No. 57/2014/VMMU-IRB), which was performed in accordance with the Declaration of Helsinki, Guidelines for Good Clinical Practice.
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Doença Pulmonar Obstrutiva Crônica , Humanos , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/imunologia , Doença Pulmonar Obstrutiva Crônica/terapia , Masculino , Feminino , Estudos Prospectivos , Idoso , Pessoa de Meia-Idade , Imunoglobulina G/sangue , Estudos de Casos e Controles , Imunoglobulina A/sangue , Progressão da Doença , Imunoglobulinas/sangue , Imunoglobulina M/sangueRESUMO
AIM: To comprehensively review the literature on multisystem inflammatory syndrome in children (MIS-C). METHODS: Narrative review of relevant studies published between April 2020 and January 2024. RESULTS: MIS-C is a SARS-CoV-2-related hyperinflammatory syndrome developing 2-6 weeks after COVID-19 in genetically susceptible individuals. Persisting fever, mucocutaneous manifestations, GI and cardiac involvement, together with lymphopenia and elevated inflammatory and cardiac markers are the main clinical features. It is believed to recognise some pathogenetic and clinical overlap with Kawasaki disease. New case definitions have been proposed after an assessment of the diagnostic performance of existing criteria; epidemiological criterion is however progressively losing its usefulness as the pandemic turns into an endemic and in the areas with the highest rates of COVID-19 vaccination. Current guidelines recommend both intravenous immunoglobulin and glucocorticoids in the first-line immunomodulatory treatment, mainly based on comparative retrospective cohorts; the actual role of biologics remains to be adequately established. Strict follow-up is mandatory, especially for those with severe cardiac involvement, as longitudinal studies evaluate the long-term evolution of cardiac damage. CONCLUSION: In this paper, we review the epidemiological, pathogenetic, clinical and prognostic features of MIS-C, and outline the main questions which still remain unanswered after more than 3 years of research.
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COVID-19 , Síndrome de Resposta Inflamatória Sistêmica , Humanos , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/terapia , COVID-19/complicações , COVID-19/epidemiologia , CriançaRESUMO
Febrile ulceronecrotic Mucha-Habermann disease (FUMHD), a lymphocyte-mediated inflammatory skin disorder, is considered a severe variant of pityriasis lichenoides et varioliformis acuta that can lead to a fatal outcome if not managed in a timely fashion. Children with FUMHD can have systemic complications involving various organs. The scarcity of reported cases and the absence of well-designed studies or randomized clinical trials to evaluate different therapeutic modalities pose a major challenge in treating this potentially life-threatening disorder. We report a five-year-old child with FUMHD and seizures treated unsuccessfully with a combination of systemic steroids, methotrexate, dapsone, and oral erythromycin, who improved rapidly and achieved disease control with just a single infusion of low-dose intravenous immunoglobulin.
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Imunoglobulinas Intravenosas , Pitiríase Liquenoide , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Pitiríase Liquenoide/tratamento farmacológico , Pré-Escolar , Masculino , Fatores Imunológicos/uso terapêutico , Febre/etiologia , Febre/tratamento farmacológicoRESUMO
Intravenous immune globulin (IVIG) is a manufactured blood product commonly used to treat immunodeficiency syndromes, inflammatory disorders, and autoimmune diseases of the skin. The use of IVIG in dermatology has evolved and expanded over time, serving as a useful therapeutic intervention for several inflammatory skin disorders. In addition to demonstrating efficacy in treating several cutaneous pathologies, IVIG also mitigates the need for steroids or other immunosuppressant medications in many dermatologic diseases. This review highlights the evidence for IVIG use across several dermatologic conditions, emphasizing the dosing regimens and safety considerations.
Assuntos
Imunoglobulinas Intravenosas , Dermatopatias , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Imunoglobulinas Intravenosas/administração & dosagem , Dermatopatias/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Fatores Imunológicos/administração & dosagemRESUMO
Advances in affinity chromatography now make it possible to analyze immunoglobulin G from plasma and its fractions with a simple chromatographic method. Ligands derived from camelid antibodies have been developed which have affinity to all 4 subclasses of human IgG without a cross reactivity to other immunoglobulins. The commercially available Capture Select FcXL is the basis for a simple method for direct quantification of immunoglobulin G from plasma or from fractions from cold ethanol precipitation. After direct injection of the sample into the column the unbound proteins are washed out with equilibration buffer and eluted with a pH-step. The elution the peak is integrated, and quantity is derived form a standard curve. The limit of detection with 40 µg/mL, and a linearity up to 250 µg/mL allows an analysis of samples ranging from 0.04 to 50 mg/mL using varying injection volume without further dilution and the two-wavelength detection. A full cycle is completed within five minutes. This method can serve as orthogonal method for in-process control but also for process development.