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Current evidence suggests that iron deficiency (ID) plays a key role in the pathogenesis of conditions presenting with restlessness such as attention deficit hyperactivity disorder (ADHD) and restless legs syndrome (RLS). In clinical practice, ID and iron supplementation are not routinely considered in the diagnostic work-up and/or as a treatment option in such conditions. Therefore, we conducted a scoping literature review of ID guidelines. Of the 58 guidelines included, only 9 included RLS, and 3 included ADHD. Ferritin was the most frequently cited biomarker, though cutoff values varied between guidelines and depending on additional factors such as age, sex, and comorbidities. Recommendations surrounding measurable iron biomarkers and cutoff values varied between guidelines; moreover, despite capturing the role of inflammation as a concept, most guidelines often did not include recommendations for how to assess this. This lack of harmonization on the interpretation of iron and inflammation biomarkers raises questions about the applicability of current guidelines in clinical practice. Further, the majority of ID guidelines in this review did not include the ID-associated disorders, ADHD and RLS. As ID can be associated with altered movement patterns, a novel consensus is needed for investigating and interpreting iron status in the context of different clinical phenotypes.
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Biomarcadores , Deficiências de Ferro , Guias de Prática Clínica como Assunto , Síndrome das Pernas Inquietas , Humanos , Síndrome das Pernas Inquietas/diagnóstico , Biomarcadores/sangue , Ferritinas/sangue , Sono/fisiologia , Transtorno do Deficit de Atenção com Hiperatividade , Anemia Ferropriva/diagnóstico , Ferro/sangueRESUMO
OBJECTIVE: Adult-onset Still's disease (AOSD) and secondary hemophagocytic lymphohistiocytosis (sHLH) are both hyperferritinemic cytokine storm syndromes that can be difficult to distinguish from each other in hospitalized patients. The objective of this study was to compare the inflammatory markers ferritin, D-dimer, C-reactive protein (CRP), and soluble CD25 (sCD25) in patients with AOSD and sHLH. These four markers were chosen as they are widely available and represent different aspects of inflammatory diseases: macrophage activation (ferritin); endothelialopathy (D-dimer); interleukin-1/interleukin-6/tumour necrosis factor elevation (CRP) and T cell activation (sCD25). METHODS: This was a single-center retrospective study. Patients diagnosed by the Hematology service at Vancouver General Hospital for AOSD or sHLH from 2009 to 2023 were included. RESULTS: There were 16 AOSD and 44 sHLH patients identified. Ferritin was lower in AOSD than HLH (median 11 360 µg/L vs. 29 020 µg/L, p = .01) while D-dimer was not significantly different (median 5310 mg/L FEU vs. 7000 mg/L FEU, p = .3). CRP was higher (median 168 mg/L vs. 71 mg/L, p <.01) and sCD25 was lower (median 2220 vs. 7280 U/mL, p = .004) in AOSD compared to HLH. The combined ROC curve using CRP >130 mg/L and sCD25< 3900 U/mL to distinguish AOSD from HLH had an area under the curve (AUC) of 0.94 (95% confidence interval 0.93-0.97) with sensitivity 91% and specificity 93%. CONCLUSIONS: These findings suggest that simple, widely available laboratory tests such as CRP and sCD25 can help clinicians distinguish AOSD from HLH in acutely ill adults with extreme hyperferritinemia. Larger studies examining a wider range of clinically available inflammatory biomarkers in a more diverse set of cytokine storm syndromes are warranted.
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Nesidioblastosis is a rare pancreatic disorder involving enlarged beta cells throughout the pancreas, causing elevated insulin production. We present the case of a 53-year-old woman with the initial symptom of fasting hypoglycemia. No pancreatic lesions were indicated on computed tomography and magnetic resonance imaging scans, and an octreotide scan was negative for insulinoma. Selective arterial calcium stimulation (SACST) showed increased insulin production from the stimulation of 3 out of 5 arteries. The SACST results suggested a diagnosis of nesidioblastosis, which was confirmed by histopathology after a subtotal distal pancreatectomy. The patient has normal glucose tolerance after surgery with no further problems of hypoglycemia, indicating that this is a rare case of nesidioblastosis extending only partially through the pancreas.
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Introduction: Hepcidin is a hormone that regulates systemic iron homeostasis. Serum hepcidin levels are under the influence of various stimuli, particularly inflammation and renal dysfunction. The measurement of hepcidin in circulation is a potentially useful clinical tool in the diagnosis, monitoring and treatment of iron metabolism disorder, although clinical interpretation of hepcidin level remains difficult. We evaluated he diagnostic potential and limitations of hepcidin-25 by investigating its relationship with iron and hematological indices, inflammation, and renal dysfunction. Methods: This retrospective study included 220 adult patients not requiring dialysis. Variations of biologically active hepcidin-25 were examined using a mass spectrometry-based assay in various inflammatory and renal states. The log[hepcidin]:log[ferritin] ratio was calculated as an hepcidin index. Results: In 220 adult patients not requiring dialysis, variation in hepcidin-25 level was significantly larger once CRP exceeded 10 mg/l (p < 0.001). Inflammation was not a determinant of hepcidin-25 in the setting of renal dysfunction. Hepcidin-25 median (7.37 nM) and variance were significantly higher (p < 0.001), once estimated glomerular filtration rate (eGFR) dropped below 30 ml/min/1.73 m2. The log[hepcidin]:log[ferritin] index normalized hepcidin levels. Patients with iron deficiency have a notably lower index when compared to controls (-0.66 vs 0.3). Conclusion: Severe renal dysfunction (eGFR < 30) affected hepcidin-25 expression and clearance to variable degree between individuals. Although, hepcidin-25 testing is not warranted in patients with infection, inflammatory autoimmune conditions (CRP > 10 mg/l) and/or severe renal dysfunction (eGFR < 30), the hepcidin index may serve as a potential biomarker for iron deficiency in complex cases.
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This Review outlines a practical approach to assessing and managing polyclonal hypergammaglobulinaemia in adults. Polyclonal hypergammaglobulinaemia is most commonly caused by liver disease, immune dysregulation, or inflammation, but can also provide an important diagnostic clue of rare diseases such as histiocyte disorders, autoimmune lymphoproliferative syndrome, Castleman disease, and IgG4-related disease. Causes of polyclonal hypergammaglobulinaemia can be divided into eight categories: liver disease, autoimmune disease and vasculitis, infection and inflammation, non-haematological malignancy, haematological disorders, IgG4-related disease, immunodeficiency syndromes, and iatrogenic (from immunoglobulin therapy). Measuring serum concentrations of C-reactive protein and IgG subclasses are helpful in diagnosis. IL-6-mediated inflammation, associated with persistently elevated C-reactive protein concentrations (≥30 mg/L), is an important driver of polyclonal hypergammaglobulinaemia in some cases. Although the presence of markedly elevated serum IgG4 concentrations (>5 g/L) is around 90% specific for diagnosing IgG4-related disease, mildly elevated serum IgG4 concentrations are seen in many conditions. In most cases, managing polyclonal hypergammaglobulinaemia simply involves treating the underlying condition. Rarely, however, polyclonal hypergammaglobulinaemia can lead to hyperviscosity, requiring plasmapheresis.
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Hipergamaglobulinemia/diagnóstico , Corticosteroides/uso terapêutico , Proteínas Sanguíneas/análise , Proteína C-Reativa/análise , Citocinas/metabolismo , Doenças Hematológicas/complicações , Doenças Hematológicas/patologia , Humanos , Hipergamaglobulinemia/tratamento farmacológico , Hipergamaglobulinemia/etiologia , Imunoglobulina G/sangue , Hepatopatias/complicações , Hepatopatias/patologiaRESUMO
SUMMARY Falsely elevated estradiol is rare, may result from heterophile antibody interference, and can result in unnecessary investigation and intervention. We present the case of a 56-year-old female with falsely elevated estradiol levels inconsistent with her overall clinical picture, which ultimately led to an unnecessary surgical procedure. With the use of alternative analytical platforms and a heterophile antibody blocking agent, we determined the false elevation was due to heterophile antibody interference. Clinicians must suspect and investigate for laboratory error when the clinical picture contradicts laboratory results.
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Humanos , Feminino , Anticorpos Heterófilos , Estradiol , Imunoensaio , Reações Falso-Positivas , Pessoa de Meia-IdadeRESUMO
Falsely elevated estradiol is rare, may result from heterophile antibody interference, and can result in unnecessary investigation and intervention. We present the case of a 56-year-old female with falsely elevated estradiol levels inconsistent with her overall clinical picture, which ultimately led to an unnecessary surgical procedure. With the use of alternative analytical platforms and a heterophile antibody blocking agent, we determined the false elevation was due to heterophile antibody interference. Clinicians must suspect and investigate for laboratory error when the clinical picture contradicts laboratory results.
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Anticorpos Heterófilos , Estradiol , Reações Falso-Positivas , Feminino , Humanos , Imunoensaio , Pessoa de Meia-IdadeRESUMO
Background: Serum IgG4 is typically measured to investigate for Immunoglobulin G4-related Disease (IgG4-RD), a fibroinflammatory condition associated with polyclonal increase in serum IgG4. However, increased IgG4 can also be monoclonal, and little is known about IgG4 myeloma. Methods: We describe two cases of IgG4 myeloma without clinical, radiologic, or laboratory features of IgG4-related disease. Results: An 84 year old man presented with anemia and compression fractures and a 77 year old man presented with anemia, hypercalcemia and renal failure. Both had markedly elevated monoclonal serum IgG4, 34 g/L and 48 g/L in the beta region, and increased IgG positive bone marrow plasma cells, 50% and 80%, respectively. Neither had clinical or radiological manifestations of IgG4-related disease (IgG4-RD) such as salivary or lacrimal gland swelling, autoimmune pancreatitis , or retroperitoneal fibrosis. Both cases responded well to standard myeloma therapy. The IgG4 paraprotein caused spuriously elevated beta-2 microglobulin of 45.2 mg/L in case two due to interference with the assay. Conclusion: These cases illustrate the importance of performing serum protein electrophoresis in tandem with IgG subclasses to distinguish between polyclonal and monoclonal increases in serum IgG4. The lack of typical IgG4-RD features in these two patients suggests that monoclonal elevation in serum IgG4 alone is insufficient to cause the organ damage characteristic of IgG4-RD. Larger studies of IgG myeloma subtypes are warranted to explore whether IgG1, IgG2, IgG3 and IgG4 myeloma differ in natural history and whether the interference with beta-2 microglobulin is specific to IgG4 monoclonal proteins.
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Doença Relacionada a Imunoglobulina G4/sangue , Imunoglobulina G/sangue , Mieloma Múltiplo/sangue , Idoso , Idoso de 80 Anos ou mais , Humanos , Imunoglobulina G/análise , Doença Relacionada a Imunoglobulina G4/diagnóstico , Masculino , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/terapia , Plasmócitos/patologiaRESUMO
BACKGROUND: A 56-year-old female, diagnosed as a carrier of the mitochondrial DNA mutation (MTTK c.8344A > G) associated with the MERRF (myoclonic epilepsy with ragged red fibers) syndrome, presented with a relatively uncommon but well-known phenotypic manifestation: severe multiple symmetric lipomatosis (MSL). After surgical resection of three kilograms of upper mid-back lipomatous tissue, the patient experienced a significant decline in her functional capacity and quality of life, which ultimately resulted in her placement on long-term disability. METHODS: Dissatisfied with the available treatment options centered on additional resection surgeries, given the high probability of lipoma regrowth, the patient independently researched and applied alternative therapies that centred on a carbohydrate-restricted diet and a supervised exercise program. RESULTS: The cumulative effect of her lifestyle interventions resulted in the reversal of her MSL and her previously low quality of life. She met all her personal goals by the one-year mark, including reduced size of the residual post-surgical lipomas, markedly enhanced exercise tolerance, and return to work. She continues to maintain her interventions and to experience positive outcomes at the two-year mark. INTERPRETATION: This case report documents the timing and nature of lifestyle interventions in relation to the reversal in growth pattern of her previously expanding and debilitating lipomas. The profound nature of the apparent benefit on lipoma growth demonstrates the intervention's potential as a new feasible non-surgical therapy for mitochondrial-disease-associated MSL, and justifies its systematic study. We also describe how this case has inspired the care team to re-examine its approach to involved patients.
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Dieta com Restrição de Carboidratos/métodos , Terapia por Exercício/métodos , Lipomatose Simétrica Múltipla/terapia , Síndrome MERRF/terapia , Terapias Complementares , Feminino , Estilo de Vida Saudável , Humanos , Lipomatose Simétrica Múltipla/cirurgia , Síndrome MERRF/cirurgia , Pessoa de Meia-Idade , Retorno ao Trabalho , Resultado do TratamentoRESUMO
This article will review the structure and function of IgG4, methods of measuring serum IgG4 concentrations, clinical conditions associated with increased and decreased serum IgG4, and the test characteristics of serum IgG4 in the diagnosis and management of Immunoglobulin G4-Related Disease (IgG4-RD). The four subclasses of IgG were discovered in 1964 through experiments on monoclonal IgG in patients with myeloma. Since 2001, interest in measuring serum IgG subclasses has increased dramatically due to the emergence of IgG4-RD, a multisystem fibroinflammatory condition wherein polyclonal serum IgG4 concentration is increased in approximately 70% of cases. Increased serum IgG4 typically manifests as a restriction in the anodal gamma region on serum protein electrophoresis, often with beta-gamma bridging, and can be mistaken as a monoclonal protein or polyclonal increase in IgA. Limitations of current clinical methods used in quantitation of serum IgG4 concentrations will be discussed, including the common immunonephelometric assays and LC-MS/MS based assays. Polyclonal IgG4 elevation is not specific for IgG4-RD, and may also occur in conditions such as eosinophilic granulomatosis with polyangiitis (EGPA), lymphoma, and multicentric Castleman disease (MCD). Race and gender differences also affect interpretation of serum IgG4 concentrations, for instance Asians have a higher serum IgG4 concentration than Whites and males have a higher concentration than females.
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Imunoglobulina G/sangue , HumanosRESUMO
Myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) is a syndrome of unknown etiology characterized by profound fatigue exacerbated by physical activity, also known as post-exertional malaise (PEM). Previously, we did not detect evidence of immune dysregulation or virus reactivation outside of PEM periods. Here we sought to determine whether cardiopulmonary exercise stress testing of ME/CFS patients could trigger such changes. ME/CFS patients (n = 14) and matched sedentary controls (n = 11) were subjected to cardiopulmonary exercise on 2 consecutive days and followed up to 7 days post-exercise, and longitudinal whole blood samples analyzed by RNA-seq. Although ME/CFS patients showed significant worsening of symptoms following exercise versus controls, with 8 of 14 ME/CFS patients showing reduced oxygen consumption ([Formula: see text]) on day 2, transcriptome analysis yielded only 6 differentially expressed gene (DEG) candidates when comparing ME/CFS patients to controls across all time points. None of the DEGs were related to immune signaling, and no DEGs were found in ME/CFS patients before and after exercise. Virome composition (P = 0.746 by chi-square test) and number of viral reads (P = 0.098 by paired t-test) were not significantly associated with PEM. These observations do not support transcriptionally-mediated immune cell dysregulation or viral reactivation in ME/CFS patients during symptomatic PEM episodes.
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Teste de Esforço/efeitos adversos , Síndrome de Fadiga Crônica/genética , Fadiga/genética , Adulto , Estudos de Casos e Controles , Exercício Físico/fisiologia , Fadiga/complicações , Síndrome de Fadiga Crônica/sangue , Síndrome de Fadiga Crônica/imunologia , Feminino , Perfilação da Expressão Gênica/métodos , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Transcriptoma/genéticaRESUMO
IgG4-related disease is a fibro-inflammatory condition that can affect nearly any organ system. Common presentations include major salivary and lacrimal gland enlargement, orbital disease, autoimmune pancreatitis, retroperitoneal fibrosis and tubulointerstitial nephritis. This review focuses on the hematologic manifestations of IgG4-related disease, including lymphadenopathy, eosinophilia, and polyclonal hypergammaglobulinemia. The disease can easily be missed by unsuspecting hematologists, as patients may present with clinical problems that mimic disorders such as multicentric Castleman disease, lymphoma, plasma cell neoplasms and hypereosinophilic syndromes. When IgG4-related disease is suspected, serum protein electrophoresis and IgG subclasses are helpful as initial tests but a firm histological diagnosis is essential both to confirm the diagnosis and to rule out mimickers. The central histopathological features are a dense, polyclonal, lymphoplasmacytic infiltrate enriched with IgG4-positive plasma cells (with an IgG4/IgG ratio >40%), storiform fibrosis, and obliterative phlebitis. Importantly for hematologists, the latter two features are seen in all tissues except bone marrow and lymph nodes, making these two sites suboptimal for histological confirmation. Many patients follow an indolent course and respond well to treatment, but a significant proportion may have highly morbid or fatal complications such as periaortitis, severe retroperitoneal fibrosis or pachymeningitis. Corticosteroids are effective but cause new or worsening diabetes in about 40% of patients. Initial response rates to rituximab are high but durable remissions are rare. More intensive lymphoma chemotherapy regimens may be required in rare cases of severe, refractory disease, and targeted therapy against plasmablasts, IgE and other disease biomarkers warrant further exploration.
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Doença Relacionada a Imunoglobulina G4/diagnóstico , Doença Relacionada a Imunoglobulina G4/terapia , Idoso de 80 Anos ou mais , Biomarcadores , Biópsia , Terapia Combinada , Diagnóstico Diferencial , Diagnóstico por Imagem , Gerenciamento Clínico , Suscetibilidade a Doenças , Humanos , Doença Relacionada a Imunoglobulina G4/epidemiologia , Doença Relacionada a Imunoglobulina G4/etiologia , Masculino , Fenótipo , Avaliação de Sintomas , Resultado do TratamentoRESUMO
Muscle biopsy identified a possibly pathogenic, mitochondrial DNA D-loop insertion, in each of 5 family members from two generations, that was otherwise undetectable in most other tissues. The tissue specific regulation of heteroplasmy is reflected in an age related increase in muscle heteroplasmy level, across the pedigree. This latter finding is in keeping with previous reports (e.g. T408A, C16327) but differs in having a very high muscle heteroplasmy level, and appears maternally transmitted.
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DNA Mitocondrial/genética , Herança Materna , Doenças Mitocondriais/patologia , Músculo Esquelético/patologia , Mutagênese Insercional , Biópsia , HumanosRESUMO
The serum-soluble interleukin-2 receptor (sIL-2r) level is considered an important diagnostic test and disease marker in hemophagocytic syndromes/hemophagocytic lymphohistiocytosis (HPS/HLH). However, this cytokine receptor is rarely measured in clinical practice and has been excluded from recent diagnostic/classification criteria such as the HScore and macrophage activation syndrome (MAS) 16. We performed a systematic scoping review of 64 articles (1975-2016) examining the clinical utility of sIL-2r in HPS/HLH. Twenty-two articles describe sIL-2r as a sensitive diagnostic marker for HLH, but only three distinct datasets actually address sensitivity. The original HLH-2004 Guidelines reported sensitivity of 93% and specificity of 100% for sIL-2r ≥ 2400, based on a pediatric dataset (n = 152) which is published for the first time in this review. Two pediatric studies reported sensitivity of 89% for sIL-2r ≥ 2400 in diagnosis of MAS complicating juvenile idiopathic arthritis (JIA) (n = 27) and 88% for secondary HLH in acute liver failure (n = 9). Twenty articles described sIL-2r as a dynamic marker of disease activity that falls with response to treatment, and 15 described high initial sIL-2r levels >10,000 U/mL as a poor prognostic marker. The ability of sIL-2r to distinguish between subtypes of HPS/HLH was inconsistent. This review confirms the importance of soluble IL-2r as a diagnostic and disease marker in HPS/HLH, but also reveals the need for more primary data about its performance characteristics, particularly in adults. More emphasis should be made in including this simple, inexpensive test in clinical practice and studies of HPS/HLH.
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Biomarcadores/sangue , Linfo-Histiocitose Hemofagocítica/sangue , Linfo-Histiocitose Hemofagocítica/diagnóstico , Receptores de Interleucina-2/sangue , Criança , Pré-Escolar , Humanos , Linfo-Histiocitose Hemofagocítica/terapia , Síndrome de Ativação Macrofágica/sangue , Síndrome de Ativação Macrofágica/diagnóstico , Prognóstico , Sensibilidade e Especificidade , SolubilidadeRESUMO
OBJECTIVE: To compare the clinical and laboratory features of IgG4-related disease (IgG4-RD) and lymphocyte-variant hypereosinophilic syndrome (L-HES), two rare diseases that often present with lymphadenopathy, gastrointestinal symptoms, eosinophilia, and elevated immunoglobulins/IgE. METHOD: Comparative case series of 31 patients with IgG4-RD and 13 patients with L-HES. RESULTS: Peripheral blood eosinophilia was present in eight of 31 patients with IgG4-RD compared to 13 of 13 patients with L-HES (median eosinophils 0.4 vs 7.0 giga/L, P=.001) and 12 of 20 patients with IgG4-RD had increased serum IgE compared to eight of 13 patients with L-HES, P=.930. Twenty-seven of 30 patients with IgG4-RD had elevated serum IgG4 compared to five of 12 patients with L-HES (median IgG4 9.6 g/L vs 0.80 g/L, P=.002). Flow cytometry demonstrated an aberrant T-cell phenotype in 7 of 23 patients with IgG4-RD and 13 of 13 patients with L-HES (P<.001). T-cell clonality by PCR was positive in 12 of 23 patients with IgG4-RD vs 10 of 13 patients with L-HES (P=.143). Patients in both groups received corticosteroids as first-line therapy. For refractory disease in IgG4-RD, rituximab was the most common steroid-sparing agent, whereas in L-HES, it was pegylated interferon-α-2a. CONCLUSION: The overlapping features of these two diseases with divergent treatment options demonstrate the importance of familiarity with both entities to optimize diagnosis and treatment.
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Corticosteroides/administração & dosagem , Síndrome Hipereosinofílica , Imunoglobulina G/sangue , Interferon-alfa/administração & dosagem , Polietilenoglicóis/administração & dosagem , Rituximab/administração & dosagem , Linfócitos T , Adulto , Idoso , Feminino , Humanos , Síndrome Hipereosinofílica/sangue , Síndrome Hipereosinofílica/diagnóstico , Síndrome Hipereosinofílica/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/administração & dosagemRESUMO
Serum soluble interleukin-2 receptor (sIL-2r) is an important disease marker in hemophagocytic lymphohistiocytosis (HLH), but there are no published data on its diagnostic value in adults. We conducted a single-center retrospective study of 78 consecutive adults who had sIL-2r measured for suspected HLH. Serum sIL-2r levels were measured by enzyme-linked immunosorbent assay (adult reference range, 241-846 U/mL). There were 38 patients with HLH and 40 with a non-HLH diagnosis (such as sepsis, liver disease, histiocyte disorders, autoimmune disease, leukemia, or lymphoma). The receiver operating characteristic curve demonstrated that sIL-2r is a good to excellent diagnostic test for adult HLH, with an area under the curve (AUC) of 0.90 (95% confidence interval, 0.83-0.97) compared with AUC 0.78 (95% confidence interval, 0.67-0.88) for ferritin. The optimal threshold for sIL-2r was 2515 U/mL (sensitivity, 100%; specificity, 72.5%). Although there was a large indeterminate range for sIL-2r, a level of 2400 U/mL or less was helpful for ruling out HLH (sensitivity, 100%), and more than 10 000 U/mL was helpful for ruling in HLH (specificity, 93%). Higher mean sIL-2r levels were seen in malignancy-associated HLH (20 241 U/mL) compared with infection-associated HLH and macrophage activation syndrome (9720 and 5008 U/mL, respectively; P < .05). Levels above 10 000 U/mL were not associated with worse prognosis in patients with HLH. Serum sIL-2r is a sensitive test for diagnosis of adult HLH, but is not as specific as previously reported in children. Additional studies enriched with patients without HLH who have conditions associated with T-cell activation, such as lymphoma and autoimmune lymphoproliferative syndrome, are needed.
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BACKGROUND: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating illness. Symptoms include profound fatigue and distinctive post-exertional malaise (PEM). We asked whether a submaximal exercise test would prove useful for identifying different patterns of tissue oxygen utilization in individuals with ME/CFS versus healthy subjects. Such a test has potential to aid with ME/CFS diagnosis, or to characterize patients' illness. METHODS: A case-control study of 16 patients with ME/CFS compared to 16 healthy controls completing a 3-min handgrip protocol was performed. Response was measured using near-infrared spectroscopy, resulting in measurements of oxygenated (O2Hb) and deoxygenated hemoglobin (HHb) over wrist extensors and flexors. Changes in O2Hb (delta (d)O2Hb) and HHb (dHHb) absorbance between the first and last contraction were calculated, as were the force-time product of all contractions, measured as tension-time index (TTI), and ratings of perceived exertion (RPE). RESULTS: Individuals with ME/CFS demonstrated smaller dO2Hb and dHHb than controls. However, after adjusting for TTI and change in total hemoglobin (delta (d)tHb), differences in dO2Hb and dHHb were reduced, with large overlapping variances. RPE was significantly higher for cases than controls, particularly at rest. CONCLUSIONS: Relative to controls, participants with ME/CFS demonstrated higher RPE, lower TTI, and reduced dO2Hb and dHHb during repetitive handgrip exercise, although considerable variance was observed. With further study, submaximal exercise testing may prove useful for stratifying patients with a lower propensity for inducing PEM, and have the ability to establish baseline intensities for exercise prescription.
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Encefalomielite/terapia , Teste de Esforço , Síndrome de Fadiga Crônica/terapia , Espectroscopia de Luz Próxima ao Infravermelho , Idoso , Estudos de Casos e Controles , Estudos de Coortes , Encefalomielite/complicações , Fadiga , Síndrome de Fadiga Crônica/complicações , Feminino , Força da Mão , Hemoglobinas/química , Humanos , Pessoa de Meia-Idade , Oxigênio/químicaRESUMO
The increased longevity afforded by combination antiretroviral therapy in developed countries has led to an increased concern regarding senescence-related diseases in patients with human immunodeficiency virus (HIV) infection. Previous epidemiologic analyses have demonstrated an increased risk of chronic obstructive pulmonary disease, as well as a significant burden of respiratory symptoms in HIV-infected patients. We performed the St. George's Respiratory Questionnaire (SGRQ) in 199 HIV-positive men, and determined the predominant factors contributing to poor respiratory-related health status. In univariate analyses, worse SGRQ scores were associated with respiratory-related variables such as greater smoking pack-year history (p=0.028), lower forced expiratory volume in 1 second (FEV1) (p<0.001), and worse emphysema severity as quantified by computed tomographic imaging (p=0.017). In addition, HIV-specific variables, such as a history of plasma viral load >100,000 copies/mL (p=0.043), lower nadir CD4 cell count (p=0.040), and current CD4 cell count ≤350 cells/µL (p=0.005), as well as elevated levels of inflammatory markers, specifically plasma interleukin (IL)-6 (p=0.002) and alpha-1 antitrypsin (p=0.005) were also associated with worse SGRQ scores. In a multiple regression model, FEV1, current CD4 count ≤350 cells/µL, and IL-6 levels remained significant contributors to reduced respiratory-related health status. HIV disease activity as measured by HIV-related immunosuppression in conjunction with the triggering of key inflammatory pathways may be important determinants of worse respiratory health status among HIV-infected individuals. Limitations of this analysis include the absence of available echocardiograms, diffusion capacity and lung volume testing, and an all-male cohort due to the demographics of the clinic population.