RESUMO
BACKGROUND: Complex regional pain syndrome type 1 (CRPS-1) is a rare, disabling and sometimes chronic disorder usually arising after a trauma. This exploratory study examined whether patients with chronic CRPS-1 have a different genetic profile compared with those who do not have the condition. METHODS: Exome sequencing was performed to seek altered non-synonymous SNP allele frequencies in a discovery cohort of well-characterised patients with chronic CRPS-1 (n=34) compared with population databases. Identified SNP alleles were confirmed by Sanger sequencing and sought in a replication cohort (n=50). Gene expression of peripheral blood macrophages was assessed. RESULTS: In the discovery cohort, the rare allele frequencies of four non-synonymous SNPs were statistically increased. The replication cohort confirmed this finding. In a chronic pain cohort, these alleles were not overexpressed. In total, 25 out of 84 (29.8%) patients with CRPS-1 expressed a rare allele. The SNPs were rs41289586 in ANO10, rs28360457 in P2RX7, rs1126930 in PRKAG1 and rs80308281 in SLC12A9. Males were more likely than females to have a rare SNP allele, 8 out of 14 (57.1%) vs 17 out of 70 (24.3%) (Fisher's p=0.023). ANO10, P2RX7, PRKAG1 and SLC12A9 were all expressed in macrophages from healthy human controls. CONCLUSION: A single SNP in each of the genes ANO10, P2RX7, PRKAG1 and SLC12A9 was associated with developing chronic CRPS-1, with more males than females expressing these rare alleles. Our work suggests the possibility that a permissive genetic background is an important factor in the development of CRPS-1.
Assuntos
Síndromes da Dor Regional Complexa , Masculino , Feminino , Humanos , Síndromes da Dor Regional Complexa/genética , Síndromes da Dor Regional Complexa/epidemiologia , Frequência do Gene , Polimorfismo de Nucleotídeo Único/genética , Alelos , Patrimônio GenéticoRESUMO
Immune-mediated necrotising myopathy (IMNM) is a severe and poorly understood complication of statin use. Prompt management with immunosuppressive treatment is often needed to control the condition, which differs from the management of the more commonly recognised statin-induced myopathy. We present a case report and brief review of the literature regarding the pathogenesis, diagnosis, and management of anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) positive IMNM (HMGCR IMNM). There are no randomised clinical trials, but several smaller studies and cases suggest a triple therapy of corticosteroids, IVIG, and a corticosteroid-sparing immunosuppressant appears efficacious in patients with IMNM and proximal weakness. The mechanism of statin-induced IMNM is uncertain, and this is further complicated by the reports of HMGCR IMNM in statin-naïve patients, including children. We present a case of biopsy-confirmed HMGCR IMNM in a woman taking daily statins for treatment of hypercholesterolaemia for 4 years. She presented with symptoms consistent with a urinary tract infection (UTI), including muscle weakness. She was treated as an isolated case of UTI. One month later, she presented again with worsening weakness in her shoulders and hips. Creatine kinase was elevated, and MRI showed increased signal with STIR sequences in both thighs. Anti-HMGCR was positive and leg biopsy-confirmed necrotising changes. Stopping her statin prescription and a short course of prednisolone did not improve her muscle weakness. Adding methotrexate resulted in eventual resolution of her symptoms. IMNM should be considered as a differential in any patient taking statins presenting with muscle weakness, and this case suggests that immunosuppressant therapy in addition to cessation of statins is effective at treating IMNM. Clinical trials are needed to further investigate the efficacy of different combinations of immunosuppressants.
Assuntos
Doenças Autoimunes , Inibidores de Hidroximetilglutaril-CoA Redutases , Doenças Musculares , Miosite , Humanos , Criança , Feminino , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Autoanticorpos , Necrose , Miosite/induzido quimicamente , Miosite/diagnóstico , Miosite/tratamento farmacológico , Doenças Autoimunes/induzido quimicamente , Doenças Musculares/induzido quimicamente , Doenças Musculares/diagnóstico , Doenças Musculares/tratamento farmacológico , Debilidade Muscular/induzido quimicamente , Imunossupressores/efeitos adversosAssuntos
Artrite Infecciosa/etiologia , Síndrome de Lemierre/complicações , Adulto , Humanos , MasculinoRESUMO
Chronic pain in complex regional pain syndrome (CRPS) has been linked to tactile misperceptions and deficits in somatotopic representation of the affected limb. In this study, we identify altered cognitive processing of tactile stimuli in CRPS patients that we propose marks heterogeneity in tactile decision-making mechanisms. In a case-control design, we compared middle- and late-latency somatosensory evoked potentials in response to pseudorandomized mechanical stimulation of the digits of both hands (including CRPS-affected and nonaffected sides) between 13 CRPS patients and 13 matched healthy controls. During a task to discriminate the digit simulated, patients (compared with controls) had significantly lower accuracy and slowed response times but with high between-subject variability. At middle latencies (124-132 ms), tactile processing in patients relative to controls showed decrements in superior parietal lobe and precuneus (that were independent of task demands) but enhanced activity in superior frontal lobe (that were task-dependent). At late latencies, patients showed an augmented P300-like response under task demands that localized to the supplementary motor area. Source activity in the supplementary motor area correlated with slowed response times, although its scalp representation intriguingly correlated with better functioning of the affected limb, suggesting a compensatory mechanism. Future research should investigate the clinical utility of these putative markers of tactile decision-making mechanisms in CRPS. PERSPECTIVE: We present evidence of altered but highly variable cognitive processing (124-268 ms latency) in response to mechanical tactile stimuli in patients with CRPS compared with healthy controls. Such mid- to late-latency responses could potentially provide convenient and robust biomarkers of abnormal perceptual decision-making mechanisms in CRPS to aid in clinical detection and treatment.
Assuntos
Transtornos Cognitivos/etiologia , Transtornos Cognitivos/reabilitação , Síndromes da Dor Regional Complexa/complicações , Córtex Motor/fisiopatologia , Estimulação Física/métodos , Tato/fisiologia , Adulto , Mapeamento Encefálico , Estudos de Casos e Controles , Eletroencefalografia , Potenciais Evocados P300/fisiologia , Feminino , Mãos/inervação , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Tempo de Reação/fisiologia , Córtex Somatossensorial/fisiopatologia , Inquéritos e QuestionáriosRESUMO
OBJECTIVES: Delays in diagnosis occur with complex regional pain syndrome (CRPS). We define and prospectively demonstrate that novel bedside tests measuring body perception disruption can identify patients with CRPS postfracture. METHODS: The objectives of our study were to define and validate 4 bedside tests, to identify the prevalence of positive tests in patients with CRPS and other chronic pain conditions, and to assess the clinical utility (sensitivity, specificity, positive predictive value, negative predictive value) for identifying CRPS within a Fracture cohort. This was a single UK teaching hospital prospective cohort study with 313 recruits from pain-free volunteers and patients with chronic pain conditions.Four novel tests were Finger Perception (FP), Hand Laterality identification (HL), Astereognosis (AS), and Body Scheme (BS) report. Five questionnaires (Brief Pain Inventory, Upper Extremity Functional Index, Lower Extremity Functional Index, Neglect-like Symptom Questionnaire, Hospital Anxiety and Depression Score) assessed the multidimensional pain experience. RESULTS: FP and BS were the best performing tests. Prospective monitoring of fracture patients showed that out of 7 fracture patients (total n=47) who had both finger misperception and abnormal BS report at initial testing, 3 developed persistent pain with 1 having a formal diagnosis of CRPS. DISCUSSION: Novel signs are reliable, easy to perform, and present in chronic pain patients. FP and BS have significant clinical utility in predicting persistent pain in a fracture group thereby allowing targeted early intervention.
Assuntos
Síndromes da Dor Regional Complexa/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Dor Crônica/diagnóstico , Dor Crônica/epidemiologia , Dor Crônica/fisiopatologia , Síndromes da Dor Regional Complexa/epidemiologia , Síndromes da Dor Regional Complexa/fisiopatologia , Feminino , Fraturas Ósseas/complicações , Fraturas Ósseas/fisiopatologia , Lateralidade Funcional , Mãos/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Medição da Dor/métodos , Testes Imediatos , Prevalência , Estudos Prospectivos , Sensibilidade e Especificidade , Inquéritos e Questionários , Adulto JovemRESUMO
Kaposi sarcoma usually occurs in immunosuppressed patients. A classic type has been reported in elderly men of Jewish and Mediterranean origin. We report a case of an elderly woman with giant cell arteritis (GCA) who developed Kaposi sarcoma while on a double blind trial for GCA with an anti-tumor-necrosis-factor medication. Our patient had none of the risk factors for Kaposi sarcoma, and when she was withdrawn from the study it was found that she was receiving only placebo along with the moderate, tapering doses of corticosteroids.
Assuntos
Arterite de Células Gigantes/tratamento farmacológico , Sarcoma de Kaposi/etiologia , Neoplasias Cutâneas/etiologia , Corticosteroides/efeitos adversos , Corticosteroides/uso terapêutico , Idoso , Método Duplo-Cego , Feminino , Arterite de Células Gigantes/complicações , Humanos , Imunossupressores/efeitos adversos , Placebos , Prednisolona/efeitos adversos , Prednisolona/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Remissão Espontânea , Sarcoma de Kaposi/sangue , Neoplasias Cutâneas/sangue , Transtornos da Visão/etiologiaRESUMO
Complex regional pain syndrome (CRPS) is a chronic, debilitating pain condition that usually arises after trauma to a limb, but its precise etiology remains elusive. Novel clinical signs based on body perceptual disturbances have been reported, but their pathophysiological mechanisms remain poorly understood. Investigators have used functional neuroimaging techniques (including MEG, EEG, fMRI, and PET) to study changes mainly within the somatosensory and motor cortices. Here, we provide a focused review of the neuroimaging research findings that have generated insights into the potential neurocognitive and neuroplastic mechanisms underlying perceptual disturbances in CRPS. Neuroimaging findings, particularly with regard to somatosensory processing, have been promising but limited by a number of technique-specific factors (such as the complexity of neuroimaging investigations, poor spatial resolution of EEG/MEG, and use of modeling procedures that do not draw causal inferences) and more general factors including small samples sizes and poorly characterized patients. These factors have led to an underappreciation of the potential heterogeneity of pathophysiology that may underlie variable clinical presentation in CRPS. Also, until now, neurological deficits have been predominantly investigated separately from perceptual and cognitive disturbances. Here, we highlight the need to identify neurocognitive phenotypes of patients with CRPS that are underpinned by causal explanations for perceptual disturbances. We suggest that a combination of larger cohorts, patient phenotyping, the use of both high temporal, and spatial resolution neuroimaging methods, and the identification of simplified biomarkers is likely to be the most fruitful approach to identifying neurocognitive phenotypes in CRPS. Based on our review, we explain how such phenotypes could be characterized in terms of hierarchical models of perception and corresponding disturbances in recurrent processing involving the somatosensory, salience and executive brain networks. We also draw attention to complementary neurological factors that may explain some CRPS symptoms, including the possibility of central neuroinflammation and neuronal atrophy, and how these phenomena may overlap but be partially separable from neurocognitive deficits.
RESUMO
We describe an immunocompetent adult with acute cytomegalovirus (CMV) infection complicated by extensive portal vein thrombosis. A literature review on the incidence, presentation, pathophysiology and management of CMV-associated thrombosis is included. Previously thought to be a rare complication, recent large case series and the present case reconfirm the increasing prevalence of CMV-associated thromboembolism in the immunocompetent adult.
RESUMO
OBJECTIVES: To determine clinical predictors of hypoxemia in children with acute lower respiratory tract infection (ALRI). DESIGN: Cross-sectional study. SETTING: Emergency department of All India Institute of Medical Sciences, a tertiary care hospital. SUBJECTS: 109 under five children, with ALRI. METHODS: Clinical symptoms and signs were recorded. Oxygen saturation was determined by a pulse oximeter. Hypoxemia was defined as oxygen saturation less than 90%. The ability of various clinical symptoms and signs to predict the presence of hypoxemia was evaluated. RESULTS: Twenty-eight (25.7%) children were hypoxemic. No symptoms were statistically associated with hypoxemia. Tachypnea, suprasternal indrawing, intercostal indrawing, lower chest indrawing, cyanosis, crepitations, and rhonchi were statistically significantly associated with hypoxemia. A simple model using the presence of rapid breathing (> or =80/min in children < or =3 m, > or =70/min in >3-12 m and > or =60/min in >12 m) or lower chest indrawing had a sensitivity of 78.5% and specificity of 66.7% for detecting hypoxemia. No individual clinical symptom/sign or a combination had both sufficient sensitivity and specificity to identify hypoxemia. CONCLUSION: None of the clinical features either alone or in combination have desirable sensitivity and specificity to predict hypoxemia in children with acute lower respiratory tract infection.
Assuntos
Hipóxia/diagnóstico , Infecções Respiratórias/diagnóstico , Doença Aguda , Distribuição de Qui-Quadrado , Criança , Pré-Escolar , Estudos Transversais , Serviço Hospitalar de Emergência , Feminino , Humanos , Hipóxia/epidemiologia , Incidência , Lactente , Masculino , Razão de Chances , Oximetria , Valor Preditivo dos Testes , Troca Gasosa Pulmonar , Testes de Função Respiratória , Infecções Respiratórias/epidemiologia , Medição de Risco , Sensibilidade e Especificidade , Índice de Gravidade de DoençaRESUMO
Complex regional pain syndrome (CRPS) is a limb-confined posttraumatic pain syndrome with sympathetic features. The cause is unknown, but the results of a randomized crossover trial on low-dose intravenous immunoglobulins (IVIG) treatment point to a possible autoimmune mechanism. We tested purified serum immunoglobulin G (IgG) from patients with longstanding CRPS for evidence of antibodies interacting with autonomic receptors on adult primary cardiomyocytes, comparing with control IgG from healthy and diseased controls, and related the results to the clinical response to treatment with low-dose IVIG. We simultaneously recorded both single-cell contractions and intracellular calcium handling in an electrical field. Ten of 18 CRPS preparations and only 1/57 control preparations (P<0.0001) increased the sensitivity of the myocytes to the electric field, and this effect was abrogated by preincubation with α-1a receptor blockers. By contrast, effects on baseline calcium were blocked by preincubation with atropine. Interestingly, serum-IgG preparations from all 4 CRPS patients who had responded to low-dose IVIG with meaningful pain relief were effective in these assays, although 4/8 of the nonresponders were also active. To see if there were antibodies to the α-1a receptor, CRPS-IgG was applied to α-1a receptor-transfected rat-1 fibroblast cells. The CRPS serum IgG induced calcium flux, and fluorescence-activated cell sorting showed that there was serum IgG binding to the cells. The results suggest that patients with longstanding CRPS have serum antibodies to α-1a receptors, and that measurement of these antibodies may be useful in the diagnosis and management of the patients.
Assuntos
Autoanticorpos/sangue , Síndromes da Dor Regional Complexa/sangue , Síndromes da Dor Regional Complexa/imunologia , Receptores Adrenérgicos alfa 1/imunologia , Adulto , Animais , Atropina/farmacologia , Cálcio/metabolismo , Células Cultivadas , Síndromes da Dor Regional Complexa/terapia , Estudos Cross-Over , Dioxanos/farmacologia , Feminino , Humanos , Imunoglobulina G/farmacologia , Imunoglobulinas Intravenosas/uso terapêutico , Masculino , Potenciais da Membrana/efeitos dos fármacos , Pessoa de Meia-Idade , Antagonistas Muscarínicos/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Técnicas de Patch-Clamp , Ligação Proteica/efeitos dos fármacos , Ratos , Transfecção , Adulto JovemRESUMO
SUMMARY Chronic musculoskeletal pain, defined as pain lasting beyond the usual healing time of 6 weeks to 3 months, is a very common condition. It adversely affects the quality of life of patients and has a significant economic impact on our society. There is an ever increasing understanding of the pathophysiology of chronic pain. This has resulted in the effective use of various medications aimed at modulating both central and peripheral sensitizations. There are also new agents being developed based on fundamental research. The pharmacological agents used in the modulation of central nociception in chronic musculoskeletal pain are reviewed in this article.
Assuntos
Acidentes por Quedas , Competência Clínica/normas , Serviço Hospitalar de Emergência/normas , Corpo Clínico Hospitalar/normas , Doenças Musculoesqueléticas/diagnóstico , Exame Físico/normas , Padrão de Cuidado , Feminino , Marcha , Fidelidade a Diretrizes , Pesquisas sobre Atenção à Saúde , Humanos , Masculino , Auditoria Médica , Atividade Motora , Doenças Musculoesqueléticas/complicações , Doenças Musculoesqueléticas/fisiopatologia , Guias de Prática Clínica como Assunto , Valor Preditivo dos Testes , Prognóstico , Encaminhamento e Consulta/normas , Reino UnidoRESUMO
BACKGROUND: A 73-year-old, previously well woman was admitted to an emergency department because of a 3-month history of severe proximal girdle pain and stiffness with loss of appetite and weight. She was referred to a rheumatologist 10 days after her initial presentation. Within 4 weeks she presented to an outpatient clinic with nausea, vomiting, shortness of breath, painful mouth ulcers, rash on her legs and a further decline in appetite; she was readmitted to hospital. Within 4 months of initial presentation she became jaundiced. INVESTIGATIONS: At initial presentation, physical examination, biochemical, hematological and autoimmune screening, radiography of the pelvis, an abdominal ultrasound, and electromyography were conducted. At referral to a rheumatologist similar tests were repeated. At presentation to the outpatient clinic, hematological and biochemical screening, and a urine dipstick test were conducted. At readmittance to hospital, infectious and autoimmune screening, radiography of the chest, electrocardiogram, ultrasound of the abdomen, and renal biopsy were conducted. At the time of development of jaundice, biochemical and hematological screening, CT of the abdomen and ultrasound-guided biopsy of a pancreatic mass were conducted. DIAGNOSIS: Polymyalgia rheumatica, antineutrophil-cytoplasmic-antibody-positive microscopic polyangiitis with renal involvement and B-cell lymphoma of the head of the pancreas. MANAGEMENT: The patient received oral prednisolone 15 mg daily for polymyalgia rheumatica along with alendronate 70 mg weekly. The patient received intravenous cyclophosphamide 500 mg and methylprednisolone 500 mg every 2 weeks for her microscopic polyangiitis with renal involvement. For B-cell lymphoma of the head of the pancreas, the patient received cyclophosphamide, doxorubicin, vincristine and prednisolone once monthly.
Assuntos
Linfoma de Células B/complicações , Polimialgia Reumática/complicações , Vasculite/complicações , Idoso , Alendronato/uso terapêutico , Anticorpos Anticitoplasma de Neutrófilos/sangue , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antirreumáticos/uso terapêutico , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Quimioterapia Combinada , Feminino , Humanos , Imunossupressores/uso terapêutico , Linfoma de Células B/diagnóstico , Linfoma de Células B/tratamento farmacológico , Polimialgia Reumática/diagnóstico , Polimialgia Reumática/tratamento farmacológico , Prednisolona/administração & dosagem , Vasculite/diagnóstico , Vasculite/tratamento farmacológico , Vincristina/administração & dosagemRESUMO
OBJECTIVES: To determine clinical predictors of hypoxemia in children with acute lower respiratory tract infection (ALRI). DESIGN: Cross-sectional study. SETTING: Emergency department of All India Institute of Medical Sciences, a tertiary care hospital. SUBJECTS: 109 under five children, with ALRI. METHODS: Clinical symptoms and signs were recorded. Oxygen saturation was determined by a pulse oximeter. Hypoxemia was defined as oxygen saturation less than 90%. The ability of various clinical symptoms and signs to predict the presence of hypoxemia was evaluated. RESULTS: Twenty-eight (25.7%) children were hypoxemic. No symptoms were statistically associated with hypoxemia. Tachypnea, suprasternal indrawing, intercostal indrawing, lower chest indrawing, cyanosis, crepitations, and rhonchi were statistically significantly associated with hypoxemia. A simple model using the presence of rapid breathing (> or =80/min in children < or =3 m, > or =70/min in >3-12 m and > or =60/min in >12 m) or lower chest indrawing had a sensitivity of 78.5% and specificity of 66.7% for detecting hypoxemia. No individual clinical symptom/sign or a combination had both sufficient sensitivity and specificity to identify hypoxemia. CONCLUSION: None of the clinical features either alone or in combination have desirable sensitivity and specificity to predict hypoxemia in children with acute lower respiratory tract infection.