A systematic review of MR imaging as a tool for evaluating haemophilic arthropathy in children

Our purposes were to determine: (i) whether there is direct evidence that currently available MRI techniques are accurate for early diagnosis of pathological findings in haemophilic arthropathy; (ii) whether there is an MRI scoring system that best correlates with clinical/radiological constructs for evaluation of haemophilic arthropathy; (iii) whether there is an MRI scoring system that best correlates with clinical/radiological constructs for evaluation of haemophilic arthropathy. Articles were screened using MEDLINE (n = 566), EMBASE (n = 201), and the Cochrane Library (n = 1). Two independent reviewers assessed articles for inclusion under the overarching purposes of the review by using the Standards for Reporting of Diagnostic Accuracy (STARD) tool, and the quality of the studies were graded using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS‐2) tool. The electronic literature search retrieved 777 references (after duplicates were removed). A total of 32 studies were chosen for inclusion from the results of the search and review of bibliographical references. Using the STARD tool, seven studies were of excellent quality of reporting, and using the QUADAS‐2 tool, 10 studies were judged to be of adequate quality. There is ‘fair’ evidence to recommend MRI as an accurate test for detecting evidence of haemophilic arthropathy and the use of second or third generation MRI scales for assessing haemophilic arthropathy. However, there is no evidence that screening of early intra‐articular soft tissue bleed with MRI improves the functional status of joints over time.     

Magnetic resonance imaging and ultrasound evaluation of “healthy” joints in young subjects with severe haemophilia A

Magnetic resonance imaging (MRI) and ultrasonography (US) are increasingly used in haemophilia A (HA) to detect early joint changes. A total of 40 clinically asymptomatic joints, never involved by bleeding events [“healthy joints” (HJ)], were evaluated by MRI and, in parallel, by US in 20 young subjects with severe HA (22.45 ± 2.72 years old; no history of arthritides, of viral infections or of inhibitors against factor VIII). The same joints were evaluated in 20 matched non‐haemophilic (no‐HA) subjects (mean age 23.90 ± 2.31 years, P = 0.078 vs. HA subjects). US images were obtained with specific probe positions according to validated procedures. A validated US score and progressive (P‐MRI) and additive (A‐MRI) MRI scores were employed for data collection and analysis. The US score was higher in HA than in no‐HA subjects (3.40 ± 1.72 vs. 0.80 ± 1.10, P < 0.001). Taking into account only moderate/severe alterations, joint effusion was found in 55% of HA and in 5% of no‐HA joints (P < 0.001); synovial hypertrophy was found in 20% of HA and in none of the no‐HA joints; cartilage erosion was found in 30% of HA and in none of no‐HA joints. MRI examinations confirmed these findings and the US score correlated with the A‐MRI (r = 0.732, P < 0.001) and with the P‐MRI (r = 0.598, P < 0.001) scores. MRI and US data significantly correlated as to effusion (r = 0.819, P = 0.002), synovial hypertrophy (r = 0.633, P = 0.036) and cartilage erosion (r = 0.734, P = 0.010). Despite inherent limitations, joint US examination identified subclinical abnormalities of HJ in young subjects with severe HA.     

Identification and expression of iron regulators in human synovium: evidence for upregulation in haemophilic arthropathy compared to rheumatoid arthritis,osteoarthritis, and healthy controls

Recurrent joint bleeding is the most common manifestation of severe haemophilia resulting in haemophilic arthropathy (HA). Iron plays a central role in the pathogenesis of the two main features of HA: synovitis and cartilage destruction. The aim of this study was to investigate the synovial presence of the iron regulator proteins ferroportin (FPN), hepcidin, haemoglobin scavenger receptor CD163 (CD163), feline leukaemia virus subgroup C (FLVCR), and heme carrier protein 1 (HCP‐1). A comparison of the expression in HA with rheumatoid arthritis (RA), osteoarthritis (OA), and healthy controls (HC) is made. Synovial expression of iron regulators was investigated by immunohistochemistry in human synovial tissue and in a murine haemophilia model. We demonstrate for the first time the synovial presence of the investigated iron regulator proteins. Expression of the iron regulator proteins FPN, CD163, FLVCR, and HCP‐1 was enhanced in HA in comparison to RA, OA, and HC synovium. In addition, in a murine haemophilia model of acute joint bleeding, synovial expression of FPN, CD163, and HCP‐1 was increased. In both human and murine experiment, synovial expression of hepcidin was not altered. These findings indicate the presence of iron regulator proteins in the synovium, demonstrate an enhanced expression of FPN, CD163, FLVCR, and HCP‐1 in HA, and suggest a synovial adaptation mechanism to maintain synovial iron homeostasis in HA.     

马尔尼菲青霉所致的骨与关节病的临床与病理研究

介绍一种病人最感痛苦而医生最易发现的马尔尼菲青霉病临床表现--溶骨性病变和关节肿痛,作者认为骨髓是易感马尔尼菲青霉的组织,应该注意骨和关节在本病中的表现作为诊断及鉴别诊断的依据,但通常骨髓感染引起弥漫性巨噬细胞反应性增生并吞噬大量病原体而不发生溶骨性病变。溶骨性病变的基础是局部化脓性反应,局部病原体数量往往不多,关键在于大量白细胞堆积而导致酶性溶解。该病的骨与关节的损害有自愈倾向,但反复发作难于根治,需要较长时间的积极抗真菌治疗。     

血友病性骨关节病的X线诊断（附15例报告）

本文报告１５例血友病性骨关节病，其中１０例为血友病甲，２例为血友病乙，１例为血友病丙，余２例未分型。均为男性。其Ｘ线表现为关节囊软组织肿胀、密度增高（１５例），骨端或骨骺增大变方（６例），关节间隙变窄、关节面硬化和囊性变（１２例），关节骨端破坏（６例），骨性关节强直（１例），股骨髁间凹和尺骨鹰咀窝增宽变深（１０例），骨膜新生骨（３例）和血友病性假肿瘤（２例）。文中分析本病的Ｘ线表现并讨论其病理基础。     

麻风性营养性关节病临床X线分析(附20例报告)

本文报告20例由麻风引起的神经营养性关节病,其中瘤型8例,结核样型11例,界线类1例.20例累及45处关节.X线表现为增生型1例,萎缩型19例,对其发病机制及原因进行了讨论,本病的特点:1)多为萎缩型;2)受累关节多为腕、踝及其以下关节;3)掌指关节受累最先始于小指和无名指.同时,对本病的诊断和鉴别诊断亦作了讨论.     

Localized amyloid deposition in cartilage is glycosaminoglycans-associated

Localized amyloid deposition is known to occur commonly in the articular cartilage of elderly patients. Its pathogenesis is uncertain and it is not known if other cartilage-containing tissues also contain amyloid deposits. Systemic amyloid deposits are known to contain highly sulphated glycosaminoglycans, a major constituent of cartilage. As the composition of articular cartilage glycosaminoglycans is known to change with age, we sought to identify whether localized amyloid deposition in cartilage was glycosaminoglycan-related. We examined specimens of articular cartilage over a wide age range and also examined a variety of cartilaginous tumours and tumour-like lesions for the presence or absence of amyloid deposits. Using mucin histochemistry (alcian blue: MgCl₂ critical electrolyte concentration) and immunohistochemistry, we found that highly sulphated glycosaminoglycans (0.9 M and 1 M MgCl₂), in particular keratan sulphate, localized to amyloid deposits in both articular cartilage and loose bodies derived from the articular surface. Other cartilaginous lesions (including loose bodies of primary synovial chondromatosis) were negative for amyloid and did not contain highly sulphated glycosaminoglycans. These findings suggest that changes in specific highly sulphated glycosaminoglycans may play a role in localized amyloid deposition in articular cartilage.     

Revision using modified transglenoid reconstruction in recurred glenohumeral instability combined with anchor-induced arthropathy

A 25-year-old man presented with a history of pain and crepitus in the right shoulder; he had been previously treated with arthroscopic anterior stabilization using four metallic suture anchors for recurrent traumatic anterior instability 1 year earlier. In this report, we present a patient with recurrent glenohumeral instability combined with anchor-induced arthropathy who was managed with modified arthroscopic transglenoid reconstruction following arthroscopic suture anchor retrieval.     

Long-term FEIBA prophylaxis does not prevent progression of existing joint disease

Activated prothrombin complex concentrates have been used to treat bleeding episodes for patients who have developed an inhibitor to factor VIII (FVIII). FEIBA-Vh (FVIII bypassing activity, FEIBA) has been used since 1970 for this purpose and with FVIII for immune tolerance programmes. Studies have not been presented to show the safety and efficacy of FEIBA when given over a long period of time to prevent haemophilic arthropathy with bleeding into the joints of these patients. This study was undertaken to ascertain the outcome of haemophilic arthropathy with FEIBA prophylaxis. Data were collected on seven patients with known long-standing high-titre FVIII inhibitors given FEIBA prophylaxis for 3-6(1/2) years. Patients were given 50-100 units of FEIBA three to four times weekly. A functional joint evaluation revealed some degree of arthropathy already present in all patients at time of prophylaxis initiation. Safety was measured by medical status, evidence of thrombosis, life-threatening bleeding and inhibitor titre. Efficacy was measured for joint outcome by a functional physical therapeutic scale. At the conclusion of the study, efficacy was mixed as all of the joints for which the patients were placed on prophylaxis had progressed and developed synovitis. Two patients had a functional improvement in their arthropathy, and all were functional enough to attend regular school. The product was deemed safe for long-term use, as there were no complications of therapy with no thrombosis, no life-threatening bleeding episodes and no anamnesis caused by FEIBA alone. Inhibitor titres fell in all patients over the course of the study. Total product usage ranged from approximately 9373-15,571 U kg(-1) year(-1). FEIBA is safe for long-term prophylaxis when given in the recommended dosage for an extended period of time. Efficacy to prevent arthropathy could not be seen as all patients had some degree of arthropathy at time of prophylaxis initiation. An additional study needs to be performed using FEIBA before arthropathy has developed.     

Practice patterns in haemophilia A therapy – global progress towards optimal care

This paper reports the findings of a global survey of practice patterns for the management of patients with haemophilia A. A total of 147 haemophilia treatment centres worldwide responded to the questionnaire, supplying data for 16 115 patients with haemophilia A. From these responses, 38% (range: 25-48%) of patients were under 18 years old. Almost half (47%) of patients were reported to have mild or moderate haemophilia A, 48% had severe haemophilia A (no inhibitor) and 5% were inhibitor patients. Less than half of patients with severe haemophilia A received prophylactic therapy (37%, excluding inhibitor patients) and 54% received on-demand treatment; the remaining 9% were inhibitor patients. Primary prophylaxis rates for severe haemophilia ranged from 73% in Sweden to 17% in the USA. Most respondents (80%) ranked infrequent bleeds as one of the top five reasons for not administering prophylactic treatment, followed by venous access (60%) and cost (45%). Of patients with severe haemophilia (non-inhibitor), 32% on primary prophylaxis and 27% on secondary prophylaxis had indwelling catheters. Risk of infection and the patient's inability to maintain the line were the key concerns cited by nurses relating to venous access. The mean ratio of nurses to patients with haemophilia A was 1:69 and nurses felt that they were either fully (26%) or mostly (45%) autonomous in assessment and treatment decisions. Results from this current survey suggest that worldwide research should be continued so as to improve outcomes through the identification of optimal treatment protocols for the management of haemophilia A.