Diagnostic and therapeutic practices in adult chronic nonbacterial osteomyelitis (CNO).

BACKGROUND: Chronic nonbacterial osteomyelitis (CNO) is a rare, and impactful auto-inflammatory bone disease occurring in children and adults. Clinical care for CNO is challenging, as the condition lacks validated classification criteria and evidence-based therapies. This study aimed to map the current diagnostic and therapeutic practices for CNO in adults, as a first step towards a standardized disease definition and future consensus treatment plans. METHODS: A primary survey was spread among global rheumatological/bone networks and 57 experts as identified from literature (May 2022), covering terminology, diagnostic tools (clinical, radiological, biochemical) and treatment steps. A secondary survey (sent to primary survey responders in August 2022) further queried key diagnostic features, treatment motivations, disease activity and treatment response monitoring. RESULTS: 36 and 23 physicians completed the primary and secondary survey respectively. Diagnosis was mainly based on individual physician assessment, in which the combination of chronic relapsing-remitting bone pain with radiologically-proven osteitis/osteomyelitis, sclerosis, hyperostosis and increased isotope uptake on bone scintigraphy were reported indicative of CNO. Physicians appeared more likely to refer to the condition as synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome in the presence of joint and skin pathology. MRI was most frequently performed, and the preferred diagnostic test for 47%. X-rays were second-most frequently used, although considered least informative of all available tools. Typical imaging features reported were hyperostosis, osteitis, osteosclerosis, bone marrow edema, while degeneration, soft tissue calcification, and ankylosis were not regarded characteristic. Inflammation markers and bone markers were generally regarded unhelpful for diagnostic and monitoring purposes and physicians infrequently performed bone biopsies. Management strategies diverged, including indications for treatment, response monitoring and declaration of remission. Step-1 treatment consisted of non-steroidal anti-inflammatory drugs/COX-2 inhibitors (83%). Common step 2-3 treatments were pamidronate, methotrexate, and TNF-a-inhibition (anti-TNFα), the latter two regarded especially convenient to co-target extra-skeletal inflammation in SAPHO syndrome. Overall pamidronate and anti-TNFα and were considered the most effective treatments. CONCLUSIONS: Following from our survey data, adult CNO is a broad and insufficiently characterized disease spectrum, including extra-osseous features. MRI is the favoured imaging diagnostic, and management strategies vary significantly. Overall, pamidronate and anti-TNFα are regarded most successful. The results lay out current practices for adult CNO, which may serve as backbone for a future consensus clinical guideline.

Healthcare professionals in research (HPiR) Facebook community: a survey of U.K. doctoral and postdoctoral healthcare professionals outside of medicine.

BACKGROUND: Healthcare professionals outside of medicine (HCPs), including nurses, midwives and allied health professionals, are increasingly involved in research for patient benefit. Their challenge is to negotiate inter-professional or professionally isolated contexts. The aims of this study were to evaluate the 'Healthcare Professionals in Research' (HPiR) Facebook group (a self-directed and confidential peer support group for doctoral and postdoctoral HCPs) including engagement, the experiences of doctoral and postdoctoral HPiR members and to identify future career challenges using an on-line survey. METHODS: The HPiR Facebook group was launched in May 2019. Five HCP Community managers (CMs) were trained in on-line platform curation, moderation and screening. An on-line survey was designed to capture data from HPiR members. A purposive sampling approach was applied. Respondents were required to be doctoral and postdoctoral HCPs and a registered member of the HPiR group. Respondents represented a range of healthcare professions, 79 % of whom had over ten years clinical experience. Membership growth and engagement was analysed. Descriptive statistics were used to present numerical data. Qualitative data were analysed thematically. RESULTS: 96 members were admitted to the group within the first month. All members were actively engaged with group content. 34/96 doctoral and postdoctoral HCPs completed the survey. Most members joined for networking (88 %) and peer support (82 %) purposes. Analysis of text responses showed difficulties in balancing a clinical academic career and highlighted the consequences of undefined clinical academic roles and pathways. CONCLUSIONS: Doctoral and postdoctoral HCPs value the opportunities that HPiR provides for peer support and connection with fellow HCPs. HPiR has the potential to strengthen research capacity, support research skill development and drive change within the clinical academic community. Clinical academic roles and pathways need to be standardised. The creation of opportunities beyond doctoral studies is a priority.

'Sink or swim': an evaluation of the clinical characteristics of individuals with high bone mass.

SUMMARY: High bone mineral density on routine dual energy X-ray absorptiometry (DXA) may indicate an underlying skeletal dysplasia. Two hundred fifty-eight individuals with unexplained high bone mass (HBM), 236 relatives (41% with HBM) and 58 spouses were studied. Cases could not float, had mandible enlargement, extra bone, broad frames, larger shoe sizes and increased body mass index (BMI). HBM cases may harbour an underlying genetic disorder. INTRODUCTION: High bone mineral density is a sporadic incidental finding on routine DXA scanning of apparently asymptomatic individuals. Such individuals may have an underlying skeletal dysplasia, as seen in LRP5 mutations. We aimed to characterize unexplained HBM and determine the potential for an underlying skeletal dysplasia. METHODS: Two hundred fifty-eight individuals with unexplained HBM (defined as L1 Z-score ≥ +3.2 plus total hip Z-score ≥ +1.2, or total hip Z-score ≥ +3.2) were recruited from 15 UK centres, by screening 335,115 DXA scans. Unexplained HBM affected 0.181% of DXA scans. Next 236 relatives were recruited of whom 94 (41%) had HBM (defined as L1 Z-score + total hip Z-score ≥ +3.2). Fifty-eight spouses were also recruited together with the unaffected relatives as controls. Phenotypes of cases and controls, obtained from clinical assessment, were compared using random-effects linear and logistic regression models, clustered by family, adjusted for confounders, including age and sex. RESULTS: Individuals with unexplained HBM had an excess of sinking when swimming (7.11 [3.65, 13.84], p < 0.001; adjusted odds ratio with 95% confidence interval shown), mandible enlargement (4.16 [2.34, 7.39], p < 0.001), extra bone at tendon/ligament insertions (2.07 [1.13, 3.78], p = 0.018) and broad frame (3.55 [2.12, 5.95], p < 0.001). HBM cases also had a larger shoe size (mean difference 0.4 [0.1, 0.7] UK sizes, p = 0.009) and increased BMI (mean difference 2.2 [1.3, 3.1] kg/m(2), p < 0.001). CONCLUSION: Individuals with unexplained HBM have an excess of clinical characteristics associated with skeletal dysplasia and their relatives are commonly affected, suggesting many may harbour an underlying genetic disorder affecting bone mass.

Evaluating bone health in women with oestrogen receptor positive breast cancer (ERBC) starting aromatase inhibitors.

AIMS: There is an increase in fractures in women with oestrogen receptor positive breast cancer (ERBC) particularly those taking aromatase inhibitors (AIs). How to identify women at osteoporosis risk, assess bone health and who to treat, are questions not adequately answered by previous studies. METHODS: We present an audit of osteoporosis risk factors, bone mineral density (BMD) measurement and other data relevant to bone health (falls and laboratory tests) in 85 women with ERBC starting AIs. RESULTS: Only 9/85 (11%) women overall and only 2/13 with previous peripheral fragility fractures had osteoporosis. Of note, secondary hyperparathyroidism was present in 40% of women <60 years; 67% of women 60-69 years and 75% of women >70 years. CONCLUSIONS: Reliance on BMD alone to guide decisions for osteoporosis prevention treatment in those taking AIs would lead to few women being treated. Osteoporosis risk in women taking AIs is likely influenced by factors other than those encompassed by BMD alone.

Relevance of thiopurine methyltransferase status in rheumatology patients receiving azathioprine.

Azathioprine (AZA) is widely used in the management of rheumatological diseases. Despite its efficacy, AZA can often cause bone marrow suppression, notably leucopenia, which has been recorded in up to 17% of patients taking AZA for rheumatoid arthritis, though this can be considered clinically significant in about 3% overall. Severe myelosuppression, associated with abnormal AZA metabolism, is linked to the thiopurine methyltransferase (TPMT) genetic polymorphism. TPMT status can be assessed prior to AZA treatment by measuring enzyme activity or genotyping techniques. Analysis of recent data suggests that by optimizing the AZA dose on the basis of TPMT status testing (with a substantial reduction in dose for patients homozygous for mutant TPMT alleles), a reduction in drug-induced morbidity and cost savings can be made by avoiding hospitalization and rescue therapy for leucopenic events. In this article we review the pharmacogenetic and clinical implications of the TPMT polymorphism, emphasizing its relevance to rheumatologists managing diseases with AZA.

Acipimox does not augment thallium-201 redistribution in the fasting state.

BACKGROUND: Recently oral glucose loading and a thallium-glucose insulin infusion have been used to augment myocardial uptake of thallium-201 (TI-201). Acipimox is a nicotinic-acid derivative that reduces serum free fatty acid (FFA) levels and enhances myocardial glucose uptake. This study was performed to assess the effects of acipimox on TI-201 redistribution. METHODS: Fourteen patients with coronary artery disease underwent 2 successive TI-201 perfusion studies. Stress was performed by adenosine coupled with ergometer exercise. Patients received either 500 mg of acipimox or placebo immediately after stress, and images were acquired. Redistribution imaging was carried out after 4 hours. Patients returned after 7 to 14 days for a repeat stress protocol, receiving the alternate test article. Both studies were carried out under identical conditions with identical medication with the patient in the fasting state. Image analysis was conducted quantitatively with polar plots and by using segmental uptake as a percentage of maximal counts with a 9-segment model. RESULTS: There were no significant differences between the acipimox and placebo arms of the study of hemodynamic parameters. On polar plot analysis, there were no differences between acipimox and placebo for mean values of stress defect extent (97 +/- 16.1 vs 96.5 +/- 18.8 pixels), defect severity (532.2 +/- 120 vs 537 +/- 133.9 standard deviations [SDs]), for defect reversibility (61.7 +/- 18 vs 55.4 +/- 15.3 SDs), and percentage reversibility (21.2% +/- 5.5% vs 19.2% +/- 5.8%), respectively. Similarly, on segmental uptake analysis there was no significant difference between the acipimox and placebo arms with regard to the proportion of segments classified as normal, fixed defect, reversible defect, or reverse redistribution. CONCLUSION: Although acipimox has been shown to augment myocardial glucose uptake and myocardial glucose uptake has been shown to improve cellular uptake of TI-201, in the fasting state acipimox does not enhance the redistribution after stress. This may be because serum insulin levels are not increased by acipimox, and insulin is instrumental in enhancing the joint transport of glucose and TI-201 into myocytes.

Double blind glucocorticoid controlled trial of samarium-153 particulate hydroxyapatite radiation synovectomy for chronic knee synovitis.

BACKGROUND: Samarium-153 particulate hydroxyapatite (Sm-153 PHYP) is a relatively new radiation synovectomy agent developed for the treatment of chronic synovitis. Although it has been shown that the levels of unwanted extra-articular radiation are lower after intra-articular injection of Sm-153 PHYP than yttrium-90 colloid, its clinical efficacy has not been rigorously studied. OBJECTIVES: To establish whether Sm-153 PHYP radiation synovectomy results in a clinically useful benefit sustained at one year. METHODS: In a randomised double blind study, patients received either intra-articular 40 mg triamcinolone hexacetonide alone or 40 mg triamcinolone hexacetonide combined with Sm-153 PHYP in an outpatient clinic. RESULTS: Sixty patients (28 male, 32 female), median age 51 (18-75) with chronic knee synovitis were studied. Diagnoses included: rheumatoid arthritis (n=29); psoriatic arthritis (n=9); ankylosing spondylitis (n=3); reactive arthritis (n=2); undifferentiated seronegative oligoarthritis (n=13) and miscellaneous inflammatory conditions (n=4). More patients who received Sm-153 PHYP/triamcinolone hexacetonide sustained clinical benefit a year after treatment compared with patients who received corticosteroid alone (12 of 31 (39%) v 6 of 29 (21%), a difference of 18% more patients (95% CI -5% to 41%)) though the difference was not significant (chi(2)=2.31, 0.2>p>0.1, n=60). Despite the variation in injected activity (median 563 MBq, range 218-840 MBq), there was no obvious relation between low levels of injected activity (<555 MBq) and relapse within 12 months of treatment (chi(2) =2.61, 0.2>p>0.1, n=31). CONCLUSIONS: There was no clear beneficial clinical effect of combined Sm-153 PHYP/triamcinolone hexacetonide injection over triamcinolone hexacetonide alone a year after treatment for chronic knee synovitis.

Changes in articular synovial lining volume measured by magnetic resonance in a randomized, double-blind, controlled trial of intra-articular samarium-153 particulate hydroxyapatite for chronic knee synovitis.

OBJECTIVE: Magnetic resonance techniques have recently been investigated as tools with which to monitor inflammatory joint disease. Our aim was to use a contrast-enhanced T1-weighted protocol to monitor the short-term changes in knee synovial lining volume in a double-blind, randomized, controlled trial of intra-articular samarium-153 particulate hydroxyapatite (Sm-153 PHYP). METHODS: Twenty-four out-patients with chronic knee synovitis, from a cohort who had been recruited to a long-term clinical efficacy trial, were recruited for this study. Patients received either intra-articular Sm-153 PHYP combined with 40 mg triamcinolone hexacetonide or 40 mg intra-articular triamcinolone hexacetonide alone. Synovial lining volumes were calculated from three-dimensional T1-weighted contrast-enhanced images made before and after contrast enhancement with thresholding and pixel counting, immediately before and 3 months after treatment. RESULTS: Paired pre- and post-treatment magnetic resonance data were obtained for 18/24 (75%) patients. There was no significant difference in mean pre-treatment synovial volume between the two treatment groups (139 vs 127 ml). A mean reduction in synovial lining volume was detected in the Sm-153 PHYP/steroid-treated group (139 to 110 ml, P = 0.07) and in the steroid-treated group (127 to 58 ml, P < 0.001). The reduction was significantly greater in the steroid-treated group (-61% vs -23%, P < 0.05). CONCLUSIONS: Short-term changes in articular synovial lining in response to intra-articular treatment for chronic synovitis may be monitored by magnetic resonance imaging. After 3 months, a greater mean reduction in synovial lining volume had occurred in response to intra-articular steroid alone compared to combined Sm-153 PHYP/steroid injection.

An insight into rheumatology resources available on the World Wide Web.

The aim of this study was to gain an overview of rheumatology resources on the World Wide Web (WWW). A list of websites was generated using a commercial search engine and 'rheumatology' as a key word. A total of 154 websites were then evaluated with respect to origin and likely target audience; 43% of this initial group were either not accessible, repeats, or in a language other than English. Of the 87 websites we were able to analyse, we found that 67% originated from medical organizations and 51% were interpreted to be directed specifically at rheumatologists. Only 16% of websites were directed at patients only. The remainder were felt to contain information useful to both groups. Over half the websites felt to be of interest to patients contained advertisements. Although there is a lot of information relating to rheumatology on the WWW, it was invariably time consuming to access and there was little directed solely at patient education.

Technetium-99m human immunoglobulin imaging in patients with subacromial impingement or adhesive capsulitis.

Although recognised as useful in detecting soft-tissue inflammation and infection, technetium-99m human immunoglobulin (Tc-99m HIG) has not been widely studied in evaluating regional inflammatory musculoskeletal conditions. Tc-99m HIG scintigraphy was undertaken for consecutive patients referred to a rheumatology clinic with unilateral shoulder pain, diagnosed with either subacromial impingement (n = 12) or adhesive capsulitis (n = 4) from clinical examination, radiographic, and in some cases arthrographic findings. In all patients there were no differences in Tc-99m HIG images between symptomatic and asymptomatic shoulders. The findings are discussed, with reference to patterns of tissue inflammation which have been associated with each of the two conditions and in the context of patients referred to hospital relatively late after onset of symptoms (4-6 months).

Foot pain: specific indications for scintigraphy.

Bone scintigraphy is requested as part of the investigation of foot pain, but its contribution to clinical management has not been comprehensively documented. Previously published data are limited; the most comprehensive series identified scintigraphic abnormalities in patients with primarily orthopaedic problems and a control group was not included (Maurice HD et al. J Bone Joint Surg 1987;69B:448 52). The aim of this study was to evaluate whether bone scintigraphy may be useful in different clinical circumstances indicated by referral request details. Regions of scintigraphic abnormality were scored and compared with clinical details drawn from case notes of 60 patients with foot pain. The commonest clinical indications for scans were: confirmation of the clinical suspicion of plantar fasciitis, documentation of the extent of inflammatory arthritis and location of focal pathology. A group of 30 asymptomatic, age- and sex-matched controls were also studied. In 14 out of 19 symptomatic feet in the plantar fasciitis group, focal uptake at the medial calcaneal tubercle was present, confirming the diagnosis. In patients with non-specific, diffuse foot pain, the bone scan identified focal abnormalities in 11 out of 14 cases, thus directing the clinician to the site of pathology. Scintigraphy also proved useful in mapping local inflammatory disease. Technetium-99m methylene diphosphonate image abnormalities occurred in the control group most commonly in the midfoot (16 regions in 13 subjects) and first metatarsophalangeal joint (19 regions in 14 subjects).

Measurement of synovial lining volume by magnetic resonance imaging of the knee in chronic synovitis.

OBJECTIVES: Current methods of monitoring chronic synovitis in a single joint rely on clinical examination derived indices, such as the detection of synovial thickening. This study aimed to develop a reproducible method for quantifying the volume of synovial lining in chronic synovitis using contrast enhanced magnetic resonance (MR) imaging. METHODS: The knees of 18 patients with chronic synovitis were examined (34 studies). A 2D T1 weighted FLASH sequence was used to evaluate the temporal enhancement of synovial structures after intravenous contrast. Synovial lining volume was calculated from subtraction of pre and post-enhancement 3D T1 weighted MP RAGE images with thresholding and pixel counting. Eleven patients were examined before and after intra-articular glucocorticoid (mean interval 14 weeks) and MR data compared with changes in clinical examination derived indices of disease activity. RESULTS: Synovial lining volume varied from 52-267 ml. The coefficient of variation in volume calculation was 3.5% for a single observer and was 3.8% for two observers. Synovial lining volume was quantified in all patients where synovial lining thickening could not be detected clinically. A decrease in synovial lining volume of > 40% was associated with an improvement in synovial lining thickening, detected clinically. Decreases in synovial lining volume were quantified by MR in two of three patients where changes in clinical examination derived indices were inconsistent. CONCLUSIONS: A reproducible method of estimating the volume of synovial lining in patients with chronic synovitis has been developed. MR measurement of synovial lining volume may quantify changes in chronic synovitis that remain unidentified by clinical measures.

Technetium-99m-MDP patterns in patients with painful shoulder lesions.

UNLABELLED: There is no consensus on the optimum mode of imaging in patients with painful shoulder lesions. There is a particular paucity of scintigraphic data. As a result, the strengths and weaknesses of scintigraphy cannot be adequately compared to other imaging techniques used in shoulder imaging. This study evaluated whether specific patterns of scintigraphic abnormality could be detected in patients with painful shoulders seen in rheumatological practice using 99mTc-methylene diphosphonate (MDP). METHODS: Scintigraphic abnormalities were recorded in consecutive patients presenting to a rheumatology clinic with unilateral shoulder pain. Patients were subdivided according to patterns of clinical abnormality consistent with a working diagnosis of a lesion located in the subacromial region, adhesive capsulitis (frozen shoulder) or a lesion likely to be located in the glenohumeral joint. Patterns of radiopharmaceutical distribution in different regions of the shoulder were evaluated in the light of clinical data and the results of shoulder radiographs. RESULTS: Technetium-99m-MDP scans were abnormal in 19 of 24 (79%) patients, and radiographs were abnormal in 8 of 24 (33%) patients. Distinct patterns of 99mTc-MDP image abnormality were identified: an increase in 99mTc-MDP uptake in the coracoid, acromion and medial humeral head on anterior planar images, together with an absence of posterior planar image abnormality, frequently occurred in association with a working diagnosis of a lesion located in the subacromial region. Posterior planar 99mTc-MDP image abnormalities always occurred in patients with clinical features consistent with a diagnosis of adhesive capsulitis. There was an 85% agreement between two observers' scores when 99mTc-MDP distribution in specific shoulder regions was graded. CONCLUSION: Distinct patterns of 99mTc-MDP distribution may be associated with clinically-distinct patterns of abnormality in patients with painful shoulder lesions. Further studies to elucidate a role for 99mTc-MDP scintigraphy in this patient group are warranted.