High Frequency of Diffuse Idiopathic Skeletal Hyperostosis in Patients With Obesity Hypoventilation Syndrome.

Diffuse idiopathic skeletal hyperostosis (DISH) is known to be associated with metabolic syndrome and with obesity in particular. The prevalence of DISH increases with age, with an average of 10% in those aged 70 years and older.

High prevalence of diffuse idiopathic skeletal hyperostosis (DISH) among obese young patients - A retrospective observational study.

OBJECTIVE: Diffuse idiopathic skeletal hyperostosis (DISH) is characterized by ossification of ligaments and entheses, and most commonly affects the spinal column. The prevalence of DISH is increasing with age and is considered uncommon before the age of 50 years, with an estimated prevalence of less than 5 %. DISH is known to be highly associated with metabolic syndrome and obesity. We aim to assess the prevalence of DISH among young (≤50 yr.) patients suffering from severe obesity (BMI of 35 kg/m2 or higher). METHODS: A retrospective analysis assessing chest and spine radiographs (including Computed Tomography, CT) of patients with BMI≥35 visiting the bariatric ambulatory clinic in an academic medical center from 2013 to 2022. Patients included in the analysis were 31-50 years old. Diagnosis of DISH was made according to the Resnick criteria. The prevalence of DISH was calculated. Demographic, clinical and laboratory data were collected and compared between the DISH and non-DISH groups. RESULTS: 183 young (mean age: 40.4; 118 females, 64.2 %) obese (BMI median: 40.6; range 35-73) patients were included in the radiographic review. DISH was diagnosed in 33 patients (18.0 %; 95 % CI: 13.1-24.2 %) which was significantly higher than the expected 10 % (Z = 3.62, p<.001); another 8 patients (4.4 %; 95 % CI: 2.2-8.4 %) were considered as "near DISH" (not fulfilling yet the Resnick criteria) as it represents a pre-disease state. Patients diagnosed with DISH were significantly older than patients without DISH (t = 4.54, p<.001), as the prevalence of DISH increased by age (linear association=14.95, p<.001). There was a statistically significantly higher prevalence of hypertension (χ2 = 8.30, p<.004), smoking (χ2 = 4.69, p<.03) and OSA (χ2 = 6.16, p<.013) in the DISH group as compared to their non-DISH counterparts. CONCLUSION: The prevalence of DISH among obese young patients was 18 %, which is much higher than in the general population. Early-onset DISH should be regarded as a musculoskeletal obesity-related complication.

IgA vasculitis in adults, pediatrics and non-vasculitic IgA nephropathy, retrospective analysis from 2 centers.

Renal involvement represents the major long-term morbidity associated with IgA vasculitis (IgAV). Our aim was to evaluate clinical characteristics and long-term renal outcomes of IgAV in pediatrics and adults comparing to IgA nephropathy (IgAN). Our retrospective study included children and adults with IgAV and IgAN patients, admitted in a 13-year period (2007-2019) to rheumatology clinics and in hospital pediatric and internal medicine departments. We compared frequencies of clinical manifestations, laboratory findings, treatments, long-term outcomes at 1 year follow-up, including all-cause mortality and dialysis until the end of follow-up time. A total of 60 adult IgAV, 60 pediatric IgAV and 45 IgAN patients were evaluated. Adult IgAV patients were significantly older than IgAN patients (53.1 ±â€…17.4 years vs 45.1 ±â€…15.7 years respectively, P = .02) and had significantly higher rates of cardiovascular comorbidities. The risk and time to dialysis were similar among IgAN and adult IgAV groups. Yet, overall mortality at long term follow up was higher in IgAV adult group compared to IgAN. No dialysis or renal transplantation were reported in pediatric IgAV patients. IgAV and IgAN adult patients were comparable regarding risk of end stage renal disease. Of note, high mortality rates were observed among adult IgAV group.

Fourth dose of BNT162b2 vaccine for patients with autoimmune rheumatic diseases in a nationwide setting.

OBJECTIVE: The effectiveness of COVID-19 vaccinations wanes due to immune evasion by the B.1.1.529 (Omicron) variant and diminished antibody titres over time. We aimed to evaluate the benefit of a fourth vaccination dose in patients with autoimmune rheumatic diseases (ARDs). METHODS: This retrospective analysis included ARD patients aged 18 years or older and members of Clalit Health Services in Israel (which at the time of the study insured 52% of the entire population), and covered the period from 16 January 2022 to 31 March 2022, when the predominant SARS-CoV-2 variant was Omicron. We compared patients without previous COVID-19 infection who had received three doses of the BNT162b2 vaccine (the control group) with those who had received the fourth dose. The primary outcome was COVID-19 infection, which was analysed using multivariate Cox regression in the entire cohort and within ARD subgroups. Secondary outcomes were COVID-19-related hospitalizations and COVID-19-related death. RESULTS: We included 43 748 ARD patients, of whom 27 766 and 15 982 were in the control and fourth vaccination groups, respectively. COVID-19 infection occurred in 6942 (25.0%) of the control group and 1754 (11.0%) of the fourth dose group (P < 0.001). Patients vaccinated with the fourth dose had a lower risk of COVID-19 infection than the entire cohort [Hazard Ratio (HR) 0.54, 95% CI 0.52, 0.58] and throughout every subgroup regardless of the baseline characteristic or medical treatment, except for rituximab. A similar association was observed for risk of COVID-19-related hospitalization (HR 0.36, 95% CI 0.22, 0.61) and of COVID-19-related death (HR 0.41, 95% CI 0.24, 0.71). CONCLUSION: A fourth BNT162b2 vaccination of ARD patients was associated with favourable outcomes compared with three doses among patients with no history of COVID-19 infection.

SARS-CoV-2 infection among patients with autoimmune rheumatic diseases; comparison between the Delta and Omicron waves in Israel.

OBJECTIVE: The Omicron variant of the coronavirus SARS-CoV-2 (COVID-19) had milder clinical impacts than prior variants. This study aimed to describe the impact of COVID-19 on Autoimmune Rheumatic Disease (ARD) patients during the Delta and Omicron variants waves. METHODS: We used data from Clalit Health Services (CHS), the largest health service in Israel. ARD patients diagnosed with COVID-19 between July 1, 2021, to December 1, 2021, were included in the Delta group. Patients diagnosed between December 2, 2021, to March 31, 2022, were included in the Omicron group based on the predominance of COVID-19 in Israel. The study outcomes were COVID-19-related hospitalization or death. RESULTS: The final study cohort included 8443 actively treated ARD patients diagnosed with COVID-19. 1204 patients were positive during the predefined Delta variant period, and 7249 were positive during the predefined Omicron variant period). Compared to the Delta group, the Omicron group showed a lower rate of COVID-19-related hospitalization (3.9% vs. 1.3% for the Delta Vs. Omicron accordingly, p<0.001) and COVID-19-related death (3.2% vs. 1.1% for the Delta Vs. Omicron accordingly, p<0.001). After applying multivariable regression models, the Omicron group showed a lower risk for COVID-19-related hospitalization (Relative risk 0.4, 95% CI 0.27-0.59) and COVID-19-related mortality (RR 0.48, 95% CI 0.31-0.75). CONCLUSION: ARD patients infected with the COVID-19 Omicron variant had a lower risk of developing COVID-19-related adverse outcomes compared to the Delta variant.

Evidence for a genetic contribution to the ossification of spinal ligaments in Ossification of Posterior Longitudinal Ligament and Diffuse idiopathic skeletal hyperostosis: A narrative review.

Diffuse Idiopathic Skeletal Hyperostosis (DISH) and Ossification of the Posterior Longitudinal Ligament (OPLL) are common disorders characterized by the ossification of spinal ligaments. The cause for this ossification is currently unknown but a genetic contribution has been hypothesized. Over the last decade, many studies on the genetics of ectopic calcification disorders have been performed, mainly on OPLL. Most of these studies were based on linkage analysis and case control association studies. Animal models have provided some clues but so far, the involvement of the identified genes has not been confirmed in human cases. In the last few years, many common variants in several genes have been associated with OPLL. However, these associations have not been at definitive levels of significance and evidence of functional significance is generally modest. The current evidence suggests a multifactorial aetiopathogenesis for DISH and OPLL with a subset of cases showing a stronger genetic component.

Hypocomplementemia during tocilizumab treatment: Long-term follow-up results.

ABSTRACT: Hypocomplementemia has been reported in patients with rheumatoid arthritis treated with tocilizumab (TCZ), but its long-term consequences are unknown. We assessed the long-term outcome of patients treated with TCZ who developed hypocomplementemia regarding serious bacterial infections or autoimmune diseases (AID).The charts of patients treated with TCZ at two rheumatology centers were reviewed retrospectively. Data regarding patients' age, gender, disease duration, autoantibodies status, previous or concomitant treatments, blood counts, liver enzymes, C3 and C4 levels at baseline and during TCZ treatment, episodes of infections, allergic reactions, and AID were analyzed. Univariate analysis was used to compare patients with low C3, C4 levels versus patients with normal C3, C4 levels. Variables that were statistically significant associated or tended to be associated with low C3 or C4 were included in multiple variable logistic regression.Of 132 patients treated with TCZ, 108 had serial measurements of serum complement concentration. Thirty-three (30%) patients developed low C4 levels and 23 (21%) had also low C3. Mean TCZ treatment period was 4.9 years (range, 1-14 years). All patients had normal complement levels at baseline. Leukopenia occurred in 18 (16.7%) patients, 14 of whom (77%) had low complement. Persistent leukopenia was observed in 8% and 5.3% of patients with normal C3 and C4 levels, respectively, as opposed to 47% and 42% of patients with low C3 or low C4, respectively. Low C3, C4 levels correlated with prolonged TCZ treatment retention time and effectiveness. There were no serious bacterial infections or new onset AID.Hypocomplementemia during TCZ treatment was accompanied by leukopenia that correlated with treatment duration. Hypocomplementemia was not associated with serious bacterial infections or new onset AID. Decreased complement levels were associated with treatment longevity. The role of monitoring complement level in predicting treatment response or assessing disease activity deserves further investigation.

BNT162b2 mRNA COVID-19 vaccine and booster in patients with autoimmune rheumatic diseases: a national cohort study.

INTRODUCTION: Emerging evidence supports the immunogenic response to mRNA COVID-19 vaccine in patients with autoimmune rheumatic diseases (ARD). However, large-scale data about the association between vaccination, and COVID-19 outcomes in patients with ARD is limited. METHODS: We used data from Clalit Health Services, which covers more than half of the population in Israel. Patients with ARD older than 18 were included between 20 December 2020 and 30 September 2021, when the BNT162b2 mRNA COVID-19 vaccine, and later a third booster dose, were available. The primary outcome was a documented positive SARS-CoV-2 PCR test. We used a Cox regression models with vaccination status as time-dependent covariate and calculated the HR for the study outcome. RESULTS: We included 127 928 patients with ARD, of whom, by the end of the study follow-up, there were 27 350 (21.3%) unvaccinated patients, 31 407 (24.5%) vaccinated patients and 69 171 (54.1%) patients who also received a third booster-dose. We identified 8470 (6.6%) patients with a positive SARS-CoV-2 PCR test during the study period. The HR for SARS-CoV-2 infection among the vaccination group was 0.143 (0.095 to 0.214, p<0.001), and among the booster group was 0.017 (0.009 to 0.035, p<0.001). Similar results were found regardless of the type of ARD group or antirheumatic therapy. CONCLUSION: Our results indicate that both the BNT162b2 mRNA COVID-19 vaccine and the booster are associated with better COVID-19 outcomes in patients with ARD.

Diffuse Idiopathic Skeletal Hyperostosis (DISH) and a Possible Inflammatory Component.

PURPOSE OF REVIEW: Diffuse Idiopathic Skeletal Hyperostosis (DISH) is considered a metabolic condition, characterized by new bone formation affecting mainly at entheseal sites. Enthesitis and enthesopathies occur not only in the axial skeleton but also at some peripheral sites, and they resemble to some extent the enthesitis that is a cardinal feature in spondyloarthritis (SpA), which is an inflammatory disease. RECENT FINDINGS: We review the possible non-metabolic mechanism such as inflammation that may also be involved at some stage and help promote new bone formation in DISH. We discuss supporting pathogenic mechanisms for a local inflammation at sites typically affected by this disease, and that is also supported by imaging studies that report some similarities between DISH and SpA. Local inflammation, either primary or secondary to metabolic derangements, may contribute to new bone formation in DISH. This new hypothesis is expected to stimulate further research in both the metabolic and inflammatory pathways in order to better understand the mechanisms that lead to new bone formation. This may lead to development of measures that will help in earlier detection and effective management before damage occurs.

Cardiovascular disease in diffuse idiopathic skeletal hyperostosis (DISH): from theory to reality-a 10-year follow-up study.

OBJECTIVE: To describe actual cardiovascular events over a decade in patients with diffuse idiopathic skeletal hyperostosis (DISH), without previously known CV diseases. METHODS: The medical records of patients with DISH and controls, beginning in 2006 (without known CV disease), were reviewed. Demographic, constitutional, and laboratory data were collected. Comparison of CV events following 2006 was performed according to the outcome definitions set by the Framingham score 2: coronary event demonstrated by a coronary imaging modality, acute myocardial infarction (MI), coronary death, congestive heart failure with a reduced ejection fraction, and angina pectoris. RESULTS: Data were available for 45 patients with DISH and 47 controls without DISH from the original cohort (91.8% and 97.9% respectively). By the Framingham score, 28.6% (± 20.33) of the DISH patients were expected to be affected with CVD at 10 years of follow-up. We observed that nearly 39% of them developed CVD during that period (95% CI 23.8-53.5%). The incidence of MI over the 10-year period was significantly higher in the DISH group (P = 0.005). The DISH group had higher morbidity with a higher composite outcome of 38.8% vs 25.5% in the control cohort, and the number of non-elective hospital admissions per patient, despite neither reaching statistical significance. CONCLUSION: Our study showed that the Framingham score underestimates the real risk for developing CVD in patients with DISH, specifically the risk for MI. We propose more scrutiny is warranted in evaluating CV risk in these patients, more demanding treatment target goals should be established, and earlier and more aggressive medical interventions should be undertaken, particularly primary prevention. Larger prospective studies are needed to corroborate these findings.

Differences between diffuse idiopathic skeletal hyperostosis and spondyloarthritis.

Diffuse idiopathic skeletal hyperostosis (DISH) is a skeletal syndrome that has been known for more than 70 years. Yet, its pathogenesis and treatment options are still under investigation. DISH and spondyloarthritidies may manifest itself clinically as very similar disorders causing impaired axial flexibility, axial pain and peripheral tendinopathies. On the other hand, these two processes are different in many ways, from different genetic and metabolic predispositions, to different clinical and imaging manifestations, and at last, a different attitude toward treatment. The knowledge of the similarities and differences between DISH and spondyloarthritidies can guide the clinician toward a better diagnostic and treatment approach. This review tries to emphasize these details.

Microangiopathy and forearm arterial blood flow in systemic sclerosis: a controlled study.

OBJECTIVE: The aim of the study was to evaluate the interrelationship between the micro- and macrovasculature. METHODS: This is a cross-sectional study that examined SSc patients and fibromyalgia (FM) patients as controls. We assessed forearm peripheral vascular status and nailfold capillaroscopy. We evaluated the association between nailfold capillaroscopy pattern of microvasculopathy reflected as microangiopathy evolution score and macrovascular changes in the forearm vessels examined by color Doppler ultrasound. We assessed relevant clinical and laboratory data, as well as intima-media thickness (IMT) and internal diameter (ID) in the radial and ulnar arteries in millimeters, and calculated the ratio IMT\ID peak systolic velocity and end-diastolic velocity were used for the calculation of the resistance index. RESULTS: We examined 73 patients: 50 patients with SSc and 23 patients with FM. Ten patients with SSc had arterial occlusions compared to 1 among FM patients (p = 0.082). The SSc group had a statistically significantly higher mean IMT to ID ratio (p < 0.001). There was no correlation between microangiopathy evolution score for both hands, RI, or mean IMT/ID ratio. Total microangiopathy evolution score was not associated with arterial occlusions. CONCLUSIONS: Our study demonstrated a high prevalence of macrovascular disease in SSc; no correlation was found between microvasculopathy and macrovascular disease, suggesting that different pathogenic mechanisms might operate in different vessels size. Key Points • This study demonstrated a high prevalence of macrovascular arterial forearm disease in systemic sclerosis patients. • This study found no correlation between capillaroscopic microangiopathy evolution score (MES) and macrovascular abnormalities. • Our findings suggest that different pathogenic mechanisms might operate in different vessels size.

Imaging of diffuse idiopathic skeletal hyperostosis (DISH).

Diffuse idiopathic skeletal hyperostosis (DISH) is a condition characterised by calcification and ossification of ligaments and entheses. The condition usually affects the axial skeleton, in particular, at the thoracic segment, though also other portions of the spine are often involved. DISH often involves also peripheral tendinous and/or entheseal sites either alone, or in association with the involvement of peripheral joints. At times, new bone formation involves the bone itself, but sometimes it involves joints not usually affected by osteoarthritis (OA) which result in bony enlargement of the epiphysis, joints space narrowing and a reduced range of motion. Because of the entheseal involvement, DISH can be mistaken for seronegative spondyloarthropathies or for a "simple" OA. Furthermore, other implications for the recognition of DISH include spinal fractures, difficult intubation and upper endoscopies, decreased response rates in DISH with concomitant spondyloarthritides, and increased likelihood to be affected by metabolic syndrome and cardiovascular diseases. This Atlas is intended to show the imaging finding in DISH in patients diagnosed with the condition by the Resnick classification criteria.

Serum adiponectin levels in patients with diffuse idiopathic skeletal hyperostosis (DISH).

To evaluate the relationship between serum adiponectin ADP (sADP) levels and the risk of metabolic syndrome (MS) and cardiovascular disease (CVD) in patients with DISH and to assess the relationship between sADP levels, and the tendency for new bone formation in these patients. sADP levels were measured in DISH and non-DISH (NDISH) patients. sADP levels were compared between the two groups and were also correlated with weight circumference, BMI, serum lipid profile, concomitant diseases, use of medications, the presence of MS, the risk of developing CVD, and the extent of bony bridges. Eighty-seven patients with DISH and 65 in NDISH were examined. A negative significant correlation between sADP and insulin resistance, and serum insulin levels in the DISH group (r = - 0.375, p = 0.0004; r = -0.386, p = 0.0002, respectively) was observed. sADP levels positively correlated with serum cholesterol and LDL levels in the DISH group. Higher sADP levels positively correlated with the extent of bony bridges (r = 0.245, p = 0.02). It appears that at least in patients with DISH, sADP has an osteogenic effect. Increasing sADP levels might reduce insulin resistance and hyperinsulinemia and reduce the CV risk and the osteogenic effect exerted by insulin. However, increasing sADP levels might directly increase new bone formation aggravating the already enhanced osteogenesis. Studies of larger populations with earlier disease might shed light on the enigmatic role played by ADP in patients with DISH and the eventual effect of manipulating its levels.

Effect of Tocilizumab on Fatigue and Bone Mineral Density in Patients with Rheumatoid Arthritis.

BACKGROUND: Chronic fatigue is common among patients with rheumatoid arthritis (RA), affecting quality of life. Osteoporosis is a prevalent co-morbidity in RA patients. OBJECTIVES: To assess the effect of long-term treatment with tocilizumab on fatigue and bone mineral density (BMD) in RA patients with inadequate response to synthetic or biologic disease-modifying anti-rheumatic drugs. METHODS: In this multicenter, open-label, non-controlled, single-arm study, patients ≥ 18 years of age received intravenous tocilizumab 8 mg/kg every 4 weeks for 96 weeks. The primary outcome was the change in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score from baseline to weeks 24, 48, 72, and 96. BMD was assessed before and 96 weeks after treatment. RESULTS: The study comprised 145 patients (mean age 53.4 ± 13.4 years, 83.4% women). Of these, 88 (60.7%) completed the 2 year treatment period. The mean FACIT-Fatigue score improved consistently starting from week 4 and showed a statistically significant increase of 5.0 ± 9.7, 6.8 ± 10.5, 7.3 ± 10.9, and 7.3 ± 10.4 from baseline to weeks 24, 48, 72, and 96, respectively (P < 0.0001). Mean BMD of femoral neck and total spine remained stable. Disease activity, acute phase reactants, and composite efficacy measures decreased during the study, while hemoglobin levels increased. Adverse events and serious adverse events were as expected for the known and previously described data. CONCLUSIONS: Tocilizumab therapy for 2 years significantly and clinically decreased fatigue. BMD remained stable and no new safety issue was reported.

Portal Vein Thrombosis and Thrombocytopenia in Eosinophilic Granulomatosis with Polyangiitis: A Paradox?

A 36-year-old woman with eosinophilic granulomatosis with polyangiitis (EGPA) presented with necrotic skin lesions and pulmonary infiltrates. There was eosinophilic vasculitis on skin biopsy, and substantial tissue eosinophilia in her bone marrow. She had unexplained worsening thrombocytopenia, which prompted a thrombophilia work-up. However, abnormalities in liver enzymes led to the extraordinary finding of portal vein thrombosis. Thrombocytopenia resolved with treatment with low molecular weight heparin. This case highlights the risk of hypercoagulability in eosinophilia specifically, and in EGPA. We suggest that thrombosis should be ruled out in all cases of EGPA. LEARNING POINTS: Eosinophilia is a hypercoagulable state.Thrombocytopenia is not part of eosinophilic granulomatosis with polyangiitis (EGPA) and may herald thrombosis.Thromboembolism should be ruled out in the setting of EGPA with eosinophilia.Prompt diagnosis can prevent unnecessary procedures.

Chronic tophaceous gout as the first manifestation of gout in two cases and a review of the literature.

OBJECTIVES: Acute gout is a common arthritis that may eventually develop into chronic tophaceous gout (CTG). CTG usually is manifested by recurrent gout attacks. The diagnosis and treatment of CTG is challenging. Although the emergence of CTG without previous gout attacks is uncommon, it is important to recognize this unusual gout presentation. METHODS: Herein, we present two cases of CTG, occurring in elderly patients with chronic kidney disease (CKD) on diuretics, who presented without a prior history of acute gout attacks. We also searched PUBMED, Ovid MEDLINE, and Google scholar (1970-2017), for "tophi as the initial manifestation of gout" and "chronic gout without previous attacks", and extracted relevant data. RESULTS: The search disclosed one retrospective study and several case reports and case series describing 96 patients. Clinical and laboratory data was extracted from 34 patients. We found that a specific group of patients, e.g., elderly patients, most often female patients, suffering from CKD, and treated with diuretics, are specifically reported in the English medical literature to present with CTG as their first manifestation of gout. CONCLUSION: The two cases and our literature review try to emphasize the many faces of chronic gout, in particular, its presentation without previous gout attacks.

Diffuse idiopathic skeletal hyperostosis (DISH): where we are now and where to go next.

Diffuse idiopathic skeletal hyperostosis (DISH) is a well-recognised entity characterised by calcifications and ossifications of the entheses affecting mainly the spine and peripheral sites. DISH is still insufficiently investigated and understood. The objective of this report is to highlight the present limitations of our understanding of the condition and suggest future research paths.

Classification criteria for diffuse idiopathic skeletal hyperostosis: a lack of consensus.

Objectives: DISH is a condition characterized by flowing ossifications of the spine with or without ossifications of entheses elsewhere in the body. Studies on the prevalence and pathogenesis of DISH use a variety of partly overlapping combinations of classification criteria, making meaningful comparisons across the literature difficult. The aim of this study was to systematically summarize the available criteria to support the development of a more uniform set of diagnostic/classification criteria. Methods: A search was performed in Pubmed, Embase, Cochrane Library and Web of Science using the term DISH and its synonyms. Articles were included when two independent observers agreed that the articles proposed a new set of classification criteria for DISH. All retrieved articles were evaluated for methodological quality, and the presented criteria were extracted. Results: A total of 24 articles met the inclusion criteria. In all articles, spinal hyperostosis was required for the diagnosis of DISH. Peripheral, extraspinal manifestations were included as a (co-)requirement for the diagnosis DISH in five articles. Most discrepancies revolved around the threshold for the number of vertebral bodies affected and to defining different developmental phases of DISH. More than half of the retrieved articles described a dichotomous set of criteria and did not consider the progressive character of DISH. Conclusion: This systematic review summarizes the available different classification criteria for DISH, which highlights the lack of consensus on the diagnosis of (early) DISH. Consensus criteria, including consecutive phases of new bone formation that characterize DISH, can be developed based upon established diagnostic/classification criteria.