M. Mazzantini

Incident Comorbidity Among Patients with Rheumatoid Arthritis Treated or Not with Low-dose Glucocorticoids: A Retrospective Study

Objective. To assess the prevalence of comorbidity in a cohort of patients with rheumatoid arthritis (RA), treated or not with low-dose glucocorticoids (GC) and who have been followed for at least 10 years. Methods. This was a retrospective study by review of medical records. Results. We identified 365 patients: 297 (81.3%) were GC users (4–6 mg methylprednisolone daily) and 68 (18.7%) were nonusers. We found that fragility fractures occurred in 18.2% of GC users and in 6.0% of GC nonusers (p < 0.02); arterial hypertension in 32.3% of GC users and in 10.4% of GC nonusers (p < 0.0005); acute myocardial infarction in 13.1% of GC users and in 1.5% of the nonusers (p < 0.01). Prevalence of diabetes mellitus, cataract, and infections was comparable. We divided GC users into groups of different duration of GC therapy: < 2, 2–5, and > 5 years; the mean duration of GC treatment was 1.3 ± 0.5, 3.6 ± 1.1, and 12.1 ± 5.1 years, respectively. GC treatment for > 5 years was associated with significantly higher prevalence of fragility fractures (26.6%; p < 0.001 vs the other groups), arterial hypertension (36.7%; p < 0.0002 vs nonusers and GC users < 2 years), myocardial infarction (16.1%; p < 0.01 vs nonusers), and infections (9.7%; p < 0.005 vs the other groups). GC treatment for 2–5 years was associated with a significantly higher prevalence of arterial hypertension (30.0%; p < 0.01) compared to nonusers. Conclusion. Patients with RA treated with low-dose GC compared to patients never treated with GC show a higher prevalence of fractures, arterial hypertension, myocardial infarction, and serious infections, especially after 5 years of GC treatment. The high prevalence of myocardial infarction and fractures in patients with RA suggests that a more accurate identification of risk factors and prevention measures should be adopted when longterm GC treatment is needed.

Adverse Events During Longterm Low-dose Glucocorticoid Treatment of Polymyalgia Rheumatica: A Retrospective Study

Objective. To assess the occurrence of adverse events in a cohort of patients with polymyalgia rheumatica (PMR), treated with low-dose glucocorticoids (GC). Methods. This was a retrospective study by review of medical records. Results. We identified 222 patients who had a mean duration of followup of 60 ± 22 months and a mean duration of GC therapy of 46 ± 22 months. We found that 95 patients (43%) had at least 1 adverse event after a mean duration of GC therapy of 31 ± 22 months and a mean cumulative dose of 3.4 ± 2.4 g. In particular, 55 developed osteoporosis, 31 had fragility fractures; 27 developed arterial hypertension; 11 diabetes mellitus; 9 acute myocardial infarction; 3 stroke; and 2 peripheral arterial disease. Univariate analysis showed that the duration of GC treatment was significantly associated with osteoporosis (p < 0.0001), fragility fractures (p < 0.0001), arterial hypertension (p < 0.005), and acute myocardial infarction (p < 0.05). Cumulative GC dose was significantly associated with osteoporosis (p < 0.0001), fragility fractures (p < 0.0001), and arterial hypertension (p < 0.01). The adverse events occurred more frequently after 2 years of treatment. Multivariate analysis showed that GC duration was significantly associated with osteoporosis (adjusted OR 1.02, 95% CI 1.02–1.05) and arterial hypertension (adjusted OR 1.03, 95% CI 1.01–1.06); GC cumulative dose was significantly associated with fragility fractures (adjusted OR 1.4, 95% CI 1.03–1.8). Conclusion. Longterm, low-dose GC treatment of PMR is associated with serious adverse events such as osteoporosis, fractures, and arterial hypertension; these adverse events occur mostly after 2 years of treatment.

Risk factors for osteoporosis in female patients with systemic lupus erythematosus

In the last years it has been recognized that patients with systemic lupus erythematosus (SLE) are at high risk of osteoporosis (OP) and fractures, both occurring through disease-specific (chronic arthritis, reduced physical activity, induction of cytokines promoting bone resorption, renal impairment, endocrine factors) and nondisease-specific mechanisms (sunshine avoidance with consequent vitamin D deficiency, glucocorticoids, immunosuppressants and chronic anticoagulants). Regarding anticoagulants, subcutaneous heparin is crucial against the risk of recurrent thromboembolism or pregnancy loss, specifically in patients with SLE and anti-phospholipid syndrome (APS). Thus heparin-induced OP represents one of the hazards of this treatment, first because heparin must be used long-term and secondly because pregnancy and lactation themselves may predispose to OP and fractures. Current data suggest the use of prophylaxis with calcium and vitamin D in all patients treated with heparin during pregnancy. Nevertheless glucocorticoid-induced OP (GIOP) is considered the most serious risk factor for OP and fractures in SLE patients. All guidelines recommend general measures and supplementation with calcium and vitamin D in all patients. However when considering premenopausal patients, there is no generally recommended treatment. Bisphosphonates, which are considered the first choice therapy for the prevention and treatment of GIOP, should be used ‘cautiously’ in these patients. Therefore the potential risks and lack of efficacy data on fracture risk reduction in premenopausal patients must be weighed against their proven efficacy in postmenopausal patients.

Reduced bone mass and normal calcium metabolism in systemic sclerosis with and without calcinosis

SummaryForty-three female patients with systemic sclerosis divided into subgroups based on the extent of skin involvement and the presence of calcinosis, and 50 sex and age-matched healthy controls were investigated for bone mineral density (BMD) on the basis of radial (dual photon absorptiometry, Osteograph, NIM), lumbar, and total body measurements (dual energy X-ray absorptiometry, Lunar DPX, Lunar Corp.), and for parameters of calcium metabolism. The patients showed a lower BMD (mean±SD; mg/cm2) than the controls at the radial (313±69 vs 347±73; p<0.005), lumbar (974±143 vs 1081±154; p<0.005), and total body (997±82 vs 1075±109; p<0.05) determinations. The patients with the diffuse form of skin involvement had lower values than those with the limited form. There was a negative correlation between BMD and the duration of the disease. The presence of calcinosis was not found to have any effect on BMD. Calcium metabolism was found to be normal in each subgroup.It may be concluded that generalized osteoporosis is a feature of systemic sclerosis, with and without calcinosis. The extent and duration of the disease may play a role in determining bone loss.

Risk factors for osteoporosis and fragility fractures in patients with systemic lupus erythematosus

Osteoporosis (OP) and fragility fractures (FFx) are a known comorbidity in patients with systemic lupus erythematosus (SLE). This work aimed at evaluating (1) the prevalence of OP and FFx in a cohort of SLE and (2) the risk factors associated with both OP and FFx. The following data were collected from clinical charts: age, sex, menopausal status (MP), body mass index, smoking habits, disease duration, daily dose and cumulative glucocorticoids (GCs), type of organ involvement, comorbidities and medications. Data on bone metabolism, calcium and vitamin D supplementation and treatment with bisphosphonates, teriparatide or denosumab were collected, together with bone mineral density (BMD) values (measured by dual-energy X-ray absorptiometry (DXA)) and history of FFx (occurred after the onset of SLE and unrelated to trauma). OP and reduced BMD were defined according to the WHO. 186 patients were included (women 175, men 11; mean age 46.4±13 years, mean disease duration 14.9±9 years). At their last visit, 97 patients (52.2%) had a reduced BMD and 52 (27.9%) had OP. 22 patients (11.8%), all women, had at least one FFx; six patients (27.3%) were pre-menopausal. On univariate analysis, age, cumulative dose of GC, MP, therapy with antiepileptics and chronic renal failure (CRF) were correlated with OP (p<0.03); age, total amount of GC, MP, CRF, anticoagulants (AC) and antiepileptic therapy were correlated with FFx (p<0.05). The multivariate logistic model confirmed a direct association of OP and age, MP and antiepileptic therapy (p≤0.01) and of FFx and age, chronic therapy with AC and antiepileptics (p<0.03). In conclusion, low BMD is frequently observed in SLE, and FFx are observed also in premenopausal patients. Together with traditional risk factors (age, MP and GC), CRF and chronic treatments with AC or antiepileptics seem to be associated with a higher risk profile for OP and FFx occurrence.

Single infusion of neridronate (6-amino-1-hydroxyhexylidene-1,1-bisphosphonate) in patients with active rheumatoid arthritis: Effects on disease activity and bone resorption markers

Aims: The aim of this study was to assess the effects of a single infusion of the bisphosphonate neridronate (N) on parameters of inflammation and bone resorption in rheumatoid arthritis (RA). Methods: Forty-five patients with active RA were randomly allocated on a double blind basis to receive a single intravenous infusion of either N 25 mg (15 patients), N 50 mg (15 patients), or placebo (15 patients). At baseline and after 7 and 21 days, we assessed the following: erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and Ritchie’s articular index as indices of disease activity; and urinary free deoxypyridinoline (DPyr), N-telopeptide of type I collagen (NTx) and hydroxy-proline (OHP) as indices of bone resorption. Results: At day 7, N 25 mg significantly decreased ESR compared to N 50 mg (p=0.002), and CRP compared to placebo (p=0.036). With regard to bone resorption markers, at day 7, both N 25 mg and 50 mg compared to placebo significantly decreased NTx (p<0.0005 and p=0.003, respectively) and OHP (p=0.001 and p=0.004, respectively). At day 21, N 50 mg significantly decreased OHP compared to placebo (p=0.017). DPyr levels remained unchanged in the three groups. Conclusions: N 25 mg and 50 mg exerted different effects on RA activity parameters, since only the lower dose significantly decreased ESR and CRP. Both doses of N inhibited bone resorption, with a transient, significant reduction in urinary NTx and OHP, but without any effect on DPyr.

Kartagener’s Syndrome and Rheumatoid Arthritis: An Unusual Association

Abstract We report the case of a 66-year-old caucasian woman affected by Kartagener’s syndrome (KS), a genetically transmitted disorder characterised by situs viscerum inversus, bronchiectasis and sinusitis, who also developed rheumatoid arthritis (RA). The impaired mucociliary function typical of KS caused recurrent paranasal sinus and lung infections, as shown by CT scans of the sinuses and chest. The coexistence of KS and RA in our patient was probably accidental. Given the small number of patients in whom an association of the two disorders has been described, it is impossible to establish whether KS might play a role in the pathogenesis of RA.

Clinical Equivalence between Deflazacort Oral Drops and Tablets in Active Rheumatoid Arthritis

Abstract: In order to assess the clinical equivalence between deflazacort oral drops and tablets, 18 patients with active rheumatoid arthritis were enrolled in an open, controlled, randomised (‘tablets → drops’ sequence, or vice versa), two-period (21 days each) crossover trial (from tablets to drops, or vice versa). Individual dose titration of deflazacort drops or tablets was made weekly on the basis of clinical need. Primary outcome measures of efficacy were changes in the joint swelling count (JSC), erythrocyte sedimentation rate (ESR), hand-grip strength (HGS), joint pain (JP), duration of morning stiffness (MS), physician’s global evaluation and patient’s self-assessment. Sixteen patients were available by the end of the study. The formulations were equivalent with respect to HGS and improvement in duration of MS, and close to equivalence with respect to JSC and ESR decrease; the drops seemed to be more effective than tablets with respect to JP reduction. No differences between the two formulations were observed with respect to physician’s and patient’s assessment. The minimum effective dose of each preparation and the relative potency ratio were also established. Drops and tablets were found to have the same potency.

THU0354 Osteopororsis and Fragility Fractures in Systemic Lupus Erythematosus: Something New to be Explored?

Background Osteoporosis (OP) and subsequent fragility fractures (FFx) are a common comorbidity in patients with Systemic Lupus Erythematosus (SLE). A chronic therapy with glucocorticoids (GC) is one of the main risk for their development. Due to the severe impairment of the quality of life they could cause, prevention and treatment of OP is a central issue in the management of SLE. Objectives In this work we aimed at evaluating (i) the prevalence of OP and clinically evident FFx in a cohort of SLE patients under chronic GC therapy, (ii) the presence of some additional risk factors with identification of possible strategies to improve their quality of care. Methods The following data were retrospectively collected from clinical charts of SLE patients under regular follow up: age, sex, menopausal status (MP), Body Mass Index, smoking habits, disease duration, daily dose and cumulative GC, presence and type of organ involvement, comorbidities and concomitant medications potentially affecting bone metabolism. Bone Mineral Density (BMD) scores, presence of FFx, phosphocalcic metabolism, supplementation with calcium and vitamin D and therapy with bisphosphonates (BPs) were also recorded. BMD of lumbar spine and non-dominant hip was measured by DXA and expressed as T-scores and in g/cm2. OP was defined according to the World Health Organization. Only FFx occurring after the onset of SLE and unrelated to trauma were included. Univariate and multivariate logistic regression were used to analyze the associations of both OP and FFx with possible risk factors. Results One hundred and eighty six patients (F 175, M 11; mean age 46.4±13 years, mean disease duration 14.9±9 years, mean fu 11±8 years) were included into the analysis. The mean BMI value was 23,95 kg/m2, 56 (30.1%) were smokers, 68 (36.8%) had a thyroid disorder, 61 women (34.9%) were MP and 26 patients (14%) had a CRF. All patients have been treated with GC: mean daily dose of 5-4±2.3 mg and mean cumulative dose of 34.9±25.3 g (prednisone equivalent). At their last visit, 97 patients (52.2%) had a reduced BMD and 52 (27.9%) had OP. At least one FFx was recorded in 22 out of 186 patients (11.8%); patients with FFx were all women and 6 (27.3%) were pre-menopausal; in 16 cases more than one FFx were present, for a total of 40 fractures. Univariate analysis showed a correlation between OP and age, cumulative dose of GC, MP, therapy with AEDs and with CRF (p<0.03); the multivariate logistic model confirmed a direct association of OP and age, MP and AEDs therapy (p≤0.01). At the univariate analysis, the development of FFx was associated with age, total amount of GC, MP, CRF, AC and AEDs therapy (p<0.05). The multivariate analysis showed age, chronic therapy with AC and with AEDs as the best independent predictors for FFx (p<0,03). Conclusions In conclusion, low BMD is frequently observed in SLE patients chronically treated with GC, and FFx are observed also in premenopausal patients. Together with well known risk factors (age, MP and GC) CRF and a chronic treatment with AC or AEDs seem to be associated with a higher risk profile for OP and FFx in these patients. Thus, these variables should be considered for a patients tailored risk stratification and, eventually, for a stricter monitoring or more aggressive treatment strategies. Disclosure of Interest None declared

AB0925 Liver Involvement in Adult Onset Still's Disease: Retrospective Analysis of 18 Cases

Background Adult-onset Stills disease (AOSD) is a multisystem inflammatory disease of unknown etiology typically characterized by high fever, arthralgias/arthritis and transient cutaneous rash. Liver involvement has been reported in AOSD, however only few studies have described it comprehensively. Objectives To describe the frequency and clinical presentation of liver involvement in a single center cohort of AOSD. Methods Retrospective observational study including unselected patients with a diagnosis of AOSD made according to the Yamaguchi criteria and admitted at our University Hospital between 2009 and 2013. Demographic, clinical and serological data were retrieved from patients files including: fever, evanescent rash, sore throat, arthritis, myalgias, pleuritis, pericarditis, pneumonitis, lymphadenopathy, splenomegaly, hepatomegaly leucocytosis >15,000/μl and high serum ferritin levels. The severity of liver-associated enzymes was based on the degree of elevation and was stratified as mild (<2 times normal), moderate (2-5 times normal), and severe (>5 times normal). Severe liver dysfunction was defined as having all of the following criteria: total bilirubin >3 mg/dL; albumin <3.2 g/dL; and prothrombin time >3 seconds prolonged. Medications used, response to treatment and long-term outcomes were also recorded. Comparison in terms of continuous data were determined using independent sample t tests or Mann–Whitney tests, and in terms of proportions using contingency table analysis and chi square test. Results Eighteen patients (9 F: 9M; mean age (SD) =37 (12) years, mean follow-up=31 (15) months) were included in the study. Twelve patients out of 18 (66.6%) presented liver test abnormalities whereas hepatomegaly occurred in 4/18 (22.2%) cases. No correlation was found between liver involvement and gender or age at the diagnosis. A mild elevation of liver enzymes was found in 4/12 cases, a moderate alteration in other 4 patients, and a severe cytolysis in the other 4. A liver biopsy was performed in 3/12 patients revealing acute hepatitis with necrosis and accompanying non specific inflammatory infiltration. Three patients presented a liver acute failure concurrently with a diffuse intravascular coagulation (DIC) and, in one case, with a fatal macrophagic activation syndrome (MAS). Prednisone therapy induced a fast improvement of liver function in all the cases but one. Hydroxychloroquine, methotrexate and cyclosporine were the most common steroid sparing agents adopted during the follow-up. Conclusions Our findings outlined the high frequency of liver involvement in AOSD. Despite generally mild or moderate, severe acute hepatitis can occur during the disease course especially in those patients with DIC or MAS features. Treatment with systemic corticosteroid therapy is generally able to control liver function during AOSD, however steroid sparing agents are crucial in maintaining a long- term remission. Larger prospective studies could clarify the pathogenetic role of macrophagic activation in AOSD severe liver involvement, leading to develop new concepts for treatment modalities. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4541