Jörg Henes

Effects and safety of rituximab in systemic sclerosis: an analysis from the European Scleroderma Trial and Research (EUSTAR) group

Objectives To assess the effects of Rituximab (RTX) on skin and lung fibrosis in patients with systemic sclerosis (SSc) belonging to the European Scleroderma Trial and Research (EUSTAR) cohort and using a nested case-control design. Methods Inclusion criteria were fulfilment of American College of Rheumatology classification criteria for SSc, treatment with RTX and availability of follow-up data. RTX-treated patients were matched with control patients from the EUSTAR database not treated with RTX. Matching parameters for skin/lung fibrosis were the modified Rodnan Skin Score (mRSS), forced vital capacity (FVC), follow-up duration, scleroderma subtype, disease duration and immunosuppressive co-treatment. The primary analysis was mRSS change from baseline to follow-up in the RTX group compared with the control group. Secondary analyses included change of FVC and safety measures. Results 63 patients treated with RTX were included in the analysis. The case-control analysis in patients with severe diffuse SSc showed that mRSS changes were larger in the RTX group versus matched controls (N=25; −24.0±5.2% vs −7.7±4.3%; p=0.03). Moreover, in RTX-treated patients, the mean mRSS was significantly reduced at follow-up compared with baseline (26.6±1.4 vs 20.3±1.8; p=0.0001). In addition, in patients with interstitial lung disease, RTX prevented significantly the further decline of FVC compared with matched controls (N=9; 0.4±4.4% vs −7.7±3.6%; p=0.02). Safety measures showed a good profile consistent with previous studies in autoimmune rheumatic diseases. Conclusions The comparison of RTX treated versus untreated matched-control SSc patients from the EUSTAR cohort demonstrated improvement of skin fibrosis and prevention of worsening lung fibrosis, supporting the therapeutic concept of B cell inhibition in SSc.

Secondary autoimmune diseases occurring after HSCT for an autoimmune disease : a retrospective study of the EBMT Autoimmune Disease Working Party

To specify the incidence and risk factors for secondary autoimmune diseases (ADs) after HSCT for a primary AD, we retrospectively analyzed AD patients treated by HSCT reported to EBMT from 1995 to 2009 with at least 1 secondary AD (cases) and those without (controls). After autologous HSCT, 29 of 347 patients developed at least 1 secondary AD within 21.9 (0.6-49) months and after allogeneic HSCT, 3 of 16 patients. The observed secondary ADs included: autoimmune hemolytic anemia (n = 3), acquired hemophilia (n = 3), autoimmune thrombocytopenia (n = 3), antiphospholipid syndrome (n = 2), thyroiditis (n = 12), blocking thyroid-stimulating hormone receptor antibody (n = 1), Graves disease (n = 2), myasthenia gravis (n = 1), rheumatoid arthritis (n = 2), sarcoidosis (n = 2), vasculitis (n = 1), psoriasis (n = 1), and psoriatic arthritis (n = 1). After autologous HSCT for primary AD, the cumulative incidence of secondary AD was 9.8% ± 2% at 5 years. Lupus erythematosus as primary AD, and antithymocyte globulin use plus CD34(+) graft selection were important risk factors for secondary AD by multivariate analysis. With a median follow-up of 6.2 (0.54-11) years after autologous HSCT, 26 of 29 patients with secondary AD were alive, 2 died during their secondary AD (antiphospholipid syndrome, hemophilia), and 1 death was HSCT-related. This European multicenter study underlines the need for careful management and follow-up for secondary AD after HSCT.

Diagnostic and Interventional MRI of the Sacroiliac Joints Using a 1.5-T Open-Bore Magnet: A One-Stop-Shopping Approach

OBJECTIVE The objective of our study was to prospectively test the hypothesis that combined diagnostic and interventional MRI of the sacroiliac joints can be performed efficiently and effectively. SUBJECTS AND METHODS Over a 12-month period, 60 patients (32 women and 28 men; median age, 28 years; age range, 18-49 years) with chronic lower back pain suspected to originate from the sacroiliac joints were enrolled in the study. Based on diagnostic MRI findings, MR fluoroscopy-guided sacroiliac joint injections were performed in 57 (95%) patients. Diagnostic injections (35, 58.3%) were performed if nonspecific or degenerative MRI findings were present. Therapeutic injections (22, 36.7%) were performed in patients with inflammatory arthropathy. In three (5%) patients, no injections were performed. Technical effectiveness was assessed by analyzing, first, the rate of intraarticular injection; second, the time required for the procedure; third, image quality; and, fourth, occurrence of complications and clinical outcome by analyzing pain intensity changes and volume and signal intensity of sacroiliac inflammatory changes. RESULTS The rate of intraarticular injection was 90.4% (103/114). The mean length of time for the procedure was 50 minutes (range, 34-103 minutes), with exponential shortening over time (p < or = 0.001). The contrast-to-noise ratios of the needle and tissues were sufficiently different for excellent delineation of the needle. No complications occurred. Diagnostic injections identified the sacroiliac joints as generating significant pain in 46.9% (15/32) of the patients. Three months after therapeutic injections, pain intensity had decreased by 62.5% (p < or = 0.001) and the volume and relative signal intensity of inflammatory changes had decreased by 37.5% (p = 0.003) and 47.6% (p < or = 0.001), respectively. CONCLUSION We accept the hypothesis that combined diagnostic and interventional MRI of the sacroiliac joints can be performed efficiently and effectively for comprehensive diagnosis and therapy of lower back pain originating from the sacroiliac joints.

The Role of Dynamic Contrast-Enhanced MRI in the Differential Diagnosis of Psoriatic and Rheumatoid Arthritis

OBJECTIVE The purpose of this study was to investigate the role of dynamic contrast-enhanced MRI in the differential diagnosis of psoriatic and rheumatoid arthritis in the hand and wrist. SUBJECTS AND METHODS Forty-five consecutive patients (31 patients with rheumatoid arthritis and 14 patients with psoriatic arthritis) were examined in a 3-T whole-body MR unit. After contrast injection, a 3D encoded spoiled gradient-echo sequence was used for measurement of the time course of contrast-medium uptake in the synovial tissue. On the basis of the gained uptake curves, the rate of early enhancement was calculated after 35 and 52 seconds, and the relative enhancement rate was calculated after 35 seconds, 52 seconds, 3 minutes, and 15 minutes (late enhancement). Dynamic contrast-enhanced MRI rates of patients with rheumatoid arthritis and psoriatic arthritis were compared and correlated with laboratory and clinical data. RESULTS A statistically significant difference between the two groups was found regarding the relative enhancement rate after 15 minutes (p < 0.01). In contrast, no difference in relative enhancement rate was found 35 seconds, 52 seconds, or 3 minutes after contrast injection (p = 0.695, p = 0.573, and p = 0.278, respectively). Regarding the rate of early enhancement at 35 and 52 seconds, no significant difference between patients with rheumatoid arthritis and those with psoriatic arthritis was found. Significant correlations were found between inflammatory parameters and dynamic contrast-enhanced parameters in patients with rheumatoid arthritis but not in those with psoriatic arthritis. CONCLUSION Fifteen minutes after contrast injection, a statistically significant difference between rheumatoid arthritis and psoriatic arthritis was found in synovial enhancement that might play an important role in differentiating the two diseases.

MRI Findings in Psoriatic Arthritis of the Hands

OBJECTIVE The purpose of this essay is to provide a practical review of the spectrum of morphologic and functional MRI findings in psoriatic arthritis of the hand joints. CONCLUSION The MRI findings of psoriatic arthritis include enthesitis, bone marrow edema, and periostitis accompanying articular or flexor tendon sheath synovitis in the early stage accompanied by destructive and proliferative bony changes, subluxation, and ankylosis in the late stage.

Mapping and predicting mortality from systemic sclerosis

Objectives To determine the causes of death and risk factors in systemic sclerosis (SSc). Methods Between 2000 and 2011, we examined the death certificates of all French patients with SSc to determine causes of death. Then we examined causes of death and developed a score associated with all-cause mortality from the international European Scleroderma Trials and Research (EUSTAR) database. Candidate prognostic factors were tested by Cox proportional hazards regression model by single variable analysis, followed by a multiple variable model stratified by centres. The bootstrapping technique was used for internal validation. Results We identified 2719 French certificates of deaths related to SSc, mainly from cardiac (31%) and respiratory (18%) causes, and an increase in SSc-specific mortality over time. Over a median follow-up of 2.3 years, 1072 (9.6%) of 11 193 patients from the EUSTAR sample died, from cardiac disease in 27% and respiratory causes in 17%. By multiple variable analysis, a risk score was developed, which accurately predicted the 3-year mortality, with an area under the curve of 0.82. The 3-year survival of patients in the upper quartile was 53%, in contrast with 98% in the first quartile. Conclusion Combining two complementary and detailed databases enabled the collection of an unprecedented 3700 deaths, revealing the major contribution of the cardiopulmonary system to SSc mortality. We also developed a robust score to risk-stratify these patients and estimate their 3-year survival. With the emergence of new therapies, these important observations should help caregivers plan and refine the monitoring and management to prolong these patients’ survival.

Does ex vivo CD34+ positive selection influence outcome after autologous hematopoietic stem cell transplantation in systemic sclerosis patients?

This EBMT Autoimmune Disease Working Party study aimed to evaluate the influence of CD34+ positive graft selection (CD34+) on the outcome of systemic sclerosis (SSc) patients after autologous hematopoietic stem cell transplantation (AHSCT). Clinical and laboratory data from 138 SSc patients at diagnosis, before and after AHSCT were retrospectively analyzed. CD34+ selection was performed in 47.1% (n=65) patients. By multivariate analysis adjusting for all factors differing between the two groups (without or with CD34+), there was no statistically significant difference in terms of overall survival (hazard ratio (HR): 0.98, 95% confidence interval (CI) 0.40–2.39, P=0.96), PFS (HR: 1.55, 95% CI 0.83–2.88, P=0.17) and incidence of relapse or progression (HR: 1.70, 95% CI 0.85–3.38, P=0.13). We demonstrate that CD34+ does not add benefit to the outcome of SSc patient treated with AHSCT. These findings should be further confirmed by prospective randomized trials.

Response Evaluation of Musculoskeletal Involvement in Patients With Deep Morphea Treated With Methotrexate and Prednisolone: A Combined MRI and Clinical Approach

OBJECTIVE The purpose of this article is to explore the role of MRI in monitoring musculoskeletal involvement in patients with morphea who are undergoing treatment with methotrexate and prednisolone. SUBJECTS AND METHODS Twenty-two consecutive patients (six men and 16 women; median age, 52 years) with systemic scleroderma and deep morphea prospectively underwent whole-body MRI twice, before treatment (time 1) and during follow-up after 6-12 months (time 2). Images were evaluated for abnormal signal intensity or thickening of sub-cutaneous fatty tissue septa, muscular fasciae, intramuscular perifascial septa, muscle signal intensity, and articular or tendon sheath synovial abnormalities on STIR and gadolinium-enhanced scans. For clinical assessment, the localized scleroderma (morphea) severity index and a 0-6 pain score were applied. RESULTS From a clinical point of view, none of our patients had progression of the disease, 12 patients were responders (defined as an improvement of localized scleroderma severity index and pain score ≥ 50%), and 10 patients had stable disease. Among responders, the number of patients with subcutaneous septal thickening (time 1, n = 9; time 2, n = 2), fascial enhancement (time 1, n = 8; time 2, n = 3), and articular synovitis (time 1, n = 5; time 2, n = 1) decreased more than in the stable disease group (subcutaneous septal thickening: time 1, n = 9; time 2, n = 8; fascial enhancement: time 1, n = 5; time 2, n = 5; articular synovitis: time 1, n = 8; time 2, n = 6). Subcutaneous thickening, fascial thickening, and fascial enhancement were scored significantly lower at follow-up MRI in responders. CONCLUSION MRI findings were sensitive to changes in musculoskeletal manifestations in patients with deep morphea undergoing systemic treatment with methotrexate and prednisolone. Thus, MRI can be recommended as an additional tool for response monitoring.

Antisignal recognition particle-positive polymyositis successfully treated with myeloablative autologous stem cell transplantation.

Patients with antisignal recognition particle (SRP)-positive myositis usually present with symmetric, progressive muscle weakness and highly elevated levels of serum creatine phosphokinase (CPK).1 A 32-year-old male patient presented with these symptoms (CPK 3601 U/l, normal range 0–190 U/l) in September 2000. Magnetic resonance imaging (MRI) of the thighs revealed a massive oedema (fig 1). After ineffective treatment with glucocorticosteroids, azathioprine, methotrexate, ciclosporine A, mycophenolate mofetil and intravenous immunoglobulins MRI assessed active myositis. The muscle biopsy revealed a necrotising myopathy. Treatment was switched to cyclophosphamide pulses with 750 mg/m2 every 3 weeks and intensified by high-dose cyclophosphamide for stem cell mobilisation with 4000 …

Quantitative chest CT analysis in patients with systemic sclerosis before and after autologous stem cell transplantation: comparison of results with those of pulmonary function tests and clinical tests

OBJECTIVES The aim of this study was to evaluate the course of SSc-related pulmonary abnormalities following high-dose chemotherapy with autologous stem cell transplantation (SCT) by quantitative chest CT analysis and compare the results with those of pulmonary function tests and the response of cutaneous involvement. METHODS Chest CT quantification was performed before, directly after [0.49 years (sd 0.20)] and at a mean of 2.2 years (sd 2.1) following autologous SCT in 26 consecutive patients with SSc between March 2001 and March 2015. Quantitative CT used fully automated software to calculate inspiratory total lung volume, mean lung density, high attenuation value and their pulmonary distribution (core vs peel). All patients underwent pulmonary function tests. We additionally analysed parallels in the response of associated skin changes by using the modified Rodnan skin score (mRSS). RESULTS The forced vital capacity (FVC) course at 6 months was used to classify patients into responders [n = 20 (76.9%)] and non-responders [n = 6 (23.1%)]. FVC, forced expiratory volume in 1 s, vital capacity (VC) as well as single-breath diffusion capacity for carbon monoxide significantly improved (P = 0.03, 0.001, 0.001 and 0.013, respectively) in responders. At quantitative CT, total lung volume increased (P = 0.018), whereas mean lung density (P = 0.026) and high attenuation value decreased (P = 0.020) after autologous SCT in responders. Correspondingly, mRSS improved from 27.35 (sd 9.25) before to 10.81 (sd 8.64) after autologous SCT (P = 0.003) in responders. Changes in mRSS before autologous SCT and thereafter correlated significantly with those 24 months after autologous SCT (r = 0.575; P = 0.031). CONCLUSIONS CT quantification of lung volume and parenchymal attenuation in SSc patients presenting with alveolitis and fibrosis that undergo autologous SCT yields parameters that match well with those of pulmonary function and even clinical tests. It might therefore be used as a substitute marker in patients who are unable to adequately perform lung function tests.