Hydroxychloroquine in patients with inflammatory and erosive osteoarthritis of the hands: results of the OA-TREAT study-a randomised, double-blind, placebo-controlled, multicentre, investigator-initiated trial.

OBJECTIVES: Hand osteoarthritis (OA) is a condition characterised by cartilage degradation and frequently erosive changes. Analgesics and non-steroidal anti-inflammatory drugs are used for symptomatic relief but are often poorly tolerated or contraindicated. Previous publications suggest hydroxychloroquine (HCQ) as a possible treatment for hand OA. The OA-TREAT study aimed to investigate the efficacy and safety of HCQ in patients with inflammatory and erosive hand OA (EOA). METHODS: OA-TREAT was an investigator-initiated, multicentre, randomised, double-blind, placebo (PBO)-controlled trial. Patients with inflammatory and EOA, according to the ACR criteria, with radiographically erosive disease were randomised 1:1 to HCQ 200-400 mg/day or PBO for 52 weeks (W52). Both groups received stable standard therapy. The primary endpoint was Australian Canadian Hand Osteoarthritis Index (AUSCAN) for pain and hand disability at W52. RESULTS: 75 patients were randomised to HCQ and 78 to PBO. At W52, mean AUSCAN pain was 26.7 in HCQ and 26.5 in PBO patients (p=0.92). Hand disability measured by AUSCAN function (mean) was 48.1 in HCQ and 51.3 in PBO patients (p=0.36). Changes in radiographic scores did not differ significantly (p>0.05) between treatment groups. There were 7 serious adverse events in the HCQ and 15 in the PBO group. CONCLUSIONS: OA-TREAT is the first large randomised PBO controlled trial focusing on EOA. HCQ was no more effective than PBO for changes in pain, function and radiographic scores in the 52-week period. Overall safety findings were consistent with the known profile of HCQ.

[Renal Involvement in Connective Tissue Diseases]. / Nierenbeteiligung bei Kollagenosen.

Renal involvement is common and heterogenous in connective tissue diseases and has a main influence on prognosis and mortality. In systemic lupus erythematosus proliferative glomerulonephritis is the most common manifestation, while in primary Sjogren's syndrome interstitial nephritis with tubular dysfunction is the predominant pathological feature. In systemic sclerosis the most serious renal manifestation is scleroderma renal crisis characterized by abrupt onset of hypertension and acute kidney injury associated with an increase in plasma renin activity. Risk factors for scleroderma renal crisis are diffuse cutaneous involvement, treatment with corticosteroids > 15 mg prednisolone/day and treatment with calcineurin inhibitors.Regular measurement of urine sediment, proteinuria-to-urine creatinine ratio, tubular proteinuria, measurement of plasma creatinine, and office as well as home blood pressure monitoring are strongly recommended. Diagnostic kidney biopsy is essential in differentiating the different types of lupus nephritis and renal involvement in sjogren's syndrome.The optimal treatment of lupus nephritis varies with the classification of the morphological findings present on renal biopsy. The treatment of interstitial nephritis in sjogren's syndrome consists of immunosuppression e. g. corticosteroids. Renal tubular acidosis should be corrected by sodium alkali and potassium alkali. Angiotensin-converting enzyme inhibitors play a major role in the treatment of scleroderma renal crisis, they should be continued also in patients progressing to end-stage renal disease.

Atherosclerotic plaques occur in absence of intima-media thickening in both systemic sclerosis and systemic lupus erythematosus: a duplexsonography study of carotid and femoral arteries and follow-up for cardiovascular events.

INTRODUCTION: The objective of this cross-sectional and retrospective cohort study was (1) to determine the usefulness of intima-media thickness (IMT) in contrast to plaque assessment, (2) to examine the value of additive femoral artery sonography and (3) to identify potential risk factors for atherosclerosis and incident cardiovascular events in systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) patients. METHODS: In this study, 90 SSc and 100 SLE patients were examined by duplexsonography. IMT was measured in common carotid and common femoral arteries, plaques were assessed in common, internal and external carotid and common, proximal superficial and deep femoral arteries. Different definitions of pathological IMT (pIMT) were compared with the presence of plaque. Results were evaluated in relation to traditional and non-traditional risk factors for baseline atherosclerosis (logistic regression) and their predictive value for cardiovascular events during follow-up (cox regression). RESULTS: Definite atherosclerosis occurred frequently without signs of subclinical atherosclerosis in both diseases: pIMT >0.9 mm was present in only 17/59 (28.9%) SSc and 13/49 (26.5%) SLE patients with already present atherosclerotic plaques. Using age-adjusted pIMT definitions, this rate was even lower (5.1-10.3% in SSc, 14.3-26.5% in SLE). Plaques were located only at the carotid or only at the femoral arteries in 26 (13.7%) and 24 (12.6%) patients, respectively. Age and nicotine pack-years were independently associated with atherosclerotic plaques in SLE and SSc patients, as well as the cumulative prednisolone dose in SSc subgroup, and ssDNA positive SLE patients had a lower risk for atherosclerotic plaque. During follow-up (available for 129/190 (67.9%) patients, 650 person-years), cardiovascular events occurred more often in patients with coronary heart disease (adjusted-hazards ratio (HR) 10.19, 95% confidence interval (CI) 3.04 to 34.17, P <0.001), male patients (adjusted-HR 8.78, 95% CI 2.73 to 28.19, P <0.001) and in patients with coexistent carotid and femoral plaques (adjusted-HR 5.92, 95% CI 1.55 to 22.67, P = 0.009). Patients with solely carotid or femoral plaque were not at higher risk. CONCLUSION: Atherosclerotic plaque lesions can be found frequently in absence of intima-media thickening in both SSc and SLE patients. As well as routine sonography of carotid arteries, the sonography of femoral arteries is recommended to identify additional atherosclerotic lesions and to detect patients at a high risk for cardiovascular events.

Nephrogenic systemic fibrosis--a rapidly progressive disabling disease with limited therapeutic options.

BACKGROUND: Nephrogenic systemic fibrosis (NSF) affects some patients on dialysis after gadolinium contrast agent-enhanced magnetic resonance imaging. It is characterized by progressive skin fibrosis of the extremities, sometimes including the trunk and internal organs. METHODS: The clinical course of 10 patients with biopsy-proven NSF was analyzed retrospectively with regard to gadolinium exposition, disease onset, and progression of NSF with special emphasis on physical mobility and impact of different therapeutic approaches. RESULTS: Despite physiotherapy and different additional therapeutic approaches (eg, immunosuppression, ultraviolet A-1 phototherapy, or extracorporal photopheresis) all patients developed progressive skin fibrosis of the lower extremities, sometimes including the trunk and arms. Kidney transplantation led to a slow improvement of skin lesions in one patient. Nine patients developed progressive joint contractures, and 8 patients became wheelchair bound within 12 months after disease onset and became dependent on the support of family members or a nursing service. LIMITATIONS: Retrospective analysis in a relatively small number of patients is a limitation. CONCLUSION: NSF appears to be a rapidly progressive disabling disease with limited therapeutic options.

Sites of inflammation in painful rheumatoid shoulder assessed by musculoskeletal ultrasound and power Doppler sonography.

Ultrasonography (US) and power Doppler sonography (PDS) was used to investigate causes of new onset of shoulder pain and sites of shoulder inflammation in 157 shoulders of 99 patients with rheumatoid arthritis (RA). US detected effusion and/or synovitis in 92/157 glenohumeral joints, subdeltoid bursitis in 56/157 shoulders and tenosynovitis of biceps tendon in 55/157 shoulders. Bursitis and/or tenosynovitis were accompanied by glenohumeral synovitis in 68/90 shoulders. 68% of serologically active and 12% of serologically inactive patients had glenohumeral synovitis. PDS showed increased microvascular blood flow in 33 of the 44 investigated shoulders. Glenohumeral synovitis was correlated to elevated C-reactive protein levels (p = 0.0001) and microvascular blood flow assessed by PDS (p = 0.02). This study shows that rheumatoid shoulder pain is not caused by glenohumeral synovitis in 32% of patients, despite serologically active RA. US and PDS are mandatory to elucidate the origin of inflammatory and noninflammatory shoulder pain.

[Neuropsychiatric involvement in systemic lupus erythematosus. Part 2: diagnostic and therapy]. / Neuropsychiatrische Beteiligung des systemischen Lupus erythematodes. Teil 2: Diagnostik und Therapie.

BACKGROUND: The diagnosis of neuropsychiatric lupus erythematosus (NPSLE) can be difficult and has to be differentiated from neurologic complications that result from hypertension, drugs, infection, uremia, and metabolic changes. DIAGNOSTICS: There is no single test which is diagnostic. Therefore, the clinical presentation, serologic tests and neuroimaging techniques have to be combined to support the diagnosis of cerebral lupus. Magnetic resonance imaging (MRI) is routinely used with a sensitivity of 50-87%. However, the abnormalities such as white matter lesions or brain atrophy are nonspecific and were also found in asymptomatic patients (16-52%). A negative MRI result does not exclude a diagnosis of cerebral lupus. Antibodies against phospholipids are an important immunoserologic marker due to the close association with thromboembolic events. Echocardiography and cerebrospinal fluid examination should be added to rule out cardiac embolic disease and CNS infection. Functional brain imaging techniques such as single-photon emission computed tomography, positron emission tomography, magnetization transfer imaging or magnetic resonance spectroscopy may be helpful especially in patients with unconspicuous MRI, but the findings are not SLE-specific. THERAPY: The treatment of cerebral lupus is empiric, due to a lack of randomized studies. Inflammatory brain lesions are treated with corticosteroids and immunosuppressive drugs (e. g., cyclophosphamide). Anticoagulant therapy with coumarins (at a target INR of 3.0-3.5) is recommended in cases of thrombotic events associated with antiphospholipid antibodies. However, no studies exist on patients with arterial thrombosis, including strokes, supporting this target INR.

[Neuropsychiatric involvement in systemic lupus erythematosus. Part 1: clinical presentation and pathogenesis]. / Neuropsychiatrische beteiligung des systemischen lupus erythematodes. Teil 1: klinik und pathogenese.

BACKGROUND: Central nervous system (CNS) involvement is a frequent complication of systemic lupus erythematosus (SLE) ranging from a subclinical to a severe disabling disease. Neuropsychiatric manifestations have been described in 18-67% of cases depending on the diagnostic criteria. The cerebral involvement may precede the full-blown picture of SLE or may develop in the course of disease, most frequently within the first 3 years. CLINICAL PRESENTATION: Neuropsychiatric manifestations in SLE comprise diffuse psychiatric symptoms, focal neurologic symptoms, and the involvement of the peripheral nervous system. Numerous CNS syndroms have been described: migraine, seizure, stroke, chorea, transverse myelopathy, psychosis, mood disorders, acute confusional state, and cognitive dysfunction. The diagnosis of cerebral involvement can be difficult and has to be differentiated from neurologic complications which may be, for instance, due to uremia, hypertension, drug toxicity, and infection. PATHOGENESIS: A large number of etiopathophysiologic processes are involved: antineuronal antibodies, antibodies against ribosimal P-protein, and cytokines have been implicated in the pathogenesis of diffuse neuropsychiatric symptoms. Focal neurologic symptoms are the consequence of vascular injury induced by circulating immune complex, occlusive vasculopathy as a result of endothelial cell activation induced by cytokines and complement activation, or macro- and microvascular thrombosis induced by antiphospholipid antibodies. In the later stages of disease, cerebrovascular manifestations are often related to accelerated atherosclerosis, which is entertained by increased intravascular complement turnover and antiphospholipid antibodies.