Disease progression in systemic sclerosis-overlap syndrome is significantly different from limited and diffuse cutaneous systemic sclerosis.

BACKGROUND: Systemic sclerosis (SSc)-overlap syndromes are a very heterogeneous and remarkable subgroup of SSc-patients, who present at least two connective tissue diseases (CTD) at the same time, usually with a specific autoantibody status. OBJECTIVES: To determine whether patients, classified as overlap syndromes, show a disease course different from patients with limited SSc (lcSSc) or diffuse cutaneous SSc (dcSSc). METHODS: The data of 3240 prospectively included patients, registered in the database of the German Network for Systemic Scleroderma and followed between 2003 and 2013, were analysed. RESULTS: Among 3240 registered patients, 10% were diagnosed as SSc-overlap syndrome. Of these, 82.5% were female. SSc-overlap patients had a mean age of 48±1.2 years and carried significantly more often 'other antibodies' (68.0%; p<0.0001), including anti-U1RNP, -PmScl, -Ro, -La, as well as anti-Jo-1 and -Ku antibodies. These patients developed musculoskeletal involvement earlier and more frequently (62.5%) than patients diagnosed as lcSSc (32.2%) or dcSSc (43.3%) (p<0.0001). The onset of lung fibrosis and heart involvement in SSc-overlap patients was significantly earlier than in patients with lcSSc and occurred later than in patients with dcSSc. Oesophagus, kidney and PH progression was similar to lcSSc patients, whereas dcSSc patients had a significantly earlier onset. CONCLUSIONS: These data support the concept that SSc-overlap syndromes should be regarded as a separate SSc subset, distinct from lcSSc and dcSSc, due to a different progression of the disease, different proportional distribution of specific autoantibodies, and of different organ involvement.

[Rheumatology -- Part 3. Research news concerning epidemiology, diagnosis, and therapy of primary systemic vasculitides]. / Rheumatologie -- Teil 3. Aktuelle Forschungsergebnisse zur Epidemiologie, Diagnose und Therapie von primär systemischen Vaskulitiden.

Antineutrophil cytoplasmic autoantibody-(ANCA-)associated vasculitides, immune complex-mediated vasculitides and granulomatous arteritides of unknown etiology belong to the group of primary systemic vasculitides. Numerous in vitro and in vivo studies have underscored the role of ANCA in the pathogenesis of ANCA-associated vasculitides (Wegener's granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome) in the meantime. Whereas the pathogenicity of myeloperoxidase (MPO) ANCA has been supported by data from various animal models in the past, the in vivo pathogenicity of proteinase 3 (PR3) ANCA has been demonstrated in an animal model only recently. Other studies showed an altered T-cell response in Wegener's granulomatosis. Hepatitis C virus-(HCV-)associated cryoglobulinemic vasculitis is mediated by immune complexes. Recent data suggest that the HCV core particles concentrated in the cryoprecipitate apparently play a role in the interaction of cryoglobulin and endothelial cells and neutrophil granulocytes. Data from the European Vasculitis Study Group (EUVAS) demonstrate the efficacy of azathioprine in maintaining remission in ANCA-associated vasculitides on the basis of large patient numbers. Biologicals play an increasing role in the treatment of refractory vasculitis.

[Rheumatology-part 2. Research news concerning pathogenesis, epidemiology, diagnosis, and therapy of connective tissue disease]. / Rheumatologie-Teil 2 Aktuelle Forschungsergebnisse zur Epidemiologie, Diagnose und Therapie von Kollagenosen.

Due to the partial elucidation of the immunopathogenesis of chronic inflammatory diseases during the last years, clinical rheumatology has made a rapid development, which by the consequent use of immunomodulatory therapies including recombinant proteins (biologicals) led to a significantly ameliorated prognosis of these diseases. On this basis, new research projects are continuously performed in the fields of pathogenesis, new drug development, outcome and therapy studies. New developments of imaging techniques and serologic testing facilitate a better classification and definition of disease activity and remission criteria. The current state of research in the field of collagen vascular diseases with its clinical consequences is reviewed in this article on the basis of the most recent data available.

Vasoactive Therapy in Systemic Sclerosis: Real-life Therapeutic Practice in More Than 3000 Patients.

OBJECTIVE: Vasculopathy is a key factor in the pathophysiology of systemic sclerosis (SSc) and the main cause for Raynaud phenomenon (RP), digital ulcers (DU), and/or pulmonary arterial hypertension (PAH). It is so far unknown how patients with SSc are treated with vasoactive agents in daily practice. To determine to which extent patients with SSc were treated with different vasoactive agents, we used data from the German Network for Systemic Scleroderma registry. METHODS: The data of 3248 patients with SSc were analyzed. RESULTS: Patients were treated with vasoactive drugs in 61.1% of cases (1984/3248). Of these, 47.6% received calcium channel inhibitors, followed by 34.2% treated with angiotensin-converting enzyme (ACE) inhibitors, 21.1% treated with intravenous (IV) prostanoids, 10.1% with pentoxifylline, 8.8% with angiotensin 1 receptor antagonists (AT1RA), 8.7% with endothelin 1 receptor antagonists (ET1RA), 4.1% with phosphodiesterase type 5 (PDE5) inhibitors, and 5.3% with others. Patients with RP received vasoactive therapy in 63.3% of cases, with DU in 70.1%, and with PAH in 78.2% of cases. Logistic regression analysis revealed that patients with PAH were significantly more often treated with PDE5 inhibitors and ET1RA, and those with DU with ET1RA and IV prostanoids. In addition, 41.8% of patients were treated with ACE inhibitors and/or AT1RA. Patients registered after 2009 received significantly more often ET1RA, AT1RA, and IV prostanoids compared with patients registered prior to 2005. CONCLUSION: These data clearly indicate that many patients with SSc do not yet receive sufficient vasoactive therapy. Further, in recent years, a marked change of treatment regimens can be observed.

Symptoms and clinical course of EHEC O104 infection in hospitalized patients: a prospective single center study.

OBJECTIVES: Shiga-toxin producing O157:H7 Entero Haemorrhagic E. coli (STEC/EHEC) is one of the most common causes of Haemolytic Uraemic Syndrome (HUS) related to infectious haemorrhagic colitis. Nearly all recommendations on clinical management of EHEC infections refer to this strain. The 2011 outbreak in Northern Europe was the first to be caused by the serotype O104:H4. This EHEC strain was found to carry genetic features of Entero Aggregative E. coli (EAEC) and extended spectrum ß lactamase (ESBL). We report symptoms and complications in patients at one of the most affected centres of the 2011 EHEC O104 outbreak in Northern Germany. METHODS: The courses of patients admitted to our hospital due to bloody diarrhoea with suspected EHEC O104 infection were recorded prospectively. These data include the patients' histories, clinical findings, and complications. RESULTS: EHEC O104 infection was confirmed in 61 patients (female = 37; mean age: 44±2 years). The frequency of HUS was 59% (36/61) in our cohort. An enteric colonisation with co-pathogens was found in 57%. Thirty-one (51%) patients were treated with plasma-separation/plasmapheresis, 16 (26%) with haemodialysis, and 7 (11%) with Eculizumab. Patients receiving antibiotic treatment (n = 37; 61%) experienced no apparent change in their clinical course. Twenty-six (43%) patients suffered from neurological symptoms. One 83-year-old patient died due to comorbidities after HUS was successfully treated. CONCLUSIONS: EHEC O104:H4 infections differ markedly from earlier reports on O157:H7 induced enterocolitis in regard to epidemiology, symptomatology, and frequency of complications. We recommend a standard of practice for clinical monitoring and support the renaming of EHEC O104:H4 syndrome as "EAHEC disease".

Do elevated plasma vasoactive intestinal polypeptide (VIP) levels cause small intestinal motor disturbances in humans?

Increased VIP plasma levels cause severe secretory diarrhea. Moreover, VIP is a major regulator of human intestinal motility. We hypothesized that VIP-mediated intestinal motility disturbances contribute to symptoms in elevated plasma VIP. Ten healthy volunteers were intubated twice with an orojejunal multilumen tube for duodenal manometry, jejunal perfusion of electrolyte and marker solution, and aspiration 10 and 40 cm more distally. All subjects randomly received intravenous infusion of saline and 300 pmol/kg x hr VIP for 5 hr. Results showed that VIP but not saline infusion induced netjejunal sodium secretion, watery diarrhea, and cardiovascular effects (P < 0.04). VIP did not alter intestinal motor activity or the mean duration of the interdigestive motility cycle or of phases I and II but nearly halved the duration of phase III (P = 0.0002). We conclude that increased plasma VIP markedly shortens human phase III activity without influencing other motility parameters. Hence, it is unlikely that VIP-mediated small intestinal motor disturbances cause symptoms in VIPOMA. Yet VIP may contribute to terminate phase III motility.