Alan Tyndall

This study describes clinical characteristics, prognostic factors, and quality of life in patients with newly diagnosed (incident) digital ulcers (DU). Observational cohort study of 189 consecutive SSc patients with incident DU diagnosis identified from the EUSTAR database (22 centres in 10 countries). Data were collected from medical charts and during one prospective visit between 01/2004 and 09/2010. Median age at DU diagnosis was 51 years, majority of patients were female (88%), and limited cutaneous SSc was the most common subtype (61%). At incident DU diagnosis, 41% of patients had one DU and 59% had ≥2 DU; at the prospective visit 52% had DU. Pulmonary arterial hypertension (PAH) and multiple DU at diagnosis were associated with presence of any DU at the prospective visit (odds ratios: 4.34 and 1.32). During the observation period (median follow-up was 2 years) 127 patients had ≥1 hospitalisation. The event rate of new DU per person-year was 0.66, of DU-associated complications was 0.10, and of surgical or diagnostic procedures was 0.12. At the prospective visit, patients with ≥1 DU reported impairment in daily activities by 57%, those with 0 DU by 37%. The mean difference between patients with or without DU in the SF-36 physical component was 2.2, and in the mental component 1.4. DU patients were not routinely prescribed endothelin receptor antagonists or prostanoids. This real world cohort demonstrates that DU require hospital admission, and impair daily activity. PAH and multiple DU at diagnosis were associated with future occurrence of DU.

Autoimmunity is an overreaction of immune competent cells to self structures resulting in an unwanted clinical outcome. Traditional therapeutic strategies, still relevant in many cases, involve broad acting immunosuppressants such as cyclophosphamide with the predictable attendant toxicity. More recent concepts include blockade of specifically defined targets such as TNF-α, with resulting immunomodulation and less toxicity. Both of these strategies require ongoing drug treatment of established disease. A long standing goal, not yet achieved, is the predictable induction of tolerance, obviating the need for chronic treatment. Experimental strategies to achieve this include pre-emptive (preclinical) treatment before chronification is established, total immune ablation and immune “resetting“ and autoantigen immunisation.

In the past 15 years, more than 1,500 patients worldwide have received a hematopoietic stem cell transplant, mostly autologous, as treatment for a severe autoimmune disease (AD). A recent retrospective analysis of 900 patients showed that the majority had multiple sclerosis, systemic sclerosis, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and juvenile idiopathic arthritis (JIA; n = 65) and idiopathic cytopenic purpura. An overall 85% 5-year survival and 43% progression-free survival was seen, with 100-day transplant-related mortality (TRM) ranging between 1% (RA) and 11% (SLE and JIA). Around 30% of patients in all disease subgroups had a complete response, despite full immune reconstitution. In many patients, morphological improvement was documented beyond any predicted known effects of intense immunosuppression alone. It is hoped that the results of three ongoing large prospective, randomized, controlled trials will allow modification of the protocols to reduce the high TRM, which relates to regimen intensity, age of patient, and comorbidity. Multipotent mesenchymal stromal cells (MSCs), including autologous MSCs, have recently been tested in various ADs, exploiting their immune-modulating properties and apparent low acute toxicity. Despite encouraging small phase I/II studies, no positive data from randomized, prospective studies are as yet available in the peer-reviewed literature.

Introduction: Erectile dysfunction (ED) is common in men with systemic sclerosis (SSc) but the demographics, risk factors and treatment coverage for ED are not well known. Method: This study was carried out prospectively in the multinational EULAR Scleroderma Trial and Research database by amending the electronic data-entry system with the International Index of Erectile Function-5 and items related to ED risk factors and treatment. Centres participating in this EULAR Scleroderma Trial and Research substudy were asked to recruit patients consecutively. Results: Of the 130 men studied, only 23 (17.7%) had a normal International Index of Erectile Function-5 score. Thirty-eight per cent of all participants had severe ED (International Index of Erectile Function-5 score ≤ 7). Men with ED were significantly older than subjects without ED (54.8 years vs. 43.3 years, P < 0.001) and more frequently had simultaneous non-SSc-related risk factors such as alcohol consumption. In 82% of SSc patients, the onset of ED was after the manifestation of the first non-Raynaud's symptom (median delay 4.1 years). ED was associated with severe cutaneous, muscular or renal involvement of SSc, elevated pulmonary pressures and restrictive lung disease. ED was treated in only 27.8% of men. The most common treatment was sildenafil, whose efficacy is not established in ED of SSc patients. Conclusions: Severe ED is a common and early problem in men with SSc. Physicians should address modifiable risk factors actively. More research into the pathophysiology, longitudinal development, treatment and psychosocial impact of ED is needed.

Over the past 15 years, more than 1500 patients have received HSCT, mostly autologous, as treatment for a severe autoimmune disease (AD). More than 1000 of these have been registered in the European Group for Bone Marrow Transplantation (EBMT) and European League Against Rheumatism (EULAR) combined database. A recent retrospective analysis of 900 patients showed that the majority had multiple sclerosis (MS; n = 345) followed by systemic sclerosis (SSc; n = 175), systemic lupus erythematosus (SLE; n = 85), rheumatoid arthritis (RA; n = 89), juvenile idiopathic arthritis (JIA; n = 65), and idiopathic cytopenic purpura (ITP; n = 37). An overall 85% 5-year survival and 43% progression-free survival was seen, with 100-day transplantation-related mortality (TRM) ranging between 1% (RA) and 11% (SLE and JIA). Approximately 30% of patients in all disease subgroups had a complete response, often durable despite full immune reconstitution. In many patients, such as in those with SSc, morphological improvement such as reduction of skin collagen and normalization of microvasculature was documented beyond any predicted known effects of intense immunosuppression alone. The high TRM was in part related to conditioning intensity, comorbidity, and age, but until the results of the 3 prospective randomized trials are known, an evidence-based modification of the conditioning regimen will not be possible.¹ In recent years, multipotent mesenchymal stromal cells (MSCs) have been tested in various AD, exploiting their immune-modulating properties and apparent low acute toxicity. Despite encouraging small phase 1/2 studies, no positive data from randomized, prospective studies are as yet available in the peer-reviewed literature.

We report a patient who presented with inflammatory back pain due to multisegmental spondylitis. Following a vertebral biopsy which failed to detect an infectious organism, the patient was treated with etanercept, a tumor necrosis factor (TNF)-α inhibitor, for suspected undifferentiated spondyloarthritis. The back pain worsened and the spondylitic lesions increased. Only in a vertebral rebiopsy with polymerase chain reaction (PCR) amplification of Tropheryma whipplei, the causative agent of Whipple's disease was identified. Tropheryma whipplei should be considered as a cause of spondylitis even with multisegmental involvement and in the absence of gastrointestinal symptoms. In this clinical setting, routine PCR for Tropheryma whipplei from vertebral biopsies is recommended.

Immunoablation with autologous hematopoietic stem cell rescue has been used in over 1,300 autoimmune disease patients, around 150 with SLE. Some patients have experienced durable remissions with loss of autoantibodies, whereas others either did not respond or died as a result of the treatment. Prospective randomised trials are required and are being planned to establish the place for this potentailly curative strategy. Mesenchymal stem cells are in an exploratory phase for the treatment of acute autoimmune disease including SLE. The principle is that they home to inflammed tissue and exert an antiinflammatory paracrine effect.