Michele Inglese

Behçet syndrome: from pathogenesis to novel therapies

Behçet syndrome is a chronic disease hallmarked by inflammation of the blood vessels that is related to an autoimmune reaction caused by inherited susceptibility due to specific genes and environmental factors, probably components of infectious microorganisms, which turn on or get going the disease in genetically susceptible subjects. The more common clinical expression of the disease is represented by a triple-symptom complex of recurrent oral aphthous ulcers, genital ulcers, and uveitis, sometimes associated with inflammatory arthritis, phlebitis, iritis, as well as inflammation of the digestive tract, brain, and spinal cord. The treatment strategies used to manage the manifestations of Behçet syndrome have gradually progressed, and a number of new therapeutic resources have been implemented in recent years, allowing better control of pathogenic mechanisms, reducing symptoms and suffering, and ameliorating patient’s outcome.

Neuroendocrine-immune interactions in healthy aging

Aim:  The nervous, endocrine and immune systems are connected by shared neurotransmitters, hormones and cytokines. The function of these systems shows patterns of circadian rhythmicity and a number of age‐related changes in the 24‐h hormonal and non‐hormonal rhythms have been found in older human beings. The aim of this study was to evaluate integration among the nervous, endocrine and immune systems in the elderly.

Digital ulcers in scleroderma patients: A retrospective observational study.

Background: The guidelines for digital ulcers (DUs) management in systemic sclerosis (SSc) indicate the use of iloprost to induce wound healing and bosentan to prevent the onset of new DU. The aim of our study was to evaluate whether the combination treatment may surmount the effect of the single drug. Methods: We analyzed data regarding 34 patients with SSc and at least one active DU persisting despite 6 months of iloprost therapy, and treated for other 6 months with a combination therapy, i.e. iloprost plus bosentan. Results: Overall, patients initially presented 69 DUs (58 on the fingers and 11 on the legs). At the end of the study 34 (49.3%) DUs were completely healed (responding, R), 18 (26.1%) started the healing process (partially responding, PR), and 17 (24.6%) did not respond (NR) to therapy. No new DU was recorded and the ulcers localized on the legs did not respond to the combination therapy. Finally, data have been analyzed by dividing the patients in two groups according to the fibrosis level on the finger. In the group with mild fibrosis, 83.4% of DUs resulted with showing complete healing while, in the group with severe fibrosis, only 18% of DUs were healed (P = 0.024). Conclusion: The treatment with iloprost plus bosentan is effective in determining healing of DUs in SSc patients with mild digital skin fibrosis. Conversely, the severity of skin fibrosis strongly influences the healing process of DUs. The study confirmed the efficacy of bosentan to prevent onset of new DUs.

The synovio-entheseal complex in enthesoarthritis

Abstract The group of diseases classified as seronegative spondyloarthritis or enthesoarthritis is characterized by typical osteoarticular and extra-articular manifestations. Diverse patterns of disease can affect different members of the same family and may show different features in the same patient, with clinical overlaps thwarting the differential diagnosis. An anatomo-pathological hallmark in enthesoarthritis is the inflammatory process in the synovio-entheseal sites. The inflammatory microenvironment of synovio-entheseal complex, named enthesitis, is characterized, after an initial inflammatory/erosive phase, by a subsequent phase of neobone apposition, which seems to progress independently from the previous erosive phase, suggesting that the physiopathogenetic mechanisms that underlay the two phases are driven by different pivots. The structural damage is characterized by excessive neobone formation, with the syndesmophyte as a typical lesion. The process underlying their formation is not fully understood, although there are many useful information to clarify the physiopathogenetic puzzle. The primum movens of the enthesitic process is the micro-trauma to which entheses are subject, especially in the lower limbs, for biomechanical reasons. The inflammatory process is facilitated by the sequential structure of the organ enthesis, constitutionally devoid of sub-enthesitic cortical bone and closely related to the underlying trabecular bone and the medullary vascular system. The reparative attempt from the vascular system, thanks to the activating action of certain loco-regional cytokines, such as TNF α, conditions the possible deposit in the enthesis of molecules derived from other organic sites and able, especially in HLA-B27+ subjects, to activate and self-renew an immune-mediated inflammatory process following the initial mechanical process.

Stem cell autograft and allograft in autoimmune diseases

Abstract Autoimmune diseases are characterized by an insufficiency of immune tolerance and, although treated with a number of useful drugs, may need more unconventional therapeutic strategies for their more severe presentations. Among such unconventional therapeutic approaches, stem cell autograft and allograft have been used, with the aim of stimulating disease remission by modifying the pathogenic mechanisms that induce anomalous responses against self-antigens. Autologous transplantation is performed with the purpose of retuning autoimmune cells, whereas allogeneic transplantation is performed with the purpose of replacing anomalous immune effectors and mediators. In this article, we comprehensively review up-to-date information on the autoimmune diseases for which the transplantation of stem cells is indicated.