Nicola Ughi

Background Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic premalignant clonal plasma cell disorder. It is defined by the presence of serum levels of a monoclonal paraprotein lower than 3 g/dl, and a clonal plasma cell infiltration of the bone marrow less than 10%, in the absence of end-organ damage related to the lymphoproliferative process (1). The prevalence of MGUS in patients with chronic inflammatory and autoimmune disorders, commonly associated to an immune system impairment, has been found to be similar to that found in otherwise healthy individuals over the age of 50 (2,3). Objectives To assess the prevalence of MGUS in a cohort of systemic sclerosis (SSc) patients from two Italian centers. Methods Two-hundred-thirty-six SSc patients consecutively enrolled at the Rheumatology Unit of Naples and at the Division of Rheumatology of Milan from 2008 to 2011 were investigated. MGUS was suspected in case of the incidental finding of a monoclonal band i...

Wound healing is a complex physiological process including overlapping phases (hemostatic/inflammatory, proliferating and remodeling phases). Every alteration in this mechanism might lead to pathological conditions of different medical relevance. Treatments for chronic non-healing wounds are expensive because reiterative treatments are needed. Regenerative medicine and in particular mesenchymal stem cells approach is emerging as new potential clinical application in wound healing. In the past decades, advance in the understanding of molecular mechanisms underlying wound healing process has led to extensive topical administration of growth factors as part of wound care. Currently, no definitive treatment is available and the research on optimal wound care depends upon the efficacy and cost-benefit of emerging therapies. Here we provide an overview on the novel approaches through stem cell therapy to improve cutaneous wound healing, with a focus on diabetic wounds and Systemic Sclerosis-associated ulcers, which are particularly challenging. Current and future treatment approaches are discussed with an emphasis on recent advances.

LETTER TO THE EDITOR Vitamin D in systemic sclerosis Laura Belloli & Nicola Ughi & Bianca Marasini ... J Rheumatol 35:2201–2205 4. Vacca A, Cormier C, Piras M et al (2009) Vitamin D deficiency and insufficiency in 2 independent cohorts of patients with systemic sclerosis. ...

ABSTRACT Background AIDs are a group of heterogeneous disorders characterized by recurrent fever and systemic inflammation (aseptic and non-autoimmune). Myalgia is a common manifestation, frequently associated with erythematous macular rash Objectives To describe the clinical, magnetic resonance imaging (MRI) and pathologic findings of myofascial involvement in AIDs Methods In 3 children with AIDs and unusual disabling myalgias, muscle involvement was investigated by biopsy and MRI Results All pts were Caucasian, two boys (4 and 5 year old, Case 1 and 2 respectively) and one girl (10 year old, Case 3), and presented with rash on limbs and eyelids, spiking fever, fatigue, and disabling myalgias, seldom blunt arthritis. Moreover, Case 2 developed annular eruptions on limbs and a maculopapular rash on palms and soles, while Case 3 had urticaria-like manifestations and arthritic episodes confirmed by ultrasounds (joint effusions and synovitis) with no erosions on X-Rays. Lab tests showed anaemia, thrombocytosis, high ESR and CRP, and extremely raised ferritin (10400-30140 ng/mL). Immunologic tests were negative. A diagnosis of AID was suspected. In relation to the unusual myalgias, muscular involvement was investigated: very high aldolase levels were detected (42.8-53.6 U/L, normal <7.6) with normal CPK. Then, MRI of the thighs in 2 pts (Case 2 and 3) displayed edema of subcutis and fascia and in Case 3 likely epimysial edema, too. Thereafter, all 3 thigh muscle biopsies showed aspecific inflammatory findings without direct myocytic involvement (Case 1 monocytic fasciitis, Case 2 perimyocitic inflammatory infiltrate, Case 3 perivascular lymphocytes and interstitial edema of skin and fascia). In Case 2 AID was confirmed by genetic analysis (mutations in exones 2, 3, 4 and 6 of TNFRSF1A and exone 3 of NLRP3 genes suggestive of TNF receptor-associated periodic syndrome [TRAPS]), while there were no specific findings in Case 1, the analysis is ongoing in Case 3. All 3 pts were treated with pulse i.v. methylprednisolone and oral steroids with clinical and inflammatory indexes amelioration. Anti-IL1 Anakinra was introduced in Case 1 and 2 with steroid sparing and obtaining complete resolution of myalgias and control of fever and rash. Lab tests improved as well. In Case 3 Cyclosporine A was started with no efficacy. Therefore, Anakinra was added showing partial response, but stopped because of reaction on injection site. Then, antiTNF Etanercept was used with no response, so all therapies were substituted for oral steroids with improvement of symptoms and Lab tests. A trial with anti-IL1 Canakinumab is on evaluation Conclusions Myalgias and severe disabling muscle pain, associated with a sharp increase in muscle-specific enzyme aldolase, seem highly suggestive of AID and may result from myofascial involvement rather than myositis. At our knowledge, similar feature are described in only few adult pts [1] and no pediatric cases of documented myofascial involvement are described so far Disclosure of Interest None Declared

Wound healing is a complex physiological process including overlapping phases (hemostatic/inflammatory, proliferating and remodeling phases). Every alteration in this mechanism might lead to pathological conditions of different medical relevance. Treatments for chronic non-healing wounds are expensive because reiterative treatments are needed. Regenerative medicine and in particular mesenchymal stem cells approach is emerging as new potential clinical application in wound healing. In the past decades, advance in the understanding of molecular mechanisms underlying wound healing process has led to extensive topical administration of growth factors as part of wound care. Currently, no definitive treatment is available and the research on optimal wound care depends upon the efficacy and cost-benefit of emerging therapies. Here we provide an overview on the novel approaches through stem cell therapy to improve cutaneous wound healing, with a focus on diabetic wounds and Systemic Sclerosis-associated ulcers, which are particularly challenging. Current and future treatment approaches are discussed with an emphasis on recent advances.

The risk of cancer with the use of biologic agents in rheumatic diseases is still a matter of debate. Published data suggest that the extent of cancer risk might differ according to the type of cancer, and there is recent clinical evidence for a significant increased risk for skin cancer, including melanoma. In contrast with the extensive literature on cancer risk in rheumatoid arthritis, little has been reported on the development of malignancies in spondyloarthroparthies. We report the case of an otherwise healthy 31-year-old Italian woman with psoriasic arthritis who developed a melanoma of left third toe with metastatic involvement of regional lymphnodes after a 3-year treatment with the TNF-alpha inhibitor adalimumab. This case illustrates the possibility of a causal relationship between TNF-alpha inhibitors and melanoma. We believe that vigilance should continue in patients treated with TNF-alpha blocking agents, until the question on the increased incidence of cancers, including skin cancers, associated with these drugs will be defined.

The sparing effect of hemiplegia in rheumatic diseases has been described, but reports on systemic sclerosis (SSc)-spectrum disorders are unusual. SSc-spectrum disorders are complex diseases of unknown origin characterized by multisystem involvement, skin and organ fibrosis, microvascular alterations, and immunologic abnormalities. We describe two cases of patients with hemiplegia who developed Raynaud׳s phenomenon and skin fibrosis of the non-paretic limb. Clinical, laboratory, and investigation findings of two cases with hemiplegia who developed scleroderma spectrum disorders of the non-paretic limb are presented. A review of the medical literature was performed in PubMed for all articles in English. A total of 46 reports from 1935 to 2012 were identified, especially on osteoarthritis and rheumatoid arthritis. Only two case reports on patients with SSc describe asymmetric SSc skin involvement and unilateral acro-osteolysis on x-ray images of the non-paretic limb. By contrast, we r...