Haematological Malignancies in Systemic Sclerosis Patients: Case Reports and Review of the World Literature

Background.The association of systemic sclerosis (SSc) and haematological cancers was reported in a large number of case reports and cohort studies, describing SSc patients with highly heterogeneous clinical pictures. Objective. We reviewed the literature to better describe SSc patients with haematological malignancies. Methods. SSc cases complicated by haematological malignancies described in the world literature were collected; other 2 cases referred to our centre were reported. Results. One hundred-thirty SSc subjects were collected from 1954 up to date. The mean age of patients at cancer diagnosis was 56.1 ± 16.7 years; 72% of patients were females. In 60% of cases, the diagnosis of haematological malignancy was described within 5 years of SSc diagnosis. In 7.8% of cases, coexistence of Sj¨ogren’s syndrome or other autoimmune disorders was cited. Sixty-six cases with lymphoma (in the majority of cases B-cell neoplasms), 28 with leukaemia (chronic lymphocytic form in 9), 14 with multiple myeloma plus one solitary IgM plasmocytoma, and 16 with myeloproliferative disorders were found. No specific SSc subsets seem to be related to haematological malignancies. Conclusions. We remarked the importance of clinical work-up in SSc, in order to early diagnose and treat eventual occult haematological malignancies, especially during the first years of the disease

Impegno cardiaco nella sclerosi sistemica

L'impegno cardiaco in corso di sclerosi sistemia consta di uno spettro variabile di manifestazioni cliniche conseguenti ad alterazioni di natura microangiopatica, elettrica e/o emodinamica. In danno ischemico e/o flogistico autoimmune del miocardio producono, in ultima analisi, il quadro istopatologico caratteristico della 'necrosi a bande' con deposizione di tessuto fibroso, responsabile della riduzione di elasticità e della capacità contrattile muscolare. ...

Cryoglobulinemic vasculitis and skin ulcers. Our therapeutic strategy and review of the literature

Objective: Cryoglobulinemic vasculitis (CV) involving small- and medium-sized vessels is very frequently associated with hepatitis C virus and may be responsible for multiple organ involvement and skin ulcers (SU). Skin ulcers are often non-healing cutaneous lesions, possibly complicated by local infection and gangrene; they may severely affect the patients[U+05F3] quality of life and the overall prognosis. Therefore, the treatment of cryoglobulinemic SU is particularly challenging in the clinical practice.The present work evaluated the prevalence and correlations of cryoglobulinemic SU with other clinico-epidemiological features of CV; moreover, our long-term experience with the management strategies of these cutaneous lesions was compared with the world literature on this topic. Methods: The study included 126 CV patients (24 male and 102 female, aged 69 ± 11.2 SD years, disease duration 7 ± 6.9 SD years), followed at our Rheumatology Unit during the past decade. All patients were carefully evaluated regarding the entire cryoglobulinemic syndrome with particular concern for clinical characteristics and treatment of SU. Results: Among 126 CV patients, 36 individuals (29%) experienced at least one episode of SU, more commonly localized at the lower limbs. Patients with complicating SU showed significantly higher percentage of purpuric manifestations (p < 0.01) and liver (p < 0.001), peripheral nerve (p < 0.02), and/or thyroid involvement (p = 0.019).Therapeutic approach to SU included both systemic (immunosuppressors, corticosteroids, and/or plasma exchange) and local treatments. Local treatments consisted of sharp or surgical debridement as well as interactive dressing according to the condition of wound bed, perilesional skin, and the possible presence of infection, detected in 29 of 36 (81%) individuals in our Rheumatology unit. All patients underwent analgesic treatment for SU-related background pain as well as procedural pain, which was critical for an effective local SU management.The large majority of patients with SU healed at a variable time interval according to the severity of the single lesion; only five patients with very severe, non-healing SU needed amputation.The updated review of the literature revealed the presence of SU in around a quarter of CV patients. Among systemic treatments, the anti-CD20 monoclonal antibody rituximab represents one of the most effective and frequently employed therapies; however, the available data focusing on local therapeutic approach are generally limited to anecdotal observations. Conclusions: Overall, the treatment of cryoglobulinemic SU should be tailored to the single patient[U+05F3]s conditions using combined systemic and local treatments; lesional sharp debridement and interactive dressing as well as procedural pain management were decisive, particularly for more severe, non-healing cutaneous lesions

Application of Agents Against Interferon-Gamma-Dependent Chemokines in Immunotherapy

The CXC chemokine receptor (CXCR) 3 and its chemokines (CXCL9, CXCL10, CXCL11) are involved in the pathogenesis of autoimmune disesases. Under the influence of interferon (IFN) γ, the IFNγ-inducible chemokines are secreted by lymphocytes, and by target cells (fibroblasts, epithelial cells, etc). In target tissues, Th1 lymphocytes are recruited; hence IFNγ is enhanced, which stimulates IFNγ-inducible chemokines (CXCL9, CXCL10, CXCL11) secretion reiterating the autoimmune process. Many studies have evaluated if blockade of ..

Rituximab in the treatment of patients with systemic sclerosis. Our experience and review of the literature

BACKGROUND: The treatment of systemic sclerosis (SSc) represents a great clinical challenge because of the complex disease pathogenesis including vascular, fibrotic, and immune T- and B-lymphocyte-mediated alterations. Therefore, SSc should be treated by combined or sequential therapies according to prevalent clinico-pathogenetic phenotypes. Some preliminary data suggest that rituximab (RTX) may downregulate the B-cell over expression and correlated immunological abnormalities. METHODS: Here, we describe a series of 10 SSc patients (4M and 6F, mean age 46±13.5SD years, mean disease duration 6.3±2.7SD years; 5 pts had limited and 5 diffuse SSc cutaneous subset) treated with one or more cycles of RTX (4 weekly infusions of 375mg/m(2)). The main indications to RTX were interstitial lung fibrosis, cutaneous, and/or articular manifestations unresponsive to previous therapies; ongoing treatments remained unchanged in all cases. The effects of RTX were evaluated after 6months of the first cycle and at the end of long-term follow-up period (37±21SD months, range 18-72months). An updated review of the world literature was also done. RESULTS: RTX significantly improved the extent of skin sclerosis in patients with diffuse SSc at 6months evaluation (modified Rodnan skin score from 25±4.3 to 17.2±4.6; p=.022). A clinical improvement of other cutaneous manifestations, namely hypermelanosis (7/7), pruritus (6/8), and calcinosis (3/6) was observed. Moreover, arthritis revealed particularly responsive to RTX showing a clear-cut reduction of swollen and tender joints in 7/8 patients; while lung fibrosis detected in 8/10 remained stable in 6/8 and worsened in 2/8 at the end of follow-up. Pro-inflammatory cytokines, namely IL6, IL15, IL17, and IL23, evaluated in 3 patients with diffuse cutaneous SSc, showed a more or less pronounced reduction after the first RTX cycle. These observations are in keeping with the majority of previous studies including 6 single case reports and 10 SSc series (from 5 to 43 pts), which frequently reported the beneficial effects of RTX on some SSc manifestations, particularly cutaneous sclerosis, along with the improvement/stabilization of lung fibrosis. Possible discrepancies among different clinical studies can be related to the etiopathogenetic complexity of SSc and not secondarily to the patients' selection and disease duration at the time of the study. CONCLUSION: The present study and previous clinical trials suggest a possible therapeutical role of RTX in SSc, along with its good safety profile. The specific activity of RTX on B-cell-driven autoimmunity might explain its beneficial effects on some particular SSc clinical symptoms, namely the improvement of skin and articular involvement, and possibly the attenuation of lung fibrosis

From Localized Scleroderma to Systemic Sclerosis: Coexistence or Possible Evolution

Background. Systemic sclerosis (SSc) and localized scleroderma (LoS) are two different diseases that may share some features. We evaluated the relationship between SSc and LoS in our case series of SSc patients. Methods. We analysed the clinical records of 330 SSc patients, in order to find the eventual occurrence of both the two diseases. Results. Eight (2.4%) female patients presented both the two diagnoses in their clinical histories. Six developed LoS prior to SSc; in 4/6 cases, the presence of autoantibodies was observed before SSc diagnosis. Overall, the median time interval between LoS and SSc diagnosis was 18 (range 0–156) months. Conclusions. LoS and SSc are two distinct clinical entities that may coexist. Moreover, as anecdotally reported in pediatric populations, we suggested the possible development of SSc in adult patients with LoS, particularly in presence of Raynaud’s phenomenon or antinuclear antibodies before the SSc onset

Thyroid Involvement in Hepatitis C Virus-Infected Patients with/without Mixed Cryoglobulinemia

Thyroid involvement is a common condition that can be recorded during the natural course of different systemic rheumatic diseases, including the mixed cryoglobulinemia (MC) syndrome or cryoglobulinemic vasculitis. MC is triggered by hepatitis C virus (HCV) chronic infection in the majority of cases; it represents the prototype of autoimmune-lymphoproliferative disorders complicating a significant proportion of patients with chronic HCV infection. HCV is both hepato- and lymphotropic virus responsible for a great number of autoimmune/lymphoproliferative and/or neoplastic disorders. The complex of HCV-related hepatic and extrahepatic manifestations, including MC and thyroid involvement, may be termed "HCV syndrome." Here, we describe the prevalence and clinico-serological characteristics of thyroid involvement, mainly autoimmune thyroiditis and papillary thyroid cancer, in patients with HCV syndrome with or without cryoglobulinemic vasculitis