BackgroundThe fertility in childbearing Systemic Lupus Erythematosus (SLE) patients can be impaired due to several conditions. In particular, treatment with alkylating agents, as cyclophosphamide (CYC), could determine menstrual irregularities and premature ovarian failure (POF). Gonadotropin-releasing hormone analogues (GnRH-a) is one of the preventive strategy suggested by the recently published EULAR recommendations (1). They are characterized by good safety profile and effectiveness in reducing POF rate in patients with malignancies and autoimmune diseases. So far, only few studies have been published focusing on the use of GnRH-a to prevent POF in SLE women receiving CYC treatment.ObjectivesIn the present case-control study, we aimed at evaluating the efficacy of GnRH-a on the ovarian function preservation in SLE patients treated with CYC.MethodsWe enrolled consecutive SLE patients, fulfilled the 1997 ACR revised criteria treated with CYC in the period between 2005 and 2012, receiving GnRH-a (GnRH-a+). As control, SLE patients treated with CYC not receiving GnRH-a (GnRH-a-) were assessed. Clinical and laboratory data were collected in a standardized, computerized and electronically filled form. Ovarian function was assessed by the evaluation of FSH and estradiol level (E2). GnRH-a (triptorelin 3.75 mg/monthly intramuscularly) was prescribed. SLE patients treated with CYC were followed after the treatment every six months during the first year and then annually.ResultsThirty-tree SLE patients treated by CYC were evaluated in the present analysis: 75.7% of patients were treated for lupus nephritis. Among [FC1] these, 18 GnRH-a+ (mean±SD age 29.3±7.6 years; mean±SD disease duration 7.2±4.2 years) and 15 GnRH-a- (mean±SD age 31.0±10.5 years; mean±SD disease duration 6.3±7.4 years). The mean±SD SLEDAI-2K score in GnRH-a+ patients was 10.1±3.7, in GnRH-a- patients 8.3±3.3 (p=NS). Moreover, no differences were identified concerning the duration of CYC treatment (GnRH-a+: 6.1±2.8 months versus GnRH-a- 6.1±2.2 months, p=NS) and follow-up (GnRH-a+: 8.11±2.2 years versus GnRH-a- 9.3±7.2 years, p=NS). The prevalence of POF was significantly higher in GnRH-a- (5 patients, 33.3%) in comparison with GnRH-a+ (2 patients, 11.1%, P=0.0002). A significantly higher mean age at the time of CYC treatment was observed in patients developing POF (37.7±5.9 years) in comparison with those not developing this complication (28.0±8.5 years, p=0.008). Moreover, the use of GnRH-a seems to be protective also in terms of menstrual cycle regularity: the cycle remained regular during treatment in 83.3% of GnRH-a+ and only in 33.3% of GnRH-a- (p=0.003). During the follow-up, 3 patients in the GnRH-a+ group underwent pregnancy, with a good outcome.ConclusionsThe results of the present study showed the protective role of GnRH-a for the preservation of ovarian function in SLE patients treated by CYC. Furthermore, the age resulted the only risk factor associated with POF development.References Andreoli L. et al. Ann Rheum Dis. 2016 Jul 25. Disclosu...

BackgroundOsteoarthritis (OA) is characterized by progressive loss of cartilage, deterioration of subchondral bone and mild synovial inflammation. Classified for a long time as a non-inflammatory arthropathy, a growing number of evidences has suggested that OA course could be driven by systemic and localized inflammation. In particular, serum levels of Interleukin (IL)-6 have been associated with higher prevalence of osteophytes in older adults with knee OA. Furthermore, high levels of other inflammatory cytokines have been identified in serum and synovial fluid of OA patients.ObjectivesIn the present cross-sectional study, we aimed at analyzing the correlation between articular inflammatory state, reflected by ultrasonographically-detected synovitis, and the serum levels of 27 cytokines, chemokines and growth factors in a cohort of primary knee OA.MethodsWe consecutively enrolled 47 patients (M/F 16/31, mean age ±SD 63.8±7.8 years, mean onset interval ±SD 70.0±78.6 months) affected by knees OA according to clinical and radiographic ACR criteria. Patients were excluded if they had received non-steroidal anti-inflammatory drugs or other analgesics within the 2 days before enrollment. Pain was assessed with a 100-mm visual analogue scale (VAS), and the Lequesne algo-functional index was used to measure the OA severity. BMI was registered. Each patient underwent ultrasonographic (US) assessment of both knees performed by a single operator. According with OMERACT definitions, we assessed the presence of synovial effusion, synovial hypertrophy and power Doppler. These elementary lesions were scored according to a semi-quantitative scale (0 = absent, 1 = mild, 2 = moderate and 3 = severe), the sum of them allows obtaining a total score of the patient's inflammatory state (0–18). Finally, blood samples for laboratory assays were obtained and commercially available multiplex bead based immunoassay kits (Human 27-plex, Bio-Rad laboratories, Hercules, CA) were used to measure concentrations of IL-1β, IL-1RA, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12, IL-13, IL-15, IL-17, FGF-Basic, G-CSF, GM-CSF, interferon-γ, IP-10, MCP-1, MIP-1α, MIP-1β, PDGF, RANTES, TNF, VEGF.ResultsAt the study enrollment, OA patients showed a mean±SD US synovitis score of 4.4±2.7, a mean±SD VAS pain rating of 53.3±16.6 mm (range 18–90 mm), a mean±SD Lequesne index of 10.2±4.2 (range 1.5–19), a mean±SD BMI of 26.8±4.2 (range 20–34.7). Positive correlations among US synovitis score and serum levels of IL-6 (r=0.3, p=0.01), IL-2 (r=0.3, p=0.01), IL-5 (r=0.3, p=0.01), IL-7 (r=0.3, p=0.03), MIP-1b (r=0.3, p=0.01), VEGF (r=0.3, p=0.02) were found. Moreover, US synovitis score positively correlated with Lequesne index (r=0.4, p=0.004) and BMI (r=0.4, p=0.04).ConclusionsThe results of the present study confirmed that OA may be associated with systemic inflammatory changes, as demonstrated by the positive correlation between US synovitis and several inflammatory cytokines serum levels.Disclosure of InterestNone declared