L'Envelliment, aproximació a un procés complex i heterogeni

L'envelliment és un procés complex i heterogeni, no tots envellim de la mateixa manera. En els últims anys s'han incorporat nous conceptes clínics i biològics que poden arribar a qüestionar la natura fisiològica del procés. En aquest capítol es defineix el procés i la seva repercussió en la nostra societat, s'incorporen conceptes com ara la fragilitat, la comorbiditat o la discapacitat, que permeten entendre millor i més bé les repercussions de l'envelliment sobre el nostre organisme, i s'analitzen les peculiaritats dels que envelleixen de manera satisfactòria i arriben a centenaris. Es discuteix el concepte anti-aging des d'una vessant científica i analitzant altres connotacions del concepte. Finalment, s'intenta relacionar l'envelliment del sistema immunitari (immunosenescència) amb algunes malalties autoimmunitàries sistèmiques com ara l'esclerodèrmia i l'arteritis de cèŀlules gegants, i es comenta la progèria i les síndromes progeroides com a models d'estudi de l'envelliment.Aging is a complex and heterogeneous process, with relevant differences between subjects. Conceptual, clinic and biological concepts which can challenge the physiologic nature of aging have been incorporated during the last years. In this chapter a proper definition of aging and the social repercussion of the phenomenon is established, and new concepts such as fragility, comorbidity and discapacity which allow a better understanding of aging and related pathology are described. Centenarians and its rationale is also discussed and analyzed, along with the anti-aging phenomenon and its repercussions on agining. Lastly, a possible relationship between some autoimmune systemic diseases such as systemic sclerosis and giant cell vasculitis (Horton’s disease) and immunosenescence, and also the progeroid syndromes as a model of aging are addressed

Efficacy and safety of lenalidomide for refractory cutaneous lupus erythematosus

Introduction: Cutaneous lupus erythematosus (CLE) is a chronic disease characterized by disfigurement and a relapsing course. Thalidomide has proven its efficacy in refractory cutaneous lupus disease, although it is not exempt from significant side effects and frequent relapses after withdrawal. New thalidomide analogues have been developed but lack clinical experience. The aim of this preliminary phase II study was to evaluate the efficacy and safety of lenalidomide in patients with refractory CLE. Methods: Fifteen patients with refractory cutaneous lupus disease were enrolled in this single-center, open-label, non-comparative pilot trial between January 2009 and December 2010. Oral lenalidomide (5 to 10 mg/day) was administered and tapered according to clinical response. Patients were followed up for a mean of 15 months (range: 7 to 30). Primary efficacy endpoint was the proportion of patients achieving complete response, defined by a Cutaneous Lupus Erythematosus Disease Area and Severity index (CLASI) activity score of 0. Other secondary endpoints included development of side effects, evaluation of cutaneous and systemic flares, and impact on the immunological parameters.Results: One patient discontinued treatment due to side effects. All remaining patients saw clinical improvement and this was already noticeable after 2 weeks of treatment. Twelve of those patients (86%) achieved complete response but clinical relapse was frequent (75%), usually occurring 2 to 8 weeks after lenalidomide's withdrawal. No influence on systemic disease, immunological parameters or CLASI damage score was observed. Side effects including insomnia, grade 2 neutropenia and gastrointestinal symptoms, were minor (13%). These resolved after withdrawing medication. Neither polyneuropathy nor thrombosis was observed. Conclusion: Lenalidomide appears to be efficacious and safe in patients with refractory CLE, but clinical relapse is frequent after its withdrawal

Intravenous Cyclophosphamide Pulse Therapy in the Treatment of Systemic Sclerosis-Related Interstitial Lung Disease: A Long Term Study

Interstitial lung disease (ILD) frequently complicates systemic sclerosis (SSc). Cyclophosphamide (CYC) is a promising immunosuppressive therapy for SSc-related ILD. Our objective was to investigate the effectiveness of an intravenous CYC (iv CYC) pulse regime in SSc-related ILD during treatment and thereafter. In a prospective observational study ten consecutive patients with SSc-related ILD were treated with iv CYC in a pulse regime lasting from 6 to 24 months. Clinical status, pulmonary functional testing (PFT) and high resolution computed tomography (HRCT) of the chest were evaluated at enrolment and 6, 12 and 24 months thereafter. After treatment withdrawal, patients were followed up every 6 months with PFT and chest HRCT to monitor lung disease. Clinical improvement was apparent in 8 out of 10 patients. The median values of forced vital capacity (FVC), forced expiratory volume in the first second (FEV1) and diffusion lung capacity for carbon monoxide (DLCO) as well as ground-glass pattern on HRCT did not change significantly after 6, 12 and 24 months of therapy. The follow-up continued in 8 out of 10 patients after treatment withdrawal for a median of 26.5 months (range: 12-48 months). The final median FVC was 54.5% of predicted value (interquartile range, IQR= 31.6%-94%). Only one patient suffered a FVC deterioration greater than 10%, even though less than 160 ml. The final median DLCO was 68% of predicted value (IQR=38.3-83.6%). Only 2 patients who developed pulmonary arterial hypertension deteriorated their DLCO values of more than 15%. An iv CYC pulse regimen over 24 months may stabilize pulmonary activity in patients with SSc-related ILD during the course of treatment and for a median of 26.5 months thereafter

Registry of the Spanish network for systemic sclerosis: survival, prognostic factors, and causes of death

Systemic sclerosis (SSc) is a rare, multisystem disease showing a large individual variability in disease progression and prognosis. In the present study, we assess survival, causes of death, and risk factors of mortality in a large series of Spanish SSc patients. Consecutive SSc patients fulfilling criteria of the classification by LeRoy were recruited in the survey. Kaplan-Meier and Cox proportional-hazards models were used to analyze survival and to identify predictors of mortality. Among 879 consecutive patients, 138 (15.7%) deaths were registered. Seventy-six out of 138 (55%) deceased patients were due to causes attributed to SSc, and pulmonary hypertension (PH) was the leading cause in 23 (16.6%) patients. Survival rates were 96%, 93%, 83%, and 73% at 5, 10, 20, and 30 years after the first symptom, respectively. Survival rates for diffuse cutaneous SSc (dcSSc) and limited cutaneous SSc were 91%, 86%, 64%, and 39%; and 97%, 95%, 85%, and 81% at 5, 10, 20, and 30 years, respectively (log-rank: 67.63, P < 0.0001). The dcSSc subset, male sex, age at disease onset older than 65 years, digital ulcers, interstitial lung disease (ILD), PH, heart involvement, scleroderma renal crisis (SRC), presence of antitopoisomerase I and absence of anticentromere antibodies, and active capillaroscopic pattern showed reduced survival rate. In a multivariate analysis, older age at disease onset, dcSSc, ILD, PH, and SRC were independent risk factors for mortality. In the present study involving a large cohort of SSc patients, a high prevalence of disease-related causes of death was demonstrated. Older age at disease onset, dcSSc, ILD, PH, and SRC were identified as independent prognostic factors

L'Envelliment, aproximació a un procés complex i heterogeni

L'envelliment és un procés complex i heterogeni, no tots envellim de la mateixa manera. En els últims anys s'han incorporat nous conceptes clínics i biològics que poden arribar a qüestionar la natura fisiològica del procés. En aquest capítol es defineix el procés i la seva repercussió en la nostra societat, s'incorporen conceptes com ara la fragilitat, la comorbiditat o la discapacitat, que permeten entendre millor i més bé les repercussions de l'envelliment sobre el nostre organisme, i s'analitzen les peculiaritats dels que envelleixen de manera satisfactòria i arriben a centenaris. Es discuteix el concepte anti-aging des d'una vessant científica i analitzant altres connotacions del concepte. Finalment, s'intenta relacionar l'envelliment del sistema immunitari (immunosenescència) amb algunes malalties autoimmunitàries sistèmiques com ara l'esclerodèrmia i l'arteritis de cè&#320;lules gegants, i es comenta la progèria i les síndromes progeroides com a models d'estudi de l'envelliment.Aging is a complex and heterogeneous process, with relevant differences between subjects. Conceptual, clinic and biological concepts which can challenge the physiologic nature of aging have been incorporated during the last years. In this chapter a proper definition of aging and the social repercussion of the phenomenon is established, and new concepts such as fragility, comorbidity and discapacity which allow a better understanding of aging and related pathology are described. Centenarians and its rationale is also discussed and analyzed, along with the anti-aging henomenon and its repercussions on agining. Lastly, a possible relationship between some autoimmune systemic diseases such as systemic sclerosis and giant cell vasculitis (Hortons disease) and immunosenescence, and also the progeroid syndromes as a model of aging are addressed

Efficacy and safety of lenalidomide for refractory cutaneous lupus erythematosus

Introduction: Cutaneous lupus erythematosus (CLE) is a chronic disease characterized by disfigurement and a relapsing course. Thalidomide has proven its efficacy in refractory cutaneous lupus disease, although it is not exempt from significant side effects and frequent relapses after withdrawal. New thalidomide analogues have been developed but lack clinical experience. The aim of this preliminary phase II study was to evaluate the efficacy and safety of lenalidomide in patients with refractory CLE. Methods: Fifteen patients with refractory cutaneous lupus disease were enrolled in this single-center, open-label, non-comparative pilot trial between January 2009 and December 2010. Oral lenalidomide (5 to 10 mg/day) was administered and tapered according to clinical response. Patients were followed up for a mean of 15 months (range: 7 to 30). Primary efficacy endpoint was the proportion of patients achieving complete response, defined by a Cutaneous Lupus Erythematosus Disease Area and Severity index (CLASI) activity score of 0. Other secondary endpoints included development of side effects, evaluation of cutaneous and systemic flares, and impact on the immunological parameters.Results: One patient discontinued treatment due to side effects. All remaining patients saw clinical improvement and this was already noticeable after 2 weeks of treatment. Twelve of those patients (86%) achieved complete response but clinical relapse was frequent (75%), usually occurring 2 to 8 weeks after lenalidomide's withdrawal. No influence on systemic disease, immunological parameters or CLASI damage score was observed. Side effects including insomnia, grade 2 neutropenia and gastrointestinal symptoms, were minor (13%). These resolved after withdrawing medication. Neither polyneuropathy nor thrombosis was observed. Conclusion: Lenalidomide appears to be efficacious and safe in patients with refractory CLE, but clinical relapse is frequent after its withdrawal