Guidelines for the management and treatment of periodic fever syndromes Cryopyrin-associated periodic syndromes (cryopyrinopathies – CAPS)

AbstractObjectiveTo establish guidelines based on cientific evidences for the management of cryopyrin associated periodic syndromes.Description of the evidence collection methodThe Guideline was prepared from 4 clinical questions that were structured through PICO (Patient, Intervention or indicator, Comparison and Outcome), to search in key primary scientific information databases. After defining the potential studies to support the recommendations, these were graduated considering their strength of evidence and grade of recommendation.Results1215 articles were retrieved and evaluated by title and abstract; from these, 42 articles were selected to support the recommendations.Recommendations1. The diagnosis of CAPS is based on clinical history and clinical manifestations, and later confirmed by genetic study. CAPS may manifest itself in three phenotypes: FCAS (mild form), MWS (intermediate form) and CINCA (severe form). Neurological, ophthalmic, otorhinolaryngological and radiological assessments may be highly valuable in distinguishing between syndromes; 2. The genetic diagnosis with NLRP3 gene analysis must be conducted in suspected cases of CAPS, i.e., individuals presenting before 20 years of age, recurrent episodes of inflammation expressed by a mild fever and urticaria; 3. Laboratory abnormalities include leukocytosis and elevated serum levels of inflammatory proteins; and 4. Targeted therapies directed against interleukin-1 lead to rapid remission of symptoms in most patients. However, there are important limitations on the long-term safety. None of the three anti-IL-1β inhibitors prevents progression of bone lesions

Endometriosis And Infertility: Cause Or Consequence? [endometriose E Infertilidade: Causa Ou Consequência?]

Endometriosis is a benign gynecological disorder affecting women of reproductive age and can have a varied symptomatology including chronic pelvic pain, dysmenorrhea, and infertility. The association of endometriosis and infertility has been recognized for years, although definite evidence of causality still eludes us. It is clear that in the advanced stage of the disease with mechanical disruption of the pelvic anatomy, infertility is easly explained. Nevertheless, the link between early stage endometriosis and infertility remains a source of controversy. The mechanisms of infertility associated with endometriosis include abnormal folliculogenesis, elevated oxidative stress, altered immune function, and hormonal milieu in the follicular and peritoneal environments, and reduced endometrial receptivity. These factors lead to poor oocyte quality, impaired fertilization, and implantation. In this manuscript we review the medical literature concerning the pathophysiology of the endometriosis-related infertility.1323338Abaé, M., Glassberg, M., Majercik, M.H., Yoshida, H., Vestal, R., Puett, D., Immunoreactive endothelin-1 concentrations in follicular fluid of women with and without endometriosis undergoing in vitro fertilization-embryo transfer (1994) Fertil Steril, 61, pp. 1083-1087Agarwal, A., Gupta, S., Sikka, S., The role of free radicals and antioxidants in reproduction (2006) Curr Opin Obstet Gynecol, 18, pp. 325-332Aitken, R.J., Krausz, C., Oxidative stress, DNA damage and the Y chromosome (2001) Reproduction, 122, pp. 497-506Al-Azemi, M., Bernal, A.L., Steele, J., Gramsbergen, I., Barlow, D., Kennedy, S., Ovarian response to repeated controlled stimulation in in-vitro fertilization cycles in patients with ovarian endometriosis (2000) Hum Reprod, 15, pp. 72-75Amaral, V.F., Bydlowski, S.P., Peranovich, T.C., Navarro, P.A., Subbiah, M.T., Ferriani, R.A., Lipid peroxidation in the peritoneal fluid of infertile women with peritoneal endometriosis (2005) Eur J Obstet Gynecol Reprod Biol, 119, pp. 72-75Awadalla, S.G., Friedman, C.I., Haq, A.U., Roh, S.I., Chin, N.W., Kim, M.H., Local peritoneal factors: Their role in infertility associated with endometriosis (1987) Am J Obstet Gynecol, 157, pp. 1207-1214Burns, W.N., Schenken, R.S., Pathophysiology of endometriosis-associated infertility (1999) Clin Obstet Gynecol, 42, pp. 586-610Cahill, D.J., Wardle, P.G., Maile, L.A., Harlow, C.R., Hull, M.G., Ovarian dysfunction in endometriosis-associated and unexplained infertility (1997) J Assist Reprod Genet, 14, pp. 554-557Carlberg, M., Nejaty, J., Fröysa, B., Guan, Y., Söder, O., Bergqvist, A., Elevated expression of tumour necrosis factor alpha in cultured granulosa cells from women with endometriosis (2000) Hum Reprod, 15, pp. 1250-1255Díaz, I., Navarro, J., Blasco, L., Simón, C., Pellicer, A., Remohí, J., Impact of stage III-IV endometriosis on recipients of sibling oocytes: Matched case-control study (2000) Fertil Steril, 74, pp. 31-34Dlugi, A.M., Loy, R.A., Dieterle, S., Bayer, S.R., Seibel, M.M., The effect of endometriomas on in vitro fertilization outcome (1989) J In Vitro Fert Embryo Transf, 6, pp. 338-341Garrido, N., Navarro, J., Remohí, J., Simón, C., Pellicer, A., Follicular hormonal environment and embryo quality in women with endometriosis (2000) Hum Reprod Update, 6, pp. 67-74Gupta, S., Goldberg, J.M., Aziz, N., Goldberg, E., Krajcir, N., Agarwal, A., Pathogenic mechanisms in endometriosis-associated infertility (2008) Fertil Steril, 90, pp. 247-257Harlow, C.R., Cahill, D.J., Maile, L.A., Talbot, W.M., Mears, J., Wardle, P.G., Reduced preovulatory granulosa cell steroidogenesis in women with endometriosis (1996) J Clin Endocrinol Metab, 81, pp. 426-429Inoue, M., Kobayashi, Y., Honda, I., Awaji, H., Fujii, A., The impact of endometriosis on the reproductive outcome of infertile patients (1992) Am J Obstet Gynecol, 167, pp. 278-282Jha, P., Farooq, A., Agarwal, N., Buckshee, K., In vitro sperm phagocytosis by human peritoneal macrophages in endometriosis-associated infertility (1996) Am J Reprod Immunol, 36, pp. 235-237Khorram, O., Lessey, B.A., Alterations in expression of endometrial endothelial nitric oxide synthase and alpha(v)beta(3) integrin in women with endometriosis (2002) Fertil Steril, 78, pp. 860-864Lebovic, D.I., Mueller, M.D., Taylor, R.N., Immunobiology of endometriosis (2001) Fertil Steril, 75, pp. 1-10Lessey, B.A., Castelbaum, A.J., Buck, C.A., Lei, Y., Yowell, C.W., Sun, J., Further characterization of endometrial integrins during the menstrual cycle and in pregnancy (1994) Fertil Steril, 62, pp. 497-506Loh, F.H., Tan, A.T., Kumar, J., Ng, S.C., Ovarian response after laparoscopic ovarian cystectomy for endometriotic cysts in 132 monitored cycles (1999) Fertil Steril, 72, pp. 316-321Mahmood, T.A., Templeton, A., Folliculogenesis and ovulation in infertile women with mild endometriosis (1991) Hum Reprod, 6, pp. 227-231Marcoux, S., Maheux, R., Bérubé, S., Laparoscopic surgery in infertile women with minimal or mild endometriosis. Canadian Collaborative Group on Endometriosis (1997) N Engl J Med, 337, pp. 217-222Mathur, S., Peress, M.R., Williamson, H.O., Youmans, C.D., Maney, S.A., Garvin, A.J., Autoimmunity to endometrium and ovary in endometriosis (1982) Clin Exp Immunol, 50, pp. 259-266Matson, P.L., Yovich, J.L., The treatment of infertility associated with endometriosis by in vitro fertilization (1986) Fertil Steril, 46, pp. 432-434Navarro, J., Garrido, N., Remohí, J., Pellicer, A., How does endometriosis affect infertility? (2003) Obstet Gynecol Clin North Am, 30, pp. 181-192Oosterlynck, D.J., Meuleman, C., Waer, M., Koninckx, P.R., Vandeputte, M., Immunosuppressive activity of peritoneal fluid in women with endometriosis (1993) Obstet Gynecol, 82, pp. 206-212Pal, L., Shifren, J.L., Isaacson, K.B., Chang, Y., Leykin, L., Toth, T.L., Impact of varying stages of endometriosis on the outcome of in vitro fertilization-embryo transfer (1998) J Assist Reprod Genet, 15, pp. 27-31Parazzini, F., Ablation of lesions or no treatment in minimal-mild endometriosis in infertile women: A randomized trial. Gruppo Italiano per lo Studio dell'Endometriosi (1999) Hum Reprod, 14, pp. 1332-1334Pellicer, A., Oliveira, N., Ruiz, A., Remohí, J., Simón, C., Exploring the mechanism(s) of endometriosis-related infertility: An analysis of embryo development and implantation in assisted reproduction (1995) Hum Reprod, 10 (SUPPL. 2), pp. 91-97Pellicer, A., Albert, C., Mercader, A., Bonilla-Musoles, F., Remohí, J., Simón, C., The follicular and endocrine environment in women with endometriosis: Local and systemic cytokine production (1998) Fertil Steril, 70, pp. 425-431Pellicer, A., Valbuena, D., Bauset, C., Albert, C., Bonilla-Musoles, F., Remohí, J., The follicular endocrine environment in stimulated cycles of women with endometriosis: Steroid levels and embryo quality (1998) Fertil Steril, 69, pp. 1135-1141Pellicer, A., Albert, C., Garrido, N., Navarro, J., Remohí, J., Simón, C., The pathophysiology of endometriosis-associated infertility: Follicular environment and embryo quality (2000) J Reprod Fertil Suppl, 55, pp. 109-119Pritts, E.A., Taylor, R.N., An evidence-based evaluation of endometriosis-associated infertility (2003) Endocrinol Metab Clin North Am, 32, pp. 653-667Qiao, J., Yeung, W.S., Yao, Y.Q., Ho, P.C., The effects of follicular fluid from patients with different indications for IVF treatment on the binding of human spermatozoa to the zona pellucida (1998) Hum Reprod, 13, pp. 128-131Said, T.M., Agarwal, A., Falcone, T., Sharma, R.K., Bedaiwy, M.A., Li, L., Infliximab may reverse the toxic effects induced by tumor necrosis factor alpha in human spermatozoa: An in vitro model (2005) Fertil Steril, 83, pp. 1665-1673Saito, H., Seino, T., Kaneko, T., Nakahara, K., Toya, M., Kurachi, H., Endometriosis and oocyte quality (2002) Gynecol Obstet Invest, 53 (SUPPL. 1), pp. 46-51Simón C, Gutiérrez A, Vidal A, de los Santos MJ, Tarín JJ, Remohí J, et al. 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Positive correlation of serum leptin with estradiol levels in patients with polycystic ovary syndrome

Patients with polycystic ovary syndrome (PCOS) usually are obese, insulin resistant and hyperinsulinemic. The known association between leptin, obesity andinsulin action suggests that leptin may have a role in PCOS but this has only been addressed peripherally. This study was designed to assess the relationship between serum leptin and the anthropometric, metabolic and endocrine variables of obese (body mass index, BMI ³30 kg/m²) and non-obese (BMI <30 kg/m²) PCOS patients. Twenty-eight PCOS patients and 24 control women subdivided into obese and non-obese groups were evaluated. Leptin, androgens, lipids, gonadotrophins and insulin-glucose response to the oral glucose tolerance test were measured by radioimmunoassay in all participants. The assays were done all in one time. The areas under the insulin curve (AUC-I) and the glycemia curve were calculated to identify patients with insulin resistance. Mean leptin levels were not significantly higher in patients with PCOS compared to the control group (21.2 ± 10.2 vs 27.3 ± 12.4 ng/ml). Leptin levels were found to be significantly higher in the obese subgroups both in patients with PCOS (26.9 ± 9.3 vs 14.1 ± 7.0 ng/ml) and in the control group (37.3 ± 15.5 vs 12.9 ± 5.8 ng/ml). The leptin of the PCOS group was correlated with BMI (r = 0.74; P < 0.0001) and estradiol (r = 0.48; P < 0.008) and tended to be correlated with the AUC-I (r = 0.36; P = 0.05). Of the parameters which showed a correlation with leptin in PCOS, only estradiol and probably insulinemia (AUC-I) did not show a significant correlation with BMI, suggesting that the other parameters were correlated with leptin due to their correlation with BMI. Estradiol correlated with leptin in PCOS patients regardless of their weight