Centre for Multidisciplinary Research in Health Science

Periodontal diseases and dental caries are the most common diseases of humans and the main cause of tooth loss. Both diseases can lead to nutritional compromise and negative impacts upon self-esteem and quality of life. As complex chronic diseases, they share common risk factors, such as a requirement for a pathogenic plaque biofilm, yet they exhibit distinct pathophysiologies. Multiple exposures contribute to their causal pathways, and susceptibility involves risk factors that are inherited (e.g. genetic variants), and those that are acquired (e.g. socio-economic factors, biofilm load or composition, smoking, carbohydrate intake). Identification of these factors is crucial in the prevention of both diseases as well as in their management. AIM: To systematically appraise the scientific literature to identify potential risk factors for caries and periodontal diseases. METHODS: One systematic review (genetic risk factors), one narrative review (role of diet and nutrition) and reference documentation for modifiable acquired risk factors common to both disease groups, formed the basis of the report. RESULTS & CONCLUSIONS: There is moderately strong evidence for a genetic contribution to periodontal diseases and caries susceptibility, with an attributable risk estimated to be up to 50%. The genetics literature for periodontal disease is more substantial than for caries and genes associated with chronic periodontitis are the vitamin D receptor (VDR), Fc gamma receptor IIA (Fc-γRIIA) and Interleukin 10 (IL10) genes. For caries, genes involved in enamel formation (AMELX, AMBN, ENAM, TUFT, MMP20, and KLK4), salivary characteristics (AQP5), immune regulation and dietary preferences had the largest impact. No common genetic variants were found. Fermentable carbohydrates (sugars and starches) were the most relevant common dietary risk factor for both diseases, but associated mechanisms differed. In caries, the fermentation process leads to acid production and the generation of biofilm components such as Glucans. In periodontitis, glycaemia drives oxidative stress and advanced glycation end-products may also trigger a hyper inflammatory state. Micronutrient deficiencies, such as for vitamin C, vitamin D or vitamin B12, may be related to the onset and progression of both diseases. Functional foods or probiotics could be helpful in caries prevention and periodontal disease management, although evidence is limited and biological mechanisms not fully elucidated. Hyposalivation, rheumatoid arthritis, smoking/tobacco use, undiagnosed or sub-optimally controlled diabetes and obesity are common acquired risk factors for both caries and periodontal diseases.

BACKGROUND: Clinical data suggest that the presence of an ovarian endometrioma may cause per se damage to the surrounding otherwise healthy ovarian tissue. However, the basic research has so far done a limited job in trying to understand the potential detrimental effect of an endometrioma presence in the context of the ovarian physiology. We have reviewed the literature with the aim of characterizing the pathophysiology of the endometrioma focusing mostly on factors and mechanisms potentially affecting the surrounding, otherwise normal, ovarian tissue. METHODS: Comprehensive searches of PUBMED were conducted to identify human studies published from 1991 to 2013 in the English language on the cellular and molecular characterization of the various endometrioma components. RESULTS: An endometrioma contains free iron, reactive oxygen species (ROS), proteolytic enzymes and inflammatory molecules in concentrations from tens to hundreds of times higher than those present in peripheral blood or in other types of benign cysts. The cyst fluid causes substantial changes in the endometriotic cells that it baths from gene expression modifications to genetic mutations The physical barrier between the cyst contents and the normal ovarian tissue is a thin wall composed of the ovarian cortex itself or fibroreactive tissue. ROS potentially permeating the surrounding tissues and proteolytic substances degrading the adjacent areas are likely to cause the substitution of normal ovarian cortical tissue with fibrous tissue in which the cortex-specific stroma is reduced. The fibrosis is associated with smooth muscle metaplasia and followed by follicular loss and intraovarian vascular injury. Follicular density in tissue surrounding the endometriotic cyst was consistently shown to be significantly lower than in healthy ovaries but this pathological change does not appear to be caused by the stretching of surrounding tissues owing to the presence of a cyst. CONCLUSIONS: There is sufficient molecular, histological and morphological evidence, in part deriving from knowledge of the pathophysiology, to support a deleterious effect of the endometrioma on the adjacent ovarian cortical tissue, independent of the mere mechanical stretching owing to its size.

Little is known about the relationship between the COVID-19 and tuberculosis (TB). The aim of this study is to describe a group of patients who died with TB (active disease or sequelae) and COVID-19 in two cohorts. Data from 49 consecutive cases in 8 countries (cohort A) and 20 hospitalised patients with TB and COVID-19 (cohort B) were analysed and patients who died were described. Demographic and clinical variables were retrospectively collected, including co-morbidities and risk factors for TB and COVID-19 mortality. Overall, 8 out of 69 (11.6%) patients died, 7 from cohort A (14.3%) and one from cohort B (5%). Out of 69 patients 43 were migrants, 26/49 (53.1%) in cohort A and 17/20 (85.0%) in cohort B. Migrants: (1) were younger than natives; in cohort A the median (IQR) age was 40 (27-49) VS. 66 (46-70) years, whereas in cohort B 37 (27-46) VS. 48 (47-60) years; (2) had a lower mortality rate than natives (1/43, 2.3% versus 7/26, 26.9%; p-value: 0.002); (3) had fewer co-morbidities than natives (23/43, 53.5% versus 5/26-19.2%) natives; p-value: 0.005). The study findings show that: (1) mortality is likely to occur in elderly patients with co-morbidities; (2) TB might not be a major determinant of mortality and (3) migrants had lower mortality, probably because of their younger age and lower number of co-morbidities. However, in settings where advanced forms of TB frequently occur and are caused by drug-resistant strains of M. tuberculosis, higher mortality rates can be expected in young individuals.

The term “hemp” refers to Cannabis sativa cultivars grown for industrial purposes that are characterized by lower levels of tetrahydrocannabinol (THC), the active principle responsible for Cannabis psychotropic effects. Hemp is an extraordinary crop, with enormous social and economic value, since it can be used to produce food, textiles, clothing, biodegradable plastics, paper, paint, biofuel, and animal feed, as well as lighting oil. Various parts of the hemp plant represent a valuable source of food and ingredients for nutritional supplements. While hemp inflorescence is rich in nonpsychoactive, yet biologically active cannabinoids, such as cannabidiol (CBD), which exerts potent anxiolytic, spasmolytic, as well as anticonvulsant effects, hempseed has a pleasant nutty taste and represents a valuable source of essential amino acids and fatty acids, minerals, vitamins, and fibers. In addition, hempseed oil is a source of healthy polyunsaturated fatty acids, and hemp sprouts are rich in antioxidants. This review article aims to provide a comprehensive outlook from a multidisciplinary perspective on the scientific evidence supporting hemp beneficial properties when consumed as food or supplement. Marketing of hemp-derived products is subjected to diversified and complex regulations worldwide for several reasons, including the fact that CBD is also the active principal of pharmaceutical agents and that regulatory bodies in some cases ban Cannabis inflorescence regardless of its THC content. Some key regulatory aspects of such a complex scenario are also analyzed and discussed in this review article.

Gender-specific medicine is the study of how diseases differ between men and women in terms of prevention, clinical signs, therapeutic approach, prognosis, psychological and social impact. It is a neglected dimension of medicine. In this review we like to point out some major issues in five enormous fields of medicine: cardiovascular diseases (CVDs), pharmacology, oncology, liver diseases and osteoporosis. CVDs have been studied in the last decades mainly in men, but they are the first cause of mortality and disability in women. Risk factors for CVD have different impacts in men and women; clinical manifestations of CVD and the influence of drugs on CVD have lot of gender differences. Sex-related differences in pharmacokinetics and pharmacodynamics are also emerging. These differences have obvious relevance to the efficacy and side effect profiles of various medications in the two sexes. This evidence should be considered for drug development as well as before starting any therapy. Gender disparity in cancer incidence, aggressiveness and prognosis has been observed for a variety of cancers and, even if partially known, is underestimated in clinical practice for the treatment of the major types of cancer. It is necessary to systematize and encode all the known data for each type of tumor on gender differences, to identify where this variable has to be considered for the purposes of the prognosis, the choice of treatment and possible toxicity. Clinical data suggest that men and women exhibit differences regarding the epidemiology and the progression of certain liver diseases, i.e., autoimmune conditions, genetic hemochromatosis, non-alcoholic steatohepatitis and chronic hepatitis C. Numerous hypotheses have been formulated to justify this sex imbalance including sex hormones, reproductive and genetic factors. Nevertheless, none of these hypothesis has thus far gathered enough convincing evidence and in most cases the evidence is conflicting. Osteoporosis is an important public health problem both in women and men. On the whole, far more epidemiologic, diagnostic and therapeutic studies have been carried out in women than in men. In clinical practice, if this disease remains underestimated in women, patients' and physicians' awareness is even lower for male osteoporosis, for which diagnostic and therapeutic strategies are at present less defined. In conclusion this review emphasizes the urgency of basic science and clinical research to increase our understanding of the gender differences of diseases.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant of concern comprises several sublineages, with BA.2 and BA.2.12.1 having replaced the previously dominant BA.1 and with BA.4 and BA.5 increasing in prevalence worldwide. We show that the large number of Omicron sublineage spike mutations leads to enhanced angiotensin-converting enzyme 2 (ACE2) binding, reduced fusogenicity, and severe dampening of plasma neutralizing activity elicited by infection or seven clinical vaccines relative to the ancestral virus. Administration of a homologous or heterologous booster based on the Wuhan-Hu-1 spike sequence markedly increased neutralizing antibody titers and breadth against BA.1, BA.2, BA.2.12.1, BA.4, and BA.5 across all vaccines evaluated. Our data suggest that although Omicron sublineages evade polyclonal neutralizing antibody responses elicited by primary vaccine series, vaccine boosters may provide sufficient protection against Omicron-induced severe disease.

Characterization of the immune responses to SARS-CoV-2 reveals a CD8 + T cell subset that likely establishes the memory to the virus.

<b>The COVID-19 infection rate was high in patients with active tuberculosis. Major clinical complications were seen only in two patients, thus requiring <i>ex novo</i> oxygen supply, one of whom with advanced tuberculosis died. Nasal swab viral clearance was rapid.</b>https://bit.ly/3cdvdZJ

Major epidemics, including some that qualify as pandemics, such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), HIV, influenza A (H1N1)pdm/09 and most recently COVID-19, affect the lung. Tuberculosis (TB) remains the top infectious disease killer, but apart from syndemic TB/HIV little is known regarding the interaction of viral epidemics and pandemics with TB. The aim of this consensus-based document is to describe the effects of viral infections resulting in epidemics and pandemics that affect the lung (MERS, SARS, HIV, influenza A (H1N1)pdm/09 and COVID-19) and their interactions with TB. A search of the scientific literature was performed. A writing committee of international experts including the European Centre for Disease Prevention and Control Public Health Emergency (ECDC PHE) team, the World Association for Infectious Diseases and Immunological Disorders (WAidid), the Global Tuberculosis Network (GTN), and members of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Mycobacterial Infections (ESGMYC) was established. Consensus was achieved after multiple rounds of revisions between the writing committee and a larger expert group. A Delphi process involving the core group of authors (excluding the ECDC PHE team) identified the areas requiring review/consensus, followed by a second round to refine the definitive consensus elements. The epidemiology and immunology of these viral infections and their interactions with TB are discussed with implications for diagnosis, treatment and prevention of airborne infections (infection control, viral containment and workplace safety). This consensus document represents a rapid and comprehensive summary on what is known on the topic.

Please cite this paper as: Vercellini P, Parazzini F, Pietropaolo G, Cipriani S, Frattaruolo M, Fedele L. Pregnancy outcome in women with peritoneal, ovarian and rectovaginal endometriosis: a retrospective cohort study. BJOG 2012;119:1538–1543. We retrospectively assessed pregnancy outcome in 419 women who achieved a first spontaneous singleton pregnancy after surgery for endometriosis. A miscarriage was observed in 87 of 419 women (20.8%) and an ectopic pregnancy in eight (1.9%). Among the remaining 324 women, 14 (4.3%) experienced gestational hypertension/pre‐eclampsia, 38 (11.7%) had a preterm delivery, five (1.5%) had placental abruption and 12 (3.7%) had placenta praevia. The incidence of placenta praevia was 7.6% in 150 women with rectovaginal lesions, 2.1% in 69 with ovarian endometriomas plus peritoneal implants, and 2.4% in 100 women with peritoneal implants only, whereas no case was observed in 100 women with ovarian endometriomas only.

BACKGROUND: Assessing caries risk is an essential element in the planning of preventive and therapeutic strategies. Different caries risk assessment (CRA) models have been proposed for the identification of individuals running a risk of future caries. This systematic review was designed to evaluate whether standardized caries risk assessment (CRA) models are able to evaluate the risk according to the actual caries status and/or the future caries increment. METHODS: Randomized clinical trials, cross-sectional studies, cohort studies, comparative studies, validation studies and evaluation studies, reporting caries risk assessment using standardized models (Cariogram, CAMBRA, PreViser, NUS-CRA and CAT) in patients of any age related to caries data recorded by DMFT/S or ICDAS indices, were included. PubMed, Scopus and Embase were searched from 2000 to 2016. A search string was developed. All the papers meeting the inclusion criteria were subjected to a quality assessment. RESULTS: One thousand three-undred ninety-two papers were identified and 32 were included. In all but one, the Cariogram was used both as sole model or in conjunction with other models. All the papers on children (n = 16) and adults (n = 12) found a statistically significant association between the risk levels and the actual caries status and/or the future caries increment. Nineteen papers, all using the Cariogram except one, were classified as being of good quality. Three of four papers comprising children and adults found a positive association. For seven of the included papers, Cariogram sensibility and specificity were calculated; sensibility ranged from low (41.0) to fairly low (75.0), while specificity was higher, ranging from 65.8 to 88.0. Wide 95% confidence intervals for both parameters were found, indicating that the reliability of the model differed in different caries risk levels. CONCLUSIONS: The scientific evidence relating to standardized CRA models is still limited; even if Cariogram was tested in children and adults in few studies of good quality, no sufficient evidence is available to affirm the method is effective in caries assessment and prediction. New options of diagnosis, prognosis and therapy are now available to dentists but the validity of standardized CRA models still remains limited.

OBJECTIVE: To detect a direct transition from a haemorrhagic corpus luteum to an endometriotic cyst by serial transvaginal ultrasonographic scans. DESIGN: Prospective observational study. SETTING: An academic tertiary care and referral centre for women with endometriosis. POPULATION: One hundred and nine women younger than 40 years, with regular menstrual cycles, undergoing first-line surgery for endometriomas, and not wanting postoperative oral contraception. METHODS: Three-monthly transvaginal ultrasonography during the luteal phase for 2 years after surgery. MAIN OUTCOME MEASURE: Sonographic identification of progression from a haemorrhagic corpus luteum to a recurrent endometriotic cyst. RESULTS: A haemorrhagic corpus luteum was identified in 13 women. Serial ultrasonographic scans demonstrated transition to an endometriotic cyst in 11 (85%) instances and resorption in two. A unilateral endometriotic cyst without previous detection of a cystic corpus luteum was observed in 14 women. CONCLUSIONS: Bleeding from a corpus luteum appears to be a critical event in the development of endometriomas.

Further information on research design is available in the Nature Portfolio Reporting Summary linked to this article.

The gut microbiota plays a crucial role in human health and disease. Gut dysbiosis is known to be associated with increased susceptibility to respiratory diseases and modifications in the immune response and homeostasis of the lungs (the so-called gut-lung axis). Furthermore, recent studies have highlighted the possible role of dysbiosis in neurological disturbances, introducing the notion of the "gut-brain axis." During the last 2 years, several studies have described the presence of gut dysbiosis during coronavirus disease 2019 (COVID-19) and its relationship with disease severity, SARS-CoV-2 gastrointestinal replication, and immune inflammation. Moreover, the possible persistence of gut dysbiosis after disease resolution may be linked to long-COVID syndrome and particularly to its neurological manifestations. We reviewed recent evidence on the association between dysbiosis and COVID-19, investigating the possible epidemiologic confounding factors like age, location, sex, sample size, the severity of disease, comorbidities, therapy, and vaccination status on gut and airway microbial dysbiosis in selected studies on both COVID-19 and long-COVID. Moreover, we analyzed the confounding factors strictly related to microbiota, specifically diet investigation and previous use of antibiotics/probiotics, and the methodology used to study the microbiota (α- and β-diversity parameters and relative abundance tools). Of note, only a few studies focused on longitudinal analyses, especially for long-term observation in long-COVID. Lastly, there is a lack of knowledge regarding the role of microbiota transplantation and other therapeutic approaches and their possible impact on disease progression and severity. Preliminary data seem to suggest that gut and airway dysbiosis might play a role in COVID-19 and in long-COVID neurological symptoms. Indeed, the development and interpretation of these data could have important implications for future preventive and therapeutic strategies.

Given the highly variable clinical phenotype of Coronavirus disease 2019 (COVID-19), a deeper analysis of the host genetic contribution to severe COVID-19 is important to improve our understanding of underlying disease mechanisms. Here, we describe an extended genome-wide association meta-analysis of a well-characterized cohort of 3255 COVID-19 patients with respiratory failure and 12 488 population controls from Italy, Spain, Norway and Germany/Austria, including stratified analyses based on age, sex and disease severity, as well as targeted analyses of chromosome Y haplotypes, the human leukocyte antigen region and the SARS-CoV-2 peptidome. By inversion imputation, we traced a reported association at 17q21.31 to a ~0.9-Mb inversion polymorphism that creates two highly differentiated haplotypes and characterized the potential effects of the inversion in detail. Our data, together with the 5th release of summary statistics from the COVID-19 Host Genetics Initiative including non-Caucasian individuals, also identified a new locus at 19q13.33, including NAPSA, a gene which is expressed primarily in alveolar cells responsible for gas exchange in the lung.

BACKGROUND: Tuberculosis (TB) is a major public health problem and at 48%, Karamoja in North-Eastern Uganda has the lowest treatment success rate nationally. Addressing the social determinants of TB is crucial to ending TB. This study sought to understand the extent and ways in which socio-economic factors affect TB treatment outcomes in Karamoja. METHODS: We conducted a convergent parallel mixed methods study in 10 TB Diagnostic and Treatment Units. The study enrolled former TB patients diagnosed with drug-susceptible TB between April 2018 and March 2019. Unit TB and laboratory registers were reviewed to identify pre-treatment losses to follow-up. Four focus group discussions with former TB patients and 18 key informant interviews with healthcare workers were conducted. Principle component analysis was used to generate wealth quintiles that were compared to treatment outcomes using the proportion test. The association between sociodemographic characteristics and TB treatment outcomes was evaluated using the chi-square test and multiple logistic regression. RESULTS: A total of 313 participants were randomly selected from 1184 former TB patients recorded in the unit TB registers. Of these, 264 were contacted in the community and consented to join the study: 57% were male and 156 (59.1%) participants had unsuccessful treatment outcomes. The wealthiest quintile had a 58% reduction in the risk of having an unsuccessful treatment outcome (adj OR = 0.42, 95% CI 0.18-0.99, p = 0.047). People who were employed in the informal sector (adj OR = 4.71, 95% CI 1.18-18.89, p = 0.029) and children under the age of 15 years who were not in school or employed (adj OR = 2.71, 95% CI 1.11-6.62, p = 0.029) had significantly higher odds of unsuccessful treatment outcome. Analysis of the pre-treatment loss to follow-up showed that 17.2% of patients with pulmonary bacteriologically confirmed TB did not initiate treatment with a higher proportion among females (21.7%) than males (13.5%). Inadequate food, belonging to migratory communities, stigma, lack of social protection, drug stock-outs and transport challenges affected TB treatment outcomes. CONCLUSIONS: This study confirmed that low socio-economic status is associated with poor TB treatment outcomes emphasizing the need for multi- and cross-sectoral approaches and socio-economic enablers to optimise TB care.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by beta-coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has rapidly spread across the globe starting from February 2020. It is well established that during viral infection, extracellular vesicles become delivery/presenting vectors of viral material. However, studies regarding extracellular vesicle function in COVID-19 pathology are still scanty. Here, we performed a comparative study on exosomes recovered from the plasma of either MILD or SEVERE COVID-19 patients. We show that although both types of vesicles efficiently display SARS-CoV-2 spike-derived peptides and carry immunomodulatory molecules, only those of MILD patients are capable of efficiently regulating antigen-specific CD4 + T-cell responses. Accordingly, by mass spectrometry, we show that the proteome of exosomes of MILD patients correlates with a proper functioning of the immune system, while that of SEVERE patients is associated with increased and chronic inflammation. Overall, we show that exosomes recovered from the plasma of COVID-19 patients possess SARS-CoV-2-derived protein material, have an active role in enhancing the immune response, and possess a cargo that reflects the pathological state of patients in the acute phase of the disease.

AIM: The long-term effects of laparoscopic cystectomy on ovarian reserve in patients with unilateral and bilateral ovarian endometriomas were evaluated. METHODS: A total of 22 patients undergoing laparoscopic cystectomy for unilateral endometrioma (n = 10) and bilateral endometriomas (n = 12) were included in the study. RESULT(S): Serum anti-Müllerian hormone (AMH) levels significantly decreased from the baseline value (3.98 ± 3.27 ng/mL) one (1.67 ± 1.56 ng/mL), three (2.01 ± 1.70 ng/mL), and six months (2.43 ± 2.39 ng/mL) postoperatively. There was no difference between preoperative and 12 month postoperative AMH levels (4.01 ± 3.39 ng/mL) (P > 0.05). Patients with bilateral endometriomas had a significantly higher rate of decline in AMH levels 12 months after surgery than patients with monolateral endometriomas (P = 0.035), but in both groups there was no difference in AMH levels at one and 12 months postoperatively (P > 0.05). CONCLUSION(S): AMH levels temporarily decreased after laparoscopic cystectomy for ovarian endometriomas, with complete recovery of preoperative AMH values at 12 months postoperatively. This pattern was equal in patients with bilateral and unilateral ovarian involvement. Patients with bilateral cysts have higher rates of decline of AMH levels compared to patients with unilateral affection.

BACKGROUND: Tuberculosis (TB) is the leading cause of death from a single infectious agent, with around 1.5 million deaths reported in 2018, and is a major contributor to suffering worldwide, with an estimated 10 million new cases every year. In the context of the World Health Organization's End TB strategy and the quest for digital innovations, there is a need to understand what is happening around the world regarding research into the use of digital technology for better TB care and control. OBJECTIVE: The purpose of this scoping review was to summarize the state of research on the use of digital technology to enhance TB care and control. This study provides an overview of publications covering this subject and answers 3 main questions: (1) to what extent has the issue been addressed in the scientific literature between January 2016 and March 2019, (2) which countries have been investing in research in this field, and (3) what digital technologies were used? METHODS: A Web-based search was conducted on PubMed and Web of Science. Studies that describe the use of digital technology with specific reference to keywords such as TB, digital health, eHealth, and mHealth were included. Data from selected studies were synthesized into 4 functions using narrative and graphical methods. Such digital health interventions were categorized based on 2 classifications, one by function and the other by targeted user. RESULTS: A total of 145 relevant studies were identified out of the 1005 published between January 2016 and March 2019. Overall, 72.4% (105/145) of the research focused on patient care and 20.7% (30/145) on surveillance and monitoring. Other programmatic functions 4.8% (7/145) and electronic learning 2.1% (3/145) were less frequently studied. Most digital health technologies used for patient care included primarily diagnostic 59.4% (63/106) and treatment adherence tools 40.6% (43/106). On the basis of the second type of classification, 107 studies targeted health care providers (107/145, 73.8%), 20 studies targeted clients (20/145, 13.8%), 17 dealt with data services (17/145, 11.7%), and 1 study was on the health system or resource management. The first authors' affiliations were mainly from 3 countries: the United States (30/145 studies, 20.7%), China (20/145 studies, 13.8%), and India (17/145 studies, 11.7%). The researchers from the United States conducted their research both domestically and abroad, whereas researchers from China and India conducted all studies domestically. CONCLUSIONS: The majority of research conducted between January 2016 and March 2019 on digital interventions for TB focused on diagnostic tools and treatment adherence technologies, such as video-observed therapy and SMS. Only a few studies addressed interventions for data services and health system or resource management.

BACKGROUND: Endometriosis has been associated with specific morphometric characteristics and pigmentary traits. The purpose of this study was to systematically review prior publications dealing with this aspect in order to revisit phenotypic information in the context of phenomics principles. METHODS: Comprehensive searches of Pubmed, Medline and Embase were conducted to identify studies, published from 1990 to 2011 in the English language literature, on the relationship between endometriosis and morphometric characteristics/pigmentary traits. RESULTS: We identified 11 studies on the association between endometriosis and body mass index (BMI) in the adult population and 5 studies on the same association during early life. While a modest inverse correlation was found between endometriosis and adult BMI, a stronger association was consistently demonstrated between endometriosis and early life body size, even after adjusting for confounding factors such as age, birthweight, age at menarche, parity and oral contraceptive use. Four papers have been published on the association between endometriosis and cutaneous naevi and five on the association between the disease and specific pigmentary traits. A skin phenotype characterized by the presence of naevi and freckles and by a high sensitivity to sun exposure is represented more frequently in women with endometriosis. CONCLUSIONS: Endometriosis appears to be associated with some phenotypic variations likely attributable to the strong effect of the environment on the expression and function of genes influencing the traits. Novel clues on endometriosis pathogenesis may derive from the analysis of the phenotypic traits associated with the disease.