Metagenomic gut microbiome analysis of Japanese patients with multiple chemical sensitivity/idiopathic environmental intolerance.

BACKGROUND: Although the pathology of multiple chemical sensitivity (MCS) is unknown, the central nervous system is reportedly involved. The gut microbiota is important in modifying central nervous system diseases. However, the relationship　between the gut microbiota and MCS remains unclear. This study aimed to identify gut microbiota variations associated with MCS using shotgun metagenomic sequencing of fecal samples. METHODS: We prospectively recruited 30 consecutive Japanese female patients with MCS and analyzed their gut microbiomes using shotgun metagenomic sequencing. The data were compared with metagenomic data obtained from 24 age- and sex-matched Japanese healthy controls (HC). RESULTS: We observed no significant difference in alpha and beta diversity of the gut microbiota between the MCS patients and HC. Focusing on the important changes in the literatures, at the genus level, Streptococcus, Veillonella, and Akkermansia were significantly more abundant in MCS patients than in HC (p < 0.01, p < 0.01, p = 0.01, respectively, fold change = 4.03, 1.53, 2.86, respectively). At the species level, Akkermansia muciniphila was significantly more abundant (p = 0.02, fold change = 3.3) and Faecalibacterium prausnitzii significantly less abundant in MCS patients than in HC (p = 0.03, fold change = 0.53). Functional analysis revealed that xylene and dioxin degradation pathways were significantly enriched (p < 0.01, p = 0.01, respectively, fold change = 1.54, 1.46, respectively), whereas pathways involved in amino acid metabolism and synthesis were significantly depleted in MCS (p < 0.01, fold change = 0.96). Pathways related to antimicrobial resistance, including the two-component system and cationic antimicrobial peptide resistance, were also significantly enriched in MCS (p < 0.01, p < 0.01, respectively, fold change = 1.1, 1.2, respectively). CONCLUSIONS: The gut microbiota of patients with MCS shows dysbiosis and alterations in bacterial functions related to exogenous chemicals and amino acid metabolism and synthesis. These findings may contribute to the further development of treatment for MCS. TRIAL REGISTRATION: This study was registered with the University Hospital Medical Information Clinical Trials Registry as UMIN000031031. The date of first trial registration: 28/01/2018.

Do somatic symptom distress and attribution predict symptoms associated with environmental factors?

OBJECTIVE: Not much is known on the development of symptoms associated with environmental factors (SAEF), also known as (idiopathic) environmental intolerances. Findings from qualitative studies suggest that appearance of symptoms might be the first step, followed by the acquisition of a specific attribution. The current study investigated cross-sectional and longitudinal (three years) associations between attribution and symptoms with respect to symptoms associated with chemical substances, certain indoor environments (buildings), sounds, and electromagnetic fields (EMFs). METHODS: We used data from the first two waves of the population-based Västerbotten Environmental Health Study (n = 2336). Participants completed the Patient Health Questionnaire Somatic Symptom Scale (PHQ-15), the Environmental Symptom-Attribution Scale, and answered single questions on the four aforementioned SAEFs. RESULTS: Using binary logistic regression analyses, all four SAEFs showed significant cross-sectional associations with somatic symptom distress and the respective attribution. In the longitudinal analysis, development of SAEF-Sound and SAEF-Chemicals were predicted by both somatic symptom distress and attribution. SAEF-EMFs was predicted only by attribution, whereas neither somatic symptom distress nor attribution forecasted SAEF-Buildings. CONCLUSION: Overall, these findings suggest that attribution (i.e., a specific expectation) plays a substantial role in the development and maintenance of many SAEFs.

Sensibilidad química múltiple en una niña de 8 años. Seguimiento durante 6 años / Multiple chemical sensitivity in an 8-year-old girl. A 6-year follow-up

La sensibilidad química múltiple (SQM) es una entidad escasamente comprendida y controvertida. La SQM es un síndrome polisintomático y multisistémico. Los sujetos con SQM muestran una sintomatología compleja debido a la intolerancia a los agentes químicos. Los síntomas incluyen malestar general, inestabilidad cardiovascular, irritación de órganos de los sentidos, desórdenes respiratorios, con hipersensibilidad que afecta a piel, recubrimiento epitelial de intestino, garganta y pulmones. Se presenta un caso de una mujer de 8 años, valorada por sensibilización química con síntomas inhalatorios y faríngeos, conjuntivitis, disfonía y accesos de tos con sensación de dificultad respiratoria. El seguimiento se ha realizado durante 6 años, durante los cuales se ha repetido el test inhalatorio en dos ocasiones con los mismos resultados concluyentes para el diagnóstico de SQM. El caso comunicado reúne los criterios de SQM, siendo excepcional el inicio de los síntomas a una edad tan temprana. (AU)

Multiple chemical sensitivity (MCS) is a controversial little understood entity. MCS is a multisystem and poly-symptomatic syndrome. MCS subjects display a complex symptomatology due to the intolerance of chemical agents. Symptoms include general discomfort, cardiovascular instability, sensory organs irritation, breath disorders, hypersensitivity affecting the skin and epithelial lining of the gut, throat and lungs. We report the case of an 8 years old female, assessed in medical consultation for chemical sensitization when presenting inhalation and pharyngeal symptoms, conjunctivitis, dysphonia, coughing spells and respiratory distress. A 6-year follow-up was carried out and the provocation inhaler test which was performed twice among that period obtained the same conclusive results for the diagnosis of MCS. The case submitted meets the criterion of MCS, being exceptional a debut of the symptons at such an early age. (AU)

Multiple chemical sensitivity scoping review protocol: overview of research and MCS construct.

INTRODUCTION: Multiple chemical sensitivity (MCS) has been characterised by reported adverse responses to environmental exposures of common chemical agents (eg, perfumes, paint, cleaning products and other inhaled or ingested agents) in low doses considered non-toxic for the general population. There is currently no consensus on whether MCS can be established as a distinct disorder. METHODS AND ANALYSIS: The scoping review of the literature will be guided by five questions: How is MCS defined and which diagnostic criteria have been proposed? What methods are used to report prevalence and incidence estimates of MCS? What are the characteristics of the body of scientific evidence that addresses whether MCS is a distinct disorder or syndrome? What underlying mechanisms for MCS have been proposed in the scientific literature? Which treatment and management approaches for MCS have been evaluated in empirical research studies? We will conduct a comprehensive search in 14 research databases. Citation screening will be supported by machine learning algorithms. Two independent reviewers will assess eligibility of full-text publications against prespecified criteria. Data abstraction will support concise evidence tables. A formal consultation exercise will elicit input regarding the review results and presentation. The existing research evidence will be documented in a user-friendly visualisation in the format of an evidence map. ETHICS AND DISSEMINATION: Determined to be exempt from review (UP-22-00516). Results will be disseminated through a journal manuscript and data will be publicly accessible through an online data repository. REGISTRATION DETAILS: The protocol is registered in Open Science Framework (osf.io/4a3wu).

Multiple Chemical Sensitivity/Idiopathic Environmental Intolerance: A Practical Approach to Diagnosis and Management.

Patients with multiple chemical sensitivity, now called idiopathic environmental intolerance, frequently present to clinical immunologists and allergists for diagnosis and treatment. Patients report a plethora of respiratory and multisystem problems attributed to a wide variety of unrelated, otherwise non-noxious, triggers. They may go to extreme, often seemingly bizarre lengths to avoid contact with everyday exposures and may become housebound, unable to work or function socially. Often beginning with exposure to odors, triggers can multiply to involve foods, clothing, medications, and even electromagnetic radiation. The condition cannot be explained by IgE-mediated or other immune processes, and clinical immunologists and allergists may feel unprepared to care for such patients. In this article, a paradigm to understand the probable mechanisms underlying this condition and a practical approach to diagnosis and management will be presented.

Prevalence and correlation of multiple chemical sensitivity and electromagnetic hypersensitivity with age, sex, and depression in the Japanese population: a retrospective study.

BACKGROUND: In Japan, there are currently no definitive conclusions regarding the characteristics of multiple chemical sensitivity (MCS) and electromagnetic hypersensitivity (EHS). This study aimed to determine the prevalence and correlation of MCS and EHS with age, sex, and depression in the Japanese population. METHODS: An anonymous self-report questionnaire was distributed to 2,007 participants. Variables such as MCS, EHS, depression score, and demographic characteristics were individually evaluated using the U-test, chi-squared test, and correlation analyses. Moreover, we performed a covariance structure analysis to build a structural equation model. RESULTS: Older individuals and women were more likely to exhibit MCS and EHS symptoms. Moreover, depression was correlated with MCS and EHS. CONCLUSIONS: Although MCS and EHS are strongly correlated, they exhibit distinct characteristics and symptoms, indicating that they can be regarded as separate conditions.

Multiple chemical sensitivity: It's time to catch up to the science.

Multiple chemical sensitivity (MCS) is a complex medical condition associated with low dose chemical exposures. MCS is characterized by diverse features and common comorbidities, including fibromyalgia, cough hypersensitivity, asthma, and migraine, and stress/anxiety, with which the syndrome shares numerous neurobiological processes and altered functioning within diverse brain regions. Predictive factors linked to MCS comprise genetic influences, gene-environment interactions, oxidative stress, systemic inflammation, cell dysfunction, and psychosocial influences. The development of MCS may be attributed to the sensitization of transient receptor potential (TRP) receptors, notably TRPV1 and TRPA1. Capsaicin inhalation challenge studies demonstrated that TRPV1 sensitization is manifested in MCS, and functional brain imaging studies revealed that TRPV1 and TRPA1 agonists promote brain-region specific neuronal variations. Unfortunately, MCS has often been inappropriately viewed as stemming exclusively from psychological disturbances, which has fostered patients being stigmatized and ostracized, and often being denied accommodation for their disability. Evidence-based education is essential to provide appropriate support and advocacy. Greater recognition of receptor-mediated biological mechanisms should be incorporated in laws, and regulation of environmental exposures.

Impact of comorbidity on symptomatology in various types of environmental intolerance in a general Swedish and Finnish adult population.

Comorbidity with various health conditions is common in environmental intolerances (EIs), which restricts understanding for what symptoms that are associated with the intolerance per se. The present objectives were to study (i) prevalence of a broad range of specific symptoms in chemical, building-related, electromagnetic field- (EMF) related, and sound EI, irrespective of comorbidity, (ii) prevalence of symptoms in body systems in exclusive EIs, and (iii) increased risk of symptoms in body systems in exclusive EIs that cannot be referred to functional somatic syndromes, inflammatory diseases or mental disorders. Cross-sectional data (n = 4941) were used from two combined population-based surveys, the Västerbotten (Sweden) and Österbotten (Finland) Environmental Health Studies. Categorization of EI cases and controls were based on self-reports. Symptoms were assessed with the Environmental Hypersensitivity Symptom Inventory, and these were converted to 27 symptoms of the International Classification of Primary Care, 2nd edition, in eight chapters of body systems. The results showed, with few exceptions, that all assessed specific symptoms were significantly more prevalent in all four EIs than in referents. Although a large overlap between EIs, characteristic body system symptoms were eye and respiratory symptoms in chemical and building-related intolerance, skin symptoms in EMF-related intolerance, and general and unspecified, digestive, eye, cardiovascular, neurological, and psychological symptoms in sound intolerance. After controlling for various comorbidities, all studied body system symptoms were positively associated with chemical intolerance, fewer with sound intolerance, only one with building-related intolerance, and none with EMF-related EI. In conclusion, a broad range of symptoms are reported in all four EIs implying common mechanisms, but symptoms of certain body systems are more likely to be reported in a certain EI that cannot be explained by comorbidity.

Social economic factors and the risk of multiple chemical sensitivity in a Danish population-based cross-sectional study: Danish Study of Functional Disorders (DanFunD).

OBJECTIVES: Multiple chemical sensitivity (MCS) is a rare multisystem and poly-symptomatic disease characterised by a report of various somatic symptoms attributed to inhalation of volatile chemicals in usually harmless doses. The aim was to explore four selected social factors and the risk of MCS in the general Danish population. DESIGN: A cross-sectional general population-based study. SETTING: The Danish Study of Functional Disorders was conducted from 2011 to 2015 which included 9656 participants. PARTICIPANTS: A total of 8800 participants were included in analyses after observations with missing data on exposure and/or outcome were excluded. A total of 164 cases fulfilled the questionnaire criteria for MCS. Of the 164 MCS cases, 101 reported no comorbid functional somatic disorder (FSD) and were included in a subgroup analysis. A total of 63 MCS cases fulfilled the criteria for at least one additional FSD, this subgroup was not included in further analysis. The remaining study population without MCS or any FSD were regarded as controls. OUTCOME MEASURES: We used adjusted logistic regression to calculate OR and 95% CIs of MCS and MCS without FSD comorbidities for each social variable separately including education, employment, cohabitation and subjective social status. RESULTS: We found an increased risk of MCS among the unemployed (OR: 2.95, 95% CI: 1.75 to 4.97), and a twofold increased risk of MCS among individuals with low subjective social status (OR: 2.00, 95% CI: 1.08 to 3.70). At the same time, 4 years or more of vocational training were protective of MCS. No significant associations were observed among MCS cases with no comorbid FSD. CONCLUSION: Lower socioeconomic status was found to be associated with a higher risk of having MCS but not with MCS without FSD comorbidities. Due to the cross-sectional design of the study, we cannot determine whether social status is a determinant or a consequence of MCS.

Time course of health complaints attributed to RF-EMF exposure and predictors of electromagnetic hypersensitivity over 10 years in a prospective cohort of Dutch adults.

BACKGROUND: Some individuals attribute health complaints to radiofrequency electromagnetic field (RF-EMF) exposure. This condition, known as idiopathic environmental intolerance attributed to RF-EMFs (IEI-RF) or electromagnetic hypersensitivity (EHS), can be disabling for those who are affected. In this study we assessed factors related to developing, maintaining, or discarding IEI-RF over the course of 10 years, and predictors of developing EHS at follow-up using a targeted question without the condition of reporting health complaints attributed to RF-EMF exposure. METHODS: Participants (n = 892, mean age 50 at baseline, 52 % women) from the Dutch Occupational and Environmental Health Cohort Study AMIGO filled in questionnaires in 2011/2012 (T0), 2013 (T1), and 2021 (T4) where information pertaining to perceived RF-EMF exposure and risk, non-specific symptoms, sleep problems, IEI-RF, and EHS was collected. We fitted multi-state Markov models to represent how individuals transitioned between states ("yes", "no") of IEI-RF. RESULTS: At each time point, about 1 % of study participants reported health complaints that they attributed to RF-EMF exposure. While this percentage remained stable, the individuals who reported such complaints changed over time: of nine persons reporting health complaints at T0, only one reported IEI-RF at both T1 and T4, and two newly reported health complaints at T4. Overall, participants had a 95 % chance of transitioning from "yes" to "no" over a time course of 10 years, and a chance of 1 % of transitioning from "no" to "yes". Participants with high perceived RF-EMF exposure and risk had a general tendency to move more frequently between states. CONCLUSIONS: We observed a low prevalence of IEI-RF in our population. Prevalence did not vary strongly over time but there was a strong aspect of change: over 10 years, there was a high probability of not attributing symptoms to RF-EMF exposure anymore. IEI-RF appears to be a more transient condition than previously assumed.

Multiple Chemical Sensitivity Syndrome: First Symptoms and Evolution of the Clinical Picture: Case-Control Study/Epidemiological Case-Control Study.

Multiple chemical sensitivity (MCS) is a chronic condition characterized by the appearance of symptoms caused by exposure to chemical compounds that are tolerable for the general population. It mainly affects middle-aged women. There are very few studies focusing on the most frequent symptoms of MCS considering age groups and gender. The main goal of this study was to find the most frequent symptoms both at the onset of the disease and at the present time describing them by age groups. The QEESI (Quick Environmental Exposure and Sensitivity Inventory) questionnaire, Scale 3 which assesses symptoms and their severity, was used as a diagnostic tool for the disease. A case-control study was conducted with the participation of 210 people. Of the cases, 94.3% were women. The symptoms that most often manifested first were airway and mucous membrane alterations (68.9%). In the development of the disease, we found cognitive alterations (OR = 31.25), heart or chest problems (OR = 22.49), neuromuscular problems (OR = 20.00) and head-related symptomatology (OR = 19.29). Identifying the most frequent pattern of symptoms by age group and sex will allow an early diagnosis of the disease to improve its prognosis and treatment.

Metabolomics analysis of plasma samples of patients with fibromyalgia and electromagnetic sensitivity using GC-MS technique.

Fibromyalgia (FM) is a chronic and systemic condition that causes widespread chronic pain, asthenia, and muscle stiffness, as well as in some cases depression, anxiety, and disorders of the autonomic system. The exact causes that lead to the development of FM are still unknown today. In a percentage of individuals, the symptoms of FM are often triggered and/or exacerbated by proximity to electrical and electromagnetic devices. Plasma metabolomic profile of 54 patients with fibromyalgia and self-reported electromagnetic sensitivity (IEI-EMF) were compared to 23 healthy subjects using gas chromatography-mass spectrometry (GC-MS) coupled with multivariate statistical analysis techniques. Before the GC-MS analysis the plasma samples were extracted with a modified Folch method and then derivatized with methoxamine hydrochloride in pyridine solution and N-trimethylsilyltrifuoroacetamide. The combined analysis allowed to identify a metabolomic profile able of distinguishing IEI-EMF patients and healthy subjects. IEI-EMF patients were therefore characterized by the alteration of 19 metabolites involved in different metabolic pathways such as energy metabolism, muscle, and pathways related to oxidative stress defense and chronic pain. The results obtained in this study complete the metabolomic "picture" previously investigated on the same cohort of IEI-EMF patients with 1H-NMR spectroscopy, placing a further piece for better understanding the pathophysiological mechanisms in patients with IEI-EMF.

Undertreatment with Osimertinib in patient with multiple chemical sensitivity. A case report.

Introduction: Multiple chemical sensitivity (MCS), is a syndrome characterised by increased sensitivity to the exposure of environmental chemicals (1). There are considerable difficulties in reaching a good estimate of the prevalence of disease and the main pathogenetic hypotheses take into account both the organic and psychiatric/psychological factors. Treatment with epidermal growth factor tyrosine kinase receptor inhibitors (tkis), like Osimertinib, results in improved progression-free survival (PFS) compared to chemotherapy, in Non-small-cell lung carcinoma (NSCLC) with epidermal growth factor receptor (EGFR) mutation (2). Case report: We describe the case of a 74 year old woman with history of MCS and fibromyalgia in treatment with Osimertinib for EGFR-mutated NSCLC. Patient initially refused any form of active therapy for lung cancer, but thanks to teamwork and the important support of the psychologist, the patient decided to start treatment with Osimertinib at a reduced dose, not 80 mg but 40 mg. Subsequently, after few days , of his own free will and without informing the staff physicians, the patient changed the treatment schedule by taking one quarter of the dose of the medicine every other day, justifying this choice in therapeutic modification because of her fear and intolerance to any type of medicine and/ or chemical substance, being influenced by MCS. Management & outcome: Despite the changes in the treatment plan, a PET scan performed after two months showed a sigificative lung response and the stability of bone metastases. Discussion. Our case describes a significative response with Osimertinib despite the change in dosage and schedule in a patient with MCS. Our experience deserves to be considered in the light of its particularity and uniqueness as it shows an excellent response to treatment with Osimertinib despite the change made to the dosage and schedule, in a patient presenting in her medical history this rare pathological condition: MCS syndrome.