Evaluation and Management of Fatigue in Patients with Systemic, Autoimmune Rheumatic Disease

Background: Fatigue affects most patients living with advanced cancer and is a symptom that healthcare professionals can find difficult to manage. Aim: To provide healthcare professionals with a pragmatic overview of approaches to management of fatigue in patients with advanced cancer that are commonly recommended by guidelines and to evaluate evidence underpinning them. Design: Scoping review methodology was used to determine the strength of evidence supporting use of interventions recommended in management of fatigue in patients with advanced cancer. Data sources: National or international guidelines were examined if they described the management of fatigue in adult cancer patients and were written within the last 6 years (2015–2021) in English. The Cochrane Database of Systematic Reviews (January 2011–December 2021) was searched for ‘cancer’ AND ‘fatigue’ in title, abstract or keywords. A PubMed search was also made. Results: Evidence indicates physical exercise interventions are effective and patients may benefit from energy conservation tactics. Evidence does not support use of psychostimulants such as methylphenidate. Limited data were found on efficacy of corticosteroids, psychological interventions, nutritional intervention, sleep optimization or complementary therapies for management of fatigue in advanced cancer. Conclusion: We recommend regular assessment, review and acknowledgement of the impact of fatigue. Exercise and energy conservation should be considered. Pharmacological interventions are not endorsed as a routine approach. Many interventions currently recommended by guidelines are not supported by a robust evidence base and further research on their efficacy is required.

Clinical aspects of autoimmune rheumatic diseases

INTRODUCTION: Breast cancer is the most prevalent cancer among women worldwide. Similar to chemotherapy, antineoplastic treatment is associated with many side effects, with fatigue being one of the most common. It is important to investigate potential treatments, especially non-pharmacological alternatives, to control symptoms that directly affect women’s quality of life. OBJECTIVE: The objective of this study was to provide scientific evidence to verify the efficacy of acupuncture in the management of fatigue in patients with breast cancer. METHODS: This study involved a systematic review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) methodology. Randomized clinical trials published in indexed scientific journals were compiled. The literature search was performed using the electronic databases, PubMed, PEDro, and BIREME, using the descriptors ‘breast cancer’, ‘fatigue’, ‘acupuncture’, and ‘randomized trial’. Inclusion criteria included fully available online articles that were classified as randomised clinical trials published from 2012 to 2017 in either English or Portuguese. Study eligibility was based on the Population, Intervention, Control, Outcome, and Study (PICO) design criteria, in which the (1) population included women 18–65 years of age with breast cancer, (2) intervention was acupuncture, (3) comparison referred to standard care or sham acupuncture, and (4) outcome was the evaluation of fatigue. The PEDro scale was applied to evaluate the quality of the studies. WebQualis was also used to evaluate the quality of the journals of the selected articles. RESULTS: In total, 66 articles were selected, but only four fulfilled all inclusion criteria, giving a total sample size of 620 women. All trials evaluated the effect of acupuncture on fatigue and other symptoms related to the treatment of breast cancer with different treatment durations. Three articles reported statistically significant results, and all articles described clinical improvement in fatigue after the application of acupuncture. The average PEDro score of the manuscripts was 6.25. All articles were published in non-Brazilian journals with WebQualis scores that ranged from B2 to A1. CONCLUSION: Scientific evidence confirms the efficacy of acupuncture in the management of fatigue reported by women with breast cancer. Acupuncture was effective in reducing fatigue in the studies selected for this review.

BackgroundFatigue is one of the most prevalent and burdensome symptoms for patients with inflammatory bowel disease (IBD). Although fatigue increases during periods of inflammation, for some patients it persists when disease is in remission. Compared to other long-term conditions where fatigue has been extensively researched, optimal management of fatigue in patients with IBD is unknown and fatigue has rarely been the primary outcome in intervention studies. To date, interventions for the management of IBD-fatigue are sparse, have short-term effects and have not been implemented within the existing health system. There is a need to integrate current best evidence across different conditions, patient experience and clinical expertise in order to develop interventions for IBD-fatigue management that are feasible and effective. Modifying an existing intervention for patients with multiple sclerosis, this study aims to assess the feasibility and initial estimates of efficacy of a cognitive behavioural therapy (CBT) intervention for the management of fatigue in patients with IBD.MethodsThe study will be a two-arm pilot randomised controlled trial. Patients will be recruited from one outpatient IBD clinic and randomised individually to either: Group 1 (CBT manual for the management of fatigue, one 60-min session and seven 30-min telephone/Skype sessions with a therapist over an eight-week period); or Group 2 (fatigue information sheet to use without therapist help). Self-reported IBD-fatigue (Inflammatory Bowel Disease-Fatigue Scale) and IBD-quality of life (United Kingdom Inflammatory Bowel Disease Questionnaire) and self-reported disease activity will be collected at baseline, three, six and 12 months post randomisation. Illness perceptions, daytime sleepiness, anxiety and depression explanatory variables will be collected only at three months post randomisation. Clinical and sociodemographic data will be retrieved from the patients’ medical notes. A nested qualitative study will evaluate patient and therapist experience, and healthcare professionals’ perceptions of the intervention.DiscussionThe study will provide evidence of the feasibility and initial estimates of efficacy of a CBT intervention for the management of fatigue in patients with IBD. Quantitative and qualitative findings from the study will contribute to the development and implementation of a large-scale randomised controlled trial assessing the efficacy of CBT interventions for IBD-fatigue.Trial registrationISRCTN Registry, ISRCTN17917944. Registered on 2 September 2016.

Fatigue is a complex and multifactorial phenomenon which is often neglected by clinicians. The aim of this review was to analyze the impact, determinants and management of fatigue in patients with Systemic Lupus Erythematosus (SLE). Fatigue is one of the most prevalent symptoms in SLE, reported by 67% to 90% of patients. It is also described as the most bothersome symptom, considering that it may impair key aspects of health-related quality of life, while also leading to employment disability. It is a multifactorial phenomenon involving psychological factors, pain, lifestyle factors such as reduced physical activity, whereas the contribution of disease activity remains controversial. The management of fatigue in patients with SLE should rely upon a person-centered approach, with targeted interventions. Some pharmacological treatments used to control disease activity have demonstrated beneficial effects upon fatigue and non-pharmacological therapies such as psychological interventions, pain reduction and lifestyle changes, and each of these should be incorporated into fatigue management in SLE.

A pilot study was conducted to develop and test a nursing intervention to facilitate the management of fatigue in patients receiving chemotherapy. The intervention, named the "Beating Fatigue" program, has 4 elements: assessment/monitoring, education, coaching in the management of fatigue, and provision of emotional support. Beating Fatigue was implemented with and evaluated by 8 patients. Overall, patients were very positive about the program and perceived the opportunity to talk to someone about fatigue as the most beneficial strategy within the program, although individual patients varied in which aspect they most preferred. Data from the pilot work supported the view that a multifaceted approach to the management of cancer-related fatigue is appropriate because it enables an intervention package to be tailored to an individual's requirements. The approach appeared both feasible and practical. Although numeric data were limited, there was some evidence that the approach had the capacity to lessen fatigue and enhance emotional well-being.

Adult patients living with heart failure: Experiences and management of fatigue in everyday life - a systematic review protocol of qualitative evidence

Thyroid function abnormalities and thyroid autoantibodies have been frequently described in patients with rheumatologic autoimmune diseases, such as Sjögren's syndrome, rheumatoid arthritis, systemic lupus erythematosus and scleroderma. Limited data are available regarding the prevalence and clinical characteristics of autoimmune thyroiditis in other rheumatologic disorders, such as rheumatic fever and juvenile systemic lupus erythematosus. The authors review the association of endocrine autoimmune and rheumatic autoimmune diseases, assessing various age groups and clinical conditions. The bibliographic survey was conducted through the search for scientific articles indexed in the general health sciences databases, such as Latin American and Caribbean Health Sciences Literature (LILACS), Medline/PubMed, and Scientific Electronic Library Online (SciELO). The following descriptors were used: "rheumatic autoimmune diseases and autoimmune thyroid diseases"; "thyroid disorders and rheumatic diseases"; "thyroiditis and rheumatic diseases"; "autoimmune diseases and thyroid"; and "pediatric rheumatic diseases and autoimmune thyroid diseases". This study showed that, despite contradictory results in the literature, there is a greater prevalence of the association between autoimmune thyroid diseases and rheumatic diseases, highlighting the possibility of common pathogenic mechanisms among them.

Background:The probability of developing an autoimmune inflammatory rheumatic disease (RMD) in one’s lifetime is 1 in 12 for women and 1 in 20 for men. [1]. Fatigue is reported as...

The cause of rheumatic diseases is poorly understood; many appear to have a dominant inheritance with low, incomplete penetrance. A recent theory poses that all DNA is continuously damaged at a constant rate, causing a constant rate of mutations. Here, the hypothesis is tested that a constant, low rate of somatic mutations explains the low, incomplete penetrance of autoimmune rheumatic diseases and the increased penetrance of monogenic inflammatory rheumatic disease driven by multiple DNA loci prone to somatic mutation. Monogenic rheumatic diseases are proposed to require two mutations according to the two-hit hypothesis by Knudson: a germline mutation on one allele, and a somatic mutation initiating rheumatic disease on the wild-type allele. Two approaches are taken. The first one investigates whether the epidemiology of autoimmune rheumatic diseases adheres to two expected characteristics: a linear prevalence of disease and a tapering distribution of multiple disease events in individuals at risk. The second approach analyses at-risk DNA for evidence of hypermutable loci: somatic hypermutation (SHM) hotspots. Autoimmune and monogenic inflammatory rheumatic diseases provide an opportunity to determine whether more than one similar SHM hotspot leads to earlier onset of disease and a higher degree of disease penetrance. Results show that examples of rheumatic diseases, such as rheumatoid arthritis, systemic sclerosis, lupus and Sjogren's syndrome, show a linear prevalence and an exponential distribution of one or more additional autoimmune diseases. SHM hotspots in HLA and non-HLA genes in at-risk people are associated with the risk of rheumatic diseases, and the difference in the number of SHM hotspots, one in autoimmune and PLB1 arthritis and several in COPA syndrome, associated with autoimmune and monogenic non-HLA rheumatic diseases, explains the time of onset of disease and the degree of incomplete penetrance. This clarifies why autoimmune rheumatic diseases are inherited as true autosomal dominant traits with incomplete penetrance and non-HLA monogenic rheumatic diseases as pseudo-dominant traits with incomplete penetrance in accordance with the two-hit hypothesis. Therefore, epidemiology and genetics are compatible with a constant rate of DNA damage and associated somatic mutations as the cause of autoimmune and monogenic rheumatic diseases among at-risk people.

This guideline presents screening, assessment, and treatment approaches for the management of adult cancer survivors who are experiencing symptoms of fatigue after completion of primary treatment. A systematic search of clinical practice guideline databases, guideline developer Web sites, and published health literature identified the pan-Canadian guideline on screening, assessment, and care of cancer-related fatigue in adults with cancer, the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines In Oncology (NCCN Guidelines) for Cancer-Related Fatigue and the NCCN Guidelines for Survivorship. These three guidelines were appraised and selected for adaptation. It is recommended that all patients with cancer be evaluated for the presence of fatigue after completion of primary treatment and be offered specific information and strategies for fatigue management. For those who report moderate to severe fatigue, comprehensive assessment should be conducted, and medical and treatable contributing factors should be addressed. In terms of treatment strategies, evidence indicates that physical activity interventions, psychosocial interventions, and mind-body interventions may reduce cancer-related fatigue in post-treatment patients. There is limited evidence for use of psychostimulants in the management of fatigue in patients who are disease free after active treatment. Fatigue is prevalent in cancer survivors and often causes significant disruption in functioning and quality of life. Regular screening, assessment, and education and appropriate treatment of fatigue are important in managing this distressing symptom. Given the multiple factors contributing to post-treatment fatigue, interventions should be tailored to each patient's specific needs. In particular, a number of nonpharmacologic treatment approaches have demonstrated efficacy in cancer survivors.

Cancer-related fatigue is one of the most important untreated symptoms of cancer, with a prevalence between 60 and 100%, but there has been a reluctance to prioritize fatigue and develop effective management strategies. The development of standards and guidelines will encourage a more systematic approach and help to stimulate further research. The Mersey Palliative Care Audit Group has developed guidelines for the assessment and management of fatigue. These guidelines were produced following a regional survey, which looked at both the educational needs of nurses, and the impact of fatigue on patients with advanced cancer.

Fatigue is a common symptom in Multiple Sclerosis (MS), and its assessment depends entirely on patient reports. Importantly, managing MS symptoms is increasingly supported by Digital Health Technology (DHT), which includes Mobile Health Technology (mHT). Considering the growing interest, we aimed to synthesise evidence about smartphone applications for the assessment and management of fatigue in MS, as well as to investigate their usability, feasibility, and reliability. We performed a literature search in PubMed, Science Direct, and Embase using a scoping review approach. We included 16 articles and, although many lacked crucial methodological details, DHT was evaluated in all MS clinical subtypes and with disease durations up to more than 20 years. Despite the marked heterogeneity in terms of the employed methods, all documented a high degree of usability, assessed both as feedback from participants and completed tasks. Moreover, the feasibility assessment also showed good results, as apps were able to discriminate between patients with and without fatigue. Importantly, most also showed excellent results in terms of reliability, and some patients reported a reduction in fatigue thanks to mHT. Despite limitations, mHT has been positively evaluated by patients, suggesting a promising role of DHT in the self-management of MS.

In autoimmune rheumatic diseases, oestrogens can stimulate certain immune responses (including effects on B cells and innate immunity), but can also have dose-related anti-inflammatory effects on T cells, macrophages and other immune cells. By contrast, androgens and progesterone have predominantly immunosuppressive and anti-inflammatory effects. Hormone replacement therapies and oral contraception (and also pregnancy) enhance or decrease the severity of autoimmune rheumatic diseases at a genetic or epigenetic level. Serum androgen concentrations are often low in men and in women with autoimmune rheumatic diseases, suggesting that androgen-like compounds might be a promising therapeutic approach. However, androgen-to-oestrogen conversion (known as intracrinology) is enhanced in inflamed tissues, such as those present in patients with autoimmune rheumatic diseases. In addition, it is becoming evident that the gut microbiota differs between the sexes (known as the microgenderome) and leads to sex-dependent genetic and epigenetic changes in gastrointestinal inflammation, systemic immunity and, potentially, susceptibility to autoimmune or inflammatory rheumatic diseases. Future clinical research needs to focus on the therapeutic use of androgens and progestins or their downstream signalling cascades and on new oestrogenic compounds such as tissue-selective oestrogen complex to modulate altered immune responses.

Sleep has an important role to play in the human immune system and it is critical in the restoration and maintenance of homeostasis. Sleep deprivation and disorders may have a profound impact on health, well being and the ability to resist infection. Autoimmune rheumatic diseases are multisystem disorders that involve complicated hormonal and immunological pathophysiology. Previous studies have suggested that sleep deprivation may lead to immunological disturbance in experimental mouse models. Sleep disorders may trigger immune system abnormalities inducing autoantibody production, possibly leading to the development of autoimmune disease such as systemic lupus erythematosus, scleroderma or rheumatoid arthritis. Indeed, in experimental models, it has been suggested that sleep deprivation may induce the onset of autoimmune disease. Chronic deprivation of sleep is common in modern society and has been seen in various autoimmune inflammatory rheumatic diseases. We have reviewed various aspects of sleep deprivation and sleep apnoea syndrome, and their effects on the immune system and their relevance to autoimmune diseases. We hope that these data will encourage greater awareness of the role that improved sleep hygiene may play in the management of these rheumatic diseases.