Pain and fatigue in adults with Loeys–Dietz syndrome and vascular Ehlers–Danlos syndrome, a questionnaire‐based study
Johansen Heidi, TRS National Resource Centre for Rare Disorders, Sunnaas Rehabilitation Hospital, Nesodden, Norway
Velvin Gry, TRS National Resource Centre for Rare Disorders, Sunnaas Rehabilitation Hospital, Nesodden, Norway
Ingeborg B. Lidal, Faculty of Health, Oslo Metropolitan University (OsloMet), Oslo Norway
September 2022, Published online 10 June, 2022
Highlights
This study showed very high proportions with chronic musculoskeletal pain and clinically relevant fatigue symptoms among persons with LDS and vEDS.
This is the first study investigating self‐reports on chronic musculoskeletal pain and fatigue symptomatology in adults with molecularly confirmed LDS and vEDS.
The main findings were high prevalence of pain and fatigue symptoms, reports of multiple pain locations, and that pain symptoms influenced participation in housekeeping, work and leisure activities in the study population.
More than half of the study population developed pain during childhood or adolescence.
Abstract
The purpose was to study self‐reported chronic pain and fatigue symptoms among adults with molecularly verified Loeys–Dietz and vascular Ehlers–Danlos syndrome using a cross‐sectional questionnaire design. Seventy adults were invited through a National Resource Centre for Rare Disorders. A study specific questionnaire including Brief Pain Inventory, Standardized Nordic Questionnaire, Fatigue Severity Scale, Hospital Anxiety & Depression Scale, questions on physical activity, and disease burden was used. Fifty‐two persons participated, n = 34 with Loeys–Dietz and n = 18 with vascular Ehlers–Danlos syndrome, aged 18–68 years, 58% women. Chronic pain (79%) and fatigue (58%) symptoms were common. Half developed pain during childhood/adolescence. Sleep problems and high multi‐organ burden were significantly associated with chronic pain (p = 0.004, p = 0.014) and high fatigue (p < 0.001, p < 0.001). Chronic pain was associated with higher scores of fatigue (p = 0.002). Higher scores of fatigue were associated with lower level of physical activity (p = 0.014), higher cardiovascular burden (p = 0.025), and higher symptoms of anxiety (p = 0.001). In this study, symptoms of chronic pain, fatigue, sleep problems, and disease burden seemed to mutually reinforce each other. Initiatives should consider interventions aimed at postponing the onset and reducing symptoms of pain, fatigue, and sleep problems and thus reduce the total disease burden at an early stage in patients with these complex conditions.
INTRODUCTION
Loeys–Dietz syndrome (LDS) and vascular Ehlers–Danlos syndrome (vEDS) are potentially life‐threatening diseases within the umbrella term of rare hereditary thoracic aortic diseases (HTAD). The most serious medical complications are vascular events. LDS hallmarks are early and aggressive aneurysms and dissections of the aorta and/or other large arteries (Velchev et al., 2021). vEDS hallmarks include arterial, intestinal, and/or uterine fragility with risk of rupture of the internal organs in addition to risk of aneurysm and dissection of middle‐sized arteries (Byers et al., 2017). Other organs affected may include the musculoskeletal system, craniofacial structures, ocular system, and cutaneous features (Meester et al., 2017). LDS is caused by a mutation of genes encoding for transforming growth factor‐beta signaling pathways TGFBR1, TGFBR2, SMAD3, and TGFB2 (Velchev et al., 2021 ). vEDS results from pathogenic variants in COL3A1, encoding type III collagen that is the major expressed collagen in blood vessels and hollow organs (Byers et al., 2017). Both diagnoses are suspected on the basis of family history, or a clinical history of arterial rupture, dissection or aneurysm, rupture of the large intestine, or pregnancy complications at young ages (Meester et al., 2017). Since there is clinical overlap between HTADs, the diagnoses should be confirmed by identification of pathogenic gene variants to allow for appropriate surveillance, treatment and family studies (Meester et al., 2017).
Typically, most individuals with LDS or vEDS live with family members with the same HTAD condition, and many have experienced close relatives die at an early age (Johansen et al., 2020a). Persons with HTADs are recommended for regular cardiovascular monitoring, including control of blood pressure with medications, and scheduling of prophylactic surgery (Byers et al., 2017; Milewicz & Regalado, 2017; Velchev et al., 2021). In connection with the diagnostic process, they receive information on lifestyle changes, including physical activity (PA) restrictions (Cheng & Owens, 2016; Thijssen et al., 2019; Johansen et al., 2020b) and sometimes job restrictions to avoid unhealthy stress or heavy physical work (Johansen et al., 2020b).
Chronic pain is a complex phenomenon covering both physiological and psychosocial aspects (Chapman & Gavrin, 1999). It is commonly described as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage, lasting more than 12 weeks” (Chapman & Gavrin, 1999). Chronic pain is the main cause of long‐term sick‐leave and disability in Norway (Rustøen et al., 2004) and Europe (Breivik et al., 2006). In the Norwegian general population (NGP), chronic pain is often found to be widespread, generalized and associated with female gender, high age, low educational level, psychological distress, chronic illness, and low PA (Breivik et al., 2006; Landmark et al., 2013; Rustøen et al., 2004). Studies of patient groups or the general population emphasize that chronic pain tends to create a cluster of problems such as chronic fatigue, sleep problems, withdrawal from activity, reduced sexual activity, compromised immune function, and mood disorders (Chapman et al., 2008).
Fatigue is often defined as an “overwhelming sense of tiredness, lack of energy and feeling of mental or physical exhaustion, or both” (Dittner et al., 2004). Fatigue is also prevalent in the NGP (Lerdal et al., 2005), and a common symptom in various chronic diseases (Dittner et al., 2004). Fatigue has been found to be a major determinant of disability, which significantly influences quality of life and impairs people's work ability (Bathen et al., 2014; Lerdal et al., 2005).
We have found sparse knowledge on chronic musculoskeletal pain and fatigue in persons with LDS and vEDS. However, from our clinical experience and descriptions of the diagnoses, we know these patients have high disease burden, including pain and fatigue symptoms (Byers et al., 2017; Johansen et al., 2020b; Meester et al., 2017). On the other hand, in Marfan syndrome (MFS), the most well‐known HTAD condition, more studies have explored the prevalence of chronic pain and fatigue (Bathen et al., 2014; Velvin et al., 2016). These studies have indicated that chronic pain and fatigue symptoms are common in these patients, and limit their daily lives and reduce quality of life (QOL) (Velvin et al., 2015). Nevertheless, there is an agreement that more research on chronic pain and fatigue within the HTADs is necessary (Velvin et al., 2016).
In two previous articles on health burden perspectives (Johansen et al., 2020a) and physical activity (Johansen et al., 2020b) among adults with LDS and vEDS, we showed that the participants reported high prevalence of pain and fatigue symptoms. With data collected from the same study group, the aim of this article was to present a more detailed description of self‐reported chronic pain (intensity, locations, and perceived impact on certain activities of daily life) and fatigue symptoms. Another aim was to explore the associations between chronic pain and fatigue scores with demographic and clinical factors in this study group of adults with LDS and vEDS.
Heidi, J. , Gry, V. , & Lidal, I. B. (2022). Pain and fatigue in adults with Loeys–Dietz syndrome and vascular Ehlers–Danlos syndrome, a questionnaire‐based study. American Journal of Medical Genetics Part A, 188A:2605–2616. 10.1002/ajmg.a.62858
Accessed February 28, 2024.