TYPE Original Research PUBLISHED 28 February 2023 DOI 10.3389/fpsyg.2023.1019863 Adjustment to disease and quality OPEN ACCESS of life in people with vascular Ehlers-Danlos and Loeys-Dietz EDITED BY Federica Galli, Sapienza University of Rome, Italy REVIEWED BY Annunziata Romeo, syndromes: A mixed-method University of Turin, Italy Ricmond Jeremy, study The University of Sydney, Australia *CORRESPONDENCE Carolina Baeza-Velasco 1,2,3*, Nuria Rodriguez 4, Laura Parra 1 and Carolina Baeza-Velasco Teresa Gutiérrez-Rosado 5 carolina.baeza-velasco@u-paris.fr SPECIALTY SECTION 1 Laboratoire de Psychopathologie et Processus de Santé (LPPS UR4057), Université Paris Cité, This article was submitted to Boulogne-Billancourt, Paris, France, 2 Department of Emergency Psychiatry and Acute Care, CHU Health Psychology, Montpellier, Montpellier, France, 3 Institute of Functional Genomics, University of Montpellier, CNRS, a section of the journal INSERM, Montpellier, France, 4 Health and Social Projects (with Heart), Barcelona, Spain, 5 Department of Frontiers in Psychology Clinical and Health Psychology, University Autonomous of Barcelona, Barcelona, Spain RECEIVED 15August 2022 ACCEPTED 30 January 2023 PUBLISHED 28 February 2023 Background: Vascular Ehlers-Danlos (vEDS) and Loeys-Dietz syndromes (LDS) CITATION Baeza-Velasco C, Rodriguez N, Parra L and are hereditary disorders of connective tissue having severe vascular complications Gutiérrez-Rosado T (2023) Adjustment to (HDCTv) which lead to an increased risk of premature death. Little is known about disease and quality of life in people with the impact of the disease in patient’s daily life. vascular Ehlers-Danlos and Loeys-Dietz syndromes: A mixed-method study. Method: Sixteen HDCTv patients (vEDS=9 and LDS=7), 16 age and sex-matched Front. Psychol. 14:1019863. hypermobile Ehlers-Danlos syndrome patients (hEDS) and 18 healthy subjects doi: 10.3389/fpsyg.2023.1019863 (HS), responded to self-questionnaires assessing psychosocial adjustment, quality COPYRIGHT of life (QoL), anxiety, depression, pain, fatigue and sleep problems. Patients with © 2023 Baeza-Velasco, Rodriguez, Parra and Gutiérrez-Rosado. This is an open-access HDCTv were also interviewed in order to explore qualitatively their experience article distributed under the terms of the with the disease. Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other Results: Compared with HS, patients with HDCTv scored significantly higher on forums is permitted, provided the original anxiety, depression, fatigue, sleep problems, and lower on QoL. Most HDCTv author(s) and the copyright owner(s) are patients (93.8%) have optimal psychosocial adjustment. In addition, HDCTv credited and that the original publication in this journal is cited, in accordance with accepted patients scored higher on QoL and psychosocial adjustment, but lower in pain, academic practice. No use, distribution or fatigue, sleep problems, and depressive symptoms than hEDS patients. Four main reproduction is permitted which does not themes were identified in qualitative analyses: living with HDCTv, knowledge/ comply with these terms. ignorance of the disease, health behaviors/self-care and coping strategies. Conclusion: Our results suggest that despite the negative impact of HDCTv on the patients’ daily lives, overall, they present an optimal disease adjustment which points to appropriate coping strategies. More research in psychosocial aspects of people with these rare diseases are needed to confirm these results and better understand their needs. KEYWORDS Ehlers-Danlos sydromes, Loeys-Dietz syndrome, psychosocial adjustment, quality of life, anxiety, depression, rare diseases, mixed-method Frontiers in Psychology 01 frontiersin.org Baeza-Velasco et al. 10.3389/fpsyg.2023.1019863 Introduction and dissection. Results of this study showed that patients may experience psychosocial distress and coping difficulties, even years The heritable disorders of connective tissue (HDCT) are a group after diagnosis. In addition, although the study by Johansen et al. of genetic diseases affecting the proteins of the connective tissue (2021) did not investigate adjustment, this explored life satisfaction in matrix such as collagens, elastins, fibrillins, and tenascins. Fragility of patients with vEDS and LDS (n = 52). Results showed that the areas tissues is a common feature of HDCT for which the prognosis can with a major proportion of participants satisfied were family life range from benign to life threating. Among HDCT with life- (69%), activities of daily living (69%), and relationships with their threatening complications are vascular Ehlers-Danlos syndrome partners (68%). In contrast, the areas of somatic health and vocations (vEDS, a.k.a. EDS type IV), and Loeys-Dietz syndrome (LDS). vEDS were those with a less proportion of participants satisfied (<33%). is caused by mutations in collagen, type III, alpha-1 (COL3A1) and its Particularly on Ehlers-Danlos syndromes, quantitative and prevalence is estimated between 1:20,0000–50,000 (Omar et al., 2021). qualitative studies on quality of life (QoL) and the influence of the Concerning LDS, it is caused by mutations in genes encoding for disease in those affected exist. However, these studies are focalized components of the transforming growth factor beta (TGFβ) signaling either in the hypermobile subtype (hEDS) which is the most frequent pathway: TGFBR1, TGFBR2, SMAD2, SMAD3, TGFB2, and TGFB3 form of Ehlers-Danlos syndrome among 13 subtypes, or these studied (Velchev et al., 2021). As vEDS, LDS is a rare disease but its prevalence samples mixing different subtypes (e.g. Berglund et al., 2000, 2015; remains unknown (Gouda et al., 2022). Bovet et al., 2016; Kalisch et al., 2019; Palomo-Toucedo et al., 2020). vEDS and LDS are part of HDCT also belonging to the group of Thus, the specificities of vEDS concerning psychosocial adjustment hereditary thoracic aortic aneurysms and dissections (Fusco et al., remain poorly known, as well as those of people with LDS. 2022). Indeed, both conditions present multi-systemic manifestations The objectives of this cross-sectional study with a mixed (i.e., cardiovascular, musculoskeletal, craniofacial, ocular, and methodology (quantitative and qualitative) are firstly, to explore the cutaneous; Velvin et al., 2019). Nevertheless, the most serious are psychosocial adjustment to disease and certain dimensions of QoL those related to the cardiovascular system such as risk of aneurism and (physical functioning, vitality and general health) in people with dissection of the aorta and other arteries (Velvin et al., 2019). vEDS HDCTv (vEDS and LDS), and compare them to two populations: and LDS can also present spontaneous organ rupture (e.g., spleen, healthy subjects (HS), and patients with hypermobile Ehlers-Danlos intestine, and uterus; Chu et al., 2014; Frise et al., 2017; Frank syndrome (hEDS) which belong to the same family of diseases (HDCT) et al., 2019). but without life-threating complications. Secondly, we explored the life Because of the exceptional arterial and organ fragility, life experience of patients with HDCTv through semi-structured interviews. expectancy has been estimated at 51 years in vEDS (Frank et al., 2019), and 37 years in LDS (Loeys et al., 2006). However, as Pyeritz (2014) stated, advances in last decades concerning diagnosis, follow-up and Method treatment including surgery in LDS decreased acute dissection events and therefore increased life expectancy. Design and participants People affected by these HDCT with vascular complications (HDCTv) may being unaware they are affected until the first This is a cross-sectional study with a mixed methodology complication appears (Chu et al., 2014). These complications may (quantitative and qualitative), carried out in Spain and focused on require emergency interventions with an increased risk of subsequent people suffering from HDCTv (i.e., vEDS and LDS). The latter are morbidity and loss of physical function (Velvin et al., 2019). Thus, the patients with genetically confirmed vEDS and LDS recruited through diagnosis of a life-threatening disease such as HDCTv can lead the Spanish National Patient Association called Asociación Nacional patients to significant life changes in order to adapt and cope with del Síndrome de Ehlers-Danlos e Hiperlaxitud (ANSEDH). For uncertainty (de Ridder et al., 2008). comparison purposes, patients with hEDS and HS were also recruited The psychosocial adjustment to illness, which is defined as the through the same association and community, respectively. The process of adjusting the internal needs to the new external demands participants were men and women, aged 18 years or older and native given by the new life situation (Livneh and Antonak, 1997), is Spanish speakers. Exclusion criteria for HS were the presence of a important in maintaining optimal quality of life (McCathie et al., chronic somatic disease or chronic pain. 2002). Sub-optimal psychosocial adjustment may inhibit the implementation of coping strategies and adherence to medical recommendations, which in turn contributes to potential fatal risk Instruments (Connors et al., 2012). In this sense, exploring the experiential aspects of patients with serious illness is necessary to identify issues such as A questionnaire collecting socio-demographic and health data anxiety, depression, loss of will to live, as well as to predict positive was used. It included questions on age, height, weight, education level, health outcomes and understand complex decision-making processes employment and marital status, diagnosis (vEDS, hEDS, or LDS), age (Schaufel et al., 2011). of onset of symptoms and age at diagnosis. Unfortunately, for HDCTv such as vEDS and LDS, works on Usual fatigue, pain, and sleep problems (during the last 15 days) psychosocial aspects are extremely rare (Velvin et al., 2019). A were measured using a verbal rating scale ranging from 0 (absent) to qualitative study by Connors et al. (Omar et al., 2021) explored 4 (very intense). adjustment and coping mechanisms in individuals with genetic aortic Adjustment to illness was measured using the Psychosocial disease (n = 21) including LDS, Marfan syndrome and other Adjustment to Illness Scale (PAIS; Derogatis, 1986). This instrument conditions in the category of unspecified thoracic aortic aneurysm is composed of 46 questions divided into seven sections: social Frontiers in Psychology 02 frontiersin.org Baeza-Velasco et al. 10.3389/fpsyg.2023.1019863 environment, extended family relationships, sexual relationships, self-questionnaires in word documents for the study by email. Once domestic environment, professional domain, health care orientation, completed, they returned the documents by email. and psychological distress. The answers are formulated in the form of HC were subjects who declared themselves free of diseases and in Likert scales. For all subscales, the lower the score, the better the fit. good physical health. They were recruited from the community and As the PAIS has not been previously used in a sample of HDCT, the social networking services (e.g., Facebook), and matched by age and internal coherence of the questionnaire was checked. The Cronbach’s sex with the HDCTv group. They received, completed and returned alpha observed is 0.98. the consent and self-questionnaire in the same way as patients. Three areas of QoL were assessed using the 36-Item Short Form Data collection for the quantitative part of the study took place Health Survey (SF-36; Mchorney et al., 1993): “Physical functioning” between June and December 2019. In order to deep understand results which is considered an optimal indicator of mobility disability of quantitative data, the research team decided to perform the qualitative (Syddall et al., 2009) and has been extensively linked to the “Activities part of the study. This was possible since all patients with HDCTv and Participations” component of the International Classification of responded favorably to the question “Would you be willing to collaborate Functioning, Disability and Health (Cieza et al., 2002). “Vitality” in another investigation in the future?” contained in the questionnaire of which assess energy and fatigue, and “General health perceptions.” the quantitative study. Thus, in September 2020, the participants of the Items of these subscales (10 items, 4 and 5 respectively) propose a HDCTv group were recontacted by email or telephone to propose them hierarchical range of difficulties with a response format of Likert-Scale. the participation in the qualitative part of the study. Those who accepted Anxiety and depressive symptomatology were assessed with the signed a consent form which was a word document sent by email. Hospital Anxiety and Depression Scale self-questionnaire (HADS; Due to the health crisis (COVID-19) and the geographical Zigmond and Snaith, 1983). The HADS consists of 14 items divided distribution of the participants, the interviews were conducted by into two subscales, one assessing depression and the other anxiety. telephone by two clinical psychologists (LP and CBV). The dates and Each item corresponds to four response modalities rated from 0 times of the interviews were chosen according to each person’s (strong disagreement) to 4 (strong agreement). A higher score availability. The interviews were audio recorded, transcribed verbatim indicates a more severe symptomatology. For each of the two subscales and analyzed. The collection of qualitative data was done between the maximum score is 21, equal or higher than 11 points meaning September and November 2020. clinically significant depressive symptomatology/anxiety. For the qualitative component, a semi-structured interview guide was prepared based on literature and knowledge of the population by one Analyses member of the team. The guide was refined as necessary during data collection (Table 1). Due to the exploratory nature of the study, the Quantitative: Descriptive analyses were performed (percentages, questions were kept broad to allow participants to share their experiences. means, standard deviation), binary logistic regression, Student t-test or Mann–Whitney U test (for continuous variables) and chi square test (for categorial variables) if binary logistic regression was not Procedure possible. The level of significance was set on.05 for all analysis. The quantitative data were analyzed using IBM SPSS version 22 First a call for participation in the study was sent by the patients statistical software. association ANSEDH to its members with HDCTv. Once this group Before to proceed with groups comparisons (i.e., HDCTv vs. HS, was recruited, the patient’s association contacted members with hEDS and HDCTv vs. hEDS) we performed intergroup comparisons on all according to age range and sex of the HDCTv group (i.e., for matching the study variables between vEDS (n = 9) and LDS (n = 7) which purpose) to proposed them the study. compose the HDCTv group. No significant differences were observed All patients (i.e., HDCTv and hEDS) who agreed to participate in sociodemographic and health variables (Supplementary Table S1) received an information note, informed consent and the which is concordant with results of Johansen et al. (2019). Qualitative: The data were processed manually using inductive thematic analysis. This method proves to be very flexible and seems TABLE 1 Interview guide. suitable for an exploratory study (Braun and Clarke, 2013). The steps What does the vEDS/LDS mean to you? followed for analyze included detailed readings of the interviews and What would you say your life is like with this disease? coding process by each researcher separately, comparison of individual Do you think the disease has changed anything in you? – If so, can you explain lists of categories identified, and refinement and agreement on a set what changes you are referring to? of categories. What are the main concerns or difficulties you are currently experiencing? Three researchers participated in this process: the first author who How do you deal with these concerns or difficulties? What strategies do you use? is a clinical psychologist with an expertise in the study of psychosocial aspects associated with HDCT, mainly hEDS. The other two How do you see the future? researchers (TGR and NR, clinical psychologist and nurse/ In your experience, do you think there are positive aspects associated with the anthropologist respectively) have experience in qualitative research disease? but no prior knowledge concerning the diseases studied at the time of Have you noticed any changes in the people around you since you were diagnosed? analyses and did not participate in the data collection. Triangulation In the way they treat you, for example. defined as “the use of multiple methods or data sources in qualitative Of all the things you've told me, what do you think is the most important thing or research to develop a comprehensive understanding of phenomena” the most important thing to remember? (Patton, 1999), was thus ensured, on the one hand, by the Frontiers in Psychology 03 frontiersin.org Baeza-Velasco et al. 10.3389/fpsyg.2023.1019863 TABLE 2 Comparison of the study variables between HDCTv and HS. HDCTv hEDS OR (95% CI) p N=16 Mean (SD)/% [n] N=18 Mean (SD)/% [n] Sociodemographics Age 39.0 (11.7) 38.9 (6.77) 0.999 (0.929–1.075) NS Sex  Women 81.3% [13] 83.3% [15] 1.154 (0.198–6.735) NS With partner 81.3% [13] 72.2% [13] 0.600 (0.118–3.046) NS With children 43.8% [7] 55.6% [10] 1.607 (0.414–6.240) NS University studies 75% [12] 94.4% [17] 5.667 (0.561–57.234) NS Health and psychosocial data p* Body mass index 21.9 (2.6) 23.4 (2.6) 1.277 (0.937–1.740) NS Usual pain intensity 1.06 (1.0) 0.61 (1.0) 0.648 (0.324–1.296) NS Usual fatigue intensity 1.38 (1.2) 0.50 (0.70) 0.399 (0.175–0.909) 0.029 Usual sleep problems 1.63 (1.3) 0.50 (0.70) 0.313 (0.124–0.791) 0.014 QoL dimensions  Physical functioning 68.7 (24.3) 97.7 (3.5) – <0.001*  Vitality 50.9 (13.5) 63.3 (12.8) 1.076 (1.012–1.144) 0.019  General health 41.0 (13.2) 77.7 (12.2) 1.316 (1.016–1.705) 0.037 Anxiety score (HADS) 8.1 (3.0) 4.1 (3.2) 0.674 (0.510–0.890) 0.006 Depression score (HADS) 3.3 (2.4) 1.2 (2.1) 0.620 (0.405–0.949) 0.028 HDCTv, hereditary disorders of connective tissue with vascular complications; HS, healthy subjects; SD, standard deviation; QoL, quality of life; HADS, Hospital Anxiety and Depression Scale; NS, non-significant.*U Mann–Whitney test. complementarity of the quantitative and qualitative approach, and, on scored significantly higher on usual fatigue and usual sleep problems the other hand, by the joint analysis of three researchers. We report than HS. In addition, participants with HDCTv have significantly lower the study according to the Consolidated Criteria for Reporting scores on physical functioning, vitality and general health but higher Qualitative Research (COREQ statement; Supplementary Table S2). scores on anxiety and depression than HS. However, from a categorial point of view, none participant from the HDCTv and HS group have scores exceeding the cutoff suggesting clinically significant levels of Results depression (HADS score ≥11). No differences were found between HDCTv and HS in terms of categorical anxiety, since four patients with Quantitative results HDCTv (25%) and one with HS (5.6%) exceeded the cut-off point suggesting clinically significant levels of anxiety (p = 0.152). From 20 patients with HDCTv contacted by the patient’s association, 16 agreed to participate in the study (response rate: 80%). Thus, vEDS (n = 9) together with LDS (n = 7; subtype 1 = 1; subtype Comparison between HDCTv and hEDS 2 = 5; subtype 3 = 1) compose the HDCTv group. Patients with HDCTv were mainly females (13 women and 3 men) and are on average Concerning sociodemographic data, only marital status is 39 years old (ET = 11.7). Ten patients (62.5%) have antecedents of different between HDCTv and hEDS. Indeed, a greater proportion of HDCT in the family and six (37.5%) have lost a family member due people with HDCTv have a partner compared with hEDS (81.3% vs. to the illness. Ten patients reported having suffered at least one 43.8%; p = 0.035). With respect to clinical and psychosocial data, symptomatic event (arterial, gastrointestinal or respiratory). binary logistic regression analyses controlled for marital status Concerning the hEDS group, from 26 patients contacted by the showed that the HDCTv group scored significantly lower on usual patient’s association, 18 participated in this study (response pain and fatigue intensity as well as in sleep problems and depression rate: 69.2%). than the hEDS group. Moreover, in the three dimensions of quality of life assessed (i.e., physical functioning, vitality, and general health) and in all dimensions of adjustment to disease the HDCTv group Comparison between HDCTv and HS obtained significantly better scores than the hEDS group. Indeed, the vast majority of patients with HDCTv present an optimal psychosocial The comparison between HDCTv (n = 16) and HS (n = 18) showed adjustment to disease (93.8%) unlike patients with hEDS, a minority that these groups are similar in all the sociodemographic variables of whom present an optimal adjustment (25%; p = 0.002). These assessed (Table 2). Concerning health variables, HDCTv patients results are summarized in Table 3. Frontiers in Psychology 04 frontiersin.org Baeza-Velasco et al. 10.3389/fpsyg.2023.1019863 TABLE 3 Comparison of the study variables between HDCTv and hEDS. HDCTv hEDS OR (95% CI) p N=16 Mean (SD)/% [n] N=16 Mean (SD)/% [n] Sociodemographics Age 39.0 (11.7) 38.1 (6.5) 0.990 (0.918–1.067) NS Sex  Women 81.3% [13] 87.5% [14] 1.615 (0.232–11.263) NS With partner 81.3% [13] 43.8% [7] 0.179 (0.036–0.887) 0.035 With children 43.8% [7] 37.5% [6] 0.771 (0.188–3.173) NS University studies 75% [12] 50% [8] 0.333 (0.075–1.489) NS Clinical and psychosocial data p* Body mass index 21.9 (2.6) 24.3 (5.3) 1.262 (0.966–1.649) NS Age at outset of first symptoms 18.6 (15.7) 12.2 (6.0) 0.949 (0.882–1.020) NS Age at diagnosis 34.0 (13.0) 33.6 (7.6) 0.986 (0.915–1.063) NS Diagnosis delay (years) 12.3 (13.2) 21.5 (10.5) 1.062 (0.988–1.143) NS Usual pain intensity 1.06 (1.0) 2.81 (0.65) 23.69 (1.63–343.60) 0.020 Usual fatigue intensity 1.38 (1.2) 2.88 (0.71) 3.951 (1.38–11.25) 0.010 Usual sleep problems 1.63 (1.3) 3.0 (0.89) 2.505 (1.132–5.543) 0.023 QoL dimensions:  Physical functioning 68.7 (24.3) 39.0 (24.4) 0.955 (0.922–0.990) 0.013  Vitality 50.9 (13.5) 27.1 (11.8) 0.856 (0.768–0.954) 0.005  General health 41.0 (13.2) 21.3 (10.7) 0.867 (0.775–0.971) 0.013 Adjustment to disease  PAIS total score 28.6 (15.7) 75.1 (16.1) 1.204 (1.019–1.434) 0.029  Good adjustment (total score <51) 93.8% [15] 25% [4] 43.85 (3.842–500.50) 0.002  Health care orientation 8.7 (3.1) 15.5 (3.4) 2.197 (1.259–3.836) 0.006  Professional domain 3.9 (3.8) 11.0 (3.7) 1.577 (1.138–2.185) 0.006  Domestic environment 3.8 (3.3) 13.7 (4.1) 1.799 (1.231–2.630) 0.002  Sexual relationships 3.3 (3.9) 8.0 (4.2) 1.284 (1.022–1.613) 0.032  Extended family relationships 0.5 (1.3) 6.1 (3.8) 3.112 (1.339–7.230) 0.008  Social environment 2.3 (2.7) 9.8 (4.8) 1.625 (1.157–2.280) 0.005  Psychological distress 5.9 (3.4) 11.5 (3.8) 1.592 (1.153–2.198) 0.005 Anxiety score (HADS) 8.1 (3.0) 10.7 (4.5) 1.192 (0.962–1.476) NS Depression score (HADS) 3.3 (2.4) 8.8 (3.7) 1.655 (1.170–2.341) 0.004 HDCTv, hereditary disorders of connective tissue with vascular complications; hEDS, hypermobile Ehlers-Danlos syndrome; SD, standard deviation; QoL, quality of life; PAIS, Psychosocial Adjustment to Illness Scale; HADS, Hospital Anxiety and Depression Scale; NS, non-significant.*Binary logistic regression controlled for marital status (“with partner”). In terms of categorical depression, both groups of patients are We present a brief description of the four major categories significantly different since none subjects with HDCTv but five with identified and the themes within the categories with hEDS (31.3%) exceeded the cut off suggesting clinically significant illustrative quotes. levels of depression (p = 0.043). However, no difference was found in 1. Living with HDCTv (functional and emotional aspects) categorical anxiety between these groups (HDCTv = 25% vs. hEDS =50%; p = 0.273). • Normality: Several testimonials (n = 11) described that outside of vascular episodes patients can lead a normal life, have a family, a job, etc. Overall, participants reported functionality in Qualitative results various aspects of their lives. Some precautions were highlight as necessary, such as avoiding certain sport and to prevent stress. The 16 patients with HDCTv who participated in the quantitative study accepted the qualitative interview. The characteristics of This is a disease that has no symptoms, it is discovered when participants are summarized in Table 4. the aorta ruptured. I had surgery to avoid this, so I could lead Frontiers in Psychology 05 frontiersin.org Baeza-Velasco et al. 10.3389/fpsyg.2023.1019863 TABLE 4 HDCTv patient’s characteristics. fear in their love ones about their own condition. Guilt is another Participants Gender Age HDCTv Length of emotion present especially concerning pregnancy and the risk of interview genetic disease in the offspring. In many cases, patients have P1 Female 44 LDS 20 min faced the premature death of a family member due to the disease which increase fears in the family. P2 Female 36 vEDS 18 min P3 Male 42 vEDS 45 min Psychologically, the only thing that annoys me is knowing that my P4 Female 38 LDS 18 min nephews and my son have it too (…) I hope that nothing is going P5 Female 47 LDS 23 min to happen to my son and that the diagnosis does not P6 Female 29 vEDS 32 min worsen… [P16] P7 Female 39 LDS 26 min I was considered doing an interruption of the pregnancy, but then P8 Female 32 vEDS 24 min we decided to go ahead. I already knew then that my eldest son P9 Female 35 vEDS 26 min had the disease, but what worried me was my youngest son, I had P10 Female 23 LDS 40 min many feelings of guilt towards him because I was the one with the disease [P5] P11 Male 28 vEDS 25 min P12 Female 39 vEDS 30 min My mother lives more alert and I suppose also in fear that P13 Female 40 LDS 16 min something might happen to us… [P2] P14 Female 54 vEDS 33 min 2. Knowledge/ignorance of disease P15 Female 42 LDS 15 min P16 Male 74 vEDS 23 min • Diagnosis: The announcement of the diagnosis was often lived as HDCTv, Hereditary disorders of connective tissue with vascular complications; LDS, Loeys- a hard experience. However, for eight patients naming the disease Dietz syndrome; vEDS, vascular Ehlers-Danlos syndrome; P, participant; min, minutes. and receiving information about it allowed them to take steps to prevent complications, understand and make sense of their early my normal life, I continue to work, I have three experience of feeling different or sick, as well as socially legitimize children … [P1] their condition. I continue to do my normal life but I take precautions, I lead a Having the diagnosis reassures me about prevention, because my quiet life [P2] mother and brother died from the disease [P5] Those who have not had an episode (vascular) lead a normal I spent 30 years without knowing the diagnosis and something life [P3] could have happened. But now with the care that I have, with the calmer life that I lead, the controls that I do, I see it more difficult • Fear and uncertainty: the majority of participants (n = 12) for something to happen to me [P7] expressed feel worried or anxious about health problems that they may suffer at any moment. Dealing with uncertainty is a Since I was diagnosed I no longer have to prove anything to constant in their lives. anyone, and to be able to prove that I really couldn't work because my hands hurt, my elbows hurt … [P13] Sometimes when I feel a strong pain, I sleep with the phone next to me in case I have to call because something happened. Even • Health professionals: Four participants describe dealing feeling that I am a strong person, my reality is that I live in frequently with the lack of knowledge and unpreparedness of fear [P14] health professionals for the management of their diseases. There are doctors who don’t know about the disease, don’t even Afraid that one of my arteries will be dissected or one of the know how to write it… You have to see several doctors, the one carotid and paravertebral kinkings that I have will create a who sees us annually doesn't even want to take a blood test for thrombus and I will suffer brain damage or death… if I feel my fear that something will happen, it’s exaggerated … In general, head hurts or feel palpitations or tachycardia, I think it may there is a lot of ignorance in the medical world about the be something bad… [P2] vEDS [P2] Nothing to worry about… except that I think about the future and Doctors hardly study this disease at university. It is a rare disease I know I'm going to have more problems [P11] and they waste time learning about it, so little is known. Sometimes I prefer not to go to medical appointments because • Negative emotions in and regarding family members: 11 patients they don't know what it is, we know more than them… That's why evoked feelings of fear, worry with respect to state and quality of we go to congresses, there we look for doctors for their ask life of relatives who also have the disease, and/or perceiving the questions [P3] Frontiers in Psychology 06 frontiersin.org Baeza-Velasco et al. 10.3389/fpsyg.2023.1019863 3. Heath behaviors/self-care They describe using strategies such as humor and optimistic thoughts to build resilience. • Medical adherence: Patients are very aware of the need to monitor their health and follow the recommendations of I take it with a lot of humor. What I have realized is that those who doctors to prevent complications. This optimal medical are worse off are usually the ones who make the most jokes. adherence/compliance, which appear in data of eight patients, I know that most people I have met take it with a lot of jokes and allow them to increase their feelings of control over events and I love that [P11]. self-efficacy. I try to think that I am fine and that everything will be fine. I try I try to be very strict with medical check-ups, I always try to carry to think that I can die at 90, without anything happening of that it as naturally as possible. But I am very strict with the could happen to me at the vascular level [P2] controls [P13] • Cognitive avoidance: Eight patients show avoid unpleasant or The truth is that any day something can happen to you, that's why I go to all my distressing thoughts about disease. Efforts to distract from negative check-ups and I try to have good trust with the doctors because I know that one day thoughts were described. theywillbethereincasesomethinghappenstomeonedayandItrytodoeverything theytellme[P6] I try not to think too much, because if I think, and think about things a lot, it's bad. So I try to live every day, I work 8 hours so • Modulation of lifestyle: In order to minimize injuries and I live busy from top to bottom … [P6] complications, several patients (n = 10) have introduced behavioral changes to their routines such as healthier eating, exercises to get I try not to think too much because if the day doesn't eat you up, fit and reduce stress, changing jobs if considered stressful, etc. negative thoughts eat you up and I don't want that [P13] I started to take better care of myself, I didn't play sports and • Focus on present: to think in the future is often anxiogenic for I started doing Pilates, watching what I eat … [P1] patients. Thus, to focus on present is a strategy frequently used by eight patients. Plans are often thought only in the short term Now I am calmer and more cautious. I also try to take better care since seem more realistic and emotionally tolerable. of my diet, to eat healthier and to exercise in a way moderate. I have become more homely [P2] Honestly, I live day to day. Before I was not so aware, because a young person plans all the time without thinking that at some point Before, I would never have gone on a diet; now I seek health … this might end, or that you are going to end up in a hospital [P7] I do yoga, I would never have done that before. I am looking for activities that calm down, I walk, I exercise to Since I have the diagnosis I do not see myself, I do not visualize be calmer … [P3] myself much further, I try to live now, I do not visualize myself when my son is older, the truth is that I do not visualize it. I try to 4. Coping strategies live in the now, to give thanks when I get up in the morning, what I do and what I want is to enjoy my family as long as possible [P13] • Positive reappraisal: 12 patients were able to find positive sides to the context of the illness or create positive meanings by focusing • Acceptance: Six patients declared have accepted their condition. on personal growth, acquired skills, identification of values They recognized this aspect as a key of the process of “normalize” and reprioritization. the day-to-day life. In addition, acceptance allows them to orientate the focus on aspects of life on which they may have I was very lucky because I was detected the disease early … I see more control. my brothers (also sick) and other people who are very bad, so I think I am lucky … [P1] Life is like that, recalculate the route and continue… there is no other option … I realize that definitely nothing is in my hands, the I have learned that I can handle things that I thought I couldn't, only thing I can do is go to the doctor and check myself [P7] I have learned to listen to myself, to relax and calm my anxiety, although I don't always succeed … to be calmer, to enjoy my home more, the tranquility, the little things … [P2] I was born like this and I cannot erase it from the DNA, but what I can do as I have been until now is to continue taking it calmly, At work I was very involved, it was the most important, there with humor, continue living my life with the greatest possible comes a time when it is no longer but the family. Priorities change, normality [P10] I enjoy other things, seeing friends … Now I’m closer to my mother, my sister … [P3] • Family and friend support: Several testimonials (n = 10) identified the support of relatives and friends on a day-to-day basis as well • Humor and optimism: Six patients consider reported that having as during medical visits as a very important help to lead with a positive cognitive approach is helpful in dealing with concerns. difficulties and negative emotions. Frontiers in Psychology 07 frontiersin.org Baeza-Velasco et al. 10.3389/fpsyg.2023.1019863 I would not have been able to overcome even half of things patients (≥68%) were satisfied with life specifically with activities of without her (mother) [P10] daily living, family life and relationships with their partners. In addition, they observed that low levels of fatigue, anxiety and multi- I have support from them (family), my brother is also sick and he’s organ burden were associated with higher scores on life satisfaction in more seriously ill since he has had significant aortic problems. My several domains. father died for this. We support each other … [P2] Diagnosis is another clue to understand the differences observed on adjustment to disease and QoL between both groups of patients. From a purely descriptive point of view, the diagnosis delay is 9 years higher in hEDS than in HDCTv. The HDCTv Discussion studied here (vEDS and LDS) can by molecularly verified which facilitate recognition. This is not the case of hEDS whose genetic This study aimed to explore the psychosocial adjustment to abnormality is still not identified. Thus, hEDS is the least disease and certain dimensions of QoL in people with HDCTv (vEDS recognized HDCT mainly due to the lack of confirmatory and LDS) through a mixed methodological approach. laboratory/molecular tests (Castori, 2012). In this regard, the As expected, the quantitative results showed that compared to diagnosis of a chronic disease favor the implementation of coping HS, people with HDCTv have lower QoL, specifically in the areas of strategies (Sacheti et al., 1997). On the contrary, a prolonged delay physical functioning, vitality and perception of general health. In in diagnosis maintains the anxiety and waiting of the affected addition, they had more usual fatigue and sleep problems as well as persons, which in turn delays adaptation (Besson et al., 2020). higher levels of anxiety and depression symptomatology compared Our qualitative results support these observations and shed some with HS. Indeed, it is well known that chronic diseases, especially light on quantitative results. Narrative data show us that for many life-threatening ones, have a negative impact on the QoL of those HDCTv patients, to receive the diagnosis was a hard experience but affected (Velvin et al., 2019). Though, no differences were observed positive and even relieving. Indeed, having the name of the disease, between patients with HDCTv and HC concerning pain intensity patients were able to seek information, learned how prevent (both groups present low usual pain intensity). This contrast with the complications, make changes in their lifestyle and legitimize their results of Johansen et al. (2019) who found a high proportion (79%) health status socially. This could contribute to their good adjustment of patients with vEDS and LDS suffering from chronic pain. Plausibly, to the disease. In this sense, we observed that most patients with these differences may be related to pain assessment. In the study of HDCTv adhere with medical recommendations showing a disciplined Johansen et al. (2019) assessment consisted in one item (yes/non) compliance with medical controls and changes to their habits to avoid asking for history of chronic musculoskeletal pain for a period of complications (e.g., modulation of physical activity, diet). This is >3 months last year, while in our study the measure was focalized in consistent with results of Connors et al. (2015), who also reported the usual pain intensity experienced during the last 15 days. Thus, optimal medical adherence in patients with different aortopathies we cannot exclude that patients of our sample had passed a chronic including HDCT such as LDS (N = 21). pain period. Moreover, qualitative data show that most patients experience Concerning the comparison between HDCTv and hEDS (the last fear and uncertainty regarding the course of their disease and that of also belonging to the HDCT but without life-threating complications), their family members who are also affected. However, patients’ patients with HDCTv have a better QoL in the three dimensions strategies to cope with stress are varied and mostly functional (e.g., assessed as well as better psychosocial adjustment to disease than positive reappraisal, social support, acceptance, and humor). This is hEDS. Indeed, the vast majority of participants with HDCTv (93.8%) confirmed by the fact that despite the great stressors with which they scored in the optimal adjustment range, which contrasts with the must deal, only four participants with HDCTv present clinically scores of patients with hEDS, who mostly (75%) show poor adjustment. significant anxiety and none have clinically significant depressive At first glance, these results may be surprising since HDCTv are symptomatology. This is consistent with the results of Connors et al. serious diseases in which those affected live with the threat of severe (2015) who explored adjustment and coping mechanisms in vascular events without warning, and having a live expectancy individuals with genetic aortic disorders including LDS. They between 31 and 51 years old (Loeys et al., 2006; Frank et al., 2019). observed that dysfunctional coping strategies were infrequent among hEDS in contrast, is a HDCT and the subtype of EDS considered as these patients and that they experienced minimal emotional distress. the least severe (Levy, 2004). Nevertheless, although hEDS is not life- Speculatively, these optimal coping strategies may appear in these threatening like HDCTv, its clinical picture is characterized by a patients from good psychological resources at individual level and by variety and accumulation of symptoms of long duration that make learning. Indeed, many patients come from families leading with the hEDS a highly disabling condition (Baeza-Velasco et al., 2018). disease from several generations. Thus, some strategies of coping Indeed, studies show that patients with hEDS have severe functional could be observed and learnt from relatives. impairment determined mainly by pain and fatigue (Voermans and The characteristics observed in HDCTv in this study are consistent Knoop, 2011; Kalisch et al., 2019). In this sense, our results show that with the literature on the individual factors associated with adjustment people with HDCTv present significantly less depression, pain, fatigue to illness (e.g., coping strategies; Dekker and de Groot, 2018). Other and sleep problems compared with people with hEDS. This may help factors impacting adjustment are those related to the illness itself. In explain the differences obtained in QoL between these two groups this sense, most of interviewees emphasize that apart from the of patients. vascular episode, the disease has no or few symptoms which allows In a similar line, Johansen et al. (2021) who studied life satisfaction them to lead a life they consider normal. In the current context where in patients with HDCTv, reported that a high proportion of these chronic diseases are on the increase, health is defined not as the Frontiers in Psychology 08 frontiersin.org Baeza-Velasco et al. 10.3389/fpsyg.2023.1019863 absence of disease but rather as the ability to adapt and self-manage Data availability statement (Huber et al., 2011). In this sense, a satisfying life in many areas is possible for these patients. The data that support the findings of this study are available from A critical point emerged in interviews is the perception of the lack the corresponding author upon reasonable request. of knowledge of the disease on the part of health professionals. This is consistent with the results of one of the few qualitative studies carried out on patients with vEDS, which identified lack of knowledge of the Ethics statement disease in emergency departments as one of the most common sources of frustration (Shalhub et al., 2020). Thus, disseminate Ethical review and approval was not required for this study of knowledge about HDCTv is needed to improve the diagnosis and human participants in accordance with the local legislation and management of these patients. institutional requirements. The patients/participants provided their Finally, in view of the important differences in psychosocial written informed consent to participate in this study. aspects observed between HDCTv and hEDS patients, more efforts are needed in order to design studies aimed to elucidate the psychosocial specificities of different subtypes of HDCT rather than Author contributions mixing subtypes as is often the case, especially with the Ehlers- Danlos syndromes. In this sense, and from a clinical perspective, CB-V designed the study, collected the quantitative data, and these results should be considered for group interventions for performed the statistical analysis. LP and CB-V conducted the semi- patients with HDCT. Patients with different HDCT in the same group structured interviews. LP transcribed interviews. NR, TG-R, and may not work optimally if there is heterogeneity regarding CB-V analyzed qualitative data. CB-V drafted the manuscript. All psychosocial functioning as observed in this study. In such a authors contributed to the article and approved the submitted version. therapeutic context, patients may not feel understood or identified with the rest of the group and present very different needs, which may interfere with adherence to the intervention and in the group Acknowledgments climate. In addition, the assessment of psychosocial adjustment and QoL should be integrated to the clinical follow-up of patients with The authors wish to thank all the participants of this study, Josefa HDCTv in order to detect difficulties beyond the somatic level and Lopez and Magdalena Pérez from ANSEDH, and Léonor Fasse for guide healthcare accordingly. their time and valuable collaboration. This study has several limitations. Concerning the quantitative component, the small sample size and the transversal design which does not allow inferences on the directionality of the associations. In Conflict of interest addition, the recruitment through a patient association which implies that the generalization of results is compromised. In addition, although The authors declare that the research was conducted in the 8 out 16 participants with HDCTv sent us the document of their genetic absence of any commercial or financial relationships that could test, the rest of patients self-reported their diagnosis. The HS status was be construed as a potential conflict of interest. also self-declared, therefore somatic health problems cannot be excluded in this group. Moreover, we do not have the data about treatment and medications which may impact overall physical factors, mental health Publisher’s note and quality of life. It was not possible neither to examine differences in psychosocial results according to the vEDS variant (not reported in this All claims expressed in this article are solely those of the authors study) and the LDS subtype due to the small sample size. These aspects and do not necessarily represent those of their affiliated should been considered in further research. organizations, or those of the publisher, the editors and the Concerning the qualitative part, data saturation was not reached reviewers. Any product that may be evaluated in this article, or and we were unable to interview more people with HDCTv since the claim that may be made by its manufacturer, is not guaranteed or convenience sample of HDCTv was limited in number (rare disease, endorsed by the publisher. adherents to an association). Thus, additional data is probably necessary to capture the experience of patients. Despite these limitations, this study contributes with data that Supplementary material make an understudied clinical population more visible from a psychosocial point of view. 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