Introduction

Joint Hypermobility (JH) is a highly heritable condition characterized by an increased distensibility of joints as a consequence of connective tissue involvement. The recognition of JH is clinical. The Beighton score [1] is the method most commonly used to assess the widespread nature of hypermobility among a selected number of joints [2] (Fig. 1). JH is not a medical problem when it is presented alone, but when it is accompanied by symptoms (articular and non-articular) occurring mainly due to the fragility of connective tissues, it may signal the presence of a heritable disorder of the connective tissue (HDCT). HDCT is a group of genetic disorders affecting connective tissue matrix proteins such as collagens, elastins, fibrillins and tenascins [3]. HDCT classically includes the Marfan syndrome, Ehlers–Danlos syndromes, osteogenesis imperfecta and joint hypermobility syndrome (JHS) [4], which is the most frequent form with an estimated prevalence between 0.75 and 2 % [5]. The clinical features of JHS overlap with those observed in Ehlers–Danlos syndrome hypermobility type (EDS-HT) and some experts consider them to be the same condition (JHS/EDS-HT) [6]. However, this opinion is not shared by other research groups [7].

Fig. 1
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Beighton score to identify JH [1]

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The diagnosis of JHS/EDS-HT remains clinical in the absence of a biogenetic confirmatory test. Two sets of diagnostic criteria are currently available: Villefranche [8] (Table 1) and Brighton criteria [9] (Table 2).

Table 1 Classification of EDS syndromes [8]
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Table 2 Brighton criteria for JHS [9]
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The abnormal collagen synthesis characterizing JHS/EDS-HT affects all the structures of support of the body (ligaments, skin, muscles, etc.). In a first approach, JHS/EDS-HT seems to be a chronic musculoskeletal condition [10]. However, recent research highlights the multisystemic nature of JHS/EDS-HT [11], which presents with a wide range of extra-articular manifestations (Table 3), some of which might have important implications in eating, weight and nutritional status. Functional gastrointestinal (GI) symptoms such as dysphagia, gastro-esophageal reflux, dyspepsia, recurrent abdominal pain, constipation/diarrhea, etc., are common in JHS/EDS-HT and often disabling [12]. The pathogenesis of GI involvement remains speculative. Abnormal connective tissue forming part of the components of the digestive apparatus and dysautonomia are two possible reasons for the development of GI problems in JHS/EDS-HT [12]. In addition, these patients have hyperalgesia [13], enhanced interoception (i.e., a greater ability to perceive changes in the physiological state of the body) [14] and a tendency to focus on physical symptoms with magnification and beliefs of catastrophic outcomes (“somatosensory amplification”) [15]. These aspects related to increased perception and/or reduced tolerance of pain [16, 17] might influence the chronic GI complaints among those affected.

Table 3 Clinical spectrum of JHS/EDS-HT [11, 22]
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Temporomandibular disturbances (i.e., clinical problems involving the temporomandibular joint and/or the masticatory musculature; TMD) are also prevalent in JHS/EDS-HT [18]. People with TMD show altered functional patterns of mastication [19] due to difficulty biting or chewing and pain. Thus, avoidance of eating hard foods [20] and restriction of mandibular opening (e.g., eating large sandwiches) [21] are some examples of eating-related problems described by TMD patients.

Although not yet studied systematically, chemosensory disorders such as abnormally acute smell (hyper/hyposmia) and taste (dysgeusia) functions are usually seen in JHS/EDS-HT patients [22, 23]. Smell and taste abnormalities have been related to decreased food acceptability, nutritionally important dietary alterations and weight changes [24].

According to our clinical experience, several JHS/EDS-HT patients present with eating and weight problems, which complicate the clinical picture and management. Clinical features related to JHS/EDS-HT, such as those mentioned above, might negatively impact eating. However, these issues have not been addressed in the literature.

In addition, for many JHS/EDS-HT patients who have difficulty eating and are underweight, the suspicion of Anorexia Nervosa (AN) has been mentioned in their medical history. The misleading diagnosis of AN when JHS/EDS-HT is unfamiliar to practitioners has been suggested by Zarate et al. [25], who described the case of a young woman with JHS/EDS-HT whose GI symptoms limited her food intake causing a 12 kg weight loss during adolescence. Before the JHS/EDS-HT diagnosis, her eating and weight problems were attributed to AN even though this was strongly denied by the patient. Notwithstanding, screening for eating disorders such as AN seems pertinent in the context of JHS/EDS-HT patients with eating and weight problems.

We describe two illustrative cases in which articular and non-articular JHS/EDS-HT features contribute to the origin and/or maintenance of eating disturbances and critical low body weight. Informed consent was obtained from both patients presented below.

Case 1: Miss D is a 26-year-old female recently diagnosed with JHS/EDS-HT at the Ehlers–Danlos reference center. Major and minor criteria for JHS/EDS-HT diagnosis according to Brighton criteria [9] were: JH (Beighton score = 9/9), chronic arthralgia, recurrent dislocations, thin skin, marfanoid habitus, unequivocally affected first-degree relative (her mother, who was diagnosed with fibromyalgia, has similar symptoms, as do her two sisters). In addition, Miss D has other symptoms of the JHS/EDS-HT clinical spectrum described in Table 3: easy bruising (resulting in a judicial inquiry of her parents for suspected abuse when she was a child), dysautonomia, chronic fatigue, migraine, respiratory dysfunction, hemorrhages (nasal and gingival), hyperosmia, enhanced audition (hyperacousia), and touch sensitivity (cutaneous hyperesthesia). GI problems are also significant and include constipation, abdominal pain, dysphagia and gastroesophageal reflux. The JHS/EDS-HT symptoms started in infancy.

In her history, a bullying experience at school because of her physical appearance (long, thin limbs) is relevant. “I found myself ugly and skinny, I could see my bones…”. Her entourage suspected AN. She explains that she did not want to lose weight, but the painful swallowing and digestion, added to nausea and vomiting caused by certain food smells, generated eating avoidance. At the age of 14, a car hit her while she was cycling. After this accident, her physical and psychological state severely deteriorated. Miss D relates that she was interned in a clinic with an AN diagnosis. At that moment, she was amenorrheic and weighed 28 kg with a height of 160 cm (body mass index; BMI = 11). Hospitalization lasted four years, with some short periods of outpatient monitoring. She comments “I was told that I had AN, and I behaved like the other girls in the clinic; I calculated the calories and such things, but in truth I had no fear of gaining weight and I did not want to lose weight”.

At the time of presentation, Miss D has a normal weight (49 kg; BMI = 19). She is single, lives alone and works as a teacher. The assessment with the International Neuropsychiatric Interview (MINI-DSM-IV) [26] was negative for current AN. However, she fulfilled the criteria for current panic attacks without agoraphobia and dependence on cannabis (which she uses as an analgesic). Her gastrointestinal problems are severe and chronic (“the issue of eating has always been difficult…”) such as musculoskeletal pain.

Case 2: Miss T is an 18-year-old patient monitored at the rehabilitation service due to JHS/EDS-HT-associated problems. Brighton criteria [9] for JHS/EDS-HT diagnosis were: JH (Beighton score = 7/9; her mother and sister also present JH), severe and chronic musculoskeletal pain, recurrent blocks, sprains and dislocations including the temporomandibular joint, thin and mildly hyperextensible skin. She also presents other symptoms of the JHS/EDS-HT clinical spectrum: easy bruising, proprioception dysfunction (clumsiness, frequent trips and falls), mild scoliosis, tachycardia, chronic fatigue, and sleep disturbances. Particularly important are her GI problems: gastroesophageal reflux, bloating, abdominal pain, chronic nausea, constipation, food intolerances and dysphagia. She comments, “I can’t even swallow my own saliva”, “I feel when small pieces of food go down my throat”. In addition, she feels compelled to select soft food to avoid temporomandibular dislocations, “Chewing hurts my jaw and face”. Thus, Miss T explains that eating often becomes a painful experience.

Miss T was diagnosed with JHS/EDS-HT at the age of 15 after several years of inconclusive medical explorations. Her symptoms started in infancy and became worse in adolescence. In this period (12 years old), she was a victim of sexual touching by a family member. After that, she refers to having experienced worsening musculoskeletal pain, depressive feelings, self-injurious behaviors, lack of appetite, weight loss until she reached 35 kg (BMI = 12.9), distorted body image (feelings of fatness), fear of gaining weight and amenorrhea, resulting in a diagnosis of depression and AN, followed by two psychiatric hospitalizations at the age of 14.

At the time of presentation, Miss T lives alone. Her level of autonomy fluctuates; some days she cannot get up and stays in bed. There is a high level of school absenteeism because of her health problems. She often uses a stick to walk. She consumes cannabis regularly to calm the pain. She weighs 45 kg (the highest weight she has had) and measures 169 cm (BMI = 15.8). Despite being underweight, an assessment with the MINI-DSM-IV revealed that she does not fulfill the diagnostic criteria for current AN. According to the Contour Drawing Rating Scale [27], Miss T is dissatisfied with her body but with a positive magnitude (i.e., she wants to increase her body size). She is proud of having gained 10 kg in recent years. She would like to gain at least 5 kg more and have “a little more voluptuous shape”. However, the GI complications of JHS/EDS-HT as well as temporomandibular-related problems such as masticatory muscle pain and dislocations continue to impact her eating behaviors in a negative way (e.g., she must be very selective with food, eat slowly and sparingly, cutting food into tiny pieces).

Discussion

These clinical cases illustrate the interrelationship between a medical condition such as JHS/EDS-HT and difficulty eating and weight loss. Despite the increase in publications about JHS/EDS-HT in recent years, little interest has been paid to these issues. The fact that patients with eating problems are often reluctant to mention it spontaneously [28] may explain the lack of exploration in this area. Thus, screening for eating difficulties and weight changes in JHS/EDS-HT patients seems necessary to avoid further complications.

Articular and non-articular problems, common in JHS/EDS-HT, can potentially affect eating. GI symptoms (e.g., dysphagia, gastro-esophageal reflux, etc.) and TMD (e.g., difficulty opening the mouth and chewing) might have painful consequences, especially for food intake and digestion [29]. The fragility of oral mucosa observed in JHS/EDS-HT [30] might also disrupt eating (e.g., reduced tolerance to some food textures and temperatures) as well as causing dental problems such as caries, often promoted by poor oral hygiene influenced by mucosal fragility and restraint of joint mobility (e.g., the wrist) [30]. Thus, for a subgroup of JHS/EDS-HT patients having some of the above-mentioned features, chronically and/or with severe intensity, the experience of pain might go beyond the musculoskeletal system and extend to the field of feeding. Those affected can potentially develop a fear of oral/abdominal pain from eating, which may lead to food selectivity, particular patterns of eating and even food aversion. In this regard, pain-related fear is linked to high bodily awareness and pain hypervigilance [31], which are increased in people with JH and JHS/EDS-HT [14, 15]. Thus, a certain parallelism can be drawn between the fear of movement or kinesiophobia [32] (with the consequent avoidance behaviors) due to musculoskeletal pain, and the fear of eating due to oral and visceral pain.

Smell and taste alterations are often reported by JHS/EDS-HT patients [22, 23] and constitute an additional obstacle to food acceptability. In addition, Cutts et al. [33] reported multiple food allergies requiring food exclusion (mainly milk, egg, wheat and soy) among children with JHS/EDS-HT while Danese et al. [34] observed an increased rate of celiac disease (i.e., a gluten-sensitive condition) in JHS/EDS-HT.

All these elements might signal the installation of a vicious circle consistent with food restriction and dysfunctional psychological/behavioral aspects related to eating in response to specific functional JHS/EDS-HT characteristics, with negative consequences in terms of weight and nutrition (Fig. 2). Poor nutritional status may in turn worsen the physical symptoms of JHS/EDS-HT or participate in the onset of certain manifestations such as fatigue, pain, osteoarthritis, reduced bone mass, etc. [12] and, by extension, diminish quality of life. In this regard, it has been reported that permanent underweight negatively impacts the immune system and worsens the course of a disease [35]. In addition, Miles et al. [36] warned about the risk of visceral perforation in Ehlers–Danlos patients with a large weight loss and intense physical activity.

Fig. 2
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Diagram illustrating possible relationships between some features or common co-occurring problems in JHS/EDS-HT might contribute to eating difficulty and weight loss

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Little is known about nutritional aspects in JHS/EDS-HT. Felice et al. [37] studied children with a history of impaired fetal growth. They observed that the proportion of JH and skin softness was greater among intrauterine growth restriction children than in controls. According to Castori et al. [12], such an association may be linked to the appropriateness of intrauterine nourishment of the fetus. JH and JHS/EDS-HT eating-related problems probably influence the diet of females affected during pregnancy. In addition, Sanjay et al. [38] observed that a high percentage of healthy Indian children with JH (57.1 %) were underweight. A significant negative correlation between JH and BMI was found in this study. Another work in Indian children found that JH was associated with moderate and severe malnutrition, and that moderate and severely malnourished hypermobile children were more likely to have musculoskeletal symptoms than non-hypermobile children [39]. Meanwhile, Cutts et al. [33] observed that most children with JHS/EDS-HT and food allergies required artificial nutrition. The relationship between JH and JHS/EDS-HT, eating and nutritional status is complex, and should be elucidated in further studies.

Investigating eating disorders such as AN as well as the accuracy of such diagnoses in the context of JHS/EDS-HT are relevant issues. AN is an eating disorder present in various somatic medical conditions such as diabetes and renal disease [28]. According to Baylé and Bouvard [40], a somatic disease with consequences on food intake and weight changes, may mask an eating disorder as observed in Crohn’s disease. Moreover, several mental disorders, including eating disorders, have been related to collagen-altered conditions [41]. In this sense, difficulty eating and weight changes in JHS/EDS-HT should warrant a thorough evaluation to screen for a comorbid eating disorder. On the other hand, misdiagnosis of eating disorders is also possible especially considering the lack of knowledge of the clinical picture of JHS/EDS-HT among the medical community [42]. This seems to be the case of the first patient (“Miss D”) presented above. According to the patient report, she was diagnosed with AN despite the fact that she denied having anorexic cognitions, such as a distorted body image and pathological fear of becoming fat, which are key features of AN (Table 4) [43]. In clinical practice, we find that this situation is not a rare event. Zarate and colleagues [25] also described a similar case of suspected AN in the context of an undiagnosed JHS/EDS-HT. In our two patients presented above, the onset of JHS/EDS-HT symptoms was prior to the suspicion of AN in adolescence. The long delay in the diagnosis of JHS/EDS-HT observed in both cases is, unfortunately, more the norm than the exception. Several authors have stressed the fact that JHS/EDS-HT is under-recognized by physicians worldwide. Russek et al. [44] revealed that 73.2 % of physiotherapists (who have a high probability of encountering patients with JHS/EDS-HT) were not familiar with the diagnostic criteria of this syndrome. Thus, it is not surprising that the diagnostic delay has been estimated at up to 20 years [22]. Early recognition of JHS/EDS-HT is essential to prevent the chronicity of symptoms and complications such as those related to eating and weight as well as misdiagnosis.

Table 4 Diagnostic criteria for AN in the fifth edition of the diagnostic and statistical manual of mental disorders (DSM-5) [43]
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In contrast, the second case presented (“Miss T”) had antecedents of distorted body image (feeling fat despite being underweight) and fear of gaining weight as typically seen in AN, suggesting the coexistence of this disorder with JHS/EDS-HT. GI symptoms and TMD might have participated in the onset and maintenance of AN in this patient. Concordantly, Goh et al. [45] stated that disorders of the connective tissue could potentially cause an eating disorder.

Although there are no systematic studies exploring the co-occurrence of JHS/EDS-HT and AN, two studies have examined the relationship between JH and AN. A study comparing 30 patients diagnosed with AN, with 29 first-degree relatives and 16 healthy subjects, found that JH was significantly more common in AN patients than in both control groups [45]. Interestingly, the AN patients in this sample also presented a high prevalence of GI problems and dysautonomia, which could be suggestive of JHS/EDS-HT, but the presence of the syndrome was not explored. The second study [46] found that hypermobile secondary school students reported anorexic experiences to a greater extent than those who were non-hypermobile. In this sense, the model “neuroconnective phenotype” by Bulbena et al. [14] postulates that people with JH and anxiety often present a wide range of somatic and psychopathological features in which ergotropism behaviors, such as decreased appetite and weight but increased activity and over control, are included. All these features are linked to AN. Moreover, the impaired proprioception (i.e., lack of awareness of the position of one’s body) observed in JHS/EDS-HT [47] causing clumsiness, abnormal posture, instability and frequents falls, may affect the body schema (i.e., non-conscious system of processes that constantly regulate posture and movement) and body image (i.e., perceptions, beliefs and attitudes pertaining to one’s own body) [48]. In addition, visible signs of illness, such as the use of a stick or orthosis in JHS/EDS-HT, may be sources of embarrassment leading to body image disturbances [49, 50]. These aspects may potentially contribute to the development of AN in which an incorrect representation of the body is a central feature.

Finally, both patients presented had experienced traumatic events in childhood and adolescence. In this regard, physical and psychological fragility caused by a medically untreated disease (diagnosis delay >8 years, since the appearance of the first manifestations of JHS/EDS-HT) might be accentuated by a traumatic experience, especially in a vulnerable period such as adolescence. These aspects facilitate the development of mental disorders and exacerbate physical symptoms. In this sense, abuse and traumatic experiences have been linked to chronic pain and AN [51].

In conclusion, features and common co-occurring problems of JHS/EDS-HT may favor difficulty eating, significant weight loss and even eating disorders such as AN with consequent poor nutrition. The relationship between eating problems and JHS/EDS-HT merits more clinical and research attention.