Morphological signs of connective tissue dysplasia as predictors of frequent post-exercise musculoskeletal disorders

Physical exercise is one of the main components of a healthy lifestyle. Recently, there has been an increase in the number of musculoskeletal disorders during physical training [1] and in the number of patients with characteristic morphological signs of connective tissue dysplasia (СTD) [2‐4]. CTD manifestation is due to inherited mutations of genes encoding the synthesis and spatial organization of collagen, structural proteins and protein-carbohydrate complexes, enzymes and their co-factors [2‐6]. At the same time, adverse environmental factors play an important role in clinical manifestation of this condition [7, 8]. The combination of these factors leads to pathological change in elastin and collagen fibers facilitating significant restructuration of connective tissue of different severity [9], which determines the large spectrum of CTD morphological manifestations [10‐15]. According to existing studies, СTD is quite common, reaching an incidence of up to 85.4% in some populations [16, 17].

CTD is characterized by a variety of clinical manifestations – from subclinical forms to polysystemic pathology [18, 19]. The classification of external and internal morphological signs of CTD has been unified [20, 21]. The combination of morphological signs is so variable that it is often difficult to integrate many individual symptoms and properly diagnose CTD [10]. Clinical interest in CTD has significantly increased largely due to the aggravating effects of this disorder on the course of almost all diseases [22]. Patients with CTD are observed by different specialists, each of whom prescribes his own treatment, which in many cases is untimely and often ineffective [23]. CTD should be considered in patients with frequent post-exercise musculoskeletal disorders, as hypersensitivity to physical exercise and predisposition to repeated injuries is a characteristic symptom of this condition [24]. It is therefore relevant to analyze the presence of morphological signs of CTD in patients with frequent post-exercise musculoskeletal disorders and injuries to determine the best course of action for prevention and treatment. In this study we assess the prevalence of morphological signs of CTD in individuals with frequent post-exercise musculoskeletal disorders in order to develop additional therapeutic-preventive measures and recommendations for choice of adequate physical activity regimen.

The minimal size sample for both groups for our dichotomous endpoint, two independent sample study (power 90%, alpha 0.05) was 14. The asthenic constitutional type was more common in Group 1. Deficit of body weight (Quetelet index ≤25) was more common in Group 1 (p < 0.05). Subjects in Group 1 more often had disproportionately long hands and feet in comparison with Group 2 (p < 0.05) (Table 1). Arachnodactyly, diagnosed by positive wrist and thumb tests was significantly more common in subjects with frequent muscular-skeletal disorders than in the control group (Table 2).

Kyphotic spinal deformation with asymmetry of shoulders, shoulder blades and pelvic bones, chest deformity, flat foot combined with valgus installation, macrodactyly of the first toe significantly prevailed in Group 1 (p < 0.05). Back pain was present in all subjects in Group 1. The hypermobility syndrome, characterized by joint instability, “crunches” and pain during movement, repeated joint dislocations and subluxations, accompanied by ligament sprains and ruptures was common in Group 1 subjects. Subjects in Group 1 had a narrow facial skeleton, malocclusion and a high gothic palate (Table 3).

Keloid scars and hemorrhagic syndrome (petechiae), hyperpigmentation along the spinous processes, atrophic skin striae, and telangiectasia were more common Group 1 (p < 0.05). Most in Group 1 had increased brittleness, softness in nails as well as disorders of the homogeneous structure of the nail plate (p < 0.05). Thin, brittle hair, areas of alopecia, auricles with excessive elasticity were common in Group 1 (p < 0.05). Patients in Group 1 showed significantly higher rates of muscular pathology (hypotrophy, muscle hypotension, diastasis of the rectus abdominis muscles and abdominal hernias) (p < 0.05) (Table 4).

Cardiovascular pathology (mitral valve prolapse, vascular dystonia, rate of tachycardia incidents, lower overall systolic pressure, varicose veins, hemorrhoids), ophthalmic manifestations (medium severity myopia) and gastrointestinal pathologies (biliary dyskinesia, failure of the stomach cardia and gastroesophageal reflux syndrome) were more common in Group 1 (Table 5). Asthenic syndrome (decreased working capacity, increased fatigue, sleepiness, general weakness, especially in the mornings) and pain were often observed in the patients with frequent post-exercise musculoskeletal disorders (p < 0.05).

The most common and diagnostically significant symptoms according to the Kadurina-Abbamukova scale [21] were kyphotic spinal deformation, myopia, asthenic syndrome and back pain. The total score of each individual patient in Group 2 was less than 20 points, which was not characteristic of CTD. Patients in Group 1 were diagnosed with medium severity CTD in 37.5% and severe CTD in 62.5% of cases. The total score of CTD signs in these patients was significantly higher (49,44 ± 13,1) compared to the control group (11,33 ± 3,29) (Table 6).

All subjects with frequent post-exercise musculoskeletal disorders in this study were diagnosed with CTD. This underlines the overlooked significance of CTD in clinical medicine [30]. Such patients should observe a specific physical regimen with proper alternation of exercise and rest [11, 23]. The necessity of adequate physical activity and training pace has long been established [31]. Patients with CTD are recommended to perform regular aerobic exercises 3 times a week for 40–60 min (swimming, walking, moderate running, cycling, badminton, bowling, table tennis). Patients with CTD have been advised no to partake in activities such as ballet, group sports associated with a high risk of injury and weight-lifting [18, 23, 32].

Our study was aimed at assessing the clinical and morphological signs which can suggest the presence of CTD in otherwise undiagnosed patients. Our results have shown that the asthenic constitutional type was a common morphological feature in patients with CTD. This phenomenon has been recognized by several population-based studies [30, 33, 34]. It is important to further consider the phenotypic manifestations of CTD in the form of appropriate clinical syndromes. Most often this pathology is characterized by osteoarticular changes (Table 3) [3, 4].

One of the important morphological signs of CTD, characterizing the involvement of the skeletal system, is dolichostenomelia (lengthening of the extremities), which is determined by measuring the tubular bones and estimating indexes [35]. Our study has shown that up to 63% of patients with frequent post-exercise musculoskeletal disorders present with a Quetelet index (BMI) ≤25, 31% with Vargi Index < 1.7, 25% with Pigne Index ≥30 and 19% with Verveka Index between 1.26 and 1.35. Limb changes in CTD often present with arachnodactyly (long, thin, “spider” fingers) [36], which, according to our study along with muscular and vascular symptoms was significantly more common in patients with frequent muscular-skeletal disorders. These findings hint towards presence undifferentiated connective tissue disease (UCTD) in the experimental group.

Ectodermal manifestations (Table 4) in examined patients were characterized by a more frequent presence of thin skin with a well-visible network of subcutaneous vasculature located on the chest, back and limbs. In a significant percentage of cases, manifestations of the vascular syndrome were seen. This is an important aspect, due to the presence of vasculature pathology in many severe connective tissue diseases, which may help early detection of underlying pathology [37‐39].

Consistent with existing data, many patients with frequent post-exercise musculoskeletal disorders have shown to have specific gastrointestinal symptoms. Therefore, gastrointestinal tract pathology was significantly more often detected in the experimental group in the form of biliary dyskinesia, failure of stomach cardia and gastroesophageal reflux syndrome (Table 5). This is characteristic of many underlying connective tissue diseases, such as eosinophilic disorders [40], gastrointestinal vasculitis [41], Ehlers-Danlos syndromes [42], and others [43, 44].

The presence of the discussed diagnostically significant morphological signs of CTD in humans is a pathognomonic predictor of high susceptibility to frequent post-exercise musculoskeletal disorders and requires compliance with additional therapeutic and preventive recommendations. Our study showed that surveying and anthropomorphic evaluation has allowed to determine predictors of high predisposition to frequent post-exercise musculoskeletal disorders. It is important to properly address these symptoms and anthropomorphic presentations in order to build a personalized approach to physical exercise regimen and lifestyle changes in this group of patients. Improper physical training in patients with CTD can lead to significant health problems. More so, early screening for CTD can help determine a large specter of predisposed diseases.

Osteopathy is recommended as part of CTD treatment. This method, restoring impaired structural-anatomical relationships between various organs and parts of the body, contributes to the normalization of body functions [45]. Regularly conducted courses of osteopathy improve reflex activity and metabolic processes, leading to strengthening of connective tissue [46]. Further research should expand upon these findings, forming a standardized approach to early diagnosis of CTD in adolescents.

All patients with frequent post-exercise musculoskeletal disorders showed signs of CTD. The analysis of the morphological prevalence depending on clinical significance allowed us to determine pathognomonic predictors of high predisposition to injuries. Their early detection can promote the timely appointment of adequate physical activity regimen and therapy of the underlying cause. Based on our research results, we recommend proper evaluation of patients with frequent post-exercise musculoskeletal disorders, as this may be the only symptom of an underlying connective tissue disorder.