Hypermobile Joints and to Diagnose the Benign Joint
Hypermobility Syndrome
Jaime. F. Bravo, MD
Rheumatology Department, Clínica Arauco and San Juan de Dios Hospital,
Santiago. Chile. *
Even though hyper mobile joints were first noted 2,000 years ago by Hippocrates, it was not described as a medical problem until 1967 by Kirk et al. (1). Nowadays for the general public as well as for many physicians, hypermobility is considered a curiosity, a kind of “party tricks” played by children, rather than a potentially serious medical problem. Many people have hyper mobile joints and this very frequent condition, is known as Hypermobility Syndrome (HMS) (2). It is present in about 10% of individuals in Western populations (3) and up to 25% in Iraqis (4). It is well known that the prevalence varies with ethnic background, sex and age, and is more frequent in Orientals than Negroes and in these more than Caucasians. More prevalent in females than in males and in children than adults. We agree with Larsson (5) that most cases are pauci-articular, rather than generalized, which makes the diagnosis more difficult. Most people do not even know that they have lax joints.
In spite of their agility and mobile joints, most HMS patients do not have joint or musculo-skeletal pain. If they develop symptoms they are rotulated as Benign Joint Hypermobility Syndrome (BJHS). The Beighton Score (6) was the first criteria used to measure hypermobility and has been used for 30 years. It considers only few joints and does not consider other involved tissues. Later Bulbena (7) devised a wider criteria, including more joints.
The awareness that these patients can have serious problems in other tissues besides the joints, resulted in the revision of the criteria. The reason for this systemic involvement, is the fact that collagen is part of most tissues. At the British Society for Rheumatology, Grahame managed to publish the validated diagnostic criteria for Benign Joint Hypermobility Syndrome known as the Brighton Criteria (8). This one includes the Beighton Score, but in addition, takes in consideration the involvement of other tissues. It is really unfortunate that the names of both criteria, namely Beighton and Brighton are so similar, because they are often confused. The Brighton Criteria has been a great step forward to facilitate the detection of patients with BJHS, who usually go undiagnosed in most parts of the world.
Most authors believe that BJHS is the same condition as the Hypermobility type of Ehlers-Danlos, formerly called EDS type III (9) and that it is a forme fruste (3) of the other hereditary disorders of connective tissue (HDCT), since it has many features of Ehlers-Danlos (EDS) and Marfan, even though at a lesser degree.
HDCT are due to alterations of the extra cellular matrix of the connective tissues. It is known that 195 proteins are involved in connective tissue metabolism. Mutations in the genes of these proteins can cause more than 200 conditions called HDCT (10).
The BJHS is probably the most prevalent rheumatological condition. Guma reported 25% in their rheumatology clinics in Spain (11). It accounts for 34% of our patients at Clinica Arauco, in Santiago, Chile. In England, Grahame considers that is probably the most frequent cause of pain, in the rheumatological practice. In spite of this, it is rarely diagnosed. Physicians do not give this condition its proper importance. Grahame wrote in 2001 a timely editorial entitled: Time to take hypermobility seriously (in adults and children) (9) and still at present, BJHS is not a well known entity by general practitioners and not even by good rheumatologists. A couple of years ago, a national survey of the rheumatologists in England, showed significant lack of perception about the hypermobility syndrome (12). The reason for this, appears to be that we rheumatologists were not trained, nor do we train our students, to examine hyper-extension of joints and many of us, were not acquainted with the proper criteria to make these diagnoses. I now have in my office printed sheets with the Brighton Criteria for BJHS and the criteria for EDS-IV (13) to be added to each patient’s chart, when one of these conditions is suspected. This has been very useful and I would recommend rheumatologists and orthopedists to do the same. Since it can affect any tissue that has collagen fibers, the symptoms and signs can appear in different organs and systems. For this reason it is necessary to have a high index of suspicion for these conditions. I am immediately alerted, if the patient in front of me, has Marfanoid features, if she has blue sclerae , has laxicity of the fingers or wrists or has atypical ears or nose. Transparent tissue of the sclera (due to the alteration of collagen fibers) results in blue sclera and transparent skin permits to see the veins.
Since this condition has Autosomic Dominant inheritance, I am always suspicious if I know that a family member has similar problems. We need to think in BJHS, in a patient who has had artralgias, tendinitis, bursitis or back pain, that are recurrent, has “double joints,” dislocations or the sensation that the joint (hip, knee, shoulder) is “going to give way.” While taking the history, after asking the routine questions to rule out the usual types of arthritis, we can not be satisfied just with what the patient tells us. We need a detailed anamnesis with direct questioning about scoliosis, hip displacia, flat feet or umbilical hernia in childhood? Was she more agile than her peers? Did she dance ballet or do Olympic gymnastics. What about “party tricks”? Do your joints make cracking noises or do you get frequent hematomas, without a good reason. ? Do you have problems with the temporo-mandibular joint. ? Do any of your relatives have or have had any of these symptoms.
To keep in mind that they are frequently associated with congenital malformations, helps to diagnose these conditions. It is not rare to see scoliosis, malformations of the feet, including flat feet, rotated knees, spina bifida occulta, transitional lumbo sacral vertebra, spondylolisthesis, urinary tract malformations, cleft palate, etc. Due to the fragility of tissues and depending which one is affected, and in which way, different complications may arise. Patients can have problems with tendons (tendinitis, mitral valve prolapse), cartilages (early osteoarthritis, Tietze syndrome), fibro-cartilages (meniscal tears, disc disease, pubalgia) and bones (osteoporosis, even in young males). Dilated tissues can give varicose veins, arterial aneurisms or cysts (including Baker’s cyst). Weakness of the tissue can produce constipation (even megacolon), diverticulosis, vaginal or rectal prolapse. Ruptured tissue can produce tendon or muscle tear or hernias (umbilical, inguinal, herniated nucleus pulposus, mielomeningocele). The lack of sphincter tonus can produce reflux, urinary and rectal incontinence. It is important to know that hypermobile children have similar problems as adults (14,15). In children, these recurrent pain or joint swelling episodes, have been referred by Gedalia as Juvenile Episodic Arthralgia/Arthritis Syndrome (JEAS) (16). Contrary to the majority of authors, we agree with Gurley-Green (17), that even though hypermobility decreases, other symptoms get worse with age, deteriorating quality of life.
Many patients have chronic fatigue, dizziness and even syncope, due to Disautonomia (18) secondary to orthostatic intolerance. This is due to a poor tone of the veins in the lower extremities, secondary to alteration of the collagen fibers. This condition, which causes severe distress and bad quality of life to many patients, usually goes undiagnosed, when if suspected, could be confirmed with a Tilt Test and treated appropriately. We need to suspect it in patients with BJHS and EDS type IV, if they have chronic fatigue as the day progresses, cold intolerance, somnolence or a history of low blood pressure. The presence of chronic fatigue and the fact that the recurrent pain of these patients are mainly in sites of entesis and bursitis, precisely at the same areas as the Fibromialgia trigger points, makes me think that some patients rotulated as Fibromialgia in truth have BJHS. I agree with Erhlich (19) that Fibromialgia is not a diagnosis. I believe that most of these patients have BJHS and others have, what with Professor Charley J. Smyth we use to call Psicogenic Rheumatism, in which there is a big emotional component. Gedalia found statistically significant associating between hypermobility and Fibromialgia in schoolchildren (20). Barron noted that chronic fatigue syndrome was 3.5 times more frequent in hypermobile adolescents as compared with controls (21).
As we can see, BJHS is not always so benign. Due to the above problems and because treatment is not too effective, patients frequently have a life long of chronic pain and suffering, many times associated to anxiety (22), fear and sometimes depression.
The Vascular EDS (former EDS type IV) that is characterized by ecchymoses and vascular problems, can produce besides cerebral aneurisms or arterial rupture, other serious complications such as spontaneous neumotorax, rupture of the colon or rupture of the gravid uterus. As early as 1975, Pope (23) noted that this condition was due to the absence or reduction of type III collagen, which is an essential component of distensible organs such as arteries, gut, uterus or lung, resulting in wear of such organs and rupture in early adult life. It is for this reason, that we have the imperative need to be able to clinically differentiate, which families have BJHS (EDS-III), and the more serious, but less frequent form, the ecchymotic or vascular type (EDS-IV). It helps to know that people with more lax joints are more likely to have EDS-III. People with EDS-IV (vascular type) have: a) Nearly no lax joints, except for the fingers, b) Extensive hematomas, at times suggesting child abuse), and c) May have the characteristic facial appearance of EDS-IV (triangular face, deep starring eyes, thin upper lip and lack of facial adipose tissue). Fortunately in places like Seattle, Washington, Peter Byers (24) can confirm these clinical diagnoses by biochemical or molecular analysis. These techniques are also available to patients from other countries, but the prices are prohibitive for them. The diagnosis of Marfan continues to be clinical.
Knowing the diagnosis in advance, can save young lives at the moment of a serious complication. At this regard is important to know that most serious problems, at times fatal in Vascular EDS and Marfan, happen in 25% of them before age 20, and 80% before the age of 40 (24).
Frequently adolescents girls with recurrent artralgias due to BJHS, are diagnosed as having Systemic Lupus Erythematosus, specially if they happen to have low titer Antinuclear Antibodies. In other cases, because of wrist and meta-carpo-phalangic joint pain, they are suspect of having Rheumatoid Arthritis, when artralgia of these joints is frequent in BJHS. A not well known sign, piezogenic papules (25), even though not path gnomonic, can be seen in EDS patients. These are small, soft, skin colored lumps of about 2 to 5 mm, that appear on the sides of the heels with weight bearing and immediately disappear when there is no pressure on the heels. They are usually painless, non tender and have no inflammatory signs. They are due to herniated fatty tissue.
The fact that some patients with EDS do no respond well to local anesthetics (26), should alert us to the diagnosis. A review of the differential diagnosis of BJHS has been recently reported by us (27). Also, as we said earlier, many of these patients are erroneously considered to have Fibromialgia.
It is well known that there are no specific laboratory tests or markers to confirm our clinical diagnosis of these conditions. X-rays and laboratory tests are needed to exclude other rheumatological diseases. We have submitted our work for publication in relation to the utility of Cintigraphic Bone Studies in the diagnosis of BJHS and EDS (28). We found statistical difference in the positivity at the wrists, carpal bones and hands of 22 patients compared with controls.
Since this is a genetic condition, for now there is no definite treatment. With the Human Genome now completed, we can only hope that in the near future, using Genetic Therapy, some of these conditions will be treated or prevented. At present, the symptomatic treatment of BJHS is not as good as we would like. We need to prevent complications, which at times can be severe. Avoiding hyper-extension of joints we can prevent pain and further damage. Analgesics and anti-inflammatories are of limited help. Detection and treatment of early osteoarthritis (29,30) and osteoporosis helps (31). The use of glucosamine alone (32) or with condroitin sulfate (33) to prevent osteoarthritis is advocated by some, but needs further confirmation.
It is well known that Folic acid deficiency during early pregnancy is associated with neural tube defects as well as cardiac, urinary tract and oral clefts (34). These malformations are also associated to BJHS and EDS-IV. Urinary tract malformations and cryptorchidism, associated to poor abdominal wall muscles in newborns (triad known as Prune Belly Syndrome), are occasionally seen in EDS-IV (35). Studies should be done to find out if folic acid, or other vitamins or nutrients, given few weeks before and during the first three months of pregnancy, could help prevent mutations of the collagen fibers. Also studies considering the effects of ozone or other physical agents during pregnancy, need consideration.
Support Groups have been of considerable help to patients suffering from chronic illnesses and already they have proven their efficiency for patients with BJHS in England (17) and Spain. I would strongly recommend them everywhere.
Counseling about the type of work, sports, hobbies, dance and musical instruments, can be of help. A Team Approach is recommended, since the help of different specialists is needed in the evaluation and treatment of these patients. Physical therapy and Occupational therapy are invaluable. At times the help of a Pain Control Clinic is necessary. Starting treatment in childhood is of paramount importance, because of this, an important role should be played by pediatricians, pediatric rheumatologists and pediatric orthopedists. It is necessary to educate parents, teachers, trainers, physical therapists, physicians and psychologists. Young people need to know the value of using protectors, while engaging in potentially dangerous sports. It is necessary to inform the public opinion about the high prevalence of BJHS, in order to improve the awareness of this frequently undiagnosed condition.
This emergent, serious and very prevalent problem, is a promising area for rheumatological research. Finally, is necessary to demonstrate that genetic alterations of the collagen fibers are very frequent and very important, so that in the near future, priority is given to it over other diseases, when money is allocated for genetic studies and genetic therapy.
References.
1.- Kirk JH, Ansell BA, Bywaters EGL. The hypermobility syndrome. Ann. Rheum Dis 1967; 26: 425.
2.- Mishra MB, Ryan P, Atkinson P, Taylor H, Bell J, Calver D et al. Extra-articular features of benign joint hypermobility syndrome. Br J Rheumtol 1996; 35: 861-66.
3.- Grahame R.
Joint hypermobility and genetic collagen disorders: are they related ?
Arch Dis Child February 1999; 80: 188-91.
4.- Al-Rawi ZS, Al-Aszawi AJ, Al-Chalabi T. Joint mobility among university students in Iraq. Br J Rheumatol 1985; 24: 326-31.
5.- Larsson L-G, Baum J, Mudholkar GS, Srivastava DK. Hypermobility prevalence and features in Swedish population. Br J Rheumatol 1993; 32: 116-19.
6.- Beighton PH, Solomon L, Soskolne CL. Articular mobility in an African population. Ann Rheum Dis 1973; 32: 413-18.
7.- Bulbena A, Duro JC, Porta M, Faus S, Vallescar R, Martin-Santos R. Clinical assessment of hypermobility of joints. Assembling criteria. J Rheumatol 1992; 19: 115-22.
8.- Grahame R, Bird HA, Child A et al. The British Society for Rheumatology Special Interest Group on Heritable Disorders of Connective Tissue criteria for the benign joint hypermobility syndrome. The revised (Brighton 1998) criteria for the diagnosis of BJHS. J Rheumatol 2000; 27: 1777-79.
9.- Grahame R. Editorial: Time to take hypermobility seriously (in adults and children). Rheumatology 2001; 40: 485-91.
10.- Pyeritz RE. Heritable disorders of connective tissue. Prim Rheum Dis 2001; 12
ed: 483-92.
11.- Guma M, Olivé A, Holgado
S, Casado E, Roca J, Forcada J, Duró JC
y Tena X Una estimación de la laxitud articular
en la consulta externa. Rev Esp Reumatol 2001; 28: 298-00.
12.- Grahame R, Bird HA. British consultant rheumatologists perceptions about the hypermobility syndrome: a national survey. Rheumatology 2001; 40: 560-63.
13.- Beighton P, DePaepe A, Steinmann B, Tsipouras P , Wenstrup RJ. Ehlers-Danlos Syndromes: revised nosology, Villefranche, 1977. Am J Med Gen 1998; 77: 31-37.
14.- Murray KJ, Woo P. Benign joint hypermobility in childhood. Rheumatology 2001; 40: 489-91.
15.- Engelbert RHH, Bank RA, Sakkers RJB, Helders PJM et al. Pediatric generalized joint hypermobility
with and without musculoskeletal complaints: localized or systemic
disorder? Pediatr
2003 (3); 111: 248-54.
16.- Gedalia A, Person DA, Brewer EJ, Giannini EH. Hypermobility of the joints in juvenile episodic arthritis/arthralgia. J Pediatr 1985; 107: 873-76.
17.- Gurley-Green S. Living with the hypermobility syndrome. Rheumatology 2001; 40: 487-89.
18.- Rowe PC, Barron DF, Calkins H, Maumenee T, Tong PY, Geraghty MT. Orthostatic intolerance and chronic fatigue syndrome associated with Ehlers-Danlos syndrome. J Pediatr 1999; 135: 494-99.
19.- Ehrlich GE. Fibromialgia is not a diagnosis: comment on the editorial by Crofford and Clauw. Arthritis Rheum 2003 Jan; 48 (1): 276; author reply 277.
20.- Gedalia A, Press J, Klein M, Buskila D. Joint hypermobility and Fibromialgia in schoolchildren. Ann Rheum Dis 1993; 52: 494-96.
21.- Barron DF, Cohen BA, Geraghty MT, Violand R, Rowe PC. Joint hypermobility is more common in children with chronic fatigue syndrome than in healthy controls. J Pediatr 2002; 141: 421-25.
22.- Bulbena A, Duró JC, Mateo A, Porta M, Vallejo J: Joint hypermobility syndrome and anxiety disorders. Lancet 1988; 2: 694.
23.- Pope FM, Martin GR, Lichtenstein JR, Penttinen R, Gerson B, Rowe DW, McKusic VA. Patients with Ehlers-Danlos type IV lack type III collagen. Proc Nat Acad Sci USA 1975; 72(4): 1314-16.
24.- Pepin M, Schwarze U, Superti-Furga A , Byers PH. Clinical and genetic features of Ehlers-Danlos Syndrome type IV, the vascular type. N Engl J Med 2000; 342: 673-80.
25.- van Straaten EA, van Langen IM, Oorthuys JW, Oosting J. Piezogenic papules of the feet in healthy children and their possible relation with connective tissue disorders. Pediatr Dermatol 1991; 8: 277-79.
26.- Arendt-NielsenL, Kaalund P, Bjerring P,
Hogsaa B. Insufficient effect of local
analgesics in Ehlers-Danlos type III patients (connective tissue disorder). Acta Anaesthesiol Scand 1990; 34:
358-61.
27.-
Bravo JF. Importancia de la
hipermovilidad articular como causa frecuente de morbilidad, no sólo músculo-esquelética, sino también
sistémica: criterios diagnósticos.
Reumatología 2003; 19(1): 33-38.
28.- Bravo JF, Arteaga MP, Coello L. Utilidad de la cintigrafía ósea en el estudio de las Alteraciones Hereditarias de la Fibra Colágena (AHFC). Alasbimn J 6(22): October 2003. http//www.alasbimnjournal.cl/revistas/22/bravo esp.html
29.- Grahame R. Clinical conundrum: how often, when and how does joint hypermobility lead to osteoarthritis ? Br J Rheumatol 1989 ; 28 : 320.
30.- Bird HA, Tribe CR, Bacon PA. Joint hypermobility leading to osteoarthritis and condrocalcinosis. Ann Rheum Dis 1978; 37: 203-11.
31.- Dolan AL, Arden NK, Grahame R, Spector TD. Assessment of bone in Ehlers-Danlos syndrome
by ultrasound and densitometry. Ann Rheum Dis 1998; 57: 630-33.
32.- Reginster JY, Deroisy R, Rovati LC, Lee RL,
Lejeune E, Bruyere O, Giacovelli G Henrotin Y, Dacre JE, Gossett C. Long term effects of Glucosamine Sulphate in
the progression of osteoarthritis: aleatory clinical study, controlled with
placebo. Lancet 2001; 357: 251-56.
33.- Leeb BF, Schweitzer H, Montag K, Smolen JS. A metaanalysis of Chondroitin Sulfate in the
treatment of osteoarthritis. J
Rheumatol 2000; 27: 205-11.
34.- Hernandez-Díaz S, Werler MM, Walker AM, Mitchel AA. Folic acid
antagonists
during pregnancy and the risk of birth defects. N Engl J Med 2000; 3431608-14.
35.- Kelalis PP, KingLR, Belman AB.
Clin Pediatr Urology 3d.
ed. Philadelphia: WB Saunders, 1992.