A).- Joint Hypermobility or Joint laxity means excessive motion of the joints.

This is a very frequent condition, affecting more than 15% of the population worldwide. These people have more mobile, more lax and more flexible joints than normal, but with no symptoms. Many of them not even know that they have hypermobility. These people used to be agile as children and frequently amused their friends by doing funny movements of the fingers (“party tricks”). Some with the years became great gymnasts, musicians, dancers and even some of them worked as contortionists at the circus. Others in spite of their agility have been forced to retire from these activities, due to repetitive musculo-skeletal lesions. In some cases, this condition is only a familiar trait, but in others it is a health problem that requires medical attention.

B).- Joint Hypermobility Syndrome (JHS). In some people this joint laxity is associated to fragile tissues, due to a genetic alteration of collagen. This produces musculo-skeletal symptoms (joint pains, bursitis, tendinitis, articular sub-luxations, back pains, etc.) as well as problems from other tissues, such as: uterine or rectal prolapse, abdominal hernias, varicose veins, transparent velvety skin, with striae, capillary fragility and poor cicatrisation, mitral valve prolapse, myopia, eyelid drop, etc. In these cases is that we speak of JHS (joint hypermobility + symptoms). At present most authors think that JHS is the same condition as the Ehlers-Danlos Syndrome (EDS) type III. Having joint hypermobility, in a way, is like having fever, a marker that something is going wrong. It is necessary to remember that these patients have weak tissues (fragile), due to the genetic collagen defect and for this reason it is necessary to rule out associated pathologies such as Dysautonomia (Chronic fatigue, dizziness and occasional syncopal episodes due to low blood pressure), early osteoarthritis, early osteoporosis, lumbar disc disease, recurrent tendonitis, etc. Some adolescents are tall and ungainly (Marfanoids) and they constitute 15% of the JHS patients. Some girls are tall and slender, with long neck, square shoulders and long fingers (looking like a pageant model). Marfanoids usually have hypermobility, back pain and they also have early osteoporosis, Dysautonomia and occasionally (1%). expontaneous rupture of the lungs (expontaneous neumothorax). Frequently women with JHS have light blue sclerae (not white as normal), but this is infrequent in males.

The Hereditary Disorders of the Collagen Tissues (HDCT) is a group of diseases in which patients have joint hypermobility and the classical forms are:

a).- Ehlers-Danlos Syndrome (EDS). Lately re-grouped from 10 to 6 types:

1.- Classic type. Formerly named EDS types I and II.

2.- Joint Hypermobility Syndrome (JHS). Formerly EDS type III.

3.- Vascular EDS. Formerly called EDS type IV (1/100.000 people as per Peter Byers)

4.- Kyphoscoliosis. Formerly EDS type VI. Usually has eye involvement.

5.- Arthrochalasia. Formerly EDS type VII A and B.

6.- Dermatosparaxis type. Formerly EDS type VII-C.

b).- Marfan Syndrome (MFS). Estimated frequency: 1/12.000 people.

c).- Osteogenesis Imperfecta (OI). Estimated frequency: 1/100.000 people.

Most HDCT are rare, but JHS is frequent worldwide (15%), but it is my impression that it is more prevalent in Spain and in Latin populations. It constitutes 25% of the rheumatological consultations in Spain (Guma). I see it in 80% of my patients, in the adult arthritis clinic, due to the fact that our Clinic has become a Referral center for Hypermobility. It is estimated that in the office of any Chilean Rheumatologist it accounts for about 50% of the patients, but it is not diagnosed. Professor Grahame, from London, who is the maximal reference in the subject, states: “The problem tends to be trivialized, including by the medical profession”. He thinks that the syndrome ”could be the principal cause of pain in the community”. I concur with this statement, since it is the principal cause of pain in my patients. JHS is due to an alteration of the collagen fiber, which forms the matrix of most tissues in the body. It is known that half of the cases are due to Autosomal Dominant Inheritance and that the others are the result of new genetic mutations (“the novo mutations”). This makes the collagen (present in tendons, ligaments, skin, cartilage, blood vessels, etc.) more elastic, but at the same time more fragile. Joints become lax, unstable and hypermobile with tendency to dislocations and vulnerable to lesions. These problems become recurrent, like having frequent ankle sprains, for example. These people complain of cracking noises of the joints and recurrent ecchymoses, due to capillary fragility. The fact that the symptoms are very variable makes the diagnosis more difficult, specially if the physician does not have a high index of suspicion. Same patients have only hypermobility of the small joints of the hands, while others may have generalized laxity. Arthralgias (joint pain), myalgias (muscle pain) and even bone pain are usual complaints. For many patients the musculo-skeletal pain and problems derived from fragility of multiple tissues, is the cause of a life of pain and recurrent problems.

We need to remember that these patients are born with tissue fragility and that children are more lax than adults and that they usually have musculo-skeletal pain, that is overlooked, or at the most labeled as “growing pains” or they are given the wrong diagnosis of Chronic Juvenile Arthritis. JHS is more frequent in females, in males is less prevalent and the diagnosis is more difficult, since the may have only a few lax joints and usually at a lesser degree. They also can have problems derived from fragile tissues such as: back pain, varicose veins, hernias, myopia, mitral valve prolapse, early osteoarthritis and early osteoporosis.

Symptoms may appear at any age, but frequently the onset is in the adolescence or young adulthood, without having had joint instability or pain before. An adult that has hypermobility may at any time, without any significant cause, start having cracking of the joints, back pain, tendinitis, sprains or sub-luxations. When seeing hypermobility, many physicians do not relate it with JHS. In some cases the patient carries the wrong diagnosis of Lupus, Rheumatoid Arthritis or Fibromyalgia. Many patients present early or erosive Osteoarthritis due to fragile cartilages and excessive joint mobility. Due to inherit weakness of the cartilages, some patients have hip displacia, scoliosis, sunken chest (pectum excavatum) or prominent ribs (in the upper part of the abdomen). Others have abnormalities of the ears and/or the nasal cartilage (prominent nose or deviated nasal septum). They may have bruxism; poor bite, cracking noises and pain of the temporomandibular joint and occasionally subluxation of the mandible.

The main problem is poor quality of tissues. I tell my patients jokingly that their tissues “are not Michelin”, that they are not optimal. For this reason these tissues wear and tear more rapidly (osteoarthritis and osteoporosis), rupture (hernias, muscle tears, degeneration of spinal discs), or dilate (cysts of any kind, varicose veins, colon diverticula’s and arterial aneurisms). The sclerae are transparent like the skin, due to the collagen alteration and as a result they develop a light blue tinge (light blue sclerae). The transparency permits to see the blood vessels in the back of the eye. This does not alter vision and helps in the diagnosis. In children light blue sclerae is normal up to age two. Physicians routinely examine the sclerae to rule out jaundice (yellow color), but fail to notice the blue tinge in JHS patients, and if they notice it, they do not realize its significance.

The lumbar pain is frequent and it can be due to scoliosis, spondylosis (bone spurs), transitional lumbar vertebra, spondylolisthesis (one vertebra slipped over the next one) or lumbar hyperlordosis. In the majority of cases the lumbar x-ray is normal and the pain is due to laxity of the spinal ligaments. I make the following analogy to my patients: “If the cables that hold the poles in place of the Esmeralda Sailing Ship (that has 3 poles) would get loose, she would have back pain”. This explanation that is good for back pain is also good to explain the joint pain in JHS, here the cables are the joint ligaments.

Due to the collagen abnormality the vessel walls are weak and get dilated, producing a decrease in blood pressure (BP), that causes Dysautonomia (Dys). This complication is very frequent and in our recent review of 1,000 JHS cases it was present in 41% of women and 17% of men. Furthermore it affected 40% of men and 64% of women with JHS below age 30. Dys happens also in part due to the vaso-vagal imbalance that exists in JHS. It is for this reason that these patients have cold, sweaty palms and feet. They do not tolerate standing for too long, without moving the feet, because the BP falls and they get tired, dizzy and they even may have syncopal episodes. Generally they are people with low BP, with cold intolerance who develop symptoms of Dys specially with high altitude, dehydration, severe emotions, severe acute pain, after eating or drinking in excess, menstrual periods, pregnancy, or when standing for too long without moving, etc. In normal people the Autonomous (involuntary) nervous system has a balance between the Sympathetic and the Para-Sympathetic (Vagal) nervous system. In JHS there is a decrease in the Sympathetic tone that causes the drop in blood pressure. These patients present chronic fatigue and usually they tell us “that at midday they feel like their batteries have become discharged”. Sometimes their face looks tired, with droopy eyelids. The Dys symptoms produce bad quality of life. This gets worse because in the great majority of cases the diagnosis is not made, and the person is stigmatized as lazy, that lacks social participation and is depressed. In most cases they are missed diagnosed as having Fibromyalgia, hypoglycemic crisis (low blood sugar) or Chronic Fatigue Syndrome. The diagnosis of Dys can be confirmed with a Tilt Test that can be performed at a cardiology unit.

Bulbena found that Endogenous Depression, Anxiety, Phobias and Panic Crisis are part of JHS, since the genes for these problems can be inherited together with the one related to hypermobility. This happens because the genes sit side by side on chromosome 15 and can be inherited together. Some patients are afraid or have anxiety to perform certain exercises or sports, because they know the possible consequences that they already have experienced in the past. Due to chronic pain, recurrent musculo-skeletal problems, problems from other tissues and chronic fatigue, it is frequent that these patients develop poor quality of life that leads to secondary depression.

The Joint Hypermobility Syndrome (JHS) is a forme fruste of the classic HDCTs such EDS, MFS and OI, with which it shares many characteristics. The fact that many patients wander from one physician to another without a good explanation for their symptoms makes them see different specialists, get multiple tests, without arriving to correct diagnosis. This creates in the patient sentiments of rage, anxiety and depression.

Diagnosis.

The diagnosis recently has become easier with the use of the Brighton Criteria (BC). It was noted that the Beighton Score (BSc), which had been used for 30 years, was insufficient for the diagnosis of JHS. It is important to note that both names are so similar that confusion arises frequently. The problem is that the BSc includes only a few joints and does not consider other problems due to tissue fragility. In our recent study of 1,000 JHS patients, the BSc was negative (3/9 or less) in 60% of the JHS patients diagnosed using the BC. This one includes and modifies the BSc and permits that the diagnosis can be done with certainty. It has been validated for patients 16 years and older. We recommend it to be used routinely by all physicians dealing with musculo-skeletal complaints, to improve detection of this usually undiagnosed condition. The diagnosis is helped by the fact that several members of the family may have the similar problems, since it has Autosomal Dominant Inheritance. This means that 50% of the offspring will inherit it.

In about half of the cases the parents do not have the condition and JHS appears due to a new mutation (the novo mutation). We feel that these new mutations could be caused by the lack of Folic Acid during the periconcepcional period (3 months before conception), similarly to what happens with Spina Bifida and other congenital malformations.

Differential Diagnosis.

It is important to differentiate JHS from:

A.- Any cause of arthralgias (joint pain). This is the reason why these patients need to be seen by a Rheumatologist, who besides a careful examination needs to request laboratory tests to rule out other rheumatological diseases such as Lupus, Rheumatoid Arthritis, Spondyloarthropaties, gout, etc.

B.- Fibromyalgia. Frequently patients with JHS are labeled with this diagnosis because of the similarity of the complaints. In both conditions the principal problem is pain and chronic fatigue. In both we find “trigger points”, which in JHS are called “enthesitis” (pain and inflammation at the junction of the tendon with the bone). In both conditions laboratory

tests are normal. I believe that Fibromyalgia exists, but in many cases the proper diagnosis is JHS. This diagnosis is better, is more organic, rather than emotional as in most cases of Fibromyalgia. It also has a genetic base, and a characteristic phenotype with a “Typical JHS facial appearance”, as described by me. (www.reumatologia-dr-bravo.cl). Further more it is well known that the Fibromyalgia Criteria is too imprecise and that the Brighton Criteria, that is used for the JHS diagnosis, is precise and has been validated.

C.- Classic forms of the Hereditary Diseases of the Collagen Tissues (HDCT), that are:

1.- Ehlers-Danlos Syndrome (EDS). There are 6 well-defined types, all of them characterized by joint hypermobility and elastic and fragile skin. They can have tendency to easy bruising, ankle sprains, cracking noises and joint pain, especially of hands and wrists. We are mainly interested in the following types of EDS:

a.- Joint Hypermobility Syndrome (JHS). For us and many authors it is the same as EDS type III. It characteristically has joint laxity, but we need to remember that not always the laxity is generalized and is some patients affects only one or a few joints.

b.- Vascular Ehlers-Danlos Syndrome (VEDS), formerly called EDS type IV. It results from the mutation in the gene type III pro-collagen. It is infrequent (1/100,000 people (Byers) and usually affects several members of a family. Has poor prognosis and for this reason it is necessary to make the diagnosis early, since it can cause serious cardiovascular problems, and organ rupture, like the lungs, colon and gravid uterus. Due to capillary fragility these patients have significant and frequently ecchymoses, many times without apparent cause. Other vascular problems include Mitral Valve Prolapse (MVP), and more serious complications like cerebral aneurisms and arterial rupture. In most cases these patients are not very lax, they usually have hypermobility only of the small joints of the hands. They can dorsi-flex the fingers more than 90°. Since they also have fragile tissues they can have spinal problems (disc disease), scoliosis, varicose veins, hernias, flat foot, tendency to early osteoarthritis and osteoporosis at a young age. Besides the vascular problems they are characterized by transparent (veins are seen), velvety skin. At times they are easy to recognize, specially if they have the “VEDS typical face” (www.reumatologia-dr-bravo.cl): triangular face, sunken eyes, thin upper lip and lack of facial fat tissue. They can also have rupture of tendons, ligaments or muscles, varicose veins in young adults, expontaneous lung rupture (pneumothorax) and gingival recession. A family history of arterial complications or organ rupture or even sudden death of a close relative, younger than 30 years old, without apparent cause. When the diagnosis of VEDS is made, it is necessary to look for other cases in the family, to prevent serious complications, like cerebral aneurismal rupture. VEDS then have poor prognosis, especially if not diagnosed early, before complications arise. From the patients that die, most of them do (80%) between ages of 20 to 40 years old.

c.- Classic type EDS. Formerly called EDS type I-II. These patients are very similar to JHS patients, but have a greater degree of hypermobility. For example they may be able to extend the thumb backwards to touch the wrist or they can reach one side of the abdomen with the opposite hand coming from the back (contortionists). The degree of active motion of the fingers (“party tricks”) is greater than in JHS. Really they are extremely lax and they usually have recurrent subluxations.

2.- Marfan Syndrome (MFS). Is another HDCT that is potentially serious and needs early diagnosis, to prevent complications that can be fatal. It is infrequent, one in 12,000 people. It is also found in family clusters, and at times is missed thinking that it is only a family trait. It has Autosomal Dominant Inheritance, meaning that 50% of the offspring will have it. It is caused by a mutation of the Fibrillin-1 gene. These patients are extremely tall, slender, have an elongated head, long extremities and long fingers (arachnodactily= like spiders) associated to hypermobility. They may have chest deformities (pectus excavatum (in) or pectus carinatus (out, like a quill) and they frequently have back and joint pain. Besides the musculo-skeletal problems they may have also other problems affecting the aortic artery, lungs (expontaneous rupture) and eyes (deviation of the lens, myopia, and retinal detachment). The diagnosis is made if besides the typical musculo-skeletal deformities there are the typical ocular or cardiovascular complications. The problem is that at times is the complications may have not appeared yet (“emergent Marfan”), so regular monitoring is essential. The diagnosis is made easier if a close relative has the condition. Both MFS and VEDS may have the signs already discussed for JHS, such as: hypermobility, transparent, velvety skin, ecchymoses and light blue sclerae. It is important to know how to differentiate MFS from JHS patients with the Marfanoid habitus., since MFS can have more serious complications. The aortic artery may start to dilate during adolescence and if not diagnosed and treated, it can rupture, usually after 10 years, causing death.

3.- Osteogenesis Imperfecta (OI). It is another HDCT that is characterized by severe osteoporosis and great tendency to fractures. These patients have true blue sclerae, not light blue. It is due to mutation of the collagen type I genes, which causes brittle bones. It is rare in adults, only one in 100,000 people. It is more frequent in new born and in certain families. Small children with this condition have recurrent fractures with minor trauma and are usually known as “glass children”.

Treatment (Of JHS and Classic EDS).

For now there is no definite treatment. Since it is a genetic problem, it is possible that in the future, with better knowledge of the Genetic Therapy, these conditions may be prevented or treated. Taking collagen pills does not help the problem. The treatment is symptomatic and tends to prevent complications, some of which can be serious. Articular pain and tendency to repetitive lesions can be reduced. We can reassure the patient and his family that the condition is common and that some of the complications can be prevented. Joint hypermobility in itself is not bad and can be an asset to the person, but it is indicating that that the organ tissues are fragile and that they may wear and tear at a younger age than people without JHS. Women are more mobile than men and children more than adults, since laxity decreases with age, but no so the pain and complications. JHS and Classic EDS do not have the severe complications as seen with the other HDCTs, such as Vascular EDS or MFS.

Prevention. Since treatment is only symptomatic, it is necessary to prevent complications. We recommend not to hyperextend the lax joints, especially the exaggerated flexion or extension of the wrists or small joints of the hands. “It is not funny” to extend the fingers beyond the normal range or to crack the joints. It is better to forbid children to do “party tricks”. Remember that a loose hinge gets broken rapidly if abused. It is better to avoid contact sports like rugby, football, soccer, volleyball, karate, roller skates, ice-skating, etc. Since they tend to produce sprains and early osteoarthritis, due to the hypermobility and weak cartilage. If these sports are practiced, the person needs to protect the affected joint (with splints for wrists, elbows, knees, ankles, etc.). It is important to evaluate the working conditions in offices and industry, to prevent carpal tunnel, sprains, tendinitis, bursitis, subluxations and fractures. It is advisable to take short brakes and not to be working at the same posture for hours. It is necessary to advise young musicians as to which instrument to choose. Students should not carry heavy backpacks, since they cause back pain and for them we suggest the use of a carry-on. It is worth remembering that JHS patients could have problems with ballet dancing or Olympic gymnastics. We suggest school children to get school accident insurance, since they are prone to traumatic lesions.

Treatment of the acute phase. Rest and immobilization of the affected joint is paramount. Occasionally splints or casts are necessary. Kinesiology is beneficial, including cold packs, massage, ultrasound, water exercises, etc. It is necessary to stop the activity that produced or aggravated the condition. Tylenol or anti-inflammatory medications are used only for short periods. If the problem persists or if it is recurrent, a consultation with the Rheumatologist or Orthopedist would be indicated, so the proper diagnosis can be established. At times a steroid infiltration with lydocaine is needed to treat a tendinitis or a bursitis. This procedure is nearly painless, has no significant side effects and usually cures the problem.

Treatment of the chronic phase. A Rheumatologist well versed in hypermobility is the indicated specialist to see these patients, since it is necessary to differentiate JHS (better prognosis) from other HDCTs (VEDS, MFS) and other conditions as Fibromyalgia, Rheumatoid Arthritis, Lupus, Spondyloarthropaties and others. Furthermore we need to diagnose and treat early osteoarthritis and early osteoporosis that are more frequent in JHS patients, appearing in young adults of both sexes. In our recent JHS study, Osteoporosis was seen in 19% of males and 19% of females younger than 30 years old. It is for this reason that we recommend to do densitometries to all JHS patients, regardless of age or sex. In adolescents we think that densitometries should be not be done before puberty, that is the time when bone mass increases significantly.

In people that have recurrent musculo-skeletal problems it is necessary to find out which hobbies, sport or work is causing or aggravating them, in order to avoid them or to take preventive measures. Modification of the type and height of the chair at work, the use of joint protectors during certain activities or sports are useful measures. In some cases it is necessary to change sports, if possible, in favor of swimming, Yoga, Tai Chi or Pilates over contact sports like hockey, volleyball, football, soccer, karate, etc. In cases of capillary fragility and ecchymoses is necessary to avoid trauma and to take Duo CVP and Vitamin C. Since Osteoarthritis appears early in the life of these patients we use Glucosamine alone or with Condroitin Sulphate, in optimal doses and taken for long periods of time, to reduce pain and prevent progression.

If the patient has Chronic Fatigue it is necessary to see if he has Dysautonomia (Dys) rather than Fibromyalgia or Depression, with which it is frequently confused. The treatment of Dys is very effective and improves markedly the patient’s quality of life. These patients get benefit with periods of rest, elastic stockings and they need to drink 2 to 3 liters of liquids a day, to elevate their blood pressure (BP). For the same reason we recommend to increase salt intake, if they do not have Hypertension or renal problems. If the problem is important, the physician will prescribe medicines to elevate the BP, to control the symptoms. Patients need to know what aggravates their Dys, like standing without moving the feet, walking slowly, dehydration, high altitude, emotions, the sight of blood, a big meal or alcohol intake.

Physiotherapy is very important and should be done by trained personnel, because if not, it can even be detrimental. Complete range of joint motion exercises are indicated to increase strength of the tendons. It is also necessary to increase potency of the key muscle of the joint, like the quadriceps for the knee. Patients are instructed to avoid joint hyperextension of hypermobile joints and to use the stronger joints, to save the weaker ones, if possible. If the patient has genu recurvatum (knee that goes backwards) it is recommended not to stand with knee hyper extended and to use a strong heel of about 3 centimeters in height. There are exercises to correct lumbar hyperlordosis (increased curvature of the lumbar spine), which frequently is the cause of back pain in JHS. Splints are used only during periods of acute pain and for short periods. They are also indicated when a lax joint is going to be overused or abused.

The evaluation by a Physiatrist, that is a physician dedicated to diagnose and treat musculo-skeletal problems, can be of great help to evaluate problems and to plan an adequate therapeutic plan and even a special way of life, regarding type of work, sports and hobbies.

Occupational therapists are very useful in teaching which joint to use with certain forms of work, hobbies or sports. They teach joint protection techniques and make splints to prevent problems, reduce pain and prevent joint damage.

In exceptional cases, if all the above indications fail, a surgical approach might be indicated. We must not forget that these patients tend to have poor cicatrisation of surgical wounds. This is even more important if we are considering esthetic surgery.

In children, in some cases it is necessary to advise them not to do gymnastics, for a period of time, if it has been exacerbating the symptoms. Children should not be forced to practice sports in which they have had recurrent lesions. On the other hand, we should not stimulate inactivity, by the contrary, moderate exercises are quite beneficial for them. Swimming, bicycling and exercises to increase muscular tone are usually indicated. Children are generally more lax than adults and frequently have bone and joint pain, including back pain (lumbar hyperlordosis, scoliosis). These pains are usually disregarded or referred as “growing pain”. At times in early life JHS children may have problems with the hips, spine, knees, feet, etc. and in these cases it is important not to loose time and to take them as soon as possible to see a Pediatric Rheumatologist or a Pediatric Orthopedist specialized in hypermobility, to correct problems that otherwise could leave sequelae for life.

Jaime F. Bravo, MD

Rheumatology-Osteoporosis

Reviewed: February 2, 2007