Progressive pseudorheumatoid arthropathy is a very rare rheumatoid-like disease that begins in childhood. However, rheumatic inflammatory factors are not found. The disease is due to impaired growth of cartilage bodies.
What is progressive pseudorheumatoid arthropathy?
There are several other alternative names for progressive pseudorheumatoid arthropathy. Progressive pseudorheumatoid arthropathy begins in childhood. First symptoms may appear between the ages of two and eleven. The disease is characterized by a combination of progressive arthropathy with spondyloepiphyseal dysplasia (short stature). It is a congenital genetic disorder of cartilage growth. There are no organic changes outside the joints. The disease is very rare and occurs mainly in the Middle East and Maghreb. Medical literature reports a frequency of one to nine per million. Inheritance is autosomal recessive. However, progressive pseudorheumatoid arthropathy should not be confused with juvenile rheumatoid arthritis. The terms spondyloepiphyseal dysplasia (SED) with progressive arthropathy, dysplasia spondyloepiphysaria tarda with progressive arthropathy, or progressive pseudorheumatoid chondrodysplasia are used synonymously. Especially the latter name already indicates cartilage alteration.
Causes
The cause of progressive pseudorheumatoid arthropathy is said to be a genetic defect. This is a mutation in the WISP3 gene. This gene is located on chromosome six and encodes a growth regulator. The proteins encoded by this gene are rich in cysteine. They play a major role in cell differentiation and growth. The gene inhibits signal transduction pathways, inhibiting signaling cascades. The loss of signal cascade inhibition results in impaired cartilage growth. Vertebral bodies are particularly affected. These appear flattened and are therefore also called flat vertebrae. As a result, the growth of the vertebral bodies is irregular. While nests of chondrocytes (cartilage cells) accumulate in the resting vertebra, hardly any cell formation takes place in the direction of the growth zone. Thus, flat vertebral bodies are formed, causing short stature (spondyloepiphyseal dysplasia) of the affected person. Due to the malformed vertebral bodies, an increasing arthropathy also develops (progressive arthropathy). The joints are subject to constant wear and tear. As a result, osteoporosis, which is not based on biochemical degradation processes, and cartilage-forming metaplasia occur. In cartilage-forming metaplasia, the cartilage tissue is transformed into an irregular cartilage mass. However, to develop the disease, the WISP3 genes of both parents must be affected by this mutation. This is an autosomal recessive inheritance. If both parents are healthy and each has a mutated WISP3 gene, there is a 25 percent chance that their children will have this hereditary disease. If one parent is already affected by this disease and the other parent has a mutated gene, there is already a 50 percent chance of transmitting progressive pseudorheumatoid arthropathy to their offspring==
Symptoms, complaints, and signs
The first symptoms in progressive pseudorheumatoid arthropathy begin between two and eleven years of age. Initially, joint swelling occurs around the finger joints. The bone ends (epiphyses) are dilated. Furthermore, joint space narrowing, flattening of the vertebral bodies and increasing joint destruction occur. This is associated with weakening of the muscles and increasing movement restrictions. Furthermore, spinal curvatures and knee malpositions develop. As a result, swelling, stiffness and pain develop in several joints. Knee, hip, finger, hand and elbow joints are particularly affected. However, there is no heating or redness at the affected joints, which rules out inflammatory processes. Patients suffer from short stature due to flattened vertebral bodies. Large asymmetric cavities sometimes form in the pelvis. As the disease progresses, the cartilage mass decreases more and more.Mechanical stress also causes the bones in these areas to degrade more and more. In the process, the restrictions on movement increase. Eventually, joint replacement may become necessary.
Diagnosis and disease progression
Progressive pseudorheumatoid arthropathy closely resembles juvenile rheumatoid arthritis. The word “pseudorheumatoid” suggests this. It means “apparently rheumatoid.” Therefore, to diagnose progressive pseudorheumatoid arthropathy, rheumatic disease must first be ruled out. If the blood count shows normal sedimentation, no leukocytosis, normal CRP, and no negative rheumatoid factors, juvenile rheumatoid arthritis can be excluded as a differential diagnosis. Furthermore, radiographic examinations are performed. In progressive pseudorheumatoid arthropathy, radiographs reveal flattened vertebral bodies, degeneration of adjacent bone, and increased irregular cartilage formation around affected joints. Histologic examination reveals nest-like collections of chondrocytes (cartilage cells) in growing and resting cartilage. At the same time, the normal columnar arrangement of chondrocytes in the growth zone is lost. This fact suggests that this disease mainly affects articular cartilage. Antirheumatic drugs are often administered before the actual diagnosis. However, these do not work. This is also already an indication that this disease does not belong to the rheumatic group of forms and requires other examinations.
Complications
Since this disease in most cases occurs in childhood, the development and growth of the child is significantly restricted by it. Thus, even in adulthood, in many cases there are limitations and discomfort. In some cases, the affected persons themselves are also dependent on the help of other people in their daily lives. In most cases, this results in muscle weakness and swelling of the joints. Movement restrictions and pain can also occur. In most cases, however, the pain itself occurs under stress. This prevents the child from participating in play or sports activities. Stiffening or malpositioning of the knee can also occur as a result of the disease and significantly reduce the quality of life of the affected person. Furthermore, some affected individuals also suffer from short stature, which can lead to teasing or bullying, especially among children. Unfortunately, it is not possible to treat this disease. Those affected are thus dependent on various therapies that can limit the symptoms. However, surgical interventions are often necessary to treat the symptoms. The patient’s life expectancy is usually not reduced with this disease.
When should you see a doctor?
Irregularities in the growth and development process of the child are considered worrisome. If swelling of the joints appears, there are malpositions, restrictions in locomotion or inconsistencies in the natural movement patterns, a doctor is needed. In case of pain, visual changes of the skeletal system as well as a narrowed joint, a visit to the doctor should be made. If short stature becomes apparent or if irregularities of the physique appear in direct comparison to children of the same age, a doctor should be consulted. Weak muscle strength, apathy or withdrawal behavior should be examined and treated. If habitual and age-appropriate leisure activities cannot be performed or if there are inconsistencies in participation in sports activities, a physician is needed. If the movement restrictions lead to emotional problems, a visit to the doctor is also advisable. Weepiness, aggressive behavior, or a strong sense of dissatisfaction should be presented to a physician. If the affected person suffers from sleep disorders, concentration and attention deficits as well as general functional disorders, a clarification of the complaints is necessary. A lack of motivation, refusal to eat, or a decrease in well-being should be discussed with a physician. In progressive pseudorheumatoid arthropathy, there is typically a steady increase in symptoms. The need for consultation with a physician therefore slowly emerges over several weeks or months.
Treatment and therapy
Progressive pseudorheumatoid arthropathy is a very rare hereditary disease. Therefore, causative treatment is not possible. Only symptomatic therapy is given. The destruction of the joints often causes severe pain, which must be reduced with painkillers. It is often necessary to surgically replace destroyed joints with an artificial joint.
Prevention
Because progressive pseudorheumatoid arthropathy is a hereditary disease, there is no way to prevent it.
Follow-up
Because no treatment exists yet that allows complete recovery, follow-up care is out of the question. Nevertheless, additional treatments are useful during or after symptomatic therapy. A specific exercise program can reduce suffering. Muscles and joints should not be subjected to excessive stress. Nevertheless, light sports activities have a positive effect. Psychotherapeutic treatments are recommended, since progressive pseudorheumatoid arthropathy can lead to severe limitations and resulting depression. Open and enlightened discussions help those affected in psychological crisis situations. Regular consultations of the physician in case of increasing complaints would be necessary. Furthermore, examinations of artificial joints must be carried out. A stay in a rehabilitation clinic often follows an operation in order to restore the greatest possible freedom from pain and movement. As a rule, the first follow-up examination takes place one year later. All further examinations take place at intervals of five years. Muscular and coordination weaknesses are examined. Physical therapy should then be considered, as well as occupational therapy. Progressive pseudorheumatoid arthropathy burdens affected individuals throughout their lives. Even after successful surgery, the patient is not considered cured. Systematic muscle weakening and joint destruction can occur anywhere throughout life.
Here’s what you can do yourself
Progressive pseudorheumatoid arthropathy in children affects physical development and often causes discomfort and limitations even with therapy. That is why patients should be treated with patience and caution. They often need the help of other people even in adulthood. This is due to the muscle weakness and the typical swelling of the joints. The muscles and joints should not be put under too much strain. This means that the children cannot play sports and should also be careful when playing. The quality of life suffers considerably. In addition, in some cases there is dwarfism, which is the cause of teasing in kindergarten or school. In this case, psychotherapy is recommended for the child. Patients often get used to their relative immobility and low resilience. Nevertheless, they often find it difficult to get help. In an open conversation, parents can talk about the situation together with the child and the doctor. This is a gentle way to combat aggression and depressive moods. Since there is no curative therapy, it is very important to be honest and not to give the child false hope. In this way, it can develop into a relatively independent, individual character within its means.