Progressive pseudorheumatoid arthropathy is a very rare rheumatic disease that begins in childhood. However, rheumatic inflammatory factors are not found. The disease is based on impaired growth of the cartilage bodies.
What is progressive pseudorheumatoid arthropathy?
There are several alternative names for progressive pseudorheumatoid arthropathy. Progressive pseudorheumatoid arthropathy begins in childhood. The first symptoms can appear between the ages of two and eleven years. The disease is characterized by a combination of progressive arthropathy with spondyloepiphyseal dysplasia (short stature). See healthknowing for What is the Definition of Rickets.
It is a congenital genetic disorder of cartilage growth. Outside the joints there are no organic changes. The disease is very rare and occurs mainly in the Middle East and the Maghreb. The medical literature gives a frequency of one to nine in a 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 designation already indicates a cartilage change.
A genetic defect is given as the cause of the progressive pseudorheumatoid arthropathy. 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 cell growth.
The gene inhibits signal transduction pathways, with signaling cascades being inhibited. The lack of signal cascade inhibition leads to impaired growth of the cartilage. Vertebral bodies are particularly affected. These appear flattened and are therefore also referred to as flat vertebrae. The growth of the vertebral bodies is therefore irregular.
While nests of chondrocytes (cartilage cells) accumulate in the resting vertebra, there is hardly any cell formation in the direction of the growth zone. This is how flat vertebral bodies form, which cause short stature (spondyloepiphyseal dysplasia) in the affected person. Due to the malformed vertebrae, increasing arthropathy (progressive arthropathy) also develops. The joints are subject to constant wear and tear.
The result is osteoporosis, which is not based on biochemical degradation processes, and cartilage-forming metaplasia. In cartilage-forming metaplasia, the cartilage tissue is transformed into an irregular cartilage mass. However, the WISP3 genes of both parents must be affected by this mutation for the disease to develop. It is an autosomal recessive inheritance.
If both parents are healthy and each have a mutated WISP3 gene, there is a 25 percent chance that their children will have this inherited condition. If one parent already has the disease and the other parent has a mutated gene, there is already a 50 percent chance of passing progressive pseudorheumatoid arthropathy to their offspring==
Symptoms, Ailments & Signs
The first symptoms of progressive pseudorheumatoid arthropathy begin between the ages of two and eleven years. First, joint swelling occurs in the area of the finger joints. The ends of the bones (epiphyses) are expanded. Furthermore, the joint space narrows, the vertebral bodies flatten and the joint is increasingly destroyed.
Associated with this are the weakening of the muscles and increasing movement restrictions. Furthermore, spinal curvature and knee misalignments develop. The result is swelling, stiffness and pain in several joints. Knee, hip, finger, hand and elbow joints are particularly affected.
However, there is no warming or blushing on the affected joints, which excludes inflammatory processes. Patients suffer from short stature due to the flattened vertebral bodies. Large asymmetrical cavities sometimes form in the pelvis. As the disease progresses, the cartilage mass decreases more and more. Due to mechanical stress, the bones in these areas are increasingly broken down. The movement restrictions increase. Eventually, a joint replacement may become necessary.
Diagnosis & course of disease
Progressive pseudorheumatoid arthropathy closely resembles juvenile rheumatoid arthritis. The word “pseudorheumatic” suggests this. It means “apparently rheumatic”. In order to diagnose progressive pseudorheumatoid arthropathy, a rheumatic disease must first be ruled out.
If the blood count shows a normal ESR, no leukocytosis, normal CRP and no negative rheumatoid factors, juvenile rheumatoid arthritis can be excluded in the differential diagnosis. X-ray examinations are also carried out. In progressive pseudorheumatoid arthropathy, x-rays reveal flattened vertebral bodies, breakdown of adjacent bone, and increased irregular cartilage formation around the affected joints.
Histological examinations reveal nest-like accumulations of chondrocytes (cartilage cells) in the growing and resting cartilage. At the same time, the normal columnar arrangement of chondrocytes in the growth zone has been lost. This fact suggests that this disease mainly affects articular cartilage. Before the actual diagnosis, antirheumatic drugs are often administered.
However, these do not work. This is also an indication that this disease does not belong to the rheumatic group and requires other examinations.
Since this disease occurs in most cases in childhood, the development and growth of the child is significantly restricted. In many cases, this also leads to limitations and complaints in adulthood. In some cases, those affected are also dependent on the help of other people in their everyday lives. In most cases, this leads to muscle weakness and swelling in the joints.
Restricted movement and pain can also occur. In most cases, however, the pain itself occurs under stress. This prevents the child from playing or participating in sports activities. Stiffening or misalignment of the knee can also occur as a result of the disease and significantly reduce the quality of life of those affected.
Furthermore, some of those affected also suffer from short stature, which can lead to teasing or bullying, especially in children. Unfortunately, it is not possible to treat this disease. Those affected are therefore 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 go to the doctor?
Irregularities in the growth and development process of the child are considered to be of concern. If the joints become swollen, if there are malpositions, limitations in locomotion or inconsistencies in the natural movement sequences, a doctor is needed. In the case of pain, optical changes in the skeletal system and a narrowed joint, a doctor should be consulted. If there are signs of short stature or if there are irregularities in the physique in direct comparison to children of the same age, a doctor should be consulted.
Weak muscle strength, listlessness or withdrawal behavior should be examined and treated. If usual and age-appropriate leisure activities cannot be undertaken or if there are discrepancies when participating in sporting activities, a doctor is required. If the movement restrictions lead to emotional problems, a doctor’s visit is also advisable. Teariness, aggressive behavior, or a strong dissatisfaction should be presented to a doctor. If the person concerned suffers from sleep disorders, concentration and attention deficits as well as general functional disorders, the symptoms need to be clarified.
A lack of motivation, refusal to eat, or a decrease in well-being should be discussed with a doctor. In progressive pseudorheumatoid arthropathy, there is typically a steady increase in symptoms. The need for a doctor’s consultation therefore gradually becomes apparent over several weeks or months.
Treatment & Therapy
Progressive pseudorheumatoid arthropathy is a very rare hereditary disease. Therefore, a causal 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.
Because progressive pseudorheumatoid arthropathy is an inherited condition, there is no way to prevent it.
Since no treatment exists yet that allows for a full recovery, follow-up treatment is out of the question. Nevertheless, additional treatments are useful during or after symptomatic therapy. A special exercise program can reduce suffering. Muscles and joints should not be subjected to excessive loads. Nevertheless, light sporting activities have a positive effect.
Psychotherapeutic treatments are recommended because progressive pseudorheumatoid arthropathy can lead to severe disability and the resulting depression. Open and enlightened discussions help those affected in psychological crisis situations. Regular consultations of the doctor with 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 freedom of movement and pain as far as possible. As a rule, the first follow-up examination takes place a year later. All further examinations at an interval of five years. Muscular and coordinative weaknesses are examined.
Physiotherapy and occupational therapy should then be considered. Progressive pseudorheumatoid arthropathy affects affected persons for a lifetime. Even after a successful operation, the patient is not considered cured. Systematic muscle weakness and joint destruction can occur anywhere in life.
You can do that yourself
Progressive pseudorheumatoid arthropathy in children affects physical development and often leads to symptoms and limitations even with therapy. Therefore, 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 in the joints. The muscles and joints should not be overstrained. This means that the children cannot play sports and should also be careful when playing. The quality of life suffers significantly. In some cases, there is also short stature, which is the cause of teasing in kindergarten or at school. In this case, psychotherapy is recommended for the child.
Patients often become accustomed to their relative immobility and limited resilience. However, they often find it difficult to seek help. Parents can talk openly about the situation 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 give the child false hope. In this way, it can develop into a relatively independent, individual character within the scope of its possibilities.