Rheumatoid arthritis

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Classification according to ICD-10
M05 Seropositive rheumatoid arthritis
M06 Other chronic polyarthritis
ICD-10 online (WHO version 2019)

The rheumatoid arthritis (including rheumatoid arthritis or (obsolete) rheumatoid arthritis and rheumatoid arthritis ) is a long-lasting rheumatic disease and the most common inflammatory disease of the joints . The disease is abbreviated as RA (rheumatoid arthritis), cP (chronic polyarthritis) or pcP (primary chronic polyarthritis, obsolete).

Morphology of the hand with cP - the characteristic ulnar deviation is shown on the right.
Peter Paul Rubens , self-portrait

The onset of the disease is often insidious, but it can also occur suddenly, with pain in the little finger or toe joints . Other joints can also be affected, especially wrists, knees, shoulders, ankles and hips. Typically, the carpal bones , the metacarpophalangeal joints ( metacarpophalangeal joints ) and the central finger joints ( proximal interphalangeal joints, PIP) are preferably affected. In contrast to psoriatic arthritis, the end joints of the fingers and toes (distal interphalangeal joints, DIP) are not affected. The affected joints swell and become overheated. Reddening of the affected joints can also occur. Symmetrical (= bilateral) synovitis of the joints distant from the trunk is typical, but not mandatory. These symptoms are usually most pronounced in the morning ; it is symptomatic morning stiffness. As the disease progresses, more and more joints are affected.

Most of the time the disease progresses in phases; an episode typically lasts between a few weeks and months. The symptoms subside between the individual attacks. An improvement in the state of health is not necessarily due to the therapy.

Special forms of rheumatoid arthritis are Felty's syndrome (severe form of RA with hepatosplenomegaly and neutropenia), Caplan syndrome (RA and silicosis), age RA (LORA - late onset rheumatoid arthritis, onset after age 60). and RS3PE syndrome (transient seronegative symmetric synovitis with compressible edema).

Epidemiology (frequency, gender and age distribution)

Symptoms corresponding to rheumatoid arthritis were described in 1802 by William Heberden , in 1800 by Augustin Jakob Landrè-Beauvais (1772–1840) and in 1852 by Jean-Martin Charcot, as well as the term "rheumatoid arthritis", which was coined in 1876 by Alfred B. Garrod . Apart from inflammatory activated osteoarthritis , rheumatoid arthritis is the most common inflammatory joint disease . Around 0.5–1% of the population are affected worldwide. In Germany, the number of diseases is estimated at 800,000, with women being affected around three times as often as men. At the rheumatoid arthritis, people can become ill of all ages. An occurrence between 35 and 45 years of age is common. However, children can also be affected; this is called juvenile idiopathic arthritis . The incidence of illness increases with age. The age between 55 and 64 years for women and between 65 and 75 years for men is seen as the peak of the incidence rate.

root cause

The causes of the disease are still largely unexplained. It is believed to be an autoimmune cause in which the body's own substances, e.g. B. the articular cartilage , are attacked by cells of the immune system . A distinction must be made between the trigger of the disruptive immune reaction and other factors that establish and maintain this reaction in the immune system. In the past, psychosomatic influences were also assumed. This illness was one of the Holy Seven of the psychosomaticist Alexander.

Triggering factors

According to a scientific hypothesis, viruses and bacteria can trigger disease , similar to the pathogenesis of rheumatic fever already described. The connection between periodontal disease and the development of rheumatoid arthritis has recently been discussed. In addition, a possible connection with the occurrence of Prevotella bacteria in the intestine was discovered. These can also be found in the oral cavity. May have autoantibodies and autoreactive T cells against the ribosomal protein RPL23A trigger for arthritis.

Contributing factors

A genetic influence has been proven several times , among other things by twin studies . A certain form of RA is therefore associated with certain MHC or HLA alleles.

In rheumatoid arthritis, the function of regulatory T cells is also weakened. This depends directly on the activity of FOXP3 , and thus on the level of TNF-α .

Pathogenesis

Changes in the joint
Penetrating cell aggregates
Degradation of cartilage and bones by proteolytic enzymes
Necrosis in the heart
Typical x-ray

The clinical picture of rheumatoid arthritis is the result of structural processes that take place in the joint and near-joint tissue. A complex of immunological joint inflammation, oncological joint destruction and extra- articular , u. U. even fatal primarily necrotizing processes. The notion of a purely inflammatory disease, which has been passed on for well over a hundred years, is based on alternately assessed clinical-immunological phenomena and is presented in the following paragraph, but is not supported by more recent research results:

It is described that faulty immune cells migrate into the affected joint and there produce inflammatory messenger substances - so-called cytokines - with the help of which immune cells communicate with each other. On the cell membrane of the target cell there are receptors to which the cytokine molecules dock using the lock and key principle and trigger the corresponding reactions there. According to the theory, this balance between the cytokines is disturbed in the sick . In particular, interleukin -1 (IL-1), IL-6 and the tumor necrosis factor -alfa (TNF-α) are excessively present and are responsible for the destructive inflammatory process in cartilage tissue and the activation of bone-degrading cells, the osteoclasts. The action of the cytokines creates a tumor-like tissue on the synovium, the pannus, which after a certain time destroys cartilage , bones and other structures of the affected joint.

In the meantime it has been shown in mice that fibroblasts of the synovia typical of RA can migrate from affected joints via the bloodstream to previously healthy joints. This could explain the typical spread of the disease. However, according to investigations by the Center for Rheumatic Pathology , Mainz, the inflammatory process is rated as low in relation to other, likewise immunologically triggered inflammatory joint diseases. Although this is usually seen as the reason for the severe destruction of the joint, evidence of the destruction of bones and cartilage by immunological inflammation has never been produced.

The destruction of joints in rheumatoid arthritis is rather the work of a specific oncological process that develops in stages from the pluripotent synovial cell matrix. The aggressive, homogeneous cell aggregates that penetrate the cartilage and bones consist of large, densely packed polygonal cells. The large, bright cell nucleus contains 1 to 2 nucleoli . These cells express a number of highly potent proteolytic enzymes that enable them to rapidly destroy the joint by degrading cartilage and bone. The vascular-free process is short-lived, the aggressive cell aggregates collapse within a few days and are resorbed by inflammatory cells and macrophages . Inflammatory factors are not involved in the process of destruction. However, the process leaves behind the familiar pannus, often falsely attributed to inflammation. This aggressive phase can repeat itself on the same joint and continue the process of destruction. This process, which is specific to rheumatoid arthritis, has been classified by the German Cancer Research Center as “tumor-like proliferation”.

Another potentially fatal component of rheumatoid arthritis in the absence of an inflammatory disorder is the acute death of tissues due to a local release of collagenases . They are processes distant from the joint and are characterized by central necrosis and a dense radial cell palisade. They destroy collagen structures that are poor in blood vessels. In tendons they lead to tendon rupture , in the eye they affect the sclera , which leads to loss of the eye. They can destroy the walls of arteries and thus lead to limb death. These are processes that are largely beyond clinical observation and are therefore often attributed to other diseases (e.g. heart attack).

Diagnosis

The diagnosis is made by laboratory, clinical and imaging methods.

  • Laboratory: A search for rheumatoid factors (RF antibodies) in the blood is carried out, the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are tested. Rheumatoid factors (RF) are not conclusive here, but only indicative; rheumatoid factors can also be detected in other diseases. Cases of seronegative arthritis are known as well as cases in which those affected have such a low RF that it is insufficient for diagnosis. However, studies have shown that a seropositive RF or ACPA status suggests a severe erosive course of the disease with rapid progressive joint destruction.
  • In recent times, the test systems for the serological detection of the so-called have ACPAs ( A NTI C itrullinated P rotein / peptides A ntibodies, A ntikörper against c itrullinierte P rotein- / P eptid- A ntigene) the classical serodiagnosis on rheumatoid factors improved. The most prominent representatives of the ACPA test systems are the CCP assay and the detection of autoantibodies against mutated citrullinated vimentin ( anti-MCV ELISA). Both achieve sensitivities of almost 80% and specificities of almost 98%.
  • Clinic: Counting and localization of painful, swollen and overheated joints, patient self-assessment (e.g. DAS28 , Disease Activity Score 28 )
  • Imaging procedures: X-ray or MRI examinations are required at the beginning and during the course of the procedure in order to be able to assess damage to the bones (erosions). Typical radiological findings are subchondral osteoporosis , destruction of the surrounding bone, ankylosis and joint malpositions ( buttonhole deformity , swan neck deformity , ulnar deviation ).
  • With soft tissue and bone scintigraphy , the distribution pattern of the inflammatory activity of the various joints can be shown quite well.

Classification criteria

With the joint 2010 ACR / EULAR criteria for the classification of rheumatoid arthritis, the American rheumatologist association ACR (American College of Rheumatology) and the association of European rheumatologists EULAR (European League Against Rheumatism) have a new basis for an international standardization of the classification the disease published. With this work, the previous ACR classification criteria from 1987 were de facto overridden.

Especially the autoimmune diagnostics and serology have with the new criteria more weight in the RA diagnosis was obtained (RA early diagnosis). According to the new ACR / EULAR criteria, a highly positive rheumatoid factor or a highly positive ACPA titer (ACPA: anti-citrullinated protein antibody, German: Antibodies against citrullinated peptides / proteins ) already contributes half of the score (3 points out of 6), who classifies an affected person as an RA patient. In the ACR criteria of 1987, only the diagnostically unspecific rheumatoid factors appeared.

The radiological changes in the joints, which were still regarded as decisive in the classification criteria from 1987, are becoming less important as a symptom of established RA (“late” RA) in favor of early RA diagnosis.

2010 ACR / EULAR Classification Criteria for Rheumatoid Arthritis

The 2010 ACR / EULAR criteria for classifying rheumatoid arthritis produce a score between 0 and 10. Any patient with a score of 6 or more is clearly classified as an RA patient. Four areas are covered in the diagnosis:

  • joint involvement (up to 5 points depending on the type and number of joints affected)
  • Serological parameters (in addition to the rheumatoid factors now also ACPA - depending on the antibody titer level up to 3 points),
  • the acute phase reaction (1 point for increased ESR or CRP values)
  • the duration of the arthritis (1 point for complaints that last six weeks or more)

The diagnosis is still left to the rheumatologist. For general practitioners, for general practitioners working internists or for orthopedic surgeons (all "non-rheumatologists") the respective suspicion criteria for rheumatoid arthritis remain valid. For doctors in Germany, these are the RA suspicion criteria of the German Society for Rheumatology (DGRh):

  • two or more swollen joints
  • Morning stiffness of more than an hour
  • Increased sedimentation rate (ESR) or CRP levels indicate rheumatoid arthritis
  • the detection of rheumatoid factors or autoantibodies against CCP (these are certain ACPA ) can substantiate the suspicion of rheumatoid arthritis. - But: A negative finding does not rule out the diagnosis of RA.

The disease activity during diagnosis and therapy control is often determined via the DAS28 .

Interstitial pulmonary fibrosis

Interstitial lung disease can be detected in up to 60% of patients with rheumatoid arthritis on high-resolution CT . In 10% of cases, the lung change is symptomatic. Mortality is also increased with simultaneous rheumatoid arthritis and interstitial pulmonary fibrosis. In English, the name RA-ILD (Rheumatoid arthritis - Associated Idiopathic Lung Disease) is used.

The formation of exudates in rheumatoid arthritis can also lead to pleural effusion . The pH value of the pleural fluid measured during a pleural puncture then shows acidosis .

therapy

Medication

In the drug therapy of rheumatic diseases, four main groups of drugs are traditionally distinguished:

  • Analgesics (pain relievers)
  • non-steroidal anti-inflammatory drugs NSAID
  • Glucocorticoids
  • Basic therapeutic agents (long-acting anti-rheumatic drugs (LWAR), disease-controlling drugs (disease modifying anti-rheumatic drugs, DMARD))

The different drug groups have different effects and therapeutic goals. They are therefore often used simultaneously, e.g. B. In addition to basic therapeutic agents, cortisone or cortisone-free anti-inflammatory drugs are often given .

Modern concepts of rheumatism treatment are characterized by the fact that different methods are combined. The success of the treatment depends to a large extent on putting together the individually correct treatment combination for the different clinical pictures and situations. The basic therapeutic agent MTX ( methotrexate ) is used very often alone or in combination , which is the " gold standard " of basic therapy due to its effectiveness and tolerability . Other so-called conventional basic therapeutic agents are leflunomide , sulfasalazine , chloroquine and hydroxychloroquine (originally developed as anti-malaria drugs), cyclosporine A , azathioprine and gold compounds such as auranofin . However, gold compounds are considered to be the basic therapeutic agents of second choice.

Newer therapeutic agents are antibodies, soluble receptors or antagonists to pro-inflammatory cytokines such as IL-1 , -6 IL or TNF-alpha are directed and biologics ( biologicals ), should be. The TNF-alpha inhibitors adalimumab , certolizumab , etanercept , golimumab and infliximab are directed against TNF-alpha . The IL-1 receptor antagonist is called anakinra . B-cell therapy with rituximab (monoclonal CD20 antibody) has been approved across Europe since July 2006. Rituximab is used after the initial TNF-alpha inhibitor fails. If the response to and / or intolerance to a TNF-alpha inhibitor is insufficient, the EULAR guidelines require a switch to another TNF-alpha inhibitor or biologics with a different mechanism of action, e.g. B. Rituximab recommended. A substance that modulates T-cell co-stimulation has been approved since May 2007. It is the completely human fusion protein CTLA4Ig ( abatacept ). Abatacept is currently used after at least one TNF-alpha antagonist has failed. The humanized antibody tocilizumab , which specifically inhibits interleukin-6 receptors, has been approved throughout Europe since January 2009 . Further active ingredients are in clinical research in phase II and phase III studies. The oral Janus kinase (JAK) inhibitor tofacitinib (trade name: Xeljanz ; manufacturer: Pfizer ) has been approved throughout the EU for patients with moderate to severe rheumatoid arthritis since May 2017.

A study showed that the much cheaper triple therapy with methotrexate, sulfasalazine and hydroxychloroquine achieves treatment results that are equivalent to the combination of methotrexate with a biological agent.

Surgical therapy for rheumatoid arthritis

a) Dislocated toes in RA b) after Stainsby correction

Rheumatism surgery has established itself as a branch of orthopedics . The doctors who use them have specialized in surgically treating the severe and sometimes most severe joint changes that can arise in the course of a rheumatic disease.

Synovialectomy

The synovium - the mucous membrane of the joint capsule - produces the synovial fluid and is the actual place where the disease occurs. Surgical synovial membrane removal was first performed towards the end of the 19th century. Removing the synovium at an early stage can have a positive effect on the overall course. Depending on the anatomical conditions of the affected joint, this often does not work completely, but a significant reduction in the diseased tissue usually has a soothing effect. Synovial tissue is also present in the tendon sheaths. Usually it provides nourishment and lubrication for the tendons there. In rheumatic diseases, strong swellings, so-called synovial cushions, develop, especially in the extensor tendon compartments on the back of the hand. The pathologically altered synovia attacks these tendons, the tendons can tear. The early synovialectomy has a braking effect on the disease process.

Later on, when joints were destroyed, such relatively small interventions are no longer sufficient. Different procedures are used depending on the location, type and function of the joint.

Joint resection

The destroyed joint is removed without replacement. The aim of post-treatment with plaster of paris and splints is to enable functionally satisfactory scar formation. These procedures are often used on the metatarsophalangeal joints.

Arthrodesis (joint stiffening)

The diseased joint is removed and the bone stumps are fixed to one another in a position that is favorable for their function. After healing, the former joint is completely stiffened, but largely painless. In rheumatism sufferers, arthrodeses are preferably performed on the thumb, the wrist joints, the end joints of the fingers (so-called DIP joints), the upper and lower ankle, the tarsus and the metatarsophalangeal and metacarpal joints of the big toe and the metacarpus and metacarpal joints.

Arthroplasty

Part of the joint is resected and the resulting defect is filled with the body's own tissue. Usually a curled tendon is used for this. This procedure can be useful in the area of ​​the wrist.

Endoprostheses

As with osteoarthritis caused by wear, attempts are made to postpone the installation of an artificial joint as long as possible. Therefore, early detection and consistent, stage-appropriate drug therapy (see basic therapy), radio- or chemosynoviorthesis (rarely synovialectomy) are very important. With increasing destruction of the joint cartilage, movement pain and pain at rest, the decision for a joint prosthesis is also made for rheumatic diseases . The aim here is to reduce pain, improve joint mobility and joint stability. A special feature of the prosthesis operation for rheumatics is the consistent removal of the rheumatic-inflammatory inner joint mucosa (synovia).

Typical regions that can be replaced with an artificial joint in rheumatism sufferers are the large joints (shoulder joint, hip joint, knee joint, upper ankle joint, elbow joint) and some small joints (metacarpophalangeal joint, metacarpophalangeal joint, big toe joint). Especially with rheumatism patients should not wait too long with the so-called endoprosthesis operation in order to forestall the inflammatory destruction of stabilizing capsular ligament structures or the development of bone defects.

In endoprosthetics (installation of artificial joints) a distinction is made between cementless and cemented joints. At the knee, one differentiates between “uncoupled” from “partially coupled” and “fully coupled” prostheses in ascending order according to the degree of forced joint guidance. The prosthesis materials and designs used do not differ from those used in conventional osteoarthritis. A special feature, however, is the artificial replacement of the base of the finger (so-called MCP joints) and middle joints (so-called PIP joints). Elastic "joint rods" containing silicone are most often implanted here.

Basically, the surgical implementation of an artificial joint in rheumatics does not differ from that in osteoarthritis patients. Due to immunomodulating drugs (e.g. cortisone, biologics, etc.), the reduced body defense as a result of the chronic illness and other factors, the number of early infections after prosthetic surgery and the loosening rate compared to other osteoarthritis patients is slightly higher. Nevertheless, the artificial joint replacement represents a very large enrichment of the treatment options with a significant increase in quality of life, especially for rheumatism patients.

Radiosynoviorthesis

Radiosynoviorthesis (RSO) is an alternative to surgical treatment . The effectiveness in rheumatoid arthritis has been confirmed by studies with a high level of evidence. The indication for the RSO is given if also after six months of therapy based intraarticular is not to control injection of cortisone-containing solutions of the disease process. The earlier it is used in the disease process, the better the success of the RSO. Pregnancy and breastfeeding are considered absolute contraindications , and treatment in children and adolescents is considered relative contraindications. The nuclides used (especially 90 Y , 186 Re and 169 Er ) depend on the size of the joint to be treated. They are pure or at least predominantly beta emitters .

Fasting and vegetarian diet

An analysis of the available clinical studies regarding a possible positive influence on RA through fasting followed by a vegetarian diet showed a statistically and clinically relevant positive influence on the long-term disease course through such nutritional therapy. It was also shown that if the patient switched to the previous diet again, symptoms of the disease could recur. Like most nutritional therapies, a fasting cure should be discussed with the attending physician or therapist. Elimination diets, which try to exclude possible allergy or disease-causing factors from the diet, could also be useful. Good results have also been obtained with raw vegan foods in conjunction with lactobacilli supplements. The results refer to studies with a small number of participants.

Guidelines

Review articles

older literature
  • Ludwig Heilmeyer , Wolfgang Müller: The rheumatic diseases. In: Ludwig Heilmeyer (ed.): Textbook of internal medicine. Springer-Verlag, Berlin / Göttingen / Heidelberg 1955; 2nd edition, ibid. 1961, pp. 309-351, here: pp. 321-333.

Web links

Individual evidence

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  22. ↑ The 2010 ACR-EULAR classification criteria for rheumatoid arthritis.
  23. ↑ Pierre-Antoine Juge, Joyce S. Lee, Esther Ebstein, Hiroshi Furukawa, Evgenia Dobrinskikh: MUC5B Promoter Variant and Rheumatoid Arthritis with Interstitial Lung Disease . In: New England Journal of Medicine . tape 379 , no. 23 , December 6, 2018, ISSN  0028-4793 , p. 2209–2219 , doi : 10.1056 / NEJMoa1801562 ( nejm.org [accessed February 16, 2019]).
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  30. ↑ Summary of the EPAR for the public , EPAR of the EMA, accessed on June 14, 2018
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