Rheumatism center erding rheumatoid arthritis

Rheumatoid ArthritisRheumatoid arthritis is a chronic, d. h. Joint inflammation lasting more than 6 weeks, usually occurring on both halves of the body at the same time (arthritis = joint inflammation). It used to be called chronic polyarthritis (poly = many) because the inflammation affects more than 3 joints at a time as it progresses. Inflammation can destroy joints over time. Restricting your mobility.

Already a few weeks after the onset of the disease, some patients can be diagnosed with modern examination methods (z. B. the magnetic resonance tomography) detect the first joint changes. It is recommended to start the treatment within the first 3 months after the onset of the disease, if possible, because the earlier the therapy is started, the less damage is likely to be caused by the arthritis in the further course of the disease. Patients with typical signs of the disease should therefore consult a specialist in internal medicine and rheumatology (rheumatologist) as early as possible.

Rheumatoid arthritis is the most common chronic inflammatory rheumatic disease of all. It is estimated that in Germany about 1% of the population (about 800.000 people) is suffering from rheumatoid arthritis. Women are affected about 3 times more often than men. Rheumatoid arthritis can occur at any age, but men often become ill between the ages of 65. and 75 years of age, women between the ages of 55. and 64. year of life. But children can also develop a form of rheumatoid arthritis (juvenile idiopathic arthritis).

Causes& Risk factors

Rheumatoid arthritis is an autoimmune disease in which the immune system attacks the body's own ties. The actual causes of this malfunction are not known, despite intensive research. There is a genetic predisposition to rheumatoid arthritis, z.B. it occurs in hereditary twins (identical) and in some families in clusters.

In addition, there are probably other largely unknown factors that can trigger or promote the outbreak of the disease. Smoking seems to strongly favor the development of the disease. Demonstrably worsens the course of the disease.

The joints are at the center of the inflammatory process in rheumatoid arthritis. The inflammation is directed against the body's own joint tie, as the immune system can no longer distinguish between "foreign" and "own" Can distinguish. The body fights itself. Destroys its own tie in this way.

A complex interaction between various inflammatory cells (phagocytes, T and B cells) and inflammation-mediating protein molecules (known as cytokines) initially leads to swelling of the mucous membrane in the inflamed joint. The joint mucosa begins to proliferate and forms substances that destroy cartilage and bone. Without anti-inflammatory treatment, the joint cartilage and bone are destroyed. This causes the joints themselves to become non-functional.

signs& Symptoms

The main feature of rheumatoid arthritis is inflammation of the joints. However, it is often not limited to the joints, but can also spread to other organs.

Typical features of rheumatoid inflamed joints in rheumatoid arthritis are:

– Joint pain, especially at rest – Morning stiffness of joints lasting longer than 30 minutes – Restriction of movement – Swelling in more than 2 joints – Bilateral joint swelling of the metacarpophalangeal and middle finger joints – Same distribution pattern of affected joints on the left and right sides of the body – Bony deformity in long-term progression

Rheumazentrum erding rheumatoid arthritis

symptoms of rheumatoid arthritis

Rheumatoid arthritis progresses very differently: it can begin insidiously in the small joints of the fingers, hands and toes on the left and right side. However, it can also occur abruptly and it can affect only a few joints on one side at the beginning, even larger ones, z. B. Knee, shoulder or elbow. However, it usually affects the finger and wrist joints on both sides first. The finger end joints are usually left out. The inflammation causes swelling of the synovial membrane. This makes the joint swellings feel soft and turgid. In addition, the flexor tendons can. Inflammation of the extensor tendons of the fingers. In other joints, such as the knee and shoulder joints, the bursa may also be affected by the inflammation.

Sometimes almost all joints are infested within weeks or months. In other cases, the disease seems to stand still for years before suddenly adding more joints in batches: Toe and ankle joints, elbows, shoulders, knees, hips and the cervical spine. Apart from the cervical spine, rheumatoid arthritis does not affect the spine.

Rheumatoid arthritis first leads to decalcification of the bone near the joint (osteoporosis). In the further course it destroys the bone at the attachment points of the joint capsule. Gradually, the articular cartilage is also degraded. The progressive inflammation destroys the joint surfaces. Joint bones move out of their normal position. A joint deformity develops. Together with the pain, this joint malalignment restricts the mobility of the affected and if necessary. of subsequent joints. Patients are often unable to perform simple tasks: opening a can of food or tying a shoelace becomes an insurmountable obstacle.

In almost half of the patients with rheumatoid arthritis, the disease affects other organs, such as the joints. B. Blood vessels, cardiovascular system, lungs, kidneys, liver, skin, nervous system or

glandular tie

rheumatoid arthritis can affect the lacrimal and salivary glands and destroy the glandular tie. This process is also called sicca syndrome. Affects about one-third of patients. The signs of the disease are dry mouth. A lack of tear fluid.

Blood vessels

Inflammation of the vessel walls can manifest itself in circulatory disturbances that lead to small punctate wounds (see Fig. 2), can lead to skin ulcers or extensive tie death. In addition, rheumatoid arthritis is associated with an increased rate of arteriosclerosis.

rheumatism center erding rheumatoid arthritisPatients with rheumatoid arthritis have an increased risk of heart attack (coronary heart disease). Arteriosclerosis of the coronary arteries is caused by the inflammatory-rheumatic disease process, and occurs more frequently with active joint inflammation, with increased disease activity. New treatment options, in particular with biologics, are associated with a significantly lower rate of cardiovascular disease. They seem to be a protective factor against corresponding heart diseases and reduce the mortality rate from heart attacks. In addition to the rheumatic inflammatory process, the use of non-steroidal anti-inflammatory drugs and cortisone also play a role in the increased incidence of cardiovascular disease and heart attacks in rheumatoid arthritis. The use of these drugs should therefore be limited to what is absolutely necessary. In addition, rheumatoid arthritis can cause a valvular heart defect. Inflammation of the heart muscle and the pericardium with pericardial effusion.

Lungs

In every 5. patient with rheumatoid arthritis the alveoli of the lungs are inflamed. The inflammation leads to fibrosis, hardening of the lungs, which may increase under certain circumstances. As a rule, this can only be detected with a special examination method (with high-resolution computed tomography, HR-CT of the lungs). In most cases, no treatment is required in the absence of relevant symptoms. In rare cases with pulmonary fibrosis = hardening of the lungs, coughing and shortness of breath on exertion up to general respiratory difficulties are the result. New drugs, new therapeutic principles have been approved since 2020 for patients with more pronounced rheumatic lung changes and can significantly mitigate the course of the disease.

Nervous system

If nerves in the wrist are squeezed by the joint and tendon inflammations, this can cause false sensations, insensitivity and pain (carpal tunnel syndrome).

Rarely, rheumatoid arthritis in combination with vascular inflammation can lead to nerve damage in the area of the feet and legs, a so-called polyneuropathy. This nerve damage is accompanied by false sensations, numbness, and often burning pain. Rarely paralysis symptoms occur.

Optimal treatment with very low disease activity or disease arrest can prevent rheumatoid vasculitis and thus distal polyneuropathy. If polyneuropathy has occurred, a strong reduction of rheumatic disease activity can mitigate the course of the polyneuropathy or even lead to a cure.

Gastrointestinal tract

Inflammation, bleeding and ulcers of the gastric and intestinal mucosa are often a consequence of treatment with non-steroidal anti-inflammatory drugs. Especially in older patients who are also treated with cortisone and/or have had a stomach or intestinal ulcer in the past, the risk of damage to the gastrointestinal wall is significantly increased.

As a rule, this gastric damage can be prevented by non-steroidal anti-inflammatory drugs, by taking a gastroprotective agent, so-called proton pump inhibitors. The risk of stomach and intestinal damage is lower when taking a special group of nonsteroidal anti-inflammatory drugs called Cox-2 inhibitors or coxibs.

Examinations& Diagnosis

In the past, therapy for rheumatoid arthritis was often started at a very late stage. Today it is known that in patients with rheumatoid arthritis the destruction of the joints progresses most rapidly within the first 2 years of the disease. The chances of successful treatment are greatest if effective treatment, usually a so-called basic therapy, is started within the first 3 months after the onset of the disease. In the DGRh guideline: Management of early rheumatoid arthritis, it is therefore recommended to consult a rheumatologist after 6 weeks at the latest in case of swelling and pain in more than 2 joints.

As a rule of thumb, rheumatoid arthritis is most likely to be present when

– A patient has more than 2 swollen joints – There is a symmetrical, soft, often prere-painful swelling of the base and middle joints of the fingers – The base joints of the fingers and the base joints of the toes are pain-sensitive to light prere – The joints remain stiff for more than 30 minutes in the morning (morning stiffness)

As a rule, patients with joint diseases first ask their family doctor for advice. For the treating physician, it is particularly difficult to recognize rheumatoid arthritis shortly after the onset of the disease, since different diseases show similar signs of disease and not infrequently the disease is not fully developed. It is therefore recommended in the case of V.a. an inflammatory form of rheumatism to consult a rheumatologist at an early stage.

To distinguish rheumatoid arthritis from other joint diseases, the rheumatologist will take a detailed medical history, obtain a precise joint status, check for joint swelling and use laboratory tests and imaging techniques such as sonography and magnetic resonance imaging to make the diagnosis. Putting this mosaic or puzzle of findings together correctly in order to find the correct rheumatological diagnosis is the central task of an internal rheumatologist.

Important information from the medical history is for the doctor:

– Do other family members have or have had rheumatoid arthritis or another chronic inflammatory form of rheumatism?? – When did swelling of the joints first occur?? – Which joints are affected? Does the disease move from joint to joint?? – Is the disease progressing rapidly or slowly? – If the joint pain occurs primarily at rest, at night, or in the early morning? – Do heat, cold, movements or stress influence the pain?? – Does the pain change during the day (improvement during the day or is there constant pain)?? – Were there any special accompanying circumstances at the beginning of the disease, e.g. B. infections, diarrhea, an eye inflammation or other diseases? Are other symptoms present at the same time (headache, fever, fatigue)??

In addition, the treating rheumatologist must perform various laboratory tests to confirm the suspicion of rheumatoid arthritis. Together, the results of blood tests and imaging techniques (especially sonography, magnetic resonance imaging, X-rays) allow a reliable diagnosis at an early stage of the disease.

Laboratory tests

If joint swelling and joint pain are indicative of rheumatoid arthritis, the physician can examine various blood values of the patient, which give him further clues as to whether arthritis is present. However, each blood value is not very meaningful on its own; only the combination of all signs of the disease enables the physician to make a reliable diagnosis.

Increased values for the so-called erythrocyte sedimentation rate or the inflammatory protein C-reactive protein (CRP) indicate that there is inflammation in the patient's body. An elevated CRP can be an aid in making the distinction, which is not always easy z.B. Be arthritis of the finger joints from rheumatoid arthritis that has developed in addition to osteoarthritis. Osteoarthritis (wear and tear disease) sometimes causes similar symptoms, but almost never triggers inflammation in the blood. Nevertheless, elevated CRP levels are not unambiguously indicative of an inflammatory form of rheumatoid arthritis, since other inflammatory diseases can also increase blood sedimentation levels. Normal CRP levels do not rule out rheumatoid arthritis. 10-30% of patients with rheumatoid arthritis do not have elevated laboratory inflammation values at the beginning of the disease.

Another important blood value is the so-called rheumatoid factor. The term rheumatoid factor is misleading, since only 65-80% of rheumatoid patients actually have this factor in their blood (seropositive). Many patients with rheumatoid arthritis do not have an elevated rheumatoid factor, which means they are seronegative. In addition, the rheumatoid factor may be elevated in other chronic inflammatory forms of rheumatism such as z.B. the Sjogren's syndrome, the systemic lupus erythematosus may be elevated. The elderly or patients with other diseases may have elevated rheumatoid factor even though they do not have rheumatoid arthritis: 15% of the elderly population and over 50% of hepatitis patients have z.B. Rheumatoid factors in the blood without the presence of rheumatoid arthritis.

A much more reliable blood value are antibodies against so-called citrullinated peptides (z.B. anti-CCP antibodies, anti-vimentin antibodies and anti-CEP1 antibodies), so-called anti-cytoplasmic antibodies (ACPA). These proteins are also present in 60-85% of patients with rheumatoid arthritis. They can rarely be detected in the blood before the actual onset of the disease. In contrast to the rheumatoid factor, they are very rarely elevated in other diseases. If a blood test is positive for these antibodies, there is a very high probability (95%) that the patient has rheumatoid arthritis. If a positive rheumatoid factor and pos. ACPA before, this probability increases to more than 98%. The likelihood of the presence of rheumatoid arthritis increases with the titer level of ACPA.

Elevated ACPA is often associated with a more severe course, or better, one that requires more intensive treatment to achieve disease arrest. The probability of suffering bone changes in rheumatoid arthritis is higher with positive ACPA.

Smoking and the presence of ACPA favor the development of rheumatoid arthritis.

In addition, the rheumatologist may examine other blood values to decide whether rheumatoid arthritis or another disease is present:

Antinuclear antibodies (ANA): antibodies directed against the cell nuclei. They are detectable in about 10% of patients with rheumatoid arthritis. In patients with systemic lupus erythematosus, ANA can be measured regularly. anti-deoxyribonucleic acid antibodies (anti-DNA antibodies): indicate systemic lupus erythematosus

Antineutrophil cytoplasmic antibodies (ANCA) and antibodies against proteinase 3 and antibodies against myeloperoxidase): Indicate specific rheumatic diseases of the blood vessels (vasculitis) such as granulomatous polyangiitis (formerly described as Wegener's disease) or microscopic polyangiitis.

HLA-B27: Can be an indication of inflammatory spinal disease (axial spondyloarthritis, z. B. be ankylosing spondylitis [formerly ankylosing spondylitis] or a so-called HLA-B 27 associated arthritis).

Pathogen detection: If the treating physician suspects that the joint inflammation has been triggered by bacteria or viruses, he can search specifically for the pathogens. In question are v.a. Blood tests for Borrelia (Lyme arthritis), Chlamydia, Yersinia, rarely Salmonella or Shigella. In women with young children who have had ringworm, joint inflammation due to ringworm should be considered and antibodies against parvo viruses determined

Elevated uric acid: in case of a clear and painful joint swelling with local redness, especially of a metatarsophalangeal joint, but more rarely of an ankle or knee joint, gout should be considered, resp. can be excluded.

Imaging procedures

Various imaging techniques also enable the rheumatologist to assess the condition of the joints. An important technique is joint examination with ultrasound, called joint sonography. This allows the doctor to detect fluid accumulation in larger joints as well as joint inflammation in small joints, which may not be visible from the outside. Also rheumatism-typical bone damage. joint destruction (z. B. in the joints of the fingers and toes) are revealed in this way. Tendon sheath inflammation and tendon tears can be detected as well as bursitis or calcium deposits in the soft tie or in the joints. An additional examination with the power Doppler can detect increased blood flow in the synovial membrane, which indicates increased inflammation and thus increased disease activity. With ultrasound in conjunction with power Doppler, in addition to improved diagnosis of rheumatoid arthritis, it is thus also possible to make a statement about the activity of the disease (s. Fig. 3).

Rheumazentrum erding rheumatoid arthritisX-rays of hands and feet make joint destruction very visible: decalcification of the joint bones can be found very early in the course of the disease. However, joint space narrowing and bone damage can usually only be found in a later stage of rheumatoid arthritis using conventional X-rays (s. Fig. 4).

However, early, guideline-compliant and optimal treatment of rheumatoid arthritis prevents the development of corresponding bone damage: The first changes detectable on conventional x-ray usually occur after 12 months of disease at the earliest and are then not infrequently the result of treatment with basic therapeutics that has occurred too late. Nevertheless, X-rays are among the examinations that are suitable for monitoring the course of the disease, for checking the success of treatment with medication. However, a success control with X-ray is hardly useful under a stable, successful and very low setting of the disease activity with biologics and Janus kinase inhibitors, since an increase in rheumatism-typical bone changes can be detected only very rarely.

A technique that, together with ultrasound, has become the standard method for the early detection of rheumatoid arthritis over the past decade and a half is magnetic resonance imaging (MRI). It shows changes in the joint already in the early stages of the disease (s. Fig. 5 and 6). Magnetic resonance imaging allows the radiologist and rheumatologist to evaluate both soft tie and bone very well without radiation and without stress to the patient. Bone damage can be seen on MRI months to years before it becomes visible on X-rays. The extent of joint inflammation and tendon sheath inflammation can be determined, as can inflammation in the bones. These bone inflammations, which can be detected as fluid in the bone, indicate a potentially bone-destructive course of rheumatoid arthritis. In the presence of clear bone marrow inflammation, it is therefore advisable to react immediately with an intensification of treatment, either via drug treatment or via cortisone injections into the affected joint. Bone marrow edema can be detected exclusively by magnetic resonance imaging. Bone erosions typical of rheumatism can be detected more completely. More detailed imaging than via ultrasound. Especially in the wrist, erosions can only be incompletely detected by joint ultrasonography compared to MRI. In the early diagnosis and also in the follow-up of rheumatoid arthritis, both methods have an increasingly important role. Both examination methods help to make a precise diagnosis of rheumatoid arthritis and to check the disease activity during the course of the disease, to avoid overlooking an erosive, progressive course and, if necessary, to identify the cause of the disease. On the basis of the imaging findings (z.B. to make a correct therapeutic decision in the presence of bone marrow edema on MRI.

Rheumazentrum erding rheumatoid arthritisRheumazentrum erding rheumatoid arthritisA less common technique is fluorescence optical imaging of the hands with the RheumaScan (s. Fig. 7). With a well-tolerated fluorescent agent, which is also used for imaging the back of the eye, inflamed joints that show increased blood flow can be visualized very impressively. Comparisons with sonography and magnetic resonance imaging have shown relatively good agreement with regard to inflammatory processes. The RheumaScan is commonly used for early diagnosis, and appears to provide a sensitive diagnosis of rheumatoid arthritis as distinct from degenerative joint changes of the hands. Likewise, differential diagnosis of joint changes in psoriatic arthritis seems to be possible in comparison to rheumatoid arthritis. A clinically often difficult differentiation of a mild course of seronegative rheumatoid arthritis from the symptoms of fibromyalgia can be made possible by a negative rheumatism scan result. On the other hand, secondary fibromyalgia associated with an inflammatory form of rheumatoid arthritis can be unmasked via a positive RheumaScan result.

Rheumazentrum erding rheumatoid arthritisBone scintigraphy allows screening of the entire body for degenerative processes and inflammation and bone tumors. It is used in patients in whom the other examinations have not produced a clear picture. The indication for skeletal scintigraphy in rheumatology is limited to rare exceptions with the imaging possibilities described above. Bone scintigraphy exposes the patient to radioactive radiation. Should therefore only be used under strict consideration of the diagnostic benefit.

Treatment

For effective treatment of rheumatoid arthritis, it is crucial that the disease is detected and treated as early as possible. Patients should therefore consult a rheumatologist if they have any suspicious signs of the disease. The treatment of rheumatoid arthritis is based on 4 pillars:

– Treatment with medication to slow down or stop the progression of the disease – Physiotherapy, occupational therapy and physical measures to ensure joint mobility and joint functionality at work and in everyday life – Patient training is suitable to improve the level of knowledge about the disease, to acquire the ability to deal positively and competently with the inflammatory joint disease, with the necessary medication, with the physical measures, to cope better with everyday life – Surgical treatment of joints. Joint replacement, as a last resort when a joint is inoperable and severely painful, surgery for tendon ruptures, surgery for carpal tunnel syndrome

Treatment with drugs

With modern treatment methods, progression of the disease can be significantly slowed or even completely halted.

An early start of treatment is crucial for the success of treatment: In order to keep joint damage to a minimum, we rheumatologists therefore recommend starting treatment with disease-modifying drugs (basic therapies) as early as possible, at the latest 3 months after the onset of the disease. Rheumatism drugs are divided into 2 groups:

1. Exclusively symptomatic medications, which are the nonsteroidal anti-inflammatory drugs and cortisone medications. These reduce the signs of the disease, such as pain and joint stiffness, but have no effect on the course of the disease. Cortisone has a strong anti-inflammatory effect and is capable of very rapidly reducing pain and inflammation in the joints, depending on the dose. 2. Disease-modifying drugs, known as basic therapies, are most important in the treatment of rheumatoid arthritis. They reduce to varying degrees the exaggerated reaction of the immune system. Can thus slow or stop the progression of the disease. The best way to stop the bone-destroying effect of rheumatoid arthritis is to use biologics and the recently approved JAK inhibitors.

Symptomatic treatment

Nonsteroidal anti-inflammatory drugs (NSAIDs), such as z. B. Ibuprofen or diclofenac, are the drugs most commonly used to treat pain. However, they also inhibit the formation of pro-inflammatory messenger substances known as prostaglandins. This means that they can reduce the inflammatory processes in the joints, but by no means stop them. Joint damage nevertheless progresses under treatment with NSAIDs alone.

Since prostaglandins also serve as a protective factor for the gastrointestinal mucosa, the nonsteroidal anti-inflammatory drugs can damage the mucosa. Feared side effects of non-steroidal anti-inflammatory drugs are gastritis and peptic ulcers. Therefore, especially patients who have already had gastrointestinal inflammation or ulceration should receive gastric protection as a precaution if they are taking a nonsteroidal anti-inflammatory drug continuously. Medications that inhibit the production of gastric acid are suitable for stomach protection, e.g. B. Proton pump inhibitors. To minimize the risk of side effects, the dose of non-steroidal anti-inflammatory drugs should be as low as possible. In addition, 2 different nonsteroidal anti-inflammatory drugs should never be taken at the same time.

The so-called COX-2 inhibitors or coxibs may be an alternative for patients who cannot tolerate traditional nonsteroidal anti-inflammatory drugs because of gastrointestinal side effects or who are at increased risk for these side effects. This applies in particular to patients over the age of 60. Patients over the age of 18, patients with a history of gastrointestinal ulcers, and patients on cortisone therapy. However, some coxibe agents have fallen into disrepute because they may increase the risk of heart attacks. However, recent studies showed that the risk of cardiovascular disease is no higher with coxibs than with traditional nonsteroidal anti-inflammatory drugs. Patients with an increased risk of cardiovascular disease should take Coxibe. Therefore, do not take traditional nonsteroidal anti-inflammatory drugs.

Traditional nonsteroidal anti-inflammatory drugs and coxibs can also damage the kidneys if used for years and at high doses. Older patients with many concomitant diseases are particularly at risk. Painkillers, such as. B. Metamizole or opioids, can then be an alternative.

As a general rule, traditional nonsteroidal anti-inflammatory drugs and coxibs should be taken in the lowest possible dosage and for no longer than absolutely necessary to keep the risk of side effects low. Whether a traditional nonsteroidal anti-inflammatory drug or a Cox-2 inhibitor is more appropriate for a patient with rheumatoid arthritis depends on the risk factors listed above and his or her personal risk for gastrointestinal disease. Cortisone is a hormone produced by the adrenal cortex. Has an anti-inflammatory effect. Several studies in early rheumatoid arthritis have demonstrated that low-dose cortisone together with basic medications (z.B. Methotrexate) can provide better protection against bone destruction caused by rheumatism than treatment with basic drugs alone. The almost unavoidable side effects of long-term treatment, however, limit cortisone therapy as a treatment option to the shortest possible therapy. If possible, cortisone should only be used in active courses of early rheumatoid arthritis until basic therapy is sufficiently effective. In less active courses of the disease, cortisone treatment should be avoided if possible.

In the case of disease relapses, cortisone can be used in a somewhat higher dosage (z.B. 15 to 20mg prednisolone/day) are given over a short period of a few days, so that the pain is quickly reduced and the joint function improves.

Taken over a long period of time, cortisone can lead to bone loss (osteoporosis). As far as is known to date, there is no threshold dose of cortisone with regard to this side effect, d.h. Osteoporosis can also occur with low doses of cortisone given over a long period of time. Patients who take cortisone regularly are recommended to have bone densitometry with DEXA (Dual Energy X-Ray Absortiometry) on a regular basis in order to detect bone loss in time and to be able to treat it preventively accordingly.

With prolonged use of cortisone above the so-called Cushing's threshold (usually more than 7.5 to 10 mg prednisolone equivalent), the risk of infection (including with the SARS-CoV-2 virus) is increased and weight gain is unavoidable. Furthermore, myocardial infarctions occur more frequently. Strokes occur under cortisone. If possible, therefore, cortisone should be avoided in the long-term treatment of rheumatoid arthritis, especially in times of pandemic.

In the acute treatment of so-called rheumatic attacks (phases with high disease activity, pronounced joint swelling, severe joint pain), however, a cortisone shot treatment carried out for a limited period of two to three weeks is very helpful, low-risk and usually very effective.

Basic therapy

We distinguish between different basic therapies:

– So-called synthetic disease modifying antirheumatic drugs (sDMARDs) – So-called biologics, biological disease modifying antirheumatic drugs (bDMARDs) – Targeted synthetic disease modifying antirheumatic drugs (tsDMARDs), so-called Janus kinase inhibitors or JAK inhibitors

The above-mentioned basic medications include all drugs that not only relieve pain but have disease-modifying properties and can thus delay or prevent joint destruction. Depending on the substance, their effect sets in with different delay times (1 to 2 weeks, up to 6 months). Basic medications are more effective and sustained when used early, within the first three months of illness onset, than when these medications are used late, d.h. Be used for more than 6-12 months, after the onset of the disease. If the basic drugs are used in an early phase of rheumatoid arthritis, the disease is halted in up to 50% to 80% of cases. Not very rarely, after successful treatment with basic drugs, the disease can remain inactive for months or years without drug treatment. There is a chance that rheumatoid arthritis is inactive after appropriate treatment, even without drug treatment, that prolonged disease arrest occurs. This chance is very good if treatment with biologics is started early. In the future, probably also greater with JAK inhibitors than with treatment with synthetic basic therapies alone.

Synthetic basic therapies

These are primarily methotrexate, sulfasalazine, and leflunomide,

In most cases, the rheumatologist recommends methotrexate at the beginning of treatment. If this does not have sufficient effect after 3 months at the latest, it can be 2. Combine the basic drug with methotrexate or prescribe a different basic drug instead of methotrexate. In the case of an active disease with an early bone-altering course, this can also be a basic therapy with a biologic or with a JAK inhibitor. As a rule, biologics and JAK inhibitors are combined with methotrexate at the beginning of treatment.

With all synthetic basic therapies, regular checks of the blood count, kidney and liver values should be carried out. Under certain circumstances, the basic drugs can lead to increased liver values, rarely to bone marrow damage with a reduction in red and white blood cells, blood platelets (thrombocytes) and, in rare cases, to impaired kidney function. These blood count checks can usually be very reliable in preventing serious liver, kidney or bone marrow damage.

Gold (as tablet or injection) and D-penicillamine, which were frequently used in the past, are virtually no longer prescribed because of their side effects and slow action (after 3-6 months). Azathioprine and cyclophosphamide play z. B. still play a role in the treatment of severe concomitant vascular inflammation or renal function impairment that precludes the use of other basic drugs. Cyclosporin A is now only rarely used as a basic therapy for rheumatoid arthritis in exceptional cases because of its limited efficacy and not inconsiderable side effects.

Biologics treatment

A new group of drugs has been available for about 20 years for patients who respond inadequately to therapy with synthetic basic drugs. These so-called biologics are genetically engineered defense substances (z. B. antibodies) that are specifically directed against certain inflammatory messengers or inhibit certain receptors and immune cells. These biologics ushered in a new era in the treatment of rheumatoid arthritis at the beginning of this millennium. For the first time, sustained remissions have been possible in the vast majority of patients, in some cases even drug-free remissions. All biologics approved for rheumatoid arthritis have an earlier onset of action compared with the synthetic basic therapies. Patients usually notice a reduction in inflammatory disease activity after 2 to 4 weeks. All biologics are significantly better at halting the bone destruction caused by rheumatoid arthritis than the older synthetic basic therapies. As a rule, only minimal or no progression of bone changes is detectable under biologics treatment. Surprisingly, this is also the case if joint swelling and joint pain still exist, i.e. if there is no disease arrest in this respect.

Approved biologics include antibodies against tumor necrosis factor alpha (TNFα), so-called TNF-alpha blockers. These are adalumumab, certolizumab, etanercept, golimumab and infliximab. TNF-alpha is an important messenger substance that amplifies inflammatory responses in the body. All TNF blockers have similar good efficacy. An almost similar side effect profile common. As a rule, the TNF blockers are combined with methotrexate, resp. is only approved for use in combination with methotrexate (z.B. Golimumab/infliximab)

– Etanercept shows a lower risk of activation, the onset of previously unrecognized tuberculosis compared to the other TNF blockers. However, by screening, by appropriate testing for tuberculosis (TB) before starting TNF blocker treatment, this risk of activation of tuberculosis has also become very low for the other TNF blockers. If the patient screens positive for tuberculosis (positive Quantiferron or Elispot TB test, and/or a tuberculosis finding in the X-ray examination of the lungs), the outbreak of tuberculosis can be prevented by taking antituberculostatica (usually isoniazid) for a period of nine months, even under TNF blockade. All TNF blockers cause a slightly increased risk of severe infections. However, this risk is no higher than in patients with rheumatoid arthritis with high disease activity and without effective basic therapy. TNF blockers are either injected into subcutaneous fat (adalimumab, certolizumab, etanercept, golimumab) or administered as an infusion (infliximab)

– Abatacept, is an antibody that targets T-cells and, through this pathway, leads to decreased release of cell messengers that maintain inflammation in the body, or. trigger. Abatacept can be administered with analogous efficacy either via weekly injections into the subcutaneous fat tie or as an infusion in a dosage adapted to body weight.

– Rituximab, an antibody that is directed against B cells and with this effect leads to a reduction in disease activity that lasts for months. Rituximab is administered as an infusion; at the beginning of treatment, two infusions are given at 14-day intervals, and the next infusion is administered after 6 months at the earliest. Studies to date show good results when this infusion treatment is continued every six months. In everyday life, it can be more effective and ultimately involves less risk of side effects if the new rituximab infusion is only administered when the first symptoms of a worsening of the disease activity occur again. It is not uncommon for new infusions to be necessary only after three quarters of a year or even significantly later. Before starting the rituximab infusion, it is very important to complete the vaccination status, since at least in the first six months after a rituximab infusion, i.e. in a period in which certain B cells important for the immune defense are not newly formed, the body does not respond or hardly responds to a vaccination with antibody formation. In principle, infections are not found more frequently with rituximab than with other biologics. The so-called memory cells, which are important for the defense against infections, are not attacked by Rituximab.

– Tocilizumab and sarilumab are antibodies against interleukin 6, a pro-inflammatory messenger that, like TNF-alpha, is also responsible for joint inflammation in rheumatoid arthritis. Tocilizumab can be injected into the subcutaneous fat tie at weekly intervals, sarilumab every 14 days. Tocilizumab is also available as an infusion, administered every 4 weeks in a body weight-dependent dose. The side effect profile of interleukin-6 receptor antagonists is similar to TNF alpha blockers and abatacept. However, for tocilizumab, sarilumab, and abatacept, the risk of tuberculosis in pre-existing and cured TB infection is lower than for TNF blockers. However, if TB screening is positive, temporary treatment with an anti-tuberculostatic agent must also be given under these medications.

– Anakinra, an interleukin-1 antibody also approved for the indication of rheumatoid arthritis, no longer plays a role in the care of patients with rheumatoid arthritis. This is due to the low efficacy in rheumatoid arthritis, and the need for daily injection into the subcutaneous fat tie.

Janus kinase inhibitors

Currently at the beginning of 2021, 4 JAK inhibitors are available. In the order of first approval, these are the Janus kinase-1 to 3 inhibitors tofacitinib and baricitinib, as well as the JAK-1 inhibitors upadacitinib and filgotinib.

Janus kinase inhibitors inhibit inflammatory metabolism at the cellular level. All 4 substances are available in tablet form. Are taken daily. They exert an inhibitory effect on the messenger substances TNF-alpha and especially interleukin 6, as well as on other inflammatory messengers. It is therefore not surprising that they show a similarly good effect as the biologics in inhibiting bone destruction and also on other joint symptoms and also have a similar side effect profile. JAK inhibitors show very good efficacy even without concomitant methotrexate therapy. Can therefore be used as monotherapy. Treatment with JAK inhibitors is therefore particularly suitable in cases of methotrexate intolerance. An analogous good efficacy when treated without concomitant synthetic baseline therapy with z.B. Methotrexate, also show the interleukin 6- receptor antagonists tocilizumab and sarilumab.

JAK inhibitors not infrequently show very rapid efficacy on the inflammatory process of rheumatoid arthritis within a few days to 2 weeks.

Drug interactions are more important than with biologics because of the special intracellular effect of Janus kinase inhibitors.

An increased risk of thrombosis and embolism has been observed for tofacitinib. For the other JAK inhibitors this risk is discussed. In patients with a history of thrombosis, or a tendency to thrombosis, JAK inhibitor treatment should be avoided if possible.

There is a significant increase in herpes zoster infections (shingles) with JAK inhibitors. Vaccination against herpes zoster has been possible for more than one year. Unfortunately, the vaccine was not available in Germany for many months. Since the end of 2020, vaccination with Shingrix (the vaccine against herpes zoster) has been possible again.

General information on DMARD therapy

For all of the above-mentioned basic therapies, vaccination against pneumococci is recommended in advance, as well as influenza vaccination. Because of the frequent occurrence of herpes zoster during JAK inhibitor treatment (s.o.), vaccination against herpes zoster should be given before starting this treatment.

So far, despite the immunosuppressive effect of the biologics and the targeted synthetic base therapies, there is no evidence of increased cancer incidence among these drugs from the registration studies and subsequent worldwide follow-up (registries). However, lymphoma rates are higher under TNF blockers than in the normal population, but not higher than in patients with active rheumatoid arthritis without TNF blockers.

For TNF blockers and rituximab, initial registry results found a higher life expectancy than in patients with rheumatoid arthritis treated only with the existing synthetic base therapies. Overall, this combined with the good effect on disease activity, bone destruction, is a good message for the use of biologics.

In patients with rheumatoid arthritis, biologics can stop joint damage faster and more effectively than methotrexate alone, especially in combination with the basic drug methotrexate. They are used according to the therapy recommendations existing in Germany in patients with rheumatoid arthritis, in whom a sole therapy with 2 different basic medications over 6 months has not worked sufficiently or who have not tolerated them. If the course of rheumatoid arthritis is very progressive with joint destruction under the first basic drug, TNF-alpha blockers can already be used as a second basic drug in accordance with the therapy recommendations of the German Society for Rheumatology.

Who should carry out the basic therapies?

In the German and European guidelines, there is agreement that the initiation and monitoring of treatment with the various basic therapies is the responsibility of the rheumatologist with further training in internal medicine.

Which basic therapeutic agent should be prescribed at what time??

Which basic therapies should best be given in which order to which patients is proposed largely analogously in a German and a European guideline and is adapted in the guidelines at intervals to new findings and new drug approvals.

For how long should basic therapies be administered?

Basically, rheumatoid arthritis is a chronic, lifelong disease. However, recent observations show that the earlier effective basic therapy is started, the higher the chance of disease arrest. Especially under early biologics therapy, this disease arrest seems to occur more frequently when treatment is started shortly after the onset of the disease. If this disease arrest persists under biologics or if necessary. even under synthetic basic therapy for more than 6 months, several studies show that a reduction and rarely a discontinuation of the medication is possible without at least the majority of patients showing a worsening of the disease.

All related studies on drug reduction in disease arrest have the limitation that only a small number of patients and not all biologics, basic therapies have been studied accordingly. Nevertheless, the results point to the reasonable possibility of a reduction of medication in the case of stable remission. Complete discontinuation is also possible, although the rate of disease recurrence and rheumatoid arthritis flare-ups is higher than with cautious drug reduction. Rapid resumption of previously effective basic therapy is necessary in the event of a flare-up of rheumatoid arthritis after dose reduction or discontinuation and, as shown by previous results, is also usually rapidly effective.

Within the framework of a nationwide project (VERhO) supported by the Innovation Fund, in which our rheumatism center also participates, the question of the success and the best procedure for a reduction in medication under stable remission is to be investigated in more than a thousand patients.

This results in the very positive perspective of a disease that can be treated increasingly successfully with early basic therapy and the new treatment options (biologics, targeted synthetic basic therapies) and for which disease arrest is an achievable goal. A disease arrest, which is not necessarily associated with a continuation of the previous immunosuppressive medication, but allows a reduction and much more rarely even a discontinuation of the medication. A discontinuation, which however can be followed after months or years by a renewed flare-up of the disease.

Other forms of therapy

A very important but ultimately only supportive and temporarily effective treatment method is to inject cortisone directly into the inflammatory affected joints if the basic therapy is not sufficiently effective in individual joints and significant joint swelling or effusion persists despite otherwise effective basic therapy. A joint puncture followed by an injection of a cortisone bound to crystals that is locally effective for a very long time, usually 6 weeks, can significantly and not infrequently permanently reduce the joint swelling and pain.

An unfavorable effect of the cortisone injected into the joint on the entire body is not to be feared, since the cortisone hardly passes into the bloodstream due to the binding to the crystals. In rare cases, transient hypersensitivity reactions occur after cortisone injection: A sensation of heat and a red head last no more than 1-2 days and are harmless. However, irritation of the synovial membrane by the injected crystals can be very painful. Require a repeat injection with an anesthetic. Bacterial infections are also very rarely reported after an injection into a joint (in 1 out of 13.000 cases) are observed and can and should be avoided by working sterilely. Because of the special experience required with the joint puncture technique, these cortisone injections into a joint should only be performed by rheumatologists or orthopedists.

In addition, the inflamed joint mucosa, especially of the knee joint, can be removed in an operation (arthroscopy) or sclerosed by means of radioactively marked substances (radiosynoviorthesis). However, surgical removal of the synovial membrane has no value as the sole treatment method for articular mucosa inflammation of the knee joint or other joints because of the high relapse rate. It should be reserved for very rare treatment-resistant cases that do not respond to drug-based, basic therapeutic treatment.

Radiosynoviorthesis can be an effective method, especially in the knee joint, to treat and reduce inflammation of the synovial membrane that has not responded to previous, varied attempts at drug treatment with basic therapies and also to joint injections with corticosteroids.

Surgery may be necessary to correct joint deformity and shift prere loads. If medium and large joints are highly destroyed by the rheumatic disease, an artificial joint replacement (endoprosthesis) or surgical stiffening is the last resort. We offer in our rheumatism center in Bad Aibling. Erding has been offering patient training for patients with rheumatoid arthritis since 2015. This training was designed by the German Society for Rheumatology, the Professional Association of German Rheumatologists and the German Rheumatism League under the acronym STRUPI-RA (Structured Patient Information for Patients with Rheumatoid Arthritis).

Patient education includes 3 modules of 2x 45 min each with the contents:

Diagnosis of rheumatoid arthritis; therapy of rheumatoid arthritis; coping with everyday life

The training is carried out by specially trained rheumatology assistants and is supervised by us rheumatologists. During and after the patient training we are available for questions. In order to provide sufficient opportunity for intensive exchange, no more than 9 patients should participate in the training course. For follow-up of the training we provide information material.

Patient education is used to better understand the disease, the medications used, and the other treatment options available. Suggestions for better coping with everyday life are discussed together. The aim of the training is to make it easier for our patients to deal with the disease, with the medication, to build up confidence and to improve their own competence in all questions concerning the disease.

Patient training is reimbursed under selective contracts by the health insurance companies TK, Pronova, BKK Mobil Oil and Barmer GEK, as well as by private health insurance companies. If patients of other health insurances want to participate in the patient training, a fee of 25 € per module will be charged. Cost absorption can be requested from the respective statutory health insurance company.

Physical measures and physiotherapy

Parallel to treatment with medication, patients with rheumatoid arthritis should try to maintain or restore the mobility of their joints with the help of physiotherapeutic measures. In addition, the joint-supporting musculature is to be strengthened. The most important measures include:

– Properly performed physiotherapy can improve joint mobility, reduce deformities and stabilize the joints. – independent movement exercises after previous physiotherapeutic instruction – movement baths under physiotherapeutic instruction

During acute inflammatory episodes, however, physiotherapeutic measures should be carried out carefully or not at all. Excessive stress on the joint can further aggravate inflammation.

Orthopedic aids, such as z. B. Splints, orthotics and functional bandages, can help maintain joint function for everyday use in cases of painful joint misalignments.

The various heat treatments such as mud, mud and hot baths can also stress inflamed joints and should therefore be used cautiously or in combination. Best not used at all with existing inflammatory activity of rheumatoid arthritis.

A cold treatment, z. B. with cryopacks, usually works well with pronounced rheumatic inflamed joints. Treatment in the cold chamber has a temporary pain-relieving effect.

Mild heat treatments (e.g.B. Patients often find cherry pit cushions or red light pleasant and improve mobility even in mildly inflamed joints.

A visit to the sauna does not usually have an adverse effect on the inflammatory process.

Occupational therapy (occupational therapy) can help patients with rheumatoid arthritis learn how to perform everyday tasks in a way that is easy on the joints. There, they also practice using joint-sparing aids that prevent joint misalignments. These aids are mostly commodities adapted to the needs of the patient, which can make life easier at home.

Other physical treatments that can be used for inflammatory joint disease include:

– High-frequency therapy – Medium- and low-frequency current – Ultrasound – Infrared radiation

These methods have not been shown to have a beneficial effect on pain symptoms, joint swelling or the progression of inflammatory rheumatoid joint disease.

Food supplements and alternative medicine

There are a variety of over-the-counter nutritional supplements and alternative healing methods that promise relief for patients with rheumatoid arthritis. The effectiveness of these offers is rarely proven beyond doubt. In addition, they are not infrequently expensive. The costs are not covered by health insurance companies.

In general, patients with rheumatoid arthritis should prefer foods that contain anti-inflammatory substances.

– Fish oil – Soybean, wheat and rapeseed oil – Evening primrose oil – Black currant seeds

Anti-inflammatory components are eicosapentaenoic acid, alpha-1-linolenic acid or gamma-linolenic acid. They seem to reduce the effects of rheumatoid arthritis on the joints.

Meat and high-fat dairy products, on the other hand, contain pro-inflammatory ingredients, arachidonic acid, and should therefore be avoided.

The effectiveness of selenium and zinc, as well as anti-oxidants, such as z. B. Vitamin E, which bind aggressive oxygen radicals, has also not been shown to be effective. Also on the benefits of homeopathy. Acupuncture there are only a few meaningful studies. There is no evidence that they can bring about lasting improvement in rheumatoid arthritis.

Patients with rheumatoid arthritis should maintain a normal body weight in order to protect their foot and knee joints. Some patients seem to benefit temporarily from a diet or fasting regimen.

Prognosis& Course

If left untreated, rheumatoid arthritis progresses in very different ways. It can affect almost all joints at once and within weeks or months, or it can remain confined to a few joints for years and suddenly become active again in episodes. In 10-30% of patients, the disease is mild and stable even with low doses of basic medications, but in 70%, the disease worsens over the years if they are not treated optimally with basic medications.

If rheumatoid arthritis is not treated, it destroys the affected joints to such an extent that they become less and less mobile and finally stiffen completely. Patients suffer severe pain, are often unable to work and lose a great deal of quality of life. Patients with rheumatoid arthritis who are not treated optimally according to current knowledge and possibilities have a mortality rate that is more than twice as high as that of the normal population, and their average life expectancy is 3-13 years shorter. The reason for this is that in addition to the joints, other organs are often affected, such as the heart and lungs in particular. Especially the damage to the heart. The blood vessel is the main cause of death in rheumatoid arthritis.

However, several studies show that modern rheumatoid therapy with methotrexate and biologics significantly reduces the increased mortality and brings it into line with the normal mortality of the population. Since the destruction of the joints progresses most rapidly at the beginning of the disease, treatment with disease-modifying drugs can have the most effective influence on the further course of the disease in this phase. In general, the earlier rheumatoid arthritis is diagnosed and treated, the more permanent damage can be avoided. For example, the risk of permanent joint damage is halved if rheumatoid arthritis is treated within 6 months of onset. The chance of stopping the disease and becoming symptom-free increases 3-fold for patients.

Although care for patients with rheumatoid arthritis has improved significantly in recent years, many patients still do not receive appropriate treatment in a timely manner. The reason for this is that patients do not go to the doctor immediately when they notice the first signs of the disease or the disease is not recognized and they are only referred to a specialist by their family doctor at a late stage. In addition, there are not enough rheumatologists in Germany, so waiting times for a treatment appointment at outpatient rheumatology facilities are not infrequently too long. Unfortunately, this is also true for our rheumatism center. In relation to the demand, there are still too few rheumatologists working at our two locations. Previous applications from our RHZ for new physician seats were unfortunately rejected by the licensing committee.

A somewhat better access to a rheumatologist, a high quality care, is already given regionally through selective contracts with individual health insurance companies, in which our RHZ also participates. In the future, the new care level of outpatient specialist care (ASV), which has been possible since 2019, can be expected to improve care with shorter waiting times due to the elimination of case number limits, the easier employment of assistants in outpatient clinics and also practices. We are also striving for admission to ASV Rheumatism. We ame that with the successful approval and the possible employment of assistants, the waiting times can be significantly reduced and the care improved.

In general, the prognosis for patients with rheumatoid arthritis is very positive. With early basic therapy and the new treatment options (biologics, JAK inhibitors), treatment is becoming increasingly successful and disease arrest is an achievable goal.

Precaution& Protection

There is as yet no possibility of preventing rheumatoid arthritis. It is uncertain whether environmental influences or nutrition can affect the development of the disease. Smoking, on the other hand, favors the development. Worsens the course of the disease in the long term. It should be avoided at all costs. be adjusted.

If you have signs of illness, such as rheumatism. B. Joint pain, swollen joints and morning stiffness lasting more than half an hour, you should definitely consult a specialist with rheumatological experience. Early treatment within the first 3 months after the onset of the disease is crucial for the progression of the disease.

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