Rheumatoid arthritis M06.9

Rheumatoid arthritis is a chronic, inflammatory systemic disease of unknown aetiology, which leads to arthritis, bursitis and tendovaginitis through synovitis and further to the destruction of the affected joints. The characteristic feature of RA is its pronounced clinical variability with broad general symptoms and extra-articular manifestations (e.g. skin symptoms).

Most common rheumatic disease. Familial clustering.

Prevalence: about 0.5-1% of the population. In the older population (> 55 years) the prevalence is 2%.

Women are affected 2-3 times more frequently than men.

The etiology is unknown. A genetic predisposition has been demonstrated (familial clustering; in about 70% of patients the HLA antigen DR4/DRB1 can be detected - in healthy individuals only in about 25%). An autoimmunological inflammatory reaction is induced by unknown trigger mechanisms (environmental factors may play a role), e.g. viral or bacterial antigens, primarily affecting the synovium. T helper lymphocytes, macrophages, B lymphocytes, plasma cells and dendritic cells are involved. Proinflammatory cytokines (IL-1, Il-6, IL-15, TNF-alpha) are formed, as well as autoantibodies (AK against the Fc fragment of immunoglobulin G = rheumatoid factor; AK against cyclic citrullinated peptide = ACPA).

Proinflammatory cytokines activate various intracellular signaling pathways by binding to a receptor, which can lead to changes in gene expression and thereby trigger the various reactions. Several signal transduction cascades are significant in the pathogenesis of rheumatoid arthritis, namely:

• MAP kinases (mitogen-activated protein kinases).
• SYK (spleen tyrosine kinase)
• PI3 kinases(phosphoinositide 3-kinases)
• NFκB kinases (nuclear factor 'kappa-light-chain-enhancer' of activated B-cells)
• JAK (Janus kinases).

Furthermore, the abnormal findings include immune complexes that are detectable in synovial fluid and are significant in the pathogenesis of vasculitides.

Silicosis and rheumatoid arthritis (data based on Michigan's 1 022-case silicosis disease registry). For silicosis patients, the risk is:

a two to eightfold risk of rheumatoid arthritis(Caplan syndrome)

a two to eightfold risk of systemic lupus erythematosus

a > than 24-fold risk for systemic scleroderma (M34.0)

a > than 24-fold risk for ANCA+ vasculitis (Makol A et al. 2011).

The most common autoimmune disease among silicosis patients is rheumatoid arthritis. ANCA-associated vasculitis is also much more common in silicosis patients than in the general population (Makol A et al. 2011) .

Predominantly occurring in adults (peak incidence: 6-8 decade).

Symmetrical arthritis beginning in the hands and feet and later in the large truncal joints. Indicated centrifugal spread. Pattern of affection of the hands with regular and high preference of the basal and middle joints. Spreading tendency on the forefeet from lateral to medial.

Skin manifestations:

• Rheumatoid nodules in about 21-33% of cases. However, in patients with positive rheumatoid factor, rheumatoid nodules may occur much more frequently.
• Rheumatoidnodulosis: The term rheumatoid nodulosis is used to describe an entity characterized by subcutaneous rheumatoid nodules, cystic bone lesions (emphasized on the hand and foot bones), positivity of rheumatoid factor, and arthralgias in patients with little or no evidence of systemic manifestations of rheumatoid arthritis or erosive joint disease. This constellation was first described in 1949
• Accelerated rheumatoid nodulosis: Sudden, episodic appearance of painful nodules accentuating the hands especially the metacarpophalangeal joints- and PIP`s is called "accelerated rheumatoid nodulosis" (see below Rheumatoid nodulosis).
• Nail changes (27% of pat.): Brittle, lackluster fingernails with transverse furrow formation and splitting of the nail matrix are common. Clock glass nails are rare.

Other skin lesions (specificity not always clear - evidenced by single case reports):

• Ephemeral erythema, smooth, taut, atrophic skin over swollen wrists.
• Sclerodactyly-like changes, possibly dirty-brownish pigmentation over the proximal interphalangeal joints.
• Interstitial granulomatous dermatitis (very rare disease): symmetrical, red, usually asymptomatic erythema, papules or plaques localized mainly on the lateral trunk, also in linear orientation (rope signs or "rope signals"). There are clinical similarities to urticarial vasculitis.
• Palisaded neutrophilic and granulomatous dermatitis (very rare condition): Usually persistent, symmetrically distributed, rather sharply circumscribed, 0.5-1.5 cm, reddish-purple plaques and papules of moderately dermal consistency. Less commonly, vesicles, pustules, or ulcers.
• Rheumatoid neutrophilic dermatitis (rare disease): truncal polymorphous exanthema, also on proximal extremities, papules, pustules and plaques.
• Chronic arthrogenic lymphedema (congestion syndrome): Due to the limitation of leg movement caused by destructive processes of the joints, chronic , arthrogenic lymphedema occurs with increased risk of CVI and tendency to ulcer formation.

• Raynaud's syndrome

• Rheumatoid vasculitis: characterized by marginal sharply marked ulcers in the ankle regions or pretibially. Digital vessels may also be affected possibly with digital necrosis.

• Pyoderma gangraenosum: versch. Investigators indicate an increased prevalence of pyoderma gangraenosum.

• Intralymphocytic histocytosis: very rare disease; usually painless, chronically persistent, nonpruritic, indistinctly circumscribed 1.0-5.0 cm, by confluence also larger, red or brownish spots, plaques or nodules. Sporadic livedo-like patterns have also been described. Some cases showed circumscribed firm, flat nodules or swellings reminiscent of Melkersson-Rosenthal syndrome (Washio K et al. 2011).

Other (less common) specific organ manifestations include:

• Pericarditis and valvular changes.
• Frequent COPD, pleuritides
• Kidneys (rarely) membranous glomerulonephritis.
• eyes: keratoconjunctivitis
• Vessels: rheumatoid vasculitis (see above)
• Neurologic symptoms: vasa nervorum vasculitis with polyneuropathy.

Variants of rheumatoid arthritis include:

• Still syndrome
• Felty syndrome
• Sjögren's syndrome
• Juvenile idiopathic arthritis

• systemic lupus erythematosus
• Vasculitides (e.g. polyarteritis nodosa)
• Spondylarthritis
• Lyme arthritis
• Rheumatic fever
• Arthritis in sarcoidosis
• Psoriatic arthritis.

Order therapy:

A healthy lifestyle includes many details: avoidance of nicotine, large amounts of alcohol, lack of sleep and excessive stress, as well as weight optimization, not least to reduce comorbidities such as hypertension, diabetes mellitus, dyslipoproteinemia, steatosis hepatis and hyperuricemia.

Exercise: Excessive joint stress should be avoided in the acute inflammation stage, but complete immobilization is also not recommended. Avoid pressure (e.g. hand pressure, tight shoes) on the inflamed joints and avoid vibrations, as these irritate the already inflamed joints and cause pain to the affected patients. In addition to movement exercises, exercise baths (34 °C), depending on the stage, overheating baths or cold therapy, possibly connective tissue massages and supplementary occupational therapy should not be missing from the treatment. This includes joint protection, self-help training, functional training, explanation of the use of ergotherapeutic aids such as specially shaped knives, bottle and can openers, dressing aids for buttons or sock or shoe pullers, depending on mobility, also special aids for locomotion such as a rollator or special rheumatism chair such as, for example, a tricycle chair with which you can walk while sitting, which makes it easier to work at different heights due to its height adjustability and which makes it easier to stand up and sit down due to the electric stand-up aid.

Nutrition: It is now recognized that there are pro-inflammatory, anti-inflammatory or antioxidant effects of individual nutrients or diets, as well as effects on the gut microbiota and the gut-associated immune system.

Preference should be given to natural fruit, vegetables, unsaturated fatty acids, fish, seafood (maritime diet) and whole grain products. Omega-3 fatty acids, essential fatty acids, have a particularly anti-inflammatory effect.
Omega-3 fatty acids are explicitly mentioned in the guidelines for the management of early rheumatoid polyarthritis as having a soothing effect. The acids are found, for example, in fish oils, particularly in oily sea fish such as mackerel, herring, farmed salmon, tuna, sprat, sardines and krill or in plants such as rapeseed, olives, linseed or algae. Omega-3 fatty acids have an anti-inflammatory effect and are suitable for supporting the treatment of inflammatory diseases such as psoriatic arthritis or rheumatoid arthritis.
Omega-6 fatty acids (e.g. linoleic acid and arachidonic acid), on the other hand, promote inflammation. These are found in animal fats, as well as in sunflower or corn oil.

The optimal ratio of omega-3 and omega-6 fatty acids consumed is crucial - about 1:1 to 1:5 and not 1:10 or 1:100 as in the Western diet.

One possibility would be the Mediterranean diet, for example.

The lactovegetable diet is also anti-inflammatory: avoid animal meat and eggs (max. 2 portions per week).

Microbiome, intestinal flora: There is increasing evidence that the strong increase in autoimmune diseases such as rheumatoid or psoriatic arthritis, chronic inflammatory bowel diseases, asthma or lupus erythematosus can also be attributed to the microbiome in the intestine. Cytokine signals (especially type 1 interferons), which have been shown to be regulated by the microbiome, could play a decisive role here. Prevotella copri, which is increasingly found in autoimmune patients, appears to be a responsible intestinal microorganism. Studies show that a high-fiber and fermented diet leads to a reduction in inflammation parameters (Durholz K et al 2020; Wastyk HC et al 2021).

Balneotherapy: Depending on the stage of inflammation, cold application for severely inflamed joints, including a cold chamber. Heat application(mud bath or pack, heat bath) has proven effective for reactive muscle tension.

According to the ACR/EULAR classification, the following criteria apply to rhematoid arthritis:

Prerequisite:

1. At least 1 joint with clinical synovitis,
2. that cannot be explained by any other disease.

Score: Scores from Tables A-D are added together: scores of 6 and above are indicative of definite RA.

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