Rheumatoid arthritis and skin manifestations 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.

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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