Rheumatoid arthritis
Epidemiology
RA affects 0.5-1% of the population. Women 2:1 men . [1]
Pathophysiology
Rheumatoid arthritis (RA) is a systemic autoimmune disease of which we don't know the cause. There are genetic and environmental factors.
Rheumatoid arthritis is associated with lower educational attainment
Rheumatoid arthritis is more common in those with lower educational attainment (educational attainment = a proxy for socioeconomic status (SES). Smoking is associated with lower socioeconomic groups. Lower SES is also associated with lower health literacy, higher BMI, exposure to air pollution, smoking and most of these are associated with risk of getting rheumatoid arthritis and severity of rheumatoid arthritis. Yet, in one set of data, difference in smoking and BMI did not underly the association of educational attainment/SES with inflammatory arthritis development.[2]
Clinical findings
Joint disease
Symmetrical swelling, pain, and stiffness, with the small joints of the hands, feet, wrist, and ankles most commonly affected in early disease. Destructive joint changes may appear early in the disease course, with nearly half of patients diagnosed with RA showing radiographic evidence of bone erosions within the first year of disease in some reports.
Extra-articular manifestations
Extra-articular (outside the joint) manifestations are frequently observed in RA and include inflammatory involvement of the
Hand deformities
Swan neck deformity
Image From Rheumatoid Arthritis (RA) By Kinanah Yaseen , MD, Cleveland Clinic Last review/revision Nov 2022 MSD Manual Online
Treatment
Treat to Target
Measure disease activity score. CDAI, DAS28. Stratify as low, mod, high disease activity. Tight control to low activity or remission improves outcomes. EULAR says low activity or remission. ACR says low activity is the goal. [3]
Disease modifying anti-rheumatic drugs (DMARD)
Initiate DMARD as soon as diagnosis is made. [3]
Conventional synthetic DMARD
Sulfasalazine (SSZ)
Monitor like MTX. CBC, ALT, AST, creatinine every 3 mos. GI intolerance is common. [3]
Hydroxychloroquine (HXC) (Plaquenil)
Low toxicity profile. Mechanism of action is unclear. Efficacy okay in mild disease as mono or in combination therapy. Takes a long time mos to start working. 200 mg .tablets. Max. dose = 5 mg per kg actual body wt. Single dose or divided. Can split tabs. Does not suppress the immune system. Hyperpigmentation on shins up to 7%. Can occur on face, too. Retinal toxicity is dose and duration dependent. Irreversible. Deposits in retina. AAO recommends not exceeding 5 mg per kg. Screen annually. OCT = ocular coherence tomography is used. Optometrists can do this screening.
Risks for hydroxychloroquine induced retinal toxicity [3]
- age>60
- duration >5 yrs
- dose > 5mg per kg.
Leflunomide (Arava)
MTX is better at preventing radiographic progression. Many of the comparison studies showed equivalence to MTX but MTX was used at a lower dose than is usually used. [3]
Methotrexate
Recommended by EULAR and ACR for mod to severe RA. Low activity, consider HXC per ACR. Used by itself or in combination with other drugs like a biologic, targeted synthetic, hydroxychloroquine or sulfasalazine. Triple therapy = MTX + HXC + SSZ. But, ACR still recommends monotherapy first. This is "the anchor drug" for RA treatment. Oral before SC recommended. Some data shows SC is better. PO is easier. Get to a minimum 15 mg. by 4-6 wks. Consider SC if not at target (conditional recommendation). Consider split dose. Increase folic acid. Consider folinic acid. Consider reducing MTX if doing well on a biologic plus MTX. Continue low dose MTX 7.5-10 mg to prevent development of anti-drug antibodies. If you can't use it, use LEF and SSZ. [3]
30% get to remission or to low disease activity. Dose is in 2.5 mg. tablets. Optimal dose per EULAR = 20-25 mg. per week. [3]
Triple therapy
MTX+HXC+ SSZ. If you taper, stop SSZ first as it is more likely to lose efficacy. [3]
Steroids
ACR recommends against short term steroid for everyone with RA (conditional rec). Use lowest dose for shortest duration. EULAR 2019 consider steroids as a bridge. Taper as quick as possible within 3 mos. Side effects = osteoporosis, diabetes, AVN. [3]
NSAIDS
Don't modify disease activity.
Biologic DMARD (monoclonal antibodies)
Synergism with MTX. Can induce anti-drug abs and this can be diminished by MTX. RCT showed no advantage >10 mg. MTX for preventing abs. [3]
- TNFI
- IL6 inhibitors
- Co-stimulation receptor inhibitors
- B cell inhibitors
TNFI drugs
Risk of reactivating TB is 18x if not on TNFI drugs. Screen at initiation for TB and hep B. Hep C screen is a good idea. Etanercept might be safer per Euro registry data. Not consistent in all studies. 10% less risk. Drug induced ANA, dsDNA (30%) or lupus. Histone ab rare. Usually rash and serositis. Psoriasis is rare 0.5% per year. More common in smokers. 41% of psoriasis induced is palmoplantar. Switch TNFI and in 1 in 3 psoriasis won't recur. CHF got worse in heart failure trials. Contraindicated in mod-severe CHF (III-IV). Only pertains to HFrEF. Demyelinating disease rare but more than in controls. 35 of 13,489 patients. ILD might be a side effect but also TNFI might improve ILD. [3]
Malignancy is a theoretical concern. Black box especially lymphoma. No increase other than non-melanoma skin cancer including no increased risk of lymphoma. [2]
No live vaccines. [3]Targeted synthetic drugs
Complications of RA
Eye disease can occur with RA. Most devastating is dissolution of the cornea known as corneal melt. It is typically in patients with long-standing RA and high positive RF level. Can it occur as a result of eye surgery?
One trial showed more cognitive dysfunction in RA patients than in age-matched controls without RA. This could be biased by selection of volunteers who might have already had concerns about their cognition. Conclusion was that"people with RA had impairments in memory, verbal fluency, visuospatial functioning, executive function and emotional recognition in faces compared with healthy controls, after adjustment for confounders."[4]
