RHEUMATOID ARTHRITIS



RHEUMATOID ARTHRITIS

DIAGNOSIS

Rheumatoid arthritis is found in approximately 1% of the population, 85% are female. Though most women present in their twenties or thirties it can be found at any age. Patients usually present with a several months history of involvement of multiple joints. It is typically a symmetrical polyarthritis, almost always involving the hands. About 90% will be seropositive with a RF or CCP.

The 2010 American College of Rheumatology/European League Against Rheumatism criteria for rheumatoid arthritis are a bit awkward to follow: a score of ≥ 6/10 is needed for definite RA

Score

A. Joint involvement

2-10 large joints 1

1-3 small joints 2

4-10 small joints 3

>10 joints 5

B. Serology

Low-positive RF or CCP 2

High-positive RF or CCP 3

C. Acute-phase reactants

Abnormal CRP or normal ESR 1

D. Duration of symptoms

≥6 weeks 1

Differential diagnosis:

- acute viral arthritis from hepatitis B, rubella, or parvovirus. These will usually resolve spontaneously in less than six weeks.

- Other CTD - lupus, especially if they have a history of Raynuads or rash. Sjogrens if sicca sx, Psoriatic arthriti. Reactive arthritis if iritis, urethritis, or inflammatory bowel disease

Lab screening: The rheumatoid factor is present in approximately 80% of patients. A high titer is associated with increased severity of disease and is more specific for rheumatoid arthritis. However, any chronic inflammatory condition, be it infectious or autoimmune, may cause a positive rheumatoid factor, particularly Hep C (40% have RF). Anti-cyclic citrullinated peptide anti-bodies (anti-CCP) have nearly the sensitivity as RF, but they are more specific for RA (>95%) and are found earlier in the disease course and among those at risk of more severe outcomes. The acute-phase reactants (ESR & CRP) are usually elevated in active rheumatoid arthritis and are correlated with severity of outcome. Approximately 30% of patients with rheumatoid arthritis will have a positive antinuclear antibody with a homogenous pattern. Patients will also have a normochromic, normocytic anemia and hypergammaglobulinemia. Early x-ray changes include periarticular osteopenia and soft tissue swelling. Later changes include joint space narrowing and erosions. X-rays are not particularly useful in the first few months of disease since the findings are not specific. Finally, synovial fluid is expected to be inflammatory with negative results on microbiologic culture and crystal analysis.

COMPLICATIONS and VARIANTS OF RA

Patients with rheumatoid arthritis have reduced life expectancy of 10 to 18 years – due to infection and increased rate of CAD. Their overall prognosis is worse if they have a positive rheumatoid factor, an elevated sedimentation rate, a positive HLA DR-4, a low educational level, morning stiffness, a large number of joints involved or significant weaknesses of grip. Extra-articular manifestations of rheumatoid arthritis include pulmonary disease (pleuritis, interstitial fibrosis or pulmonary hypertension), rheumatoid nodules, Felty’s syndrome (splenomegaly and neutropenia) and vasculitis. Occasionally patients present with recurrent transient signs and symptoms of RA—this variant is known as palindromic RA. Another unusual variant of RA is RS3PE (remitting seronegative symmetrical synovitis with peripheral edema) - patients present with a RA picture with massive edema of hands and feet. They respond quickly to prednisone.

TREATMENT

General Measures

Patients should be encouraged to remain active. Exercise has been shown to be useful in improving outcome. However, patients must also learn joint protection techniques to avoid excess stress on involved joints. Occupational therapy can teach patients activities of daily living skills, provide adaptive devices and offer modalities to decrease pain including icing and heat. They can also provide patients with splints. In patients with lower extremity involvement, a physical therapist should evaluate the patient for need of a cane, walker or wheelchair.

NSAIDs

Patients can use NSAIDs throughout the course of their arthritis as tolerated. Patients on chronic NSAIDs should be routinely questioned about dyspepsia or signs of GI bleeding. They should be periodically monitored with CBC’s, ALT and creatinine.

Corticosteroids

Prednisone is extremely effective in reducing the discomfort from rheumatoid arthritis on a short-term basis. It is not as useful on a long-term basis and can induce significant osteopenia and muscle wasting. A trial of prednisone should be considered if a patient has severe/acute onset of disability and they cannot wait a few months to respond to remittive meds. They will rarely require a dose higher than 10 mg a day of prednisone and patients should be slowly tapered by approximately 1 mg per month when possible. It is not clear that prednisone acts to decrease disease activity over time. Therefore, any patient who is begun on prednisone should also be started on a long acting remittive agent as discussed below. Intra-articular steroid injections are quite useful for treating limited flares, and an injection of depomedrol 80 mg IM is useful for temporary relief of a polyarticular flare. Keep in mind that a monoarticular flare of could be infectious and appropriate cultures should be considered.

Remittive Agents – DMARDs (disease modifying anti rheumatic drugs)

Everyone should be treated – usually start with methotrexate, add a biologic if incomplete response. In general all biologics similar potency and risk.

Non-biologics

Group I: low toxicity, mild efficacy (60-80%)

1. Hydroxychloroquine (Plaquenil) Oral daily. Primary toxicity is retinopathy and patients require annual screening ophthalmologic exam.

2. Sulfasalazine. Oral BID. Major toxicity is diarrhea with occasional rashes or bone marrow suppression.

3. Minocycline. Oral daily. inhibits metalloproteinase activity. Slow onset

Group II: moderate toxicity, high efficacy (90%).

1. Methotrexate. Oral one day a week. Our workhorse med. Major toxicities are hematologic and hepatic fibrosis. Avoid use in alcoholics or patients with renal failure. Occasional pneumonitis. Fetal toxicity.

2. Leflunomide (Arava).Oral daily. A pyrimidine inhibitor. Similar profile as methotrexate—liver and fetal toxicity.

3. Azathioprine. Oral daily. Major toxicity is bone marrow suppression. Not as potent as MTX or arava, and more nausea. Useful “crossover” treatment for associated ILD.

Biologics

4. Anti TNFs: Infliximab (Remicade) IV q 6 weekw, Etanercept (Enbrel) SQ weekly, Adalimumab (Humira) SQ q 2 weeks, Golimumab (Simponi) SQ monthly, Certolizumab (Cimzia) SQ monthly. Very potent. Very expensive. Rapid onset action (2 weeks). Infection (particularly TB) and maybe worsening heart failure.

5. Abatacept (Orencia) IV monthly or SQ weekly. T-cell costimulatory blocking agent. Expensive. Infection, worsening of COPD.

6. Tocilizumab (Actemra) IV monthly. IL-6 inhibitor. Infections, increased lipids. Liver toxicity.

7. Tofacitinib (Xeljanz) – Oral BID. First oral biologic, JAK inhibitor. Liver toxicity, heme, lipids.

8. Rituximab (Rituxan) IV every 6 months. B-cell depleting agent. The most common side effects occur during infusion (fever, rigors and chills) that arise during administration of the first dose of drug. More than 80% of patients experience these side effects.

Drug Monitoring

Drugs used in the treatment of RA and SLE are listed below. Suggested laboratory exams represent a review of the PDR, general texts, and community rheumatologists. We usually screen all patients for TB and Hep B/C prior to treatment

1. Methotrexate—2.5 mg

Check for stomatitits, GI upset, hepatitis, BM suppression

Labs: Baseline CBC, LFTs, creatinine, then every 3 months.

Avoid use if Hx of hepatitis B/C, ETOH use, or abnormal LFTs

2. Hydroxychloroquine—Plaquenil 200 mg

Check for rash, retinopathy

Labs: Ophthalmology exam q 12 months. Annual CBC, LFTs

3. NSAID—Check CBC, creatinine several times a year. LFTs q year

4. Sulfasalazine—500 mg

Watch for rash, diarrhea, occasional neutropenia

Labs: CBC, ALT, creatinine every 3 months

5. Leflunomide—20 mg

Watch for hepatitis. Avoid pregnancy

Labs: CBC, LFT every 3 months

6. Anti TNF:

Watch for infection, neuropathy, annual TB screening

Labs: CBC, LFT annually

7. Abatacept - orencia

Watch for infection, annual TB screening

Labs: CBC annually

8. Rituximab:

Watch for infections (Hep B Sag or core, PML), infusion rx, rash

Labs: CBC every 3 months, consider immunoglobulin levels before retreat

11. Tocilizumab - actemra

Watch for heme, liver or lipids

Labs: CBC, ALT, creat every 3 months. Lipids every 6 months

12. Tofacitinib - xeljanz

Watch for heme, liver or lipids

Labs: CBC, ALT, creat every 3 months. Lipids every 6 months

13. Cyclophosphamide—Cytoxan 25 mg, 50 mg, IV infusion

Watch for leukopenia, alopecia, hemorrhagic cystitis, sterility

Labs: Follow CBC weekly, UA frequently.

For IV therapy check CBC 8-10 days after each infusion

14. Azathioprine—Imuran 50 mg

Watch for leukopenia, hepatitis

Labs: CBC and LFT every 3 months

15. Mycophenolate – Cellcept

Watch for liver, heme. Teratogenic

Labs; CBC, LFT, creat every 3 months

TB 2016

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