Rheumatoid Arthritis

There is no difference in prevalence among races (True/False)

True.

Rheumatoid Arthritis - Tends to have an earlier onset in women (True/False)

True. Likely due to hormonal onset, frequently in child bearing years.

Onset can occur at any age (True/False)

True. Although frequently starts at age 40-50.

Rituximab only works on RF positive patients (True/False)

True. It won't work on RF negative patients.

The prevalence of RA increases with _________

age

We often see signs of ____ with chronic immune activation or chronic disease.

anemia

RA is a systemic disease with a varety of ____________ and __________________ manifestations

articular; extra-articular

Etiology of RA involves both __________ and _____________ factors

genetic; environmental

RF is present in 5% of ________________

healthy people (ie. elderly)

What is arthritis?

inflammation of one or more joints

NSAID therapy - Guidelines for use

Mainly for analgesic effect, not much use in inflammatory process.

What is pannus?

Mass of synovial stroma consisting of inflammtory cells, granulation tissue, and fibroblasts, which grows over the articular cartilage and causes its erosion resulting in bony ankylosis

SSZ onset of action?

May see benefit in *approximately 1 month*

ESR and C reactive protein lab results are ___.

Non specific signs of inflammation

Inflammation is restricted to the joints only in the body (True/False)

False. Inflammation can affect any of the connective tissue in the body(eg. blood vessels, lungs, eyes, heart).

Rheumatoid Arthritis - Affects more men than women by a factor of 3 to 1. (True/False)

False. 3 times as many women suffer from RA than men.

A positive for Rheumatoid factor confirms the diagnosis of RA. (True/False)

False. Rheumatoid factor can be present with other auto-immune disorders(eg. lupus, sarcoidosis)

HCQ - SE?

*Generally well tolerated* Nausea most common - take with food. Rash and diarrhea are rare. Ocular damage rare. Get a baseline eye exam then q 6-12 months.

Anti TNFalpha biologics: ___ is approved only if given with MTX. Why?

*Infliximab*. To reduce immune reaction to the murine component. Without MTX immune antibody response is upwards of 50%.

HCQ - MOA?

*Inhibits locomotion* of neutrophils and *chemotaxis* of eosinophils

IL-1 Biologic: Anakinra - Efficacy? SE?

*Less effective than other biologics* and now not commonly used. Local injection site infections up to 70%. Also watch for reversible neutropenia and thrombocytopenia (monitor CBCs q6months)

What do you call the growth of synovial tissue due to chronic inflammation? Why is it a concern?

*Pannus* - membrane of granulation tissue that grows in response to chronic inflammation. Eventually can invade cartilage and eventually bone, causing an erosion.

Complication affecting the pleural lining

*Pulmonary fibrosis*. Risk increases with smoking. Causing interstitial pneumonitis

What is RF?

*Rheumatoid factor*: - an IgM auto-antibody that is reactive with the FC portion of patient's own IgG

Complication affecting blood vessel wall

*Vasculitis* - invasion of blood vessel wall by inflammatory cells. Causes infarction of distal tissues (similar to DM). Larger vessels to nerves or organs can be life threatening. Treat with aggressive steroid therapy.

Rheumatoid Arthritis - Pathophysiology

- Autoimmune reaction where body cannot tell self from non self - Immune system starts attacking synovial and connective tissue - Chronic inflammation of synovial tissue leads to growth (pannus)

What are some ocular manifestations of RA?

- Eye inflammation (episcleritis, scleritis) - Retinal nodules - Dry eyes

Joints commonly affected are ___ (6). Less common joints are ___ (2).

- Hands, Elbows, Knees, Wrists, Shoulders, Ankles - Hips, Neck

HCQ - Testing prior/during?

- Have to see optometrist prior to starting HCQ and *every 6-12 months*. Worried about corneal deposits.

SSZ - SE?

- Headache - GI problems (NVD) - Photosensitivity - Rash - Oligospermia (reversible) - low sperm count

Symptoms of RA (3)

- Joint pain and stiffness lasting more than 6 weeks - May have fatigue, weakness, low grade fever and decreased appetite (ie. Flu like symptoms) - Muscle pain and afternoon fatigue

Other Non Pharmacological Tx:

- Multidisciplinary team approach: OT/PT (skills and exercises) - Weight loss advised - Hot/Cold packs - Surgery

What some other manifestations of RA?

- OA secondary to RA (aggrevated by glucocorticoid therapy) - Felty's syndrome (chronic RA, splenomegaly, neutropenia, thrombocytopenia, and anemia)

Criteria for diagnosis (2)

- Presents with *at least 1 joint with clinical synovitis* - Synovitis is not better explained by another disease

Goals of treatment (3)

- Prevent/control joint damage (ASAP) - Prevent loss of function - Decrease pain

DMARDS are first line and prescribed immediately on diagnosis. What should you tell the patient?

- There is no immediate effect, slow onset: *max effect is in 3-6 months* - Patient should be seen every 1-3 months while their disease is active. - Target of remission or low disease activity in 3-6 months.

RF may be positive in other diseases such as?

- Tuberculosis - Leprosy - Hep B

Corticosteroid Therapy - Guidelines for use in RA

- Use *lowest effective dose* - Use only as a *bridge* for effective DMARD therapy - Will not need prednisone doses > 10mg/day

Given mild RA (less than 2 swollen joints, negative RF, ESR and C-protein normal) then we can do monotherapy with ___ or ___.

HCQ or SSZ

Prevalence of RA is about ______% of the population

0.8

What are 2 Neuromuscular manifestations of RA?

1) Carpal tunnel syndrome 2) Peripheral neuropathy

What are 3 enviromental factors that could cause RA?

1) Climate 2) Cigarettes 3) Infectious factors

What are 5 early non-specific symptoms of RA that may last weeks to months?

1) Fatigue 2) Anorexia 3) Generalized weakness 4) Vague musculoskeletal symptoms 5) Mild fever

What are 2 hematologic manifestations of RA?

1) Lymphadenopathy 2) Anemia

What are some infectious agents that could cause RA response in genetically susceptible host?

1) Mycoplasma 2) Epstein-Barr virus 3) Cytomegalovirus 4) Parvovirus 5) Rubella virus

What are 2 cardiac manifestations of RA?

1) Pericarditis 2) Myocarditis

What are 5 later specific manifestations of RA?

1) Symmetric polyarthritis 2) Pain (in 2 or more joints) 3) Morning stiffness (> 20min) or difficulty moving after rest 4) Synovial inflammation (swelling, tenderness, limitation of motion) 5) Warmth (esp in large joints, ie knee)

What are 2 "diagnostic" methods for RA?

1) Synovial fluid analysis 2) Radiologic evaluation (no specific test available)

What are 4 types of factors that can cause arthritis?

1) physical 2) bacterial 3) viral 4) immune

Inflammatory response process(4)

1. Antigen-presenting cell eats antigen 2. Antigen presented to T lymphocyte (Activation) 3. Activated T cell stimulates T and B lymphocyte production (Promotes inflammation) 4. Activated T cell and macrophage release factors: Tissue destruction, Increased blood flow, Cellular invasion of synovial tissue and joint fluid

What is the end result of the inflammatory response?

1. Loss of joint cartilage (joint space) 2. Formation of scar tissue (loss of joint motion or bony fusion) 3. Laxity of tendons (loss of joint support) 4. Tendon contractures (chronic deformity)

Main Pharmacological Tx: (4)

1. NSAIDS 2. Biologics 3. Corticosteroids 4. DMARDS

Anti TNFalpha biologics - Caution using in ___ (2)

1. Patients who have active or chronic infections(including TB) 2. Demyelinating or HF patients

Rituximab dosing schedule

2 doses 2 weeks apart. Time to re-treatment is generally 20 months after.

HCQ onset of action?

2-3 months

What is the usual dosing regimen for MTX?

20-25mg q1week po or parenterally x 3 months

Corticosteroid Therapy - Injection into joint should not be done sooner than once every ____.

3 months

Joint damage occurs early in course of RA. ___ % of patients have x-ray evidence of bone erosion at time of diagnosis. It goes up to ___% in two years.

30% 60%

What is the peak age for RA?

35-50y.o

Women are affected about ________ more than men

3X

SSZ is cleaved to ___ and ___.

5-ASA and sulfapyridine

RF is detectable in _____% of RA patients

70

Other combinations are ___.

MTX with gold salts, leflunomide, azathioprine, or cyclosporine.

What is the pathogenesis of RA?

An autoimmune disease triggered by exposure of geneticaly susceptible host to unknown antigen

IL-1 Biologic: ___. MOA?

Anakinra Blocks the interleukin-1 receptor.

What is ACPA?

Anti-citronilated protein antigen (antibodies against own proteins)

Hydroxychloroquine belongs to what class?

Anti-malarial

What lab tests should be performed prior and during MTX use? How often to test?

Baseline hep B and C, CXR, CBC, LFT, Albumin, Creatinine each month x 6 months, then every 2 months thereafter

Rituximab MOA. Difference between this biologic vs others?

Binds to B lymphocytes and *mediates lysis of B cells*. By attacking the B cells, remove the disease memory cells.

Anti TNFalpha biologics: ___ is PEGylated which should reduce immunogenicity and increase half life.

Certolizumab

What are 2 pulmonary manifestations of RA?

Chronic cough COPD (looks like pneumonia on X-ray)

Define rheumatoid arthitis

Chronic systemic inflammatory disorder that mainly attacks the joints leading to joint destruction, deformity and loss of function

Anti TNFalpha biologics: ___ has the most frequent dosing(inconvenient) while ___ has the least frequent dosing(convenient).

Entanercept (twice weekly or once weekly) Golimumab (once monthly)

___ is special that it reversibly binds to free TNF alpha and beta.

Entanercept.

Presence of ___________ reflects severe systemic disease

Eosinophillia

What do we give along with MTX to minimize its SE?

Folic acid 5mg

Name the TNFalpha antagonists (5)

G.I ACE: - Golimumab - Infliximab - Adalimumab - Certolizumab - Etanercept

Anti TNFalpha biologics - ___ has been shown to be effective for patients who have failed other Anti-TNFalpha biologics.

Golimumab

Name the DMARDS (6)

HS CLAM: 1. Hydroxychloroquine (HCQ) 2. Sulfasalazine (SSZ) 3. Cyclosporine 4. Leflunomide 5. Azathioprine 6. Methotrexate (MTX)

Extra-articular symptoms are usually observed in patients with what?

High titres of RF

Immune system has ___ and ___ mediated function. It involves production of ___.

Humoral and Cell Mediated T and B cells, antibodies, cytokines, macrophages, neutrophils.

Erythrocyte sedimentation rate is _____________ in nearly all RA patients

Increased

SSZ - MOA?

Interferes with inflammatory process by *inhibiting prostaglandin synthesis*.

An alternative to MTX if that is CI is ___. Although it is no longer recommended due to loading dose diarrhea.

Leflunomide.

___ is the reference DMARD and is an anchor drug in treatment of RA.

MTX

Anti TNFalpha biologics are most effective when combined with ___.

MTX or other DMARDs

"Triple therapy" refers to ___.

MTX with HCQ and SSZ combination

Given moderate to severe RA (>3 swollen joints), one can combine ___ with ___ and/or ___.

MTX with HCQ and/or SSZ ("Triple Therapy")

WBC count is usually ________ in RA patients

Normal

What type of anemia is usually present in active RA?

Normochromic normocytic

For all Anti TNFalpha biologics, a concern with use is ___ and ___.

Opportunistic bacterial infections Reactivation of TB.

Complication affecting the heart

Pericarditits (lining around heart)

What is the characteristic feature of RA?

Persistent inflammatory SYNOVITIS that usually involves the peripheral joints in a SYMMETRIC distribution

Sulfasalazine (SSZ) is a ___.

Prodrug

What are Rheumatoid nodules? Should they be treated?

Raised bumps/swelling on the joint, commonly found at "pressure or stress points" (eg. on elbow). They are usually asymptomatic and require no treatment.

In terms of non-pharmacological treatment, what is the most essential component?

Rest. Relieves stress on inflamed joint. Although do not rest too much such that muscle atrophies and ROM decreases.

The damage and deformity of the joints are irreversible (True/False)

True

1st line biologics are the ___.

TNFalpha antagonists.

What is the RF test used for?

To CONFIRM diagnosis in individuals with suggestive clinical presentation

Side effects of MTX? (7)

VAG FUND: Vomiting Anorexia Gingivitis Flu like symptoms (fever, muscle ache, malaise) Ulcerative stomatitis Nausea Diarrhea