Rheumatoid Arthritis Concept Map | Pathophysiology | Signs and symptoms | Medications for RA

Rheumatoid Arthritis Concept Map
Rheumatoid Arthritis Concept Map - Click to enlarge image

Rheumatoid Arthritis Concept Map: An Overview

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Definition

Rheumatoid Arthritis is a chronic inflammatory autoimmune disease that involves the joints and may cause systemic manifestations.

Etiology

It is an autoimmune disease with unknown cause and contributing factors (genetic & environmental factors). Environmental factors like: viral infections and cigarette smoking; trigger and maintain joint inflammation.

Epidemiology

- Prevalence; 1% worldwide
- Gender; Women : Men = 3:1 (after 50 years old, gender difference is less marked)
- Age; peaks at 35-45 years old, although it can occur at any age - when it occurs in childhood, it is called "Juvenile Idiopathic Arthritis"
- Limitations of activities:
     * 33% have major activities limited
     * 29% cannot perform major activities

Pathophysiology

Rheumatoid arthritis pathophysiology is shown in the map in the form of a cascade process that starts by an "Autoimmune Reaction" and ends by "Joint Destruction."

Etiology and Pathophysiology of Rheumatoid Arthritis
Etiology and Pathophysiology of Rheumatoid Arthritis

Clinical Presentation

Nonspecific signs & symptoms (for weeks/months): fever,malaise,arthralgias, and weakness 
Specific signs and symptoms that take weeks to months to appear
Joint symptoms are characteristically symmetric, include:
- Stiffness lasts > 60 minutes after rising in the morning but may occur after any prolonged inactivity (called gelling).
- Erythema, warmth, swelling, and limitation of motion.
Joints involved in rheumatoid arthritis, include
The most common joints involved are;
-          Wrists, feet (MTP), and the index (2nd) and middle (3rd) metacarpophalangeal (MCP) joints
Other joints include;
-          Proximal interphalangeal (PIP) joints, shoulders, elbows, hips, knees, and ankles.
Any joint, except the distal interphalangeal (DIP) joints
Irreversible Joint Deformities may occur due to disease progression

  1.  Ulnar deviation of the fingers
  2. Boutonniere Deformity (hyperextension of the DIP & flexion of the PIP joint)
  3. Swan Neck Deformity (hyperextension of the PIP & flexion of the DIP joint)
  4. Hammer toe deformity
Progression
Disease progresses most rapidly during the first 6 years, particularly the first year; 80% of patients develop some permanent joint abnormalities within 10 years.

Extra-articular Manifestations

Most of rheumatoid arthritis extra-articular manifestations are collected in this image:
Rheumatoid arthritis extra-articular manifestations
Rheumatoid arthritis extra-articular manifestations

Diagnosis

This part of the map includes: History and Examination - Laboratory tests - Radiographic test
(x-ray) - ACR Rheumatoid Arthritis Diagnostic Criteria (2010). In addition, a comparison between rheumatoid arthritis and osteoarthritis is included.
Rheumatoid Arthritis vs Osteoarthritis
Rheumatoid Arthritis vs Osteoarthritis

Treatment

Treatment goals for rheumatoid arthritis are linked to medications used in managing the diseases.

Medications to Reduce Pain and Inflammation

1) Non-Steroidal Anti-inflammatory Drugs (NSAIDs)

e.g., ibuprofen, naproxen, ketoprofen, piroxicam, and diclofenac
- adjunctive therapy
- treat symptoms and decrease inflammation  but do not affect disease progression.
- dose can be decreased or discontinued with successful Disease-modifying antirheumatic drugs (DMARDs) therapy.
- adverse effects: GI toxicity, headache, confusion and other CNS symptoms, increased BP, worsening of hypertension, edema, and decreased platelet function. NSAIDs increase cardiovascular risk. 
Non-steroidal anti-inflammatory drug drugs mechanism of action is shown in this diagram:
Non-steroidal Anti-inflammatory Drugs - Mechanism of Action
Non-steroidal Anti-inflammatory Drugs - Mechanism of Action

2) COX-2 inhibitor (only celecoxib)

See the map. 

3) Low-dose systemic corticosteroids (CS)

  • adjunctive therapy      
  • decrease inflammation and other symptoms rapidly and efficiently
  • slow bone erosion
When to use low-dose systemic CS in RA?
  • In early RA, low-dose oral prednisone (<10 mg/day) in combination with DMARDs for up to 6 months, as symptomatic effects ↓ with time
  • In established RA, CS may be used as 'bridging' therapy when DMARDs are initiated, and should be withdrawn once DMARDs have controlled the disease
  • May be used for severe joint or systemic manifestations of RA (eg, vasculitis, pleurisy, pericarditis)
Contraindications
  • Relative contraindications include PUD, HTN, untreated infections, DM, and glaucoma
  • The risk of latent TB should be considered before CS therapy is begun

4) Intraarticular depot corticosteroids

- Temporarily control severe monarticular or even oligoarticular symptoms
- Triamcinolone hexacetonide may suppress inflammation for the longest time
- Triamcinolone acetonide and methylprednisolone acetate are also effective
- No single joint should be injected with a corticosteroid more than 3 to 4 times a year, as too-frequent injections may accelerate joint destruction
- Because injectable corticosteroid esters are crystalline, local inflammation transiently increases within a few hours in < 2% of patients receiving injections
- Although infection occurs in only < 1:40,000 patients, it must be considered if pain occurs > 24 h after injection

Medications to Prevent Disease Progression & loss of joint function

1)      Disease-modifying antirheumatic drugs (DMARDs)

Also called "nonbiologic DMARDs," include: methotrexate (MTX), hydroxychloroquine (HCQ), azathioprine (AZA), sulfasalazine (SSZ), and leflunomide.
Other available but rarely used DMARDs include minocycline, azathioprine, cyclosporine, and tacrolimus.
  • Early treatment of RA (< 6 months after the onset of symptoms) with DMARDs retard disease progression more efficiently and induce more remissions.
  • Until the full action of DMARDs takes effect, anti-inflammatory or analgesic medications may be required as bridging therapy to reduce pain and swelling.
  • They differ from each other chemically and pharmacologically.
  • Patients should be informed about the risks of DMARDs and monitored closely for evidence of toxicity.
  • Combinations of DMARDs may be more effective than single drugs. Also, combining a DMARD with another drug, such as methotrexate plus a TNF-α antagonist or an IL-1 receptor antagonist or a rapidly tapered corticosteroid, may be more effective than using DMARDs alone.

A comparison between DMARDs is available in the map. The comparison is showing: mechanisms of actions, indications, doses, adverse effects, monitoring parameters, and contraindications.

Disease Modifying Anti-Rheumatic Drugs (DMARDs) - Table Comparison - Zoom out - Pharmacotherapy
Disease Modifying Anti-Rheumatic Drugs (DMARDs) - Table Comparison

2)      Biologic Agents

  • Also called "biologic DMARDs"
  • They are not given in combination with each other due to increased frequency of infections.
  • Approved by the FDA to treat moderate to severe RA not responded to an one or more of the traditional DMARDs
  • They may be used alone, but are often in combination with other DMARDs, to increase the efficacy and decrease AE
  • Start biologic agents while patients remain on NSAID and/or corticosteroid

A comparison between biologic agents is available in the map. The comparison is showing: mechanisms of actions, indications, doses, onset of action, adverse effects, contraindications, and warnings/cautions.
Biologic DMARDs - Table Comparison - Zoom out - Pharmacotherapy
Biologic DMARDs - Table Comparison

3)      Other immunomodulatory, cytotoxic, and immunosuppressive drugs

e.g., Azathioprine, and cyclosporin A.  Rarely cyclophosphamide and d-Penicillamine
  • Efficacy is similar to DMARDs but more toxic.
  • Used in case of treatment failure with DMARDs or to ↓ the need for CSs.
  • Used infrequently unless there are extra-articular complications.
And here is a comparison between them:
Other immunomodulatory, cytotoxic, and immunosuppressive drugs - Table Comparison

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See also (Osteoarthritis Concept Map)

Rheumatoid Arthritis concept map by Maha Atef, B Pharm.
Version: 2.0
Last updated in: 10 June 2014

References
1-      Altman, Roy D., MD. "Rheumatoid Arthritis (RA)." Merck Manual Professional. Merck Sharp & Dohme Corp., Nov. 2012. Web. <http://www.merckmanuals.com/professional/musculoskeletal_and_connective_tissue_disorders/joint_disorders/rheumatoid_arthritis_ra.html>.
2-      Temprano, Katherine K., MD. "Rheumatoid Arthritis ." Rheumatoid Arthritis. Medscape, n.d. Web. 08 June 2014. <http://emedicine.medscape.com/article/331715-overview>.
3-      DiPiro, Joseph T. "Rheumatoid Arthritis." Pharmacotherapy: A Pathophysiologic Approach. 8th ed. New York: McGraw-Hill Medical, 2011. N. pag. Print.
4-      Trombetta, D. (2014). Geriatrics - Rheumatoid Arthritis. In ACCP Updates in Therapeutics® 2014: Pharmacotherapy Preparatory Review and Recertification Course (pp. 68-73).
5-      Moses, Scott, MD. "Rheumatoid Arthritis Diagnosis." Family Practice Notebook. N.p., 17 May 2014. Web. <http://www.fpnotebook.com/Rheum/R_2/RhmtdArthrtsDgns.htm>.
6-      RINDFLEISCH, J. ADAM, and Daniel MULLER. Diagnosis and Management of Rheumatoid Arthritis. Digital image. American Family Physician. 15 Sept. 2005. Web.
7-      Hodkinson, B., E. Van Duuren, C. Pettipher, and A. A. Kalla. "SAMJ: South African Medical Journal - South African Recommendations for the Management of Rheumatoid Arthritis: An Algorithm for the Standard of Care in 2013 - Part 2." SAMJ: South African Medical Journal - South African Recommendations for the Management of Rheumatoid Arthritis: Table 4. Synthetic DMARDs. N.p., n.d. Web. 11 June 2014.
8-      Lipton, Sarah, MD, and Atul Deodhar, MD. "Managing RA in 2011: An Update." Rheumatology Network. UBM Medica, 9 Jan. 2011. Web. 17 Nov. 2013. <http://www.rheumatologynetwork.com/rheumatoid-arthritis/managing-ra-2011-update>.
9-      Cush, John J., MD. "Biologic Treatments for Rheumatoid Arthritis." American College of Rheumatology. American College of Rheumatology, Dec. 2004. Web. <http://www.rheumatology.org/Practice/Clinical/Patients/Medications/Biologic_Treatments_for_Rheumatoid_Arthritis/>.
10-   Hodkinson, B., E. Van Duuren, C. Pettipher, and A. A. Kalla. "SAMJ: South African Medical Journal - South African Recommendations for the Management of Rheumatoid Arthritis: An Algorithm for the Standard of Care in 2013 - Part 2." SAMJ: South African Medical Journal - South African Recommendations for the Management of Rheumatoid Arthritis: An Algorithm for the Standard of Care in 2013 - Part 2. N.p., n.d. Web. 11 June 2014. <http://www.scielo.org.za/scielo.php?pid=S0256-95742013000800030&script=sci_arttext>.
11-    Celecoxib (Rx) - Celebrex. (n.d.). Retrieved from http://reference.medscape.com/drug/celebrex-celecoxib-343282
12-   RINDFLEISCH, J., & MULLER, D. (2005, September 15). Diagnosis and Management of Rheumatoid Arthritis. Retrieved from http://www.aafp.org/afp/2005/0915/p1037.html
13-   Abatacept - Drug Information Provided by Lexi-Comp. (2014, May). Retrieved from http://www.merckmanuals.com/professional/lexicomp/abatacept.html#N213B7F
14- Tocilizumab (Rx) - Actemra. (n.d.). Retrieved from http://reference.medscape.com/drug/actemra-tocilizumab-999419#4
15-   Keystone, E., Smolen, J., & Riel, P. (2012, March 30). Developing an effective treatment algorithm for rheumatoid arthritis. Retrieved from http://rheumatology.oxfordjournals.org/content/51/suppl_5/v48.long
16-   Bingham, Clifton, and Victoria Ruffing. "Rheumatoid Arthritis Treatment." Johns Hopkins Arthritis Center. Johns Hopkins Arthritis Center, 24 Sept. 2013. Web. <http://www.hopkinsarthritis.org/arthritis-info/rheumatoid-arthritis/ra-treatment/>.
17-   "Osteoarthritis vs. Rheumatoid Arthritis." Diffen. Diffen. Web. <http://www.diffen.com/difference/Osteoarthritis_vs_Rheumatoid_Arthritis>.
18-   "Comparing Rheumatoid Arthritis and Osteoarthritis - Topic Overview." Rheumatoid Arthritis Health Center. Healthwise, 5 June 2012. Web. <http://www.webmd.com/rheumatoid-arthritis/tc/comparing-rheumatoid-arthritis-and-osteoarthritis-topic-overview>.
19-   Table 4. The Updated ACR/EULAR 2010 Criteria for the Diagnosis of Rheumatoid Arthritis Patients Who Have at Least 1 Joint with Definite Clinical Synovitis (swelling) with the Synovitis Not Better Explained by Another Disease. Digital image. Journal of the Korean Medical Association. Web.

20-   Pannus. Digital image. The Free Dictionary by Rarlex. Web.


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