Rheumatoid Arthritis(RA)
Definition :
Rheumatoid arthritis (RA): is a chronic and usually progressive inflammatory disorder of
unknown etiology characterized by polyarticular symmetric joint involvement and systemic
manifestations (1).
Epidemiology:
Rheumatoid arthritis is more common in women than men and is an important cause of disability and
morbidity. There is also significant mortality associated with the disorder (2). RA can occur at any
age, but 80% of the patients develop rheumatoid arthritis between the ages of 35 and 50 years (3).
Etiology:
The cause of the chronic inflammation characteristic of rheumatoid arthritis isn't known. Possible
theories include :
abnormal immune activation leading to the formation of antibody (also called rheumatoid factor,
RF; which generates inflammation-------------causing cartilage and bone damage(3).
Pathophysiology:
1-In early rheumatoid arthritis the synovium becomes inflamed (synovitis) and effusion into the joint
space occurs which causes pain, stiffness and joint swelling (2).
2-Infiltration by lymphocytes, macrophages, and neutrophils. These cells, produce enzymes that help
to degrade bone and cartilage (3).
3-Chronic inflammation of the synovial tissue lining the joint capsule results in tissue proliferation
(pannus formation). Pannus invades cartilage and eventually the bone surface, producing erosions of
bone and cartilage and leading to joint destruction. The end results may be loss of joint space, loss of
joint motion, and chronic deformity (1).
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Figure 1
Clinical presentation:
The clinical manifestations of rheumatoid disease are highly variable. Although acute
presentations may occur, the onset of articular signs of inflammation is usually insidious, with
prodromal symptoms of malaise, weight loss, and vague periarticular pain or stiffness. Symmetric
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joint swelling with stiffness, warmth, tenderness, and pain are characteristic. Stiffness persisting for
more than 30 minutes (and usually many hours) is prominent in the morning, subsiding later in the
day (4).
Joint involvement tends to be symmetric and affect the small joints of the hands, wrists, and feet; the
elbows, shoulders, hips, knees, and ankles may also be affected (1).(see figure 2).
After months or years, deformities may occur; the most common are deformities
of the fingers (4) : (see Figure 3)
Figure 3 Hand Deformity in RA
Figure 2 :Joints that
may affected by RA
Extra-articular involvement may include: pleural effusions, pulmonary fibrosis, ocular
manifestations, cardiac conduction abnormalities, bone marrow suppression, and
lymphadenopathy,………. (1).
Diagnosis(1,2) :
Rheumatoid arthritis is classified using the revised 1988 American Rheumatism Association (ARA)
criteria, at least four of which must be present for at least six weeks for a positive diagnosis of
rheumatoid arthritis. These criteria include :
1-morning stiffness in and around the joints, lasting for at least one hour .
2-Arthritis of three or more joint areas.
3-Arthritis of at least one area in the wrist or hand.
4-Symmetrical arthritis.
5-rheumatoid nodules.
6-Positive serum rheumatoid factor.
7-Radiographic changes typical of rheumatoid arthritis on hand and wrist X-rays.
Desired Outcome (1) :
1-the ultimate goal of RA treatment is to induce a complete remission, although this is seldom
achieved.
2
2-The primary objectives are to reduce joint swelling, stiffness, and pain; preserve range of motion
and joint function; improve quality of life; prevent systemic complications; and slow destructive joint
changes.
Treatment:
A-Nonpharmacological Treatment (2)
1-Adequate rest, weight reduction if obese, and physiotherapy.
2-patient education about the disease and its therapies is important.
3-Occupational therapists (appliances and devices to help patients with the activities of daily living).
B-Surgery (2)
Joint replacement has been one of the greatest advances in the management of rheumatoid arthritis.
Other surgical procedures that are beneficial include tendon repair, synovectomy (removal of the
synovial membrane resulting in reduced pain.)
C-Pharmacological Treatment (1)
General Approach
1-A disease-modifying antirheumatic drug (DMARD) should generally be started within the
first 3 months of symptom onset . DMARDs should be used in all patients except those with limited
disease. Early use of DMARDs results in a more favorable outcome and can reduce mortality.
First-line DMARDs include methotrexate, hydroxychloroquine, sulfasalazine, and
leflunomide (1).
2-Biologic agents with disease-modifying activity include the anti-Tumor necrosis factor (anti-TNF)
agents (etanercept, infliximab, adalimumab) and the interleukin-1 receptor antagonist
anakinra. Biologic agents are effective for patients who fail treatment with other DMARDs.
3-DMARDs that are less frequently used include azathioprine, penicillamine, gold salts (including
auranofin), minocycline, cyclosporine, and cyclophosphamide. These agents have either less efficacy
or high toxicity, or both.
4-Combination therapy with two or more DMARDs may be effective when single-DMARD treatment
is unsuccessful. Combinations that are particularly effective include:
(1) methotrexate plus cyclosporine
(2) methotrexate plus sulfasalazine and hydroxychloroquine.
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TABLE 1 :Usual Doses and Monitoring Parameters for Antirheumatic Drugs
Drug
Usual Dose
Initial Monitoring
Tests
Maintenance
Monitoring Tests
Scr or BUN, CBC every
2-4 wk after starting
therapy for 1-2 months;
salicylates: serum
salicylate levels if
therapeutic dose and no
response
Baseline: AST, ALT,
ALK-P, albumin, total
bilirubin, hepatitis B
and C studies, CBC with
platelets, Scr
Baseline: ALT
Same as initial plus stool
guaiac every 6-12
months
NSAIDs
See Table 4
Methotrexate
Oral or IM: 7.5-15 mg/wk
Leflunomide
Oral: 100 mg daily for 3
days, then 10-20 mg daily
Hydroxychloroquine
Oral: 200-300 mg twice
daily; after 1-2 months may
decrease to 200 mg once or
twice daily
Oral: 500 mg twice daily,
then increase to 1 g twice
daily max
25 mg SC twice weekly or
50 mg every 7 days
3 mg/kg IV at 0, 2, and 6
wk, then every 8 wk
40 mg SC every 2 wk
Baseline: color fundus
photography and
automated central
perimetric analysis
Baseline: CBC with
platelets, then every
week for 1 month
None
100 mg SC daily
Oral: 3 mg once or twice
daily
IM: 10-mg test dose, then
weekly dosing 25-50 mg;
after response may increase
dosing interval
Oral: 50-150 mg daily
Sulfasalazine
Etanercept
Infliximab
Adalimumab
Anakinra
Auranofin
Gold thiomalate
Azathioprine
Cyclophosphamide
Oral: 125-250 mg daily,
may increase by 125-250
mg every 1-2 months; max
750 mg/day
Oral: 1-2 mg/kg/day
Cyclosporine
Oral: 2.5 mg/kg/day
Corticosteroids
Oral, IV, IM, IA, and softtissue injections: variable
Penicillamine
CBC with platelets, AST,
albumin every 1-2
months
ALT monthly initially,
and then periodically
when stable
Ophthalmoscopy every
9-12 months and Amsler
grid at home every 2 wk
Same as initial every 1-2
months
None
None
None
None
None
None
Baseline: UA, CBC with
platelets
Baseline and until
stable: UA, CBC with
platelets preinjection
None
Same as initial every 1-2
months
Same as initial every
other dose
CBC with platelets, AST
every 2 wk for 1-2
months
Baseline: UA, CBC with
platelets, then every
week for 1 month
Same as initial every 1-2
months
UA, CBC with platelets
every week for 1 month
Scr, blood pressure every
month
Glucose; blood pressure
every 3-6 months
Same tests as initial but
every 2-4 wk
Same as initial
Same as initial every 1-2
months, but every 2 wk
if dose changes
Same as initial
ALK-P, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase;
BUN, blood urea nitrogen; CBC, complete blood cell count; IA, intra-articular; IM, intramuscular;
IV, intravenous; SC, subcutaneously; Scr, serum creatinine; UA, urinalysis
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Table 2 : Clinical Monitoring of Drug Therapy in Rheumatoid Arthritis
Toxicities Requiring
Monitoring
Drug
NSAIDs and
salicylates
Gl ulceration and bleeding, renal
damage
Corticosteroids
Hypertension, hyperglycemia,
osteoporosisb
Azathioprine
Myelosuppression, hepatotoxicity,
lymphoproliferative disorders
Gold (intramuscular Myelosuppression, proteinuria, rash,
stomatitis
or oral)
Hydroxychloroquine Macular damage, rash, diarrhea
Methotrexate
Myelosuppression, hepatic fibrosis,
cirrhosis, pulmonary infiltrates or
fibrosis, stomatitis, rash
Leflunomide
Hepatitis, Gl distress, alopecia
Penicillamine
Myelosuppression, proteinuria,
stomatitis, rash, dysgeusia
Sulfasalazine
Myelosuppression, rash
Etanercept,
adalimumab,
anakinra
Infliximab
Local injection-site reactions,
infection
Immune reactions, infection
Symptoms to Inquire Abouta
Blood in stool, black stool,
dyspepsia, nausea/vomiting,
weakness, dizziness, abdominal
pain, edema, weight gain, shortness
of breath
Blood pressure if available,
polyuria, polydipsia, edema,
shortness of breath, visual changes,
weight gain, headaches, broken
bones or bone pain
Symptoms of myelosuppression
(extreme fatigue, easy bleeding or
bruising, infection), jaundice
Symptoms of myelosuppression,
edema, rash, oral ulcers, diarrhea
Visual changes including a
decrease in night or peripheral
vision, rash, diarrhea
Symptoms of myelosuppression,
shortness of breath,
nausea/vomiting lymph node
swelling, coughing, mouth sores,
diarrhea, jaundice
Nausea/vomiting, gastritis,
diarrhea, hair loss, jaundice
Symptoms of myelosuppression,
edema, rash, diarrhea, altered taste
perception, oral ulcers
Symptoms of myelosuppression,
photosensitivity, rash,
nausea/vomiting
Symptoms of infection
Postinfusion reactions, symptoms
of infection
a Altered immune function increases infection, which should be considered, particularly in patients
taking azathioprine, methotrexate, corticosteroids, or other drugs that may produce
myelosuppression.
b Osteoporosis is not likely to manifest early in treatment, but all patients should be taking
appropriate steps to prevent bone loss.
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5-Nonsteroidal anti-inflammatory drugs (NSAIDs) and/or corticosteroids may be used for
symptomatic relief if needed. They provide relatively rapid improvement compared with DMARDs,
which may take weeks to months before benefit is seen. However, NSAIDs have no impact on
disease progression, and corticosteroids have the potential for long-term complications.
TABLE 3. Dosage Regimens for Some Nonsteroidal Anti-Inflammatory Drugs
Drug
Aspirin
Celecoxib
Diclofenac
Recommended Total Daily Antiinflammatory Dosage
Adult
Children
2.6-5.2 g
200-400 mg
150-200 mg
1.2-3.2 g
Ibuprofen
Indomethacin 50-200 mg
60-100 mg/kg
-
Ketoprofen
150-300 mg
20-40 mg/kg
2-4 mg/kg (max, 200
mg)
-
Meloxicam
Naproxen
7.5-15 mg
0.5-1.0 g
10 mg/kg
Piroxicam
10-20 mg
-
Dosing Schedule
4 times daily
Once or twice daily
3-4 times daily Extended
release: twice daily
3-4 times daily
2-4 times daily Extended
release: once daily
3-4 times daily Extended
release: once daily
Once daily
twice daily Extended release:
once daily
Once daily
Evaluation of Therapeutic Outcomes(1)
1-Clinical signs and Symptom of improvement include: reduction in joint swelling, pain and
morning stiffness, and improvement in ability to perform daily activities.
2-Laboratory monitoring is of little value in monitoring response to therapy but is essential for
detecting and preventing adverse drug effects.
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