MINISTRY OF HEALTH OF UKRAINE

Vinnytsya national medical university named after M.I.Pirogov

"Approved"
At methodical meeting of chair
Internal medicine №1
Head of the department
____________ prof. Stanislavchuk M. A.
«______» _______________ 20 ___

METHODICAL RECOMMENDATIONS
For students

Subject matter Foundation of internal medicine

Module № 2 Cardiology, Rheumatology, Nephrology
Substantial module № 1 Foundations of diagnostics, treatment and prevention of the
most common cardiovascular diseases
Subject of the lesson RHEUMATOID ARTHRITIS
Course 5
Faculty Medical № 1

Vinnytsya
1. The subject of the lesson: Rheumatoid arthritis
Study-hours : 4
The aim: The students must be able to diagnose Rheumatoid arthritis, determine the complications
and prescribe the proper treatment.

Educational goal:
1. Determine main etiological factors of Rheumatoid arthritis,
2. Define the clinical symptoms of Rheumatoid arthritis
3. Make the plan of additional investigation of the patient and analyze their results.
4. Make the clinical diagnosis of the patient with Rheumatoid arthritis.
5. Prescribe the proper treatment.

The student must know:

1. Etiology and pathogenesis of Rheumatoid arthritis.
2. Clinical symptoms of Rheumatoid arthritis.
3. Modern classification of Rheumatoid arthritis.
4. Methods of diagnostics of Rheumatoid arthritis.
5. Methods of treatment of Rheumatoid arthritis.

The student must be able:

1.To choose the symptoms of Rheumatoid arthritis from the history data.
2. In examination of the patient to choose the symptoms of Rheumatoid arthritis.
3. To make the scheme of investigation for the determination of the cause of Rheumatoid arthritis.
4. To assess the result of lab tests.
5. To determinate the treatment depending on the cause of Rheumatoid arthritis.
6. To prescribe the proper treatment for the patient with Rheumatoid arthritis.

2. Basic level of training

№ The names of The obtained skills
previous courses
1. Normal anatomy To know the anatomical structure, topography, blood supply and
innervation of the musculoskeletal system .
2. Histology Aware of the muscles and connective tissue histological structure.
3. Biochemistry Know the metabolic processes that occur in muscles and connective
tissue.
4. Normal Know the physiology of the musculoskeletal system.
physiology
5. Physiopathology To know changes in physiologic parameters of the musculoskeletal
system. Know the pathogenetic mechanisms of RHEUMATOID
ARTHRITIS. Know the physiological explanation of basic clinical
and laboratory syndromes of RHEUMATOID ARTHRITIS.
6. Pharmacology To know the mechanism of action, indications and contraindications
of medicines, which is used in treating patient with RHEUMATOID
ARTHRITIS and be able to write them in the form of recipes.
8. Propaedeutic Demonstrate skills in examination of patients with RHEUMATOID
therapy ARTHRITIS (collecting complaints, history of disease and life, doing
an objective examination, analyzing the results diagnostic testing).
 3. CONTENTS OF THE TRAINING MATERIALSSubject of the lesson:
- Aetiology and pathogenesis of the disease.
Rheumatoid arthritis (RA) is the most common inflammatory arthritis and hence an
important cause of potentially preventable disability. Many of the clinical features and
management strategies in RA are relevant across the spectrum of inflammatory joint disease. The
typical clinical phenotype of RA is a symmetrical, deforming, small and large joint polyarthritis,
often associated with systemic disturbance and extra-articular disease features. The clinical course
is usually life-long, with intermittent exacerbations and remissions. Some patients have mild
disease; in others it is more severe. It is currently not possible to predict prognosis at presentation
accurately, so caution and appropriate treatment are needed in all patients.
No single factor has been identified to date. Evidence for the importance of genetic
susceptibility comes from higher concordance rates in monozygotic (12-15%) than in dizygotic
twins (3%) and an increased frequency of disease in first-degree relatives of patients with RA. Up
to 50% of the genetic contribution to susceptibility is due to genes in the HLA region. HLA-DR4
is the major susceptibility haplotype in most ethnic groups. However, DR1 is more important in
Indians and Israelis and DW15 in Japanese. It is likely that genetic factors influence both
susceptibility and severity, with DR4 positivity more common in those with severe erosive disease.
RA has a significant genetic component, and the so-called shared epitope of the HLA-
DR4/DR1 cluster is present in up to 90% of patients with RA, although it is also present in more
than 40% of controls.
Female gender is a risk factor and this susceptibility is increased post-partum and by
breastfeeding. No infectious agents have been consistently isolated and there is no evidence of
disease clustering. Cigarette smoking is a risk factor for RA and for positivity for rheumatoid factor
in non-RA subjects. Whatever the initiating stimulus, RA is characterised by persistent cellular
activation, autoimmunity and the presence of immune complexes at sites of articular and extra-
articular lesions. This leads to chronic inflammation, granuloma formation and joint destruction
Major cellular roles are played by CD4 T cells, mononuclear phagocytes, fibroblasts,
osteoclasts, and neutrophils, while B lymphocytes produce autoantibodies (ie, rheumatoid factors
[RFs]). Abnormal production of numerous cytokines, chemokines, and other inflammatory
mediators (eg, tumor necrosis factor alpha [TNF-alpha, interleukin (IL)–1, IL-6, transforming
growth factor beta, IL-8, fibroblast growth factor, platelet-derived growth factor) have been
demonstrated in patients with RA. Ultimately, inflammation and exuberant proliferation of
synovium (ie, pannus) leads to destruction of various tissues such as cartilage, bone, tendons,
ligaments, and blood vessels. Although the articular structures are the primary sites, other tissues
are also affected.
Pathology
The earliest change is swelling and congestion of the synovial membrane and the
underlying connective tissues, which become infiltrated with lymphocytes (especially CD4 T
cells), plasma cells and macrophages. Effusion of synovial fluid into the joint space takes place
during active phases of the disease. Hypertrophy of the synovial membrane occurs, with the
formation of lymphoid follicles resembling an immunologically active lymph node. Inflammatory
granulation tissue (pannus) spreads over and under the articular cartilage, which is progressively
eroded and destroyed. Later, fibrous or bony ankylosis may occur. Muscles adjacent to inflamed
joints atrophy and there may be focal infiltration with lymphocytes.
 Subcutaneous nodules consist of a central area of fibrinoid material surrounded by a
palisade of proliferating mononuclear cells. Similar granulomatous lesions may occur in the
pleura, lung, pericardium and sclera. Lymph nodes are often hyperplastic, showing many lymphoid
follicles with large germinal centres and numerous plasma cells in the sinuses and medullary cords.
Immunofluorescence confirms rheumatoid factor synthesis by plasma cells in synovium and
lymph nodes
Clinical classification of the RA
I. Clinico-immunological characteristic :
1. RA seropositive
- Polyarthritis, oligoarthritis, monoarthritis
- Rheumatoid vasculitis
- Rheumatoid nodules
- Polyneuropathy
- Rheumatoid lung disease (alveolitis, rheumatoid lung)
- Felty ”s syndrome
2. RA seronegative
- Polyarthritis, oligoarthritis, monoarthritis
- Adult Still”s disease
II Activity degree
0 – remission
1 – low
2 – average/medium/moderate
3 – high
Indexes 0 1 2 3
Pain 0 <4 4-6 >6
Morning stiffness 0 30-60 12 h >12 h
min
ESR <16 16-30 31-45 >45
“С”-RP 0-1 1-2 2-3 >3

III Radiographic stage

І – juxta-articular osteoporosis
ІІ – an osteoporosis + narrowing of the joint space, single erosions
ІІІ – the same + plural erosions, there can be subluxations
ІV – the same + the ankylosis

IV – Loss of functional activity

1. The vital manipulations are carried out without difficulties
2. With difficulties
3. With assistance

The American College of Rheumatology developed the following criteria for the
classification of RA.
 1. Morning stiffness: This occurs in and around the joints and lasts at least 1 hour before
maximal improvement.
2. Arthritis of 3 or more joint areas: At least 3 joint areas simultaneously have soft tissue
swelling or fluid (not bony overgrowth) observed by a physician. The 14 possible areas are
right or left proximal interphalangeal (PIP), metacarpophalangeal (MCP), wrist, elbow,
knee, ankle, and metatarsophalangeal (MTP) joints.
3. Arthritis of hand joints of at least one area swollen in a wrist, MCP, or PIP joint
4. Symmetric arthritis with simultaneous involvement of the same joint areas on both sides
of the body: Bilateral involvement of PIPs, MCPs, and MTPs is acceptable without
absolute symmetry.
5. Rheumatoid nodules: Subcutaneous nodules are present over bony prominences or
extensor surfaces or in juxta-articular regions.
6. Serum RF: Abnormal amounts of serum RF are demonstrated by any method for which
the result has been positive in fewer than 5% of healthy control subjects.
7. Radiographic changes typical of RA on posteroanterior hand and wrist radiographs,
which must include erosions or unequivocal bony decalcification localized in or most
marked adjacent to the involved joints: Osteoarthritic changes alone do not qualify.
A patient can be classified as having RA if 4 of 7 criteria are present. Criteria 1-4 must be
present for at least 6 weeks, and a physician must observe criteria 2-5. These criteria are intended
as a guideline for classification of patients, often for research purposes. They do not absolutely
confirm or exclude a diagnosis of RA in a particular patient, especially in those with early arthritis
The most common presentation is with a gradual onset of symmetrical arthralgia and
synovitis of small joints of the hands, feet and wrists. This insidious onset has traditionally been
considered to imply a poor prognosis, possibly because of the delay in presenting for medical
advice.
Those most commonly affected joints, in decreasing frequency, are the MCP, wrist, PIP, knee,
MTP, shoulder, ankle, cervical spine, hip, elbow, and temporomandibular. Joints show
inflammation with swelling, tenderness, warmth, and decreased range of motion. Atrophy of the
interosseous muscles of the hands is a typical early finding. Joint and tendon destruction may lead
to deformities
Specific joints
The typical features are symmetrical swelling of the metacarpophalangeal (MCP) and proximal
interphalangeal (PIP) joints. Note that erythema is not a feature of rheumatoid arthritis and usually
implies coexistent sepsis. Specific hand abnormalities include 'swan neck' deformity, the
boutonnière or 'button hole deformity', and a Z deformity of the thumb. Dorsal subluxation of the
ulnar styloid of the wrist is common and may contribute to rupture of the fourth and fifth extensor
tendons. Triggering of fingers may occur due to nodules in the flexor tendon sheath.
In the forefoot dorsal subluxation of the metatarsophalangeal (MTP) joints results in 'cock-up'
toe deformities. This causes pain on weight-bearing on the exposed MTP heads and development
of secondary adventitious bursae and callosities. In the hindfoot, calcaneovalgus (eversion) is the
most common deformity, reflecting damage to the ankle and subtalar joint. This is often associated
with loss of the longitudinal arch (flat foot) due to rupture of the tibialis posterior tendon.
Popliteal ('Baker's') cysts usually occur in combination with knee synovitis, with synovial fluid
communicating with the cyst but being prevented from returning to the joint by a valve-like
mechanism. Rupture, often induced by knee flexion in the presence of a large effusion, leads to
calf pain and swelling. Differentiation from a deep vein thrombosis (DVT) can usually be made
by the presence of pre-existing joint problems, but a Doppler ultrasound or arthrogram is required
to establish the correct diagnosis, since DVT and Baker's cyst may coexist. It is important to be
aware of this differential diagnosis, as anticoagulating a Baker's cyst can cause further leg swelling
and lead to a compartment syndrome

Extra-articular manifestation
o Skin: Subcutaneous nodules (rheumatoid nodules) occur in many patients with RA
whose RF value is abnormal. They are often present over pressure points (eg,
olecranon). Vasculitic lesions of the skin may manifest as palpable purpura or skin
ulceration.
o Cardiac: The incidence of cardiovascular morbidity and mortality is increased in
patients with RA. Nontraditional risk factors appear to play an important role.
Myocardial infarction, myocardial dysfunction, and asymptomatic pericardial
effusions are common; symptomatic pericarditis and constrictive pericarditis are
rare. Myocarditis, coronary vasculitis, valvular disease, and conduction defects are
occasionally observed.
o Pulmonary: RA involvement of the lungs may take several forms, including pleural
effusions, interstitial fibrosis, nodules (Caplan syndrome), and bronchiolitis
obliterans-organizing pneumonia.
o GI: Intestinal involvement, as with kidney involvement, is often secondary to
associated processes such as medication effects, inflammation, and other diseases.
The liver is often affected in patients with Felty syndrome (ie, RA, splenomegaly,
and neutropenia).
o Renal: The kidneys commonly are not affected directly by RA. Secondary
involvement is common, including that due to medications (eg, nonsteroidal anti-
inflammatory drugs [NSAIDs], gold, cyclosporin), inflammation (eg, amyloidosis),
and associated diseases (eg, Sjögren syndrome with renal tubular abnormalities).
o Vascular: Vasculitic lesions can occur in any organ but are most commonly found
in the skin. Lesions may present as palpable purpura, skin ulcers, or digital infarcts.
o Hematologic: Most active patients have an anemia of chronic disease. Several
hematologic parameters parallel disease activity, including normochromic-
normocytic anemia, thrombocytosis, and eosinophilia, although the latter is
uncommon. Leukopenia is a finding in patients with Felty syndrome. Felty's
syndrome is the association of splenomegaly and neutropenia with RA.
Lymphadenopathy may be found in nodes draining actively inflamed joints, but
generalised lymphadenopathy should be investigated by biopsy since there is an
increased risk of lymphoma in patients with long-standing disease.
o Neurologic: Entrapment of nerves is common, such as with the median nerve in
carpal tunnel syndrome. Vasculitic lesions, mononeuritis multiplex, and cervical
myelopathy may cause serious neurological consequences.
o Ocular: Keratoconjunctivitis sicca is common in RA and is often the initial
manifestation of secondary Sjögren syndrome. The eye may also have episcleritis,
uveitis, and nodular scleritis that may lead to scleromalacia.
o Amyloidosis is a rare complication of prolonged active disease and usually presents
with nephrotic syndrome
• The American College of Rheumatology developed criteria to aid in determining the
progression, remission, and functional status of patients with RA.

• Progression of RA (clinical and radiological staging)

o Stage 1 (early RA)

▪ No destructive changes observed upon roentgenographic examination
▪ Radiographic evidence of osteoporosis possible

o Stage II (moderate progression)

▪ Radiographic evidence of periarticular osteoporosis with or without slight
subchondral bone destruction
▪ Slight cartilage destruction possible
▪ Joint mobility possibly limited; no joint deformities observed
▪ Adjacent muscle atrophy
▪ Extra-articular soft tissue lesions (eg, nodules, tenosynovitis) possible

o Stage III (severe progression)

▪ Radiographic evidence of cartilage and bone destruction in addition to
periarticular osteoporosis
▪ Joint deformity (eg, subluxation, ulnar deviation, hyperextension) without
fibrous or bony ankylosis
▪ Extensive muscle atrophy
▪ Extra-articular soft tissue lesions (eg, nodules, tenosynovitis) possible

o Stage IV (terminal progression)

▪ Fibrous or bony ankylosis
▪ Criteria of stage III

• Remission of RA - Five or more of the following conditions present for at least 2

consecutive months

o Duration of morning stiffness not exceeding 15 minutes

 o No fatigue
o No joint pain
o No joint tenderness or pain with motion
o No soft tissue swelling in joints or tendon sheaths
o ESR of less than 30 mm/h for a female or less than 20 mm/h for a male

• Functional status of patients with RA

o Class I - Completely able to perform usual activities of daily living

o Class II - Able to perform usual self-care and vocational activities but limited in
avocational activities
o Class III - Able to perform usual self-care activities but limited in vocational and
avocational activities
o Class IV - Limited in ability to perform usual self-care, vocational, and
avocational activities
Investigations

Lab Studies:

• No pathognomonic test is available to help confirm the diagnosis of RA; instead, the
diagnosis is made using clinical, laboratory, and imaging features.

• Markers of inflammation, such as ESR and CRP, are associated with disease activity;
additionally, the CRP value over time correlates with radiographic progression.

• Hematologic parameters include a CBC count and synovial fluid analysis.

o Complete blood cell count

▪ Anemia of chronic disease is common and correlates with disease activity;
it improves with successful therapy.
▪ Hypochromic anemia suggests blood loss, commonly from the GI tract
(associated with NSAIDs).
▪ Anemia may also be related to disease-modifying antirheumatic drug
(DMARD) therapy.
▪ Thrombocytosis is common and is also associated with disease activity.
▪ Thrombocytopenia may be a rare adverse event of therapy and may occur
in patients with Felty syndrome.
▪ Leukocytosis may occur but is usually mild.
▪ Leukopenia may be a consequence of therapy or a component of Felty
syndrome, which may then respond to DMARD therapy.

o Synovial fluid analysis

▪ An inflammatory synovial fluid (WBC count >2000/mL) is present with
counts generally from 5,000-50,000/mL.
▪ Usually, neutrophil predominance (60-80%) is observed in the synovial
fluid (in contrast with mononuclear cell predominance in the synovium).
▪ Note that because of a transport defect, the glucose levels of pleural,
pericardial, and synovial fluids from patients with RA are often low
compared to serum glucose levels.
 • Immunologic parameters include RF, antinuclear antibodies, and, possibly, other newer
antibodies (anti-RA33, anti-CCP).

o Rheumatoid factor
▪ RF is present in approximately 60-80% of patients with RA over the
course of their disease but is present in fewer than 40% of patients with
early RA.

o Antinuclear antibodies: These are present in approximately 40% of patients with

RA, but test results for antibodies to most nuclear antibody subsets are negative.

o Newer antibodies (eg, anti-RA33, anti-CCP): Recent studies of anti-CCP

antibodies suggest a sensitivity and specificity equal to or better than those of RF,
with an increased frequency of positive results in early RA. The presence of both
anti-CCP antibodies and RF is highly specific for RA. Additionally, anti-CCP
antibodies, as do RF, indicate a worse prognosis.

Imaging Studies:

• Radiographs: Note that erosions may be present in the feet, even in the absence of pain
and in the absence of erosions in the hands.

o Extremities - Hands, wrists, knees, feet, elbows, shoulders, hips, cervical spine

o Others when indicated

• MRI: This modality is primarily used in patients with abnormalities of the cervical spine;
early recognition of erosions based on MRI images has been sufficiently validated.

• Sonography: This allows recognition of effusions in joints that are not easily accessible
(eg, hip joints, shoulder joints in obese patients) and cysts (Baker cysts). High-resolution
ultrasound images may allow visualization of tendon sheaths, changes and degree of
vascularization of the synovial membrane, and even erosions; however, this needs further
validation. Sonography may be used as an office-based procedure.

• Bone scanning: Findings may help to distinguish inflammatory from noninflammatory

changes in patients with minimal swelling.

• Densitometry: Findings are useful for helping diagnose changes in bone mineral density
indicative of osteoporosis.

- The principles of pathogenetic therapy (undrug and drug treatment)

Medical Care:
The following are the key management goals in RA:
• relief of symptoms
• suppression of inflammation
• conservation and restoration of function in affected joints (joint protection)
• environmental modification if appropriate
Optimal care of patients with RA requires an integrated approach of pharmacologic and
nonpharmacologic therapies.
• Nonpharmacologic
o Education is important in helping patients to understand their disease and to learn how to
 cope with its consequences.
o Physiotherapy and physical therapy are initiated to help improve and sustain
range of motion, increase muscle strength, and reduce pain.
o Occupational therapy is initiated (1) to help patients to use joints and
tendons efficiently without stressing these structures, (2) to help patients decrease
tension on the joints through the use of specially designed splints, and (3) to help
patients to cope with daily life through the use of adaptations to the patients'
environment and the use of different aids.
o Orthopedic measures include reconstructive and replacement-type surgical
measures.
• Pharmacologic treatment of patients on RА
• DMARDs appointment in first three months
• NSAIDs appointment in need
• Appointment of GCS low doses in need
DMART (basic agents)
Preparation Introduction regimen The action
beginning
Plaquenilum, 600 mg during 4-6 weeks then on 400 3-6 months
200 mg mg/day
Methotrexatum, 2,5 - 7,5 mg/week, the max dose is 20-25 1-2 months
2,5; 10 mg mg/week
Sulfasalazinum, Begin with 0,5 enlarging on 0,5 weekly 1-3 months
0,5 to 40 mg/kg, a maintenance dose is 1 g 2-3/day
Azathioprinum, 50-150 mg/day, maintenance dose is 50- 2-3 months
0,05 100 mg/day
Аurotiomalat The first dose is 10 mg, then on 50 3-6 months
sodium, myocrizinum, mg/week, a maintenance dose is 50 mg on 2-4
25-50 mg, i/m week
D-penitsilamin, 125 mg/d, enlarge by 125 1/month to 750 3-6 months
0,15-0,25 mg/d
Leflunomidum On 100 mg 3 days then on 20 mg/day 1-2 months
0,1, 0,02, 0,01
Monocyclinum 2 times a day 1-3 months
0,1
Inphlecsimab 3 mg/kg in 2, 4, 8 weeks, then each 8 1-16 weeks
weeks
Etanerceptum 25 mg int/derm twice a week 1-12 weeks

o Biologic agents
▪ The recognition of TNF-alpha and IL-1 as central proinflammatory
cytokines has led to the development of agents that block these cytokines or their
effects. The TNF blockers include etanercept, infliximab, and adalimumab. Etanercept,
a bivalent p75–TNF receptor linked to the Fc portion of human IgG, is administered at
25 mg SC twice weekly or 50 mg SC weekly, with or without concomitant MTX.
Infliximab, a chimeric monoclonal antibody against TNF-alpha, is administered at
doses of 3 mg/kg IV at weeks 0, 2, and 6 and then every 4-8 weeks, usually with MTX.
Adalimumab, a recombinant human IgG1 monoclonal antibody specific for human
TNF monoclonal antibody, is administered 40 mg SC every 2 weeks.
▪ These agents are expensive. Consensus statements do not recommend their
use until at least one xenobiotic DMARD, usually MTX, has been administered without
 sufficient success. In clinical trials, up to 70% of patients achieve significant responses,
but remissions are not usually observed.
▪ These agents bind TNF and thus prevent its interaction with its receptors;
infliximab binds to cells that express membrane TNF, while etanercept binds
lymphotoxin (formerly termed TNF-beta) in addition to soluble TNF-alpha. Failure to
respond to one TNF blocker does not preclude response to another. As with
xenobiotics, the decision to continue or stop biologic agents can often be made within
3 months after initiation of therapy.
▪ Adverse effects associated with the biologic agents include the generation
of antibodies against these compounds, emergence of antinuclear antibodies,
occasional drug-induced lupuslike syndromes, and infections (including tuberculosis).
Rarely, demyelinating disorders and bone marrow suppression may occur. Acute and
chronic infections, demyelinating disorders, and recent malignancies are
contraindications for TNF blockers. Thoroughly searching for latent tuberculosis using
chest x-ray films and/or purified protein derivative (PPD) testing is recommended
before starting these agents.
▪ Another biologic is anakinra (IL-1 receptor antagonist [IL-1ra]). IL-1ra
occupies the IL-1 receptor without triggering it and prevents receptor binding of IL-1.
It is given at a dose of 100 mg/d SC. In clinical trials, a significant response was
observed in approximately 40% of patients with RA.
▪ Abatacept is a selective costimulation modulator that inhibits T-cell
activation by binding to CD80 and CED86, thereby blocking CD28 interaction. CD28
interaction provides a signal needed for full T-cell activation that is implicated in RA
pathogenesis. It is dosed according to body weight (vida infra); after initial infusion,
repeat on week 2 and week 4, then every 4 weeks following.
▪ In addition to improving signs and symptoms and quality of life, all
biologics significantly retard radiographic progression of joint erosions.
o Glucocorticoids
▪ Glucocorticoids are potent anti-inflammatory drugs and are commonly used
in patients with RA to bridge the time until DMARDs are effective.
▪ Doses of up to 10 mg of prednisone per day are typically used, but some
patients may require higher doses.
▪ Timely dose reductions and cessation are important because of the adverse
effects associated with long-term steroid use.
o Nonsteroidal anti-inflammatory drugs
▪ NSAIDs interfere with prostaglandin synthesis through inhibition of the
enzyme cyclooxygenase (COX), thus reducing swelling and pain. However, they do
not retard joint destruction and, therefore, when used alone, are not sufficient to treat
RA. Similar to glucocorticoids, they can be reduced in dose or discontinued with
successful DMARD therapy.
▪ Several dozen NSAIDs are available and can be classified into different
groups of compounds. Commonly used NSAIDs include ibuprofen, naproxen,
ketoprofen, piroxicam, and diclofenac.
▪ In the early 1990s, 2 isoforms of COX were discovered, ie, COX-1 and
COX-2. Traditional NSAIDs inhibit both COX-1 and COX-2.
▪ The coxibs (COX-2 inhibitors), a new group of compounds, have recently
been developed. These compounds have a significant preference for COX-2 over COX-
1. COX-1 has a protective role, particularly in the stomach, while COX-2 is strongly
up-regulated during inflammation.
▪ Coxibs, with their selectivity for COX-2, have been shown to be clinically
efficacious and are accompanied by significantly reduced GI toxicity, the major
adverse event related to the use of nonselective COX inhibitors (ie, NSAIDs). Other
 adverse effects, such as water retention, hypertension, and abnormal transaminase
levels, are observed with both nonselective and COX-2–selective drugs. Whether and
to what degree nonaspirin NSAIDs, coxibs, or both have cardiovascular toxicity has
not been definitively settled.
o Analgesics
▪ Acetaminophen/paracetamol, tramadol, codeine, opiates, and a variety of
other analgesic medications can also be employed to reduce pain.
▪ These agents do not affect swelling or joint destruction.
o Experimental therapies
▪ Despite significant advances over the past decades, RA continues to be an
incurable disease. The disease remains active in many patients whose conditions
partially or completely fail to respond to DMARDs. Therefore, a vigorous search is
underway for new therapeutic agents.
▪ Although not truly experimental because it has been approved for use in
RA, an immunoadsorbent column (Prosorba) is used on occasion to treat patients with
resistant disease. Weekly exchanges are given for 12 weeks.
▪ New TNF blockers are in clinical trials and include CDP 870, a Fab
fragment of a humanized monoclonal antibody; and a pegylated version of the p55 TNF
receptor.
▪ Biologics capable of blocking IL-6 or interfering with T-cell/non–T-cell
interactions may also be promising.
▪ Xenobiotics directed at molecules involved in transduction of TNF or IL-
1–mediated signals could prove helpful.
▪ Inhibition of matrix metalloproteinases, although initially unsuccessful,
could prove to be efficacious, as could agents that inhibit activation of osteoclasts.
▪ Apheresis procedures are being investigated.
▪ High-dose immunosuppression combined with autologous stem cell
transplantation has been used in study protocols for patients whose conditions are
resistant to other therapies.
o Early therapy
▪ Many studies have revealed that early treatment of RA (ie, within 3-12 mo
of onset) with DMARDs can not only more efficiently retard disease progression than
later treatment, but also may induce more remissions. Thus, early therapy with
DMARDs has become the standard of care.
▪ Importantly, note that patients with early forms of arthritis should be
evaluated by, and if necessary, referred to physicians who are experienced in the
diagnosis and treatment of this disease.

4. Plan and organizational structure of educational sessions on discipline.

Time
№ Stages of class distribu- Types of control Equipment training
tion
1. The starting phase 15%
1.1. Organizational matters 20-25
min.
1.2. Formation of motivation
 1.3. Control of entry-level
training
2. The main stage
- demonstration of the
patient - his clinical
examination (history,
physical examination,
additional methods of
investigation);
- interpretation received
symptoms
3. The final stage
3.1. Control of the final level of
training
- written computer -textbooks
testing; treatment of internal
- oral questioning by the diseases;-
standardized list of guidelines;
questions. - situational
problem in therapy
of internal
medicine;
- tests "Step 2";
- practical skills at the - themed patients.
bedside (collecting
complaints, history of
65%
illness, physical
120-
examination, assessment
130
of results of additional
mn.
methods investigation);
- interpretation of the
results.
20%
25-30 - situational tasks;
min. - structured written work.

3.2. The total score of student

workload
3.3. Informing students about
the topic the next lesson

5. Methods of educational process in the practice.

5.1. The starting phase.
To reveal the theme sessions for medical profession to develop the motivation for focused
learning activities. To acquaint students with specific goals and plan activities.
In class, students solve a specific problem, learn to make diagnosis, conduct differential
diagnosis of diseases, prescribe appropriate treatment regimens and prevention.
5.2. The main stage
At this stage the student will continue to build professional skills. Particularly at the bedside
student demonstrates the ability to collect complaints, history of disease and life, to make an
objective examination of the patient by different systems and organs and on the basis of the data
to the differential diagnosis to establish a preliminary diagnosis. To support his opinion, the student
makes the plan an additional examination of the patient. Synthesizing all the data obtained during
examination of the patient, the student formulates a final clinical diagnosis according to modern
classification and diagnostic criteria.
Analysis of the results allows the student to prescribe appropriate treatment of the patient
depending on clinical variant and degree of activity, complications, comorbidities and give
recommendations for further treatment and lifestyle.
5.3. The final stage
 Assessment of action of each student during class and standardized end control. It
conducted the analysis of student achievement, announced rating of each student and put in the
book of visits and student achievement. Parish groups simultaneously puts rating in accounting
performance and attendance of students. The teacher assures them his signature.
Brief information for students on the theme of the next lesson and instructional techniques
to prepare for it.
Recommended literature:
А. Main:
1. Davidson’s Principles and Practice of Medicine, 2010, P.1092-1098.

Materials for self-control:

А. The questions for self-control:
1. Name the main etiological factors of Rheumatoid arthritis.
2. What are the main clinical symptoms of Rheumatoid arthritis?
3. What are the main clinical symptoms of Rheumatoid arthritis?
4. Make the plan of additional investigation of the patient with Rheumatoid arthritis.
5. Name the main complications of Rheumatoid arthritis.
6. Name the main principles of the modern management of the patient with Rheumatoid arthritis.

Methodic recommendations made by Ph.D. Ostapchuk O.I.