MINISTRY OF HEALTH OF UKRAINE

Zaporizhzhya state medical university

It is recommended
on a methodical conference
department of faculty pediatrics

Head of the chair professor Nedel'ska S.M.

"_31__" ______01_____ 2020_

METHODICAL RECOMMENDATIONS
FOR students self work

Educational discipline Pediatrics

Module №1 Widespread somatic children diseases
Substantial module Cardio-rheumatologic disorders in children
Topic of lesson#13 Juvenile rheumatoid arthritis and reactive arthritis in children.
Systemic connective tissue disorders

Course 4
Faculty Medical
 [Link] of the topic:

[Link]:
1. Define etiologic factors of JRA and reactive arthropathies
2. Classify and analyse typical clinical presentation of JRA and reactive arthritis (RA)
3. Define clinical peculiarities of JRA and RA in children and formulate clinical diagnosis
4. To perform examining plan and analyse instrumental and lab data
5. Demonstrate knowledge of treatment approach, rehabilitation and profilaxis of JRA, RA
6. To differentiate JRA and RA
7. To ground prognosis in peculiuar forms of JRA and RA
8. Demonstrate moral , seontological principles of physiscian according to subordination in
cardirheomatology.

3. Base level of training, skills and knowledge.

Discipline Skills which must be got by students
Anatomy,
Physiology To know the anatomo-physiological features of immune,
muscle, bone, connective systems in children
Path. аnatomy, To define the indexes To define immune reactions stages,
mechanisms of connective tissue reactivity. To know the
Path. рhysiology etiology and pathogenesis aspects of CTD

Introduction to the child's diseases To use research methods and to know semiotics of
diseases of immune, bone and joints, muscle, connective
tissue systems , to intrpretate clinical blood biochemical
tests, results of instrumental examining ( ultrasound
diagnostics, ECG, X-ray of joints).

Dignostic imaging To own the instrumental methods of diagnostics of

inflammation. To appoint and estimate the results of
instrumental methods.
 Pharmacology To write preparations: glukokortikosteroides, antibiotics,
desagregants, anticoagulants, cytostatics, and other.
To study indications, to prescribe and write recipes with
the proper remedies

4. Plan and methodical organization of classes.

means of studies
Time
(objects which are used in an
distribu-
№ Stages of lesson Types of control educational process as carriers
tion
of data and instruments of
teacher’s and student)
1. Preparatory stage 20 min (writing work, (equipment, textbooks, manuals
structured)
1.1 Organizational questions. the writing and reference books, atlases,
computer testing, methodical recommendations,
1.2 Forming of motivation. practical tasks, preparations, plaster casts,
situational tasks, results of researches
verbal questioning (sciagrams), results of analyses
1.3 Control of initial level of is after the and inspections, computers with
preparation (control is standardized lists the proper informative
standardized). of questions) providing, electronic reference
books, and others like that)

2. Basic stage 90 min

(curation of patients, making a
plan of management, treatment,
differential diagnosis)

3. Final stage 25 min

3.1. Control of eventual level of
preparation.
3.2. General estimation of
educational activity of student.

3.3 Informing students about the

theme of next lesson.

Content of educational material

Synonyms and related keywords: RA, systemic inflammatory disease, rheumatoid factor, RF,
cyclooxygenase, COX-1, COX-2, nonsteroidal anti-inflammatory drugs, NSAIDs, disease-
modifying antirheumatic drugs, disease-modifying anti-rheumatic drugs, DMARDs, joint
destruction, uncontrolled inflammation, cartilage destruction, bone destruction, morning
stiffness, rheumatoid nodules
Background: Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease of unknown
cause that primarily affects the peripheral joints in a symmetric pattern. Constitutional
symptoms, including fatigue, malaise, and morning stiffness, are common. Extra-articular
involvement of organs such as the skin, heart, lungs, and eyes can be significant. RA causes joint
destruction and thus often leads to considerable morbidity and mortality. The treatment of RA is
rapidly advancing with the recent addition of new and innovative therapies.
Pathophysiology: RA has an unknown cause. Although an infectious etiology has been
speculated (eg, Mycoplasma organisms, Epstein-Barr virus, parvovirus, rubella), no organism
has been proven responsible. RA is associated with a number of autoimmune responses, but
whether autoimmunity is a secondary or primary event is still unknown.
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. Synovial cell hyperplasia and endothelial cell activation are early events in the
pathologic process that progresses to uncontrolled inflammation and consequent cartilage and
bone destruction. Genetic factors and immune system abnormalities contribute to disease
propagation.
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.
Frequency:
 Internationally: The worldwide incidence of RA is approximately 3 cases per 10,000
population, and the prevalence rate is approximately 1%. RA affects all populations,
although a few groups have much higher prevalence rates (eg, 5-6% in some Native
American groups) and some have lower rates (eg, black persons from the Caribbean
region). First-degree relatives of patients with RA have an increased frequency of disease
(approximately 2-3%). Disease concordance in monozygotic twins is approximately 15-
20%, suggesting that nongenetic factors play an important role. Because worldwide
frequency is relatively constant, a ubiquitous infectious agent has been postulated to play
an etiologic role.
Mortality/Morbidity: RA does not usually follow a benign course. It is associated with
significant morbidity, disability, and mortality.
 Daily living activities are impaired in most patients. Spontaneous clinical remission is
uncommon (approximately 5-10%). After 5 years of disease, approximately 33% of
patients will not be working; after 10 years, approximately half will have substantial
functional disability. Poor prognostic factors include persistent synovitis, early erosive
disease, extra-articular findings (including subcutaneous rheumatoid nodules), positive
serum RF findings, family history of RA, male sex, and advanced age.
 Life expectancy for patients with RA is shortened by 5-10 years, although those who
respond to therapy may have lower mortality rates. Increased mortality rates are
associated with poor functional status, age, male sex, socioeconomic factors (eg, level of
education), positive RF findings, extra-articular disease, elevated acute phase response
(erythrocyte sedimentation rate [ESR], C-reactive protein [CRP]), and increased clinical
severity (eg, more involved joints). Mortality is increased by causes such as infections,
cardiovascular disease, renal disease, GI bleeding, and lymphoproliferative disorders;
these events may be directly due to the disease and its complications (eg, vasculitis,
amyloidosis) or to therapy-induced adverse effects.
Race: RA affects all populations, although a few groups have much higher prevalence rates (eg,
5-6% in some Native American groups) and some have lower rates (eg, black persons from the
Caribbean region).
Sex: Females are 2-3 times more likely to develop RA than males.
Age: The frequency of RA increases with age and peaks in persons aged 35-50 years.
Nevertheless, the disease is observed in both elderly persons and children.
 Juvenile inflammatory arthritis (JIA) has been classified as polyarticular (multiple joints),
pauciarticular (<5 joints), and systemic. Systemic JIA is often associated with fever, rash,
and organ involvement; it is also called Still disease.
 Children with polyarticular RF-positive arthritis generally have a clinical course similar
to those with adult RA.
History: 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.
Patients often present with constitutional complaints including malaise, fever, fatigue, weight
loss, and myalgias. They may report difficulty performing activities of daily living (eg, dressing,
standing, walking, personal hygiene, using their hands).
Most patients with the disease have an insidious onset. It may begin with systemic features, such
as fever, malaise, arthralgias, and weakness, before the appearance of overt joint inflammation
and swelling. A small percentage of patients (approximately 10%) have an abrupt onset with the
acute development of synovitis and extra-articular manifestations. Spontaneous remission is
uncommon, especially after the first 3-6 months.
Physical: Joint involvement is the characteristic feature of patients with RA. In general, the
small joints of the hands and feet are affected in a relatively symmetric distribution. 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 such as ulnar deviation, bouton and swan-neck deformities, hammer toes, and
occasionally joint ankylosis.
Other commonly observed musculoskeletal manifestations are tenosynovitis and associated
tendon rupture (due to tendon and ligament involvement, most commonly involving the fourth
and fifth digital extensor tendons at the wrist), periarticular osteoporosis due to localized
inflammation and generalized osteoporosis due to systemic chronic inflammation,
immobilization-related changes or corticosteroid therapy, and carpal tunnel syndrome. Most
patients have muscle atrophy from disuse, which is often secondary to joint inflammation.
 Effect of RA on organs and organ systems
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: 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 are not commonly directly affected 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.
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.
 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
Causes: The cause(s) of RA is unknown. Genetic, environmental, hormonal, immunologic, and
infectious factors may play significant roles. Socioeconomic, psychological, and lifestyle factors
may influence disease outcome.
 Genetic
o Approximately 60% of US patients with RA carry the so-called shared epitope of
the HLA-DR4 cluster, which constitutes one of the peptide binding sites of certain
HLA-DR molecules associated with RA (eg, HLA-DR beta *0401, 0404, or
0405); in addition, HLA-DR1 (HLA-DR beta *0101) also carries this shared
epitope and confers risk, particularly in certain southern European areas.
o Other HLA-DR4 molecules (eg, HLA-DR beta *0402) do not share the same
epitope and do not confer risk. Genes other than those of the major
histocompatibility complex are also involved, and results from sequencing genes
of RA families suggest the presence of several susceptibility genes and several
resistance genes.
 Environmental
o For many decades, numerous infectious agents have been suggested to induce
RA. Among these are Mycoplasma organisms, Epstein-Barr and rubella viruses,
and others.
o This supposition is further supported indirectly by the following:
 Occasional reports of flulike disorders preceding the start of arthritis
 The inducibility of arthritis in experimental animals with different bacteria
or bacterial products (eg, streptococcal cell walls)
 The presence of bacterial products including bacterial RNA in patients'
joints
 The activity of several agents that have antimicrobial effects as disease-
modifying drugs (eg, gold salts, antimalarials, minocycline)
  Hormonal
o Sex hormones may play a role, as evidenced by the disproportionate number of
females with RA, its amelioration during pregnancy, its recurrence in the early
postpartum period, and its reduced incidence in women using oral contraceptives.
o Hyperprolactinemia may be a risk factor for RA.
 Immunologic
o T cells are assumed to play a pivotal role in the initiation of RA, and the key
player in this respect is assumed to be the Th1 CD4 cells. (T helper 1 cells
produce IL-2 and interferon gamma.)
o These cells may subsequently activate macrophages and other cell populations,
including synovial fibroblasts. The latter 2 populations are the main producers of
the proinflammatory cytokines TNF-alpha and IL-1 that appear to be the major
driving forces of inflammation.
o Experimental models suggest that synovial macrophages and fibroblasts may
become autonomous and thus lose responsiveness to T-cell activities in the course
of the disease.
o The hyperactive and hyperplastic synovial membrane is ultimately transformed
into pannus tissue and invades cartilage and bone, the latter being degraded by
activated osteoclasts.
o The major difference between RA and other forms of inflammatory arthritis, such
as psoriatic arthritis, does not lie in their cytokine patterns but rather in the highly
destructive potential of the RA synovial membrane and in the local and systemic
autoimmunity. Whether these 2 events are linked is unclear; however, the
autoimmune response conceivably leads to the formation of immune complexes
activating the inflammatory process to a much higher degree than is otherwise the
case. This theory is supported by the much worse prognosis of RA among patients
positive for RF.
o In patients with RA, autoantibodies are not only directed against immunoglobulin
G (IgG), ie, RFs, but also against a variety of other antigens such as nuclear
antigens (RA 33, EBNA), citrullinated proteins (anti-CCP antibodies), collagen,
and glucose-6-phosphate isomerase.
Amyloidosis, Overview
Calcium Pyrophosphate Deposition Disease
Cryoglobulinemia
Fibromyalgia
Hepatitis B
Hypothyroidism
Inflammatory Bowel Disease
Lyme Disease
Mediterranean Fever, Familial
Multicentric Reticulohistiocytosis
Myelodysplastic Syndrome
Osteoarthritis
Paraneoplastic Syndromes
Polychondritis
Polymyalgia Rheumatica
Psoriatic Arthritis
Sarcoidosis
Sjogren Syndrome
Systemic Lupus Erythematosus
Whipple Disease
Other Problems to be Considered:
 Infectious arthritis - Bacteria (eg, Lyme disease, fungi, mycobacteria), viruses (eg,
hepatitis B, rubella, parvovirus, human T-cell leukemia virus 1)
 Autoimmune connective tissue diseases (eg, systemic lupus erythematosus, progressive
systemic sclerosis, mixed connective tissue disease, Sjögren syndrome, vasculitis,
cryoglobulinemias)
 Other rheumatic diseases (eg, polyarticular gout, seronegative spondyloarthropathy [eg,
ankylosing spondylitis, reactive arthritis])
 Subacute bacterial endocarditis
 Hemoglobinopathies
 Angioimmunoblastic lymphadenopathy
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/
L) is present with
counts generally from 5,000-50,000/
L.
 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.
 RF values fluctuate somewhat with disease activity, although high-titered
RF generally remains present even in patients with drug-induced
remissions.
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)
  These need further validation before their general use can be
recommended.
 Recent studies of anti-CCP antibodies suggest a sensitivity and specificity
similar to RF but an increased frequency of positive results in early RA.
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.
Other Tests:
 HLA-DR4 (shared epitope) may constitute a helpful marker in early undifferentiated
arthritis.
Procedures:
 Joint aspiration, diagnostic arthroscopy (histology), and biopsies (eg, skin, nerve, fat,
rectum, kidney) may be considered if vasculitis or amyloidosis is suggested.
Histologic Findings: The lymphoplasmacytic infiltration of the synovium with
neovascularization seen in RA is similar to that seen in other conditions characterized by
inflammatory synovitis. Early rheumatoid nodules are characterized by small vessel vasculitis
and later by granulomatous inflammation.
Medical Care: 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
o The most important measure to successfully treat RA is the use of DMARDs.
DMARDs can retard or prevent disease progression and, thus, joint destruction
and subsequent loss of function.
o Successful DMARD therapy may eliminate the need for other anti-inflammatory
or analgesic medications.
o Until the full action of DMARDs takes effect, anti-inflammatory or analgesic
medications may be required as bridging therapy to reduce pain and swelling.
o DMARDs can be classified into xenobiotic and biologic agents.
o Xenobiotic agents
 The xenobiotic DMARDs, ie, gold salts (eg, aurothiomalate, auranofin,
others), D-penicillamine, chloroquine and hydroxychloroquine,
sulfasalazine (SSZ), methotrexate (MTX), azathioprine, and cyclosporin
A, have been widely used to treat RA; some have been used for decades.
 MTX and SSZ are the most active compounds in terms of frequency of
remissions and time to onset of action and provide the best risk-benefit
ratios. MTX alone or in combination with other agents has become the
standard of care for moderate-to-severe RA.
 Interest in the use of minocycline has recently been increasing because of
its capacity to act as a DMARD.
 Leflunomide is the most recent addition to the xenobiotics and has an
activity similar to that of SSZ and MTX.
 SSZ is dosed up to 2-4 g/d, while MTX is administered up to 25 mg once
a week (PO, IV, IM, or SC). Both SSZ and MTX are started at low
dosages and are increased to full dosages within approximately 4-6 weeks.
Monitoring of CBC counts and liver enzymes is important because of the
drugs' hematologic and hepatic toxicities. Approximately 1% of patients
develop agranulocytosis to SSZ or pneumonitis to MTX. Leflunomide is
usually initiated with a loading dose of 100 mg/d for 3 days and is then
continued at 20 mg/d. CBC counts and liver enzymes also must be
monitored. Most of these drugs have been shown to improve signs and
symptoms (as well as quality of life) and to significantly retard
radiographic progression of RA.
 Combination therapy appears to be helpful in patients whose RA
insufficiently or completely fails to respond to monotherapy with a
DMARD. Several compounds have been successfully combined without
unexpected added risks; these usually include MTX as one of the drugs,
ie, MTX plus cyclosporine A, MTX plus SSZ plus an antimalarial, MTX
plus leflunomide, or MTX plus biologics. In general, the same precautions
are needed as with the single compounds, although liver and bone marrow
toxicity may be increased if compounds affecting these organs are
combined.
 The most important and most common adverse events relate to liver and
bone marrow toxicity (MTX, SSZ, leflunomide, azathioprine, gold
compounds, D-penicillamine), renal toxicity (cyclosporine A, parenteral
gold salts, D-penicillamine), pneumonitis (MTX), allergic skin reactions
(gold compounds, SSZ), autoimmunity (D-penicillamine, SSZ,
minocycline) and infections (azathioprine, cyclosporine A). Antimalarials
may cause ocular toxicity. Nevertheless, these drugs, when used with
appropriate clinical and laboratory control monitoring, are usually
tolerated well. Adverse events typically become more rare after the first 2-
3 months. Most adverse events are reversible with cessation of the drugs
or with reduction of the doses.
 In clinical trials, 30-70% of patients using DMARDs, either alone or in
combination therapy, achieve partial responses according to the American
College of Rheumatology's disease activity score. Predicting which
patients will not respond is impossible. In clinical practice, attempting to
reduce disease activity as much as possible by (1) increasing the dose of
medication (eg, MTX), (2) switching to other DMARDs in those who do
not respond or in those with responses regarded as insufficient, or (3)
 initiating combination therapy is important. Because patients may require
2-3 months to achieve a full response to DMARDs, decisions regarding
changes in medication are often delayed until that time.
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 first such biologics were the TNF blockers etanercept
and infliximab. Etanercept, a bivalent p75–TNF receptor linked to the Fc
portion of human IgG, is administered at 25 mg SC twice 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.
 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.
 A new addition to the biologics 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.
 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.
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 Another 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 adalimumab, a fully
human monoclonal antibody; 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.
Surgical Care: Cervical spine involvement usually affects C1-C2 and may potentially cause
serious neurological consequences. Patients who are to undergo intubation or procedures that
may involve manipulation of the neck should have careful evaluation of the cervical spine.
Patients with RA often need multiple operations over time (eg, synovectomy, tendon corrections,
joint replacements).
Consultations:
 Orthopedists
 Physical and rehabilitative medicine specialists
Optimal care of patients with RA requires an integrated approach of pharmacologic and
nonpharmacologic therapies.
Drug Category: Disease-modifying antirheumatic drugs -- Can be classified into xenobiotic and
biologic agents. Xenobiotics include gold salts (eg, aurothiomalate, auranofin, others), D-
penicillamine, chloroquine and hydroxychloroquine, SSZ, MTX, azathioprine, and cyclosporin
A and have been widely used to treat RA.
Leflunomide (Arava) -- First new DMARD
approved in more than 10 years. Blocks
autoimmune antibodies and reduces
inflammation. Inhibits dihydroorotate
Drug Name dehydrogenase, an enzyme in the de novo
pyrimidine synthesis pathway. Studies indicate
that it reduces symptoms, possibly better than
MTX, and may even slow progression of RA. Use
with caution in renal insufficiency
Initial: 100 mg PO qd for 3 d
Adult Dose
Maintenance dose: 10-20 mg/d PO
Pediatric Dose Not established
Contraindications Documented hypersensitivity
Cholestyramine and charcoal reduce effects;
Interactions
concomitant rifampin increases toxicity
Pregnancy X - Contraindicated in pregnancy
Serious adverse reactions include hepatotoxicity
and immunosuppression; other reactions include
nausea, diarrhea, abdominal pain, rash, bronchitis,
headache, hypertension, dizziness, and alopecia;
caution if impaired liver or renal function or if
Precautions
immunodeficient; leflunomide is a prodrug and
active metabolite has a very long plasma half-life
(approximately 15 d); with serious toxicity, can
be cleared more quickly using cholestyramine 8
mg tid
Methotrexate (Rheumatrex, Folex PFS) --
Unknown mechanism of action in treatment of
inflammatory reactions, although it is a known
inhibitor of dihydrofolate reductase and causes
Drug Name extracellular release of adenosine, a known
inhibitor of immune and inflammatory pathways.
Ameliorates symptoms of inflammation (eg, pain,
swelling, stiffness). Gradually adjust dose to
attain satisfactory response.
Adult Dose 7.5-25 mg PO/IV/IM/SC qwk
Pediatric Dose 5-20 mg PO/IV/IM/SC qwk
Documented hypersensitivity; alcoholism; hepatic
inflammation or insufficiency; documented
immunodeficiency syndromes; preexisting blood
Contraindications
dyscrasias (eg, bone marrow hypoplasia,
leukopenia, thrombocytopenia, significant
anemia); renal insufficiency
Oral aminoglycosides may decrease absorption
and blood levels of concurrent oral MTX;
charcoal lowers levels; coadministration with
etretinate may increase hepatotoxicity; folic acid
or its derivatives contained in some vitamins may
Interactions
decrease response; probenecid, NSAIDs,
salicylates, procarbazine, and sulfonamides,
including TMP-SMZ, can increase plasma levels;
may decrease phenytoin plasma levels; may
increase plasma levels of thiopurines
Pregnancy D - Unsafe in pregnancy
Monitor CBC counts monthly and liver and renal
function every 1-3 mo during therapy (monitor
more frequently during initial dosing, dose
adjustments, or when risk of elevated MTX
levels, eg, renal insufficiency, dehydration); has
toxic effects on hematologic, GI, and pulmonary
Precautions
systems; discontinue if significant drop in blood
counts occurs; fatal reactions reported when
administered concurrently with NSAIDs or in
setting of significantly impaired renal function;
folic acid supplementation (1 mg/d) may decrease
adverse GI effects
Sulfasalazine (Azulfidine, Azulfidine EN-tabs) --
Drug Name Acts locally to decrease inflammatory response
and systemically inhibits prostaglandin synthesis.
Initial: 1 g PO tid/qid
Adult Dose
Maintenance: 2 g/d PO in divided doses
<2 years: Not established
>2 years: 40-60 mg/kg/d PO in 3-6 divided doses,
Pediatric Dose
followed by maintenance dose of 20-30 mg/kg/d
divided qid
Documented hypersensitivity to sulfa drugs or
Contraindications
any component; GI or GU obstruction
Decreases effects of iron, digoxin, and folic acid;
Interactions conversely, increases effect of oral anticoagulants,
oral hypoglycemic agents, and MTX
B - Usually safe but benefits must outweigh the
Pregnancy
risks.
Precautions Caution in patients with renal or hepatic
 impairment, blood dyscrasias, or urinary
obstruction; adverse effects include anorexia,
nausea/vomiting, diarrhea (enteric-coated tabs
may reduce adverse GI effects), photosensitivity,
headache, dizziness, urticaria/pruritus, hemolytic
anemia, interstitial nephritis, acute nephropathy,
hematuria, cirrhosis, jaundice, and hepatic
necrosis (rare)
Etanercept (Enbrel) -- Soluble p75 TNF receptor
fusion protein (sTNFR-Ig). Inhibits TNF binding
Drug Name
to cell surface receptors, which, in turn, decreases
inflammatory and immune responses.
25 mg SC twice weekly with or without
Adult Dose
concomitant administration of MTX
Pediatric Dose Administer as in adults
Documented hypersensitivity, sepsis, concurrent
Contraindications
live vaccination
Interactions None reported
B - Usually safe but benefits must outweigh the
Pregnancy
risks.
Caution in impaired renal function and asthma;
discontinue administration if serious infection
develops; adverse effects may include injection
Precautions
site pain, localized erythema, rash, URI
symptomology, GI upset, nausea, vomiting,
rhinitis, cough, and drug-induced lupus
Infliximab (Remicade) -- Chimeric IgG1k
monoclonal antibody that neutralizes cytokine
TNF-alpha and inhibits its binding to TNF-alpha
Drug Name receptor. Reduces infiltration of inflammatory
cells and TNF-alpha production in inflamed areas.
Used with MTX in patients who have inadequate
response to MTX monotherapy.
3 mg/kg IV at weeks 0, 2, and 6; then q4-8wk,
Adult Dose usually with MTX; some patients require higher
doses (4-5 mg/kg)
Pediatric Dose Not established
Contraindications Documented hypersensitivity
Interactions None reported
C - Safety for use during pregnancy has not been
Pregnancy
established.
TNF-alpha modulates cellular immune responses;
anti–TNF therapies, such as infliximab, may
adversely affect normal immune responses and
Precautions
allow development of superinfections; may
increase risk of reactivation of TB in patients with
certain granulomatous infections; PPD-positive
 patients require TB prophylaxis; may cause anti-
DNA antibodies and drug-induced lupus
Adalimumab (HUMIRA) -- Recombinant human
IgG1 monoclonal antibody specific for human
TNF. Indicated to reduce inflammation and
inhibit progression of structural damage in
moderate-to-severe rheumatoid arthritis. Reserved
Drug Name
for those who experience inadequate response to
one or more DMARDs. It can be used alone or in
combination with MTX or other DMARDs. Binds
specifically to TNF-alpha and blocks interaction
with p55 and p75 cell-surface TNF receptors.
40 mg SC q2wk; may increase to 40 mg SC qwk
Adult Dose
in some patients not taking concomitant MTX
Pediatric Dose Not established
Contraindications Documented hypersensitivity; active infection
May interfere with immune response to live virus
vaccine (MMR) and reduce efficacy; MTX
Interactions
decreases clearance (available data do not support
adjusting dose of either HUMIRA or MTX)
B - Usually safe but benefits must outweigh the
Pregnancy
risks.
Causes immunosuppression; may reactivate
tuberculosis infection; increases risk for
lymphoma development; associated with CNS
Precautions
demyelination (rare); discontinue if serious
infection develops; autoantibody development
may occur, causing lupuslike syndrome
Drug Category: Nonsteroidal anti-inflammatory drugs -- Interfere with prostaglandin synthesis
through inhibition of the COX enzyme, thus reducing swelling and pain. However, they do not
retard joint destruction and alone are not sufficient to treat RA. As with glucocorticoids, dose can
be reduced or drug discontinued with successful DMARD therapy.
Several dozen NSAIDs are available, which can be classified into different groups of
compounds. Commonly used NSAIDs include ibuprofen, naproxen, ketoprofen, piroxicam, and
diclofenac.
Selective COX-2 inhibitors may be considered for patients at risk for GI bleed.
Ibuprofen, ketoprofen, naproxen, piroxicam,
diclofenac -- Ibuprofen (Motrin, Advil),
ketoprofen (Oruvail), naproxen (Naprosyn),
Drug Name piroxicam (Feldene), and diclofenac (Voltaren,
Cataflam) are DOC for patients with mild to
moderate pain. Inhibits inflammatory reactions
and pain by decreasing prostaglandin synthesis.
Ibuprofen: 200-400 mg PO q4-6h while
symptoms persist; not to exceed 3.2 g/d
Adult Dose Ketoprofen: 25-50 mg PO q6-8h prn; not to
exceed 300 mg/d
Naproxen: 250-500 mg PO bid; may increase to
 1.5 g/d for limited periods
Piroxicam: 10-20 mg/d PO qd
Diclofenac: Up to 100 mg hs may help relieve
persistent night pain or morning stiffness; not to
exceed total daily dose of 200 mg
Ibuprofen
6 months to 12 years: 4-10 mg/kg/dose PO tid/qid
>12 years: Administer as in adults
Ketoprofen
3 months to 12 years: 0.1-1 mg/kg PO q6-8h
>12 years: Administer as in adults
Naproxen
Pediatric Dose <2 years: Not established
>2 years: 2.5 mg/kg/dose PO; not to exceed 10
mg/kg/d
Piroxicam
0.2-0.3 mg/kg/d PO qd; not to exceed 15 mg/d
Diclofenac
<12 years: Not established
>12 years: Administer as in adults
Documented hypersensitivity; peptic ulcer
Contraindications disease, recent GI bleeding or perforation, renal
insufficiency, or high risk of bleeding
Administration with aspirin increases risk of
inducing serious NSAID-related adverse effects;
probenecid may increase concentrations and,
possibly, toxicity; may decrease effect of
hydralazine, captopril, and beta-blockers; may
Interactions decrease diuretic effects of furosemide and
thiazides; may increase PT when taking
anticoagulants (instruct patients to watch for signs
of bleeding); may increase risk of MTX toxicity;
phenytoin levels may be increased when
administered concurrently
B - Usually safe but benefits must outweigh the
Pregnancy
risks.
Category D in third trimester of pregnancy;
caution in congestive heart failure, hypertension,
Precautions and decreased renal and hepatic function; caution
in coagulation abnormalities or during
anticoagulant therapy
Rofecoxib (Vioxx) -- On September 30, 2004,
Merck & Co, Inc, announced a voluntary
withdrawal of rofecoxib (Vioxx) from the US
and worldwide market because of its
Drug Name association with an increased rate of
cardiovascular events (including heart attacks
and strokes) compared to that of placebo.
Primarily inhibits COX-2. COX-2 is considered
an inducible isoenzyme, induced during pain and
 inflammatory stimuli. Inhibition of COX-1 may
contribute to NSAID GI toxicity. At therapeutic
concentrations, COX-1 isoenzyme is not
inhibited, thus GI toxicity may be decreased. Seek
lowest dose for each patient. Suspension dose,
12.5 mg/5 mL or 25 mg/5 mL, may be substituted
for 12.5- or 25-mg tabs, respectively.
50 mg PO qd; subsequent doses are 50 mg qd prn;
use for >5 d in management of pain not
Adult Dose
established; tabs may be taken with or without
food
Pediatric Dose Not established
Contraindications Documented hypersensitivity
Coadministration with fluconazole may cause
increase in rofecoxib plasma concentrations
Interactions because of inhibition of rofecoxib metabolism;
coadministration with rifampin may decrease
rofecoxib plasma concentrations
B - Usually safe but benefits must outweigh the
Pregnancy
risks.
May cause fluid retention and peripheral edema;
caution in compromised cardiac function,
hypertension, and conditions predisposing to fluid
retention; caution in severe heart failure and
hyponatremia because may deteriorate circulatory
hemodynamics; NSAIDs may mask usual signs of
infection; caution in the presence of existing
controlled infections; evaluate therapy when
symptoms or lab results suggest liver dysfunction
Alert: On September 30, 2004, Merck & Co,
Inc, announced a voluntary withdrawal of
rofecoxib (Vioxx) from the US and worldwide
market because of its association with an
increased rate of cardiovascular events
(including heart attacks and strokes) compared
Precautions
to that of placebo. A major FDA study of
rofecoxib found an apparent 3-fold increase in the
risk of sudden cardiac death or heart attack among
patients who had taken higher doses of the drug
compared to the risk of patients who had not
recently received similar medication. The report
showed that even patients taking the standard
starting dose of 12.5 mg or 25 mg of rofecoxib
had a 50% greater chance of heart attack or
sudden cardiac death than patients on any dose of
celecoxib (Celebrex). The large-scale study was
conducted after analyzing the medical records of
1.4 million people insured by Kaiser Permanente
in Oakland, Calif, between 1999-2001. Note: The
study has inherent limitations in that it is
 observational, rather than randomized and
controlled.
Celecoxib (Celebrex) -- Primarily inhibits COX-
2. COX-2 is considered an inducible isoenzyme,
induced during pain and inflammatory stimuli.
Drug Name Inhibition of COX-1 may contribute to NSAID GI
toxicity. At therapeutic concentrations, COX-1
isoenzyme is not inhibited, thus GI toxicity may
be decreased. Seek lowest dose for each patient.
Adult Dose 200 mg/d PO qd; alternatively, 100 mg PO bid
Pediatric Dose Not established
Contraindications Documented hypersensitivity
Coadministration with fluconazole may cause
increase in celecoxib plasma concentrations
Interactions because of inhibition of celecoxib metabolism;
coadministration with rifampin may decrease
celecoxib plasma concentrations
B - Usually safe but benefits must outweigh the
Pregnancy
risks.
Category D in third trimester of pregnancy; may
cause fluid retention and peripheral edema;
caution in compromised cardiac function,
hypertension, and conditions predisposing to fluid
retention; caution in severe heart failure and
Precautions
hyponatremia because may deteriorate circulatory
hemodynamics; NSAIDs may mask usual signs of
infection; caution in the presence of existing
controlled infections; evaluate therapy when
symptoms or lab results suggest liver dysfunction
Valdecoxib (Bextra) -- Alert: On April 7, 2005,
valdecoxib (Bextra, by Pfizer, Inc) was
voluntarily withdrawn from the US market,
pending further discussion with the US Food
and Drug Administration (FDA). The
association of valdecoxib with potentially life-
threatening risks, including myocardial
infarction, stroke, and serious skin reactions,
initiated an investigation to determine whether
Drug Name
the benefits of the drug outweighed the risks.
Second-generation COX-2 inhibitor that offers a
very rapid onset and prolonged efficacy. Primarily
inhibits COX-2. COX-2 is considered an
inducible isoenzyme, induced during pain and
inflammatory stimuli. Inhibition of COX-1 may
contribute to NSAID GI toxicity. At therapeutic
concentrations, does not inhibit COX-1
isoenzyme, thus decreasing GI toxicity.
Adult Dose 10 mg PO qd
Pediatric Dose Not established
Contraindications Documented hypersensitivity
Coadministration with fluconazole may cause
increase in plasma concentrations;
Interactions
coadministration of with rifampin may decrease
valdecoxib plasma concentrations
B - Usually safe but benefits must outweigh the
Pregnancy
risks.
Category D in third trimester of pregnancy;
abdominal pain, nausea, and diarrhea may occur;
caution in compromised cardiac function,
hypertension, and conditions predisposing to fluid
retention; caution in severe heart failure and
hyponatremia because may deteriorate circulatory
hemodynamics; NSAIDs may mask usual signs of
infection; caution in presence of existing
controlled infections; evaluate therapy when
symptoms or lab results suggest liver dysfunction
Alert: On April 7, 2005, valdecoxib (Bextra, by
Pfizer, Inc) was voluntarily withdrawn from
the US market, pending further discussion
with the US Food and Drug Administration
(FDA). The association of valdecoxib with
potentially life-threatening risks, including
myocardial infarction, stroke, and serious skin
reactions, initiated an investigation to
determine whether the benefits of the drug
outweighed the risks. In 2004, the FDA had
Pfizer add a boxed, bolded warning to the
Precautions prescribing information to alert health care
professionals and patients about the serious
adverse effects.
Serious, potentially fatal skin reactions, including
Stevens-Johnson syndrome and toxic epidermal
necrolysis, may occur. These reactions are most
likely to happen in the first 2 weeks of treatment,
but they can occur any time during therapy.
Valdecoxib should be discontinued at the first
sign of rash, mouth sores, and/or allergic reaction
(eg, swelling, itching, shortness of breath). Other
COX-2 inhibitors (eg, rofecoxib [Vioxx],
celecoxib [Celebrex]) and traditional NSAIDs
(eg, naproxen [Aleve, Naprosyn], ibuprofen
[Motrin]) also have a risk for these rare, serious
skin reactions, but the reported rate of the
reactions appears to be greater for valdecoxib.
New data regarding cardiovascular risks are also
highlighted, including data from more than 1500
patients treated after CABG. The patients treated
with valdecoxib showed an increased
cardiovascular risk compared to those treated with
 placebos. Observed cardiovascular events
included myocardial infarction, cerebrovascular
accident, deep vein thrombosis, and pulmonary
embolism.
Pfizer submitted the final report of the new
CABG study to the FDA on November 5, 2004.
The report confirms the risk of the intravenous
form (~2% of patients experienced adverse
cardiovascular events) and also shows that oral
valdecoxib is associated with a lower risk (~1% of
patients) immediately following CABG surgery.
In the placebo group, about 0.5% of patients had
an adverse cardiovascular event.
Drug Category: Analgesics -- Acetaminophen/paracetamol, tramadol, codeine, opiates, and a
variety of other analgesic medications can be employed to reduce pain. Do not affect swelling or
joint destruction.
Acetaminophen (Tylenol, Feverall, Tempra) --
DOC for pain in patients with documented
Drug Name
hypersensitivity to aspirin or NSAIDs, with upper
GI disease, or who are taking oral anticoagulants.
325-650 mg PO q4-6h or 1000 mg tid/qid; not to
Adult Dose
exceed 4 g/d
<12 years: 10-15 mg/kg/dose PO q4-6h prn; not
to exceed 2.6 g/d
Pediatric Dose
>12 years: 325-650 mg PO q4h; not to exceed 5
doses in 24 h
Documented hypersensitivity; known G-6-PD
Contraindications
deficiency
Rifampin can reduce analgesic effects;
coadministration with barbiturates,
Interactions
carbamazepine, hydantoins, and isoniazid may
increase hepatotoxicity
B - Usually safe but benefits must outweigh the
Pregnancy
risks.
Hepatotoxicity possible in persons with chronic
alcoholism following various dose levels; severe
or recurrent pain or high or continued fever may
Precautions indicate serious illness; contained in many OTC
products, and combined use with these products
may result in cumulative doses exceeding
recommended maximum dose
Tramadol (Ultram) -- Inhibits ascending pain
pathways, altering perception of and response to
Drug Name
pain. Also inhibits reuptake of norepinephrine and
serotonin.
Adult Dose 50-100 mg PO q4-6h; not to exceed 400 mg/d
Pediatric Dose Not established
Contraindications Documented hypersensitivity; opioid-
 dependency; concurrent use of MAOIs or within
14 d; use of SSRIs, TCAs, or opioids or acute
alcohol intoxication
Decreases carbamazepine effects significantly;
cimetidine increases toxicity, risk of serotonin
Interactions
syndrome with coadministration of
antidepressants
C - Safety for use during pregnancy has not been
Pregnancy
established.
Can cause dizziness, nausea, constipation,
sweating, or pruritus; additive sedation with
alcohol and TCAs; abrupt discontinuation can
precipitate opioid withdrawal symptoms; adjust
Precautions
dose in liver disease, myxedema, hypothyroidism,
or hypoadrenalism; pregnancy and breastfeeding;
seizure; development of tolerance or dependency
with extended use
Drug Category: New biologic agents
Anakinra (Kineret) -- Competitively and
selectively inhibits IL-1 binding to type I receptor
(IL-1RI). IL-1 is found in excess in patients with
RA and is produced in response to inflammatory
Drug Name stimuli. By blocking IL-1 binding, inflammation
and pain associated with RA are inhibited.
Indicated for RA in patients in whom one or more
DMARDs have failed. Should be administered at
approximately the same time every day.
Adult Dose 100 mg SC qd
Pediatric Dose Not established
Documented hypersensitivity to product or
Contraindications Escherichia coli–derived products; active
infections
None reported; higher rate of serious infections
and neutropenia possible when coadministered
Interactions with TNF blocking agents (eg, etanercept,
infliximab); may decrease response to live virus
vaccines
B - Usually safe but benefits must outweigh the
Pregnancy
risks.
Serious infections may occur (discontinue
treatment if serious infection develops);
neutropenia may occur (especially if administered
Precautions
concomitantly with TNF blocking agents); most
common adverse effect is local reaction at site of
injection; caution in breastfeeding
Drug Category: Glucocorticoids -- Potent anti-inflammatory drugs commonly used in patients
with RA to bridge the time until DMARDs are effective. Doses of up to 10 mg/d of prednisone
are typically used, but some patients may require higher doses. Adverse events associated with
long-term steroid use make dose reductions and cessation important in due course.
Prednisone (Deltasone, Meticorten, Orasone) --
Immunosuppressant for treatment of autoimmune
disorders; may decrease inflammation by
Drug Name reversing increased capillary permeability and
suppressing PMN activity. Stabilizes lysosomal
membranes and also suppresses lymphocytes and
antibody production.
10-60 mg/d PO qd or divided bid/qid; generally,
maintenance dose should be <10 mg/d;
Adult Dose
alternatively, may be given IM, IV, or intra-
articularly
Pediatric Dose Not established
Documented hypersensitivity; viral infection,
peptic ulcer disease, hepatic dysfunction,
Contraindications
connective tissue infections, and fungal or
tubercular skin infections; GI ulceration
Coadministration with estrogens may decrease
clearance; concurrent use with digoxin may cause
digitalis toxicity secondary to hypokalemia;
Interactions phenobarbital, phenytoin, and rifampin may
increase metabolism of glucocorticoids (consider
increasing maintenance dose); monitor for
hypokalemia with coadministration of diuretics
B - Usually safe but benefits must outweigh the
Pregnancy
risks.
Hyperglycemia, edema, osteonecrosis, myopathy,
peptic ulcer disease, hypokalemia, osteoporosis,
Precautions euphoria, psychosis, growth suppression, and
infections may occur with glucocorticoid use;
abrupt discontinuation may cause adrenal crisis
Deterrence/Prevention:
 RA is a progressive inflammatory disease historically treated according to a pyramid or
sequential strategy, beginning with NSAID therapy.
o Early use of DMARDs has traditionally been avoided until patients show signs of
joint damage; however, this strategy has proved ineffective over several years.
Patients experience poor long-term outcomes, including severe functional
declines, radiographic progression of disease, work disability, and premature
mortality.
o The current approach to management emphasizes aggressive control of
inflammation to prevent long-term damage using early DMARD therapy
including use of single or combination DMARDs.
 Two issues appear to be sources of confusion regarding long-term outcomes of treatment.
o First, a small percentage of patients who meet diagnostic criteria for RA have a
self-limited process with spontaneous remission. Thus, in the absence of signs of
progression, some patients are diagnosed with, and subsequently treated for, other
conditions.
o Second, measures of inflammatory activity, such as joint swelling or ESRs, are
often used to assess inflammatory activity. However, these indices are less useful
 end points for evaluation than severe long-term outcomes such as work disability
or joint deformity and radiographic changes, in which the latter two are
irreversible. During a period in which inflammatory markers may be stable or
even improved, radiographic progression and functional decline can occur.
 Traditional DMARDs, such as injectable gold salts and penicillamine, rarely induce
sustained remission and are usually discontinued within 2 years.
 Newer DMARDs, such as MTX and SSZ, have greater long-term effectiveness but still
rarely induce true remission.
 Optimal control may require combination therapy. Recent studies have shown that MTX
combined with other DMARDs is more effective and has acceptable toxicity when
compared with use of a single agent. In combination with cyclosporine, MTX results in
greater clinical improvement than MTX alone. Triple therapy with MTX, SSZ, and
hydroxychloroquine provides substantially greater clinical improvement than MTX alone
or SSZ plus hydroxychloroquine. In combination with infliximab, MTX provides a
superior response to monotherapy. In combination with etanercept, MTX provides a
higher rate of meaningful clinical response. Toxicities of these drug combinations are
rarely more significant than those occurring with any of the individual agents used alone.
 The goal of contemporary management of RA should be complete remission or no
evidence of disease activity.
o Achieving this goal likely requires ongoing drug therapy, probably using a
combination of MTX with some other DMARD, although some patients may still
respond satisfactorily to monotherapy.
o More long-term studies are needed to evaluate potential important adverse effects
associated with combination therapy before definite recommendations can be
made.
Complications:
 RA is not fatal, but complications of the disease may shorten survival by a few years in
some individuals. Although generally RA is progressive and cannot be cured, the disease
gradually becomes less aggressive and symptoms may even improve. However, if bone
and ligament destruction and any deformities have occurred, the effects are permanent.
 Joint disability and pain with daily life are common. Affected joints can become
deformed, and the performance of even ordinary tasks may be very difficult or
impossible. According to one survey, 70% of patients with RA believe the disease
prevents them from living a fully productive life. A 2000 study in England found that
approximately one third of individuals stop working within 5 years of the onset of
disease.
 RA is a systemic disease that can affect other parts of the body in addition to joints.
These effects include the following:
o Peripheral neuropathy: This condition affects nerves, most often those in the
hands and feet. It can result in tingling, numbness, or burning.
o Anemia
o Scleritis: This is an inflammation of the blood vessels in the eye that can result in
corneal damage, scleromalacia, and, in severe cases of nodular scleritis,
perforation.
o Infections: Patients with RA have a higher risk for infections, particularly from
some of the immunosuppressive drugs required for treatment.
o GI problems: Although patients may experience stomach and intestinal distress, a
2000 study reported lower rates of stomach and colorectal cancers among patients
with RA.
o Osteoporosis: Osteoporosis is more common than average in postmenopausal
women with RA. The hip is particularly affected. The risk for osteoporosis also
appears to be higher than average in men with RA who are older than 60 years.
 o Lung disease: One small study found a very high prevalence of lung disease
(pulmonary inflammation and fibrosis) in patients newly diagnosed with RA.
However, the association between a history of smoking and a higher risk for RA
may at least partially account for this finding. Cigarette smoking, in any case,
may increase the severity of the disease.
o Heart disease: RA can affect the blood vessels and possibly increase the risk for
coronary ischemic heart disease.
o Sjögren syndrome: Keratoconjunctivitis sicca is a common complication of RA.
Oral sicca and salivary gland enlargement are less common.
o Felty syndrome: The combination of splenomegaly, leukopenia (neutropenia), and
recurrent bacterial infections, this syndrome sometimes responds to DMARD
therapy.
o Lymphoma and other cancers: Alterations in the immune system associated with
RA may play a role in the higher risk for lymphoma observed in patients with
RA. Aggressive treatments for RA that suppress the immune system may help
prevent this cancer, but more research is needed to evaluate this possibility. Other
cancers that may occur with increased frequency in patients with RA include
prostate and lung cancers.
o Macrophage activation syndrome: This is a life-threatening complication of RA
and requires immediate treatment with high-dose steroids and cyclosporin A.
Patients should be aware of symptoms, which include persistent fever, weakness,
drowsiness, and lethargy.
Prognosis:
 The clinical course is generally one of exacerbations and remissions. Approximately 40%
of patients become disabled after 10 years, but outcomes are highly variable. Some
patients experience a relatively self-limited disease, and others have a chronic
progressive illness.
 Improvements in the detection of early joint injury have provided a previously
unappreciated view of the ubiquity and importance of early joint damage. Nonetheless,
predicting the course of an individual case at the outset remains difficult, although the
HLA-DRB1*04/04 genotype, a high serum titer of RF, extra-articular manifestations, a
large number of involved joints, age younger than 30 years, female sex, and systemic
symptoms all correlate with an unfavorable prognosis with joint damage and disability.
Insidious onset is also an unfavorable sign.
 Disease that remains persistently active for more than a year is likely to lead to joint
deformities and disability. Cases in which periods of activity lasting only weeks or a few
months are followed by spontaneous remission have a better prognosis.
 The absence of RF does not necessarily portend a good prognosis. Outcome is
compromised when diagnosis and treatment are delayed. Other laboratory markers of a
poor prognosis include early radiologic evidence of bony injury, persistent anemia of
chronic disease, and elevated levels of the C1q component of complement.
 The overall mortality rate for patients with RA is reportedly 2.5 times that of the general
population. In those with severe articular and extra-articular disease, the mortality rate
approaches that of patients with 3-vessel coronary disease or stage IV Hodgkin disease.
Much of the excess mortality derives from infection, vasculitis, and poor nutrition.
Mortality from cancer is unchanged.
 Most data on rates of disability derive from specialty units caring for referred patients
with severe disease. Little information is available on patients cared for in primary care
community settings. Estimates suggest that more than half of these patients remain fully
employed, even after 10-15 years of disease, with a third having only intermittent low-
grade disease and another third experiencing spontaneous remission.
Patient Education:
 Patient education and counseling are well worth the time invested because they help to
reduce pain, disability, and frequency of physician visits. They represent the most cost-
effective intervention.
 Informing the patient of the diagnosis
o With a potentially disabling disease such as RA, the act of informing the patient
of the diagnosis takes on major importance. The goal is to satisfy the patient's
informational needs regarding the diagnosis, prognosis, and treatment without
going into an overwhelming and excessive amount of detail. Careful questioning
and empathic listening are required to understand the patient's perspective,
requests, and fears.
o Telling patients more than they are intellectually or psychologically prepared to
handle (a common practice) risks making the experience so intense as to trigger
withdrawal. Conversely, failing to address issues of importance to the patient
compromises the development of trust. The patient needs to know that the
primary physician understands the situation and is available for support, advice,
and therapy as the need arises. Encouraging the patient to ask questions helps to
communicate interest and caring.
 Discussing prognosis and treatment
o Patients and families do best when they know what to expect and can view the
illness realistically. Uncertainty greatly contributes to the disease of RA. Many
patients fear crippling consequences and dependency.
o The most common disease manifestations should be described. Without building
false hopes, the physician can point out that spontaneous remissions can occur
and that more than two thirds of patients live independently without major
disability. In addition, emphasize that much can be done to minimize discomfort
and to preserve function. A review of available therapies and their efficacy helps
to overcome feelings of depression stemming from an erroneous expectation of
inevitable disability.
o Even in patients with severe disease, guarded optimism is now appropriate, given
the host of effective and well-tolerated disease-modifying treatments that are
emerging.
o Abandonment is a major fear. Patients are relieved to know that they will be
closely observed by the primary physician and health care team, working in
conjunction with a consulting rheumatologist and physical/occupational therapist,
all of whom are committed to maximizing the patient's comfort and independence
and to preserving joint function.
 Dealing with misconceptions
o Several common misconceptions deserve attention. A substantial proportion of
patients and their families feel that they have done something to cause the illness.
Explaining that no known controllable precipitants exist helps to eliminate much
unnecessary guilt and self-recrimination.
o Dealing in an informative, evidence-based fashion with a patient who expresses
interest in alternative and complementary forms of therapy can help limit
expenditures on ineffective treatments.
o Another misconception is that a medication must be expensive to be helpful.
Aspirin, generic NSAIDs, low-dose prednisone, and the first-line disease-
modifying agents are quite inexpensive, yet remarkably effective, a point that
bears emphasizing. The sense that one must be treated with a COX-2 NSAID or
the latest TNF inactivator can be addressed by a careful review of the overall
treatment program and the proper role of such agents in the patient's plan of care.
 o The active participation of the patient and family in the design and
implementation of the therapeutic program helps to boost morale and ensure
compliance, as does explaining the rationale for the therapies used.
 Preserving a sense of self-worth
o A major goal is to preserve the patient's sense of worth and independence.
However, when fatigue, morning stiffness, or specific joint disease interferes with
a patient's capacity to carry out the usual responsibilities at work and at home,
counseling will be necessary to recommend modification of work responsibilities
and perhaps retraining. Recognition and treatment of concomitant depression is
important.
o With the use of occupational therapy, the treatment effort is geared to helping the
patient maintain a meaningful work role within the limitations of the illness.
o The family plays an important part in striking the proper balance between
dependence and independence. Household members should avoid overprotecting
the patient (eg, refraining from intercourse out of fear of hurting the patient) and
should work to sustain the patient's pride and ability to contribute to the family.
Allowing the patient with RA to struggle with a task is sometimes constructive.
 Supporting the patient with debilitating disease
o Persons with long-standing severe disease who have already sustained much
irreversible joint destruction benefit from an emphasis on comfort measures,
supportive counseling, and attention to minimizing further debility. Such patients
need help in grieving for their disfigurement and loss of function.
o An accepting, unhurried, empathic manner allows the patient to express feelings.
The seemingly insignificant act of touching does much to restore a sense of self-
acceptance. Attending to pain with increased social support, medication, and a
refocusing of attention to function are useful. A trusting and strong patient-doctor
relationship can do much to sustain a patient through times of discomfort and
disability.

Discoid lupus erythematosus (DLE)

is a chronic inflammatory condition ofthe [Link] lesions begin aswell-demarcated
erythematous macules or papules with a scaly surface, and frequently evolve into larger coin-
shaped plaques. In most DLE patients the condition remains confined to the skin; antinuclear
antibodies (ANA) are often negative or present in a low titre. Approximately 5% to 10% of
patients may develop a mild form of systemic lupus erythematosus (SLE).[2] DLE-like lesions
occur in up to 25% of patients with SLE
Pathophysiology The precise pathophysiology ofDLE and otherforms of cutaneous lupus
erythematosus (CLE) is not yetfully understood. Interest has been concentrated on the region of
the dermal-epidermal junction as the principal site of injury, because ofthe detection of IgG and
C3 along the epidermal basement membrane, suggesting an immune-mediated process. The
inflammatory cells in DLE are mostly T cells in the dermis. Chronic scarring DLE lesions have a
denser inflammatory cell infiltrate, which extends into the deeper reticular dermis and/or
subcutis, in contrast with acute CLE and subacute CLE lesions, which contain less dense
inflammatory infiltrates confined to the upper dermis. It has been suggested that keratinocyte
apoptosis may be the key event in the initiation of CLE lesions. The nucleated layer of the
epidermis is generally not thickened and may be atrophic. There is prominent hyperkeratosis and
follicular plugging.
Key diagnostic factors
1. disc-shaped erythematous maculopapular scaly lesions (common) • DLE lesions typically
present on the face, neck, scalp, ears, and extensor surfaces of arms. • The lesions usually
begin as flat or slightly elevated, well-demarcated, erythematous macules or papules with a
scaly surface. • These lesions commonly become larger and coalesce, leading to
 erythematous plaques with prominent, adherent scales extending into dilated hair follicles.
2. age 10 to 40 years (common) • The most common age of onset
3. hx of UV light exposure (common). Can precipitate or aggravate DLE lesions, especially
UV-B light exposure.
Other diagnostic factors
1. absence of pruritus and/or pain (common) • Characteristically, the lesions are neither painful
nor pruritic, but some patients may experience occasional pain within the lesion and/or mild
pruritus.
2. telangiectasia, hyperpigmentation and/or hypopigmentation (common) • Over time, the
lesions slowly expand, producing areas of peripheral inflammation or hyperpigmentation,
leaving a central region of scarring with telangiectasia and hypopigmentation. •
Hyperpigmentation is a late sign and usually post-inflammatory in white skin.
Hypopigmentation may be post-inflammatory or a sign of scarring.
3. permanent scarring alopecia (common) • If left untreated, DLE scalp lesions inevitably result
in alopecia, which becomes permanent once scarring occurs
4. systemic features (arthritis, pleuritis, pericarditis, seizures, psychosis) (uncommon) •
Approximately 5% to 10% of patients develop a mild form of systemic lupus erythematosus
(SLE). Therefore, a complete physical examination should be performed to look for signs
suggestive of underlying systemic disease, such as arthritis, serositis (pleuritis, pericarditis),
central nervous system involvement (seizures, psychosis), or renal involvement. • DLE is
considered to have progressed to SLE if systemic features are present and the patient has ≥4
of the 11 criteria required to make the diagnosis. However, if the patient does not meet
diagnostic criteria for SLE, a diagnosis of undifferentiated connective tissue disease is made.
LE treatment details
 5. Methods of organization of educational process on the lesson

Basic stages of lesson, Educational Methods of Materials of the Time

their function and aims during control and methodical providing ( (min)
maintenance. the levels of studies control, instructions
mastering
1 2 3 4 5
1. Preparatory stage: See pt.1 ”Actuality of
Organization of theme”; 20 min.
employment See pt. the ”Concrete
Raising of educational aims”
aims II Interview.
Control of initial level Individual Questions for the
of knowledge questioning. individual questioning.
Test control.
Tests.

2. Basic stage Practical Curation of thematic

Forming of the system III professional patients. 130 min.
of professional abilities training for the Case histories. Case
and skills. decision of records.
Table of contents - See various (typical Archival case histories.
pt. the ”Concrete aims” and offtype) Situational tasks.
clinical tasks .

[Link] stage Individual Tests

Control and correction III control of Situational tasks 30 min
of level of professional practical skills
skills and abilities and
Working out the totals professional
of lesson abilities of
A home task with the students.
list of thematic Analysis of
educational literature typical
(basic, additional) mistakes.
Test control.

6. Additions. Control of knowledge

Questions
[Link] and epidemiology of JRA in children
[Link] pathogenic mechanisms in JRA and RA in children
3. Classification of JRA and RA
4. Clinical presentation of JRA and RA
5. Differential-diagnostic approach in JRA , RA, LE
6. Diagnostic methods in JRA and RA, LE.
7. Indications for X-ray diagnostics in articular disorders
8. Define X-ray signs and symptoms of JRA. RA
9. Treatment of JRA and RA, LE
10. Prevention of JRA and RA.

Tasks
Task 1
In 8 years old febrile fever, macular rash all over the trunk and limbs has appeared. He
complains on phalangial joints in wrists and feet edema with morning stiffness in these joints.
Doctor diagnoses besides these signs exudative pericarditis, lymphadenopathy,
hepatospleenmegaly.
Propose your priliminary diagnosis
What is your examining plan?
Prescribe treatment and propose preventive measures
Answer:
- Juvenile rherumatoid arthritis
- Blood test, urine test, ANA, liver tests, acute phase reactants, RF,
creatinephosphokinase, lactatedihydrogenase, circulated immune complexes, X—
ray, ECG, Echo-CG
- NSAIDs, ( diclofenac, prednisone, methotrexate)

Task 2
A 3-year-old girl presents with stiffness and limp of several weeks' duration. The onset was
insidious and her parents do not recall any specific injury or prior infections. Her parents
mention that one of her knees is swollen and cannot be straightened, although it is not especially
painful. Her symptoms are particularly bad in the mornings when she wakes, but her
gaitimproves as the day goes on. She has not had any fevers,rashes, or other constitutional
symptoms.
Propose your priliminary diagnosis
What is your examining plan?
Prescribe treatment and propose preventive measures

Task 3
Fill in Differential-diagnostic table for articular diaeases
Symptoms Diseases
JRA Subsepsis ARF RA
Vissler-Fanconi
Acute onset
Constant articular
syndrome
Morning stiffness
Arthritis of 3 and
more joints
Wrist joints
affection
Symmetrical
arthritis
Rheumatoid nodes
Hyperthermia
Rash
Uveitis
Visceral
involvement
Hepatospleenmegaly
RF
Muscle atrophy
X-ray changes
Blood test changes
ANA

TESTS. Primary control.

1. Rheumatoid arthritis peak morbidity is in the age
A. 8 mo old
B. 2 years old
C. 5 years old
D. 10 years old
E. 16 years old
2. Main changes in JRA are
A. pathologic immune response
B. pseudoallergic reactions
C. allergic mechanisms
D. infectious process
E. trauma
3. JRA peculiar feature is,except:
A. pain
B. edema
C. morning stiffness
D. mono and olygoarthritic damages
E. arthritis damage assymmetry
4. JRA is chronic inflammatory disease with more frquent onset in:
A. infant period
B. less than 2 y old
C. less than 5 y old
D. less than 10 y old
E. less than 16 y old
5. What symptoms are not typical for polyarticular form of JRA:
A. affection of wrist and feet small joints with predominance of prolifirative
processes
B. lab data show low activity
C. 1/3 of patients has affection of column and neck spondylus
D. Frequent involvement of mandibular joint
E. Frequent onset with knee joints affection
6. What symptoms are typical for extraarticular affection in JRA
A. uveitis
B. heart and vessels affection
C. skin and reticularendothelial system affection
D. inner organs amiloidosis
E. all listed above
[Link] symptoms are typical for chronic uveitis in JRA, except
A. iridicyclite, catharact, linear cornea dystrophy
B. In 60%-70% eyes involvement is bilateral
C. has asymptomatic course, diagnosed only by split lamp
 D. in 1/5 of children can be developed before articular syndrome
[Link]’t cause blindness
8. What specialists must examine every patient with JRA,except
A. traumatologist
B. cardiologist
C. gastroenterologist
D. ophthalmologist
E. neurologist
9. What index is the most indicative for JRA
A. rheumatoid factor
B. antinuclear factor
C. LE-cells
D. all listed above
E. rheumatoid factor +ANA
[Link] signs are typical for articular- visceral form of JRA,except
A. fever
B. rash
C. lymphadenopathy and hepatolienal syndrome
D. arthralgia
E. hypertension

TESTS. Final control.

1. For systemic onset of JRA is typical everything, except
A. fever
B. systemic features can precede joint manifestations
C. maculopapular rash
D. negative CRP
E. Positive rheumatoid factor and antinuclear factor
2. What indexes are not typical for septic form of JRA
A. neutrophyl leucocytosis with shift to the left
B. ESR 60-70 mm/h
C. anemia, thrombocytosis
D. elevated acute reactants like CRP, sial acids, fibrinogen
E. hyperbilirubinemia
3. What radiologic signs are typical for JRA, except
A. osteoporosis
B. narrowing of interarticular space
C. abnormality of bone growth
D. Cartilage erosion
E. bone sequestration
4. What complications can be due to JRA, except
A. Joint contracture
B. growth disturbancies
C. secondary amiloidosis
D. osteoporosis
E. bleeding
5. Reactive arthritis are characterised by symptoms, except
A. affection of lower limb joints
B. symmatrical joint involvement
C. has concurrent gastrointestinal or genitourinary infection
D. can be provoked by Shigella, Chlamidia etc.
E. can progress to spondyloarthropathy
6. Choose the mainstay of drug treatment of Discoid lupus erythematosus
A. tacrolimus topical:
B. topical corticosteroids or antimalarials.
C. Penicillin
D. Skin transplantation
E. Indomethacin
7. What is the most common presentation of the Systemic lupus erythematosus (SLE,except?
A. Skin manifestations
B. Kidney affection
C. Bone marrow affection
D. Arthritis
E. Ocular lesion
8. What are the main laboratory markers of the Systemic lupus erythematosus (SLE)?
A. ESR and leucocytosis
B. High-titre ANA, anti-double-stranded DNA antibodies, and anti-ribonucleoprotein
antibodies
C. immunological disorder
D. anti-La (SS-B) antibodies
E. Anti-Ro (SS-A) antibodies
9. Continue the sentence: “Treatments for mild to moderate serositis or arthritis in patients with
Systemic lupus erythematosus (SLE) include the next..”
A. NSAIDs, hydroxychloroquine, or systemic corticosteroids
B. topical corticosteroids or antimalarials.
C. Penicillin
D. Skin transplantation
E. Indomethacin
10. What prognosis may patients with SLE have when treatment was started in time?
A. Poor prognosis
B. High risk of sudden death
C. Prognosis depends on the severity grade
D. Treatment does not modify the prognosis
E. SLE may occasionally resolve spontaneously

Answers
Primary control:
1-B,C,D,E
2-A
3-E
4-E
5-A
6-A
7-E
8-C
9-E
10-E

Final test
1-D
2-E
3-E
4-E
5-E
6-B
7-E
8-B
9-A
10-C

7. Reference
2. Kliegman R. M., Geme J. St. Nelson Textbook of Pediatrics, 2-Volume Set, 21st Edition,
Elsevier, 2019. - 4264 p.
3. Pediatrics: textbook (IV a. l.) / T.O. Kryuchko, O.Y. Abaturov, T.V. Kushnereva et al.;
edited by T.O. Kryuchko, O.Y. Abaturov. — 2nd edition, revised = Педіатрія, 2017. – 208
p.
4. Ghai O.P. Esential Pediatrics. Eighth Edition: 2013. – 783 p.
5. Pediatrics. Textbook. / O.V. Tiazhka, T.V. Pochinok, A.N. Antoshkina et al. / edited by [Link], - Vinnytsia
: Nova Knyha Publishers, 2011 – 584 pp.
6. Piyush Gupta, V.V. Paul Essential pediatrics- Textbook for students and practitioners.- 6 Ed.- New Delhi. -
2008. - 719 p
7. Abatacept, adalimumab, etanercept andtocilizumabfortreating juvenile idiopathic arthritis,
2015: [Link]
8. International League ofAssociations forRheumatology classification ofjuvenile idiopathic
arthritis: second revision, 2004: [Link]
9. BSPAR standards of care for children and young people with juvenile idiopathic arthritis,
2010: [Link]
Standards-of-Care-for-children-and-young
10. 2013 update of the 2011 American College of Rheumatology recommendations for the
treatment of juvenile idiopathic arthritis, 2013: [Link]
Quality/Clinical-Support/Clinical-Practice-Guidelines
11. Patel P, Werth V. Cutaneous lupus erythematosus: a review. Dermatol Clin. 2002;20:378-
385.
12. Pediatrics / Edited by O.V. Tiazhka, T.V. Pochinok, A.M. Antoshkina/ - Vinnytsa: Nova
Knyha Publishers, 2011. - 584 p.
13. Nelson Textbook of Pediatrics, XX Edition. - Expert Consult Premium Edition - Enhanced
Online Features and Print / by Robert M. Kliegman, MD, Bonita M.D. Stanton, MD, Joseph
St. Geme, Nina Schor, MD, PhD and Richard E. Behrman, MD. - 2016. - 2680 p.
14. Local relevant literature:
15. Pediatrics: Manual on Faculty Pediatrics for Foreign Students/Y.V. Odynets, A.F. Ruchko,
I.N. Poddubnaya. – Kharkov: «Kruk», 2003.-224p.
16. Pediatric clinical methods/Kaushal Singh. – SAGAR PUBLICATIONS, 2006. – 333p.
17. Basic Clinical Pediatrics/Mohammed El-Naggar. – National library, 2006. – 84p.