RHEUMATOLOGY DISORDERS
General Information:
I.
Didactic Lecture:
Discussion of the common rheumatic diseases of childhood including JRA, SLE,
vasculitis, Kawasaki disease, dermato/polymyositis, scleroderma, the sero-negative
spondyloarthropathies, and arheumatic fever.
II.
References:
1.
2.
III.
Nelson: Textbook of Pediatrics
Brewer, Giannini, Person: Juvenile Rheumatoid Arthritis
Course Concepts:
The student should become:
A.
Competence (from lecture, reading, patient care) in:
1.
2.
3.
4.
5.
6.
7.
JRA
SLE
Vasculitis
Kawasaki disease
Dermato/polymyositis
Scleroderma
Seronegative spondyloarthropathies including:
a.
b.
c.
d.
e.
JAS
Reiter’s syndrome
Spondylitis in psoriasis
Spondylitis in inflammatory bowel disease
Reactive arthritis
8. Acute rheumatic fever
B.
and be Aware (reading) of:
The medical and surgical management of the rheumatic disease of childhood.
1
I.
Juvenile Rheumatoid Arthritis
A. Subtypes
1.
Pauciarticular – 4 or fewer joints (45%)
a. irirs: ANA+, young girls
b. JAS:
HLA-b27+, older boys
c. good prognosis: ANA-, HLA-B27-, HLA-DTMo+
2.
Polyarticular – 5 or more joints (25%)
a. RF+: older girls with progressive erosive disease (Classic A)
b. RF-: better prognosis
3.
Systemic (30%) - high spiking fever, rheumatoid rash, arthritis,
and multisystem disease.
Pauciarticular JRA
Children who experience pauarticular onset JRA have disease in four
or fewer joints that lasts for six or more weeks. Clinically there appear
three subtypes.
Subtype I. this subtype includes children with four or fewer involved
joints, who are girls in a ratio of 6:1 or more (girls > boys). This
subgroup is at risk for the development of iritis and a large percentage
have relatively low tittered circulating antinuclear antibodies (ANA,
i.e. < 1:500).
Subtype II. The expression of this subtype is characterized by an
older boy (boy : girl ratio 9:1) who has lower extremity arthritis or heel
pain and is HLA-B27 positive. Later these boys develop sacroilitis and
still later axial arthritis at which time a diagnosis of ankylosing
spondylitis is made. Uveitis does occur in some of these children but
less frequently than in subgroup I.
Subtype III. This third subgroup includes children with arthritis in
four or fewer joints who do not develop iritis, who are ANA and HLAB27 negative, and who have the best prognosis. As many as 60
percent have an increased frequency of an HLA antigen, termed HLADTMo.
Polyarticular JRA
Polyarticular JRA is characterized by a girl who has the insidious onset
of arthritis in five or more joints with involvement of both upper and
lower extremities. This disease is more persistent and only 25 percent
of these children are in remission five years after onset. Progressive,
erosive, destructive arthritis is more common in this and systemic JRA.
Two subtypes have been suggested for polyarticular JRA, namely:
2
Subtype I. This subtype includes older girls with severe, progressive,
erosive disease and circulating rheumatoid factor (RF). Recently these
children were found to have the HLA-DR3/HLA-Dw3, associated with
adult classic or definitive RA.
Subtype II. These children are RF negative, HLA DR3/Dw3
neagative and have less severe JRA.
Systemic JRA
The classic clinical presentation of a child with systemic JRA is a
young boy or girl with the sudden onset of spiking, intermittent fever
to 1040 – 1050 F (400C) lasting for several weeks or months. Almost
simultaneously a salmon pink, usually flat, nopruritic, evanescent rash
develops on the trunk, arms, legs, or face. Multiple joints are typically
affected with arthritis.
Extra-articular manifestations include
hepatosplenomegaly, lymphadenopathy, pericarditis, pleuritis,
peritonitis and / or mesenteric arteirtis, and occasional iritis. These
children are typically ANA, RF, and hLA-B27 negative. Abnromal
laboratory findings include: an elevated erythrocyte sedimentation
rate, leukocytosis (leukemoid reaction with WBC counts > 50,000),
thrombocytosis (platelet count > 500,000), anemia (H/H < 10/30)
sometimes Coomb’s complexes (Clq binding > 10%). After five years
only ten percent will be in complete remission and some 40 percent
will develop severe destructive joint disease with no remission in alter
years. It is in this type of JRA where all of the mortality occurs.
B.
Exclusions
A.
Other rheumatic diseases
1.
2.
3.
4.
5.
Rheumatic fever
systemic lupus erythematosus
Ankylosing spondylitis
Polymyositis and dermatomyositis
Vasculitis
a. Anaphylactoid purpura (Henoch-Schönlein)
b. Polyarteritis
c. Mucocutaneous lymph node syndrome; Kawasaki
disease; infantile polyarteritis
6. Scleroderma
7. Psoriatic arthritis
8. Reiter’s syndrome
9. Sjögren’s syndrome
10. Mixed connective tissue disease
11. Behcet’s syndrome
3
B.
Infectious arthritis
1.
2.
3.
4.
Bacterial arthritis (including tuberculosis)
Viral, fungal, and mycoplasmal arthritides
Bacteriologically sterile arthritis associated with
bacterial infections
Other
C.
Inflammatory bowel disease
D.
Neoplastic disease including leukemia
E.
Nonrheumatic conditions of bones and joints
1.
2.
3.
4.
Osteochondritis
Toxic synovitis of the hip
Slipped capital femoral epiphysis
Trauma
a. Battered child syndrome
b. Fractures
c. Joint, ligamentous, and muscular injuries
d. Congenital indifference to pain
e. Acute chondrolysis
F.
Hematologic diseases
1. Sickle cell anemia
2. Hemophilia
G.
Psychogenic arthralgia
H.
Miscellaneous
1. Immunologic abnormalities
2. Sarcoidosis
3. Hypertrophic osteoarthropathy
4. Villondular synovitis
5. Chronic active hepatitis
6. Familial Mediterranean fever
4
Classification of Juvenile Rheumatoid Arthritis
Mode of Onset
Percent
of all
JRA
Cases
Incidence
Age
Sex
Clinical Findings
Laboratory
Findings
Prognosis
Systemic
30
<10
1.5:1
F:M
Fever, rash,
polyarticular arthritis,
heart, liver, spleen,
and lympnodes
involved; iridocyclitis
seen occasionally
Anemia,
leukocytosis,
ESR elevated;
ANA rarely +;
RF -
All disease
mortality in this
group (1-2% of all
JRA patients); 40%
evidence of joint
destruction
Pauciarticular (< 5
joints)
40
<10
6:1
F:M
Lower extremity
arthritis
ANA +, ESR
Continuous – 25%;
arthritis rarely
erosive; eventual
remission 60%
Subtype I (iritis)
<10
Almost
all
females
Iritis
ANA +
HLA-DRw5 +
10% - functional.
Blindness
55% - acute
45% - chronic
Subtype 2
(HLA-B27 + 1)
<10
1:9
F:M
Heel pain, tendonitis,
SI and lumbar spine
arthritis later
No iritis or HLA-B27
+
HLA-B27 +
Juvenile ankylosis
spondylitis later
HLA-DTMo
Best outlook for
recovery
Acute or insidious
onset symmetric
arthritis, upper and
lower extremities
ESR
Mortality – 0
Duration longer,
more crippling
25% remission
Resembles adult RA
RF +
Subtype 3
(arthritis only)
Polyarticular
(>4 joints)
Subtype 1
(RF +)
Subtype 2
(RF-)
25
<10
Mostly
female
RF -
Less crippling than
RF +
5
Steppingstones to Successful Management of JRA
Basic
Program
Planned LongRange
Program
(Rheumatologist)
Parent and
Patients\
Education
and
Counseling
Social
Worker
Psychiatrist
if necessary
Physical and
Occupational
Therapies
Swimming
and
Exercise
Program
Assistive
Exercise for
loss of
Motion
Good
Health
Habits
Rapidly acting
Agents Nosteroidal
Anti-inflammatory
Drugs (NSAIDs)
Slower Acting Agents
Slower Acting
Anti-Rheumatic Drugs
(SAARD)
Steroids
Experimental
Treatment and
Drugs
Orthopedic
Consultation
Spines and
Braces
Soft Tissue
Release of
Scar tissue
Periodic Eye
Examination
Satisfactory
Control
Altropine Drops
And/or Steroids
for
limits
Operative Eye
Procedures
Synovectomy
Joint
Implants
6
II. Systemic Lupus Erythematosus (SLE)
A.
B.
C.
D.
E.
Clinical manifestations
Immunologic parameters of the disease
Antinuclear antibody and anti DNA antibody in SLE
Nephritis in SLE
Extrarenal aspects of SLE
SLE can be extremely difficult to differentiate from JRA. Usually the
disease manifests itself in children after ten years of age and it is is
more frequent in girls than boys (10:1 ratio). The malar rash or flush is
extremely helpful in the differential diagnosis. The classic rheumatoid
rash does not occur in SLE. A high tittered ANA is present in most
patients with SLE (> 1:500).
Anti-DNA antibody is almost
pathonomic of SLE. Patients with SLE produce antibodies to a
number of nuclear and cytoplasmic antigens, recently Tan et al
published the revised American Rheumatism Association (ARA)
criteria for diagnosis of SLE.
SLE CRITERIA*
1.
2.
3.
4.
5.
6.
7.
8.
Malar Rash
Discoid Rash
Photosensitivity
Oral Ulcers
Arthritis
Serositis (pleuritis, pericarditis)
Renal Disorder (proteinuria > 0.5g or casts)
Neurolgoic Disorder (hemolytic anemia, or leucopenia, or
lymphopenia, or thrombocytopenia)
9. Immunologic Disorder (LE prep, or anti-DNA, or Anti-Sm, or
STS)
10. Antinuclear Antibody.
* Diagnosis of SLE with 4/11 criteria present.
Modified from Tan et al, aRthreitis Rheum., 1972; 25:1271.
III. Raynaud’s Phenomenon
A. Clinical – pain, palor, cyanosis, erythema
B. Related rheumatic disease
1.
2.
3.
4.
5.
6.
Scleroderma
SLE
JRa
Dermatomyositis
MCTD
Other
7
IV. Vasculitis
A.
B.
C.
D.
E.
F.
G.
Polyarteritis nodosa
Allergic angitis and granulomatosis
Connective tissue disease
Giant cell arteritis
Hypersensitivity angitis
Wegener’s granulomatosis
Miscellaneous
V. Kawasaki Disease – Diagnostic Criteria
A. Fever for 5 or more days
B. Presence of 4 of the following 5 conditions:
1.
2.
3.
4.
5.
C.
Bilateral conjunctivitis
Involvement of mucous membranes:
Injected pharynx, injected lips, dry and fissured lips,
“strawberry” tongue
Involvement of extremities:
Peripheral edema, peripheral erythema, desquamation,
periungual desquamation
Rash: polymorphous, truncal, non-vesicular
Cervical lymphadenopathy
Illness cannot be explained by other known disease process
VI. Scleroderma
A.
Epidemiology
Incidence
Race
Sex
Adult pattern
Predisposing factor
B.
:
:
:
:
:
12 cases/1,000,000/year
1.5:1 (Black to White)
2:1 (female to Male)
peaks at 45-64 years
none known
Clinical
VII. Dermatomyositis
A. Epidemiology
Incidence
:
10 cases/1,000,000/year
Race
:
3:1 (Black to White)
Sex
:
2:1 (female to Male)
Adult pattern
:
peaks at 45-64 years
Predisposing factor :
none known
B. Clinical
8
VIII. Seronegative Spondyloarthropathies
A.
B.
IX.
Conditions
Clinical
Acute Rheumatic Fever (ARF)
A. Modified Jones Criteria
Major Manifestations
Minor Manifestations
Carditis
Migratory polyarthritis
Sydenham’s chorea
Erythema marginatum
Clinical
Fever
Arthralgia
Previous rheumatic fever or
Rheumatic heart disease
Laboratory
Elevated acute phase reactants
Elevated erythrocyte
sedimentation rte
Elevated C-reactive protein
Leukocytosis
Prolonged PR interval
Plus
Supporting evidence of preceding streptococcal infection (increased
ASO or other streptococcal antibodies, positive throat culture for group
A B-hemolytic streptococcus, or recent scarlet fever).
The presence of two major and one minor or one major and two minor
with supporting evidence of a recent streptococcal infection make a
diagnosis of ARF likely.
9
X.
Some Antirheumatic drugs studied in children
Name
Dose
NSAIDs
Aspirin
Tolmetin (Tolectin)
Fenoprofen (Nalfon)
Ketoprofen (Orudis)
Piroprofen (Rengasil)
Proquazone (Biarsam)
Na-meckofenamate (Meclomen)
Ibuprofen (Motrin, Advil)
Naproxen (Naprosyn)
Sulindac (Clinoril)
60-80 mg / kg / day
15-30 mg/ kg / day
900-1,800 mg / M² / day
100-200 mg / M² / day
600 mg / M² / day
400-800 mg / M² / day
3-7.5 mg / kg / day
40 mg / kg / day
10-15 mg / kg / day
± mg / kg / day
SAARDS
Gold
Penicillamine
Hydroxychloroquine
0.7-0.1 mg / kg / week
5-10 mg / kg / day
3-6 mg / kg / day
10
XI. LABORATORY STUDIES
Sedimentation rate
Hematocrit and CBC
May be elevated in rheumatic disease.
In systemic onset JRA or SLE there may be:
a. striking anemia
b. striking neutrophilic leukocytosis (white cell count
may reach 50,000 cells / mm³ (JRA) / or
leucopenia < 4000 / mm³ (SLE)
In all onset types of JRA, there may be lowgrade anemia.
Reumatoid factor (RF)
Present in 15% of all JRA patients. May be
associated with other connective tissue
diseases and SBE.
Sreptococcal antibodies (ASO, Anti –
DNaseB, Antihyaluronidase
Elevated levels in rheumatic fever.
Antinuclear antibodies (ANA)
Present in 30 – 40% of all JRA patients.
Unusual in systemic onset JRA.
Absent in Juvenile ankylosing spondylitis.
Frequently associated with systemic lupus
erythematosus (SLE), scleroderma,
dermatomyositis, & pauci JRA.
Depression characteristic of active SLE.
Elevation seen in JRA.
Serum complement (C3, C4, CH50)
Immunoglobulins
Gives indication of severity of inflammation
In JRS. Decreased IgA associated with some
CTD Increased IgC in JRA.
HLA-B27 histocompatibility
Positive in about 95% of ankylosing JRA
Spondylitis patients.
High incidence in Reiter’s syndrome (75%)
Positive test in JRA suggests possible later
Ankylosing spondylitis
Serum muscle enzymes (CPK, aldolase,
SGOT, SGPT, LDH)
May be markedly elevated or normal in
dermatomyositis.
Urinalysis
Liver function tests, Occult blood in stool
Abnormal urinalysis suggests SLE or drug
Toxicity in JRA.
May show liver function abnormalities
and side effects of anti- inflammatory
agents.
11