Rheumatic Diseases in
Children
Objectives
By the end of this presentation you will:
Review Rheumatic Diseases
Discuss the medications utilized to treat
Rheumatic Conditions
The Immune System 101
Antibodies
Lymphocytes
T-cells
B-cells
B and T cells and their products
are the target for many of the
treatments
for
Autoimmune diseases
seen in
Rheumatology
3rd line
Phagocytoes
Natural killer cells
Granulocytes
macrophils
Skin, mucus membranes, enzymes
Natural microbial flora
Complement proteins
2nd line
1st line
The Factors
of Autoimmune Disease
Genetic
predisposition
Environment
Timing
Rheumatic Conditions
Systemic Lupus Erythematosus (SLE)
Juvenile Arthritis
Uveitis
Linear Scleroderma
Systemic Sclerosis
Juvenile Dermatomyositis
Vasculities
Juvenile Arthritis
•85,0000-115,000 children in the United States have
Juvenile
Arthritis
•Most Common Rheumatic Disorder in Children
•Diagnostic Criteria
•Age at onset <16
•Arthritis in one or more joints
•Duration of disease 3 months or longer (6weeks for ACR)
Criteria Juvenile Arthritis
Types defined by characteristics of disease
Pauciarticular (Oligoarthritis for JIA) <5 joints
Polyarticular: >5 joints
Systemic:arthritis with characteristic fever
(rash)
• Juvenile Psoriatic arthritis
• Spondyloarthropathies
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• Juvenile Anklylosing Spondyloarthritis
• Enthesitis-related arthritis
Clinical Manifestations
Juvenile Arthritis
Joint specific
Morning stiffness
Pain on motion
Loss of motion
Tenosynovitis
Joint inflammation: Swelling, redness, heat, pain, loss of function
Extra-articular
Abnormalities in growth and development
Osteopenia
Organ-Specific
Nodules
*** Systemic or rare involvement=vasculitis, cardiac disease, pleuropulmonary
disease, GI tract, Lympadenopathy and splenomegaly, hepatosplenomegaly,
neurologic, renal
Systemic JA – Rash
Juvenile Arthritis
prior to the age of methotrexate and biologics
Treatment JA
NSAIDS
Ibuprofen
Naprosyn
Diclofenac
Intra-articular injection:
Aristospan
Glucocorticosteroids
Prednisone
Methylprednisolone
DMARDS
Methotrexate
Sulfasalazine
Leflunomide
Biologic Response Modrifiers
Etanercept(Enbrel);
Adalimumab (Humira)
Infliximab (Remicade);
Anakinra (Kineret)/systemic
Abatacept (Orencia)
Rituximab(Rituxan)
Tocilizumab(in study)
Laboratory Studies
No laboratory testing is diagnostic for JA
Used for evidence of inflammation, determine
pathogenesis, support diagnosis, and monitor
treatment
Laboratory Studies
Antinuclear antibody (ANA)
– Pauciarticular disease (+) demonstrates increase risk of
uveitis
• Rheumatoid Factor
– More indicative erosive disease 3% (Cassidy, 2005)
• Sedimentation rate (ESR)
– Non specific measure of inflammation
• C reactive protein (CRP)
– more reliable monitor of inflammatory response
• CBC
• Chem 14
– monitoring potential side effects NSAIDS and
methotrexate increased LFT’s
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UVEITIS
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Inflammation of uveal tract
◦ Iris, ciliary body, and/or choroid
Asymptomatic until very late stages
 Uveitis is often progressive & difficult to control
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◦ Possible Symptoms: synichiae, reduced vision, glaucoma,
increased inflammation in the other eye, and blindness
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Slit Lamp examination for diagnosis and followup
Uveitis
Treatment Uveitis
Opthalmology: Topical steroid drops
Systemic Treatment
DMARD
Methotrexate
Corticosteroids
Prednisone
Methylprednisonlone
Biologic Response Modifiers
Infliximab (Remicade)
Etanercept(Enbrel);
Adalimumab (Humira)
Diclizumab (Zenapak)
Systemic Lupus
Erythematosus (SLE)
Incidence: 0.5 -0.6/100,000 children
• Prevalence: 5-10,000 children in the USA
• Onset: 15% in childhood
• Female to Male ratio
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– Higher female onset post pubescent
– Equal pre pubescent
Affects multiple systems
• Characterized by inflammation of the small
blood vessels and connective tissue
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Diagnosis of SLE
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4 out of 11 criteria
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Malar rash
Discoid rash
Photosensitive rash
Mucosal ulcers
Serositis
Arthritis
Renal disease/cellular casts
CNS: Seizure or psychosis
Hematology: Leukopenia <4000/cubic mm; lymphopenia < 1500/cubic
mm; thrombocytopenia <100,000/mm3
◦ Immunoserology: anti double stranded DNA (anti ds DNA), anti Smith specific marker for active SLE, false + (VDRL)
◦ Positive AntiNuclear Antibody test (ANA) (95%, typical pattern is
homogeneous)
SLE rashes
Upper
Malar
Lower left
Discoid
Lower right
Mixed rashes
Laboratory Studies:
Diagnostic
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Cytopenia
◦ Thrombocytopenia
◦ Anemia: hemolytic (Coombs +)
◦ Leucopenia
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Positive Immunoserology
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dsDNA: (+) presence of antibodies
Sm nuclear antigen: (+) presence of antibodies
Antiphospholipid antibodies: (+) risk of clotting
VDRL (syphilis) false (+)
Antinuclear antibody (ANA)
◦ antibody most commonly found in SLE
Laboratory Studies:
Monitoring
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CBC
Chem 14
Antinuclear Antibody
dsDNA:
Complement 3 and 4
– low in most active SLE disease, used for tracking not
diagnostic
Urinalysis with micro
– initial indication of renal disease
– usually shows lots of blood, protein and high specific
gravity!!!
Spot urine protein and creatinine
– monitoring of renal disease (UP/UC ratio)
Treatment SLE
Plaquenil
Aspirin
Prednisone
NSAIDS
Methotrexate
Imuran
Rituximab
Orencia
Cellcept
Cytoxan IV
Daily Cytoxan
Plasmapheresis
Nitrogen Mustard
Campath
BMT
IVIG
Features of Juvenile
Dermatomyositis
Gottran’s Papules
Heliotrope Rash
Juvenile Dermatomyositis:
Radiographical features
Calcinosis
Thigh of 12yr old male
Inflammation is bright white
Laboratory JDMS
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CBC
Chem 14: monitoring medication side effects
Aldolase: elevated with muscle inflammation:
monitoring and confirmation not diagnostic
Neopterin: same as aldolase
CPK: same as aldolase and Neopterin
ESR: inflammation unspecified location
Urinalysis
Treatment
Dermatomyositis
Stem Cell Transplant
Campath
Biologics
Infliximab Etanercept
Abatacept
Methotrexate
Glucocorticosteroids
Cyclosporin
Hydroxychloroquine
IVIG
Cyclophosphamide
Linear Scleroderma
11 yr old girl
10 year old girl
Diagnosis age 4
Coupe de Sabre
Systemic Sclerosis
Children
0.2-0.9% of the Major Mixed Connective Tissue Disorders
•Prevalence: 0.8/100,000 children in the USA
•Onset: 3 % in childhood
•Female to Male ratio: 1:1= <8yrs old and 3:1 = >8yrs old
•Average age onset in childhood: undefined
•Affects multiple systems connective tissue disorder
•Characterized by thickening and hardening of the skin in
conjunction with fibrous and degeneration of multiple
organs
Cassidy, 2005
Systemic Sclerosis:
Clinical Manifestations
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Raynaud’s phenomenon
Skin changes
– Sclerosis, edema, atrophy, Telangiectases, calcinosis
Sclerodactyly
Musculoskeletal Disease estimated 35%
– Morning stiffness, joint pains, contractures, tendon tightening
Gastrointestinal Disease 25%
– Ulcerations of the mouth
Digestive problems
Kidneys
– high blood pressure
– kidney failure
Heart and lung
– arrhythmias, heat failure
– scaring of the lung tissue
Scleroderma: Acrolysis
and calcinosis
Unaffected
Scleroderma
Renal arteriogram:
Left is normal
Right is renal insufficiency
Pulmonary x-ray
Interstitial Fibrosis
Laboratory Scleroderma
 CBC
 Chem. 14
 Urinalysis
 SCL70
antibody (diagnostic for SSc
<30% of children, >70% in adults)
Treatment Scleroderma
Stem Cell Transplant
Campath
Mycophenolate Mofetil
Methotrexate
IVIG
Cyclosporin
Hydroxychloroquine
Glucocorticosteroids
Cyclophosphamide
Classification of
Vasculitides
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Small Vessel Vasculitis
– ANCA associated
• microscopic polyangitis; Wegener’s granulomatosis;
Churg-Strauss Syndrome; Drug induced
– Immune complex
• Henoch-Schonlein purpura; (SLE,JIA, Sjogrens); Bechets;
Drug associated; Infection associated
– Paraneoplastic
• lymphoproliferative neoplams induced, myeloproliferative
neoplasm induced, carcinoma induced
– Inflammatory Bowl Disease (IBD)
Classification of
Vasculitides
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Medium Vessel Vasculitides
◦ Polyarteritis nodosa
◦ Kawasaki disease
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Large Vessel Vasculitides
◦ Giant Cell arteritis
◦ Takayasus’s arterititis
Wegener’s
Granulomatosis
•Prevalence: 0.1/100,000 children
•Onset: 3 % in childhood
•Female to Male ratio: undefined
•Average age onset in childhood: 15.4
•Characterized by granulomatous vasculitis in the upper and
lower respiratory tracks
•Criteria for diagnosis: 2 of 4 must be present
• Nasal of Oral Inflammation
• Abnormal appearing chest radiograph
• Abnormal urinary sediment
• Granulomatous inflammation
Cassidy, 2005
Wegeners Granulomatosis
Saddle Nose
Wegener Granulamotosis
granulomas and cavitations
Treatment Wegener’s
Granulomatosis
Cyclophosphamide
IVIG
Glucocorticosteroids
Methotrexate
Takayasu’s Arteritis
•Most common in young women of Japanese origin
•Classification criteria for diagnosis
• Sub clavian or aortic bruit
• Decreased brachial artery pulse
• Blood pressure difference of >10mm between arms
• Claudication of extremities
• Arteriographic evidence of narrowing or occlusion of aorta, its primary branches
or large arteries in the proximal, upper, or lower extremities
Cassidy, 2005
Takayasu: Angiograms
Treatment Takayasu’s
Arteritis
Cyclophosphamide
Methotrexate
Glucocorticosteroids
Infliximab