RHEUMATIC DISEASES OF CHILDHOOD
Disease Etiology and Pathogenesis
JUVENILE IDIOPATHIC
ARTHRITIS
• chronic idiopathic inflammation
of joints for children less than
16 yo
• one of the MC rheumathic
diseases
• girls are more affected than
boys
• Oligular JIA
▪ MC form of JIA
▪ Two peaks: 1-3 yo/ 8-12
yo
• Polyarticular JIA
▪ Can present in any age
▪ Two peaks:
o Early childhood (-)
RF
o Adolescence (+) RF
• Systemic Onset JIA
▪ Do not present with onset
of arthritis
Signs and Symptoms
• Unknown
• Immunogenetic susceptibility
• External trigger: possible
nongenetic triggers
Diagnostics
• Arthritis
• Fatigue and loss of appetite
• Uneven growth
• Fever and rash
• Swollen lymph nodes and
internal organs
• Arthritis in fewer than 5 joints
in the 6 months of diagnosis
• Systemic symptoms usually
absent.
• Arthritis in 5 or more joints
within 6 months of diagnosis
• Symmetric arthritis
• Cervical spine involvement
• Malaise
• Low-grade fever
• Growth retardation
• Anemia of chronic disease
• Manifest with typical recurring,
spiking fever, usually once or
twice a day, for several weeks
to months.
• Rash – morbilliform & salmon
colored
• Lymphadenopathy
• Hepatosplenomegaly
• Serositis
Treatment
Goals:
• To control pain
• Improve and preserve the
function of the joints
• Promote normal growth &
dev’t
• Prevent irreversible joint
damage
Pharmacologic:
• NSAIDS: Naproxen,
Ibuprofen, Meloxicam
• DMARD: Methotrexate,
Sulfasalazine, Leflunomide
• Biologic Agents: Anti-tumor
necrosis factor -- Etanercept,
Infliximab, Adalimumab
• (+) ANA
• (-) RF
• X-ray findings:
▪ Soft tissue swelling
▪ Periarticular osteoporosis
▪ Growth disturbance
▪ Loss of joint space
• Elevated markers of
inflammation
• (+) ANA
• X-ray findings:
▪ Soft tissue swelling
▪ Periarticular osteoporosis
▪ Joint space narrowing
▪ Erosions
• Laboratory findings of
inflammation
• (-) RF & ANA
• X-ray: Soft tissue swelling
 JUVENILE
SPONDYLOARTHROPATHY
• Diverse group of chronic,
systematic inflammatory
conditions linked by clinical,
radiographic, and genetic
features.
• Common in boys and
adolescents
• Juvenile Ankylosing
Spondylitis
▪ Affects 18-30 yo
▪ M>F
• Psoriatic Arthritis
▪ Seronegative oligoarthritis
▪ Chronic disease
characterized by a form of
inflammation of the skin
and joints.
REACTIVE ARTHRITIS
• Reiter’s syndrome
• Painful form of inflammatory
arthritis that develops in
reaction to an infection by
bacteria or virus
• RF-seronegative, HLA-B27-
linked arthritis often
• Not fully understood
• Family history of the disease
• High frequency of HLA-B27
• Not fully understood
• Environmental and genetic
factors
• HLA-B27 antigen associated
hereditary marker
• TNF: Cytokine involved
systemic inflammation
• IL 1 a & b
• Affects the joints in the spine
and the sacro-ilium in the
pelvis  fusion of the spine 
complete rigidity of the spine
• Unknown etiology
• Genetic factors: HLA-B27
• Immune factors: stressors or
changes in the immune system
may affect the dev’t or
progression of the disease
• Environmental factors
• Streptococcal throat infection
• Glandular fever
• Viral flu
• Food poisoning
• Sexually Acquired
• Inflammation of the joints of
the axial skeleton, large joints
of the lower extremities, and of
the entheses.
• Presence of extraarticular
features
• •
• Swollen, painful, hot, red joints
• Swollen fingers or toes
• Joint stiffness
• Pitted nails or nails separating
from the nail bed
• Lower back pain
• Inflammation of the tendons
• Burning pain on urination
(dysuria) or an increased
frequency of urination
• Prostatitis in men and
cervicitis, salpingitis and/or
vulvovaginitis in women.
• Absence of the RF or other
serologic abnormalities
History and PE
• Serologic tests (ESR & CRP)
• Radiography
• Power Doppler UTS
• Genetic Testing
• Combining the clinical criteria
of inflammatory back pain and
enthesitis orarthritis
• Combination of the ff:
• NSAIDs
• DMARDs
• Glucocorticoids
• TNF-blockers
• Physical and Occupational
Therapy
• Nutrition
• Disease modifying anti-
rheumatic drugs
• NSAIDs
• Regular exercise
• Warm-up stretching or
applying heat to muscles
before exercises, and ice after
exercise can decrease the
soreness in the joints.
• If NSAIDs are not sufficient
 Methotrexate,
Corticosteroids, Antimalarial
medications
• Devices to protect the joints
• Surgery may be indicated to
some cases
• The main goal of treatment is
to identify and eradicate the
underlying infectious source
with appropriate antibiotics if
still present
• NSAIDs
• Sulfasalazine
• Steroids
 precipitated by genitourinary • Penile lesions called balanitis
or gastrointestinal infections circinata (circinate balanitis)
• With arthritis  Reiter’s can be found in
arthritis • males
• Arthritis may be additive or • Inflammation of the eyes in the
migratory form of conjunctivitis or
• 20-40 yo uveitis
• F>M • Swelling and pain in large
joints such as the knee.
• Enthesitis can involve the
Achilles tendon resulting in
heel pain
• A small percentage of men and
women develop small hard
nodules called
• keratoderma blennorrhagia on
the soles of the feet
SYSTEMIC CONNECTIVE TISSUE DISEASE
Disease Etiology and Pathogenesis Signs and Symptoms
SYSTEMIC LUPUS • Unknown • Presentation and course are
ERYTHEMATOSUS • Genetic abnormalities highly variable ranging from
• Complex, chronic, multisystem, • Generation of autoantibodies indolent to fulminant
autoimmune disease directed against self-antigen • Malar rash
• Multisystem inflammation particularly nuclei acids • Raynaud’s Phenomenon
• • Abnormal cytokines • Discoid Rash
• Functional impairment of B • Livedo reticularis
and T cells • Ulcers/Mucocutaenous
involvement
• Renal involvement
• Proteinuria
• Urinary cellular casts
• Seizures
• Thrombocytopenia
• Hemolytic anemia
• Fever
• Lymphadenopathy
• Classic triad of fever, joint
pain and rash in a woman on
childbearing age should prompt
• Immunosuppresants
Physio Mngt:
• Electrotherapy
• Social support education
• Circulatory movements
• Deep tissue massage
• Rest when pain is felt
• Wrist splints and shoe insoles
• Relaxation exercises
• Hydrotherapy for soothing
pains
Diagnostics Treatment
• Comprehensive clinical • Suppress symptoms and
and laboratory assessment prevent organ damage
• Excluded other etiologies • Depends on the severity of the
like malignancies and disease
infection • Prevention of complications of
• Renal disease: Proteinuria disease and its treatment
(>500 mg/24 hr) or • Treatment plans are based on
cellular casts (RBC, age, sex, health and lifestyle
granular, or tubular) • Glucocorticoids
• Hematologic disease: • Steroid-sparing
hemolytic anemia with immunosuppressive drugs:
reticulocytosis or Methotrexate,
leukopenia or Cyclophosphamide
lymphopenia or • Hydroquinolones
thrombocytopenia • NSAIDs
• Serologic data: (+) •
Nonpharmacologic treatment:
immunoserology, (+) o Sunscreen
ANA o Avoidance of prolonged
• MRI direct sun exposure, and
• Joint radiography other UV light

JUVENILE
DERMATOMYOSITIS
• MC inflammatory myositis in
children
• Systemic vasculopathy causing
nonsuppurative inflammation of
the skin and muscles
characterized as symmetric
proximal muscle weakness with
characteristic skin rash
• Amyopathic JDM – presents
with classic rash with no
apparent weakness or
inflammation.
SCLERODERMA
• Presence of fibrosis on the skin
• Localized and Systemic
Sclerosis
• Unknown etiology
• Vascular and muscle damage
• Autoantibodies directed against
an unknown endothelial
antigen may cause vascular
injury, resulting in ischemia
and subsequent muscle damge
with increased expression of
MHC 1 & II.
• Unknown
• Vasculopathy
• Autoimmunity
• Immune activation
• Fibrosis
• Triggers:
o Trauma
o Infection
investigation into the diagnosis
of SLE.
• Rash, insidious onset of
weakness or both
• Fever
• Dysphagia
• Dysphonia
• Arthritis
• Muscle tenderness
• Fatigue
• Rash – 1st symptom
o Shawl sign
o Heliotrope rash
o Facial erythema crossing
nasolabial folds is
common
o Gottron papules
o Mechanic’s hands
o Telangiectasia
• Weakness
o Gower sign
o Aspiration or respiratory
failure
o Respiratory muscle
weakness
o Lipodystrophy
o Calcinosis
Localized Scleroderma
• Erythema or bluish hue around
an area of waxy induration
Systemic Scleroderma
• Periods of remission and
exacerbation ending in either
chronic disability or death.
• Skin manifestations – most
dramatic
• CXR and chest CT
scanning
• Echocardiography,
Cardiac MRI
• Biopsies of skin lesion:
Immunoglobulin deposits;
lupus band test
Laboratory Findings:
• Elevated muscle enzymes
o Creatine kinase
o Aldolase
o Aspartate
aminotransferase
o Lactic dehydrogenase
• Normal ESR
• (-) RF
• (-) Test for antibodies
• Electromyography – myopathy
& denervation
• Muscle biopsy – for grading
Radiographic Findings:
• Guide in dx and mngt
• Dystrophic calcification in
muscle and soft tissues
Localized Scleroderma – based on
the distribution and depth of
characteristic lesions
Systemic Scleroderma – proximal
sclerosis/induration of the skin
Laboratory Findings
• Localized Scleroderma
o Elevated ESR
o Smoking cessayion
o Weight loss
o Cholesterol monitoring
o Optimal BP control
o Avoidance of high-dose
estrogen therapy, oral
contraceptions
o Avoidance of culprit
medications
o Avoid pregnancy
Corticosteroids
• Mainstay of treatment
• Oral prednisolone 2
mg/kg/day
Methotrexate 0.5-1 mg/kg or 15-20
mg/m2
Hydroxychoroquine 4-6 mg/kg/day
PO
IV Ig
Physical and Occupational therapy
Vitamin D and Calcium
supplements
• Corticosteroids or UV Therapy
– Superficial morphea
• Corticosteroid and
Methotrexate – deeper lesions;
systemic therapy
• Raynaud’s Phenomenon
o Cold avoidance
o Nifedipine, Amlodipine,
Losartan, Prazosin
• Endothelial cell injury 
Fibroblast activation
• Environmental factors: Silica,
solvent exposure, radiation
• Viruses: CMV, Parvovirus,
HPV
• Drugs: Bleomycin, Pentazocin
• Raynaud’s phenomenon o Eosinophilia • HPN with renal ds – ACEi
Major organ involvement: o Hypergammaglobulinemia • Pulmonary Alveolitis --
Pulmonary o Elevated muscle enzymes Cyclophosphamide
• Affects interstitium or the • Systemic Scleroderma
arteries o Anemia
• Asymptomatic to exercise o Leucocytosis
intolerance, dyspnea at rest, o High titer (+) ANA
and right-sided heart failure
Gastrointestinal Tract
• Mostly asymptomatic
• Esophageal and intestinal
dysmotility: dysphagia, reflux,
dyspepsia, gastroparesis
Renal
• Chronic or episodic
hypertension
Cardiac – infrequent
Calcinosis
Raynaud’s phenomenon
Esophageal dysfunction
Sclerodactyly
Telangiectasia

Disease
HENOCH SCHONLEIN
PURPURA
• MC vasculitis of childhood
• Leucocytoclastic vasculitis
• IgA deposition in the small
vessels in the skin, joints, GIT
and kidney
TAKAYASU ARTERITIS
• Pulseless disease
• Chronic large vessel vasculitis
of unknown etiology
• Aorta and its major branches
Etiology and Pathogenesis
• Unknown
• Infectious triggers: Group A
beta hemolytic streptococcus,
S. aureus, Mycoplasma,
Adenovirus
• Unknown
• Presence of abundant T cells
and T cell receptors in TA
vascular lesions
• High levels of IL1, IL6 & TNF
alpha
• Genetic predisposition
VASCULITIS SYNDROMES
Signs and Symptoms
Rash
• Hallmark
• Palpable purpura starting ass
pink macules and wheals
MSK – arthritis, arthralgia
GI – abd pain, vomiting, diarrhea,
paralytic ileus, melena
Renal – microscopic hematuria.
Proteinuria, HPN, frank nephritis,
nephrotic syndrome, acute/chronic
GN
Neurologic – ICH, seizures,
headaches, behavioral changes
Arthritis – oligoarthritis
Pre-pulseless Phase
• Fever
• Malaise
• Weight loss
• Headache
• HPN
• Myalgias
• Arthralgias
• Dizziness
• Abd pain
Later Manifestations
• Diminished pulses
• Asymmetric BP
• Limb claudication
• Raynaud’s Phenomenon
• Renal failure
• Symptoms of pulmonary or
cardiac ischemia
Diagnostics Treatment
Clinical Dx – typical rash present • Supportive – adequate
Acute hemorrhagic edema hydration, nutrition, analgesia
Papular-purpuric gloves-and-socks • Steroids – significant GI
syndrome involvement; Prednisone 1
mg/kg/day
• IV Ig
Thorough PE • Glucocorticoids – Prednisone
• Aortic murmur 1-2 mg/kg/day
• Diminished asymmetric pulse • Steroid-sparing therapy –
• VAsscular bruit Methotrexate, Azathioprine
• 4 extremities BP >10 mg • Cyclophosphamide
• Asymmetry in SBP
Lab Findings
• Elevated ESR, CRP
• Leukocytosis, thrombocytosis,
anemia of chronic
inflammation
• Hypergammaglobulinemia
Radiographic Assessment
• Conventional arteriography of
aorta – luminal defects,
dilation aneurysms, stenoses
• MR & CT angiography –
vessel wall thickness
• UTZ with duplex color flow
doppler imaging – vessel wall
thickening, and assess arterial
flow
• 2DEcho – assess aortic
valvular involvement
 KAWASAKI DISEASE
• Mucocutaneous LN Syndrome
• Infantile polyarteritis nodose
• Acute febrile illness of
childhood seen worldwide
• Highest incidence in Asian
children
• Leading cause of acquired
heart disease in children
• Remains unknown
• Infections – trigger
• Genetics
• Affects medium sized arteries
• Coronary arteries – most
commonly involved
• Popliteal arteries
• Brachial arteries
• Prolonged fever usually >5
days induration
• At least 4 of the ff:
o Bilateral nonexudative
conjunctival injection
with limbal sparing
o Erythema on the oral and
pharyngeal mucosa with
strawberry tongue and red
cracked lips
o Edema and erythema of
the hands and feet
o Polymorphic rash usually
truncal
o Nonsuppurative cervical
lymphadenopathy
Fever
• High grade, unremitting,
unresponsive to antibiotics
• w/o treatment – 1-2 weeks but
may persist for 3-4 weels
• Defervesence w/n 1-2 days of
treatment w/ IV Ig
Laboratory Findings in Acute
Kawasaki Disease
• Leukocytosis with
neutrophilia and immature
forms
• Elevated erythrocyte
sedimentation rate
• Elevated C-reactive protein
• Anemia
• Abnormal plasma lipids
• Hypoalbuminemia
• Hyponatremia
• Thrombocytosis
• Sterile pyuria
• Elevated serum transaminases
• Elevated serum gamma
glutamyl transpeptidase
• Pleocytosis of CSF
• Leucocytosis in synovial fluid
Acute Stage
• IV Ig 2 g/kg over 10-12 hr
• Aspirin 80-100 mg/kg/day
divided every 6 hr orally until
px is afebrile
Convalescent Stage
• Aspirin 3-5 mg/kg once daily
until 6-8 wk after illness onset
of normal coronary findings
Long-term Therapy for Px w/
coronary abnormalities
• ASA 3-5 mg/kg once daily
• Clopidogrel 1 mg/kg/day
• Warfarin or LMW heparin
Acute Coronary Thrombosis
• Prompt fibrinolytic therapy

Conjunctivitis
• Nonpurulent conjunctival
injection
• Bulbar conjunctivitis with
limbic sparing
• Begins shortly after the fever,
resolves promptly and may
have disappeared by
presentation

Oropharyngeal Changes
• Lipstick sign – erythema,
dryness, swelling and peeling
lips
• Erythema of the oropharyngeal
mucosa
• Strawberry tongue

POLYARTERITIS NODOSA
• Systemic necrotizing vasculitis
affecting small and medium
size arteries
• Aneurysm and stenoses form at
irregular intervals throughout
affected arteries
• Preferentially at vessel
bifurcations resulting in
microaneurysm formation
• Inflammation may start in the
vessel intima and progress to
include the entire arterial wall,
destroying the internal and
external lamina – fibrinoid
necrosis
• Aneurysms may develop 
rupture
Changes in the Extremities
• Edema
• Peeling of fingers and toes
often periungal
• Peeling of hands and feet in
subacute ohasse
• Beau’s line
Polymorphous rash
• Generally, occurs with onset of
fever and fades within a week
• Morbilliform rash or
erythematous plaques at flexor
creases
• Erythema and desquamation of
the inguinal/perianal area
Lymphadenopathy
• Maybe unilateral single node
>1.5 cm
• Erythematous but non-
fluctuant
Constitutional & MSK: Laboratory findings • Mainstay of therapy:
• Fever, malaise, fatigue, • Elevated ESR and C-Reactive Prednisone
anorexia/ weight loss, mtalgia, Protein - Oral (1-2mg/kg/day)
arthralgia in large joints, • Leukocytosis, normochromic - IV pulse
arthritis anemia, thrombocytosis (30mg/kg/day)
Renovascular arteritis: • Hepatitis B surface antigen & • Adjunctive therapy:
• HPM, hematuria, proteinuria hepatitis C serology - Oral or IV
Cutaneous: • Elevated creatinine level Cyclophosphamide
• Purpura, livedo reticularis, • Proteinuria • For life threatening disease:
ulcerations, digital ischemia • Elevated levels of liver - Plasma exchange
and painful nodules enzymes • Hepatitis B identified:
CNS Arteritis • Hypergammaglobulinemia - Antiviral therapy
• CVA, TIA, psychosis, 30% of cases • Infectious trigger is identified:
ischemic motor or sensory • Cryoglobulins, circulating - Antibiotic
peripheral neuropathy immune complexes prophylaxis
• decreased levels of serum
complements (C3, C4)
Demonstration of vessel
involvement on biopsy or
angiography

ANCA-ASSOCIATED
VASCULITIS
• Small vessel involvement
• Pauci-immune complex
deposition in affected tissues
3 distinct forms:
• Granulomatosis with
Polyangitis
• Microscopic plyangitis
• Eosinophilic granulomatosis
with polyangiitis – Churg-
Strauss Syndrome
• Necrotizing granulomatous
vasculitis – cardinal histologic
feature f GPA and MPA
• Perivascular eosinophilic
infiltrates – CSS
• Kidney biopsies: crescenteric
glomerulonephritis with little or
no immune complex deposition
(pauci-immune)
Early specific nonconstitutional
symptoms:
• Fever
• Malaise
• Weight loss
• Myalgias
• Arthralgias
GPA
• Upper airway involvement:
sinusitis, nasal ulceration,
epistaxis, OM, hearing loss
• Lower respiratory tract
symptoms: Cough, wheezing,
dyspnea, hemoptysis
• Ophthalmic involvement:
conjunctivitis, scleritis,
uveitis, invasive pseudotumor
causing proptosis
• Perineural vasculitis: direct
compression on nerves 
cranial and peripheral
neuropathies
• Renal: Proteinuria, hematuria,
HPN
• Cutaneous lesions: Palpable
purpura, ulcers
• Childhood GPA: More
frequently complicated by
subglottic stenosis
MPA
• Systemic: fever, malaise,
weight loss, myalgias,
arthralgias
• Frequently affects the kidney
and lungs
Conventional arteriography –
beads on string appearance
Biopsy of cutaneous lesions
Kidney biopsy – necrotizing
arteritis
Electromyography – identifies
affected nerves
GPA • Lower respiratory tract or
• CXR: Nodules, ground glass kidneys:
opacities, mediastinal • Initial induction therapy:
lymphadednopathy & cavitary ▪ Corticosteroids
lesions 2mg/kg/day oral or
• (+) ANCA 30mg/kg/day x 3
• Presence of anti-PR3-specific days IV plus
ANCAs • Cyclophosphamide
• Necrotizing granulomatous 2mg/kg/day PO
vasculitis on pulmonary, sinus • Upper respiratory tract:
or renal biopsy • First line treatment:
▪ Corticosteroid 1-
MPA 2mg/kg/day
• ANCAs present w/ reactivity to ▪ Methotrexate 0.5-
MPO 1mg/kg/wk
• 3-6 months before
CSS transitioned to less toxic
• Presence of chronic asthma & maintenance medication:
peripheral eosinophilia Methotrexate,
Azathioprine or
Mycophenolate mofetil.

BEHCET’S DISEASE
• Autoinflammatory disease
• Primary variable vessel
vasculitis
• Involvement of any size and
type of vesse;
• Polygenic
autoinflammatory disease
• Genetic: association with
HLA-B5101
o familial cases
o sibling and twin
recurrence rate
o interleukins,
interferons & ERAP
• Infectious agents:
streptococci
o herpes simplex virus
type I
o parvovirus B19 • Eye involvement 30-60%
• Endoplasmic reticulum-
expressed amino-
peptidase that functions in
processing of peptides
onto major
histocompatibility
complex class I.
• The autoinflammatory
nature of the disease is
suggested by the episodic
nature, prominent innate
immune system activation,
absence of identifiable
autoantibodies and the co-
association with the
MEFV (Mediterranean
fever)
CSS
• Inflammation of upper and
lower respiratory tract but
cartilage destruction is rare
• Initially demonstrate
rhinitis/sinusitis, nasal
polyposis & difficult to treat
asthma
• Eosinophilia w/ pulmonary
infiltrates may precede a
vasculitis
• Oral ulcer – the most • Genital and oral ulcers : Topical
frequent initial symptom steroids
o very painful • Eye disease : Azathioprine
o single or multiple, 2-10 • Erythema nodosum or arthritis:
mm Colchicine
o any location in the oral • CNS disease & vasculitis:
cavity Steroids
o last 3-5 days w/o scarring o Azathioprine
o often recurrent o Cyclophosphamide
• Genital ulcers -60% o Interleukin a
o occur after puberty • Major organ involvement:
o seen on the labia, scrotum, Colchicine
o penis or anal area • Vascular involvement/venous
thrombosis:
o blurred vision, redness o Steroids
o periorbital or global pain o Azathioprine
o photophobia • Pulmonary arterial/cardiac:
• Skin lesions – erythema Cyclophosphamide
nodosum
o papulopustular acneiform
o folliculitis
o purpura
o ulcers
• Vasculitis – involves both
arterial or venous
o thrombosis
o aneurysm formation or
occlusions
o stenosis in arteries of any
size
• Deep venous vein thrombosis
LE:
 o most frequent vasculitis
• Pulmonary aneurysms – most
severe feature of BD, with
highest mortality
• Coronary artery aneurysm may
confuse with KD
• Central nervous system
manifestations:
• Meningoencephalitis:
headache, meningismus, CSF
pleocytosis
• Encephalomyelitis
• Pseudotumor cerebri
• Dural sinus thrombosis –
most common CNS
manifestation in children
• Organ psychiatric disorders :
psychosis, depressiondementia
• Gastrointestinal involvement:
o Abdominal pain
o diarrhea
o Intestinal ulcerations-
ileocecal region
• Arthritis/arthralgia >50%
o recurrent, non-deforming