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Title: Often we have to look beyond to see what we are supposed to


1
Often we have to look beyond to see what we are
supposed to
2
Pediatric Board Review Course
  • L. Nandini Moorthy, MD MS
  • Pediatric Rheumatology
  • 2007

This presentation is specifically prepared for
the board review course by Dr. L. Nandini
Moorthy. This may not be reproduced without the
permission of Dr. L. Nandini Moorthy ( June 9,
2007)
3
Case 1 One swollen joint
  • A three year old Caucasian girl with two-month
    history of swollen left knee
  • No history of fevers
  • No rash
  • No weight loss
  • No other joints are involved
  • CBC and differential within range
  • CMP, ESR, CRP, Ig within range
  • LDH within range
  • ANA titer 1320
  • RF negative

4
JIA Definition
Juvenile Rheumatoid Arthritis (JRA)Now Juvenile
Idiopathic Arthritis (JIA)
  • Objective arthritis in 1 joint(s) for six
    weeks
  • Children 16 years
  • 6 mo necessary to examine the clinical features
    exception SoJIA

Clinical recognition of each phenotype is
critical Different courses, complications,
treatments and prognosis
5
Oligo-articular onset JIA Pauciarticular JIA
(PaJIA)
  • Commonest subtype ( 50)
  • 1-5 years of age
  • Girls gt boys
  • Arthritis in four joints
  • Large joints-knees, ankles, elbows
  • Usually spares hips
  • Rarely affects wrists, small joints of hands
    feet

6
PaJIA
  • Swollen joint (warm, not erythematous)
  • Limp, or an abnormal gait
  • Rarely complain of pain.
  • No constitutional symptoms
  • Routine lab values -normal
  • May be ANA ve

7
Differential Diagnosis of PaJIA
  • Other causes of oligoarthritis
  • Reactive arthritis
  • Lyme arthritis
  • Septic arthritis
  • Trauma
  • Neoplastic disease
  • Dactylitis (lt 4 ?psoriatic arthritis)

In older children Spondyloarthropathy Leg Calve
Perthes disease Osteoid osteoma Slipped capital
femoral epiphysis Exclude structural
abnormalities Discoid meniscus Hemophilia Sarco
idosis? if repeated bouts
8
PaJIA-Course and Complications
  • Benign course, good prognosis
  • Recurrences 20
  • May progress to extended-oligoarticular arthritis
    requiring aggressive treatment
  • Discrepancy in limb lengths
  • Persistent inflammation
  • Orthotic/surgical correction
  • Fixed flexion contractures
  • PT OT

Usually do well with NSAIDS Intra-articular
steroid injections Rarely require systemic
steroids or immunosupressives
And
9
Uveitis
Silent, chronic, anterior uveitis Mostly ANA
positive girls ( 20) Irreversible damage
blindness Ophthalmologic monitoring
10
Case 2 Many swollen joints
  • Consider the case of a 6 year old girl who
    presents with multiple swollen joints, morning
    stiffness mild anemia

11
Extended Oligoarticular JIA Polyarticular JIA
(PoJIA)
  • 30 -40 of JIA
  • Girls gt boys
  • Bimodal peaks 2-5 years 10-14 years
  • Insidious onset, sometimes acute, with
    progressive involvement of gt/5 joints in the
  • first 6 months
  • In younger children, onset is usually
    pauciarticular
  • AM stiffness and fatigue
  • May have low-grade fever
  • Arthritis intermittent or persistent
  • RFve or RF-ve
  • Small joints of hands feet
  • Tenosynovitis of flexor tendon sheaths

12
PoJIA
Atlanto-axial subluxation C2-C3 fusion
Early carpal fusion (more often in JIA)
Symmetrically affecting the large joints of
knees, elbows, ankles and wrists
Hallmark of JIA posterior cervical fusion
Ruddy Kelley's Textbook of Rheumatology, 6th ed
13
PoJIA
  • Labs - normal or suggest an inflammatory state
  • Anemia
  • High ESR
  • Hypergammaglobulinemia
  • Leukocytosis
  • 5-10 RF
  • 40-50 ANA Cassidy, 2001
  • Late-onset PoJIA
  • Subset of RF girls mimics adult RA
  • Chronic course into adulthood

14
PoJIA-Differential diagnosis
  • Infectious causes of polyarthritis
  • Viral
  • Septic
  • Lyme
  • Other
  • Serum sickness
  • Other rheumatic diseases
  • Inflammatory Bowel Disease (IBD)
  • Systemic Lupus Erythematosis (SLE)
  • Dermatomyositis
  • Sarcoidosis
  • Scleroderma
  • Spondyloarthropathies (enthesitis, axial
    involvement)
  • Rarer causes
  • Malignancy
  • Other immunodeficiences

15
PoJIA-Course Complications
  • Guarded prognosis
  • Poorer prognosis
  • Adolescent girls RF with late-onset, rapidly
    progressive erosive arthritis often have RA like
    disease as adults
  • Early involvement of small joints of hands feet
  • Persistent inflammation
  • Subcutaneous nodules
  • RF
  • Destructive hip disease among other joints
    eventual disability
  • Contractures ankylosis
  • Short stature (more in children)
  • Often require joint replacements
  • Chronic uveitis 5 Cassidy, 2001

Usually require aggressive management
(immunosupressives/ biologics) May need systemic
steroids
16
Systemic onset JIA (SoJIA)
  • High spiking quotidian fevers, that returns to
    normal daily, for at least 2 weeks, with
    arthritis in one or more joints
  • Often with chills
  • Children appear very ill when febrile, but seem
    drastically improved when afebrile

Formerly called Stills disease 10-20 of JIA
diagnoses Affects boys girls equally Half
of them have onset in childhood
Cassidy, 2001
17
SoJIA
  • Salmon-colored evanescent
  • Erythematous
  • Macular rash
  • Trunk and proximal extremities
  • Non-pruiritic
  • Migratory
  • Fleeting nature
  • Disappears from one area within few hours without
    any residual mark

18
SoJIA
Other systemic symptoms Anorexia, arthralgias,
hepatosplenomegaly, lymphadenopathy Widespread
serositis Arthritis - concomitantly or years
after the first presentation Wrists, knees,
ankles, hands, hips, C-spine TMJ Lab Microcytic
anemia Elevation of acute phase reactants
Leukocytosis, thrombocytosis, ESR, CRP,
Complements, Ferritin. ANA in 10 of
patients RF rarely
Differential for FUO Infectious and oncologic
etiologies Inflammatory bowel disease SLE Vasculit
ides such as polyarteritis nodosa
Cassidy, 2001
19
SoJIA- Course Complications
  • Systemic features may persist for 4-6 months with
    varying degrees of joint involvement
  • Prognosis
  • Complete recovery
  • Polyarticular pattern
  • Persistent inflammation / or chronic destructive
    arthritis
  • Long standing SoJIA
  • Micrognathia, c-spine fusion and destructive hip
    disease
  • Short stature FTT
  • Uveitis - rare
  • Amyloidosis -rare in the US
  • Macrophage Activation Syndrome
  • More common in children

NSAIDS Usually require immunosuppressives,
thalidomide, biologics systemic steroids.
20
Gastrointestinal diseases
  • IBD
  • Crohns
  • UC
  • ASCA, ANCA
  • Celiac disease (TTG, Endomysial, Gliadin ab)

21
Enthesitis-related arthritis Spondyloarthropathy
  • Commonly complain of
  • Pain in the back heel
  • Morning stiffness
  • Arthritis /or enthesitis with any 2 of the
    following
  • Sacroiliac joint tenderness, Inflammatory spinal
    pain or both
  • Positive family history
  • Acute anterior uveitis
  • Arthritis onset in boys gt 8 yrs
  • HLA-B 27 (higher likelihood of developing
    debilitating ankylosing spondylitis)

22
Spondyloarthropathy
Treatment NSAIDS, although immunosuppressive
treatment may be necessary
Bamboo spine in Ankylosing spondylitis
Acute anterior iritis
23
What screening test will you send a 14 yo male
teen withHLA B 27 ve arthritis?
QUESTION
24
HLA B 27 associated Aortitis, AR
  • HLA B27 is a risk factor for endo-/myocardial
    damage in patients with B27-JA, even in the
    presence of only short and mild articular
    disease.
  • Patients with B27-JA should be screened by
    color-flow Doppler echocardiography for the
    presence of aortic regurgitation and myocardial
    inflammation with increased mitral blood flow
    velocity at atrial contraction due to impaired
    myocardial relaxation.
  • Regular monitoring may be required.
  • These patients might benefit from early
    pharmacologic intervention by afterload reduction
    (i.e., with ACE inhibitors). All patients with
    juvenile arthritis and
  • Endocarditis prophylaxis should be instituted
    when necessary.

25
Psoriatic Arthritis
  • Arthritis psoriasis
  • Or arthritis with at least two of the
    following
  • Dactylitis
  • Nail abnormalities
  • Family history of psoriasis.
  • May run a course PoJIA require aggressive
    treatment
  • Associated with uveitis

Psoriatic nail involvement and sausage digits
Pencil-in-cup appearance on X-rays
26
Pathogenesis
  • Cytokine dysequilibrium -- increased IL-1, TNF

Increased inflammation, angiogenesis, cartilage
degradation and joint destruction
EARLY INTERVENTION IS CRITICAL
27
Management
  • NSAIDS
  • Disease Modifying Agents (DRUGS)
  • Joint Replacement
  • Physical and Occupation therapy
  • Ophthalmologic monitoring
  • Social support, education and family counseling

28
NSAIDS
  • Naproxen
  • Nabumetone
  • Diclofenac
  • Indomethacin
  • Ibuprofen, Naprosyn, Celebrex and Tolmentin are
    approved for children
  • Used for all types
  • Usually sufficient for PaJIA, mild
    spondyloarthropathy mild cases of other types.
  • Follow LFTs, UA
  • Watch for GI, skin and psychiatric symptoms

29
Disease Modifying Anti-Rheumatic Drugs (DMARD) or
Slow Acting Anti-Rheumatic Drugs (SAARDS)
  • Cyclophosphamide
  • Leflunamide (Arava)
  • Thalidomide-in SoJIA
  • Tacrolimus
  • Novel Biologics
  • Gold
  • Autologous bone marrow transplantation in severe
    cases of SoJIA
  • Monitor- LFTs, CBC, UA, BP, neuropathy

Methotrexate- current gold standard Sulfasalazine-
in enthesitis-related arthritis Cyclosporine -
SoJIA (superior in combination with
Mtx) Azathioprine Hydroxychloroquine Doxycycline
30
NOVEL BIOLOGICS
  • Etanercept is a recombinant fusion dimeric
    protein (sTNFR)
  • Infliximab -Monoclonal Anti-TNF antibody (murine
    component)
  • Combination of Etanercept and Methotrexate
  • Adalimumab (Humira) Fully humanized TNF alpha
    Mab with human derived heavy and light chain
    variable regions and human IgG constant regions.
  • Anakinra (Kineret) IL-1 Receptor antagonist
    blocks cellular activation
  • Anti-IL-6R ab Anti-IL-6 receptor antibody
    prevents the formation of IL-6/IL-6R complex and
    eventually inhibits the function of IL-6 in
    children with SoJIA
  • Abatacept
  • Adverse events

31
Not every bird is this easily identifiable
Case 3 10 year old Caucasian boy presented with
new-onset right swollen knee of three days
duration. He has been afebrile and without rash.
32
The swollen joint
Case 4 7 year old Caucasian girl presented with
left swollen knee. 10 days ago she developed a
sore throat. She has been afebrile and without
rash.
33
Case 5 14 year old Hispanic boy had bloody
diarrhea a month ago and for the last 2 weeks is
complaining of swelling of his left and right
wrists, his left ankles, and left and right 3rd
and 4th toes. He has been afebrile and without
rash.
34
Now all three children feel generally well except
for arthritis
35
Work-up
  • All three children have an unremarkable exam
    except for arthritis
  • Complete blood count and differential,
    electrolytes, blood urea nitrogen, creatinine,
    and urine analysis are within normal limits
  • Erythrocyte sedimentation rate range from 30-40
    mm/hour
  • The X-rays of the respective joints show only
    soft tissue swelling
  • They were all started on non-steroidal
    anti-inflammatory drugs

36
Diagnosis and management
  • Patient 3 tested positive for Lyme Western Blot
    IgG Treated with oral Doxycycline for Lyme
    disease.
  • Patient 4 had elevated Antistreptolysin-O titre
    and anti-strep-DNAse B antibodies and had normal
    electrocardiogram and echocardiogram Started on
    oral Penicillin treatment and prophylaxis for
    Post-Streptococcal Reactive Arthritis.
  • Patient 5 had stool culture positive for
    Salmonella Treated with Amoxicillin for Reactive
    Salmonella Arthritis.

All became asymptomatic in three months.
37
Reactive infection-related arthritis
8-41 of Peds Rheum Clinic patients (UK, US
Canada) Hallmark Peripheral arthritis,
asymmetric arthritis history preceding infection
  • Viral Ebstein Barr Virus, Rubella, Parvovirus,
    Hepatitis, Mumps, Herpes, HIV, Echovirus
  • Bacterial Poststrepococcal arthritis, Rheumatic
    fever, Gonococcal, Chlamydia, Yersinia,
    Salmonella, Shigella, Campylobacter, Mycoplasma,
    Clostridium
  • Lyme disease
  • Septic, Tuberculosis, Fungal, Protozoal
  • Reiters syndrome

38
Reactive arthritis
  • Non-specific arthritis after an extra-articular
    infection with one of the arithritogenic bacteria
    such as Chlamydia, Shigella, Salmonella, Yersinia
    or Campylobacter
  • Here the term encompasses arthritis related to
    extra-articular infections
  • Berlin Diagnostic Criteria
  • Typical peripheral arthritis PLUS
  • Evidence of preceding illness
  • Exclude juvenile idiopathic arthritis and other
    arthritis of known causes
  • Usually clinical features characteristic of
    primary infection

39
Case 6 A teenage Asian girl with 3 month history
of malar rash
  • She also presented with
  • Palatal ulcers
  • Photosensitivity
  • Fatigue
  • Myalgias and arthralgias
  • Mild anemia
  • ANA titre of 1320

40
Systemic lupus erythematosus 1982 classification
criteria --4/11
Renal disorder Neurologic disorder Hematologic
disorder Immunologic disorder Antinuclear antibody
Malar rash Discoid rash Photosensitivity Oral
ulcers Arthritis Serositis
Systemic lupus erythematosus 1982 classification
criteria Tan EM, Cohen AS, Fries JF, et al. The
1982 revised criteria for the classification of
systemic lupus erythematosus. Arthritis Rheum
1982251271-1277.
41
Some facts
  • Incidence 0.36 -0.9 per 100,000 per year
  • Prevalence lt1- 4.5 of patients in pediatric
    rheumatology
  • Age Childhood onset 15-17 , Rare (but still
    occurs) below 5 years
  • Sex More in females (MaleFemale ratio 14.5)
  • In younger age group, the ratio is almost equal
  • Race African-American, Hispanic, Asian
  • Genetics Family and Twin studies
  • Etiology Unknown!!! Genetic-abnormalities in
    immune function regulation-Environmental Hormonal

42
Clinical presentation --SLE
  • PRESENTATION - fever, fatigue, weight loss,
    irritability
  • SKIN
  • Malar rash-Fixed erythema, flat or raised, over
    the malar eminences, tending to spare the
    nasolabial folds
  • Discoid rash-Erythematous raised patches with
    adherent keratotic scaling and follicular
    plugging atrophic scarring may occur in older
    lesions
  • Other types of rash, nail involvement, hair loss
    (alopecia)

Photosensitivity Skin rash as a result of unusual
reaction to sunlight, by patient history or
physician observation
Alopecia
43
Clinical presentation --SLE
Oral ulcers -Oral or nasopharyngeal ulceration,
usually painless, observed by physician
Telangiectasias
Vasculitis
44
Clinical presentation --SLE
Joints and Muscles joint pain and swelling
(arthralgias and arthritis), muscle pain and
inflammation (myalgias and myositis)
Arthritis-Nonerosive arthritis involving 2 or
more peripheral joints, characterized by
tenderness, swelling, or effusion
45
Renal
Clinical presentation --SLE
  • Clinical nephritis in 75 of children, blood in
    the urine (hematuria- cannot always see with your
    eye-need to get urine tests with your physician),
    swelling, high BP
  • Renal disorder
  • a) Persistent proteinuria greater than 0.5 grams
    per day or grater than 3 if quantitation not
    performed
  • OR
  • b) Cellular casts--may be red cell, hemoglobin,
    granular, tubular, or mixed

46
Clinical presentation --SLE
WHO classification of nephritis Normal
glomeruli Nil by all techniques Normal by light
but deposits on EM/IF Mesangial
glomerulonephritis (GN) Focal GN Diffuse
GN Diffuse membranous GN Advanced sclerosing GN
47
Clinical presentation --SLE
  • Serositis
  • a) Pleuritis--convincing history of pleuritic
    pain or rubbing heard by a physician or evidence
    of pleural effusion
  • OR
  • b) Pericarditis--documented by ECG or rub or
    evidence of pericardial effusion
  • Cardiac - inflammation of different parts of the
    heart (pericarditis, myocarditis,valuvilitis),
    Myocardial infarction
  • Lungs

48
Central Nervous System-- SLE
  • 20-40 of affected children, depression,
    difficulty in concentrating, cognitive impairment
    (52 of children), lupus headache, seizures
    etc.
  • a) Seizures--in the absence of offending drugs or
    known metabolic derangements e.g., uremia,
    ketoacidosis, or electrolyte imbalance
  • OR
  • b) Psychosis--in the absence of offending drugs
    or known metabolic derangements, e.g., uremia,
    ketoacidosis, or electrolyte imbalance

PUNCTATE AREAS OF INFARCTS
  • Antiphospholipid antibody syndrome
  • Sjogrens
  • Endocrine abnormalities

49
Laboratory exam
  • General
  • Hematologic disorder
  • Hemolytic anemia--with reticulocytosis OR
  • Leukopenia--less than 4,000/mmltgt3ltgt total on 2 or
    more occasions OR
  • Lyphopenia--less than 1,500/mmltgt3ltgt on 2 or more
    occasions OR
  • Thrombocytopenia--less than 100,000/mmltgt3ltgt in
    the absence of offending drugs
  • Evidence of immune dysfunction
  • Bleeding and clotting abnormalities
  • Liver functions
  • Sedimentation rate (inflammation)
  • Blood and protein in urine

50
Laboratory abnormalities
  • Low complements- C3, C4
  • Autoantibodies -ANA, Anti-ds-dna, ENA
  • Antiphospholipids
  • Immunologic disorder
  • a) Positive LE cell preparation OR
  • b) Anti-DNA antibody to native DNA in abnormal
    titer OR
  • c) Anti-Sm presence of antibody to Sm nuclear
    antigen OR
  • d) False positive serologic test for syphilis
    known to be positive for at least 6 months and
    confirmed by Treponema pallidum immobilization or
    fluorescent treponemal antibody absorption test

51
ANA Fluorescence Patterns
  • Rim (peripheral) SLE
  • Homogeneous (diffuse) Drug-induced LE SLE
  • Nucleolar Scleroderma
  • Speckled SLE Sjogren's MCTD
    Scleroderma

52
Approach to management
  • General
  • Routine/flare-worsening
  • Team approach
  • Adequate rest
  • Sun-protection
  • Immunizations
  • Prompt management of infection
  • Subspeciality visits
  • Call doctor prior to any procedure-may need extra
    antibiotics or steroids
  • Evaluate mood (patients may get depressed!!!)

53
Approach to management
  • Medications
  • NSAIDS (motrin, naprosyn, relafen etc)
  • Steroids (Prednisone)
  • Immunosuppressives
  • Azathioprine
  • Mycophenolate mofetil
  • Methotrexate
  • Cyclophosphamide
  • Cyclosporin
  • Tacrolimus
  • Rituximab
  • Try to wean them off steroids as they are stable
    on an immunosuppressive agent
  • Monitoring side effects
  • Other medications-for high BP, diabetes,
    osteoporosis etc.

54
Hydroxychloroquine toxicity
Medication Side effects
NSAIDS (Motrin, Aspirin, Relafen) - Liver and
kidney function, gastritis Antimalarial drugs
(Plaquenil)- Retinal damage Steroids-Cushingoid
appearance, thinning of skin, acne, short
stature, suppresses immunity, osteoporosis,
avascular necrosis (may need joint replacement),
cataracts, etc. Very important to not miss any
doses/ or drastically change without speaking to
your physician! Other immunosuppressive agents
-risk of infection, liver and kidney function,
blood counts, risk for cancer, risk for
infertility, affects bladder
55
Prognosis
  • Infections, steroid complications,
    atherosclerosis
  • New treatments and better survival
  • Survival has improved in the past 20 yrs
  • 10-year survival approaches 90
  • Extent of organ involvement (renal, central
    nervous system), apparent vasculitis, and
    multisystemic character of the disease
  • Sepsis (severe life-threatening infection) is the
    commonest cause of death
  • Important determinants families ability to
    cope, socioeconomic status, compliance,
    teen-related issues, contraception
  • Atherosclerosis

56
Neonatal lupus erythematosus
Heart block Rash Liver disease Low
platelets Anti- Ro and -La antibodies
57
Case 7 Proximal muscle weakness and rash
A 5 year-old Caucasian girl had sudden onset of
muscle pains followed by weakness, symmetric,
scaly, erythematous papules over the
metacarpophalangeal and proximal interphalangeal
joints of the hands, and reddish purple facial
rash.
58
Juvenile Dermatomyositis (JDM)
  • Vasculitis frequent often severe
  • Calcinosis common in recovery phase
  • Polymyositis uncommon
  • Malignancy rare

59
Epidemiology
  • Incidence 0.5 per 100, 000/year
  • 20 Onset in childhood
  • 4-10 years Boys 6 years Girls 6, 10 years
  • FM - 1.41 to 2.71 higher for gt/10yrs
  • Widely distributed
  • Blacks gt Whites

60
Clinical features
  1. Constitutional Fever 38-40C, easily fatigued,
    anorexia, malaise, wt loss
  2. MSKS symmetric proximal- weakness of LE limb
    girdle anterior neck flexors/back abdo, Gowers
  3. Pelvic girdle- stairs, Trendelenburg- weak hip
    adductors
  4. Severe (10)
  5. Threat of aspiration
  6. DTRs usually nl

61
Clinical features
  • Visceral vasculitis (pancreatitis, melena,
    hematemesis, perforation)- poor
    prognosis--rapidly leads to death
  • Also gall bladder, bladder, uterus, vagina,
    testes, retinitis, mild GN
  • Cardiopulmonary
  • Lipodystrophy 20 (assoc. with insulin
    resistance)

62
Diagnosis
  • Proximal muscle weakness
  • Classic rash
  • Elevated serum muscle enzymes
  • Electromyographic changes
  • Histopathology

Name the muscle enzymes
63
Diagnostic tests
  • Leukocytosis, anemia -rare unless GI bleed
  • High CRP, ESR
  • Microscopic hematuria
  • IgA, IgG, IgE
  • CPK, AST, Aldolase, LDH, ALT
  • ANA 10-85
  • MSA MAA
  • MRI
  • T1-fibrosis, fat infiltration, atrophy
  • T2-fat suppressed-edema/inflammation
  • EMG
  • Muscle biopsy

64
Treatment and Prognosis
  • Presteroid-1/3 1/3 1/3
  • Steroids
  • Hydroxychloroquine
  • Methotrexate, Cyclosporine, Cyclophosphamide,
    Azathioprine, anti-TNF
  • IVIG
  • Plasmapheresis
  • Supportive care
  • PT, OT
  • Calcinosis

Prodrome-progressive-persistent-recovery
Monocyclic, Chronic ulcerative, Chronic
non-ulcerative Poor severe disease activity,
cutaneous ulcerations, calcinosis, distal
involvement, dysphagia/dysphonia, nailfold
changes, noninflammatory vasculopathy, specific
MSAs Long term survival gt90
65
Rheumatology Case 8
  • 3 year old boy with a 3 day history of swollen,
    painful ankles
  • Low grade fever
  • Physical examination normal except for swelling,
    pain on motion, warmth, tenderness of both ankles
  • Found on routine laboratory tests to have
    moderate hematuria, heavy proteinuria
  • Purpura

66
Clinical picture varies with size of vessel
involved
67
Vasculitis
  • Characterized by size of vessel
  • Large (Takayasu)
  • Medium and small (Kawasaki, PAN)
  • Small (SLE, JDM, serum sickness,
    hypersensitivity, HSP, neoplasm associated)
  • Characterized by cellular infiltrate
  • Giant cells (Takayasu, WG-ANCA)
  • Neutrophils with nuclear debris (HSP)

68
Antineutrophilic cytoplasmic antibodies
(ANCA)-cytoplasmic and perinuclear
pANCA -Microscopic polyarteritis, Churg-Strauss
syndrome, rapidly progressive glomerulonephritis,
inflammatory bowel disease, and a variety of
other conditions. cANCA -Wegener's
granulomatosis and closely related vasculitides
69
Classification criteria for Henoch-Schonlein
Purpura
  • At least two of the following 4 should be present
    (ACR criteria 1990)
  • Palpable purpura
  • lt20 years
  • Bowel angina (Diffuse abdominal pain that is
    worse after meals/ bowel ischemia, bloody
    diarrhea)
  • Wall granulocytes on biopsy

70
Henoch-Schonlein Purpura
22/100,000 children MgtF children Associated
with Rheumatic fever Group A strep antigens on
glomeruli of patients with HSP nephritis
Siblings with HSP following infectious
mononucleosis are described, although one of
these siblings had hematuria before the HSP--
genetic predisposition?
Tuberculosis Colitis /GI lesions
Winters Infections such as streptococcus,
bartonella, hepatitis A, H. parainfluenzae Vaccina
tions - Hepatitis B and Meningococcal Azithromyci
n Insect bite
71
PATHOGENESIS
Antiendothelial cell antibodies
(AECAs) Interleukin 1 receptor antagonist gene
polymorphisms HLA B subtypes may play a role in
renal disease and HSP (HLA B 35)
72
Henoch-Schonlein Purpura
  • Cutaneous manifestations occurs in 96-100
  • Palpable purpuric lesions
  • Dependent/pressure bearing areas
  • Acute, symmetric, erythematous, macular or
    urticarial
  • Coalesce to form palpable purpura
  • Occur in crops and change color from red to
    purple to brown

73
Clinical Features
  • GI involvement (1-4 weeks) in 75
  • Abdominal pain (80) colicky, periumbilical
  • Vomiting, abdominal distention
  • Melena, hematemesis, ileus
  • Submucosal bleeding
  • Intussusception (3), ileoileal (easily missed by
    barium enema)
  • Mesenteric vasculitis
  • Rare pancreatitis, gallbladder hydrops,
    pseudomembranous colitis
  • Genitourinary complications
  • Musculoskeletal involvement (50-85)
  • CNS vasculitis
  • Thrombotic complications
  • Brain infarcts (IgA APLA)

74
Renal Involvement
  • One-third of the children
  • Life threatening/Serious is lt10
  • Within one month of rash
  • Spectrum mild proteinuria/microscopic hematuria
    to NS, HTN, renal failure, acute nephritic
    syndrome
  • Risk factors for renal diseasegt7 years of age,
    persistent pupuric lesions, severe GI complaints,
    decreased factor XIII activity
  • Focal or segmental mesangial proliferation to
    crescentric

Crescentric GN
75
Henoch-Schonlein Purpura
  • High WBC
  • Nl/high Platelets
  • Normochromic anemia, guaic ve stools
  • High IgA, high IgA ANCA
  • Low complement
  • D/D- ITP, Acute post strep, SLE, Septicemia, DIC,
    HUS, Acute Hemorrhagic edema
  • Opposite IgA deposition in skin

76
Prognosis
  • Recurrence is 16-40 (6wk-2yr)--rash and
    abdominal pain
  • Prognosis is usually excellent
  • Poor prognosis
  • Major indications of renal disease in the first 3
    mo after onset or numerous exacerbations assoc.
    with nephropathy
  • Decreased factor XIII activity
  • Hypertension and renal failure at disease onset
  • Increased number of glomeruli with
    crescents,macrophage infiltration and
    tubulointerstitial disease
  • Nephritic or nephrotic syndrome at onset

77
Prognosis
  • Renal outcome is variable
  • Minimal lesions-gt75 recover in 2 years
  • 2/3rds with crescentric GN progress to renal
    failure within the first year
  • Overall HSP accounts for lt1 of children with
    renal failure of all causes
  • Renal failure can develop up to 10 years after
    onset
  • 1-5 may develop ESRD

78
Treatment
  • Usually none or supportive with acetaminophen
    (analgesia)
  • Short term steroids (initially IV) for severe GI,
    urologic manifestations and orchitis
  • 1-2 mg/kg/d for 1 week then taper over 2-3 wks
  • Renal prophylaxis with steroids?
  • Severe renal disease pulse steroids,
    azathioprine or cyclophosphamide, urokinase plus
    warfarin, IVIG, plasmapheresis
  • (Wang et al)

79
Rheumatology Case 9
18 month old boy with daily fever for 7 days
associated with irritability, polymorphous rash,
diffuse swelling of all fingers and dorsum of
hands Also had adenopathy, cheilosis,
conjunctivitis, and mucous membrane changes
80
Kawasaki Disease
  • An acute febrile illness of childhood with medium
    and small sized necrotizing vasculitis first
    described by Kawasaki in 1967

Classification criteria
Fever persisting for at least 5 days (mandatory
criterion) plus 4 of the following 5 should be
present
81
KD
1) Changes in peripheral extremities or perineal
area (80)
2) Polymorphous exanthema (gt90)
3) Bilateral conjunctival injection (80-90) 4)
Changes of lips and oral cavity injection of
oral and pharyngeal mucosa (80-90)
82
KD
5) Cervical Lymphadenopathy one nodegt1.5 cm
(50) In the presence of coronary artery
involvement detected on echocardiography and
fever, fewer than 4 of the remaining 5 criteria
are sufficient (exact number of criteria required
to be defined in the validation phase)
83
KD other clinical
  • Arthritis/arthralgia (acute, subacute,
    convalescent phases)
  • Meningitis, irritability
  • Encephalopathy, seizures, ataxia Pneumonitis
  • Iritis
  • Gastroenteritis, watery diarrhea
  • Meatitis, sterile pyuria, priapism
  • Otitis, cough, coryza
  • Intestinal ischemia, infarcts

84
KD Phases
  • Acute febrile period lasting approximately 10
    days (range 5-25d).
  • Associated rash, carditis, CHF, mucous membrane,
    conjunctiva, adenitis, abdo pain, hydrops
  • Subacute period of approximately 2-4 weeks
  • Arthritis, perineal and extremity desquamation,
    coronary artery aneurisms
  • Plt, ESR returns to normal
  • Convalescent phase lasting months
  • Nail changes, aneurisms, arthritis

85
Pathogenesis
  • Postulated theories
  • Infectious/Viral
  • Superantigen
  • Cytokine related
  • Aberrant immune response triggered by a pathogen
    acquired through respiratory route
  • Oligoclonal antigen driven response
  • Endothelial cell activation, CD68
    monocyte/macrophages, CD8 (cytotoxic)
    lymphocytes, and oligoclonal IgA plasma cells
    appear to be involved.
  • Subtle maturational defect in immune
    responsiveness
  • Genetic variations in the receptor-ligand pair
    CCR5 and CCL3L1 (Burns et al)

86
KAWASAKI DISEASE OUTCOMES
ACUTE MORBIDITY Cardiac complications 25
aneurism, 1 mortality without IVIG
treatment 4-7 aneurysms with IVIG
treatment Vascular complications Gangrene Thrombo
sis
CHRONIC MORBIDITY Coronary arteries Alterations
in morphology and function Myocardium Lymphocytic
infiltrate Fibrosis
87
KD
  • MgtF
  • 6-11 months
  • AsiansgtEuropeans
  • Acute febrile, subacute, covalescent
  • CAA in 5 many develop coronary artery ectasia
  • Giant aneurysms (gt 8 mm)
  • Stenotic leading to MI
  • Rupture acutely or develop later thrombosis due
    to stasis of blood flow and the procoagulant
    endothelial surface
  • ? Anticoagulant therapy

Death rare after first 2 mo Recurrence is rare
(3) May result in CAD in later years (up to 12
years) and cause sudden death in acquired CAD
12 of cardiac causes of sudden death in
children and young adults
88
THERAPY
  • ASA 80 to 100 mg/kg per day in 4 doses with IVIG
    for 3-14 days
  • High-dose ASA and IVIG appear to possess an
    additive anti-inflammatory effect.
  • Low-dose ASA (3 to 5 mg/kg per day) until no
    evidence of coronary changes
  • For children with coronary abnormalities,
    aspirin may be continued indefinitely
  • Naproxen

89
THERAPY
  • IVIG (2 g/kg) with aspirin (5080100 mg/kg)
    given within 10 days of fever onset
  • Second infusion of IVIG (2 g/kg) in addition to
    high-dose aspirin is strongly recommended in all
    children with persistent or recurrent fever
  • How to treat the small group (34) still
    remaining febrile?
  • Either a third dose of IVIG (2 g/kg)
  • Corticosteroids
  • Cyclophosphamide, cyclosporin and ulinastatin
  • Anti-TNF agents (Infliximab)
  • Weiss J, Eberhard A, Chowdhury D, Gottlieb B, J
    Rheum, 2004

90
Case 10 10 year old black male with cough and
weight loss for one month
  • Fever for one month
  • Increasing tiredness and myalgias
  • Asthma exacerbation
  • Unable to exercise or play as much as he used to
  • Palpable bilateral non-tender cervical lymph
    nodes
  • Hepatomegaly with mild tenderness
  • Mild wheezing on auscultation
  • Lymphopenia and anemia
  • Normal ESR, CRP 4.2 mg/dl
  • Negative for HIV, Hepatitis A, B, C and
    Parvovirus and TB
  • Serum calcium 9.1 mg/dl (8.5 - 10.5)

91
Sarcoidosis
Chest X-Ray and chest CT scan showed diffuse,
bilateral, pulmonary interstitial infiltrate and
perihilar adenopathy Gallium scan showed
multiple areas of enhancement
92
Older vs. Younger children
  • Asymptomatic
  • Clinical presentation can vary greatly
  • Older children --- multisystem disease similar to
    the adult manifestation, with frequent hilar
    lymphadenopathy and pulmonary infiltration
  • Early-onset childhood sarcoidosis --- triad of
    rash, uveitis, and arthritis in patients
    presenting before age 4 years.
  • Lofgren's syndrome - EN, bilateral hilar
    adenopathy, joint symptoms

93
Pediatric Sarcoidosis
  • Lymphadenopathy -most common
  • Intrathoracic - 75 to 90
  • hilar nodes bilaterally
  • unilateral enlargement
  • paratracheal nodes
  • Peripheral - cervical, axillary, epitrochlear,
    inguinal
  • Non-tender, non-adherent, with a firm, rubbery
    texture
  • Chronic cough (2nd most common)
  • Parenchymal disease (infiltrates, effusions,
    atelectasis), restrictive
  • Half with pulmonary symptoms
  • Dyspnea, cough, chest pain
  • 20 with abnl CXR and minimal/ no symptoms

25 with constitutional symptoms
Hepatosplenomegaly Skin disease 30 Eye
disease Neurological-7th, 3rd, 10th
CN Musculoskeletal lt5-50 -ankles, knees,
minimal pain/ limitation Bone cysts 5
GI Salivary glands Heart Renal,
nephrocalcinosis Testicular mass Muscle
granulomatous involvement 50-80 Nodular vs.
Myopathic
94
Diagnosis
  • Anemia 5
  • Leukopenia 30
  • Eosinophilia 25
  • Thrombocytopenia
  • High ESR with EN, acute phase
  • Hypercalcemia, hypercalciuria ---2-63
  • High Bili, Alk phos
  • Proteinuria ---30
  • ACE
  • Kveim test
  • CXR, Gallium
  • BAL --- high Lymphocyte count and macrophages
    high CD4/CD8
  • High IL-1B, IL-6, TNF alpha
  • Anergy to PPD
  • Biopsy- Non caseating granuloma

95
Linear scleroderma
Management Observation Emollients Methotrexate
Phototherapy PT and OT Surgery
96
Systemic Sclerosis
  • Major criterion - sclerodermatous skin changes
    affecting areas proximal to the
    metacarpophalangeal or metatarsophalangeal joints
  • Minor criteria are as follows
  • Sclerodactyly
  • Digital scars resulting from digital ischemia
  • Bibasilar pulmonary fibrosis not attributable to
    pulmonary disease
  • Diffuse Interstitial pulmonary fibrosis Anti
    Scl 70 ab
  • Limited (CREST) Pulmonary hypertension
    Anticentromere ab

97
Case
  • A 10yo high-achieving Caucasian girl S/P injury
    to her right foot 2 months ago presents with a
    swollen and cold right foot to your clinic. She
    is in a wheelchair and will not let you touch her
    foot. She is in excruciating pain.

98
  • Functional joint complaints
  • Reflex neurovascular dystrophy
  • Fibromyalgia
  • Amplified Pain Syndrome

99
Other topics
  • Hypermobility syndrome
  • Disorders of connective tissue
  • Marfan syndrome
  • Ehlers-Danlos syndrome

100
Thank You
This presentation is specifically prepared for
the board review course by Dr. L. Nandini
Moorthy. This may not be reproduced without the
permission of Dr. L. Nandini Moorthy ( June 9,
2007)
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