3. What is vasculitis?
• Inflammation of the blood vessels
• Can be idiopathic, infectious related or due to medications and
immune mediated
• Some forms of small vessel vasculitis can also be associated with Anti-
neutrophil cytoplasmic antibodies (ANCA)
• Classification based on vessel size:
• Large- aorta and proximal branches
• Medium- renal arteries, mesenteric vasculature, coronary arteries
• Small- capillaries, arterioles, post-capillary venules
4. Vasculitis definition
Pathologist
Inflammatory destruction of
blood vessels
Infiltration of vessel wall with
inflammatory cells
Leukocytoclasis
Elastic membrane disruption
Fibrinoid necrosis of the vessel
wall
Ischemia, occlusion, thrombosis
Aneurysm formation
Rupture, hemorrhage
Rheumatologist
A clinicopathologic process
characterized by inflammatory
destruction of blood vessels that
results in occlusion or destruction of
the vessel and ischemia of the tissues
supplied by that vessel.
“Systemic vasculitides”
7. Clinical Features
• Fever, weight loss, fatigue of unknown origin
• Skin lesions (palpable purpura, vasculitic urticaria, livedo reticularis,
nodules, ulcers)
• Neurologic lesions (headache, mononeuritis multiplex, focal central
nervous system lesions)
• Arthralgia or arthritis, myalgia or myositis – Joint pain or swelling,
calf pain
• Serositis
• Hypertension
• Pulmonary infiltrates or hemorrhage
8.
9. Purpura - bleeding under the skin or into mucosal membranes. May be an
innocent finding related to mild childhood trauma or may be the presenting
sign of a life threatening disease
Purpura can be subdivided based on size into –
(do not blanch when pressure is applied to the skin)
Petechiae - Pinpoint areas (less than 2 mm) of hemorrhage,
which are reddish-purple lesions
Ecchymoses - larger confluent lesions
10. DISRUPTIONS IN VASCULAR INTEGRITY
Trauma - common etiology. Red, blue, or purple bruises suggest
recent lesions. Yellow, brown, or green bruises tend to be older
Infection - result of microvascular thrombosis – Purpura fulminans
(PF) - Erythema is followed by central areas of blue or black
hemorrhagic necrosis with a surrounding erythematous border. -
Neisseria meningitides, varicella, Group A Streptococcus,
Streptococcus pneumoniae
Immunoglobulin A vasculitis (IgAV; Henoch-Schönlein purpura [HSP]) - most
common cause of vasculitis in children - palpable purpuric lesions 2 to 10 mm in
diameter that often coalesce – results of IgA1 deposition in blood vessel walls
Vitamin C deficiency - pale halo ring around
a central erythematous core - impaired
collagen synthesis
Leukemia, and coagulopathies
16. Doctor, Doctor, my child has a high fever and a
red tongue…..
• 3 year old Asian girl is brought in for persistent fevers of 39oC for more than two
weeks. Patient was taken to primary pediatrician and was given antibiotics for a
sorethroat 10days ago but no improvement in fevers, neck masses or the redness
of the tongue and oral cavity. Fevers are improving but the girl has conjunctival
injection and has periungual and perianal desquamation and incredibly irritable
and poor appetite. No N/V/D/myalgias but reporting joint pains.
• QUESTIONS?
• DIFFERENTIAL DIAGNOSES?
• WORK UP?
17.
18. Kawasaki Disease
• Aka MUCOCUTANEOUS LYMPH NODE SYNDROME
• febrile vasculitis of childhood
• cause is unknown
• unlikely in <4 months due to maternal Ab
• 80% are under 5 years of age
• Path: severe inflammation of medium sized vessels, with strong affinity for the
coronary arteries, leading to destruction of the intimal layer (all 3 layers involved
in severe cases)
• Cardiac disease: MOST COMMON, decreased ventricular function 2o
myocarditis, pericarditis, and coronary aneurysms, thrombosis, stenosis, and
sudden death.
19. Kawasaki disease cont...
• Clinical manifestations:
• Acute phase: 1-2 weeks with fevers upto 104F and unresponsive to Antibiotics
• Subacute phase: irritability, anorexia, conjuctival infection, desquamation of periungual
and perineal regions and arthritis
• Convalescent stage: 6-8 weeks post onset of disease
• bilateral bulbar conjunctival injection without exudate
• strawberry tongue and oral erythema
• erythema and edema of arms and legs
• CERVICAL LYMPHADENOPATHY > 1.5 cm
• Rash
• Differential Diagnoses:
• Scarlet fever, TSSS, Measles, SJS, JRA, and RMSF
20.
21.
22. Kawasaki Disease – small and medium
• An angiogram of the ascending
aorta and coronary vessels
showing aneurysmal dilatation
of the coronary vessels in a
patient with Kawasaki disease,
another vasculitis that
• Cardiovascular features of
vasculitis may include
claudication; bruits over major
arteries; pulselessness,
inequality of pulses, or blood
pressure differences between
limbs; presyncope or syncope;
or abnormal heart sounds.
• The slides to follow present
examples of small- to medium-
vessel disease.
25. Kawasaki disease KD - treatment
• IVIg at a dose of 2g/kg as a single infusion over 12h, should be started
early preferably within the first 10 days of the illness.
• Aspirin 30–50mg/kg/day in 4 divided doses. The dose of aspirin can
be reduced to 2–5mg/kg/day when the fever settles (disease
defervescence). Aspirin at antiplatelet doses is continued for a
minimum of 6 weeks.
• In refractory cases infl iximab, a human chimeric anti-TNF A
monoclonal antibody, given IV at a single dose
26. Doctor, Doctor, my son has a rash for 3
days…..
• 8 year old male who is very active in sports, presents with complaints of rash and
swelling of the feet and ankles. Pt’s mother noticed a progressive bumpy red rash
and the swelling over the past three days. Rash is also present on buttocks
bilaterally and onset similar to that of the feet. Low grade fevers for a week, no
nausea or vomiting but reported frothy urine and intermittent abdominal pain
over the past few hours. History of a URI in the family, including the child, 2-3
weeks ago. No family history. No PMHx.
• QUESTIONS?
• DIFFERENTIAL DIAGNOSES?
• WORK UP?
28. What is IgA vasculitis (Henoch-Schönlein
purpura)?
• Small vessels vasculitis associated with IgA immune complexes. Self limited
• IgAV (HSP) occurs primarily between the ages of 3 and 15 years
Clinical features:
✔Skin rash: - Palpable purpura over buttocks and lower
legs, edema over dorsum of hands an feet, scrotum and
periorbital area.
✔Arthritis: Typically short-lived, affecting large joints
(knees, ankles or elbows).
✔Gastrointestinal: colicky abdominal pain, melena and
hematemesis.
✔Renal: Dipstick hematuria and proteinuria are present
(20%-50%) - nephritis
The ACR criteria for the diagnosis of
IgAV (HSP) are as follows:
- Palpable purpura
- Age at onset ≤20 year
- Acute abdominal pain
- Biopsy showing granulocytes in
the walls of small
arterioles and/or venules
29. Henoch-Schönlein purpura HSP
Investigations: No laboratory test is diagnostic for IgAV
▪ CBC and coagulation tests (PPt, PT and bleeding time)
▪ Urine analyses - for evidence of renal involvement: microscopic hematuria
71%, macroscopic hematuria, proteinuria 48%, renal function creatinine in
children with hypertension
▪ Skin biopsy is rarely necessary.
▪ Abdominal ultrasonography
Treatment: Self- limited within 6 weeks
▪ May be need NSAIDs for pain and arthritis symptoms.
▪ Is severe cases corticosteroids may speed symptoms resolution and prevent
renal disease.
30. Juvenile idiopathic arthritis JIA
• chronic idiopathic inflammatory disorder primarily involving joints.
• Previous – JRA in US and JCA in EU
• It a diagnose of exclusion in children < 16 years old with a history of at least 6 weeks of
persistent arthritis.
• JIA is divided into 7 subsets
• the female:male ratio ranges from 2:1 to 3:1
International League of Association of Rheumatology (ILAR) classification of JIA
Systemic arthritis 10-13%
Oligoarthritis (persistent or extended) 40-50%
Polyarthritis (Rheumatoid factor +) 3%
Polyarthritis (Rheumatoid factor -) 27%
Psoriatic arthritis 2-15%
Enthesitis-related arthritis 1-7%
Undifferentiated arthritis 2-15%
31. Differential diagnoses of childhood arthritis
Infection Bacterial: sepstic arthritis, osteomyelitis.
Viral: Rubella, Parvovirus B19, Cocksackie, IBV
Lyme, Brucella, TUB, gonorrhea
Post infection Reactive arthritis
Post streptococcal reactive arthritis
Rheumatic fever
Malignancy Leukemia or Lymphoma, Neuroblastoma, Primary bone tumors, Joint
Hypermobility
Orthopedic Perthe’s disease, Hip dysplasia, Chondromalacia
SID Crohn’s disease, Ulcerative colitis, Celiac disease
Metabolic Disorders Gout
Mucopolysaccharidoses
Immunodeficiency
syndromes
IgA and IgG deficiency, DiGeorge syndrome
Hematologocal Sickle cell diseases, other hemoglobionopathies, hemophilia
32. Differential diagnoses of childhood arthritis
Rheumatic diseases Systemic lupus erythematous (SLE)
Juvenile dermatomyositis
Systemic sclerosis – localized or systemic
Vasculitis: HSP, Kawasaki, Takayasu arteritis
Other inflammatory
disorders
Sarcoid
Chronic reccurent multifocal osteomyelitis
SAPHO (S- ynovitis, A- cne, P-ustulosis, H-yperostosis amd Osteoitis)
Idiopathic pain
syndromes
Fibromyalgia
“Nonorganic pain” – a cry for help
33. General clinical principles for JIA
Persistent objective signs of joint inflammation must be present for at least
6 weeks.
HISTORY:
▪ Limp, stiffness and loss of function, pain or malaise. Parents describe “like
a little old person in the morning”
▪ Onset it usually gradual. Beware of misleading history of trauma, as young
children frequently fall without significant injury.
▪ Pain in child and irritability in infants
▪ Inflammatory symptoms being worse after rest or inactivity
▪ History of associated rash, fever, and weight loss
▪ Family History of arthritis, psoriasis, IBD, rheumatic fever
34. Examination:
▪ Observe the child before they become self-conscious
▪ Watch them playing and walking
▪ Examine all the joints and spine for swelling, pain, movement
▪ Measure for leg length inequality and pelvic tilt
▪ Examine muscle bulk around the affected joints
▪ Examine the skin, hair, and nails for rashes and psoriasis
▪ General examination: Vital signs
▪ Examine the mouth and palate for ulcer, dentition and asymptomatic
tonsillitis and the heart for murmurs and bruits.
General clinical principles for JIA
35. Systemic arthritis - formerly called Still's disease
Clinical features:
▪ The fever must be present for at least two weeks and the arthritis for at least six
weeks in order to make a definitive diagnosis. Fever is essential up to 39C and must return
to normal or lower between daily attacks.
▪ children must have one or more of the following findings: evanescent, erythematous
rash; hepatomegaly or splenomegaly; mylgia, lymph node enlargement; or serositis
▪ Rash present in 80% - is salmon pink, macular or urticarial on chest, trunk. May be present the
Koebner phenomenon – condition that causes lesions to appear near skin injures
▪ Late complication include amyloidosis
Investigation:
▪ CBC: - anemia, thrombocytosis. ESR/CRP can be very high
▪ Hypoalbuminemia
▪ ANA and RF are usually negative
▪ Viral titers and blood cultures
▪ Malignancy screen: LDH, uric acid, chest X-ray, ultrasound of abdomen
▪ ECG and Echo
36. Systemic arthritis
Management
▪ NSAIDs for pain, fever and serosotis
▪ Pulsed IV corticosteroids 20-30 mg/kg/day
▪ Oral steroids
▪ Intra-articular corticosteroids
▪ Biological therapy Anti TNF and abti-IL-1 cases
Prognosis:
Prognosis
History more than third patients have a permanent disability with active disease
into adult life.
37. Scenario
An 11 years old boy attended in ER with the joint pain that had
first appeared four days before. The joint involve were ankles,
wrists, knees, and fingers. They were painful and accompanied
by redness, swelling and warm sensation. The patient was
unable to walk more in the morning. There was a fluctuating high
fever.
The history of illness started four years ago. Many joints were
affected, including the knees, elbows, wrists, ankles, and fingers,
where all of the inter phalanx joints were involved. The subject’s
complains continued periodically and disappeared after receiving
medication bur reappeared after some time. Each attack lasted two
months
38. Physical examination:
• P – 114’ RR – 48 BP – 105/85
• Examination of the lower extremities showed pes valgus of the left foot,
with the knee and ankle being swollen, tender, red and painful in motion.
The rest of the examination was normal. Auscultation of lung – vesicular
sound was decreased on the left side.
• Lab: Le – 30*109/L, neutrophil 89.9%, PLT – 485*104/L, CRP 385 mg/l
• RF and ANA – negative
• Urine – protein 3+, Le – 0, Er - +1, neg gluc.
• Chest X-ray – pulmonary edema, in the left lung and pericardial effusion
QUESTIONS?
DIFFERENTIAL DIAGNOSES?
WORK UP?
39. Oligoarticular JIA
Duration at least 6 weeks, absent of systemic findings and fewer than 5 joints
affected
The peak incidence of oligoarticular JIA is in the second and third years of
life. It is less common over five years of age and rarely begins after age
10 years.
Clinical features:
▪ Diagnosing of exclusion: rule out infection
▪ Milder symptoms than reactive arthritis
▪ Joint swelling or limping > pain
Investigation:
▪ CBC: CRP (often normal), ANA positive 40-75% - prognostic value for uveitis
Management:
- Regular review to assess joint, eyes and general growth
- NSAIDs for pain and stiffness, in severe cases intra-articular steroids or MTX
- Screen for uveitis initially 3 monthly
The typical child with
oligoarticular JIA is a toddler girl
who is noticed to be limping
without complaint
40. Scenario
This is a 4 year old female who has been limping with swelling of her
right knee for several months. Her parents note that she cannot fully
extend her right knee. She sometimes does not want to walk in the
morning, but seems fine later in the morning and the rest of the day.
Her past medical history is unremarkable. Physical examination
demonstrates swelling (effusion) of her right knee, flexion contracture
of 10 degrees and flexion to 120 degrees. No increased heat or pain
upon range of motion is present. She appears unconcerned about her
limp and swelling. Labs: WBC 8,600 with 45 polys, 47 lymphs, 8 monos.
Hgb 12. ESR 20. UA normal. Rheumatoid factor negative, ANA 1:640
speckled.
41. Rheumatoid factor (RF) – positive polyarthritis
Duration at least 6 weeks, 4 or more criteria. Typically for teenage girls.
ARA CRITERIA for diagnosis of rheumatoid arthritis
1. Morning stiffness - > 1 hour at peak illness
2. Arthritis in at least 5 joints, witnessed by a physician
3. Hand arthritis – wrist, MCPs, or PiP
4. Symmetrical arthritis
5. Rheunmatoid nodules
6. Rheumatoid factor positive
7. Erosions on X-ray
Treatment:
- Start early aggressive therapy
- MTX alone or with steroids
- Bilogocal agents: Anti TNF
42. 30% of cases; Duration at least 6 weeks and 5 or > affected joints within te
first 6 month. Girls- boys 4:1
Clinical features:
▪ Systemic features - low grade fever and transient rashes
▪ Joint swelling leads flexion contractures
▪ Any joint can be affected
▪ Tenosynovitis and bursitis develop
around the finger and feet
Rheumatoid factor (RF) – negative polyarthritis
Treatment:
- Start as soon as possible
- NSAIDs+intra-articular steroids
- MTX
43. Scenario
A 14 year old female presents with a 6 week history of fatigue and facial
rash. Her rash seems to be exacerbated by sun exposure. She has recently
developed pain and swelling in her fingers and wrists. She has no significant
past illnesses. Family history is significant for an aunt with lupus and a
grandmother with thyroid disease.
Exam: VS T 37.8, P 88, R 20, BP 110/66. Height and weight are at the 20th
percentile. She is alert and cooperative. She has thinning hair over her front
scalp with some fine short hairs. She has an erythematous maculopapular
rash over her malar areas spanning the bridge of her nose, erythema of the
hard palate and a few shallow gingival ulcers. Joint exam reveals mild
swelling and tenderness to palpation and range of motion in the proximal
interphalangeal joints of several of her fingers and both wrists. Heart, lung,
abdomen, back and neurological examinations are within normal limits.
Laboratory: WBC 2.5 with 87% segs, 5% lymphs, 6% monos, 2% basophils.
Hgb 10. Platelet count 167,000. ANA 1280. ESR 45. Urinalysis without
protein or blood. No cellular casts or significant red or white cells
44. Systemic lupus erythematosus (SLE)
Complex multisystem autoimmune disorders affecting adolescents (rare in younger children;) SLE is
one of the great MIMICS of the conditions
Revised ACR criteria for classification of SLE
1. Malar rash – “butterfly”
2. Discoid rash (50-70%)
3. Photosensitivity
4. Mucus membranes ulcers (hard palate, nasal septum)
5. Arthritis (non-erosive), may be myositis (61-64%)
6. Renal disease: Persistent proteinuria > 0.5g/24 hours or cellular casts (27-59)
7. Serositis: Pleuritis or pericarditis
8. Neurological disorders: Psychosis or seizures
9. Hematological abnormality: Hemolytic anemia or leukopenia <4.0*10 9/L or Trombocytopenia <100*10
5/L (55-70%)
10. Immunological: Raised anit-DNA-binding antibody, anti-Sm antibody; positive antiphospholipid
antibodies
11. ANA antibody
SLE is
diagnosed if 4
out of 11
45. Hematologic abnormalities, lupus nephritis, fever, ocular symptoms,
seizures, and lymphadenopathy are more common in cSLE than
adult-onset SLE (aSLE), whereas Raynaud phenomenon, pleuritis,
and sicca symptoms (dry eyes, dry mouth) are more common
manifestations in aSLE
Low-grade fever, fatigue, anorexia, and lymphadenopathy are common
manifestations of SLE at onset but do not differentiate the diagnosis of SLE
from other systemic illnesses. Persistent high fevers above 38.6°C (101.5°F)
may occur; however, coexisting infection and MAS should always be
excluded in these cases.
46. Investigation:
▪ BP measurement
▪ CBC, renal function, ANA (98%) – but not every positive ANA means lupus
▪ Coagultaion screen
▪ Anticardiolipin an antiphospholipid test
▪ ESR is often raised.
▪ C3 and C4 are low
Systemic lupus erythematosus (SLE)
Management:
1. Avoid sun exposure
2. Prednisone and steroid-sparing drugs (azathioprine AZA,
MTX)
3. Methylprednisolone pulses and cyclosporine's
4. Experimental therapy – Rituximab, stem cell
replacement
47. Juvenile dermatomyositis JDM
JDM – is an inflammatory disease of skin and muscles, with unknown causes,
host predisposition with infectious and environmental triggers.
The Diagnostic criteria for JDM
1. Symmetrical weakness of proximal muscles – Gowers’ sign when weakness in
limb girdles (LOWER MORE THAN UPPER)
2. Periorbital edema with heliotrope discoloration; scaly rash over MCPs, PiP
(Grottron’s papules); knees, elbows and malleoli
3. Elevation of one or more muscles enzyme: Creatinine kinase, AST, LDH and
aldolase
4. EMG changes of myopathy and denervation
5. Muscle biopsy evidence of necrosis and inflammation
6. MRI
48. Acute Rheumatic Fever
• Develops in susceptible children following infection with the group A,
betta –hemolytic streptococcus
• Most frequently seen in children aged 5-15 years.
• Triggered by an immune-mediated delayed response to infection
with specific strains of group A streptococci – Antigens that may
cross-react with cardiac myosin and sarcolemmal membrane protein
• Latent period 2-6 weeks between the onset of symptoms and
previous streptococcal infection (e.g. pharyngitis)
• Clinical features can be categorized into Jones major and minor
features
49.
50.
51.
52. Carditis
• Involves the endocardium, myocardium and pericardium to varying degrees
• Incidence declines with increasing age - ranging from 90% at 3 years to around 30%
in adolescence.
• It manifest as
- Breathlessness
- heart failure or pericardial effusion
- Palpitations or chest pain
- pericarditis or pancarditis
- Other features include tachycardia, cardiac enlargement and new or changed
cardiac murmurs.
- Aortic regurgitation - 50% of cases but the tricuspid and pulmonary valves are
rarely involved
- Syncope: Conduction defects
- ECG changes: ST and T wave changes
53. Arthritis
▪ Most common and early manifestation
▪ Acute painful asymmetric and migratory inflammation of the large
joints
▪ Typically affects the knees, ankles, elbows and wrists.
▪ Pain characteristically responds to aspirin
▪ If not, the diagnosis is in doubt
54. Skin lesions
Erythema marginatum
– occurs in < 5% of patients
– lesions start as red macules (blotches)
that fade in the centre
– but remain red at the edges
– occur mainly on the trunk and proximal extremities but not the face
Subcutaneous nodules
– occur in 5–7% of patients
– Small (0.5–2.0 cm), firm and painless
– Best felt over extensor surfaces of bone or tendons
– typically appear more than 3 weeks after
- help to confirm rather than make the diagnosis
55. Sydenham’s chorea (St Vitus dance)
• Late neurological manifestation
• Appears at least 3 months after the episode of ARF
• all the other signs may have disappeared
• Occurs in up to 1/3rd of cases and is more common in
females
• Emotional breakdown or changes may be the first
feature
• Typically followed by purposeless involuntary
choreiform movements of the hands, feet or face
• Speech may be explosive and halting
• Spontaneous recovery usually occurs within a few
months
56.
57. Case scenario
• A previously healthy 11-year-old boy presented with rapid, irregular,
aimless, involuntary movements of the limbs, neck, and trunk that
resembled continuous restlessness. These uncontrollable movements
had begun 1 month earlier, initially affecting only his left limbs but later
extending to other parts of his body. The movements were absent
during sleep and were exacerbated with stress. He had no previous
movement disorders. The patient reported having a sore throat 4
months before presentation. Neither his schoolmates nor members of
his family were affected. Physical examination revealed the presence of
uncoordinated jerking movements, emotional lability, hypotonic speech,
muscular weakness, hypotonia, hyperactive tendon reflexes, and gait
disturbance
58. Continue
A throat culture obtained on admission was positive for group A beta-
hemolytic streptococcus. Laboratory evaluation showed a level of
antistreptolysin O that was five times the normal level and was a
weakly positive test for mitochondrial antibodies. Magnetic resonance
imaging of the brain was unremarkable.
The patient received a diagnosis of Sydenham's chorea, associated
with group A streptococcus infection. Penicillin and tiapride were
administered, and there was a slight reduction in choreic movements.
The patient's symptoms completely resolved within 1 month after
presentation.
59. Investigations
• ESR and CRP: monitoring progress of the disease
• Positive throat swab cultures are obtained in only 10–25% of cases
• Chest X-ray
• ECG -
• Echocardiography
– Mitral regurgitation with dilatation of the mitral annulus
– Prolapse of the anterior mitral leaflet
– May also show aortic regurgitation and pericardial effusion
60. Management
In acute process:
- bed rest
- Anti-infflamatory drugs (aspirin)
- corticosteroids (-2-3 weeks)
- diuretics and ACE inhibitors if there is heart failure
- Antibiotics for concurrent streptococcal infection
Lon term therapy – secondary prevention attack of Rheumatic fever and
development of chronic rheumatic heart disease. Oral penicillin therapy
or IN penicillin G injection
