Early in the
course of a vasculitis, nonspecific findings reflecting systemic inflammation
fever
malaise
fatigue
failure to
thrive
elevated
acute-phase reactants
As vessel damage
progresses
evidence of
vascular compromise
elevation of
markers of vascular injury
von
Willebrands factor antigen,
pentraxin 3
distinctive
autoantibodies
especially
antineutrophil cytoplasmic antibodies [ANCA]
or
anti-endothelial antibodies
Catch-22
becomes more
evident only after severe and irreversible morbidity is present.
little
information suggestive of vasculitis when the diagnosis needs to be made.
Size of
vessel
Large vessels to the extremities claudication.
visceral vessels.
hypertension (renal arteries),
abdominal pain (mesenteric and celiac axes),
chest pain (aortic or coronary artery involvement),
neurologic symptoms (focal neurologic deficits or neuropathic pain).
Inflammation of smaller arteries and arterioles
Symptoms
in richly vascularized organs.
Skin
involvement.
livedo
reticularis,
purpuric
(generally palpable) or nonblanching lesions,
palmar
or plantar rashes.
Pulmonary,
renal, and gastrointestinal arterial.
hemoptysis,
hematuria,
hypertension.
abdominal
pain, or melena.
Capillary
and venous.
less of an acute emergency
than arteritis.
Clues to Dg
history
and general physical examination
recent
illnesses, in particular infections,
over-the-counter
drugs
travel
family
history
All
pulses must be palpated carefully
Allens
tests
auscultation
for bruits,
blood
pressures in all four extremities
skin
nodules
ocular
fundi and nailbed capillaries
Laboratory studies specific for the diagnosis of vasculitis are not yet
available.
CBC
ESR
C-reactive
protein [CRP])
Immunoglobulines
ANCA
Von
Willebrand factor antigen
PTX3,
a pentraxin expressed by endothelial cells and monocytes
Imaging procedures
large- or medium-sized vessels
Vascular imaging
Doppler US studies
CT or MRI
angiograms
Histopathologic demonstration of vascular inflammation
The
reference standard for diagnosing a vasculitis.
Inaccessibility
of lesions or patchiness of the vascular involvement.
Classification
Clinical
manifestations.
Size of blood
vessels involved.
Histology of
vascular damage.
Presumed disease
pathogenesis.
An etiologic
classification
TNF seems to be effective
in TA
But apparently is
less so in Wegeners
Rituximab effective
in ANCA-associated vasculitides
Classification
of pediatric vasculitides
Primary vasculitides
Large vessel
diseases
Takayasu arteritis
Giant cell (temporal) arteritis
Medium vessel
disease
Polyarteritis nodosa
Cutaneous
Systemic
Cogans syndrome
Kawasaki disease
Small-vessel
disease
Henoch-Schonlein
purpura
Hypersensitivity
vasculitis
Primary
angiitis of the central nervous system
ANCA-positive
vasculitis
Wegeners
granulomatosis
Microscopic
periarteritis
ChurgStrauss
syndrome
Secondary
vasculitides
Infection-related
vasculitis
Hepatitis viruses
Herpes viruses (EBV,
CMV, varicella)
Vasculitis
secondary to connective tissue disease
Dermatomyositis,
Systemic lupus
erythematosus,
Rheumatoid arthritis
Hypocomplementemic
uticarial vasculitis
Drug
hypersensitivity related vasculitis
Malignancy-related
vasculitis
Postorgan
transplant vasculitis
Pseudovasculitic
syndromes
Myxoma
Endocarditis
Sneddon
syndrome
Vasculitides with strong genetic component
Periodic fever
syndromes.
Behets disease.
Modified
from Hunder GG, Wilking AP.
Classification
of the vasculitides.
in
children. UpToDate, 2005. Available at:
http://www.utdol.com/application/search.asp.
Epidemiology
Primary vasculitis
among children < 17 years of age was 20.4/100 000,
Henoch-Schfnlein
purpura (HSP) the most prevalent.
Pathogenesis
Generally
not understood
1. Humoral
factors:
Vascular damage
secondary to specific antibodies is best demonstrated in the ANCA-associated
vasculitides
Activate
neutrophils, causing vascular inflammation,
Antiendothelial
antibodies are also present in a variety of vasculitides
2. Immune complexes:
The size, charge,
and immunoreactivity of immune complexes help explain aspects of the
pathogenesis of HSP and cryoglobulinemic vasculitis
Similarly, PAN
associated with hepatitis B or C seems to be triggered by inflammation incited
by immune complexes deposited upon vessel walls
3.
T lymphocytes attracted to
damaged or infected
endothelium
Suppression
of autoreactive lymphocytes.
T-regulatory
cells - breaking of tolerance and development of autoimmunity.
Biopsy samples from
different types of vasculitis demonstrate different populations of cells
invading vessel walls (eg, macrophages in KD and eosinophils in ChurgStrauss
syndrome [CSS])
4. The characteristic
predilection of different vasculitides for different anatomic
sites
Remains unexplained,
Depend on a variety
of factors, including.
specificity of the
triggering antigen,
regional variations
in cell surface receptors,
and unidentified
contributions of surrounding tissues.
Recluse
Spiders
Genus Loxosceles
Family Sicariidae
Six-eyed sicariid spiders
Necrotic arachnidism
Loxoscelism gangrenous spot of Chile"
At least 56 species
One from the Mediterranean region
Inside houses
Hiding in the folds of clothing, shoes, or
underneath boxes in storage rooms
Henoch-Schonlein
purpura
IgA
immune complexmediated small-vessel.
leukocytoclastic
vasculitis.
Triad
of:
nonthrombocytopenic
palpable purpura,
colicky
abdominal pain.
arthritis.
May
progress to chronic renal failure in 1%.
A wide
variety of infections may trigger HSP.
Group A
streptococcus is the most common precipitant, (one third).
Bartonella,
Haemophilus
parainfluenza, and numerous vaccines and drugs.
In rare cases, CNS
or respiratory lesions may.
lead to hemorrhage
with serious sequelae.
HSP
Slightly
more common in boys
More
commonly during winter and spring
May
begin as urticaria, progresses to dramatic purple, nonblanching lesions
Predilection
to lower body
Activation of the alternate pathway of complement by large IgA
containing immune complexes.
Gravity causes
immune complexes to deposit and incite inflammation in dependent areas.
Gastrointestinal
involvement
Ranges from colicky
abdominal pain to profuse bleeding, intussusception (typically ilio-ilial) and
perforation
Pancreatitis,
cholecystitis, and protein-losing enteropathy
Renal
disease
In
most cases, the first days or weeks.
First
3 months of the illness in 97% of patients.
Risk
factors:
age
over 47 years,
gastrointestinal
bleeding,
purpura
of more than 1 months duration,
factor
XIII activity < 80% of normal,
factor XIII concentrate
treatment.
Recurrence
HSP
recurs in about one third of patients,
especially
those with nephritis.
first 4 to 6 months.
Outcome
Patients
demonstrating both nephritic and nephrotic changes at greatest risk.
Renal biopsy is
useful for confirming the extent and severity of nephritis and planning treatment:
The higher the
percentage of glomeruli with crescents, the more likely is development of
end-stage renal disease.
High
serum levels of nitric oxide and urinary nitrate excretion.
Increased
urinary excretion of the tubular proteins N-acetyl b-d-glucoseaminidase and a-1-microglobulin also
proved useful in identifying.
Patients
at higher risk of long-term renal disease.
1%
to 5% of HSP patients develop some degree of chronic renal disease.
Acute hemorrhagic edema of infancy
Fever,
Large purpuric lesions,
and edema.
A self-limited
condition,
Likely to resolve
within weeks.
Hypersensitivity vasculitis
Clinical
features.
Fever,
Urticaria,
Lymphadenopathy,
Arthralgias,
low
serum complement levels, and elevated ESR.
Low
serum concentrations of C3 and C4 and the absence of IgA.
deposition
in vessel walls help to distinguish this entity from HSP.
Therapy of
HSP is primarily supportive
NSAIDs, no evidence
of increased likelihood of GI hemorrhage in HSP.
Use of steroids
continues to be controversial.
Prednisone
Prednisone, 2
mg/kg/day,
Relieve symptoms
rapidly in most cases,
Must avoid
excessively rapid tapering of the steroids,
precipitate a flare
of symptoms
Immunosuppressive
agents
Such as
cyclophosphamide or azathioprine,
Reserved for children
with biopsy-proven crescentic glomerulonephritis
other
life-threatening complications such as cerebral or pulmonary hemorrhage
Kawasaki disease
Although KD or
mucocutaneous lymph node syndrome it is a self-limited condition, with fever
and manifestations of.
Acute inflammation
lasting for an average of 12 days without therapy.
Diagnosed by
clinical criteria not histology or angiography.
Kawasaki disease
80% to 90% of
>fifth birthday.
1.5% of untreated
children died from KD.
More than 140,837 cases of KD have
been registered in Japan since its initial description in 1967.
Kawasaki disease
susceptibility
of different ethnic groups to KD
Genetic
factors,
polymorphisms
of chemokines
and
TNF receptors
variations
in HLA haplotypes
Overall,
Asians are affected 5 to 10 times as frequently as whites;
blacks and Hispanics have an intermediate risk
The cause of KD remains
unknown.
Criteria for diagnosis of
Kawasaki disease
Fever lasting 5 days
or more (4 days if treatment with IVIG
eradicates fever)
plus at least four of the following clinical signs
not explained by
another disease process
Modified from Centers for
Disease Control. Revised diagnostic criteria
for Kawasaki disease. MMWR Morb Mortal Wkly Rpt 1990;
39(No. 44-13):278.
1. Bilateral conjunctival injection
(80%90%)
2.
Changes in the oropharyngeal mucous membranes (including
one or more of the
following symptoms: injected or fissured
lips, strawberry
tongue, injected pharynx) (80%90%)
3.
Changes in the peripheral extremities, including erythema
or edema of the hands
and feet (acute phase) or periungual
desquamation
(convalescent phase) (80%)
4. Polymorphous rash, primarily truncal;
nonvesicular (N 90%)
5. Cervical lymphadenopathy: anterior
cervical lymph note at
least 1.5 cm in
diameter (50%)
Pathologically, however, KD
seems to be unique:
Macrophages
and IgA-producing plasma cells in
the vessel walls, features recognized in no other conditions.
Many
aspects of KD suggest that it is caused by a transmissible agent.
A
synthetic monoclonal IgA antibody was found to bind to an unidentified
cytoplasmic.
Component
of macrophages within the coronary arteries of 9 of.
12
fatal cases of KD but in none of 10 controls.
Kawasaki disease
Similar binding to
the respiratory epithelium of proximal bronchi was noted in 77% of fatal cases,
never in controls.
One interpretation
is that a particular respiratory pathogen may be associated with KD.
Kawasaki disease
Many epidemiologic
data also support the.
theory that KD is
triggered by a transmissible.
agent or agents;
Boys > 50% more
commonly than girls, a feature typical of infectious diseases.
The average age of
children with KD is.
about 2 years, and
occurrence beyond late childhood is extremely rare.
nonetheless
viruses
(eg, EpsteinBarr virus, parvovirus, HIV-2) or bacterial toxins (eg,
streptococcal erythrogenic toxin, staphylococcal toxic shock toxin) account for
the majority of cases have not been substantiated
Thus,
many researchers now believe that KD represents a final common pathway of
immune-mediated vascular inflammation following a variety of inciting
infections.
Clinical
manifestations
Guidelines for the
diagnosis of KD were established by Tomisaku Kawasaki 1967.
Diagnosis requires
the presence of fever lasting 5 days or more without any other explanation,
combined with at least four of five manifestations of mucocutaneous
inflammation.
Children who
do not meet the criteria may have an incomplete or atypical form of KD.
at least 10% of
children who develop coronary artery aneurysms never meet criteria for KD
Fever is probably
the most consistent manifestation of KD.
It reflects elevated
levels of proinflammatory cytokines such as TNF and interleukin (IL)-1 that are
also thought to mediate the underlying vascular inflammation.
The fever is
typically hectic, minimally responsive to antipyretic agents, and remains >
38.58C during most of the illness.
Bilateral
nonexudative conjunctivitis is present in as many as 90% of cases.
Bulbar
injection
Begins within days
of the onset of fever, and the eyes have a brilliant erythema that spares the
limbus.
Children are also
frequently photophobic, and anterior uveitis may develop.
Slit-lamp
examination may be helpful in ambiguous cases; the presence of uveitis.
Cracked,
red lips
Cracked, red lips
and a strawberry tongue are characteristic.
caused by sloughing
of filiform papillae and denuding of the inflamed glossal tissue.
Discrete oral
lesions, such as vesicles or ulcers, as well as tonsillar exudate, suggest a viral
or bacterial.
cutaneous
manifestations
Polymorphous rash
typically begins as perineal erythema and desquamation,
followed by macular,
morbilliform,
or targetoid lesions
of the trunk and extremities.
Vesicular or bullous lesions are rare.
Changes in
the extremities
generally the last
manifestation of KD to develop.
an indurated edema
of the dorsum of the hands and feet and.
a diffuse erythema
of the palms and soles.
The
convalescent phase of KD
sheetlike
desquamation that begins in the periungual region of the hands and feet and by linear nail creases
(Beaus lines).
The
convalescent phase of KD
one third of
children have arthritis.
The arthritis is
typically a small joint polyarthritis during the first week of illness,
followed by a large joint pauciarthritis.
It never persists
beyond 1 to 2 months, nor is it erosive.
Cervical
lymphadenopathy
is the least
consistent.
absent in as many as
50% of children with the disease.
involve
primarily the anterior cervical nodes overlying the sternocleidomastoid muscle.
Children suspected
of having KD who have fewer than four signs of mucocutaneous inflammation may
have incomplete or atypical KD.
.
most incomplete and
atypical in the youngest patients.
In a retrospective
review of 45 cases of KD,
5 of 11 infants
(45%) had atypical disease,
compared with 4 of
33 older children (12%)
Coronary artery
complications occurred in 64% infants
compared with 9%
older children (and occurred in all five infants with incomplete
disease).
Japanese nationwide survey
of KD in 1995 and 1996
Infants < 1 year
of age had an odds ratio of 1.54 for developing cardiac sequelae.
Similarly, in a
recent retrospective survey, the rate of treatment failure was 8.5% in patients
under 12 months of age.
compared with a 1.8%
incidence of coronary artery abnormalities in those at > 12 months of age.
Japanese nationwide survey
of KD in 1995 and 1996: 140,837
The incidence rates
per 100,000 children of <5 years old were 102.6.
Recurrent cases
35%.
Peak age of
incidence 1 year of age.
8085% of cases <
5 years.
Male to female ratio
is 1.5:1.
Epidemiology of Kawasaki
Disease in Ontario, Canada, 1995-1997
408
cases - 81% typical KD
annual
incidence (per 100,000) by age was 13.6 in <5 yrs
males vs.
females of 1.73
Epidemiology of Kawasaki
Disease in Ontario, Canada, 1995-1997
Coronary
artery involvement included ectasia in 35%.
non-giant
aneurysms in 9%.
giant
aneurysms (>8 mm) in 1.4%.
with
ventricular dysfunction noted in 2.7%.
Laboratory
Elevation
of acute phase reactants (eg, CRP, ESR, and alpha-1 antitrypsin),
Leukocytosis,
and a left shift.
By
the second week of illness, platelet counts > 1,000,000/mm3 in the most
severe cases.
Normocytic,
normochromic anemia;
urinalysis
- white blood cells on microscopic.
The
pyuria is of urethral origin and therefore will be missed on urinalyses
obtained by bladder tap or catheterization.
.
Renal
involvement may occur in KD but is uncommon.
elevated
transaminase levels or mild hyperbilirubinemia caused by intrahepatic
congestion.
Cerebrospinal fluid
(CSF) typically displays a mononuclear pleocytosis without hypoglycorrhachia or
elevation of CSF protein.
Review of 46 children with KD found that
39% had elevated CSF white cell counts.
Obstructive jaundice
from hydrops of the gallbladder.
Differential
diagnosis
KD is most commonly
confused with infectious exanthems of childhood
Measles, echovirus,
and adenovirus may share many of the signs of mucocutaneous
Differential
diagnosis
Toxin-mediated
illnesses, especially b
hemolytic streptococcal infection and toxic shock syndrome,
Rocky
Mountain spotted fever and leptospirosis
Drug
reactions such as StevensJohnson syndrome or serum sickness
Systemic-onset
juvenile idiopathic arthritis
Mercury
hypersensitivity reaction (acrodynia)
Therapy
IVIG and aspirin.
Markers of increased risk
of developing coronary artery aneurysms,
age under 1 year,
signs of severe
systemic inflammation
consumptive
coagulopathy,
Aspirin was the
first medication used for treatment of KD because of its antiinflammatory and
antithrombotic effects
Therapy
within the first 10 days of illness reduces the incidence of coronary artery
aneurysms by more than 70%
IVIG
therapy also largely eliminates the
development
of giant coronary artery aneurysms (more than 8 mm in diameter), which are
associated with the highest risk of morbidity and mortality,
and
rapidly restores disordered lipid metabolism and depressed myocardial
contractility to normal
Aspirin
traditionally is given initially in relatively high doses to achieve an
anti-inflammatory effect; doses of 30 mg/kg/day to more than 80 mg/kg/day in
four divided doses have been used during the acute phase of illness.
Subsequently,
aspirin is administered in low doses (3 to 5 mg/kg/day) for its antiplatelet
action.
No study has
demonstrated long-term benefit from the use of aspirin, and a recent trial
found no differences in outcomes between children treated with IVIG alone and
those who also received aspirin
aspirin
100 mg/kg/day.
Once fever resolves,
patients receive a dose of 3 to 5 mg/kg/day.
Treatment with
aspirin is continued until laboratory studies (eg, platelet count and
sedimentation rate) return to normal, unless coronary artery abnormalities are
detected by echocardiography.
corticosteroids
A retrospective
survey of the records of almost 300 children treated with or without steroids
between 1982 and 1998.
and
two open, randomized, prospective trials found that patients who received
corticosteroids in addition to IVIG had shorter durations of fever and more
rapid decrease in inflammatory markers than those in the standard-therapy
group.
Corticosteroids
In all reports,
corticosteroid therapy has been well tolerated, with no significant adverse
effects.
At present, most
clinicians who specialize in the care of KD use pulsed doses of intravenous
methylprednisolone (IVMP) in children whose inflammation persists despite at
least two doses of IVIG.
IVMP
A
trial supported by the National Institutes of Health comparing outcomes in
children who received initial therapy with IVMP plus IVIG versus IVIG alone has
completed enrollment.
Results
of this trial soon should supply definitive information concerning the
potential role of steroids in the primary treatment of KD.
Re-treatment
Fever persists or
returns 48 hours after the start of initial treatment with IVIG in 10% to 15%
of patients
Persistent or
recrudescent fever is particularly concerning, indicating ongoing vasculitis
with increased risk of developing coronary artery aneurysms (12.2% versus 1.4%
in one analysis)
In another study,
persistent fever was the only factor that predicted subsequent development of
aneurysms
It is extremely
important not to dismiss mild temperature elevations in children with KD;
Patients who remain
febrile after the first dose of IVIG are usually treated with a second and
perhaps even a third dose of IVIG, 2 g/kg
This practice is
based on the apparent doseresponse effect of IVIG
most specialists
treat children who have not responded to IVIG and still have active KD with one
to three daily doses of pulsed methylprednisolone (30 mg/kg)
If this treatment is
ineffective, a single dose of infliximab, 5 mg/kg, may be beneficial
Additional
considerations
An echocardiogram
should be obtained early in the acute phase of illness and 6 to 8 weeks after
onset to confirm the efficacy of treatment
Children with
coronary artery abnormalities receive long-term antithrombotic therapy with
aspirin, dipyridamole, or other agents, as well as regular cardiac evaluations.
Coronary artery
dilatation of less than 8 mm regresses over time, and most smaller aneurysms
fully resolve by echocardiogram.
Healing
is by fibrointimal proliferation, often accompanied by calcification, and
vascular reactivity does not return to normal despite grossly normal appearance
Children
should thus be followed indefinitely after KD, a point highlighted by a report
of the sudden death of a 3.5-year-old child 3 months after dilated coronary
arteries had regained a normal echocardiographic appearance
Autopsy revealed obliteration of the lumen of the
left anterior descending coronary artery by fibrosis, with evidence of ongoing
active inflammation in the epicardial arteries.
Children
with severe KD who develop coronary occlusion may experience myocardial
infarction, arrhythmias, or sudden death, and those who develop peripheral
artery occlusion may experience ischemia or gangrene.
At least one report
suggests a potential role for abciximab, a monoclonal antibody that inhibits
platelet glycoprotein IIb/IIIa receptor.
increased resolution of aneurysms in
patients with KD who received abciximab compared with those who received
conventional treatment.
Overall, with modern
treatment and cardiologic follow-up, the prognosis of children with KD is
excellent.
Long-term follow-up
of children without persistent coronary artery abnormalities in Japan has
demonstrated no increase in morbidity or mortality after 25 years.
In fact, studies
suggest that fear of a cardiac event is more disabling than actual medical problems
in most children who have had KD.
Thus, caregivers
should be particularly careful to reassure families when appropriate.
Polyarteritis
nodosa
A systemic
necrotizing vasculitis.
With aneurysm
formation.
Medium or small
arteries.
Historically as the
first noninfectious cause of vascular damage.
1866,
Kussmaul and Maiers
At
least one third of children with PAN, have a more limited form, restricted
largely to the skin and joints.
is
most commonly associated with hepatitis B or C infections.
pediatric
PAN is quite rare,
peaks
at 9 to 10 years of age,
No
clear genetic association.
association
with familial Mediterranean fever (FMF).
Up
to 1% of FMF patients develop PAN, milder than idiopathic disease.
Cutaneous
PAN
limited to skin and
the musculoskeletal system.
Post streptococcal
pharyngitis.
Livedo reticularis,
maculopapular rash,
painful skin
nodules, panniculitis,
brawny edema,
Arthritis mostly
affect the knees and ankles.
Acute-phase
reactants may be normal or elevated,
Constitutional symptoms
are generally mild.
Tends to persist or
relapse,
Many patients
require steroid-sparing agents for long-term management.
Methotrexate or
other immunosuppressive agents;
TNF inhibitors have
been reported to be effective, as well
Penicillin prophylaxis
Systemic
PAN
Any
muscular artery.
Constitutional
symptoms.
A
vast array of organ dysfunction.
Palpable
purpura, livedo, necrotic dermal lesions.
Abdominal
pain, arthritis/arthralgia, myositis/myalgia,
Renovascular
hypertension,
Neurologic
deficits,
Pulmonary
disease, coronary arteritis.
PAN DD
Systemic-onset
juvenile rheumatoid arthritis,
KD,
Dermatomyositis.
Glomerulonephritis
typically is not a feature of this condition.
Laboratory
evaluation
Anemia,
leukocytosis, thrombocytosis, and elevated ESR, CRP, and immunoglobulins.
A
positive ANCA generally indicates pauci-immune glomerulonephritidies rather
than PAN.
Proteinuria,
hematuria, and increases in serum urea nitrogen and creatinine levels are also
common findings.
Complement
levels are normal.
The diagnosis usually
requires tissue biopsy or radiologic documentation of vasculitis.
Typical
beading of vessels.
Alternating
areas of vascular narrowing and dilatation that give PAN its name.
Pathologically
this manifestation corresponds to segmental vascular involvement with nodule
and aneurysm formation resulting from panmural fibrinoid necrosis.
No
overt complement or immunoglobulin deposition is seen.
Treatment
High-dose steroids.
Other
immunosuppressive agents,
daily oral or
monthly intravenous doses of cyclophosphamide,
Azathioprine,
methotrexate, IVIG, and,
TNF-inhibitors,
A 4-year mortality
rate under 5%.
Takayasu arteritis
TA is the third most
common form of childhood vasculitis
The cause of TA
remains unknown,
a primarily T-cellmediated
mechanism
granulomatous
changes progressing from the vascular adventitia to the media,
indistinguishable
from those seen in giant cell arteritis and temporal arteritis
The
diagnosis of TA is based on the distribution of involvement
primarily the aorta
and its branches
and the young age of
patients,
typically under 40
years
Takayasu arteritis
childhood disease
has been reported as early as the first year of life
significant
preponderance of female patients in children with TA,
mean age of onset
was 11.4 years,
two thirds of the
patients were female
Takayasu arteritis
Signs
and symptoms.
hypertension,
cardiomegaly,
elevated
ESR,
fever,
fatigue, palpitations,
vomiting,
nodules, abdominal pain,
arthralgia,
claudication,
weight
loss, and chest pain.
The
delay in diagnosis in children was 19 months.
Angiography the standard
method used for diagnosis.
CT and MR angiograms
have proven to be as useful as traditional angiograms.
MRI has the added
advantage of revealing evidence of ongoing vessel wall inflammation.
.
Laboratory markers
may be entirely normal despite ongoing inflammation.
Steroids
cyclophosphamide,
methotrexate,
Azathioprine
TNF-inhibitors
Primary
angiitis of the central nervous system
one of the most
challenging diseases a physician might face,
systemic
manifestations of the disease are usually absent,
acute-phase
reactants are typically normal,
and examination of
CSF might be unrevealing as well
high level of
suspicion when children have even scanty suggestion of a vasculitis.
A recent review 62
patients with childhood PACNS (cPACNS)
Headache (80%) and
focal neurologic
deficits (78%)
hemiparesis in 62%.
Normal
MRI together with normal CSF have high negative predictive value for cPACNS.
5%
to 10% of cases of cPACNS, only a meningeal and brain biopsy proved the
vasculitis.
PACNS
may be rapidly progressive and neurologically devastating,
Treatment
invariably includes
corticosteroids and
a potent immunosuppressive agent, usually cyclophosphamide.
methotrexate or
azathioprine for maintenance therapy, excellent results
Anti-neutrophil cytoplasmic
antibody-associated vasculitides Wegeners granulomatosis Wegeners
granulomatosis (WG)
is uncommon in
children.
a necrotizing
granulomatous inflammation of small- to medium-sized vessels
kidneys and upper
and lower respiratory tracts.
biopsies - a
microscopic pauci-immune polyangiitis.
cANCA directed
against PR-3.
nasal and sinus
involvement were seen in 100%,
respiratory disease
in 87%,
arthralgias, ocular
findings, or skin or renal involvement each in just over 50%,
gastrointestinal
disease in 41%,
and CNS involvement
in 12%
subglottic stenosis
in almost 50%
cause of
WG
ANCA
most likely stabilize adherence of rolling neutrophils to endothelium and
activate neutrophils and monocytes to undergo an oxidative burst.
Activation
of phagocytic cells causes increased expression of proinflammatory cytokines
(eg, TNF-a and IL-8), with resultant localized endothelial cell cytotoxicity
Upper
respiratory symptoms
Epistaxis,
sinusitis, otitis media, or hearing loss.
Cough, wheezing,
dyspnea, and hemoptysis.
Kidney involvement
may initially be asymptomatic.
Chest
radiographs - one third have radiographic abnormalities in asymptomatic
children
diagnosis
of WG relies heavily on biopsy
Necrotizing
granulomatous vascular inflammation is strongly suggestive
cANCA
targeted against PR-3 is positive in most patients
Although
this autoantibody is highly specific, it may be found in other diseases, such
as cystic fibrosis,
ANCA
titer should not replace a tissue biopsy.
role
of monitoring of ANCA titers as a marker of disease activity is controversial.
Without
immunosuppressive therapy, WG is rapidly progressive and even fatal.
cyclophosphamide,
azathioprine,
methotrexate, and, more recently, mycophenolate mofetil and.
TNF-a
blockers.
Preliminary data showed that the
anti-TNF agent etanercept did vasculitis in children.
.
but
infliximab apparently was effective.
trimethoprim/sulfamethoxazole
has been shown to be beneficial.
perhaps by
suppressing upper respiratory infections that might activate vascular
inflammation.
Microscopic
polyangiitis
A
necrotizing vasculitis of the small vessels without.
granuloma
formation.
Clinical
manifestations;
kidney
and pulmonary involvement,
focal
segmental glomerulonephritis and pulmonary hemorrhage.
positive
pANCA with reactivity to myeloperoxidase (MPO).
Microscopic
polyangiitis
Most patients seem
to require cyclophosphamide.
Milder agents may be
adequate for maintaining remissions.
Most recently, a
single 4-week course of rituximab might replace both cyclophosphamide and
long-term steroids.
ChurgStrauss
syndrome
CSS is extremely
rare in children.
A prodromal phase of
an allergic rhinitis and asthma,
may persist for many
years.
The second phase -
worsening asthma,
peripheral
eosinophilia, and pulmonary infiltrates.
the
third or vasculitic phase - systemic vasculitis
weight
loss,
fever,
arthralgia,
myalgia,
nodular
rash,
neuropathy.
Asthma
symptoms usually subside during the vasculitic phase.
ChurgStrauss
syndrome
Tissue biopsy is
generally diagnostic,
Significant
perivascular eosinophilic infiltrates and occasional extravascular granulomas.
ANCA directed
against both PR-3 and MPO may be seen in CSS.
ChurgStrauss
syndrome
An initial
aggressive remittive therapy,
Followed by milder
maintenance treatment,
Most deaths are
caused by cardiac involvement,
followed by severe
gastrointestinal and CNS disease.
exquisitely
sensitive to corticosteroids,
Secondary
vasculitides
Infections,
Medications,
Systemic diseases.
Secondary
vasculitides
viruses (parvovirus
B19, HIV, varicella),
Rickettsia,
bacteria,
fungi,
mycobacteria,
systemic
inflammatory conditions
SLE,
juvenile dermatomyositis [JDMS], juvenile rheumatoid arthritis, sarcoidosis,
inflammatory bowel syndrome, tumors), CF.
Drugs.
Both
leukocytoclastic and necrotizing vasculitis have been reported.
Removal
of the trigger or control of the inciting condition leads to remission of the
vasculitis.
Behcets
disease
A
multisystem inflammatory disorder
BD
is characterized by the triad of
recurrent
oral ulcers,
genital
ulcers,
and
uveitis,
Any
organ system may be involved including
skin,
joints
CNS,
or
gastrointestinal tract,
Behcets disease
Vascular
inflammation is often a prominent feature.
Both
arteries and veins may be affected.
A
particular predilection for the venules.
A
propensity for development of thromboses,
Including
deep vein thrombosis and thrombophlebitis.
Arterial
aneurysms may also occur -
pulmonary aneurysms.
Behcets
disease
BD
is thought to occur when an infectious agent triggers an amplified inflammatory
response in a genetically susceptible host.
In
the Japanese and Turkish vasculitis populations, in whom the disease is most
prevalent, HLA-B51 is a marker for BD.
and
the aberrant cellular immune response seems to involve gd-T
cells.
Antibody-mediated
immune mechanisms may also play a role.
Various
immunomodulatory agents
IFN-a,
thalidomide,
dapsone,
steroids,
cyclophosphamide,
azathioprine
Periodic fever syndromes
During the past 5
years,
novel
autoinflammatory conditions caused by mutations in regulators of inflammation
have been described.
Summary
Vasculitis is rare
in children,
Apart from HSP and
perhaps KD,
Most practicing
pediatricians will never encounter a case.
Summary
It is important to
consider vasculitis as a.
potential cause of;
unexplained
inflammation,
perplexing rashes,
or strange
combinations of symptoms.