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INTRODUCTION
Background: Takayasu
arteritis (TA) is a chronic inflammatory disease of the large arteries,
usually affecting the aorta and its large branches and the pulmonary
arteries. It is one of the vasculitides and can manifest systemically,
involving any or all of the major organ systems. The brain is a prime
target.
Dr Mikito Takayasu first described TA in 1905, when he described a
patient with a wreathlike coronary anastomosis of retinal vasculature
surrounding the papilla. Since then, the disease has been reported in all
parts of the world, although it appears to be more prevalent in Asians.
Pathophysiology: TA is an inflammatory disease of
large- and medium-sized arteries, with a predilection for the aorta and
its branches. Advanced lesions demonstrate a panarteritis with intimal
proliferation.
Lesions produced by the inflammatory process can be stenotic,
occlusive, or aneurysmal. All aneurysmal lesions may have areas of
arterial narrowing. Vascular changes lead to the main complications,
including hypertension, most often due to renal artery stenosis or, more
rarely, stenosis of the suprarenal aorta; aortic insufficiency due to
aortic valve involvement; pulmonary hypertension; and aortic or arterial
aneurysm. Congestive heart failure is a common finding, much more so than
dilated cardiomyopathy, myocarditis, and pericarditis, which also have
been reported. In patients in whom the pulmonary artery is involved, the
right artery appears to be affected more than the left, with patients
developing pneumonia, interstitial pulmonary fibrosis, and alveolar
damage.
Other pathophysiologic consequences include hypotensive ischemic
retinopathy, vertebrobasilar ischemia, microaneurysms, carotid stenosis,
hypertensive encephalopathy, and inflammatory bowel disease. Rarely, TA
has also been associated with glomerulonephritis, systemic lupus,
polymyositis, polymyalgia rheumatica, rheumatoid arthritis, Still disease,
and ankylosing spondylitis.
Frequency:
- In the US:
- The prevalence is 2.6-6.4 persons per 1,000,000 population. The
discrepancy is attributed to genetic factors and difficulty in
diagnosis.
- Between 1971-1983 in Olmstead County, Minnesota, 3 cases were
recorded, thus giving an annual incidence of 2.6 cases per 1,000,000
population.
- Internationally:
- Worldwide incidence is estimated at 2.6 cases per million per
year.
- Many cases of TA are reported from Southeast Asia, where the
condition is believed to be most common. However, it has been reported
in all parts of the world and in all racial groups.
- The prevalence in Sweden is similar to that in the United States
(ie, 2.6-6.4 persons per 1,000,000 population).
- In the United Kingdom, the annual incidence is 0.15 case per
million.
Mortality/Morbidity:
- Because TA is rare, data on mortality and morbidity are limited. The
site of the lesions and the degree of involvement determine the extent
and the clinical severity. A National Institutes of Health (NIH) study
of 60 patients with TA prospectively demonstrated a 3% mortality rate.
This result was similar to data from Japan and China but markedly
different from other reports (which reported mortality as high as 35%).
Such disparity may reflect differences in access to care, definitions of
disease activity, and indications for treatment.
- The same NIH study showed that 20% of patients had a monophasic
illness, which was self-limiting; they did not require immunosuppressive
treatment. In the remaining 80% of patients who did not have a
monophasic illness and experienced one exacerbation, immunosuppressive
therapy resulted in remission in 60%. Of these, one half experienced
relapse after immunosuppressive therapy was stopped. The overall
morbidity depends on the severity of the lesions and their consequences.
Race: Cases have been reported worldwide, but TA is
most common in Southeast Asia and the Indian subcontinent.
Sex: TA is primarily a disease of young women. Men are
rarely affected.
Age: TA primarily affects young women, especially
those in the childbearing ages. Peak onset is in individuals in their 30s.
Fewer than 15% of cases present in individuals older than 40 years.
CLINICAL
History: TA progresses
through 3 stages. Thus, symptoms that clinicians encounter depend on how
soon the patient presents; most patients present late, delaying the
diagnosis. However, in actual practice, most patients do not fall readily
into such groupings, and this 3-stage scheme is an oversimplification of
the complex clinical presentation. Symptoms encountered can occur early or
late in the course of the disease. In the NIH series including 60 patients
observed over 20 years, only 33% of patients had constitutional symptoms
(corresponding to stage 1); 18% of patients never progressed to the third
stage.
- The first stage is an early systemic stage during which the patient
may complain of constitutional symptoms (eg, fatigue, malaise,
giddiness, fever). This stage is considered to be prevasculitic.
- The second stage is the vascular inflammatory stage, when stenosis,
aneurysms, and vascular pain (carotidynia) tend to occur.
- Symptoms characterizing the vascular inflammatory stage include
fatigue, fevers, malaise, pain in extremities and joints, dyspnea,
palpitations, headaches, rash (erythema nodosum or a lupuslike
butterfly rash, which can be photosensitive), hemoptysis, ulceration,
and weight loss.
- Symptoms of vascular insufficiency include arm numbness,
claudication in the legs (rare), blurry vision, double vision (which
can be posture dependent), amaurosis fugax, stroke, transient ischemic
attacks (TIAs), hemiplegia, seizures, and paraplegia.
- The constitutional systemic symptoms and vascular symptoms may
occur at the same time, rendering the classification into stages
practically impossible.
- The third stage is the burned-out stage, when fibrosis sets in, and
generally is associated with remission.
- This stage does not occur in all patients, and even in patients
who are in remission, relapses can occur.
- Presumably, the burned-out stage manifests with minimal symptoms,
but little supportive evidence is found in the literature.
- Special mention should be made regarding pregnant women.
- The inflammatory activity is not enhanced by the pregnancy, but
the perinatal period may be complicated by the associated
symptoms.
- Blood pressure may not be measurable due to pulselessness, thus
making patient monitoring difficult, if not impossible. Often, calf
pressures need to be obtained.
- In pregnant women with TA, uncontrolled blood pressure may lead to
subarachnoid/intracranial hemorrhage and subsequent seizures, eye
changes, preeclampsia, aortic regurgitation, syncope, fetal
complications, and nephrotic syndrome.
Physical:
- The main finding is absent pulse(s) or a pulse discrepancy of
greater than 30 mm Hg between the right and left arms.
- Other significant findings include the following:
- Vascular bruits, most commonly in the carotid and abdominal
arteries but also in the subclavian and femoral arteries
- Focal neurologic deficits consistent with cerebral infarction or
TIA
- Hypertension, sometimes leading to hypertensive encephalopathy,
usually due to renal artery stenosis
- Retinal ischemia and microaneurysms
- Subarachnoid hemorrhage, probably secondary to
hypertension
- Leg edema due to renal failure secondary to renal artery stenosis
and glomerulonephritis
- Less common associations have been seen with the following:
- Sensorineural hearing loss
- Blood pressure may not be measurable due to the pulselessness,
making patient monitoring difficult or impossible. Often, calf blood
pressures must be obtained.
- A case report of sensorineural hearing loss associated with TA also
has been reported. Whether a firm connection between the two syndromes
exists, other than the inflammatory manifestations, has not been
demonstrated. The pathologic etiology of the hearing loss was attributed
to an immune-mediated process in the membranous labyrinth.
- A case report of Cogan syndrome with TA also has been reported.
Cogan syndrome, first described in 1945, involves interstitial keratitis
and a vestibuloauditory syndrome. Variations of this with other types of
inflammatory eye disease and vestibuloauditory arteritis have been
reported.
Causes: The etiology is unknown. The underlying
pathologic process is inflammatory, with several etiologic factors having
been proposed, including spirochetes, Mycobacterium tuberculosis,
streptococcal organisms, and circulating antibodies due to an autoimmune
process.
- In a case report, the role of M tuberculosis and its 65-kDa
heat shock protein has been implicated in the etiology. Patients with TA
were found to have higher immunoglobulin G (IgG), immunoglobulin M
(IgM), and immunoglobulin A (IgA) titers against the M
tuberculosis extract than patients without the condition.
- A recent article reports the presence of CD3+ T cells and
IgG antibodies reactive to circulating antimycobacterial heat shock
protein 65 (mHSP65) antibodies and to its human homologue, hHSP60. This
suggests a possible cross reactivity of immune response between mHSP65
and hHSP60.
- Other case reports involving the role of antiendothelial,
anticardiolipin, and antiaorta antibodies also exist.
- In Japanese patients, human leukocyte antigen Bw52 (HLA-Bw52), which
is in linkage disequilibrium with human leukocyte antigen DR4 (HLA-DR4),
has been observed with increased frequency. Patients with the Bw52
genotype had a higher rate of aortic regurgitation. However, studies of
HLA antigens in North American populations have not confirmed
this.
- A recent study demonstrated an association between several cases of
TA and CD36 deficiency (CD36d). The human CD36 antigen is a
multifunctional membrane glycoprotein that belongs to the class B
scavenger receptor family. It is expressed on monocytes, platelets, and
endothelial cells, and contributes to myocardial fatty acid transport.
In patients with CD36d, myocardial I-15-(p-iodophenyl)-3-(R,S)-methyl
pentadecanoic acid (BMIPP) uptake was absent.
DIFFERENTIALS
Cerebral Aneurysms
Churg-Strauss Disease
Intracranial Hemorrhage
Lacunar Syndromes
Neurofibromatosis, Type 1
Neurofibromatosis, Type 2
Polyarteritis Nodosa
Sarcoidosis and Neuropathy
Subarachnoid Hemorrhage
Syncope and Related Paroxysmal Spells
Wegener Granulomatosis
Other Problems to be Considered:
Cogan syndrome
Dilated cardiomyopathy
Erythema
nodosum
Relapsing polychondritis
Amaurosis fugax
Ocular
pathology
Giant cell arteritis
Other arteritides
Other large
vessel diseases (eg, neurofibromatosis of the abdominal aorta)
Carotid
disease and stroke
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WORKUP
Lab Studies:
- Laboratory tests in individuals with TA tend to be nonspecific. The
erythrocyte sedimentation rate (ESR) may be high, generally greater than
50 mm/h, in early disease but normal later. Leukocyte count may be
normal or slightly elevated. A moderate, normochromic anemia may be
present in individuals with active disease.
- Autoantibodies observed in other connective tissue diseases,
including rheumatoid factor, antinuclear antibodies, anticardiolipin
antibodies, and antineutrophil cytoplasmic antibodies (ANCA), are as
common as in the general population. Circulating antiendothelial
antibodies may be present in high titers. This finding is considered
nonspecific, because it is reported sporadically and may be present in
other connective tissue diseases and in angiitis obliterans. Antiaorta
antibodies may be present, but testing for them seldom is performed, if
ever.
- Hypoalbuminemia and increased levels of fibrinogen, alpha2-globulin,
and gamma globulin are common.
- Urinalysis may be consistent with nephrotic syndrome.
- HLA typing has not confirmed any definite association in North
American patients. Presumably, a finding of HLA-Bw52 in such patients
reinforces the diagnosis; it is not a definite diagnostic tool.
Imaging Studies:
- Angiography is the criterion standard.
- The Ishikawa criteria (1986) have been useful in defining
TA.
- One criterion is age younger than 40 years at diagnosis or at
onset of characteristic signs and symptoms of 1-month duration in the
patient's history.
- Two major criteria involve the left and right midsubclavian
artery, with the most severe stenosis or occlusion present in the mid
portion from a point 1 cm proximal to the left and right,
respectively, vertebral artery orifices to that 3 cm distal to the
orifice as determined by angiography.
- The minor criteria consist of annuloaortic ectasia or aortic
regurgitation as shown by angiography or echocardiography and
pulmonary artery, left mid common carotid, distal brachiocephalic
trunk, descending aorta, or abdominal aorta lesions.
- The American College of Rheumatology (ACR; 1990) states the
following:
- Angiographic criteria must show narrowing or occlusion of the
entire aorta, its primary branches, or large arteries in the proximal
upper or lower extremities.
- These changes are not due to arteriosclerosis, fibromuscular
dysplasia, or similar causes.
- Changes are usually focal or segmental.
- These criteria probably allow greater flexibility to account for
variability in actual clinical practice.
- In comparison to the Ishikawa criteria, which were established
based on Japanese patients only, the ACR criteria may better reflect
the North American population.
- The lesions can include stenosis, occlusion, or
aneurysms.
- Computed tomography (CT) scanning or ultrasound may be used to
assess thickness of the aorta.
- Magnetic resonance angiography (MRA) can be used to assess the
vasculature, but it is not as accurate as angiography.
- Gallium scanning has been used to assess inflammatory involvement of
the vessels.
- Single-photon emission computed tomography (SPECT) scanning has been
used to assess cerebral blood flow and may be useful in patients who
undergo bypass surgery. Several recent studies have shown that the use
of whole-body positron emission tomography (PET) scanning provides
useful information demonstrating anatomic changes consistent with the
diagnosis of TA.
- Ultrasonography has been used to determine flow characteristics in
stenosed vessels.
Procedures:
- Few procedures are necessary. Grafts have been used to bypass
regions of severe stenosis or occlusion. Usually, the graft is a
saphenous vein graft. Examples of grafts performed include bypass of
renal artery stenosis for renal salvage; bypass of innominate or carotid
artery; and bypass between subclavian-axillary and common carotid
arteries. Extraintracranial bypass operations generally are performed
for stenosis of the internal carotid or middle cerebral
arteries.
- Other procedures include aneurysm clipping and
revascularization.
Histologic Findings:
- Lesions are initially inflammatory and later become occlusive. In
the early phase of TA, histologic features include granulomatous changes
in the media and adventitia of the aorta and its branches, followed by
intimal hyperplasia, medial degeneration, and adventitial fibrosis of
the sclerotic type. The duration is variable. Inflammatory
cells—predominantly CD4 and CD8 lymphocytes, macrophages, plasma cells,
histiocytes, and giant cells—invade the adventitia and media but not the
intima.
- In the vasoocclusive stage, the lesions are characterized by
occlusion and signs of ischemia. The adventitia and media are replaced
by fibrous scarring, the vasa vasorum are obliterated, and the intima
undergoes irregular thickening. Medial degeneration, disruption of the
elastic lamellae, and thrombosis can occur. Aneurysms can form, but no
aneurysms attributed to TA have been identified in the intracranial
circulation. The literature reports a few cases of intracranial
aneurysms that are considered to be incidental.
- The ground substance in the intima is increased markedly,
histochemically showing a basophilic acid mucopolysaccharide in a state
of gelatinous swelling.
- An increase in CD4 and decrease in CD8 lymphocytes, along with
reduced B lymphocytes, have suggested a defect in T-cell regulation
(cell-mediated immunity). Biopsy samples exhibit infiltrates of
lymphocytes and monocytes in both the vessel walls and a peripheral
nerve vasculitis. Lymphocytes and monocytes are attracted to the vessel
wall either by an infectious agent or an autoimmune response, modulated
by intercellular adhesion molecules (ICAMs).
TREATMENT
Medical Care: Medical
management depends on the disease activity and the complications that can
develop. Some patients have only mild forms of TA; others deteriorate
considerably. The two most important aspects of treatment are controlling
the inflammatory process and controlling the hypertension. Corticosteroids
are the most important therapeutic agents and are necessary in active
disease. Therapy is continued until patients achieve remission.
- For patients who do not achieve remission on corticosteroids,
cytotoxic agents such as methotrexate (0.3 mg/kg/wk) or cyclophosphamide
(1 mg/kg/d) may prove effective; azathioprine (1 mg/kg) is another
possible option. For relapses, combinations of the above can be
tried.
- Hypertension is treated with antihypertensive agents, and aggressive
therapy is necessary to prevent complications.
- Antiplatelet agents and heparin may prove useful in preventing
stroke. Warfarin also has been used. The literature reports a case of
improvement in renal and systemic function with low-dose intravenous
(IV) heparin therapy (10,000 U/d) followed by oral anticoagulant and
antiplatelet agents.
- Anti–tumor necrosis factor (TNF) agents have recently shown
encouraging results in a small number of patients with relapsing TA.
Anti-TNF may be a useful adjunct to glucocorticoid therapy; however, to
date, a controlled clinical trial is lacking.
Surgical Care: Bypass surgery has been performed on
patients with critical thoracic aortic arch arterial stenosis, upper and
lower extremity ischemia, cerebrovascular accidents, and renal artery
stenosis. The procedures are generally case specific. Certain issues, such
as the timing of surgery in relation to disease activity or the
advisability of surgery in symptom-free patients, have not been resolved.
Anastomotic stenoses or graft occlusion is a potential complication of
surgery. Short lesions respond well to percutaneous transluminal
angioplasty.
Consultations:
- Obstetrics-gynecology for pregnant patients
Diet: Diet modification is necessary to manage
hypertension or renal failure.
Activity: Any limitations depend on the severity of
the disease and complications.
MEDICATION
The goals of therapy are to reduce
inflammation and suppress autoimmune disease. To treat the active disease,
corticosteroids are used and gradually tapered. Cytotoxic agents are the
main therapeutic agents when the response to steroids is
unsatisfactory.
Drug Category: Corticosteroids -- These
agents have anti-inflammatory properties and cause profound and varied
metabolic effects. They modify the body's immune response to diverse
stimuli.
Drug Name
|
Prednisone (Deltasone) -- Used in
treatment of various allergic and inflammatory diseases. Also used
as an immunosuppressant to treat autoimmune disorders. Decreases
inflammation by reversing increased capillary permeability and
suppressing PMN activity.
|
| Adult Dose |
0.05-2 mg/kg/d PO divided bid/qid
for 1-3 mo; after obtaining a satisfactory response, taper slowly
|
| Pediatric Dose |
4-5 mg/m2/d PO;
alternatively, administer 1-2 mg/kg PO qd; taper over 2 wk as
symptoms resolve
|
| Contraindications |
Documented hypersensitivity; viral,
fungal, or tubercular skin lesions
|
| Interactions |
Clearance may decrease when used
concurrently with estrogens; when used concurrently with digoxin,
may increase digitalis toxicity secondary to hypokalemia;
phenobarbital, phenytoin, and rifampin also may increase metabolism
of glucocorticoids (consider increase in maintenance dose); monitor
patients for hypokalemia when taking this medication concurrently
with diuretics
|
| Pregnancy |
B - Usually safe but benefits must
outweigh the risks.
|
| Precautions |
Patients who receive
glucocorticoids are at risk of multiple complications, including
severe infections; abrupt discontinuation of glucocorticoids may
cause an adrenal crisis; hyperglycemia, edema, osteonecrosis,
myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria,
psychosis, myasthenia gravis, growth suppression, and infections are
possible complications of glucocorticoid use | Drug Category: Cytotoxic agents -- In patients not
responding to prednisone, cyclophosphamide or methotrexate—either in
combination with prednisone or alone—can be used to suppress the active
disease.
Drug Name
|
Cyclophosphamide (Cytoxan) --
Alkylating agent chemically related to nitrogen mustards. Mechanism
of action of active metabolites may involve cross-linking of DNA,
which may interfere with growth of normal and neoplastic cells; used
as second-line agent in treating exacerbations of immune-mediated
processes.
|
| Adult Dose |
1 mg/kg/d IV
|
| Pediatric Dose |
Administer as in adults
|
| Contraindications |
Documented hypersensitivity;
severely depressed bone marrow function
|
| Interactions |
Allopurinol may increase risk of
bleeding or infection and enhance myelosuppressive effects of
cyclophosphamide; also may potentiate doxorubicin-induced
cardiotoxicity; conversely, digoxin serum levels may be reduced;
antimicrobial effects of quinolones also may be reduced
May
increase cyclophosphamide half-life while decreasing metabolite
concentrations; may increase effects of anticoagulants
Rates
of metabolism and leukopenic activity of cyclophosphamide are
increased by long-term administration of high doses of
phenobarbital; thiazide diuretics may prolong
cyclophosphamide-induced leukopenia; also may prolong neuromuscular
blockade by inhibiting cholinesterase activity
| Pregnancy |
B - Usually safe but benefits must
outweigh the risks.
|
| Precautions |
Regularly monitor patient's
hematologic profile (particularly neutrophils and platelets) during
treatment to determine degree of hematopoietic suppression; examine
urine regularly for red cells, which may precede hemorrhagic
cystitis | |
Drug Name
|
Methotrexate (Folex, Rheumatrex) --
Mechanism of action in treatment of autoimmune diseases is unknown.
May affect immune function. Effects can be observed as early as 3-6
wk following administration; used as second- or third-line drug to
suppress active disease.
|
| Adult Dose |
0.3 mg/kg/wk PO
|
| Pediatric Dose |
Not established
|
| Contraindications |
Documented hypersensitivity;
alcoholism, alcoholic liver disease, or other chronic liver disease;
patients with laboratory evidence of immunodeficiency syndromes or
preexisting blood dyscrasias (eg, bone marrow hypoplasia,
leukopenia, thrombocytopenia, significant anemia) should not take
this medication
|
| Interactions |
Oral aminoglycosides may decrease
absorption and blood levels of concurrent PO MTX; charcoal lowers
plasma levels of both PO and IV MTX and may be particularly
significant with high-dose therapies; etretinate may increase
hepatotoxicity of MTX; folic acid or its derivatives (found in some
vitamins) may decrease response
NSAIDs administered
concurrently with MTX can cause a fatal
interaction
Indomethacin and phenylbutazone can increase MTX
plasma levels (mechanism of action is unknown but may involve
inhibition of renal prostaglandin synthesis or competitive renal
secretion)
Phenytoin serum concentrations may be decreased by
MTX; probenecid, salicylates, and sulfonamides (including TMP-SMZ)
may increase therapeutic and toxic effects of MTX; inhibition of
renal tubular secretion, competition for a common elimination
pathway, or protein displacement may be the mechanisms; if protein
displacement is the mechanism, it may involve displacement of the
highly bound metabolic 7-hydroxymethotrexate, since the parent drug
is only 50% bound; procarbazine may increase nephrotoxicity of MTX;
MTX may increase plasma levels of thiopurines
| Pregnancy |
C - Safety for use during pregnancy
has not been established.
|
| Precautions |
Monitor hematology at least monthly
and liver and renal function every 1-3 mo during therapy; during
initial or changing doses or periods of increased risk of elevated
MTX blood levels (eg, dehydration), more frequent monitoring may be
indicated
Stop MTX immediately if significant drop in blood
count; aspirin, NSAIDs, or low-dose steroids may be continued,
although possibility of increased toxicity with concomitant use of
NSAIDs (eg, salicylates) is unknown | | Drug
Category: Antihypertensive agents -- Can be used to treat
hypertension associated with arteritis. On occasion, combinations are
required. Therapy can be individualized.
Drug Name
|
Nifedipine (Procardia) -- One of
the more common channel blockers used for hypertension associated
with arteritis.
|
| Adult Dose |
Immediate release dosage form:
10-30 mg PO tid; not to exceed 120-180 mg/d
Sustained-release
dosage form: 30-60 mg PO qd; not to exceed 90-120 mg/d
| Pediatric Dose |
0.25-0.5 mg/kg/dose PO tid/qid prn
|
| Contraindications |
Documented hypersensitivity to
agent or adenosine
|
| Interactions |
May cause severe hypotension when
taken concurrently with fentanyl; cimetidine may increase toxicity
of nifedipine
|
| Pregnancy |
C - Safety for use during pregnancy
has not been established.
|
| Precautions |
Lower extremity edema has been
associated; rare instances of allergic hepatitis have been
reported | | Drug Category: Antiplatelet
agents -- Help prevent CVAs and improve renal and systemic
function. A formulation of extended-release dipyridamole and aspirin
(Aggrenox) also recently has become available.
Drug Name
|
Ticlopidine hydrochloride (Ticlid)
-- Interferes with platelet membrane function by inhibiting
ADP-induced platelet-fibrinogen binding and subsequent
platelet-platelet interaction. Used as second-line antiplatelet
therapy for patients who are intolerant to aspirin therapy or in
whom such therapy fails.
|
| Adult Dose |
250 mg PO bid
|
| Pediatric Dose |
Not established
|
| Contraindications |
Documented hypersensitivity;
caution in liver damage, neutropenia, or thrombocytopenia and with
active bleeding disorders
|
| Interactions |
Corticosteroids and antacids may
decrease effects; toxicity increases when taken concurrently with
aspirin, theophylline, cimetidine, and NSAIDs
|
| Pregnancy |
B - Usually safe but benefits must
outweigh the risks.
|
| Precautions |
Discontinue if absolute neutrophil
count falls to less than 1,200/mm3 or if platelet count
falls to less than 80,000/mm3 |
Drug Name
|
Clopidogrel (Plavix) --
Thienopyridine derivative chemically related to ticlopidine that
inhibits platelet aggregation; selectively inhibits ADP binding to
its platelet receptor and subsequent ADP-mediated activation of
glycoprotein GPIIb/IIIa complex, thereby inhibiting platelet
aggregation.
|
| Adult Dose |
75 mg PO qd
|
| Pediatric Dose |
Not established
|
| Contraindications |
Documented hypersensitivity; active
pathologic bleeding (eg, peptic ulcer, intracranial hemorrhage)
|
| Interactions |
Concomitant administration of
clopidogrel with naproxen associated with increased occult GI blood
loss; administer NSAIDs and clopidogrel with caution
Prolongs
bleeding time; safety of coadministration with warfarin has not been
established, thus administer these 2 agents with caution
| Pregnancy |
C - Safety for use during pregnancy
has not been established.
|
| Precautions |
Caution in patients who may be at
risk of increased bleeding from trauma, surgery, or other pathologic
conditions; caution in patients who have lesions with a propensity
to bleed (eg, ulcers)
Cautiously use drugs such as aspirin
and other NSAIDs that may increase such lesions in patients who are
taking clopidogrel | |
Drug Name
|
Aspirin and extended-release
dipyridamole (Aggrenox) -- Drug combination with antithrombotic
action.
Aspirin inhibits prostaglandin synthesis, preventing
formation of platelet-aggregating thromboxane A2. May be used in low
dose to inhibit platelet aggregation and improve complications of
venous stases and thrombosis.
Dipyridamole is a platelet
adhesion inhibitor that possibly inhibits RBC uptake of adenosine,
itself an inhibitor of platelet reactivity. In addition, may inhibit
phosphodiesterase activity leading to increased cyclic-3',
5'-adenosine monophosphate within platelets and formation of the
potent platelet activator thromboxane A2.
| Adult Dose |
25/200 mg PO bid
|
| Pediatric Dose |
Not established
|
| Contraindications |
Documented hypersensitivity; liver
damage; hypoprothrombinemia; vitamin K deficiency; bleeding
disorders; asthma; due to association of aspirin with Reye syndrome,
do not use in children (<16 y) with flu
|
| Interactions |
Theophylline may decrease
hypotensive effects of dipyridamole; antiplatelet activity of
dipyridamole may increase heparin toxicity
Aspirin effects
may decrease with antacids and urinary alkalinizers; corticosteroids
decrease salicylate serum levels; additive hypoprothrombinemic
effects and increased bleeding time may occur with coadministration
of anticoagulants; may antagonize uricosuric effects of probenecid
and increase toxicity of phenytoin and valproic acid; doses >2
g/d may potentiate glucose-lowering effect of sulfonylurea drugs
| Pregnancy |
D - Unsafe in pregnancy
|
| Precautions |
Aspirin may cause transient
decrease in renal function and aggravate chronic kidney disease;
avoid use in patients with severe anemia, with history of blood
coagulation defects, or who are taking anticoagulants
Caution
in hypotension; dipyridamole has peripheral vasodilating
effects | | | Drug Category:
Anticoagulants -- In patients with renal failure due to
crescentic glomerulonephritis and nephrotic syndrome, low-dose heparin
followed by oral anticoagulation leads to improved renal and systemic
function. It probably reduces the destructive effects of fibrin thrombi in
the small vessels of the kidney.
Drug Name
|
Warfarin (Coumadin) -- Interferes
with hepatic synthesis of vitamin K-dependent coagulation factors.
Used for prophylaxis and treatment of venous thrombosis, pulmonary
embolism, and thromboembolic disorders.
Tailor dose to
maintain an INR in the range of 2-3.
| Adult Dose |
5-10 mg/d PO qd for 2-3 d; adjust
dose according to desired INR
|
| Pediatric Dose |
Not established
|
| Contraindications |
Documented hypersensitivity; severe
liver or kidney disease; open wounds or GI ulcers
|
| Interactions |
Drugs that may decrease
anticoagulant effects include griseofulvin, carbamazepine,
glutethimide, estrogens, nafcillin, phenytoin, rifampin,
barbiturates, cholestyramine, colestipol, vitamin K, spironolactone,
oral contraceptives, and sucralfate
Medications that may
increase anticoagulant effects of warfarin include oral antibiotics,
capecitabine, phenylbutazone, salicylates, sulfonamides, chloral
hydrate, clofibrate, diazoxide, anabolic steroids, ketoconazole,
ethacrynic acid, miconazole, nalidixic acid, sulfonylureas,
allopurinol, chloramphenicol, cimetidine, disulfiram, metronidazole,
phenylbutazone, phenytoin, propoxyphene, sulfonamides, gemfibrozil,
acetaminophen, and sulindac
| Pregnancy |
X - Contraindicated in pregnancy
|
| Precautions |
Do not switch brands after
achieving therapeutic response; caution in active tuberculosis or
diabetes; patients with protein C or S deficiency are at risk of
developing skin necrosis | | |
Drug Name
|
Heparin (Hep-Lock) -- Augments
activity of antithrombin III; does not actively lyse but is able to
block further thrombogenesis; prevents reaccumulation of a clot
after a spontaneous fibrinolysis.
|
| Adult Dose |
Loading dose: 40-170 U/kg
IV
Maintenance infusion: 18 U/kg/h IV
Alternatively,
start with 50 U/kg/h IV, followed by a continuous infusion of 15-25
U/kg/h; increase dose by 5 U/kg/h q4h prn using aPTT results
| Pediatric Dose |
Loading dose: 50 U/kg/h
IV
Maintenance infusion: 15-25 U/kg/h IV; increase dose by
2-4 U/kg/h q6-8h prn using aPTT results
| Contraindications |
Documented hypersensitivity; active
bleeding and subacute bacterial endocarditis; history of
heparin-induced thrombocytopenia
|
| Interactions |
Digoxin, tetracycline, nicotine,
and antihistamines may decrease effects; NSAIDs, aspirin,
dipyridamole, dextran, and hydroxychloroquine may increase toxicity
|
| Pregnancy |
C - Safety for use during pregnancy
has not been established.
|
| Precautions |
Some preparations contain the
preservative benzyl alcohol; when used in large amounts, benzyl
alcohol has been associated with fetal toxicity (gasping syndrome);
preservative-free heparin is recommended in neonates; use with
caution in patients who are diagnosed with shock or severe
hypotension | | | Drug Category:
Immunosuppressant agents -- Inhibit key factors
responsible for immune reactions.
Drug Name
|
Azathioprine (Imuran) --
Antagonizes purine metabolism and inhibits synthesis of DNA, RNA,
and proteins. May decrease proliferation of immune cells, which
results in lower autoimmune activity.
|
| Adult Dose |
1 mg/kg/d PO for 6-8 wk; increase
by 0.5 mg/kg q4wk until response or dose reaches 2.5 mg/kg/d
|
| Pediatric Dose |
Initial dose: 2-5 mg/kg/d
PO/IV
Maintenance dose: 1-2 mg/kg/d PO/IV
| Contraindications |
Documented hypersensitivity; low
levels of serum thiopurine methyltransferase (TPMT)
|
| Interactions |
Toxicity increases with
allopurinol; concurrent use with ACE inhibitors may induce severe
leukopenia; may increase levels of methotrexate metabolites and
decrease effects of anticoagulants, neuromuscular blockers, and
cyclosporine
|
| Pregnancy |
D - Unsafe in pregnancy
|
| Precautions |
Increases risk of neoplasia;
caution with liver disease and renal impairment; hematologic
toxicities may occur; check TPMT level prior to therapy and monitor
liver, renal, and hematologic function; pancreatitis rarely
associated | |
FOLLOW-UP
Further Inpatient Care:
- Management is long-term. Inpatient care is limited to managing acute
manifestations of the disease, usually resulting in complications from
organ failure, stroke, complications of pregnancy, seizures, and
intracranial hemorrhage.
- ICU admission is indicated for patients with critical
deterioration.
- Fetal monitoring is indicated in patients with suspected
complications.
Further Outpatient Care:
- Monitoring long-term immunosuppressive therapy and hypertension
control is necessary.
Complications:
- Complications include stroke, intracranial hemorrhage, seizures,
graft stenosis and/or occlusion, ischemia, organ failure, complications
of hypertension, and fetal injury.
- Long-term use of corticosteroids can lead to infection, adrenal
suppression, cataracts, hyperglycemia, hypertension (which complicates
blood pressure control), osteoporosis, and aseptic necrosis.
Prognosis:
- Prognosis varies according to the severity of the disease and the
response to therapy. In some series, mortality is high. Two main North
American series showed survival figures of greater than 90%.
Patient Education:
- Patients need to understand the nature of the disease and the need
to take medications to prevent complications. When in remission or in
mild forms, patients are tempted to stop the antihypertensive drugs,
thus increasing risk of serious neurologic and other systemic
complications.
MISCELLANEOUS
Medical/Legal Pitfalls:
- TA is rare and difficult to diagnose. Initially, symptoms are vague;
disease may progress considerably until the angiogram is performed. Some
individuals may find fault with the provider if they feel diagnosis was
delayed.
Special Concerns:
- Pregnancy is an important concern; aggressively treat these
patients.
|