Page 194 - The Vasculitides, Volume 1: General Considerations and Systemic Vasculitis

170 Lindsay Lally and Stephen A. Paget

vaccination should also be vaccinated. The CDC recommends that the interval between
vaccination and initiation of immunosuppressive therapy should be at least 2 weeks.

Treatment Side-Effects and Longterm Sequela

A leading cause of preventable corticosteroid-related morbidity is the increased risk of
bone fracture due to drug-induced osteoporosis. In 2010, The American College of
Rheumatology (ACR) issued guidelines for the prevention of and treatment of corticosteroid-
induced osteoporosis [46] that includes the determination of fracture risk by the Fracture Risk
Assessment Tool (FRAX). It categorizes patients into low, medium or high risk categories
depending on the estimated 10-year risk for major osteoporotic fracture. Patients at low risk
should be offered bisphosphonate, whereas those at the highest risk of a major fracture should
be treated with bisphosphonate therapy and teriparatide. The guidelines do not address
duration of therapy. Women yet to bear children are warned of the long half-life of
bisphosphonates and teratogenic effects, likewise patients are cautioned about intra-nasal
salmon because of the increased malignant risk associated with long-term use. Patients should
be monitored closely for hyperglycemia, hyperlipidemia, hypertension, fluid retention,
cardiac arrhythmia, mood disorders, anxiety, and sleep disturbances, especially those with
pre-existing risk. Corticosteroids should not be abruptly discontinued however when tapering
is unfeasible or unsuccessful, such side effects should be proactively managed.

Premature atherosclerosis is a substantial source of morbidity and mortality for patients
with systemic vasculitis especially in premenopausal women with TAK since postmortem
studies have revealed extensive atherosclerotic changes and increased carotid plaque and
increased intimal-media thickness compared to healthy age-matched controls [47]. While
those with GCA have mortality rates comparable to age-matched controls, such patients
nonetheless have higher rates of stroke, aortic aneurysm and aortic dissection related to LVV
for 81 mg of prophylactic aspirin is recommended.

Patients with AAV also demonstrate accelerated atherosclerosis and increased
cardiovascular morbidity including increased rates of carotid plaque and aortic stiffness
compared to age-matched controls. There is a two- to four-fold increased incidence of
myocardial infarction and stroke [48] that may amenable to early intervention of AAV to
prevent prolonged inflammation and endothelial damage.

The risk of malignancy related to medication toxicity, immune-dysregulation, and
chronic inflammation comparable to other autoimmune diseases is increased two-fold in
AAV compared to the general population. Cyclophosphamide is associated with a dose-
related risk of uroepithelial and bladder cancers and hematologic malignancies, however the
thresholds dose at which this risk begins is not known. Oral cyclophosphamide carries an
increased risk of bladder cancer compared to cyclophosphamide administered by the pulse
intravenous [49]. Similarly, a history of hemorrhagic cystitis increases the risk of bladder
cancer. Uroprotective measures during cyclophosphamide treatment include co-
administration of mesna to bind the toxic metabolite acrolein and adequate hydration.

Cessation of cigarette smoking further reduces the risk of uroepithelial malignancy.
Cyclophosphamide should be discontinued if hemorrhagic cystitis arises. Patients with
cyclophosphamide-related microscopic hematuria should undergo prompt urologic evaluation

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