Page 239 - The Vasculitides, Volume 1: General Considerations and Systemic Vasculitis

214 Loic Guillevin

Prognosis

Untreated, 12% to 13% of untreated patients with PAN survived [35], however with
effective therapy the overall survival rate exceeded 80% [79] for PAN alone, and 70% in
those with associated HBV infection [3]. A systematic retrospective study of 348 patients
with PAN registered in the French Vasculitis Study Group (FVSG) database [36] satisfying
ACR [4] and CHCC Nomenclature [5], and followed for 68.3 months showed relapses in 76
(21.8%). Relapse rate, mortality, and 5-year relapse-free survival rate, were significantly
associated with the presence of HBV infection. Overall, 63 (28%) relapsed with PAN alone
versus 13 (10.6%) with associated HBV infection (P<0.001). Overall, 86 (24.7%) patients
died (44 [19.6%] with PAN versus 42 (34.1%) with associated HBV infection (P=0.003). The
5-year relapse-free survival rate for PAN alone was 59.4% (95% confidence interval [CI]
52.6–67.0) for PAN alone versus 67.0% (95% CI 58.5–76.8) with associated HBV infection.

Relapse

In contrast to GPA and MPA, remission once obtained, tends not to recur in PAN.
In one large cohort of patients with and without HBV infection-associated PAN [79] 8% of
the former and 19% of the latter demonstrated a first relapse at 37 months and 29 months
from disease onset, while 10% of another cohort [3] with HBV-related PAN relapsed.
Relapses associated with HBV infection occur in those with persistent active virus replication
after treatment. A stepwise multivariate analysis [36] calculated hazard ratios (HR) and CI for
independent predictors of relapse that included, HBV-related PAN (2.27 [95% CI 1.11–4.63)
and cutaneous manifestations at diagnosis (HR 1.85 [95% CI 1.08–3.23]), especially when
only nodules were considered (HR 2.21 [95% CI 1.30–3.78]) Although the severity of
relapses was unpredictable, rash and arthralgia conferred a more favorable prognosis for a
less severe disease status compared to the initial clinical presentation.

Mortality

The major causes of mortality in PAN are shown in Table 5. Mortality can be divided
into two types: those attributed to the vasculitic process involving major organ and others due
to severe treatment-related side effects. While a few patients may die during the first few
months of the disease due to unresponsiveness to treatment [60], the majority occur with
longer durations of multi-organ involvement associated with fever and rapid weight loss,
especially those with gastrointestinal involvement. Mortality related to treatment side effects
generally occur in the years following treatment for controlled or uncontrolled vasculitis with
infections representing the primary cause of death due to intense initial therapy with
corticosteroids and cytotoxic agents. Viral infections, notably Pneumocystis carinii, occur
later in the course associated with profound drug-induced immunosuppression [80, 81].

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