Paradoxical adverse events (
PAEs) have been reported during biological treatment for chronic immune-mediated diseases.
PAEs are defined as the occurrence during biological agent
therapy of a pathological condition that usually responds to this class of drug. A wide range of
PAEs have been reported including dermatological, intestinal and ophthalmic conditions, mainly with antitumour
necrosis factor α (TNF-α) agents. True
PAEs include
psoriasis,
Crohn's disease and
hidradenitis suppurativa. Other
PAEs may be qualified as borderline and include
uveitis,
scleritis,
sarcoidosis and other granulomatous diseases (
granuloma annulare, interstitial granulomatous
dermatitis),
vasculitis,
vitiligo and
alopecia areata. Proposed hypotheses to explain these
PAEs include an imbalance in
cytokine production, the differential immunological properties between the
monoclonal antibodies and TNF-α soluble receptor, an unopposed
type I interferon production and a shift towards a Th1/Th2 profile. Data from registries suggest that the risk for paradoxical
psoriasis is low and non-significant. We discuss management of these
PAEs, which depends on the type and severity of the adverse events, pre-existing treated conditions and the possibility of alternative therapeutic options for the underlying disease. Paradoxical adverse events are not restricted to anti-TNF-α agents and close surveillance of new available biological drugs (anti-
interleukin-17/23, anti-
integrin) is warranted in order to detect the occurrence of new or as yet undescribed events.