Side Effects and Long-term Toxicity of Synthetic Retinoids

Abstract

The observation that vitamin A (retinol) has antikeratinizing properties has led to the development of synthetic retinol derivatives (retinoids) for the treatment of a variety of skin disorders characterized by abnormal keratinization. The goal of research in this area is the synthesis of retinoids that would have a more favorable therapeutic: toxic ratio than retinol itself. A limiting factor in the use of any vitamin A analogue is that, even with a more favorable therapeutic: toxic ratio, large pharmacologic doses are required that produce side effects related to the drug's action in most individuals. With few exceptions, all of the side effects are those seen from mega-vitamin A ingestion, primarily affecting the mucocutaneous, skeletal, and central nervous systems. Most of the side effects from excess vitamin A are reversible, with notable exceptions being those involving hepatic and osseous tissues. In terms of reversibility from synthetic retinoids, the experience to date has been incomplete, so there remains imprecise information as to the incidence and the persistence of toxic effects after drug withdrawal.

Retinoids: Fascinating Up‐and‐Coming Scenario

“…Side‐effects (Table 5) ‐Mucocutaneous side effects are tolerable, treatable, and dose dependent (35, 36) and are considered as signs of compliance (36, 37); cheilitis is the most frequent and universally accepted. Although xerosis is common, palmo‐plantar peeling is an uncommon and troublesome sequela (36, 37). Atrophy and skin fragility may also occur; occasionally there may be stimulation of granulation tissue and associated pyogenic granulomas (36).…”

“…Atrophy and skin fragility may also occur; occasionally there may be stimulation of granulation tissue and associated pyogenic granulomas (36). Thinning of the hair and fragility of the nails may follow 3 to 8 weeks after therapy (35, 37). Most of the side effects are tolerable.…”

“…Adverse ophthalmological effects are a consequence of decreased Meibomian gland secretion, which causes loss of the corneal tear film, resulting in an increased evaporation of tears, in turn causing xerophthalmia, exposure keratitis, corneal opacity, and corneal ulceration (37, 38). Night blindness is an outcome of the inhibition of ocular retinol dehydrogenase (37). Patients should be advised to use wetting agents and contact lens use should be avoided in cases of severe eye complications (35).…”

“…Corneal opacity usually resolves itself in 6 to 8 weeks (35). Inhibition of ocular retinol dehydrogenase with decreased formation of 11‐ cis ‐retinal may cause night blindness (37, 38).…”

“…Musculoskeletal complaints include myalgias fatigue, and lethargy (35–37). Persistent headaches associated with signs of papilledema and pseudotumor cerebri necessitate discontinuation of therapy (37).…”