Visual and cutaneous toxicity which occurs during N-(4-hydroxyphenyl) retinamide therapy for psoriasis

Abstract

Summary Vitamin A (retinol) has been used both topically and systemically in the treatment of skin disease for approximately 40 years (Berson, 1983). Retinol taken in high doses over a period of time can cause fatigue, headaches, cheilitis, anorexia, peeling of the skin and can cause papillary oedema and hepatotoxicity (Dahl et al., 1977). These symptoms form the hypervitaminosis A syndrome and can be caused by acute or chronic intoxication with vitamin A or vitamin A analogues (retinoids). Because of this toxicity and the only marginal therapeutic benefit, the use of systemic vitamin A declined. Since 1977 two synthetic retinoids, isotretinoin (13‐cis‐retinoic acid) (Korner & Vollum, 1975) and etretinate (Meyskens et al., 1983) have been found to be of clinical use in the treatment of acne, psoriasis and the disorders of keratinization. These drugs have been found to be of such therapeutic benefit to patients that some of their side‐effects (Moon et al., 1979) have become acceptable. The realization of the therapeutic potential of retinoids for skin disease has led to an expansion in retinoid pharmacology research. As a consequence new retinoids are reaching the stage of clinical testing in patients. We report our experience of unusual side‐effects which occur during a phase II clinical trial of (N‐[4‐Hydroxyphenyl] retinamide)(4HPR) in the treatment of severe chronic plaque psoriasis.

The Bioactive Lipid 4-Hydroxyphenyl Retinamide Inhibits Flavivirus Replication

“…Ceramides and ceramide metabolism have been implicated in DENV replication (32) and DENV-induced apoptosis (33)(34)(35), making 4-HPR an attractive antiviral molecule that interacts with known lipid pathways important for DENV infection. Additionally, 4-HPR has been investigated in the clinic as a potential treatment or preventative agent for various cancers (36,37), psoriasis (38), obesity-associated insulin resistance (39), and macular degeneration (40). The known safety and bioavailability profiles of 4-HPR therefore make it an attractive candidate for repurposing as an antiviral agent.…”

“…The molecular targets of 4-HPR relevant to cancer (36,37), macular degeneration (40), psoriasis (38), obesity-associated insulin resistance (39), and other diseases are still elusive, despite considerable investigation over the previous decades. A recurring theme complicating these studies has been the polypharmacology of 4-HPR.…”

Ocular toxicity and cancer chemotherapy: A review

“…[136][137][138][139][140][141] The usual manifestations of blepharoconjunctivitis include dry eyes, blurred vision, and intolerance of contact lenses. Blackman et al reported blepharoconjunctivitis in 42 of 97 patients receiving isotretinoin.136 Symptoms and signs disappeared within a week after discontinuation of therapy.…”

Secretion of N-(4-hydroxyphenyl) retinamide-retinol-binding protein from liver parenchymal cells: Evidence for reduced affinity of the complex for transthyretin

“…Initial clinical studies with 4-HPR at high doses (Kingston et al, 1986;Kaiser-Kupfer et al, 1986) were hampered by the fact that it has profound effects on the normal metabolism of vitamin A. It has been demonstrated that the regulation of RBP is greatly affected both in humans and experimental animals treated with 4-HPR (Formelli et al, 1987(Formelli et al, , 1989.…”