Etretinate and the nails (study of 130 cases) possible mechanisms of some side-effects

Abstract

Summary With the exception of acropustulosis, nail disease responds poorly to etretinate. When used to treat other dermatological conditions etretinate is frequently toxic to the normal nail and may affect any or all of its epidermal components. The desquamative dermatitis, induced by etretinate, may account for many of the drug's side‐effects on the nail. These include chronic paronychia, onycholysis, onychomadesis, nail shedding, onychoschizia, fragility and the formation of excess granulation tissue. Some of these changes resemble those found in psoriatic paronychia and similarities are drawn between psoriasis and the retinoid dermatitis which presents with identical features in the discharge from beneath the proximal nail‐fold. The desquamative reaction in patients taking etretinate always affects the lips and, in addition, may be widespread or mainly localized to the nail apparatus.

Modulation of linear nail growth to treat diseases of the nail

“…65 The literature on retinoids has been mixed, with the majority of studies reporting slower growth of nails while on therapy. 66 Baran,64 in a study of 130 patients on etretinate, found that linear nail growth was reduced in almost half the patients treated. Conversely, increased growth rate with retinoid therapy has also been described.…”

“…Intralesional corticosteroids are frequently used to treat psoriatic nails, but response to steroids seems to be limited to improvement in the pitting 62 and nail thickening 63 with less effect on onycholysis and the hyperkinetic state. Furthermore, some medications such as methotrexate and other cancer therapeutics may cause onycholysis, a factor known to accelerate nail growth, 64 but the antimitotic effects on growth predominate, resulting in overall growth rate reduction. Recently, the new biologic medications have been making an impact on the treatment of psoriasis.…”

Paronychia with Pyogenic Granuloma in a Child Treated with Indinavir: The Retinoid-Mediated Side Effect Theory Revisited

“…It has already been mentioned in the recent reports on paronychia and pyogenic granuloma, observed during therapy of adult patients with IDV [4, 5, 6], that similar symptoms have also been seen during systemic treatment with oral retinoids, such as etretinate, its nonesterified derivative acitretin or isotretinoin [8, 9, 10, 11, 12]. Based on homologies of the amino acid sequences of the HIV-1 protease and cytoplasmic retinoic-acid-binding protein type 1 (CRABP-1), Carr et al [2]have proposed that HIV-1-protease-inhibitor-associated peripheral lipodystrophy represents a consequence of impaired retinoid metabolism due to protease inhibitor effects.…”

“…Several adverse effects associated with HIV-1 protease inhibitors (and in part also observed in our patient), such as hyperlipidemia, dermatitis, dry skin, hair loss or pyogenic granuloma of nail folds, resemble symptoms of retinoid toxicity mediated by retinoic acid receptors and observed after treatment with retinoids like isotretinoin, etretinate and acitretin [8, 9, 10, 11, 12, 20]. Thus, considerable evidence advocates mediation of IDV side effects by an impaired oxidative metabolism of retinoic acid through inhibition by IDV of cytochromes P450 3A rather than by impaired formation of 9-cis-RA.…”

Pyogenic granulomas during isotretinoin therapy

“…In general, retinoids are known to decrease the attachments between keratinocytes and cause nail brittleness that allows for fragment penetration between the nail bed and adjacent tissue. 10 Retinoids also promote the early stages of wound healing, cause the accumulation of mononuclear cells in the dermis, and stimulate collagen synthesis. Some or all of these factors combined may increase an individual's susceptibility to the growth of excess periungual granulation tissue.…”