Summary
Most patients with psoriasis have variable nail involvement with clinical manifestations, including irregular pitting, "oil spot" discoloration of the nail bed, and onycholysis. Additional secondary, less specific inflammatory changes include leukonychia, nail thickening, and dystrophic malformation of the nail plate.[1] Patients with severe nail psoriasis are more likely to develop psoriatic arthritis. Additional burdens of psoriatic nail disease include pain, a predisposition to secondary infections (eg, onychomycosis, paronychia, and Pseudomonas colonization), and cosmetic malformation. Unfortunately, topical therapies, such as corticosteroids and calcipotriene, have proven relatively ineffective. In contrast, potentially effective systemic therapies -- such as methotrexate and cyclosporine -- are associated with significant adverse effects, including myelosuppression and renal and hepatic toxicity.
Recently, investigators noted cosmetic improvement in the nails of patients with psoriasis who were using biologic drugs (infliximab, adalimumab) to manage their cutaneous and/or joint disease.[2,3] The subset of patients with isolated nail psoriasis or nail psoriasis associated with only mild skin involvement may, however, be unwilling to take these drugs given their potential for rare but significant side effects, eg, infections and malignancy. In this context, Tosti and colleagues proposed low-dose acitretin therapy as a relatively safe alternative.
In their open-label study, the study authors enrolled 36 patients (27 men and 9 women; mean age, 41 years) with moderate-to-severe nail psoriasis to take low-dose acitretin (0.2-0.3 mg/kg/day) daily for 6 months. Patients were monitored for clinical improvement every 2 months during therapy, and for 6 months following treatment. Primary outcome measures included the Nail Psoriasis Severity Index (NAPSI) score and modified NAPSI score.[4,5] Both systems grade disease severity with the cardinal manifestations of nail psoriasis, eg, irregular pitting, salmon-colored patches, and onycholysis with erythematous borders; however, the modified NAPSI score only considers changes seen in 1 "target nail" per patient. In addition, investigators also graded nail clearance with a 4-point score: complete or almost complete clearance, moderate improvement, mild improvement, and no improvement. Tosti and colleagues excluded the following groups from their study: premenopausal women, patients with significant skin lesions and/or symptomatic psoriatic arthritis, patients with medical contraindications to oral retinoid use (eg, hepatic or renal disease, and patients with clinically confirmed onychomycosis.
At baseline, all patients had moderate-to-severe nail psoriasis (mean NAPSI score, 31.5; mean modified NAPSI score, 7.6). Six months of daily low-dose acitretin therapy yielded the following results:
Mean NAPSI score reduction of 41%;
Mean modified NAPSI score reduction of 50%;
Complete or almost complete nail clearance in 9 patients (25%), moderate improvement in 9 patients (25%), mild improvement in 12 patients (33%), and no improvement in 6 patients (17%);
Although nail psoriasis recurred in all responders after stopping acitretin, both mean NAPSI and modified NAPSI scores remained lower than baseline levels at 6 months' follow-up;
Low-dose acitretin was well tolerated, with only 1 patient developing an adverse event (periungual dryness and pyogenic granulomas), which regressed after lowering the acitretin dose; and
No other significant drug-related clinical or laboratory side effects were observed.
Viewpoint
Nail psoriasis is not a trivial concern to those who suffer from it. Many complain of chronic pain, recurrent infections, and the work and social stigma associated with having chronically discolored, dystrophic fingernails. Topical treatments, although safe, are typically ineffective. In contrast, biologic agents, such as infliximab and adalimumab, have been reported to yield NAPSI score reductions of 57% (after 24 weeks) and 69% (after 20 weeks), respectively. However, patients with psoriasis limited to the nails may have a hard time justifying the risks associated with these targeted immunosuppressive drugs.
In this context, the study authors presented low-dose acitretin as a viable alternative therapy for isolated nail psoriasis. As an important caveat, they noted that this response is dose-dependent, with a previous study showing that higher doses of oral retinoids may actually worsen nail psoriasis or trigger complications, such as paronychia and nail fragility.[6]
The above study is limited by a small sample size (n = 36); lack of placebo controls; and exclusion of patients with significant skin and/or joint disease, which raises the question of whether oral retinoid therapy would be as effective in patients with more extensive psoriasis. As expected, psoriatic nail changes recurred in all patients after stopping the acitretin; however, clinical improvement was still evident in many, even 6 months after drug cessation. It would be interesting to see how long this modest improvement persists, or whether it could be augmented with the addition of topical therapies, such as corticosteroids or calcipotriene.
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