Laddered treatment for pityriasis rubra pilaris

For some patients with pityriasis rubra pilaris (PRP) who do not respond to standard systemic treatments, biologic therapy may result in marked clinical improvement, according to Scott Worswick, M.D., a UCLA dermatologist speaking at the American Academy of Dermatology annual meeting in San Diego on Feb. 18.

While there are no randomized clinical trials of biologic treatments for pityriasis rubra pilaris, case reports and clinical experience suggest an eight-week course may be sufficient to see if a patient may respond, he said.

Mainstays for initial treatment of PRP have included topical steroids, oral retinoids (isotretinoin/acitretin), methotrexate, cyclosporine and phototherapy. Dr. Worswick, who sees many of the PRP patients in the Los Angeles area, said his first choice of therapy is a retinoid.

“In the patient population that I’ve seen, there is maybe a 50% response rate to acitretin. If they don't respond to that, it's usually taken me one or two, and only a few times three treatments of different types to get to the treatment that works for a patient,” he said.

When initial therapy is ineffective, Dr. Worswick considers the TNF inhibitor etanercept as the next choice, and if that doesn’t work, ustekinumab may be his next choice.

That laddered approach is based in part on a recent research project Dr. Worswick undertook with UCLA colleagues Lisa Hisaw, M.D., and Nolan Maloney, a second-year medical student.

In a systematic review of medical literature, they found 54 reported cases of patients with adult-onset PRP who received biologics, usually after relapse on a previous systemic therapy. Biologics tried in these patients included etanercept, infliximab, ustekinumab, secukinumab, and adalimumab.

Of those 54 cases, 37 had a marked improvement (i.e., >75% reduction in body surface area) after biologic treatment, while another 3 patients had a partial response.

In the cases where there was a marked improvement,  more than 90% of cases (37/40) showed an improvement before week eight of treatment. The median time to response was four weeks.

“It's hard to make a rule that biologic regimens shouldn't be continued past a certain point. But we did find that if a patient isn't improving after, say, the 10th week, they're perhaps less likely to improve, and they could potentially benefit from potentially a different class of biologic,” Dr. Maloney said.

Although 40 responses out of 54 biologic-treated cases may be encouraging, Dr. Hisaw noted that the response rate may be somewhat overstated due to publication bias. “What we've seen is there's a good smattering of several different biologics that have been shown to have some efficacy for PRP … but (investigators) might not be presenting the data in the cases that fail,” she said.

Based on these findings, which have been provisionally accepted for publication in the Journal of the American Academy of Dermatology, Dr. Worswick said it is reasonable to consider a trial of a specific biologic, but to switch to an alternative approach if no response is seen after a certain length of time.

“We would probably recommend at least a 3- or 4-month course of acitretin for a patient for PRP before abandoning therapy,” he said. “In contrast, if we were to start a PRP patient on etanercept, for example, and they had gotten to week eight without any benefit, we think it would be pretty unlikely to see a benefit past that point.”

CHALLENGING DIAGNOSIS

Diagnosing PRP is challenging because it can mimic eczema, psoriasis, or even ichthyosis. Some drug rashes can mimic PRP, and some drugs may trigger PRP, including insulin, vaccines, and sorafenib and imatinib, two kinase inhibitors used in the treatment of certain cancers.

Clinicians should consider PRP in the differential diagnosis of any patient with chronic eczematous or psoriasiform rash, regardless of morphology or distribution, Dr. Worswick said. In some cases, the patient may have classic signs of PRP, such as waxy keratoderma on the palms or soles, or characteristic “islands of sparing” of unaffected skin, often on the trunk or limbs.

REFERENCES

Scott Worswick, MD. “Hidradenitis Suppurativa and Pityriasis Rubra Pilaris: Updates on Treatments for Two Conditions that are Difficult to Manage.” American Academy of Dermatology 2018 Annual Meeting, San Diego, Calif. Feb. 18, 7:00-8:00 am.