CHICAGO – If you’ve ever found that making a diagnosis of pityriasis rubra pilaris is difficult, you’re not alone.

In a recent case series of 100 patients with a median age of 61 years, only 50 patients had an undeniable diagnosis of pityriasis rubra pilaris (PRP). Of those patients, only 26% were diagnosed at initial presentation. The mean delay to diagnosis was 29 months, and 54% required two or more biopsies (JAMA Derm. 2016 Jun 1;152[6]:670-5).

“This is one of those conditions that sometimes you’re going to follow patients and not know what it is right away,” Patricia M. Witman, MD, said at the World Congress of Pediatric Dermatology. Although eczema and contact dermatitis are common diseases where the diagnosis is missed, it’s easy to mistake pityriasis rubra pilaris for psoriasis.

“On the flip side, follicular psoriasis is easy to mistake for PRP,” said Dr. Witman, chief of the division of dermatology at Nationwide Children’s Hospital, Columbus, Ohio. “It’s an uncommon variant that occurs in only about 2.1% of all pediatric psoriasis. These patients can have keratoderma, but they have classic psoriasis on biopsy. Pediatric patients with this subtype do not typically have classic psoriasis plaques.”

PRP is an anti-inflammatory papulosquamous disease with an incidence that ranges between 1:3,500 and 1:400,000. It occurs equally in men and women and has a bimodal onset, with 52%-60% of cases occurring in the 6th or 7th decade of life, and 6%-12% occurring in the 1st or 2nd decade of life, with a mean age of 7 years. Characteristic clinical features include cephalocaudal spread, keratotic follicular papules, well-demarcated orange/red plaques, fine scale, islands of sparing, erythroderma, and palmoplantar keratoderma.

“Even though it’s characteristic, there is a wide spread in the type of disease manifestations,” Dr. Witman said. “There are six different types based on how old you are and on the presentation.”

She limited her presentation to a discussion of three types:

Classic juvenile type. This type usually presents between ages 5 and 10 and resembles the type I, or classic adult, type, with cephalocaudal spread, follicular keratotic erythematous papules coalescing into plaques, islands of sparing, and typically keratoderma. The scalp dermatitis it causes “often has a little finer scale than the thick micaceous scale we see in psoriasis,” she noted. “Patients can have a photoaggravated presentation with relative sparing of areas protected from the sun.”
Circumscribed juvenile type. This is the most common pediatric variant. It usually presents between the ages of 3 and 10, with a mean age of 6. It is characterized by sharply demarcated plaques on extensor elbows and knees, as well as follicular hyperkeratosis. About 70% will also have keratoderma. “The Achilles tendon involvement is considered to be fairly pathognomonic for this condition and helps differentiate it from psoriasis, as well as an orange to yellow color of the keratoderma,” Dr. Witman said.
The atypical juvenile type, or type V. This the familial variant of PRP. It’s also the rarest, occurring in just 6.5% of cases. “It’s autosomal dominant and has incomplete penetrance and variable expression,” she said. “It typically presents in infancy or in the first few years of life. Patients with this form also tend to have a more sclerodermoid palmoplantar keratoderma and ichthyosiform features. It is typically a lifelong condition, but there have been occasional case reports of self-resolution.”

The clinical features of PRP often overlap with psoriasis.

“Although there are some things that are more pathognomonic for PRP, like the Achilles tendon involvement and the keratoderma, for psoriasis we have nail pitting, which we don’t usually see in PRP,” Dr. Witman said. “Sometimes, it’s the skin biopsy that helps us distinguish those defining features, and it may take more than one biopsy to make the diagnosis.”

Dermoscopy can also be helpful. One analysis found that dermoscopy features of PRP include multiple keratotic papules with peripheral rings of erythema that coalesce into a yellow-orange plaque, linear vessels at the periphery of papules, and papules centered on hair (J Am Acad Dermatol. 2015 Jan;72[1]:S58-9).

“Even when you have that definite diagnosis of PRP, you have to remember that PRP can be seen within the context of other disease,” Dr. Witman cautioned. “Malignancy is usually limited to our adult patients with PRP, but infection can certainly trigger PRP in our pediatric patients, most commonly streptococcus. Medication reactions, especially to the biologics, have also been reported to cause PRP-like reactions, as well as autoimmune disease.”

One such entity is referred to as “Wong-like” dermatomyositis, in which patients present with a rash that looks identical to PRP (Ped Dermatol. 2007;24[2]:155-6). “It can occur in both the juvenile and adult populations,” she said. “It has clinical and histopathologic features of PRP, yet it may precede or occur concurrently with a diagnosis of dermatomyositis.”

In 2012, a group of researchers discovered that a gain of function mutation in CARD14 leads to atypical juvenile-type PRP (Am J Hum Genet. 2012 Jul 13;91:163-70). CARD14 is a member of a protein family known as caspase recruitment domain, family member 14, which also is mutated in a variant of familial psoriasis.

“It’s a protein that’s predominantly expressed in the skin, and it’s a known activator of transcription factor nuclear factor kappa light chain enhancer in activated B cells [NFkB], which is responsible for inflammation in the epidermis,” Dr. Witman explained. “What we know is that if you have a gain of function mutation in CARD14, we think that this activates the NFkB pathway and leads to increased inflammation of the skin. The same process would be expected in cases of familial psoriasis.”

Current treatment of PRP is challenging, he said. A recent survey of patients found that 76% found emollients most effective, followed by topical steroids (50%) and salicylic acid (45%) (JAMA Derm. 2016 Jun 1;152[6]:670-5). When it came to systemic therapies, 59% found retinoids most effective, followed by methotrexate (42%) and tumor necrosis factor inhibitors (40%). Only 8% found phototherapy helpful.

Dr. Witman noted that the discovery of the CARD14 mutation as the cause of the familial variant “brings us closer to an understanding of juvenile PRP,” and to the potential for targeted therapy.

“This really raises the question: Do ustekinumab and similar drugs have a future role in the treatment of PRP?” she asked. “We do see anecdotal evidence of clearance in adults using ustekinumab, both those with and without type V PRP and a CARD14 mutation. It has been tried in adult patients, predominantly in those who have failed multiple therapies. But this is anecdotal evidence with isolated case reports. These patients did respond to dosing that is typical for psoriasis.

“At this point, it is not approved for PRP, nor is it approved in children – but it’s something to think about once we have more information,” Dr. Witman noted. “The newer biologics targeting IL[interleukin]-23 and IL-17 may hold promise for PRP, based on what we have learned in psoriasis. But at this point, the safest and most effective therapy for the different variants of PRP in our pediatric patients remains to be seen.”

Dr. Witman reported having no relevant financial disclosures.

dbrunk@frontlinemedcom.com

Targeted therapy may be possible for pityriasis rubra pilaris