Analysis of CARD14 Polymorphisms in Pityriasis Rubra Pilaris: Activation of NF-κB

TO THE EDITOR Pityriasis rubra pilaris (PRP) is a rare inflammatory papulosquamous disorder manifesting with palmoplantar keratoderma and follicular hyperkeratotic papules that tend to coalesce into large, scaly, erythematous plaques often progressing to exfoliative erythroderma (Klein et al., 2010; Petrof et al., 2013). PRP is often misdiagnosed as psoriasis, a more common papulosquamous inflammatory disorder. Nevertheless, the two conditions, in their classic presentations, are clearly distinct, and can be distinguished by clinical findings and histopathologic features (Magro and Crowson, 1997). Clinically, PRP manifests with characteristic “sparing islands” of apparently normal skin, palmoplantar keratoderma, and follicular papules. The disease is frequently self-limiting within a few years’ timeframe. Histopathology of PRP is characterized by alternating orthoand parakeratosis rete ridges oriented in vertical and horizontal arrays (“checkerboard pattern”), acanthosis with broadened bases, follicular plugging, perivascular lymphocytic infiltrate in the dermis, and lack of neutrophils in the epidermis. Currently, there is no specific or uniformly effective treatment for PRP. Most cases of PRP are sporadic without family history, but a familial form with an autosomal dominant inheritance with partial penetrance representso6% of all cases. We recently demonstrated that patients with the familial form of PRP harbor gain-offunction mutations in the CARD14 gene encoding the caspase recruitment domain family, member 14 (CARD14) (Fuchs-Telem et al., 2012). This protein is an activator of NF-κB (Blonska and Lin, 2011), and it has also been implicated in cases of familial psoriasis (Jordan et al., 2012a, b). This study investigates whether CARD14 mutations might also underlie cases of sporadic PRP. Patients with PRP were solicited through a website (www.prp-support. org) that serves as a focus of PRP information exchange, frequently visited by patients. A total of 156 patients requesting enrollment were sent an institutional review board (IRB)– approved informed consent, a questionnaire, and a saliva collection kit for DNA isolation. This study was approved by the IRB of Thomas Jefferson University. Of these, 48 patients returned a Q Li et al. CARD14 Polymorphisms in PRP