An update on generalized pustular psoriasis

ABSTRACT Introduction: Generalized pustular psoriasis (GPP) is a rare, severe relapsing/remitting, multisystem disease that can be difficult to treat. Recent clinical, histological, and genetic evidence suggests that GPP is a distinct clinical entity from plaque psoriasis and requires a separate diagnosis. The interleukin-36 pathway appears to be central to GPP pathogenesis. As no therapeutic agents have been approved for GPP to date in the United States or Europe, the introduction of anti-IL-36 therapies may change disease management. Areas covered: Using PubMed and Google Scholar, we reviewed the literature for articles related to GPP, psoriasis, and the genetics, pathogenesis, and treatment thereof. Expert opinion: New therapeutic options and updated guidelines for GPP treatment are needed. Ideal agents would have rapid onset of action and rapid time to achieve disease clearance, have the ability to prevent acute flares and avert recurrence, and possess a favorable safety profile. Such therapies should be readily accessible via approval or listing on formularies. Scoring systems to establish GPP disease burden and objective outcome measures could also help with further evaluation of therapies and treatment access issues. IL-36 remains a promising target, as supported by early phase data suggesting efficacy and safety for a novel anti-IL-36 therapy. Plain language summary Generalized pustular psoriasis (GPP) is a rare dermatological condition; it is characterized by the sudden appearance of multiple small blisters filled with pus (called pustules) on large areas of the skin of the body, arms, and legs, that also become red and painful. The pustules are not infectious. Other symptoms may include fever, chills, and loss of appetite. These episodes are called flares, and can cause – in the most severe cases – life-threatening complications (such as heart failure, and/or serious infection) that may require emergency medical treatment. GPP can last from days to weeks, and often comes back. The cause of GPP is unknown, but specific factors are known to trigger a flare (such as taking certain medicines, or suddenly stopping steroid medicines). Problems with the immune system are likely to be important in causing GPP. The interleukin-36 pathway involves a group of proteins that act on immune cells in the skin (and other tissues). These proteins are linked to the development of GPP in some people. This article aims to provide a summary of the main features of GPP, including possible immune and genetic factors (particularly the interleukin-36 pathway), and the limitations of treatment options available to doctors. Video Abstract Read the transcript Watch the video on Vimeo. Copyright is retained by Boehringer Ingelheim Pharmaceuticals, Inc., under a CC-BY license.