Abstract
To the Editor,
Generalized pustular psoriasis (GPP) is a rare psoriasis subtype where the mean age of onset is 40 years old. 1 Currently, there is no review on elderly-onset GPP. This systematic review characterizes the clinical course and treatment outcomes in patients who develop GPP over 60 years of age.
Following PRISMA guidelines, PubMed, MEDLINE and Embase databases were searched on June 17, 2023, using specific keywords (Supplementary Material 1, available via Mendeley at https://doi.org/10.17632/mw5xwd99g8.1). Following screening, 19 articles were included (n = 491 patients) (Supplementary Material 1). Both interventional and observational studies were included if they featured patients older than 60 years. The mean age was 72.96 years (range: 60-92), and there were 21 females (53.8%) and 18 males (46.2%) in the cohort with reported data (n = 39). Among 24 patients with available data for IL36RN, CARD14 or AP1S3 mutation testing, 5 (20.8%) had a significant mutation. Additionally, 46.2% (12/26) experienced symptoms of other psoriasis subtypes prior to GPP onset, including psoriasis vulgaris, pustular psoriasis and an unspecified type of psoriasis. Comorbidities most commonly included diabetes mellitus (4/23, 17.4%) and dyslipidemia (4/23, 17.4%).
Clinical presentation described erythematous patches with pustular lesions typically involving the face, limbs, and trunk. Provocative factors were frequently drug-related, including the use of methotrexate, oral prednisone, and propranolol. Other factors included flu vaccination, respiratory and urinary tract infections, and stress.
Clinical course varied and some studies described elderly onset-GPP to be atypical, where a relatively slower appearance and slower response to treatment were observed relative to mean age of onset. 1,2 Multimodal treatment was employed in 62.0% (18/29). Common treatments included: etretinate (10/29, 34.5%), acitretin (7/29, 24.1%), topical corticosteroids (7/29, 24.1%), methotrexate (6/29, 20.7%), calcipotriol plus betamethasone dipropionate (5/29, 17.2%), vitamin D3 (5/29, 17.2%), oral steroids (5/29, 17.2%), and others (6/29, 20.7%). Biologics were used in 24.1% (7/29), where brodalumab was most common (3/29, 10.3%), followed by secukinumab (2/29, 6.9%), adalimumab (2/29, 6.9%), and infliximab (1/29, 3.4%). Overall, among 33 patients with reported treatment responses, 5 (15.2%) achieved complete resolution, 24 (72.7%) achieved partial resolution, and 4 (12.1%) achieved no resolution.
Among elderly patients, oral retinoids and methotrexate were the most common treatments, which is similar to management in patients with younger age of onset. 3 Clinicians may consider biologics, particularly in patients presenting with erythroderma or systemic symptoms, as observed in several of the studies which utilized IL-17 and TNF-alpha inhibitors. 1 The release of cytokines such as IL-17 and TNF-alpha cause the activation of neutrophils, Th17 cells, and dendritic cells, leading to neutrophilic infiltration. 4 Additionally, the IL-36 inhibitor spesolimab, which recently received FDA approval for GPP management, could be considered. The IL-36 axis drives the release of these cytokines and plays a central role in stimulating pustular formation. 5
Study limitations included: lack of patient-specific outcomes reported in 434 patients, possible selection bias towards cases with better outcomes, and inconsistent reporting of the Psoriasis Area Severity Index. Regardless, this study further characterizes the clinical presentation and management of GPP in a population subset with limited literature.
Supplemental Material
Supplementary Material 1 - Supplemental material for Elderly Onset Generalized Pustular Psoriasis: A Systematic Review
Supplemental material, Supplementary Material 1, for Elderly Onset Generalized Pustular Psoriasis: A Systematic Review by Mahek Shergill, Rochelle F. McAdam, Nawar Tarafdar, Muskaan Sachdeva, Khalad Maliyar, Jorge R. Georgakopoulos, Asfandyar Mufti and Jensen Yeung in Journal of Cutaneous Medicine and Surgery
Footnotes
Declaration of Conflicting Interests
The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr Yeung has been a speaker, consultant, and investigator for AbbVie, Allergan, Amgen, Astellas, Boehringer Ingelheim, Celgene, Centocor, Coherus, Dermira, Eli Lilly, Forward, Galderma, GSK, Janssen, Leo, MedImmune, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi Genzyme, Takeda, UCB, Valeant, and Xenon. Dr. Mufti has also been a speaker for AbbVie and Janssen. Dr. Sachdeva, Mahek Shergill, Dr. Maliyar, Dr. Georgakopoulos, Rochelle F. McAdam, and Nawar Tarafdar, have no conflicts of interest to declare.
Funding
The authors received no financial support for the research, author-ship, and/or publication of this article.
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References
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