GPP typically has an acute course, but fewer than 5% had clear or almost clear skin between GPP flares [1]. Although plaque-type psoriatic lesions may occur both in GPP patients with or without IL36RN mutation, some morphological differences were observed in the present study. The co-existing psoriatic plaques in patients with GPP may represent either partially controlled/abortive pustular psoriatic lesions, especially in those with IL36RN mutation, or alternatively, an independent psoriasis vulgaris (PV) pathogenesis in PV-susceptible patients. Phenotypically, psoriasis vulgaris has been classified as either thin or thick plaque types [5] with differences in phenotypes and endotypes and treatment efficacy [6]. Thinner plaques in patients with DITRA might result from the linkage disequilibrium between genes for GPP and for thin plaque type psoriasis. Previously, a history of psoriasis vulgaris was found more frequent in GPP patients with CARD14 mutation [7]. CARD14-associated papulosquamous eruption (CAPE) shared features of psoriasis and pityriasis rubra pilaris, which is typified by thin plaques [8]. It is also possible for a single GPP patient carrying two pathogenic genes [9].
Previously, a correlation with HLA-C∗06:02 was observed in GPP patients with PV. [10], but its effects on the characteristic of psoriatic plaques have not been investigated. In this study, those without IL36RN mutation had thicker plaques and more vivid erythema, which might be a reflection of the increased IL-22 [11] and neoangiogenesis/vascular endothelial growth factor [12] in typical plaque type psoriasis. However, the actual explanation for the difference is unknown. Recently, the effect of IL-36 on corneodesmosin has been reported to be associated with stratum corneum exfoliation [13].
The co-existence of psoriatic plaques in GPP is common, but the clinical features of these plaques and pathogenesis are not well studied. Spesolimab, an IL36R antagonist, has been approved for the acute flare treatment in GPP. Some evidences also imply a better response in patients with IL36RN mutation for both flare treatment [14] and prevention [15]. However, it is unknown if spesolimab works as well in the co-existing or residual psoriatic plaques and if cytokines other than IL-36 are involved in the pathogenesis of plaques lesions associated with GPP.
There are several limitations of this study. First, as only one picture was sent for evaluation for each patient, there might be some selection bias and the selective pictures might be non-representative. Second, PASI assessment might have subjective components. Nonetheless, due to the retrospective design of this study, using other objective tool for evaluation is not feasible. Thus, re-evaluation after 7 days or picture substitution were designed to ensure inter-rater reliability. Finally, the concurrent treatment might affect the phenotypes of the lesions, although the treatments between the two groups were not statistically different.
Despite the discovery of IL36RN mutation, GPP remains a heterogeneous diseases and other modifying factors and genes may affect its clinical manifestations and treatment responses. Although we found a statistically significant difference in terms of thickness and erythema subscore of psoriatic plaques between IL36RN mutation positive and negative groups, the clinical, therapeutical and pathophysiological implications of the findings remain to be studied.