Generalized pustular psoriasis (GPP) is a rare, severe form of psoriasis manifesting in pustular psoriatic lesions combined with a multi-systemic inflammatory, potentially life-threatening reaction. The IL36RN gene with autosomal recessive inheritance was identified as the first GPP gene. Two IL36RN mutations were identified in 37% of the first 19 patients from Germany by the group of PD Dr. Ulrike Hüffmeier (Körber et al. 2013), while in an extended patient group (n = 61), 15% of patients with IL36RN mutations, carried additional risk variants in other genes relevant for GPP (Mössner et al. 2018). This indicates a rather oligogenic than purely monogenic mode of inheritance in GPP. In individual GPP cases, the information of genetic risk factors was helpful for therapeutic decision making (e.g. Hüffmeier et al. 2014).
Since the majority of GPP patients do not carry a risk allele in one of the known GPP genes, other genetic risk factors are likely. Thus our research aims at identifying additional genes and pathways by systematic analysis of GPP patients, e.g. by means of new sequencing technologies, in order to discover novel therapeutic targets. The group also pursues similar strategies for SAPHO syndrome, which is characterized by various manifestations of skin and joints ("synovitis-acne-pustulosis-hyperostosis-osteitis syndrome") and which overlaps clinically, but not genetically with psoriasis vulgaris, psoriasis arthritis and pustular psoriasis.
Moreover, the group is also interested in genetic risk factors of palmoplantar pustular psoriasis (PPP), a psoriasis form manifesting at palms and soles. From a genetic perspective, PPP is so far poorly understood. Neither variants in the GPP associated genes (IL36RN, CARD14, AP1S3) nor to the common HLA-C risk allele relevant in psoriasis vulgaris were detectable (Mössner et al. 2015; Mössner et al. 2018). Various approaches are currently being pursued to unravel the genetic basis of GPP.