# Generalized Pustular Psoriasis and Systemic Organ Dysfunctions
## 6 Liver Dysfunction in GPP  
Some isolated cases of GPP have indicated its possible involvement with liver disorders. A previous study examined the prevalence and characteristics of liver abnormalities in GPP. Twenty-two patients diagnosed with GPP underwent liver function tests, during an acute episode and in subsequent weeks [82]. This study focused on patients consecutively admitted for a GPP attack at one of two dermatology departments, where the diagnosis of GPP was confirmed based on clinical criteria validated by two dermatologists and histological analysis of skin biopsies. Remarkably, 90% (20 patients) displayed at least one abnormal liver examination result. Half of the patients exhibited significant liver disturbances: jaundice was observed in four cases (18%), elevated gamma-glutamyl transferase (more than five times the normal limit) in ten cases (45%), high alkaline phosphatase (over double the normal limit) in seven cases (32%), and increased aminotransferase (more than three times the normal limit) also in seven cases (32%). These liver abnormalities normalized upon the remission of the psoriasis, indicating a potential link between severe liver issues and the intensity of the skin manifestations.  
The specific biological pathways through which GPP leads to liver impairment are not fully understood. However, there is a particularly notable case that sheds light on this issue. In this instance, a patient suffering from primary biliary sclerosis (PBS), which was exacerbated by GPP, experienced significant improvements in both skin inflammation and liver function following treatment with an IL-17 antibody [83]. Furthermore, detailed histological analysis revealed the presence of IL-17-producing cells within the liver tissue, specifically concentrated in the portal tract areas [83]. This observation supports the hypothesis that GPP may induce liver damage through a mechanism involving the activation of IL-17 by IL-36. This finding not only enhances our understanding of the inflammatory mechanisms at play, but also suggests that therapies targeting IL-17 could have a dual benefit. They might not only alleviate the cutaneous symptoms of GPP, but also offer protective effects against liver damage. This dual potential makes the role of IL-17 inhibitors a promising area for further research in the treatment strategies for GPP, especially for those patients presenting with concurrent liver complications.  
Although the specific mechanisms of liver diseases such as non-alcoholic fatty liver disease (NAFLD), commonly associated with psoriasis, have not been thoroughly delineated in the context of GPP, it is plausible to consider that similar pathophysiological processes could potentially be involved the development of liver dysfunction in GPP. In cases of GPP, the release of IL-36, which in turn stimulates the production of IL-17, might contribute to the development of these liver conditions. Given the intricate interplay of these cytokines in inflammatory responses, it is conceivable that the activation of IL-17 by IL-36 in GPP could also trigger or exacerbate liver diseases such as NAFLD [84; 85; 86; 87]. This connection warrants a deeper exploration to understand the full spectrum of systemic implications associated with GPP. Future research in this area is not only crucial but also expected to provide significant insights that could lead to better management and treatment strategies for patients suffering from both GPP and associated liver diseases.