A team from Nagoya University in Japan has identified previously unidentified gene variants associated with the development of generalized pustular psoriasis (GPP). The team’s findings, published in Journal of the American Academy of Dermatologyoffer hope for improved diagnosis and treatment.
GPP is rare, but its effects are often serious. People with GPP may experience recurrent flare-ups of the disease, which include multiple erythematous lesions and sterile pustules all over the body, often accompanied by fever and chills. This can lead to emergency treatment and even death.
So far, researchers have reported six genes associated with GPP. Although these genes are widely used for diagnosis and treatment, there remain patients with GPP who do not have variants of these genes. This suggests unknown genetic factors associated with the development of GPP.
To address this problem, a team led by Professor Masashi Akiyama, Takenori Yoshikawa and Dr. Takuya Takeichi from the Department of Dermatology, Nagoya University School of Medicine used next-generation sequencing to investigate the genes of Japanese patients with GPP. They found that higher frequencies of two MEFV gene variants, p.Arg202Gln and p.Ser503Cys, were associated with GPP. Specifically, 21% of patients carried the p.Arg202Gln variant and 13% the p.Ser503Cys variant.
Pyrin, the product of MEFV, regulates inflammatory pathways. But specific variants of pyrin cause excessive migration of neutrophils into tissues, ultimately causing excessive inflammation. This finding therefore suggests a possible course for the disease.
The researchers believe that therapies that target inflammatory pathways associated with MEFV are a promising therapeutic strategy for patients with these variants. According to Yoshikawa, their findings suggest a new use for a drug commonly used to treat familial Mediterranean fever (FMF).
As these variants are associated with both FMF and GPP, therapies for FMF may also be effective in treating patients with MEFV-associated GPP.
Takenori Yoshikawa, Nagoya University
Source:
Journal Reference:
Yoshikawa, T., et al. (2023) MEFV variants are a predisposing factor for generalized pustular psoriasis. Journal of the American Academy of Dermatology. doi.org/10.1016/j.jaad.2023.10.070.
