A recent study published in The Journal of Dermatology has concluded that the p.Pro82Leu variant of the IL36RN gene, discovered in an adult-onset generalized pustular psoriasis (GPP) patient with psoriasis vulgaris, is unlikely to exert a substantial influence on GPP development.
“Considering our findings and the fact that the prevalence of GPP is not higher in Japan than in other countries, this variant is unlikely to be associated with the development of GPP. Further studies, including functional assays, are needed to clarify this,” the study’s authors concluded.
In this study, the researchers further investigated the connection between the new variant and GPP through the case of a 72-year-old Japanese male eventually diagnosed with GPP harboring the p.Pro82Leu variant.
Genetic analysis uncovered a heterozygous mutation in IL36RN (c.245C>T). Polymerase chain reaction analysis of the patient’s hair follicles demonstrated IL36RN mRNA expression, while immunohistochemical staining revealed IL-36Ra expression in keratinocytes, comparable with a GPP patient without the mutation.
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In addition, the results indicated that IL-36Ra expression in the patient’s keratinocytes was elevated compared with healthy controls and was not significantly lower than GPP patients without the mutation. Also, there was no evidence of irregular splicing in the variant.
Insights from the 1000 Genomes Project indicated that this variant could potentially be a founder mutation. Taking into consideration all these elements, the researchers concluded that the p.Pro82Leu variant is unlikely to be causatively associated with the development of GPP.
The patient was initially diagnosed with rheumatoid arthritis. Two years after the diagnosis, he developed body-wide eruptions and was clinically diagnosed with psoriasis vulgaris. Despite undergoing topical therapy, oral etretinate, and phototherapy, his condition worsened, leading to a referral to a specialized department.
Subsequent treatment with adalimumab was ineffective, and he developed arthritis in the his middle finger’s metacarpophalangeal joint. Ixekizumab was then initiated but discontinued due to the discovery of esophageal cancer. Three months later, he received secukinumab, which further exacerbated the eruption, arthritis, and fever.
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A skin biopsy revealed pathological features, including acanthosis and hyperkeratosis with small spongiform pustules. Laboratory results indicated a normal white blood cell count, low serum albumin level, and elevated serum C-reactive protein level.
He was diagnosed with GPP, and ixekizumab, oral etretinate, prednisolone, and granulocyte and monocyte adsorptive apheresis were started. The treatment regimen led to improvements in skin manifestations and systemic inflammation.
The IL36RN gene encodes the interleukin-36 receptor antagonist, a key player in countering the effects of interleukin-36α, -36β, and -36γ.
Reference
Mizukawa I, Kamata M, Shimizu T, et al. Expression of interleukin-36 receptor antagonist in a patient with generalized pustular psoriasis harboring the p.Pro82Leu variant in the IL36RN gene. J Dermatol. Published online July 31, 2023. doi:10.1111/1346-8138.16914
