Association of IL36RN mutations with clinical features, therapeutic response to acitretin, and frequency of recurrence in patients with generalized pustular psoriasis.

Previous studies have revealed that IL36RN mutations play a pivotal role in the pathogenesis of generalized pustular psoriasis (GPP), however, the clinical relevance is unclear. To investigate the correlation between IL36RN mutations and clinical features, recurrence frequency, and therapeutic response to acitretin in GPP patients with long-term follow-up. This retrospective cohort study, lasting 2-4 years, included 61 GPP and 48 psoriasis vulgaris (PV) patients. Sequence analysis of all five exons of the IL36RN gene revealed two genetic variants (c.115+6 T>C and c.227C>T). The cohort was divided into three subgroups according to the c.115+6 T>C mutation (present in 52.5% of the patients): homozygous mutation group (HOMG), heterozygous mutation group (HEMG), and non-mutation group (NMG). Initially, 21/25 HOMG patients were diagnosed with GPP with provocative factors, but 13 developed erythrodermic psoriasis after the pustular phase. Patients in the HEMG (5/7) and NMG (23/29) maintained PV diagnosis before and after the pustular phase. Most patients exhibited a marked response to acitretin, but patients who were prescribed a maintenance dosage (10-30 mg/d) had mild recurrence (0-2 times/year) during follow-up. IL36RN mutations were strongly linked with early onset and hyponychial pustules, but not with therapeutic efficacy of acitretin or recurrence frequency. Early onset and hyponychial pustules may be specific to IL36RN mutation, however this alone is an insufficient biomarker for acitretin therapy. Other provocative factors play important roles in disease onset, clinical manifestations, and disease outcome. Low-dose maintenance therapy with acitretin might help reduce the recurrence of GPP.