Zhu Teng, Jin Hongzhong, Shu Dan, Li Feng, Wu Chao
Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, China.
Eur J Dermatol. 2018 Apr 1;28(2):217-224. doi: 10.1684/ejd.2018.3245.
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.
既往研究表明，IL36RN突变在泛发性脓疱型银屑病（GPP）的发病机制中起关键作用，但其临床相关性尚不清楚。为了研究IL36RN突变与GPP患者的临床特征、复发频率以及对阿维A治疗反应之间的相关性，并进行长期随访。这项为期2至4年的回顾性队列研究纳入了61例GPP患者和48例寻常型银屑病（PV）患者。对IL36RN基因的所有五个外显子进行序列分析，发现了两个基因变异（c.115+6 T>C和c.227C>T）。根据c.115+6 T>C突变（52.5%的患者存在该突变），该队列被分为三个亚组：纯合突变组（HOMG）、杂合突变组（HEMG）和非突变组（NMG）。最初，21/25例HOMG患者被诊断为伴有诱发因素的GPP，但13例在脓疱期后发展为红皮病型银屑病。HEMG组（5/7）和NMG组（23/29）的患者在脓疱期前后均维持PV诊断。大多数患者对阿维A表现出显著反应，但接受维持剂量（10 - 30mg/d）治疗的患者在随访期间有轻度复发（每年0 - 2次）。IL36RN突变与早发和甲下脓疱密切相关，但与阿维A的治疗效果或复发频率无关。早发和甲下脓疱可能是IL36RN突变所特有的，但仅靠这一点作为阿维A治疗的生物标志物是不够的。其他诱发因素在疾病发作、临床表现和疾病转归中起重要作用。低剂量阿维A维持治疗可能有助于降低GPP的复发率。
