Abstract
Background
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.
Objectives
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.
Materials & Methods
This retrospective cohort study, lasting 2-4 years, included 61 GPP and 48 psoriasis vulgaris (PV) patients.
Results
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.
Conclusions
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.
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References
Teoh YL, Tay YK. Generalized pustular psoriasis with a novel mutation of interleukin-36 receptor antagonist, responding to methotrexate. JAAD Case Rep 2015; 1: 51–3.
Adachi A, Komine M, Hirano T, et al. Case of generalized pustular psoriasis exacerbated during pregnancy, successfully treated with infliximab. J Dermatol 2016; 43: 1439–40.
Posso-De Los Rios CJ, Pope E, Lara-Corrales I. A systematic review of systemic medications for pustular psoriasis in pediatrics. Pediatr Dermatol 2014; 31: 430–9.
Sugiura K. The genetic background of generalized pustular psoriasis: IL36RN mutations and CARD14 gain-of-function variants. J Dermatol Sci 2014; 74: 187–92.
Marrakchi S, Guigue P, Renshaw BR, et al. Interleukin-36-receptor antagonist deficiency and generalized pustular psoriasis. N Engl J Med 2011; 365: 620–8.
Onoufriadis A, Simpson MA, Pink AE, et al. Mutations in IL36RN/IL1F5 are associated with the severe episodic inflammatory skin disease known as generalized pustular psoriasis. Am J Hum Genet 2011; 89: 432–7.
Navarini AA, Simpson MA, Borradori L, Yawalkar N, Schlapbach C. Homozygous missense mutation in IL36RN in generalized pustular dermatosis with intraoral involvement compatible with both AGEP and generalized pustular psoriasis. JAMA Dermatol 2015; 151: 452–3.
Sugiura K, Takemoto A, Yamaguchi M, et al. The majority of generalized pustular psoriasis without psoriasis vulgaris is caused by deficiency of interleukin-36 receptor antagonist. J Invest Dermatol 2013; 133: 2514–21.
Körber A, Mössner R, Renner R, et al. Mutations in IL36RN in patients with generalized pustular psoriasis. J Invest Dermatol 2013; 133: 2634–7.
Setta-Kaffetzi N, Navarini AA, Patel VM, et al. Rare pathogenic variants in IL36RN underlie a spectrum of psoriasis-associated pustular phenotypes. J Invest Dermatol 2013; 133: 1366–9.
Li M, Han J, Lu Z, et al. Prevalent and rare mutations in IL-36RN gene in Chinese patients with generalized pustular psoriasis and psoriasis vulgaris. J Invest Dermatol 2013; 133: 2637–9.
Umezawa Y, Ozawa A, Kawasima T, et al. Therapeutic guidelines for the treatment of generalized pustular psoriasis (GPP) based on a proposed classification of disease severity. Arch Dermatol Res 2003; 295: S43–54.
Jin H, Li F, He C, et al. Efficacy and safety of Tripterygium wilfordii hook F versus acitretin in moderate to severe psoriasis vulgaris: a randomized clinical trial. Chin Med J 2015; 128: 443–9.
Lv Z, Fan J, Zhang X, et al. Integrative genomic analysis of interleukin-36RN and its prognostic value in cancer. Mol Med Rep 2016; 13: 1404–12.
Tauber M, Bal E, Pei XY, et al. IL36RN mutations affect protein expression and function: a basis for genotype-phenotype correlation in pustular diseases. J Invest Dermatol 2016; 136: 1811–9.
Farooq M, Nakai H, Fujimoto A, et al. Mutation analysis of the IL36RN gene in 14 Japanese patients with generalized pustular psoriasis. Hum Mutat 2013; 34: 176–83.
Sugiura K, Haruna K, Suga Y, Akiyama M. Generalized pustular psoriasis caused by deficiency of interleukin-36 receptor antagonist successfully treated with granulocyte and monocyte adsorption apheresis. J Eur Acad Dermatol Venereol 2014; 28: 1835–6.
Wang TS, Chiu HY, Hong JB, Chan CC, Lin SJ, Tsai TF. Correlation of IL36RN mutation with different clinical features of pustular psoriasis in Chinese patients. Arch Dermatol Res 2016; 308: 55–63.
Aizu T, Matsui A, Takiyoshi N, et al. Elderly-onset generalized pustular psoriasis without a previous history of psoriasis vulgaris. Case Rep Dermatol 2015; 7: 187–93.
Arakawa A, Ruzicka T, Prinz JC. Therapeutic efficacy of interleukin 12/interleukin 23 blockade in generalized pustular psoriasis regardless of IL36RN mutation status. JAMA Dermatol 2016; 152: 825–8.
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Table S1.
Primer sequences of IL36RN.
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Zhu, T., Jin, H., Shu, D. et al. Association of IL36RN mutations with clinical features, therapeutic response to acitretin, and frequency of recurrence in patients with generalized pustular psoriasis. Eur J Dermatol 28, 217–224 (2018). https://doi.org/10.1684/ejd.2018.3245
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DOI: https://doi.org/10.1684/ejd.2018.3245