An update on genetic basis of generalized pustular psoriasis (Review).

Generalized pustular psoriasis (GPP) is a rare and severe auto­inflammatory skin disease that is characterized by recurrent, acute onset, and generalized pustular eruptions on erythematous, inflamed skin. GPP is traditionally classified as a variant of psoriasis vulgaris, even though recent clinical, histological and genetic evidence suggests that it is a heterogeneous disease and requires a separate diagnosis. In recent years, variants of IL36RN, CARD14, AP1S3 and MPO genes have been identified as causative or contributing to genetic defects in a proportion of patients affected by GPP. These disease­related genes are involved in common inflammatory pathways, in particular in the IL­1/IL­36­chemokines­neutrophil pathogenic axis. At present, no standard therapeutic guidelines have been established for GPP management, and there is a profound need for novel efficacious treatments of GPP. Among them, biological agents antagonizing the IL­36 pathway are promising therapeutics. The aim of the present review is to provide the most recent updates on the genetics, genotype­phenotype correlation and pathological basis of GPP, as well as on biologic treatments available for GPP and relative clinical courses.

Research progress of deficiency of interleukin-36 receptor antagonist and cutaneous sterile pustulosis / 中华实用儿科临床杂志

Cutaneous sterile pustulosis is categorized as a non-infectious and non-follicular impetigo, with a low prevalence and difficulty in the treatment.Deficiency of interleukin(IL)-36 receptor antagonist (DITRA) is an auto inflammatory disease featured by the decreased interleukin-36 receptor antagonist (IL-36Ra) activity caused by IL36 RN mutation.Functional or structural defects of IL-36Ra increase the secretion of inflammatory and pro-inflammatory factors by keratinocytes, macrophages and dendritic cells.Upregulation of IL-36 receptor agonists induce type 17 helper T lymphocytes to secrete IL-17, which is essential for the onset of multiple subtypes of aseptic pustulosis.Research on the relationship between DITRA and cutaneous sterile pustulosis is important for developing targeted therapies.

Clinical profiles of pediatric patients with GPP alone and with different IL36RN genotypes.

BACKGROUND: IL36RN mutation has been identified as one pathogenesis of generalized pustular psoriasis, but the existence of GPP patients without mutation makes this controversial. OBJECTIVE: Our study aimed at assessing the differences in clinical profiles of children with GPP, with and without IL36RN mutation. METHODS: An ambispective case series study involved review of the records of 66 childhood patients with pediatric-onset GPP and without previous psoriasis vulgaris. RESULTS: c.115+6T>C was the most common mutation in this Chinese population with GPP alone. The age at onset was nearly halved in the homozygotes/compound heterozygotes than in IL36RN-negative patients. Besides a more severe inflammatory progression, three minor signs could prioritize patients with GPP for IL36RN screening (confluent lakes of pus (P=0.002), perianal erosion (P=0.014), and flexural erosion (P=0.007)). More patients with the pathogenic mutation converted to ACH than those without mutation (χ2=4.773, P=0.029). Children with GPP with or without IL36RN mutation responded well to oral low-dose acitretin, but IL36RN-positive cases suffered a much higher half-year recurrence rate after withdrawl of acitretin treatment(χ2=10.370, P=0.001). CONCLUSIONS: Specific clinical features can remind dermatologists of the necessity of sequencing diagnosis. The mild pustular phenotype of those without mutation may imply the possible role of the epigenetic changes of IL36RN, or other IL36-blockers in the pathogenesis. Pediatric patients with GPP alone, both with and without IL36RN mutation responded well to low-dose acitretin.