Correlation of IL36RN and CARD14 mutations with clinical manifestations and laboratory findings in patients with generalised pustular psoriasis

Abstract

Background Generalized pustular psoriasis (GPP) is a chronic disease associated with genetic factors related to mutations of the interleukin 36 receptor antagonist gene (IL36RN) and the caspase recruitment domain 14 gene (CARD14). However, the relevance of these mutations to the clinical features and severity of GPP remains unclear. Aims Our objective was to correlate the presence of IL36RN and CARD14 mutations with the clinical and laboratory findings in patients with GPP. Methods This cross-sectional descriptive study was conducted in 64 subjects with GPP. Clinical manifestations were recorded and the severity was graded as mild, moderate, or severe. Routine laboratory tests were performed and blood samples were collected for Sanger sequencing. The clinical data of patients were compared among the different mutation groups. Results The two main variants of IL36RN were c.115+6T > C (p.Arg10ArgfsX1) and c.227C > T (p.Pro76Leu). The major CARD14 mutations were c.2458C > T (p.Arg820Trp), c.1641C > T (p.Arg547Ser), and c.1753G > A transitions. Provocative factors were uncommon in the group with both IL36RN and CARD14 mutations. Drugs (unspecified), especially herbals, were the most common triggers. A history of psoriasis was frequent in patients with only CARD14 mutations, but fever was uncommon. The c.1641C > T mutation was associated with leukocytosis > 15000/mm3 and the c.1753G > A mutation was associated with hypoalbuminemia <3.8g/dL. Both the c.115+6T > C and c.227C > T variants of IL36RN were associated with fever ≥38.5°C while the c.115+6T > C variant was also associated with geographic tongue. No gene mutations were associated with the total severity and severity grades. Limitations Four patients without the two major IL36RN mutations were excluded from the study. Conclusion The presence of IL36RN and CARD14 mutations were associated with a history of psoriasis, various provocative factors, fever, leukocytosis, hypoalbuminemia, and geographic tongue. Further studies to explore the role of these mutations in therapeutic efficacy and disease outcomes are necessary.

Clinical profile of patients with acute generalized pustular psoriasis with and without IL36RN mutations in multi‐ethnic Johor Bahru, Malaysia

“…Unlike other studies 10,16,17 which showed that IL36RN mutations predict a higher risk of systemic inflammation, defined as fever >38°C and leucocytosis >12 × 10 8 /L, we found no difference in the rate of fever, leucocytosis in the two patient groups. As previously described in the literature, 10‐12,16,17 we also found that the age of disease onset was significantly lower in patients with than those without IL36RN mutations (mean age:30.6 vs. 39.2 years, p = 0.027). However, we are not able to confirm the reported dosage effect of IL36RN on disease onset.…”

“…Recent studies from Vietnam and China also showed a significantly higher prevalence of geographic tongue (GT) in patients who carried the c.115 + 6 T > C allele. 17,26 Unlike other studies 10,16,17 which showed that IL36RN mutations predict a higher risk of systemic inflammation, defined as fever >38°C and leucocytosis >12 × 10 8 /L, we found no difference in the rate of fever, leucocytosis in the two patient groups. As previously described in the literature, [10][11][12]16,17 we also found that the age of disease onset was significantly lower in patients with than those without IL36RN mutations (mean age:30.6 vs. 39.2 years, p = 0.027).…”

“…We did not find any significant difference in the common clinical manifestations of GPP between patients with and without IL36RN mutations except for the predominance of geographic tongue in IL36RN ‐positive patients. Recent studies from Vietnam and China also showed a significantly higher prevalence of geographic tongue (GT) in patients who carried the c.115 + 6 T > C allele 17,26 . Unlike other studies 10,16,17 which showed that IL36RN mutations predict a higher risk of systemic inflammation, defined as fever >38°C and leucocytosis >12 × 10 8 /L, we found no difference in the rate of fever, leucocytosis in the two patient groups.…”

“…IL36RN mutations account for 20% to 50% of GPP cases 8–18 . Here, we found IL36RN mutations in 29.7% and 17.3% of Chinese and Malay patients, respectively but in none of the 19 Indian cases that we examined.…”

“…A female preponderance in both IL36RN-positive and IL36RN-negative patients was also reported in other studies and may be due to hormonal or environmental influences rather than genetic factors. 12,17 Comorbid conditions namely hypertension, dyslipidemia, obesity and diabetes mellitus are common in both groups.…”