Figure 1.
The process begins with suspected STAT3-HIES with immunological or non-immunological features. For adults, it checks if the NIH-score is greater than or equal to 20. If yes, genetic testing via next generation sequencing is conducted. If a pathogenic or likely pathogenic STAT3 variant is detected, STAT3-HIES is confirmed, and baseline organ assessment and management pathway is proceeded. If no, or if the NIH-score is less than 20, STAT3-HIES is considered unlikely, and other IEI or alternative diagnoses are considered. For children, the process directly proceeds to genetic testing. If the result is negative with high clinical suspicion, whole genome sequencing and functional STAT3 testing are considered. The flowchart also mentions examples of monogenetic IEL which may present with elevated serum IgE levels.
Diagnostic algorithm for STAT3-HIES.