From Pustules to Pruritus: A Novel IL36RN Frameshift Variant Reveals a Triple Biologic Paradox and a Th17-To-Th2 Phenotypic Transition.
Furkan Çalıcıoğlu, Neşecan Çalıcıoğlu, Muhammet Ensar Doğan et al.
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Case in brief
A 64-year-old woman with longstanding psoriasis vulgaris, asthma, allergic rhinitis, and a family history of atopy developed generalized pustular psoriasis after biologic treatment. Testing found a heterozygous IL36RN frameshift variant, c.319del (p.Leu107Serfs65). Over subsequent months, pustulation gave way to intensely pruritic, xerotic eczematous dermatitis meeting Hanifin-Rajka criteria; biopsies showed mild spongiosis and an eosinophil-rich superficial perivascular infiltrate. Risankizumab and adalimumab were temporally associated with pustular exacerbations, and dupilumab with worsening eczema but no recurrent pustulation. Methotrexate 15 mg weekly plus topical treatment was associated with near-complete clearance through Month 12.
What made this case unusual
The patient had sequential pustular and eczematous phenotypes alongside a novel heterozygous IL36RN frameshift variant, with different biologic classes temporally associated with worsening of each phenotype.
Diagnostic / clinical pearl
In refractory inflammatory dermatoses, consider an inborn error of immunity even in older adults; a change in morphology may signal a shift in the dominant inflammatory phenotype.
Why it matters
This case illustrates that pathway-specific biologics may be associated with divergent skin responses when immune regulation is genetically perturbed; the report advises caution in this setting.