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Published on: September 12, 2019
OTULIN Haploinsufficiency-Related Fasciitis and Skin Necrosis Treated by TNF Inhibition
Rob J W Arts1,2, Tristan J van der Linden3, Caspar I van der Made4,5
1Department of Internal Medicine, Radboud Institute of Molecular Life Sciences (RIMLS) and Radboudumc Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, Netherlands. rob.jw.arts@radboudumc.nl.
A rare genetic mutation in OTULIN caused severe inflammation and skin issues in a patient. Tumor necrosis factor (TNF) inhibition effectively treated the autoinflammatory condition, offering a new therapeutic approach.
Area of Science:
- Immunology
- Genetics
- Dermatology
Background:
- OTULIN (OTULIN-like protein) is a key regulator of deubiquitination, crucial for intrinsic immunity, particularly against bacterial toxins like staphylococcal alpha-toxin.
- Genetic variations in OTULIN can disrupt its function, potentially leading to immune dysregulation and autoinflammatory conditions.
Observation:
- An adult female presented with severe fasciitis and skin necrosis, carrying a heterozygous, predicted deleterious missense mutation in OTULIN.
- Standard treatments including antibiotics and surgical interventions were ineffective, suggesting an underlying inflammatory or genetic etiology.
Findings:
- The patient's condition was characterized by predominant autoinflammation, despite the absence of infection.
- Initiation of Tumor Necrosis Factor (TNF) inhibition therapy resulted in a significant clinical improvement, indicating its efficacy in managing OTULIN-related autoinflammation.
Implications:
- This case highlights OTULIN haploinsufficiency as a cause of severe autoinflammatory disease with dermatological manifestations.
- Targeting TNF with biologic agents represents a promising therapeutic strategy for patients with OTULIN-related autoinflammation, offering an alternative to conventional treatments.
