Objective:

To describe an adult-onset presentation of deficiency of adenosine deaminase 2 (DADA2) that mimicked cutaneous polyarteritis nodosa (cPAN) for over ten years until acute retinal ischemia prompted a molecular diagnosis, and to propose chronic nail-bed splinter hemorrhages as an additional cutaneous clue in DADA2. 

Background:

DADA2 is a rare monogenic autoinflammatory vasculopathy that usually presents in childhood with recurrent lacunar strokes. Adult-onset disease without cerebral infarction is under-recognized and frequently misclassified as idiopathic vasculitis or cPAN, which often delays the diagnosis. 

Design/Methods:

A 55-year-old woman with history of recurrent lower-extremity cutaneous eruptions and fevers beginning in her mid-30s evolved to persistent livedo reticularis accompanied by chronic nail-bed splinter hemorrhages. At age 43, she developed sudden painless unilateral vision loss from a central retinal artery occlusion (CRAO) with cotton-wool spots and retinal vasculitis. Brain MRI showed no cerebral infarction, and workup for embolic and thrombotic etiologies was unrevealing. Skin biopsy demonstrated medium-vessel vasculitis confined to the subcutis, which is histologically characteristic of cPAN. Although the livedo reticularis and biopsy findings were typical of cPAN, the splinter hemorrhages and CRAO suggested vascular involvement beyond the medium-vessel territory of cPAN, which prompted a reconsideration of the diagnosis.  

Results:

Targeted genetic testing identified compound heterozygous pathogenic ADA2 variants (c.336C>G, p.His112Gln; c.882-1G>A), thereby confirming DADA2. Treatment with adalimumab achieved sustained clinical stability without additional ischemic events. 

Conclusions:

Chronic nail-bed splinter hemorrhages, an under-recognized cutaneous manifestation of DADA2, should prompt consideration of this diagnosis in adults with a cPAN-like phenotype, particularly when accompanied by retinal ischemia. This underscores the importance of general examination in Neurology. Early recognition redirects management from empiric immunosuppression to disease-modifying anti-TNF therapy.