Table 3.

Red flags of interferonopathies.

Clinical red flags in pediatric settings	Laboratory red flags
Neonatal setting: • TORCH-like syndrome without infection • Encephalopathy with skin involvement	• Systemic inflammation with leukopenia • Increased ESR with normal or slightly increased CRP • Fluctuating low-titer ANA and other autoantibodies • Leukocytes and IFN increased in cerebrospinal fluid • IFN signature
Neurological setting: • Leukodystrophy, especially if associated with fever, chilblains, and/or cytopenia • Spasticity, demyelination, seizures, microcephaly associated to skin manifestations and/or glaucoma • Subacute encephalopathy with basal ganglia calcifications in the first years of life, especially if associated with recurrent fever and microcephaly
Rheumatological setting: • Chiblains • Raynaud's phenomenon • Panniculitis/lipodystrophy • Recurrent unexplained fever • Inflammation signs with slightly increased CRP • Autoimmune characteristics similar to SLE • Poor efficacy of common biologic drug used in other autoinflammatory diseases
Pulmonary setting: • Interstitial lung disease associated with skin manifestations like painful ulcerative lesions evolving into digital amputation • Pulmonary arterial hypertension

CRP, C reactive protein; SLE, Systemic Lupus Erythematosus; ESR, Erythrocyte Sedimentation Rate; ANA, Antinuclear antibodies; IFN, Interferon.