The process begins with clinical suspicion based on symptoms such as early-onset Behcet-like disease, recurrent fevers, oral slash genital ulcers, refractory autoimmunity, IBD-like symptoms, unexplained cytopenias, multiple immunologic diagnoses, or a family history of autosomal dominant immune dysregulation. Genetic testing follows, with different paths for known and unknown family history, including options like multigene panel, WES, WGS, and targeted TNFAIP3 testing. If a TNFAIP3 variant is found, proceed to baseline assessment and initiate targeted therapy. Baseline assessment includes standard labs, autoantibodies, mandatory biomarkers, and immunology tests. Treatment strategy is guided by phenotype and biomarkers, with different approaches for mild slash mucocutaneous, autoinflammatory-predominant, GI slash joint slash vasculitis, and autoimmune-predominant conditions. Other considerations include biomarkers, flares, infections, and surgery, with specific recommendations for each.
Diagnostic and therapeutic algorithm for HA20. Flowchart presents a proposed algorithm outlining our diagnostic and therapeutic approach for patients with suspected HA20. This includes symptoms prompting clinical suspicion (classical and atypical phenotypes), options for genetic and functional testing, baseline and serial clinical studies for assessment and monitoring, and other considerations. WES, whole-exome sequencing; WGS, whole-genome sequencing; CBC with diff, complete blood count with differential; CMP, complete/comprehensive metabolic panel; TSH, thyroid-stimulating hormone; ANA, anti-nuclear antibody; ENA, extractable nuclear antigen antibody; RF, rheumatoid factor; CCP, cyclic citrullinated peptide; ESR, erythrocyte sedimentation rate; CRP, C reactive protein; C3/C4, complement 3/complement 4; IL-, interleukin; SAA, serum amyloid A; CXCL9, CXC motif chemokine ligand 9; PDE4, phosphodiesterase 4; GI, gastrointestinal; TNF, tumor necrosis factor; JAK, Janus kinase; MTX, methotrexate; MMF, mycophenolate mofetil/mycophenolic acid; CNI, calcineurin inhibitor; AZA, azathioprine; PRN, pro re nata (as needed); IGRT, immunoglobulin replacement therapy.