IL-17A inhibitor-induced leucocytoclastic vasculitis is responsive to IL-23 blockade in a psoriatic arthritis patient

Abstract

Secukinumab is monoclonal antibody that targets interleukin 17 (IL-17) for treatment of psoriatic arthritis, psoriasis, and ankylosing spondylitis. We herein present a psoriatic arthritis patient who developed leukocytoclastic vasculitis (LCV) following treatment with secukinumab. Genetic studies identified amino acid changes in two different IL-17 receptors, IL-17RA and IL-17-RC, and interacting DOCK8, Rab27A, and STX1 proteins. LCV completely resolved after withdrawal of the drug, transient treatment with dapsone and methylprednisolone, and switching to long-term therapy to IL-23 inhibitor tildrakizumab. This case reveals potential molecular bases of disease pathogenesis, intolerance of IL-17 blockade, and responsiveness to IL-23 inhibition in psoriatic arthritis.

Keywords: Antirheumatic Agents; Biological Therapy; Psoriatic Arthritis.

Figure 1.

Leukocytoclastic vasculitis. A) Erythematous palpable purpura on the skin of both anterior lower legs. B) Skin lesions have been eliminated after discontinuation of secukinumab and replacement with tildrakizumab for over two years. C) Histological examination showing prominent perivascular neutrophilic infiltrates, fibrinoid necrosis of blood vessels walls, and red cell extravasation consistent with leukocytoclastic vasculitis. D) Degeneration of neutrophils with fragmentation of nuclei. Nuclear dust and fragment are indicated with red arrows. Magnification is represented by embedded scale bars in panels B and C. E) Schematic diagram of evidence-based interactome amongst immune response-regulating genes that carried amino acid-altering mutations.