Update on ocular manifestations of the main monogenic and polygenic autoinflammatory diseases

Abstract

Autoinflammatory diseases include disorders with a genetic cause and also complex syndromes associated to polygenic or multifactorial factors. Eye involvement is present in many of them, with different extent and severity. The present review covers ophthalmological lesions in the most prevalent monogenic autoinflammatory diseases, including FMF (familial Mediterranean fever), TRAPS (TNF receptor-associated periodic syndrome), CAPS (cryopyrin-associated periodic syndromes), Blau syndrome, DADA2 (deficiency of adenosine deaminase 2), DITRA (deficiency of the interleukin-36 receptor antagonist), other monogenic disorders, including several ubiquitinopathies, interferonopathies, and the recently described ROSAH (retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and headache) syndrome, and VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome. Among polygenic autoinflammatory diseases, ocular manifestations have been reviewed in Behçet's disease, PFAPA (periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis) syndrome, Still's disease and autoinflammatory bone diseases, which encompass CRMO (chronic recurrent multifocal osteomyelitis) and SAPHO (synovitis, acne, pustulosis, hyperostosis and osteitis) syndrome.

Keywords: autoinflammatory diseases; conjunctivitis; monogenic autoinflammatory diseases; ocular inflammation; polygenic autoinflammatory diseases; retinal vasculitis; uveitis.

Figure 1

Ocular involvement in monogenic autoinflammatory diseases. (A) Conjunctivitis in a 32 years old female patient with familial Mediterranean fever; (B) Unilateral anterior uveitis with typical perilimbal hyperemia (arrow) in a 68 years old woman with Muckle-Wells syndrome, a cryopyrin-associated periodic syndrome (CAPS); (C) Fundoscopy revealing papilledema with optic nerve hyperemia (arrow) in a 36 years old woman with Muckle-Wells syndrome; (D) Ultra-wide field retinography showing diffuse lesions of multifocal choroiditis in a 17 years old male patient with Blau syndrome; (E) Ultra-wide field retinography displaying severe retinal atrophy (asterisks) and vessel attenuation (dashed arrow) with marked optic nerve swelling (arrow) in a 42 years old man with ROSAH syndrome, with long term loss of visual acuity and systemic symptoms; (F) Lid edema in a 72 years old male patient with VEXAS syndrome; (G) Prominent conjunctival chemosis due to orbital inflammation in the same patient (F) with VEXAS syndrome.

Figure 2

Ocular involvement in Behçet disease, a polygenic autoinflammatory disease. (A) Retinography showing a typical inflammatory infiltrate above the fovea (arrow) and mild vitritis (asterisk) in a 32 years old man consulting for acute loss of visual acuity; (B) Retinography revealing a retinal vasculitis with an ischemic area (black asterisk), phlebitis (arrows), retinal hemorrhages (dashed arrow) and severe vitritis (white asterisk) in a 21 years-old woman; (C) Anterior segment inflammation showing a hypopyon (arrow) (courtesy of Dr. Díaz-Valle); (D) Retinography detecting a severe retinal degeneration and ghost vessels (arrow) in a 32 years old male patient with long-term sequelae because he had only received glucocorticoids for managing panuveitis; and (E) Macular structural optical coherence tomography [in patient (D)] showing foveal atrophy, outer retinal abnormalities (asterisk), cystic changes in the inner nuclear layer (arrow) and a thickened posterior hyaloid (dashed arrow).