AB1299 DIFFERENCES IN THE CLINICAL SPECTRUM OF HAPLOINSUFFICIENCY OF A20 (HA20) CASES DIAGNOSED DURING ADULTHOOD

Abstract

BackgroundHaploinsufficiency of A20 (HA20) is a monogenic autoinflammatory disease caused by heterozygous loss-of-function mutations in TNFAIP3 gene and characterized by Behçet disease (BD)-like manifestations such as mucocutaneous, articular, gastrointestinal, ocular symptoms as well as recurrent fever, elevated acute-phase reactants during relapses; and it usually starts during early childhood. Autoimmunity is another component of HA20 with autoantibodies and variable clinical features resembling systemic lupus erythematosus (SLE) and other autoimmune diseases.ObjectivesWe herein present three cases of HA20 with different clinical features and diagnosed during adulthood.MethodsWe used the Ion Torrent platform for deep sequencing.ResultsCase 1: A 51-year old woman diagnosed with BD because of oral and genital aphthous ulcers, arthralgias, erythema nodosum, and pathergy positivity starting from age of 40 in 2012. She developed sudden vision loss (diagnosed with bilateral optic neuropathy), sixth nerve palsy, and entrapment neuropathies in the lower limbs in 2014; and she had flares of neurologic findings between 2014-2020. The only laboratory abnormality was elevated acute-phase reactants, and no pathologic finding was reported for cranial MRI. Pathological examination of sural nerve biopsy revealed chronic inflammatory demyelinating polyneuropathy (CIDP). She received adalimumab and then tofacitinib, and her treatment was switched to certolizumab and IVIG (30 g/6 weeks) in 2020. At the last visit, she was asymptomatic with normal acute phase response, and her examination revealed normal eye movements.Case 2: A 33-year old woman was followed for 12 years with the diagnosis of SLE, based on fever, photosensitivity, alopecia, polyarthritis, serositis, positive anti-nuclear antibody (ANA) at a titer of 1:1280 with a homogeneous pattern, positive anti-dsDNA, anti-Sm, anti-Sm/RNP, and lupus anticoagulant test, and leukopenia, lymphopenia, hypocomplementemia in 2008. She developed shrinking lung syndrome and Jaccoud arthropathy during the disease course. She received several drugs including corticosteroids, hydroxychloroquine, cyclophosphamide, mycophenolate mofetil, belimumab, rituximab, tocilizumab, abatacept, tofacitinib because of fever, arthritis, skin rash, increased acute-phase reactants, pancytopenia, anti-dsDNA positivity. Her fever, red arthritis attacks with high CRP values did not respond, and after the genetic diagnosis of HA20, anakinra was added to treatment. Due to the high dose anakinra requirement, her treatment was switched to canakinumab (150 mg/2 week), and at the last visit, her attacks were significantly reduced.Case 3: A 44-year old woman was evaluated because of recurrent prolonged >38°C fever attacks (2 days-2 weeks duration), arthritis of the elbow, wrist, knee joints, and high acute phase reactant in 2004. She did not have a history of recurrent oral and genital aphthous ulcers, intermittent periorbital edema, rash, any ocular symptoms, or sensorineural hearing loss. ANA, RF, anti-CCP, and MEFV gene mutation were negative on admission. PET-CT demonstrated FDG uptake in the wall of the ascending aorta, aortic arch, and descending aorta in 2011. She had used colchicine in 2004, etanercept between 2009 and 2010, anakinra in 2011, tocilizumab in 2012, and canakinumab in 2013. She repeatedly received IV methylprednisolone pulse therapy, but she experienced a relapse of fever when she reduced the dose of methylprednisolone to <8 mg/day. Her knee arthritis did not respond to adalimumab, and she is currently on infliximab treatment since 2019 with a Daily methylprednisolone dose of 8-12 mg.ConclusionHA20 can be diagnosed even in adult patients, and the clinical picture of presented cases suggests that monogenic autoinflammatory disorders including HA20 should be suspected in any patient with flares of described manifestations along with strong acute phase response even in adults. Response to corticosteroids and targeted treatments may also be variable.Disclosure of InterestsNone declared