Bilateral Optic Disc Swelling as a Plausible Common Ocular Sign of Autoinflammatory Diseases: Report of Three Patients with Blau Syndrome or Cryopyrin-Associated Periodic Syndrome.

Toshihiko Matsuo,Takehiro Tanaka,Akira Manki,Osamu Yamasaki,Masato Yashiro

doi:10.3390/life11121433

Toshihiko Matsuo, Takehiro Tanaka + Show 3 more

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https://doi.org/10.3390/life11121433

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Abstract

The aim of this study is to describe bilateral optic disc swelling in three consecutive patients with Blau syndrome or cryopyrin-associated periodic syndrome at a single institution. Case 1 was a 30-year-old woman receiving 25 mg etanercept twice weekly who had been diagnosed as early-onset sarcoidosis by biopsy of skin rashes at 5 months old and genetically diagnosed with Blau syndrome with CARD15/NOD2 mutation (N670K) at 13 years old. At 10 years old, she began to have uveitis with optic disc swelling in both eyes, resulting in macular degeneration and optic disc atrophy at 17 years old only when etanercept was introduced. Case 2 was a 21-year-old man receiving adalimumab every 2 weeks who had been diagnosed as early-onset sarcoidosis by biopsy of skin rashes at 1.5 years old and genetically diagnosed as Blau syndrome with CARD15/NOD2 mutation (C495Y) at 5 years old. At 8 years old, around the time of adalimumab introduction, he began to show bilateral optic disc swelling which continued until the age of 16 years when the dose of adalimumab was increased. Case 3 was a 20-year-old woman receiving canakinumab every 8 weeks for systemic symptoms such as fever, headache, vomiting, and abdominal pain and later for sensorineural hearing disturbance on both sides. She had been diagnosed genetically with cryopyrin-associated periodic syndrome with NLRP3 mutation (Y859C) at 7 years old. At 5 years old, she was found to have bilateral optic disc swelling, which continued until the age of 10 years when she began receiving canakinumab (IL-1β inhibitor). Bilateral optic disc swelling might be tentatively designated as a plausible common ocular feature, if it occurred, in autoinflammatory diseases to pay more attention to ophthalmic complications in rare diseases.

Highlights

Autoinflammatory diseases are a recently established collection of monogenic diseases, which are characterized by abnormal activation of the innate immune system [1,2,3].In the entity of autoinflammatory diseases, familial Mediterranean fever is most common in the sub-entity of periodic fever diseases, which show remittent fever, skin rashes, and 4.0/).joint pain
The spectrum of cryopyrin-associated periodic syndromes consists of clinical diagnoses of familial cold autoinflammatory disease, Muckle–Wells syndrome, and chronic infantile neurological cutaneous and articular (CINCA)/neonatal onset multisystem inflammatory disease (NOMID) syndrome
Cryopyrin-associated periodic syndromes are caused by gain-of-function mutations in the NLRP3 gene, which lead to overproduction of a proinflammatory cytokine, IL-1β

Summary

Introduction

Autoinflammatory diseases are a recently established collection of monogenic diseases, which are characterized by abnormal activation of the innate immune system [1,2,3]. Cryopyrin-associated periodic syndromes, which have been called cryopyrinopathies, follow at the rate of diseases in the sub-entity of periodic fever diseases. Cryopyrin-associated periodic syndromes are caused by gain-of-function mutations in the NLRP3 gene, which lead to overproduction of a proinflammatory cytokine, IL-1β. Previously called early-onset sarcoidosis, is caused by gain-of-function mutations in the NOD2 gene and characterized as a disease linked to nuclear factor-κB (NF-κB) activation, leading to overexpression of inflammatory genes, such as tumor necrosis factor-α (TNF-α). We focused on bilateral optic disc swelling, which happened to be shared by three consecutive Japanese patients with Blau syndrome or cryopyrin-associated periodic syndrome at our single institution. The optic disc swelling in both eyes might be a plausible common eye manifestation, if it occurred as a complication, in autoinflammatory diseases. We report the ocular and systemic manifestations in these three patients to enhance the understanding of eye complications of the rare diseases among pediatricians and ophthalmologists as a subject for further evaluation

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