The Primary Immunodeficiency Database in Japan

The Primary Immunodeficiency Database in Japan (PIDJ) is a registry of primary immunodeficiency diseases (PIDs) that was established in 2007. The database is a joint research project with research groups associated with the Ministry of Health, Labor and Welfare; the RIKEN Research Center for Allergy and Immunology (RCAI); and the Kazusa DNA Research Institute (KDRI). The PIDJ contains patient details, including the age, sex, clinical and laboratory findings, types of infections, genetic analysis results, and treatments administered. In addition, web-based case consultation is also provided. The PIDJ serves as a database for patients with PIDs and as a patient consultation service connecting general physicians with PID specialists and specialized hospitals. Thus, the database contributes to investigations related to disease pathogenesis and the early diagnosis and treatment of patients with PIDs. In the 9 years since the launch of PIDJ, 4,481 patients have been enrolled, of whom 64% have been subjected to genetic analysis. In 2017, the Japanese Society for Immunodeficiency and Autoinflammatory Diseases (JSIAD) was established to advance the diagnosis, treatment, and research in the field of PIDs and autoinflammatory diseases (AIDs). JSIAD promotes the analysis of the pathogenesis of PIDs and AIDs, enabling improved patient care and networking via the expansion of the database and construction of a biobank obtained from the PIDJ. The PIDJ was upgraded to “PIDJ ver.2” in 2019 by JSIAD. Currently, PIDJ ver.2 is used as a platform for epidemiological studies, genetic analysis, and pathogenesis evaluation for PIDs and AIDs.

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

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.

Biologic disease-modifying antirheumatic drugs in the treatment of major monogenic autoinflammatory diseases: literature review and clinical observation

Autoinflammatory diseases (AIDs) are a heterogeneous group of rare genetically determined conditions, the main manifestations of which are episodes of fever in combination with other signs of systemic inflammation: skin rashes, musculoskeletal and neurological disorders, damage to the organs of vision, hearing, etc., as well as acute phase markers and the absence of autoantibodies. The use of biological therapy, especially inhibitors of interleukin 1 (iIL1), in most common monogenic AIDs (mAID) – FMF, TRAPS, HIDS/MKD, CAPS – has shown its high efficiency and led to significant progress in the treatment of these patients. Currently, iIL1 are the first-line drugs for mAIDs therapy, primarily CAPS. In the case of their ineffectiveness or intolerance in certain situations, other biologic disease-modifying antirheumatic drugs can also be used – inhibitors of tumor necrosis factor α and iIL6, but this issue needs further investigation. The article describes a patient with mAID, in whom the diagnosis was made more than 40 years after the onset; administration of targeted therapy even in the late stages of the disease led to a significant improvement in many symptoms and quality of life.

Performance of Recent PRINTO Criteria Versus Current ILAR Criteria for Systemic Juvenile Idiopathic Arthritis: A Single-Center Experience

Objectives The purpose of this study is to evaluate the performances of recently proposed Pediatric Rheumatology International Trials Organization (PRINTO) criteria versus current International League of Associations for Rheumatology (ILAR) criteria, for systemic juvenile idiopathic arthritis (sJIA). Methods The study was performed at the Department of Pediatric Rheumatology in Istanbul Faculty of Medicine with a retrospective design, covering the date range 2010 to 2021. Patients being followed-up with a diagnosis of sJIA, Kawasaki disease (control group-1), and common autoinflammatory diseases (control group-2) were included in the study. Both the ILAR and PRINTO classification criteria were applied to each patient and compared against expert rheumatologist diagnosis. Results Eighty-two patients with a diagnosis of sJIA compared against 189 [74 Kawasaki disease, 83 familial Mediterranean fever (FMF), 16 mevalonate kinase deficiency (MKD), 10 cryopyrin-associated periodic syndromes (CAPS), 6 tumor necrosis factor receptor-associated periodic fever syndrome (TRAPS)] patients. The PRINTO criteria demonstrated higher sensitivity (62.2% vs 80.5%, p=0.003), but comparable specificity (90.5% vs 91%) as regards the ILAR criteria. Conclusions The revised criteria appear to enhance the ability to provide early recognition and pertinent classification of sJIA. The two criteria were not superior to each other in segregating sJIA from common autoinflammatory diseases and Kawasaki disease, namely in terms of specificity.

AA-amyloidosis in autoinflammatory diseases

AA amyloidosis complicates various chronic inflammatory disorders and is characterized by the accumulation of amyloid fibrils composed of serum amyloid A protein, an acute phase reactant. In recent decades, the role of chronic infections and rheumatoid arthritis in the ethiology of AA amyloidosis have decreased significantly as a result of their treatment improvement, whereas both monogenic (familial Meditarranean fever, cryopirin-associated periodic syndrome, etc.) or polygenic (ankylosing spondilitis, psoriatic arthritis, adult onset Still’s disease, etc) autoinflammatory diseases more frequently account for AA-amyloidosis today. Autoinflammatory diseases are a consequence of innate immunity disorders although the latter can contribute to the pathogenesis of autoimmune diseases as well. In patients with autoinflammatory diseases, the suppression of inflammation, even subclinical, is essential to prevent development or progression of AA amyloidosis. The choice of inflammatory agents that can be used to achieve this aim depends on the pathogenesis of autoinflammation, e.g. key mediators that are involved in the activation of inflammatory cascade.