The 2021 European Alliance of Associations for Rheumatology/American College of Rheumatology Points to Consider for Diagnosis and Management of Autoinflammatory Type I Interferonopathies: CANDLE/PRAAS, SAVI, and AGS

Abstract

Objective Autoinflammatory type I interferonopathies, chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature/proteasome‐associated autoinflammatory syndrome (CANDLE/PRAAS), stimulator of interferon genes (STING)–associated vasculopathy with onset in infancy (SAVI), and Aicardi‐Goutières syndrome (AGS) are rare and clinically complex immunodysregulatory diseases. With emerging knowledge of genetic causes and targeted treatments, a Task Force was charged with the development of “points to consider” to improve diagnosis, treatment, and long‐term monitoring of patients with these rare diseases. Methods Members of a Task Force consisting of rheumatologists, neurologists, an immunologist, geneticists, patient advocates, and an allied health care professional formulated research questions for a systematic literature review. Then, based on literature, Delphi questionnaires, and consensus methodology, “points to consider” to guide patient management were developed. Results The Task Force devised consensus and evidence‐based guidance of 4 overarching principles and 17 points to consider regarding the diagnosis, treatment, and long‐term monitoring of patients with the autoinflammatory interferonopathies, CANDLE/PRAAS, SAVI, and AGS. Conclusion These points to consider represent state‐of‐the‐art knowledge to guide diagnostic evaluation, treatment, and management of patients with CANDLE/PRAAS, SAVI, and AGS and aim to standardize and improve care, quality of life, and disease outcomes.

Evaluation and Management of Deficiency of Adenosine Deaminase 2

“…In the absence of clinical trials or natural history studies on DADA2, the consensus statements rely heavily on published case series and expert experience or opinions, resulting in relatively low evidence grading. This is a challenge for the development of guidelines for rare diseases in general, as illustrated by recent efforts in creating consensus statements for IL-1-mediated autoinflammatory diseases and type I interferonopathies . Given the limited evidence, we favor the use of statements instead of guidelines or recommendations.…”

Diffuse alveolar hemorrhage in children with interstitial lung disease: Determine etiologies!

“…Depending on concomitant symptoms and laboratory findings, genetics for other autoinflammatory/interferonopathy disorders such as SAVI (stimulator of interferon genes [STING]-associated vasculopathy with onset in infancy) should be considered as well (Table S3). 52 Overall, efforts to identify the underlying cause of DAH are of great relevance, as definite diagnosis enables clinicians not only to treat these patients more precisely using disease-specific therapeutic approaches but may also support estimation on patient's prognosis. It enables disease-specific follow-up with description of response to standard treatment and/or inclusion of patients in disease-specific clinical trials.…”

“…Despite of a high rate of genetic testing (73%), no variants were identified in these subjects suggesting that COPA syndrome accounts for a relevant, but small proportion of patients with DAH ( n = 5; Table 1). Depending on concomitant symptoms and laboratory findings, genetics for other autoinflammatory/interferonopathy disorders such as SAVI (stimulator of interferon genes [STING]‐associated vasculopathy with onset in infancy) should be considered as well (Table ) 52 …”

Phenotypic spectrum in recessive STING-associated vasculopathy with onset in infancy: Four novel cases and analysis of previously reported cases

“…Moreover, the half-life of baricitinib in patients weighing less than 40 kg was shorter than that in adult subjects, which raised the necessity of more frequent dosing (up to four times daily especially for patients weighing <20 kg) ( 48 ). Considering the severe disease manifestations in SAVI, a higher dose of baricitinib and weight-based dosing regimen has been recommended in pediatric patients ( 48 , 50 ). With regard to the application of JAK-inhibitor therapy, it is too soon to evaluate treatment effects comprehensively in our newly identified cases of AR SAVI.…”