Clinical Care Recommendations
The European Alliance of Associations for Rheumatology (EULAR) and American College of Rheumatology (ACR) assembled a task force of experts and patient advocates to review the most recent information and studies and develop a document of recommendations for diagnosis and care of AGS and other related disorders (Type I Interferonopathies). Further below, we repeat some of the overarching principles and clinical care considerations.
We encourage you to share this with your doctor, as soon as possible. Additionally, we hope that by reading some of the document and conclusions you will better understand AGS and internalize the following :
AGS is a disorder of the immune system.
Consequently, as an immune disorder AGS can both acutely and chronically injure organs other than the brain.
Therapies that suppress the immune system offer benefit (JAK Inhibition for long term care, Glucocorticoids/steroids in acute situations).
Multi-modal clinical care should include a doctor that specializes in disorders of the immune system (e.g. a rheumatologist, hematologist).
Overarching Principles
Chronic systemic and organ-specific inflammation is present in patients with CANDLE/PRAAS, SAVI, and AGS. When untreated, chronic inflammation results in progressive organ damage, early morbidity, and increased mortality.
Diagnosis of CANDLE/PRAAS, SAVI, and AGS must be confirmed by genetic testing, which facilitates initiation of targeted treatments, genetic counseling, screening for complications, and informed prognosis.
The goal of treatment of autoinflammatory type I interferonopathies is to prevent and/or decrease systemic and organ inflammation, thereby improving the quality of life.
A multidisciplinary team is required to manage patients with CANDLE/PRAAS, SAVI, and AGS, which includes long-term monitoring of disease activity, managing and treating organ-specific injury/damage, and addressing treatment-related complications.
Points-to-Consider
Clinical Evaluation
For patients with suspected CANDLE/PRAAS, SAVI, and AGS, providers must perform screening tests to assess disease- and treatment-related comorbidities.
Skin manifestations: nodular rashes, violaceous annular rashes, panniculitis, lipodystrophy, and vasculopathic skin lesions
Neurologic manifestations: intracerebral calcifications, leukoencephalopathy, progressive microcephaly, and cerebral atrophy
Pulmonary manifestations: interstitial lung disease/pulmonary hypertension
Hepatic manifestations: hepatic steatosis, hepatitis, and hepatosplenomegaly
Metabolic manifestations: hypertension, hyperlipidemia, and glucose intolerance (metabolic syndrome)
Musculoskeletal manifestations: arthritis, contractures, and myositis
Growth and development: growth retardation, osteoporosis, bone development delay, and pubertal delay
Hematologic manifestations: cytopenias (eg, lymphopenia, thrombocytopenia)
Ophthalmologic manifestations: episcleritis, keratitis, retinopathy, and glaucoma
Cardiac manifestations: cardiomyopathy
Neuroimaging should be considered in patients with suspected neurologic symptoms.
Magnetic resonance imaging (MRI) to best identify white and grey matter changes.
Computed tomography (CT) to detect cerebral calcification; this can be considered when calcium-sensitive modalities on MRI are not available or do not detect calcification.
Appropriate tissue sampling may help in the diagnosis of patients with presumed CANDLE/PRAAS, SAVI, and AGS.
A basic immunodeficiency workup that includes a history of infections, lymphocyte subsets, and immunoglobulin levels is required for all patients.
Treatment
For patients with CANDLE/PRAAS, SAVI, and AGS, treatment should achieve disease control or low disease activity to prevent the progression of organ damage; for patients with SAVI and CANDLE/PRAAS, disease control should be maintained with the lowest possible dose of glucocorticoids.
For improving CANDLE/PRAAS, SAVI, and AGS symptoms, Janus kinase (JAK) inhibitors are beneficial.
For patients with CANDLE/PRAAS, SAVI, and AGS who are receiving treatment with Janus kinase (JAK) inhibitors, screening for treatment-related side effects is important; current recommendations include monitoring BK viral loads in urine and blood to prevent viral organ injury, such as nephropathy.
For improving symptoms in CANDLE/PRAAS and SAVI, glucocorticoid therapy is beneficial; chronic glucocorticoid therapy does not improve the neurologic features of AGS though acute courses of glucocorticoids may be beneficial in treating noncentral nervous system inflammatory conditions.
Long-Term Monitoring and Management
For optimal care of patients with CANDLE/ PRAAS, SAVI, and AGS, a multidisciplinary management team is required based on patient-specific disease manifestations.
Regular monitoring of disease activity and disease burden should be performed based on disease activity and severity.
Assessment of disease-specific symptoms using validated patient-reported outcomes and quality of life assessments by recording missing school or workdays can be used to monitor symptom control.
For children, disease and development should be monitored during each visit.
There taskforce did not note any evidence suggesting that COVID-19 risks to patients with CANDLE/PRAAS, SAVI, and AGS were different from those in the healthy population. Therefore, treatment for interferonopathy should not be stopped unless a specific contraindication to ongoing treatment arises.
Overall, routine vaccines (live and attenuated) are indicated when patients with CANDLE/PRAAS and SAVI are not receiving immunosuppressive treatments or glucocorticoids. However, this guidance should be considered on a case-by-case basis.