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uSAID – Undifferentiated Systemic Autoinflammatory Disease

The term uSAID stands for “undifferentiated Systemic Autoinflammatory Disease” and may additionally be referred to as undiagnosed or unclassified and is considered to be of undefined disease etiology. This terminology is used for patients who have been genetically tested but have negative results meaning that no mutations for autoinflammatory diseases were identified.

Characteristics of Undifferentiated autoinflammatory diseases


Despite the negative result, the patient’s clinical presentation must lead the clinician to diagnose uSAID due to symptoms of recurring fevers, joint pain, various skin rashes/urticaria, ulcers, GI manifestations, hearing loss, eye issues, neurological symptoms, chest pains, etc. These patients may be challenging to treat and manage. Additionally, these patients do not present with elevated antibodies typically seen in autoimmune diseases. Finally, these patients may or may not present with elevated acute phase reactants (CRP, ESR, SAA).

While there are no standard guidelines or recommendations for targeted therapy, uSAID patients may potentially respond to the typical treatments used for autoinflammatory diseases such as FMF, CAPS, TRAPS, HIDS, etc. Typically, patients with these cases begin with the use of colchicine to control inflammation. However, it is common for many patients to add biologics such as IL-1 inhibitors (e.g. Kineret, Ilaris) or others, to their treatment protocols. Additional medications for uSAID patients, may include use of corticosteroids, NSAIDs, pain medications, etc.

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