Nonallergic hypersensitivity Nonallergic hypersensitivity We have not modeled

Non-allergic hypersensitivity

Non-allergic hypersensitivity • We have not modeled intolerance 782197009 |Intolerance to substance (finding)|with a pathological process as an intolerance process may represent multiple, diverse pathological processes • We have modeled 609405001 |Non-allergic hypersensitivity condition (finding)|and its descendants with a pathological process of 609404002 |Non-allergic hypersensitivity process (qualifier value)| even though non-allergic hypersensitivity also involves multiple, diverse pathological processes.

Definitions • WAO/EAAACI • Hypersensitivity: Hypersensitivity causes objectively reproducible symptoms or signs, initiated by exposure to a defined stimulus that is tolerated by normal subjects. • Non-allergic hypersensitivity: Non-allergic hypersensitivity is the preferred term to describe hypersensitivity in which immunological mechanisms cannot be proven

Definition in SNOMED CT (for non-allergic hypersensitivity reaction) • A pathological nonimmune process generally directed towards a foreign substance, which results in tissue injury, which is usually transient. It is the realization of the pseudoallergic disposition. A variety of mechanisms such as direct histamine release, complement activation, cyclooxygenase activation and bradykinin generation may be involved.

Mechanisms involved in non-allergic hypersensitivity Drug Presumed mechanism Aspirin and other NSAIDs Inhibited prostaglandin production and enhanced leukotriene production Opiates Direct stimulation of mast cells and/or basophils causing release of mediators Vancomycin Direct stimulation of mast cells and/or basophils causing release of mediators Radiocontrast media Unknown mechanism Ciprofloxacin Direct stimulation of mast cells and/or basophils causing release of mediators Amphotericin B colloidal suspension Complement activation Paclitaxel Complement activation due to excipient Cremophor EL micelles Angiotensin converting enzyme inhibitors Bradykinin generation

Non-allergic hypersensitivity dispositions and reactions A variety of different non-allergic hypersensitivity processes are represented

New subtypes of 609404002 |Non-allergic hypersensitivity process (qualifier value)|

Questions • Should subtypes of non-allergic hypersensitivity be modeled with specific kinds of non-allergic hypersensitivity processes rather than non-allergic hypersensitivity process? • Should 609404002 |Non-allergic hypersensitivity process (qualifier value)|be inactivated as it represents a variety of different processes and should 609405001 |Non-allergic hypersensitivity condition (finding)|be remodeled with GCIs representing the different processes comprising non-allergic hypersensitivity?

Example of complement mediated process

Example of cyclooxygenase 1 inhibition process

Example of bradykinin generation process

Example of non-immunologic histamine release process

Example of unknown mechanism process

Current GCI model for Non-allergic hypersensitivity condition

Proposed revision of GCI model for nonallergic hypersensitivity condition

Final questions • Is the current definition of Non-allergic hypersensitivity in which the main mechanisms are mentioned sufficient to use 609404002 |Nonallergic hypersensitivity process (qualifier value)| to define nonallergic hypersensitivity conditions, reactions and disorders as they currently are Or • Should we adopt a more robust but more complex model for nonallergic hypersensitivity