DIDMOHS: A Proposed Consensus Nomenclature for the Drug-Induced Delayed Multiorgan Hypersensitivity Syndrome

While reviewing a manuscript on the "sulfone syndrome," it occurred to us how inconsistent the literature is in referring by name to this rather distinctive syndrome that was initially characterized almost half a century ago.¹ Such ambiguity in nomenclature can be harmful since prompt recognition and treatment of this potentially life-threatening but reversible pattern of drug hypersensitivity can be delayed. In addition, terms such as sulfone syndrome and dapsone syndrome are not fully informative because structurally different drugs can produce this hypersensitivity reaction pattern (eg, phenytoin, carbamazepine, phenobarbital, lamotrigine, trimethoprim-sulfamethoxazole, minocycline, procarbazine, allopurinol, or terbinafine). We see this pattern of drug hypersensitivity most often at the inpatient services in our medical center as a result of phenytoin administration. It is not infrequent that the primary care physicians have failed to recognize this syndrome at the time of our evaluation, perhaps reflecting the general medical community's relative lack of familiarity with this particular drug hypersensitivity syndrome.

It is not that the clinical illness is indistinct: a mononucleosis-like syndrome consisting of fever, facial edema, a generalized papulopustular or exanthematous eruption, lymphadenopathy, hepatitis (less commonly nephritis, pneumonitis, or hypothyroidism), and eosinophilia characteristically occurring in a delayed fashion 3 to 6 weeks after starting treatment with the inciting drug for the first time.^{2 - 4} What is ambiguous about this potentially life-threatening clinical entity that is often initially recognized by its cutaneous manifestations is the multitude of names that have been used to describe this pattern of drug hypersensitivity over the past 50 years: sulfone syndrome, dapsone syndrome, dapsone hypersensitivity syndrome, dapsone-induced sulfone syndrome, disulone hypersensitivity syndrome, sulfonamide hypersensitivity syndrome, phenytoin/Dilantin syndrome, Dilantin hypersensitivity reaction, phenytoin/Dilantin hypersensitivity syndrome, carbamazepine-induced anticonvulsant hypersensitivity syndrome, allopurinol hypersensitivity syndrome, hypersensitivity syndrome reaction, anticonvulsant hypersensitivity syndrome, hypersensitivity to aromatic anticonvulsant agents, aromatic anticonvulsant hypersensitivity reactions, and "a potentially fatal drug reaction."

Sometimes a good acronym can serve to pull together and focus attention on a complex array of clinical findings (eg, POEMS syndrome and SAPHO syndrome). One such acronym has recently been proposed by Bocquet and Roujeau⁵ for this pattern of drug hypersensitivity: DRESS syndrome (drug rash with eosinophilia and systemic symptoms). However, to underscore the delayed and multiorgan aspects of this pattern of drug hypersensitivity that have been emphasized by others,^{2 ,6} we suggest that the term drug-induced delayed multiorgan hypersensitivity syndrome (DIDMOHS) could be helpful in providing a framework for relating and integrating major clinical and laboratory elements of this pattern of illness. To emphasize subtle differences in the syndrome that might be associated with different triggering drugs,² the specific drug name could be used to modify the term DIDMOHS (eg, dapsone DIDMOHS, phenytoin DIDMOHS, minocycline DIDMOHS, etc).

One is always at risk in proposing a new name for an existing medical entity. However, the harm to patients that can result from unfocused thinking concerning this potentially life-threatening but reversible pattern of drug hypersensitivity would seem to justify an effort to arrive at a more precise terminology for this clinical entity. Admittedly, the term DIDMOHS may not be the ideal designation; however, it is the best we have been able to conjure up and is offered as a starting point to generate further discussion on this important clinical issue.