Stevens-Johnson Syndrome

Stevens-Johnson Syndrome (SJS) is a thankfully rare reaction to a wide variety of medications: PMID 7477195. Within psychiatry, this reaction is especially concerning and common in lamotrigine, and less common but also present in carbamazepine and oxcarbazepine.

Lamotrigine, carbamazepine, and oxcarbazepine share expected AMP/adenosine deaminase inhibition. Purines mediate blood cell differentiation and survival: PMID 12734342.

Adenosine deaminase deficiency is associated with dramatic reduction in B-cell immune response, causing immune collapse. Temporary adenosine deaminase inhibition may cause agranulocytosis/ neutropenia (B-cell deficiencies).

Stevens Johnson syndrome (SJS) is thought to be an excessive T-cell immune response, perhaps due to temporarily inhibited B-cell response.

Although the medications that cause Stevens Johnson syndrome (SJS) include a variety of chemical structures, the 2,6 di-amino structure is preserved among some of the medications most frequently associated with SJS.

Another diaminopurine used clinically is phenazopyridine, used for urinary analgesia: I can't find evidence of association with SJS: in fact, urinary tract SJS lesions can be symptomatically treated with phenazopyridine 32523661 IMG

Typically considered a drug-reaction, SJS can also be caused by viral infections, raising difficult questions about mechanism until spring 2021, when it was shown that a wide variety of viruses synthesize and preferentially use 2,6 di-amino purine/adenosine: PMID 33926955, 33926956.

Abacavir shares the 2,6 di-amino adenosine structure, and is preferentially utilized by HIV, consistent with the viral di-amino trait. HIV is among the most common viral causes of SJS. As expected, abacavir is associated with SJS: PMID 12228837.

Gradual dose titration and limiting treatment interruptions are standard ways to reduce lamotrigine-induced Stevens-Johnson syndrome risk. Lamotrigine may be safely restarted after treatment interruptions less than 5 days in duration: PMID 12444815.

In my clinical experience, adding a competitive non-specific adenosine deaminase inhibitor (e.g. low-dose, 2-3 day course of benzodiazepine) seems to reduce SJS risk during oxcarbazepine initiation/titration. 

Note that the suffix -a/epine typically suggests a 7 member ring, often with 1-2 nitrogen substitutions, typically similar enough to expect some amount of AMP/adenosine deaminase inhibition.

Unfortunately, hydralazine, despite being an adenosine deaminase inhibitor XXXX,XXXX is also associated with SJS 24588409, 24719674

I have seen several cases of catatonia associated with co-administration of clozapine and mirtazepine, suggesting caution with this combination.