Dupilumab-associated ectropion and punctal stenosis treated with tacrolimus ointment (0.03%) in a 15-year-old girl.

A 15-year-old Asian girl with severe atopic dermatitis was referred for dupilumab-associated blepharoconjunctivitis. Medical history was significant for severe atopic dermatitis. She was started on prednisolone acetate 1% ophthalmic suspension three times daily, and dupilumab injections were withheld after the initial visit. The patient was noted to have right lower eyelid ectropion, cicatricial occlusion, and severe punctal stenosis 6 weeks later. She was started on 0.03% tacrolimus ointment to the eyelid margin. Resolution of ectropion and restoration of punctal patency with residual stenosis were observed 4 weeks later. This is the first reported adolescent case of dupilumab-associated ectropion and punctal stenosis successfully treated with topical tacrolimus ointment.

Mutual potentiation drives synergy between trimethoprim and sulfamethoxazole.

Trimethoprim (TMP)-sulfamethoxazole (SMX) is a widely used synergistic antimicrobial combination to treat a variety of bacterial and certain fungal infections. These drugs act by targeting sequential steps in the biosynthetic pathway for tetrahydrofolate (THF), where SMX inhibits production of the THF precursor dihydropteroate, and TMP inhibits conversion of dihydrofolate (DHF) to THF. Consequently, SMX potentiates TMP by limiting de novo DHF production and this mono-potentiation mechanism is the current explanation for their synergistic action. Here, we demonstrate that this model is insufficient to explain the potent synergy of TMP-SMX. Using genetic and biochemical approaches, we characterize a metabolic feedback loop in which THF is critical for production of the folate precursor dihydropterin pyrophosphate (DHPPP). We reveal that TMP potentiates SMX activity through inhibition of DHPPP synthesis. Our study demonstrates that the TMP-SMX synergy is driven by mutual potentiation of the action of each drug on the other.