Delayed-type hypersensitivity to GnRH agonists
Question:
9/17/2019
A 62 year-old male with h/o recurrent prostate cancer. Radical prostatectomy in 1998, followed by salvage radiation in 2/19. On 5/13/19, he received his 1 month Lupron injection and c/o rash/hives to his face and neck with skin peeling 1 week after the injection. He received a 3-month Lupron injection on 6-24-19 and developed a more severe skin rash with peeling. He stated it was too painful for him to go outside. The rash resolved somewhat but then worsened. He was seen by his urologist who stated it was an allergic reaction and to stop theses injections. He was prescribed a Medrol Dose pak, which temporarily resolved his rash by 8/5/19 but returned 8/10 and was intolerable 8/12. He received PNS 10 mg/day which resolved the rash. Topical treatments were too painful as they burned. He c/o hot flashes on his face and neck. His rash itches but sweating increases his 'burning' sensation.
I questioned severe systemic cutaneous allergic reaction and switched him to po PNS and trial with mixture of Desonide and Protopic ointments, along with Allegra or Zyrtec. I explained that I agreed his next injection would be worse and to stop the Lupron. Now I get a fax from his doctor, wondering if Firmagon, Trelstar, or Zoledex could be used. My understanding is that these are all GnRH analogs and shouldn't be used. Am I correct?
Answer:
There is no data on the likelihood of another similar delayed-onset T-cell hypersensitivity reaction to any of the alternative GnRH agonists. Delayed-onset reactions to leuprolide have been reported, but only very rarely. Please review J Drugs Dermatol. 2014;13:755-7. Continue to avoid leuprolide as it has been clearly proven to be implicated by rechallenge. If there is no other alternative to GnRH agonists and the patient is will to undergo a challenge with a significant risk of a recurrent reaction as severe as previous reactions, a challenge could be attempted with nafarelin acetate or goserelin acetate. I would recommend a challenge of 1/10 of a therapeutic dose with at least 2 weeks of observation. If no rash occurs, a full therapeutic dose could be administered. If a rash occurs, consider a biopsy and also check for liver enzyme abnormalities and peripheral blood eosinophilia.
I hope this information is of help to you and your patient.
Regards,
Eric Macy, MD, MS, FAAAAI