Can fluoxetine (selective serotonin reuptake inhibitor) cause a skin rash?

Can Fluoxetine Cause Skin Rash?

Yes, fluoxetine can cause skin rash, occurring in approximately 7% of patients, and while most cases are mild, serious cutaneous reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported, requiring immediate drug discontinuation. 1

Incidence and Types of Rash

• In US clinical trials involving 10,782 patients, 7% developed various types of rashes and/or urticaria during fluoxetine treatment 1
• Almost one-third of patients who developed rash were withdrawn from treatment due to the rash itself or systemic signs and symptoms associated with it 1
• The rash typically appears as morbilliform (measles-like), pruritic eruptions that are generalized over the trunk and limbs, with possible facial involvement 2

Serious Cutaneous Reactions

• Two patients in premarketing trials developed serious cutaneous systemic illness: one with leukocytoclastic vasculitis and another with severe desquamating syndrome considered to be either vasculitis or erythema multiforme 1
• Stevens-Johnson syndrome has been documented with fluoxetine, presenting with skin rash that can progress to involve the liver concomitantly 3
• Anaphylactoid events including bronchospasm, angioedema, laryngospasm, and urticaria (alone or in combination) have been reported 1

Associated Systemic Symptoms

• Clinical findings reported with rash include fever, leukocytosis, arthralgias, edema, carpal tunnel syndrome, respiratory distress, lymphadenopathy, proteinuria, and mild transaminase elevation 1
• Systemic events possibly related to vasculitis, including lupus-like syndrome, have developed in patients with rash, and death has been reported in association with these systemic events 1
• Pulmonary events including inflammatory processes and/or fibrosis have been reported rarely, sometimes with dyspnea as the only preceding symptom 1

Mechanism and Cross-Reactivity

• The skin contains a serotonin production system and serotonin receptors, and SSRIs increase serotonin concentrations, which can cause pruritus and dermal side effects 4
• Cross-reactivity between different SSRIs is possible despite different chemical structures, as patients who developed rash with fluoxetine have experienced similar reactions with other SSRIs like paroxetine and sertraline 2, 5
• Dermal reactions may be due to high activity in the serotonergic system at the dermal and epidermo-dermal junctional area rather than hypersensitivity to the drug molecule itself 4

Management Algorithm

Upon appearance of rash:

• Discontinue fluoxetine immediately if the rash is accompanied by systemic symptoms, involves mucous membranes, or shows signs of blistering or desquamation 1
• Most patients improve promptly with discontinuation of fluoxetine and/or adjunctive treatment with antihistamines (such as clemastine or diphenhydramine) or topical/systemic steroids (such as betametasone or hydrocortisone cream) 1, 4, 2
• All patients experiencing rash with systemic symptoms have been reported to recover completely with appropriate management 1

Critical Monitoring Points

• Watch for progression to severe cutaneous reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, or drug rash with eosinophilia and systemic symptoms (DRESS) 6, 1
• Monitor for signs of vasculitis, serum sickness-like syndrome, or lupus-like syndrome in patients with persistent or worsening rash 1
• Do not rechallenge with fluoxetine or potentially any other SSRI if serious cutaneous reactions occurred, as cross-reactivity is possible 2, 5

Common Pitfall

• The most important pitfall is continuing fluoxetine when rash appears with systemic symptoms or when an alternative etiology cannot be identified, as this can lead to progression to life-threatening conditions 1
• Prophylactic use of antihistamines or corticosteroids at the time of fluoxetine initiation to prevent rash has not been studied and is not recommended 6