Severe Tacrolimus-Induced Granulomatous Rosacea Recalcitrant to Oral Tetracyclines

Topical tacrolimus-induced GR presents acutely, with onset of symptoms within 3 days to 28 months after initiation of therapy (average time to onset is 5 months). Tacrolimus-induced GR may also develop after the dosage is escalated in patients who previously used topical tacrolimus without complications. ⁴ Our patient had used tacrolimus intermittently for several years and developed symptoms after increasing the frequency and quantity of application. In tacrolimus-induced GR, histology typically reveals a perifollicular lymphohistiocytic infiltrate with non-caseating granulomas. Unlike corticosteroid-induced rosacea-like eruptions, no epidermal atrophy is appreciated in this condition. When making the diagnosis of tacrolimus-induced GR, other granulomatous disorders and rosaceiform eruptions to be considered include sarcoidosis, lupus vulgaris, pyoderma faciale, and lupus miliaris disseminatus faciei.

The exact pathogenesis of topical tacrolimus-induced GR remains unknown. Some case reports have suggested that the immunosuppressive properties of tacrolimus may facilitate overgrowth of Demodex folliculorum, which has been implicated in the pathogenesis of rosacea⁸ and GR.⁹ Other reports postulate that rosacea is an inflammatory disorder and that an exaggerated innate immune response (whereby