Table I.

Drugs that induce cutaneous sarcoidosis and proposed biologic mechanisms of induction

Drug	Biologic mechanism
IL-1Ra: anakinra1	•Unopposed type I IFN production •Failure of immune regulatory mechanisms •Immunosuppression favoring infection with bacterium implicated in sarcoidosis
Interferon-α3	•Induction of Th1 cytokines
anti-TNF agents4, 5: entanercept,6 infliximab,7 adalimumab8	•Unopposed type I IFN production •Move toward a Th1/Th17 profile •Decreased TNF-mediated suppression of Treg expansion/activity •Alteration in ratio of membrane bound to soluble TNFR2 •Process of anti-IFX antibody production •Predisposition secondary to genetic variation of TNF-α gene
PD-1 inhibitors: pembrolizumab,9 nivolumab10	•Increased T-cell proliferative capacity •Note: PD-1 up-regulation has also been associated with sarcoidosis with a proposed mechanism of decreased T-cell proliferative capacity leading to immunologic derangements conducive to sarcoidosis
BRAF inhibitor: vemurafenib11	•Increased TNF-α and IFN-γ levels •Note: Study suggests patients who have sarcoidosis with vemurafenib therapy carry a better prognosis
anti-CTLA4 mAb: ipilimumab12	•Enhanced T-cell responses
anti-IgE mAb: omalizumab13	•Decreased expression of dendritic cell IgE high affinity receptor/Th2 cytokine production with subsequent shift from Th2 to Th1 cytokine profile •Unmasking of sarcoidosis with prednisone taper accompanying omalizumab treatment initiation
Fillers for aesthetic procedures: hyaluronic acid14	•Tissue injury and foreign body reaction to filler
Insulin15, 16	•Traumatic induction (Koebnerization) and foreign body reaction to materials introduced with insulin injection •Inflammatory response to zinc component of insulin formulation
Botulinum neurotoxin A17	•Foreign body reaction after deposition of crystalline preparation of botulinum neurotoxin A in the skin •Foreign body reaction after accidental inoculation of a separate material during injection
Desensitization injections18	•Inoculation of antigens (aluminum and others) into the subcutaneous tissue at time of injection
Ophthalmic drops with sodiumbisulfate19 Leuprorelin injections20	•Foreign body reaction to known sensitizer implicated in delayed type hypersensitivity reactions (sulfur)
	•Subcutaneous granulomatous hypersensitivity reaction