Table 3.

Mechanism of action of oral agents (including oral antimicrobials) in HS. Canonical effects are compared with documented anti-inflammatory effects proposed in HS. The quality of evidence regarding their use in HS is also listed in the far-right column.

Oral therapy	Mechanism(s) of action		Quality of evidence15
	Canonical effect(s)	Documented anti-inflammatory effect(s)
Metformin	Decreased mTORC1 activity	Decreased IL-6, TNF-α, TH17, NLRP3	C
DPP4 Inhibitors	Reduction of metabolism of GLP, slow gastric emptying, promote weight loss	Reduce adipose tissue associated TNF-α, IL-6 via NF-κB signaling	C
GP1 Analogues	Stimulate GP1 receptor		C
PPAR-γ Agonists	Stimulate PPAR-γ activity	Decrease IL-6 anti-proliferative activity	C
Oral Contraception	Estrogen-response elements on gene transcription	Dendritic cell, T-cell, possible role of 16-α estrogens NF-κB, AP-1, PI3/Akt pathway modulation	C
Finasteride	5-α reductase inhibitor	IGF-1 dependent: possibly increased activity in insulin resistance/diabetic patients	C
Spironolactone	Aldosterone antagonist	Reduction in TNF-α, IL-6, NOS	C
Oral antimicrobials
Doxycycline	30S ribosomal inhibition	Decreased IL-1, IL-6, IL-8, TNF-α, chemotaxis, lipo-oxygenase inhibition, MMP inhibition, NF-κB signaling inhibition	B
Minocycline		Downregulation of LPS-stimulated TLR2 activity; upregulated TIMP-1	C
Erythromycin	50S ribosomal inhibition	Decreased IL-6, IL-8, TNF-α, GM-CSF activity. Downregulated AP-1 and NF-κB activity	C
Clindamycin			C
Rifampicin	Controversial: glucocorticoid receptor,	Reduced iNOS transcription, reduced NF-κB activity. Reduces TH17 differentiation	C
Ciprofloxacin	Inhibition of DNA gyrase and topoisomerase IV	Effects upon cAMP, NF-κB, AP-1, IL-8, IL-6 and gastrointestinal microbiome	C
Moxifloxacin		Reduction of IL-1ß, IL-8, TNF-α. Stabilization of IXb protein. Suppresses NF-κB signaling. Reduction in IL-17A	C
Metronidazole	Inhibition of nucleic acid synthesis	Impacts on gastrointestinal microbiome	C
Ertapenem	Binding to Penicillin-binding proteins and disruption of cell wall synthesis	Reduction in IL-6, IL-12, TNF-α	C
Linezolid	Inhibition of protein synthesis initiation	Reduction in IL-1β, IL-6, IL-8, TNF-α. Possible ERK1/2 signaling modulation	C

AP-1, activator protein 1; cAMP, cyclic adenosine monophosphate; GLP, glucagon like peptide; GM-CSF, granulocyte-macrophage colony-stimulating factor; HS, hidradenitis suppurativa; IGF-1, Insulin Like Growth Factor- 1; IL, interleukin; iNOS, inducible nitric oxide synthase; LPS, lipopolysaccharide; MMP, matrix metalloproteinase; NF-κB, nuclear factor kappa B; NOS, nitric oxide synthase; PPAR, peroxisome proliferator-activated receptor; TLR2, Toll-like receptor; TNF, tumor necrosis factor.