Table 1.

Proposed mechanisms of action for pemphigus therapies.

Drug	Mechanism	Reference
Autoantibody-targeted therapy	Specific binding or inhibition of disease-associated anti-Dsg autoantibodies.	[66•]
Azathioprine	Prodrug of 6-mercaptopurine, which is metabolized to 6-thioguanine purine analog and 6-thioinosinic acid, a de novo and salvage purine synthesis inhibitor.	[68]
CD40/CD154 blockade	Blocks a critical co-stimulatory signal for initiation of the T-cell dependent humoral immune response.	[56•]
Cholinergic agonists	Unknown, but may modulate overall keratinocyte cell adhesion.	[61]
Corticosteroids	Multiple proposed mechanisms for immunosuppression, including inhibition of NFκB. May upregulate keratinocyte adhesion molecules.	[69,70]
Cyclophosphamide	Prodrug metabolized by tissue oxidases to the alkylating agent phosphoramide mustard.	[71]
Dapsone	Inhibits leukocytes through multiple proposed mechanisms, including reversible inhibition of myeloperoxidase; mechanism in PV unclear.	[72]
Etanercept	Soluble TNFα receptor fusion protein; TNFα may play a role in the pathogenesis of PV.	[38]
Infliximab	Anti-TNFα chimeric mAb; TNFα may play a role in the pathogenesis of PV.	[38]
IVIg	May saturate serum neonatal Fc receptors, allowing more rapid catabolism of serum IgG; may also prevent keratinocyte apoptosis.	[25,26,27•]
MMF	Noncompetitive inhibitor of inosine monophosphate dehydrogenase (de novo nucleotide synthesis inhibitors preferentially target lymphocytes).	[13]
p38 MAPK inhibitors	First generation competitive and second generation allosteric inhibitors regulate TNFα production and may have direct effects on keratinocytes.	[47]
PI-0824 vaccine (Peptimmune Inc/Orphan Europe SARL)	Synthetic Dsg3 186–204 peptide intended to induce anergy of disease-associated T-cells.	[46]
Rituximab	Anti-CD20 chimeric mAb; may deplete autoreactive B-cells, as well as Dsg3-specific CD4+ Th cells.	[M Hertl, personal communication]

Dsg desmoglein, IVIg Intravenous Ig, MMF mycophenolate mofetil, PV pemphigus vulgaris.