Sulfur has been used to treat acne for hundreds of years for its peeling and drying actions, and it is found in various washes, soaps, and creams. It is an antifungal and antibacterial agent. Its keratolytic activity is somewhat controversial, with some authors showing even a comedogenic effect (51). It is not fully understood how sulfur works in the treatment of acne lesions. The claimed keratolytic properties may derive from the interaction between sulfur and keratinocytes, producing hydrogen sulfide. Smaller sulfur particles could allow greater interaction with keratinocytes and, therefore, produce greater therapeutic efficacy (52). Because of its unpleasant odor, sulfur is rarely used alone. As an OTC ingredient, it is most frequently found in combination with resorcinol. Sulfur is also present in prescription acne products in combination with sodium sulfacetamide.
Resorcinol has antibacterial, antifungal and mild keratolytic activity. When used as resorcinol monoacetate, this slowly liberates resorcinol, generating a milder but longer lasting effect. In the Acne Monograph, the OTC panel concluded that resorcinol is safe for human applications but did not find it efficacious in acne as a single ingredient (53). Therefore, resorcinol and resorcinol monoacetate are currently approved as OTC acne ingredients only in combination with sulfur. Side effects of sulfur and of resorcinol include
mostly mild irritation. Unpleasant odor (sulfur) of the formulation may also be a problem for patients.
Sulfur preparations for acne treatments are not as popular as they were in the past decades. Although sulfur is found in the forms of cream, lotion, ointment, spot-treatment mask, and bar soap, the more common use is in its prescription combination with sodium sulfacetamide.
Published peer-reviewed studies on the efficacy of sulfur, alone or in combination with resorcinol, are basically non-existent. Few controlled efficacy studies are, however, described in the OTC Acne Monograph and were presented to the OTC panel as substantiating material for the approval of these ingredients (54). Based on these studies, sulfur was approved as an acne ingredient in the concentrations of 3-8%. Resorcinol (2%) and resorcinol monoacetate (3%), however, were not found to be effective as single ingredients, and they were approved only in combination with sulfur 3-8% (55). The Acne Monograph reports that in a 12-week study (56), more subjects treated with 3% sulfur showed a good to excellent response, compared to the vehicle group, although no statistical analysis was conducted. A series of split-face, vehicle-controlled studies (57) showed a better reduction in lesion count in the subjects treated with a 5% sulfur product compared to vehicle.
Another study compared an 8% sulfur-2% resorcinol cream against placebo cream in 25 subjects using a split-face design (58). After eight weeks of treatment sulfur-resorcinol was significantly better in reducing open comedones, papules and pustules compared to placebo. A third study compared four treatment cells of 60 acne subjects each. The treatments were applied three times daily for eight weeks and consisted of: (i) 2.66% sulfur-1% resorcinol; (ii) 8% sulfur-2% resorcinol; (iii) 2.66% sulfur; and (iv) placebo. The two combinations of sulfur-resorcinol were found equivalent and were superior to both the placebo and the sulfur alone in the reduction of papules and “whiteheads” (59).
While the effect of sulfur on non-inflammatory lesions is not clear, its combination with resorcinol seems to increase its efficacy in both inflammatory and comedonal lesions.