Sulfur (Monograph)

Drug class: Keratolytic Agents

Medically reviewed by Drugs.com on Nov 10, 2024. Written by ASHP.

Introduction

Sulfur is a keratolytic agent and scabicide.

Uses for Sulfur

Acne

Topical sulfur preparations are used principally for the symptomatic treatment of acne vulgaris. Although the drug may relieve plugging and rupturing of follicles, ease the evacuation of comedones, and promote peeling of the skin, some clinicians believe that topical sulfur may also promote the formation of new comedones. Sulfur generally has been shown to be more effective than a placebo vehicle in decreasing the number of comedones and other lesions in patients with acne. Although several studies have shown a combination of sulfur and benzoyl peroxide to be more effective than either drug alone in the treatment of acne, other studies have shown no substantial difference between sulfur, benzoyl peroxide, or combined therapy. Combined therapy with 5% sulfur and 7.5% benzoyl peroxide generally is considered effective in the topical treatment of acne vulgaris; however, there is some evidence that the cutaneous toxicity (i.e., hypersensitivity) of benzoyl peroxide is enhanced by sulfur. Sulfur (8%) is commonly used in combination with resorcinol (2% resorcinol or 3% resorcinol monoacetate) for the treatment of acne. Combined sulfur-resorcinol therapy generally has been shown to be more effective than a placebo vehicle in decreasing the number of comedones and other lesions in patients with acne, and some clinicians believe that resorcinol enhances the activity of sulfur. The efficacy of sulfur compared with other forms of therapy (e.g., benzoyl peroxide, topical anti-infectives, retinoic acid) in the treatment of acne vulgaris has not been fully determined using well-designed, controlled studies.

Scabies

Topical 5–10% sulfur ointment (in a petrolatum base; no longer commercially available in the US) has been used for the treatment of scabies. Because sulfur ointment is messy, malodorous, tends to stain, and can produce an irritant dermatitis, its use has largely been supplanted by permethrin, lindane, or other scabicides for most patients. Many clinicians and the US Centers for Disease Control and Prevention (CDC) consider permethrin 5% to be the scabicide of choice because of its safety and efficacy profile relative to other available agents, particularly lindane. Recommendations for alternative therapy differ among various clinicians. The CDC and others recommend sulfur 6% ointment or lindane 1% as preferred alternative scabicides, and cost and convenience considerations may factor into the choice for certain patients. Crotamiton 10% or oral ivermectin 200 mcg/kg as a single dose also have been suggested as alternative scabicides.

The CDC and other clinicians currently recommend permethrin 5% as preferred therapy for scabies in infants and young children and in pregnant and lactating women because of its low percutaneous absorption and relative topical safety. Some clinicians also consider sulfur 5–10% ointment a scabicide of choice in such patients, although systemic toxicity has been reported in several infants receiving such therapy at high doses.

Norwegian scabies is a particularly severe and highly infectious form of scabies that presents as crusted, hyperkeratotic, scaling plaques, which may be generalized or localized to the hands and feet. In this condition, the patient is infested with large numbers (thousands to millions) of Sarcoptes mites. In less than 10% of patients with scabies, nodular scabies may develop, which is characterized by intensely pruritic nodules that persist for months after effective scabies therapy; mites seldom are identified in these nodules. For further information on the management of Norwegian and nodular scabies, see Uses: Scabies in Permethrin 84:04.12.

The CDC states that patients with human immunodeficiency virus (HIV) infections who have uncomplicated scabies should receive the same treatment as those without HIV infection. Patients with HIV infection and other immunocompromised patients are at increased risk of developing Norwegian scabies, and the CDC recommends that such patients be managed in consultation with an expert. For further information on the management of scabies in patients with HIV infection, see Uses: Scabies in Permethrin 84:04.12.

Other Uses

Sulfur (e.g., 2–5%) is used topically for its keratolytic effect alone or, usually, in combination with salicylic acid (e.g., 2%) for controlling dandruff. Sulfur, alone or in combination with salicylic acid, generally has been shown to be more effective than a placebo vehicle in controlling dandruff, producing a decrease in corneocyte counts in some studies. Sulfur has also been used topically in combination with salicylic acid for controlling seborrheic dermatitis. Sulfur has been used topically for the symptomatic treatment of many other dermatologic conditions (e.g., fungal infections), but other treatments are usually preferred.

Precipitated sulfur also has been available in combination with oral laxative products, but there has been no objective evidence that systemic sulfur may be useful in the treatment of any disease.

Sulfur Dosage and Administration

Acne

Sulfur, in the form of 1–8% creams, jellies, lotions, or soaps, is applied topically for the treatment of acne vulgaris. In these topical products, precipitated or colloidal sulfur usually is used and usually is available in combination with topical anti-infectives, detergents, and/or other keratolytics. The higher concentrations of sulfur produce a more intense keratolytic effect; a concentration of at least 2% sulfur generally is required for effectiveness. Sulfur is contained in some acne cleansers but because contact with the skin is only brief, the value of sulfur in these products is questionable. In acne vulgaris, the frequency with which topical preparations are applied should be determined by the severity of the acne and patient response. Generally, preparations intended to be applied and left on the skin are applied to thoroughly cleansed skin, covering the entire affected area with a thin layer of the preparation 1–3 times daily or as directed by a physician. To avoid excessive drying, therapy generally is initiated with a single application daily and then the frequency is increased gradually if necessary.

Scabies

For the treatment of scabies, a thin layer of a 5–10% precipitated sulfur ointment (in a petrolatum base) has been applied uniformly and gently massaged into all skin surfaces (entire trunk and extremities) from the neck to the toes (including the soles of the feet); the CDC and others currently recommend a 6% ointment as the preferred concentration. This treatment has been repeated on each of 2–3 successive days. Usually, a bath has been taken before each application of the ointment and 24 hours after the last treatment in order to remove the drug. In an adult, 30 g of the ointment usually has been sufficient for one application; children have received a proportionately smaller amount.

All clothing and bed linen that may have been contaminated by a patient with scabies should be decontaminated (dry-cleaned or either machine-washed or machine-dried using the hot cycle) or removed from body contact for at least 72 hours following treatment to avoid reinfestation or transmission of scabies. Fumigation of living areas is not necessary in these cases. Many experts recommend particular attention to thorough cleaning of areas inhabited by patients with Norwegian scabies because of the large numbers of mites infesting these patients.

The CDC recommends that scabies epidemics in institutional settings (e.g., nursing homes, hospitals, residential facilities and communities) be managed in consultation with an expert. Control of such epidemics requires treatment of the entire population at risk. Permethrin has been recommended as a scabicide of choice in institutional outbreaks; other clinicians recommend either permethrin or lindane.

Dandruff

For relief of itching and scalp flaking associated with dandruff, 2–5% sulfur alone or, most often, in combination with salicylic acid, usually is used as a lotion shampoo. The lotion should be applied to wet hair and massaged vigorously into the scalp; the scalp then is rinsed thoroughly and application of the lotion and rinsing is repeated. The lotion usually is used as a shampoo twice weekly.

Cautions for Sulfur

Adverse Effects

When used in appropriate dosage, topically applied sulfur preparations have a low order of toxicity. Topical preparations containing 2–5% sulfur generally are well tolerated. Local irritation of the skin, eyes, or respiratory tract may occur and, therefore, contact with the eyes should be avoided. Allergic reactions to sulfur occur rarely. Repeated applications may cause dermatitis, sometimes severe (e.g., dermatitis venenata). In concentrations greater than 15%, sulfur is very irritating to the skin however, commercially available preparations contain up to 8% of sulfur. Sulfur ointment stains clothing, bedding, and metal, including jewelry.

Systemic toxicity (e.g., headache, vomiting, muscle cramps, dizziness, collapse) has reportedly occurred following topical application of precipitated sulfur powder or sulfur ointment to patients with eczema, but symptoms resolved within several hours. Topical application of a 10% sulfur ointment (no longer commercially available in the US) for 3 days on infants with scabies reportedly caused systemic toxicity and several deaths. There have been no reports of systemic toxicity to date following topical application of preparations containing 2–5% sulfur, and such concentrations are generally considered safe for topical use.

Precautions and Contraindications

Topical preparations containing sulfur are intended for external use only. Topical sulfur-containing preparations should not be used near the eyes; if contact with the eye(s) occurs, the affected eye(s) should be rinsed thoroughly with water. If topical sulfur-containing preparations are used for self-medication and the condition worsens or persists after regular use as directed, a physician should be consulted. If excessive skin irritation develops or increases during self-medication with a topical sulfur-containing preparation, the drug should be discontinued and a physician or pharmacist consulted. Combination topical preparations containing sulfur and resorcinol should not be used for self-medication of large areas of the body or of areas with broken skin. When used for self-medication of acne, topical sulfur-containing preparations generally should not be used concurrently with other topical acne medications unless otherwise directed by a physician.

Pediatric Precautions

Topical preparations containing sulfur should not be used in children younger than 2 years of age except under the direction and supervision of a physician.

Pharmacology

Topically applied sulfur is a keratolytic agent. Sulfur has keratoplastic activity at low concentrations, correcting abnormal keratinization, and keratolytic activity at high concentrations, causing peeling of skin; these effects apparently result from the same action of the drug. Following topical application of a 5% sulfur ointment (no longer commercially available in the US) on hairless mouse skin for a 4-week period, there was increasing edema during the first week, followed by thickening of the prickle cell layer. This reaction was maximal at 2 weeks and resulted in nonadherent cells in the stratum corneum; these cells retained their nuclei. When a 20% sulfur ointment (no longer commercially available in the US) was used, similar but more severe reactions occurred. A 40% ointment (no longer commercially available in the US) caused almost complete loss of the stratum corneum at 4 weeks, and intercellular and intracellular edema with resultant separation of epidermis from dermis. Thus, at lower concentrations, sulfur causes epidermal injury which is followed by repair. When sulfur concentrations greater than 5% are applied topically, injury exceeds the reparative process, and peeling (keratolytic effect) occurs in severity proportionate to the sulfur concentration. Although the mechanism of sulfur’s keratolytic action has not been determined, this action may depend on formation of hydrogen sulfide when the drug comes in contact with skin; the production of the characteristic odor of rotten eggs when sulfur comes in contact with skin results from hydrogen sulfide formation. Hydrogen sulfide may be formed within the epidermis by sulfur reacting with cysteine.

Topically applied sulfur has mild antifungal and antibacterial activity. It has been suggested that when applied topically to the skin, sulfur forms hydrogen sulfide and/or polythionic acid, which may exert germicidal activity. In vitro studies indicate that sulfur has little if any fungistatic or fungicidal activity. Therefore, sulfur’s antifungal activity probably results largely from its keratolytic action, causing shedding of fungal spores and hyphae embedded within the stratum corneum. In vitro, sulfur has been shown to have some antibacterial activity; the drug has a potent inhibitory effect against some streptococci, a moderate inhibitory effect against Staphylococcus aureus, and no activity against gram-negative bacteria. It has been suggested that the drug’s antibacterial activity may partly result from inactivation of sulfhydryl groups contained in bacterial enzyme systems, since the antibacterial effect of the drug has reportedly been neutralized by addition of cysteine and other sulfhydryl-containing compounds to the culture medium. Topically applied sulfur is reportedly toxic to the parasitic arthropod Sarcoptes scabiei.

The exact mechanism(s) of action of sulfur in the treatment of acne is not fully understood but is presumed to involve the drug’s keratolytic and antibacterial effects. Although some studies indicate that sulfur may also be comedogenic, other studies have been unable to substantiate this effect and the drug generally is considered effective in the topical treatment of acne.

When administered orally, sulfur reportedly has a laxative or cathartic effect.

Sulfur Pharmacokinetics

The absorption, distribution, and elimination of sulfur following topical application have not been fully characterized. Topically applied sulfur reportedly penetrates the skin and is detectable in the epidermis within 2 hours after application and throughout the skin within about 8 hours; the drug is not detectable in skin 24 hours after application. Percutaneous absorption of the drug into systemic circulation reportedly occurred following topical application of a 25% sulfur ointment to abraded skin of animals but did not occur when the drug was applied to intact skin.

Chemistry and Stability

Chemistry

Sulfur is a keratolytic agent. Sulfur is a naturally occurring element found in the free state in deposits in the US and Sicily. Sulfur also is distributed widely and abundantly in nature as sulfides and sulfates of metals.

Two official (USP) forms of sulfur, precipitated sulfur and sublimed sulfur, of at least 99.5% purity (on an anhydrous basis), are used in topical preparations. Precipitated sulfur (milk of sulfur), made by boiling sulfur with lime and precipitating the filtered solution with hydrochloric acid, occurs as a very fine, pale yellow, amorphous or microcrystalline powder. Sublimed sulfur (abric, flowers of sulfur), made by cooling and condensing sulfur vapors in a chamber, occurs as a fine, yellow, crystalline powder having a faint odor and taste. Precipitated sulfur is practically insoluble in water, very slightly soluble in alcohol, and slightly soluble in olive oil. Sublimed sulfur is practically insoluble in water and in alcohol and sparingly soluble in olive oil. The particles of precipitated sulfur are finer than those of sublimed sulfur and, therefore, are preferred for dermatologic preparations.

Sulfur also is available as ground roll sulfur (flour of sulfur) which has different physical properties than sublimed sulfur. Commercially available topical preparations also may contain sulfur in the form of colloidal sulfur or washed sulfur. Colloidal sulfur contains the drug as a colloidal complex in which minute particles of sulfur are stabilized in an aqueous medium containing a colloid such as egg albumin or gelatin. Washed sulfur, made by washing sublimed sulfur with ammoniated water, occurs as a fine, yellow, crystalline powder.

Stability

Preparations containing sulfur may react with metals including silver and copper, resulting in discoloration of the metal. Preparations containing sulfur should be stored in well-closed containers.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Reload page with references included

Medical Disclaimer