Sulfur

Introduction

• Sulfur is a keratolytic agent and scabicide.

Uses• 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 theskin, 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 benoyl

 pero!ide to be more effective than either drug alone in the treatment of acne, other studies have shown nosubstantial difference between sulfur, benoyl pero!ide, or combined therapy. "ombined therapy with #$ sulfur

and %.#$ benoyl pero!ide generally is considered effective in the topical treatment of acne vulgaris& however,

there is some evidence that the cutaneous to!icity 'i.e., hypersensitivity( of benoyl pero!ide is enhanced bysulfur. Sulfur ')$( is commonly used in combination with resorcinol '*$ resorcinol or +$ resorcinol

monoacetate( for the treatment of acne. "ombined sulfurresorcinol 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., benoyl pero!ide, topical antiinfectives, retinoic acid( in the treatment of acne

vulgaris has not been fully determined using welldesigned, controlled studies.• Scabies

Topical #-$ sulfur ointment 'in a petrolatum base& no longer commercially available in the US( has been used

for the treatment of scabies. /ecause 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.0any clinicians and the US "enters for 1isease "ontrol and 2revention '"1"( consider permethrin #$ to be the

scabicide of choice because of its safety and efficacy profile relative to other available agents, particularly

lindane.-+, -3, -#, -4, -%, --- 5ecommendations for alternative therapy differ among variousclinicians.-+, -3, -4, -% The "1" and others recommend sulfur 4$ ointment-*, -3 or lindane -$ as

 preferred alternative scabicides,--, -+, -3 and cost and convenience considerations may factor into the choice

for certain patients.-*, -3, -# "rotamiton -$-+, -% or oral ivermectin * mcg6kg as a single dose alsohave been suggested as alternative scabicides.-+, -%

The "1" and other clinicians currently recommend permethrin #$ 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.-+, -3 Some clinicians also consider sulfur #-$ ointment a scabicide of choice in such patients,-7 although systemic to!icity has been reported in several infants receiving such therapy at high doses.

'See "autions8 Adverse 9ffects.(

 :orwegian scabies is a particularly severe and highly infectious form of scabies that presents as crusted,

hyperkeratotic, scaling pla;ues, which may be generalied or localied to the hands and feet.-*, -+, -7, --+ In

this condition, the patient is infested with large numbers 'thousands to millions( of Sarcoptes mites.-*, -), -7,--+ In less than -$ of patients with scabies, nodular scabies may develop, which is characteried by intensely

 pruritic nodules that persist for months after effective scabies therapy&-+, -- mites seldom are identified in these

nodules.-- <or further information on the management of :orwegian and nodular scabies, see Uses8 Scabies in

2ermethrin )383.-*.

The "1" states that patients with human immunodeficiency virus '=I>( infections who have uncomplicated

scabies should receive the same treatment as those without =I> infection.-3 2atients with =I> infection andother immunocompromised patients are at increased risk of developing :orwegian scabies,-+, -3, --+ and the

 

"1" recommends that such patients be managed in consultation with an e!pert.-3 <or further information on the

management of scabies in patients with =I> infection, see Uses8 Scabies in 2ermethrin )383.-*.• ?ther Uses

Sulfur 'e.g., *#$( is used topically for its keratolytic effect alone or, usually, in combination with salicylic acid

'e.g., *$( for controlling dandruff. Sulfur, alone or in combination with salicylic acid, generally has been shownto 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.

2recipitated sulfur also has been available in combination with oral la!ative products, but there has been no

ob@ective evidence that systemic sulfur may be useful in the treatment of any disease.

1osage and Administration• Acne

Sulfur, in the form of -)$ creams, @ellies, 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 combinationwith topical antiinfectives, detergents, and6or other keratolytics. The higher concentrations of sulfur produce a

more intense keratolytic effect& a concentration of at least *$ sulfur generally is re;uired 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 ;uestionable. In acne vulgaris, the fre;uency with which topical preparations are applied should be

determined by the severity of the acne and patient response. enerally, 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 -+ times daily or as directed by a physician. To avoid e!cessive drying, therapy generally is initiated

with a single application daily and then the fre;uency is increased gradually if necessary.

• Scabies

<or the treatment of scabies, a thin layer of a #-$ precipitated sulfur ointment 'in a petrolatum base( has beenapplied uniformly and gently massaged into all skin surfaces 'entire trunk and e!tremities( from the neck to the

toes 'including the soles of the feet(& the "1" and others currently recommend a 4$ ointment as the preferred

concentration. This treatment has been repeated on each of *+ successive days. Usually, a bath has been taken before each application of the ointment and *3 hours after the last treatment in order to remove the drug. In an

adult, + 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

'drycleaned or either machinewashed or machinedried using the hot cycle( or removed from body contact for at

least %* hours following treatment to avoid reinfestation or transmission of scabies.-3 <umigation of living areas

is not necessary in these cases.-3 0any e!perts recommend particular attention to thorough cleaning of areasinhabited by patients with :orwegian scabies because of the large numbers of mites infesting these patients.-*,

-+

The "1" recommends that scabies epidemics in institutional settings 'e.g., nursing homes, hospitals, residentialfacilities and communities( be managed in consultation with an e!pert.-3 "ontrol of such epidemics re;uires

treatment of the entire population at risk.-*, -3, --* 2ermethrin has been recommended as a scabicide of choice

in institutional outbreaks&--* other clinicians recommend either permethrin or lindane.-*• 1andruff

<or relief of itching and scalp flaking associated with dandruff, *#$ 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.

"autions

• Adverse 9ffectsBhen used in appropriate dosage, topically applied sulfur preparations have a low order of to!icity. Topical

 preparations containing *#$ sulfur generally are well tolerated. Cocal 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.

5epeated applications may cause dermatitis, sometimes severe 'e.g., dermatitis venenata(. In concentrationsgreater than -#$, sulfur is very irritating to the skin however, commercially available preparations contain up to

)$ of sulfur. Sulfur ointment stains clothing, bedding, and metal, including @ewelry.

Systemic to!icity 'e.g., headache, vomiting, muscle cramps, diiness, collapse( has reportedly occurred followingtopical application of precipitated sulfur powder or sulfur ointment to patients with ecema, but symptoms

resolved within several hours. Topical application of a -$ sulfur ointment 'no longer commercially available in

the US( for + days on infants with scabies reportedly caused systemic to!icity and several deaths. There have beenno reports of systemic to!icity to date following topical application of preparations containing *#$ sulfur, and

such concentrations are generally considered safe for topical use.

• 2recautions and "ontraindications

Topical preparations containing sulfur are intended for e!ternal use only. Topical sulfurcontaining preparationsshould 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 sulfurcontaining preparations are used for selfmedication and the condition worsens or

 persists after regular use as directed, a physician should be consulted. If e!cessive skin irritation develops orincreases during selfmedication with a topical sulfurcontaining preparation, the drug should be discontinued and

a physician or pharmacist consulted. "ombination topical preparations containing sulfur and resorcinol should not

 be used for selfmedication of large areas of the body or of areas with broken skin. Bhen used for selfmedicationof acne, topical sulfurcontaining preparations generally should not be used concurrently with other topical acne

medications unless otherwise directed by a physician.

• 2ediatric 2recautionsTopical preparations containing sulfur should not be used in children younger than * years of age e!cept under the

direction and supervision of a physician.

2harmacologyTopically applied sulfur is a keratolytic agent. Sulfur has keratoplastic activity at low concentrations, correcting

abnormal keratiniation, and keratolytic activity at high concentrations, causing peeling of skin& these effects

apparently result from the same action of the drug. <ollowing topical application of a #$ sulfur ointment 'nolonger commercially available in the US( on hairless mouse skin for a 3week period, there was increasing edema

during the first week, followed by thickening of the prickle cell layer. This reaction was ma!imal at * weeks and

resulted in nonadherent cells in the stratum corneum& these cells retained their nuclei. Bhen a *$ sulfur ointment'no longer commercially available in the US( was used, similar but more severe reactions occurred. A 3$

ointment 'no longer commercially available in the US( caused almost complete loss of the stratum corneum at 3

weeks, and intercellular and intracellular edema with resultant separation of epidermis from dermis. Thus, at lower

concentrations, sulfur causes epidermal in@ury which is followed by repair. Bhen sulfur concentrations greaterthan #$ are applied topically, in@ury e!ceeds the reparative process, and peeling 'keratolytic effect( occurs in

severity proportionate to the sulfur concentration. Although the mechanism of sulfurDs keratolytic action has not

 been determined, this action may depend on formation of hydrogen sulfide when the drug comes in contact withskin& the production of the characteristic odor of rotten eggs when sulfur comes in contact with skin results from

hydrogen sulfide formation. =ydrogen 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 and6or polythionic acid, which may e!ert germicidal activity.

In vitro studies indicate that sulfur has little if any fungistatic or fungicidal activity. Therefore, sulfurDs antifungal

activity probably results largely from its keratolytic action, causing shedding of fungal spores and hyphaeembedded 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 gramnegative bacteria. It has been suggested that the drugDs antibacterial activitymay partly result from inactivation of sulfhydryl groups contained in bacterial enyme systems, since the

antibacterial effect of the drug has reportedly been neutralied by addition of cysteine and other sulfhydryl

 

containing compounds to the culture medium. Topically applied sulfur is reportedly to!ic to the parasitic

arthropod Sarcoptes scabiei.The e!act mechanism's( of action of sulfur in the treatment of acne is not fully understood but is presumed to

involve the drugDs 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 consideredeffective in the topical treatment of acne.

Bhen administered orally, sulfur reportedly has a la!ative or cathartic effect.

2harmacokineticsThe absorption, distribution, and elimination of sulfur following topical application have not been fully

characteried. Topically applied sulfur reportedly penetrates the skin and is detectable in the epidermis within *

hours after application and throughout the skin within about ) hours& the drug is not detectable in skin *3 hours

after application. 2ercutaneous absorption of the drug into systemic circulation reportedly occurred followingtopical application of a *#$ sulfur ointment to abraded skin of animals but did not occur when the drug was

applied to intact skin.

"hemistry and Stability• "hemistry

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 'US2( forms of sulfur, precipitated sulfur and sublimed sulfur, of at least 77.#$ purity 'on an

anhydrous basis(, are used in topical preparations. 2recipitated 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, amorphousor 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. 2recipitated 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 precipitatedsulfur 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 sublimedsulfur. "ommercially available topical preparations also may contain sulfur in the form of colloidal sulfur or

washed sulfur. "olloidal sulfur contains the drug as a colloidal comple! in which minute particles of sulfur are

stabilied in an a;ueous medium containing a colloid such as egg albumin or gelatin. Bashed sulfur, made bywashing sublimed sulfur with ammoniated water, occurs as a fine, yellow, crystalline powder.

• Stability

2reparations containing sulfur may react with metals including silver and copper, resulting in discoloration of the

metal. 2reparations containing sulfur should be stored in wellclosed containers.

Preparations

"olloidal Sulfur 

2owder "olloidal Sulfur "ombinations

Topical

  "ream )$ with 5escorcinol *$ /ensulfoidE, 'with alcohol  -$( 2oythress

  Cotion #$ with 5esorcinol *$ SulforcinE, 'with S1 alcohol

  3 --.4#$( =ealthpoint

  Shampoo #$ with Salicylic Acid +$ 0etedE Improved,

en1erm

  0 *-%E 0edicated Tar<ree

 

  Shampoo, Triton

2recipitated Sulfur 

2owder 

Topical  "ake +$ SulfoCoE Soap, 0ed

  1erm

  #$ SulphoCacE 0edicated Soap,

1oak 

  -$ SAStidE Soap,Stiefel

  Sulfur Soap, Stiefel

  Cotion 3$ Ci;uimatE, 'with alcohol **$&

  light and medium shades(  Summers

  SulfoCoE, 0ed  1erm

2recipitated Sulfur "ombinations

Topical  "ake #$ with Salicylic Acid +$ Salicylic Acid and Sulfur Soap

  , Stiefel

  "ream )$ with 5esorcinol *$ AcnomelE, 'with alcohol --$ w

  6w( 0enley F Games

  Cotion *$ with /enoyl 2ero!ide #$ Sulfo!ylE Cotion 5egular,

'with propylene glycol(

  Stiefel

  #$ with /enoyl 2ero!ide -$ Sulfo!ylE Cotion Strong, 'with

  propylene glycol( Stiefel

  #$ with 5esorcinol *$ 5eamidE, 'with S1 alcohol 3

  *).#$( Summers

  #$ with Sulfacetamide Sodium :ovacetE,-$ en1erm

  Sodium Sulfacetamide and

  Sulfur Cotion, lades

  =ope

  Sulfacet5E, 'with parabens,

  propylene glycol, and inc  o!ide& regular and tintfree(

  1ermik 

 

Sublimed Sulfur 

2owder Topical

  "ream #$ SulphoCacE Acne 0edication,

1oak 

  Cotion *$ <ostrilE, 'with parabens(

  BestwoodS;uibb

  Shampoo *$ SulfoamE 0edicated

  Antidandruff, 1oak 

Sublimed Sulfur "ombinations

Topical

  "leansing *$ and Salicylic Acid -.#$ 2erno!E Scrub "leanser, 'lemon  Suspension and regular( BestwoodS;uibb

  "ream +$ with 5escorcinol *$ "learasilE Adult "areE,2rocter F amble

  Cotion *$ and Salicylic Acid -.#$ 2erno!E, Bestwood  S;uibb

  Shampoo *$ with "oal Tar .#$ and SebutoneE, 'cream or lotion(  Salicylic Acid *$ BestwoodS;uibb

  *$ with Salicylic Acid *$ Sebule!E, Bestwood  S;uibb

  Sebule!E with "onditioners,'with propylene glycol(

  BestwoodS;uibb