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Acne Vulgaris: A Guide to Diagnosis, Treatment, and Management

By Jacob Mathew, Jr. DO, FACOI, FACP, CHSE, FAWM

Unless otherwise stated, all treatments and doses are for adults and not weight based for the pediatric population.

Case Example:

acnevulgaris_129983.jpgA 21-year-old female presents to you because she is upset with her facial appearance. Since high school, she has suffered from acne but has not had medical insurance to get it taken care of. She has tried the most popular over-the-counter remedies without much success. She has finished college and plans to go into marketing, and she is concerned with her appearance. She is hoping you can help.


What is acne vulgaris, and how does it present?

Acne is defined as an inflammatory and obstructive disease affecting the pilosebaceous glands most commonly of the face. (Usatine, Bambekova, & Shiu) Initially caused by the overproduction of sebum (see potential causes below), keratin plugging develops and allows for the proliferation of Propionibacterium acnes, which then fully obstructs the follicles and causes reactant inflammation. (Toyoda & Morohashi, 2001) Contrary to prior belief, newer research suggests that follicular hyperproliferation does not occur. (Persson, et al., 2018)

How common is acne vulgaris?

In the dermatological field, acne is one of the three most common skin conditions experienced. (GM, 1998) The etiology of its increased prevalence remains unclear; however, a Western diet, earlier age of puberty (due to the well documented association between sex steroids and acne production), and other unknown environmental factors have been postulated risk factors. (Lynn, Umari, Dunnick, & Dellavalle, 2016) (Evgenia Makrantonaki, 2011) Young adults aged 12-25, males more so than females (especially with severe disease), make up the majority of patients, with no predilection for specific ethnicities. (Hay, Williams, & Johns, 2014) (Wilkins & Voorhees, 1970) While the majority of those affected are younger than 25 years, 3% of men's disease and 12% of women’s disease will persist well into adulthood. (Usatine, Bambekova, & Shiu)

Before assuming it's acne, what else could it be?

Acne Keloidalis Nuchae:

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Often seen in black patients; lesions localized to the posterior neck; initially papules and pustules that may progress to confluent keloids


Acneiform Eruptions:

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Secondary to systemic medicationstopical corticosteroid medications, contrast dye, and cosmetic products; may be abrupt in onset and correlate with exposure; improvement with cessation of exposure (see Table 2 for agents that cause drug-induced acne)


Bacterial Folliculitis:

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  • Non-Gram Negative: Erythematous papules and pustules that are follicular-based (look for hairs centrally located in the inflammatory papule); often affects the trunk and extremities
  • Gram Negative: Frequently occurs in patients with acne who have been on long-term antibiotic medications; pustules and nodules; may also occur in HIV-infected patients, and after hot tub exposure; lesions may be cultured if acneiform lesions do not respond to typical antibiotic regimen


Milia:

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White keratinaceous cysts; lesions are usually persistent; noninflammatory


Rosacea:

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Made up of two components: vascular and acneiform; various forms; background erythema with inflammatory, asymptomatic, dome-shaped papules and pustules often superimposed; environmental factors often can trigger, most commonly diagnosed in older adults rather than the characteristic 12- to 25-year-old population affected by acne.

 

Sebaceous Adenoma:

sebaceousadenoma_82303.jpg sebaceousadenoma_98335.jpg

Small, waxy papules over the medial cheeks, nose, and forehead; multiple lesions associated with tuberous sclerosis; skin biopsy test results show dermal fibrosis and vascular proliferation and dilatation (angiofibromas). Facial angiofibromas are also a feature of multiple endocrine neoplasia type I and, rarely, Birt-Hogg-Dubé syndrome.

 

I think it's acne; how do I diagnose it for sure?

acnevulgaris_32908.jpgHigh clinical suspicion as well as documented improvement with acne treatment help confirm the diagnosis. Biopsies and invasive procedures in general are not necessary unless diagnostic uncertainty exists. Lack of improvement with treatment should warrant re-evaluation of the diagnosis. (Al-Natour, 2012) Look for risk factors for acne production, such as using face products that occlude the pores, medications (see below), increased reported stress, dietary changes (with high glycemic indices), smoking exposure, occupational hazards (high sweat production with tight-fitting clothes), and obesity. For the primary care providers out there, ensure that you have ruled out Cushing syndrome in the right clinical setting. Furthermore, in women, hyperandrogenism suggestive of polycystic ovarian syndrome may present as a woman concerned about acne (typically, they will have concurrent hirsutism and menstrual irregularities). (Oon, et al., 2019)

 When it comes to treating acne vulgaris, where do I start?

Before initiating treatment, we need to make sure the acne is not caused by a medication or supplement that the patient is taking, known as drug-induced acne. (Kazandjieva Jana, 2017) (Al-Natour, 2012) Be suspicious when your patient presents with sudden onset eruptions at an older age (older than 25 years), appearing on the face or neck or unusual locations in the setting of recent new medication use that is resistant to typical acne treatments. A helpful distinction is that patients with drug-induced acne will not have comedones and will complain of pruritus. (Al-Natour, 2012) In women, common culprits include hormonal contraceptives. In all genders, be aware of these medications that can cause acne: steroids, lithium, and TNF-alpha inhibitors, among others.  (Kazandjieva Jana, 2017)

For the most part, first-line acne treatments have not changed in the past few years; however, there are a plethora of adjunctive treatments now available. Acne treatment is based on severity and type. For the purposes of this article, we are assuming you have made a diagnosis of acne vulgaris.

When initiating treatment, it’s important to be able to characterize the severity of the disease. Characterized as either mild, moderate, or severe, the grading system does vary based on what clinical trial you are referencing; however, without delving into the minutia, in general, quantitative measurements looking at lesion counts and the types of lesions help determine the severity of disease. By grading the disease severity, you can then determine how aggressive you want to be with treatment. For example, the comprehensive acne severity scale (CASS) grades the severity of acne from 0-5, with 0 representing clear skin with no or barely noticeable comedones and papules and 5 representing very severe, highly inflammatory acne (see Table below).

In general, no matter the severity, if using a topical medication, cream and other non-alcohol-based types are advised for better absorption.

 

Comprehensive acne severity scale of the face, chest, and back (Tan, et al., 2007)      
Grade 
Appearance 
Description

0

Clear

No lesions, or they are barely noticeable

1

Almost Clear

Hard to visualize from a short distance; few scattered comedones, pustules, and papules

2

Mild

Easily recognizable comedones, papules, and pustules, but <1/2 of the area is involved 

3

Moderate

> 1/2 of the area is involved with comedones, papules, and pustules

4

Severe

The entire area is involved, with scant nodules and cysts present

5

Very Severe

Severe inflammation with multiple nodules and cysts present

 

Grade 0-2 acne can be treated with topical therapies such as antimicrobial agents targeting P acnes. Monotherapy is not advised, given both the increasing prevalence of antibiotic resistance as well as decreased effectiveness compared to combination therapy.

acnevulgaris_6190.jpgAlternatives to topical antimicrobials include benzoyl peroxide, salicylic acid, dermocosmetics, and topical retinoids. Benzoyl peroxide is available over the counter and comes in different formulations; 2.5%-5% are the most commonly prescribed; 10% is likely to cause irritation without much benefit. (Usatine, Bambekova, & Shiu) Topical retinoids include tretinoin (Retin-A; gel, cream, liquid), adapalene gel (Differin), and tazarotene (Tazarac 0.1%). Adapalene is less irritating than tretinoin and is available over the counter (which would be beneficial in our patient without insurance). While tazarotene is the strongest of the retinoids, it also is the most associated with irritation, which may limit patient compliance. Retinoids are utilized with either comedonal or inflammatory acne as well as in maintenance for treated acne. Azelaic acid is helpful in treating postinflammatory hyperpigmentation. (Usatine, Bambekova, & Shiu)

If topical therapy is not enough, oral medications can be considered; however, they should never be used in combination. Oral antibiotics, such as doxycycline 100-200 mg/d, tetracyline 500-1000 mg/d, and erythromycin 250-500 mg/twice a day, are considered first line. Bactrim double strength has also been used previously; however, its association with Stevens-Johnson syndrome has limited its use, as safer alternative antibiotics exist. Typically, antibiotics require at least 6 weeks before effects are seen but are not prescribed for longer than 3-4 months at a time. If a pulse style of prescribing is desired, azithromycin can be considered, as it has not been found to be inferior to longer course doxycycline. Azithromycin is commonly prescribed at 500 mg daily for 4 days each month. (Parsad D, 2001) (Naieni FF, 2006) This is a great option if patient compliance is a concern, and the pulse dose cost is less than longer term antibiotic regimens. Those who are pregnant can safely take erythromycin but should avoid this if they have concurrent seizure or bipolar disorder (on carbamazepine). Doxycycline is a good option in patients with chronic kidney disease but not in those who have dysphagia or burn easily with sun exposure. Avoid tetracycline if renal or liver disease is present in your patient. 

Women with moderate-to-severe papulopustular acne, hyperandrogenism, or need for contraception, and those already on topical or systemic therapies, may benefit from consideration of combined oral contraceptives. In comparison to the oral antibiotics above, oral contraceptives have similar efficacy in reducing lesions after 6 months of treatment. Given the limited duration of treatment with antibiotics, patients requesting a prolonged treatment option may benefit from contraceptives. Medications containing levonorgestrel (Microgynon) and drospirenone (Yaz, Yasmin) have been found to be effective in both inflammatory and noninflammatory acne. Those containing cyproterone may not be more effective than those without. Typically starting on the first day of the menstrual cycle, patients will take the medication for 21 days straight, with a 7-day free period, then repeat this cycle for 6-12 months. As with any oral contraceptive, avoid prescribing in women who smoke, are postpartum, have uncontrolled hypertension, have history of deep venous thromboses or pulmonary emboli, or have migraines with auras, among others. 

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If severe nodulocystic acne is present and oral antibiotics have failed, or scarring is present, a referral toa dermatologist is advised. Prior to referral, liver function tests and a lipid panel should be checked. These patients may be candidates for systemic isotretinoin. It is typically prescribed in 6-month periods; pulse dosing, while previously done, is no longer utilized. Pregnancy is absolutely contraindicated while on this medication due to the high occurrence of teratogenic events. A pledge application is required for all patients on systemic isotretinoin.

Other than medications, adjunctive treatments such as chemical peels (40% glycolic acid), topical 5-aminolevulinic acid, and phototherapy with blue or red light have been studied with varying success rates. Chemical peels have limited supporting trials in treating moderate acne; more research is advised before I would considering this for your patient. Light treatments involving 5-aminosalicylic acid and phototherapies such as intense pulsed light can help with inflammatory lesions and scarring. Those with alternating red- and blue-light LEDs may decrease inflammatory lesions.

 

Acne Vulgaris Treatment Classes With Examples

Benzoyl Peroxide

  • Benzoyl peroxide 2.5%, 5%, 10%* as lotion, gel, cream, wash
  • *10% is not advised, as it has not been found to be any more efficacious than 5%

Retinoids

  • Tretinoin 0.025%
  • Isotretinoin by mouth 10 mg, 40 mg
  • Adapalene 0.1%
  • Alitretinoin 0.1%
  • Tazarotene 0.05%, 0.1%

Topical Antibiotics

  • 1% / 2% clindamycin
  • 1% / 2% / 3% erythromycin
  • 5% / 7% dapsone

Oral Antibiotics

  • Doxycycline 50 mg / 100 mg daily or twice a day
  • Tetracycline 500-1000 mg / day
  • Erythromycin 500 mg twice a day


Commonly Studied Acne Vulgaris Treatment Combinations (Gold, 2010)

Benzoyl Peroxide plus Retinoid

  • Epiduo® gel (benzoyl peroxide + adapalene)

Benzoyl Peroxide plus Topical Antibiotic

  • Duac® or BenzaClin (benzoyl peroxide 5% plus clindamycin 1%)
  • Benzoyl peroxide 2.5% plus adapalene 0.1% (may be better tolerated than benzoyl peroxide 5%)
  • Benzamycin (benzoyl peroxide 5% plus erythromycin 3%)

Topical Antibiotic plus Retinoid

  • Clindamycin 1% plus tretinoin 0.025%
  • Clindamycin 1% plus adapalene gel 0.1%
  • Erythromycin 4% plus tretinoin 0.025%

 

 Acne Vulgaris Management (Papadakis MA, 2020)       

Bullets are not ordered by recommendation. 

Primary treatments are recommended by the American Dermatologic Association as initial treatment for that severity class. 

Severity Treatment

Mild Comedones

(stick with topical retinoids, adapalene, and tazarotene)

Primary:

  • Topical tretinoin 0.025% cream (pea-sized) twice a week at bedtime (notify patients that lesions may flare in the first 4 weeks of treatment)
  • Topical benzoyl peroxide (2.5%, 5%)
  • Topical combination of:
    • Benzoyl peroxide plus antibiotics
    • Tretinoin plus benzoyl peroxide
    • Tretinoin plus benzoyl peroxide plus antibiotics

Alternative:

  • Can add either benzoyl peroxide or  tretinoin if not done previously
  • Consider azelaic acid
  • Consider topical adapalene 0.1% gel
  • Consider tazarotene 0.05%-0.1% gel

Mild Papulopustules

(topical antibiotics are helpful when pustules are present). Combination topical antibiotics with retinoids are more effective than monotherapy in mild to moderate acne.

Topical clindamycin (Cleocin T; solution, gel) or erythromycin (solution, gel) used twice a day with benzoyl peroxide added with morning application. Add tretinoin 0.025% cream or 0.01% gel at bedtime to increase efficacy.

Others:

  • Adapalene plus benzoyl peroxide (available as single formulation)
  • Antibiotics plus benzoyl peroxide plus topical retinoid / azelaic acid
  • Topical retinoid plus benzoyl peroxide
**Combination benzoyl peroxide and clindamycin is dispensed as BenzaClin gel; combination benzoyl peroxide and erythromycin is dispensed as Benzamycin (1% clindamycin or 3% erythromycin respectively, each with 5% benzoyl peroxide)

 

Moderate Papulopustules

(antibiotics, typically oral, are the mainstay)

Primary

Topicals Only:

  • Benzoyl peroxide plus topical antibiotic
  • Benzoyl peroxide plus topical retinoid
  • Benzoyl peroxide plus topical retinoid plus topical antibiotic
  • Oral antibiotic plus topical retinoid plus benzoyl peroxide
  • Oral antibiotic plus topical retinoid plus benzoyl peroxide plus topical antibiotic

Topicals and Orals:

  • Oral antibiotic plus topical adapalene plus benzoyl peroxide
  • Oral antibiotic plus topical adapalene plus benzoyl peroxide
The addition of a topical retinoid and benzoyl peroxide helps decrease antibiotic  resistance when combined with an oral antibiotic. In these situations, continue using the topical therapy until the skin is clear, then taper the oral antibiotic by 50% every 6-8 weeks while maintaining topical retinoid application (for long-term maintenance)


Alternative

Oral antibiotic plus topical azelaic acid plus benzoyl peroxide

Female patients:

  • Oral anti-androgen plus topical retinoid
  • Azelaic acid plus or minus benzoyl peroxide

Very Severe Nodulocysts

Oral isotretinoin 0.5-1 mg/kg/d for 20 weeks

Should be prescribed by a dermatologist, not primary care; contraindicated with current or planned pregnancy.

 

Adjuvant Treatment Options

Cleansers

  • Use gentle soap-free types when possible
  • Twice a day is adequate for most patients

Moisturizers

  • Provide hydration
  • Those specific for acne can be used without causing comedones to form

Comedolytics

  • Improve skin texture and can reduce inflammation

Sunscreen

  • Use oil-free types; daily use is recommended


So, how will we treat this patient?

After confirming the diagnosis of acne based on physical exam, if the patient is not considering oral contraceptives, which may be helpful in treating and controlling acne, I would start with oral antibiotic therapy (assuming her appearance on exam is consistent with moderate papulopustules), prescribing doxycycline 100 mg a day (less frequent dosing may lead to better patient compliance) combined with a topical retinoid (Retin-A) and benzoyl peroxide.


References

Burris, K. (n.d.). Molluscum Contagiosum. Retrieved from DynaMed: https://www.dynamed.com/condition/molluscum-contagiosum

Cong, T.-X., Wen, X., Li, X.-H., He, G., & Jian, X. (2019). From Pathogenesis of Acne Vulgaris to Anti-Acne Agents. Arch Dermatol Res, 337-349.

Ely John W, R. S. (2014). Diagnosis and Management of Tinea Infections. Am Fam Physician, 702-710.

Evgenia Makrantonaki, R. G. (2011). An update on the role of the sebaceous gland in the pathogenesis of acne. Dermato-Endocrinology, 41-49.

Gehris, R. P. (2018). Dermatology. In B. J. Zitelli, S. C. McIntire, & A. J. Nowalk, Zitelli and Davis' Atlas of Pediatric Physical Diagnosis (pp. 275-330).

GM, W. (1998). Recent findings in the epidemiologic evidence, classification, and subtypes of acne vulgaris. J Am Acad Dermatol., S34-37.

Gold, L. S. (2010). Fixed-Combination Products in the Management of Acne Vulgaris. Cutis, 160-167.

Hay, R., Williams, H., & Johns, N. (2014). The global burden of skin disease in 2010: an analysis of the prevalence and impact of skin conditions. J Invest Dermatol., 1527–1534.

Johnson, J. (2016, May). Skin Infections in Athletes. Retrieved from OrthoInfo.

Kazandjieva Jana, T. N. (2017). Drug-induced Acne. Clin Dermatol, 156-162.

Likeness, L. (2011). Common Dermatologic Infections in Athletes and Return-to-Play Guidelines. The Journal of the American Osteopathic Association, 373-379.Lynn, D. D., Umari, T., Dunnick, C. A., & Dellavalle, R. P. (2016). The epidemiology of acne vulgaris in late adolescence. Adolescent Health, Medicine and Therapeutics.

Naieni FF, A. H. (2006). Comparison of three different regimens of oral azithromycin in the treatment of acne vulgaris. . Indian J Dermatol, 255-7.

Oon, H., Wong, S.-N., Wee, D., Cheon, W., Goh, C., & Tan, H. (2019). Acne Management Guidelines by the Dermatological Society of Singapore. J Clin Aesthet Dermatol, 34-50.

Papadakis MA, M. S. (2020 ). Acne Vulgaris. In Quick Medical Diagnosis & Treatment. New York, NY: McGraw-Hill.

Parsad D, P. R. (2001). Azithromycin monthly pulse vs daily doxycycline in the treatment of acne vulgaris. J Dermatol., 1-4.

Persson, G., Johansson-Jankanpaa, E., Ganceviciene, R., Karadag, A. S., Bilgili, S. G., Omer, H., & Alexeyev, O. A. (2018). No evidence for follicular keratinocyte hyperproliferation in acne lesions as compared to autologous healthy hair follicles. Exp Dermatol, 668-671.

Sahoo, A. K., & Mahajan, R. (2016). Management of tinea corporis, tinea cruris, and tinea pedis: A comprehensive review. Indian Dermatol Online J., 77-86.

Tan AU, S. B. (2018). A review of diagnosis and treatment of acne in adult female patients. Int J Womens Dermatol, 56-71.

Tan, J. K., Tang, J., Fung, K., Gupta, A. K., Thomas, D., Sapra, S., . . . Sebalt, R. J. (2007). Development and Validation of a Comprehensive Acne Severity Scale. Journal of Cutaneous Medicine and Surgery, 211-216.

Taplin D, M. T. (1990). Comparison of crotamiton 10% cream (Eurax) and permethrin 5% cream (Elimite) for the treatment of scabies in children. Pediatr Dermatol. .

Toyoda, M., & Morohashi, M. (2001). Pathogenesis of acne. Med Electron Microsc, 29-40.

Usatine, R. P., Bambekova, G. P., & Shiu, V. F. (n.d.). Chapter 118: Acne Vulgaris . In S. M. Usatine RP, The Color Atlas and Synopsis of Family Medicine. New York, New York.

Wilkins, J., & Voorhees, J. (1970). Prevalence of nodulocystic acne in white and Negro males. Arch Dermatol., 631-634. 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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