- Impact of Long-Term Antibiotic Use for Acne on Bacterial Ecology and Health Outcomes: A Review of Observational Studies
- Antimicrobial Resistance
- Acne Alternative Remedies: Manuka Honey, Tea Tree Oil, Zinc, Yeast, and More
- Skin conditions by the numbers
- Acne Vulgaris Treatment & Management: Medical Care, Surgical Care, Consultations
- 10 Potential Natural Remedies for Acne + Risk Factors and Conventional Treatments
- Why Does Acne Form?
- Who is at Risk for Acne?
- Treatments for Acne
- Research on Complementary Treatments
- 1) Fish Oil
- 2) Alpha Hydroxy Acids (AHAs)
- 3) Zinc
- 4) Tea Tree Oil
- 5) Probiotics
- 6) Aloe Vera
- 7) Guggul
- 8) Green Tea
- 9) Resveratrol
- 10) Honey
Impact of Long-Term Antibiotic Use for Acne on Bacterial Ecology and Health Outcomes: A Review of Observational Studies
Acne is among the most common cutaneous disorder affecting most individuals by the time they reach adulthood. Management of acne can be quite a challenge and includes medications with significant side effects. We discuss the potential side effects of long-term antibiotic use. These side effects should be carefully weighed and monitored when designing a treatment plan.
Acne vulgaris is the most common cutaneous disorder affecting humans. This disorder most often affects the adolescent population. It typically resolves by adulthood; however, it may also start during adulthood. It is estimated that acne affects between 35% and 90% of adolescents.
In adolescence, acne has a male predominance, although adult onset acne has a female predominance. Despite being a nonfatal disease, the psychological ramifications of the condition lead to emotional distress .Optimizing the treatment for acne continues to be a challenge, especially given the potential side effects of the typical regimens .
This article focuses on the potential consequences of long-term antibiotic use.
Propionibacterium acnes (P. acnes), the microbe that resides and can be abundant in the pilosebaceous unit, is associated with the severity of acne. P. acnes is an anaerobic organism that is part of the normal skin flora .
Obstruction of the follicular opening of the pilosebaceous unit provides an ideal environment for these bacteria to grow. Obstruction of the follicular opening is associated with the inflammatory component of acne through various suggested mechanisms. P. acnes can metabolize sebaceous triglycerides into fatty acids.
P. acnes, along with sebum and keratin, generate proinflammatory mediators that recruit T lymphocytes, neutrophils, and foreign body giant cells .
It activates TLR2 (toll- receptor 2) on monocytes and neutrophils, which activates the innate immunity pathway, generating proinflammatory cytokines including interleukin-12 (IL-12), interleukin-8 (IL-8), and tumor necrosis factor (TNF) [4, 5].
Antibiotics are used in acne for both the eradication of P. acnes and for their anti-inflammatory properties. The antibiotics used in the management of acne include both topical and systemic forms. The topical agents are generally clindamycin, erythromycin, dapsone, and sodium sulfacetamide.
Topical clindamycin and erythromycin are often used in combination with other agents, such as benzoyl peroxide, a non-antibiotic agent used for its antimicrobial properties . Oral options include macrolides, tetracyclines, trimethoprim-sulfamethoxazole and clindamycin.
However, the most commonly used oral antimicrobials to treat acne are the tetracyclines, which are the main focus of this article.
Tetracyclines are antibiotics that function through the inhibition of protein synthesis and have anti-inflammatory properties. These agents share similar diverse antibacterial spectrum against pathogens from families as diverse as Staphylococcus, Rickettsia, Chlamydia, Listeria, and Neisseria.
Drugs in this category include tetracycline, doxycycline, and minocycline. Doxycycline and tetracycline should be taken on an empty stomach because absorption is affected by food, dairy products, iron, and antacids. Minocycline is an exception, where its intake is not limited by the aforementioned agents.
Tetracyclines should not be given to pregnant women or those under the age of 9 years. Tetracyclines carry risk of reduced bone growth and discoloration of the permanent teeth. Lastly, these agents can be photosensitizing. It has been claimed that the most photosensitizing agent is doxycycline and the least is minocycline (http:www.
In the past 15 years, research has further elucidated additional consequences of long-term antibiotic use. Various observational studies have examined certain complications that can be seen in long-term antibiotic use that may not be directly related to bacterial resistance.
These studies describe increased infections, collagen vascular diseases, autoimmune diseases, and cancer. Observational studies by design cannot determine causation, only association.
However, it is important to realize that many adverse events of interest are uncommon and occur several years after exposure, making it impossible to understand their natural history or association with an exposure using a randomized clinical trial design.
In the remainder of this article, we highlight various studies that focus on each potential complication as a possible consequence of the use of antibiotics to treat acne.
Antimicrobial resistance is the result of excessive antibiotic use in the ambulatory setting . Even with proper use of antibiotics to treat acne vulgaris, resistance can occur. Patel et al.
 discussed the following factors that could influence the development of antibiotic resistance in patients with acne.
These include antibiotic monotherapy, long-term administration of antibiotics, indiscriminate use outside their indications, inappropriate dosing, and the administration of antibiotics without concurrent use of benzoyl peroxide or topical retinoids .
Change in antimicrobial resistance patterns is the most frequent effect of long-term antibiotic use. In terms of infectious outcomes, patients on long-term antibiotics for acne seem to have a higher incidence of upper respiratory tract infections. In 2005, Margolis et al.  performed a retrospective cohort study using the United Kingdom General Practice Research Database.
That database contains medical record information from general practitioners. The authors reviewed the data spanning from 1987 through 2002. Of the 84, 977 individuals, 71.7% required a topical or an oral antibiotic. During the first year of observation, 15.4% (18,281) of those individuals with acne suffered from at least one upper respiratory tract infection.
An association was found between patients with acne who were treated with antibiotics seeking medical care for upper respiratory tract infections as compared to those with acne who were not treated with antibiotics. Specifically, the odds of an upper respiratory tract infection developing in an individual with acne receiving antibiotics was 2.
15 times greater than in one who was not receiving antibiotics (P
Acne Alternative Remedies: Manuka Honey, Tea Tree Oil, Zinc, Yeast, and More
People with acne often turn to complementary or alternative treatments. These may include gels, creams, and lotions; dietary supplements and herbs; and special dietary routines.
Many people swear by alternative acne treatments. But the American Academy of Dermatology (AAD) says that “all-natural supplements” have not been shown to be effective, and some may even be harmful.
For example, the group cites an over-the-counter (OTC) acne supplement that contained more than 200 times the amount of selenium stated on the label. It caused a wide range of toxic reactions.
The AAD also states that there is emerging research that suggests that high glycemic index diets (those high in processed carbs and sugar) and dairy (particularly skim milk) may be associated with acne.
Alternative acne treatments haven't been well-studied. Therefore, sources such as the Natural Medicines Comprehensive Database typically offer only tepid recommendations.
For instance, oral zinc supplements are rated as only “possibly effective.” The same is true for topical preparations that contain zinc.
Until there is better research, it's impossible to say which alternative acne treatments work and which ones don't.
Conventional acne treatments don't always work for everyone. They can also cause side effects ranging from skin irritation to birth defects.
Another concern, since antibiotics are used in so many conventional acne treatments, is antibiotic resistance. A study in the U.K.
reported that more than one every two acne patients treated with antibiotics carried resistant strains of two different bacteria often found on the skin.
Proponents of alternative treatments point out that acne is unknown in so-called “Stone Age” societies. On the other hand, it affects up to 95% of adolescents in industrialized societies. This suggests, they say, that a Western diet may be a major factor in the development of acne.
Hundreds of alternative treatments for acne are promoted on the Internet and elsewhere as being safe and effective. Alternative treatments, though, do not need to be tested and shown to be safe before they are sold online or placed on store shelves in the U.S. So, be sure to discuss the pros and cons of any alternative remedy with your doctor or dermatologist before starting treatment.
Research is not conclusive, but some preliminary studies suggest that the following alternative acne treatments might offer some benefits.
Manuka honey comes from New Zealand where the manuka bush is indigenous. So-called “active” manuka honey is widely promoted on the Internet as an acne remedy. The claim is mostly studies that suggest it has significant antibacterial and wound-healing properties.
In one study, researchers observed that honey-impregnated wound dressings have gained increasing acceptance in hospitals and clinics worldwide. But they also pointed out it's unclear how they work. So they investigated the ability of three different types of honey to quench the production of free radicals. In their report, they stated that manuka honey was the most effective.
On the Internet, patient testimonials about manuka honey's effects on acne range from glowing to dismissive. To date, however, there have been no definitive studies to prove or disprove the effectiveness of manuka honey.
Tea tree oil is an essential oil extracted from the leaves of a small tree native to Australia. It has long been touted as a safe and effective alternative treatment for acne. In 1990, researchers studied 124 acne patients. Some were treated with 5% tea tree oil in a water-based gel. Others were treated with 5% benzoyl peroxide, an ingredient found in many over-the-counter acne remedies.
This widely-cited study reported that tea tree oil did not work as quickly as benzoyl peroxide. But, the researchers said, its use resulted in a similar reduction in acne lesions after three months. They also reported a significantly lower incidence of side effects such as dryness, irritation, itching, and burning.
Topical treatment with tea tree oil is considered safe for most adults. It may, though, trigger an allergic skin reaction in some people. This is especially true if it has oxidized after exposure to air. Tea tree oil should never be taken orally. It can cause toxic reactions ranging from rash to coma.
Some practitioners of alternative and complementary medicine recommend topical treatments containing tannins or fruit acids.
Tannins have natural astringent properties. They can be gotten by boiling a mixture of 5 to 10 grams of extract of bark from such trees as witch hazel, white oak, or English walnut in one cup of water. Commercial preparations, though, are not recommended. The distillation process removes the tannins.
Fruit acids include citric, gluconic, gluconolactone, glycolic,malic, and tartaric acids. These have natural properties that help them remove skin.
Other practitioners recommend treatments which have been approved by the German Commission E. The German Commission E is a European agency that studies herbal remedies. These include oral acne treatments such as:
- Vitex, a whole-fruit extract for treating premenstrual acne. It's thought to act on follicle-stimulating hormone and luteinizing hormone levels in the pituitary. It's said to increase progesterone levels and reduce estrogen levels. Vitex should not be taken by pregnant or nursing women.
- Brewer's yeast, which has antimicrobial effects.
These practitioners also recommend topical bittersweet nightshade, which also has antimicrobial effects.
SkinCarePhysicians.com: “The Naked Truth About Natural Acne Treatments.”
Bedi, M. Archives of Dermatology, 2002.
Yarnell, E. Alternative and Complementary Therapies, December 2006.
NCCAM: “Tea Tree Oil.”
Honey Research Unit of the University of Waikato.
Henriques, A. Journal of Antimicrobial Chemotherapy, October 2006.
Del Rosso, J. Journal of Clinical Aesthetic Dermatology, August 2009.
Shalita, A. International Journal of Dermatology, June 1995.
Medline Plus Drug Information: “Azelaic Acid Topical.”
The Gale Encyclopedia of Alternative Medicine, 3rd ed., Laurie Fundukian, ed., Gale, 2009.
© 2020 WebMD, LLC. All rights reserved. Phototherapy
Skin conditions by the numbers
- Acne is the most common skin condition in the United States, affecting up to 50 million Americans annually.1
- Acne usually begins in puberty and affects many adolescents and young adults.
- Approximately 85 percent of people between the ages of 12 and 24 experience at least minor acne.2
Acne can occur at any stage of life and may continue into one’s 30s and 40s.3-5
- Acne occurring in adults is increasing, affecting up to 15 percent of women.3-5
In 2013, the costs associated with the treatment and lost productivity among those who sought medical care for acne exceeded $1.2 billion.6
- More than 5.1 million people sought medical treatment for acne in 2013, primarily children and young adults.6
- The lost productivity among patients and caregivers due to acne was nearly $400 million.6
- One in 10 people will develop atopic dermatitis during their lifetime.7
- It affects up to 25 percent of children and 2 to 3 percent of adults.8
- An estimated 60 percent of people with this condition develop it in their first year of life, and 90 percent develop it before age 5. However, atopic dermatitis can begin during puberty or later.8-9
- In 2013, the costs associated with the treatment and lost productivity among those who sought medical care for atopic dermatitis was $442 million.6
- The total medical cost of treating atopic dermatitis was $314 million, for an average of $101.42 per treated patient.6
- The lost productivity among patients and caregivers due to atopic dermatitis was $128 million.6
- The most common cause of hair loss is hereditary thinning or baldness, also known as androgenetic alopecia.10
- This condition affects an estimated 80 million Americans — 50 million men and 30 million women.11
- Other Potential causes of hair loss, some of which are temporary, include:
- Excessive or improper use of styling products such as perms, dyes, gels, relaxers or sprays, which can cause weathering or hair breakage.
- Hairstyles that pull on the hair, ponytails and braids.
- Shampooing, combing or brushing hair too much or too hard
- Hair pulling, which may be a sign of a disorder called trichotillomania.
- A variety of diseases, including thyroid disease and lupus.
- Childbirth, major surgery, high fever or severe infection, stress, or even the flu.
- Inadequate protein or iron in the diet, or eating disorders such as anorexia and bulimia.
- Certain prescription drugs, including blood thinners, high-dose vitamin A, and medicines for arthritis, depression, gout, heart problems and high blood pressure.
- Use of birth control pills (usually in women with an inherited tendency for hair thinning).
- Hormonal imbalances, especially in women.
- Ringworm of the scalp, a contagious fungal infection most common in children.
- Some cancer treatments, such as radiation therapy and chemotherapy.
- Alopecia areata, a type of hair loss that can affect all ages and causes hair to fall out in round patches.12
- Approximately 7.5 million people in the United States have psoriasis.13
- Psoriasis occurs in all age groups but is primarily seen in adults, with the highest proportion between ages 45 and 64.6
- Approximately 25-30 percent of people with psoriasis experience joint inflammation that produces symptoms of arthritis. This condition is called psoriatic arthritis.14-16
- Approximately 80 percent of those affected with psoriasis have mild to moderate disease, while 20 percent have moderate to severe psoriasis affecting more than 5 percent of the body surface area.13
- The most common form of psoriasis, affecting about 80 to 90 percent of psoriasis patients, is plaque psoriasis. It is characterized by patches of raised, reddish skin covered with silvery-white scale.13
- In 2013, the total direct cost of treatment associated with psoriasis was estimated to be between $51.7 billion and $63.2 billion.6
- Rosacea is a common skin disease that affects 16 million Americans.17-19
- While people of all ages and races can develop rosacea, it is most common in the following groups:
- People between age 30 and 60.20
- Individuals with fair skin, blond hair and blue eyes.20-21
- Women, especially during menopause.20
- Those with a family history of rosacea.21
In 2013, the costs associated with the treatment and lost productivity among those who sought medical care for rosacea was $243 million.6
- More than 1.6 million people sought treatment for rosacea in 2013.6
- The total medical cost of treating rosacea was $165 million, for an average of $102.26 per treated patient.6
- The lost productivity among patients and caregivers due to rosacea was $78 million.6
- Skin cancer is the most common cancer in the United States.22-23
- It is estimated that more than 9,500 people in the U.S. are diagnosed with skin cancer every day.24-26
- The majority of diagnosed skin cancers are NMSCs. Research estimates that NSMC affects more than 3 million Americans a year.6, 24
- The overall incidence of BCC increased by 145 percent between 1976-1984 and 2000-2010, and the overall incidence of SCC increased 263 percent over that same period.27
- Women had the greatest increase in incidence rates for both types of NMSC.27
- NMSC incidence rates are increasing in people younger than 40.27
More than 1 million Americans are living with melanoma.28
It is estimated that 192,310 new cases of melanoma, 95,830 noninvasive (in situ) and 96,480 invasive, will be diagnosed in the U.S. in 2019.25-26
- Invasive melanoma is projected to be the fifth most common cancer for both men (57,220 cases) and women (39,260 cases) in 2019.25-26
Melanoma rates in the United States doubled from 1982 to 2011 and have continued to increase.23, 26
Caucasians and men older than 50 have an increased risk of developing melanoma compared to the general population.25-26
Melanoma is the second most common form of cancer in females age 15-29.29
- Melanoma incidence is increasing faster in females age 15-29 than in males of the same age group.30
Skin cancer can affect anyone, regardless of skin color.
- Skin cancer in patients with skin of color is often diagnosed in its later stages, when it’s more difficult to treat.31
- Research has shown that patients with skin of color are less ly than Caucasian patients to survive melanoma.32
People with skin of color are prone to skin cancer in areas that aren’t commonly exposed to the sun, the palms of the hands, the soles of the feet, the groin and the inside of the mouth. They also may develop melanoma under their nails.31
- Skin cancer in patients with skin of color is often diagnosed in its later stages, when it’s more difficult to treat.31
Nearly 20 Americans die from melanoma every day. In 2019, it is estimated that 7,230 deaths will be attributed to melanoma — 4,740 men and 2,490 women.25-26
The five-year survival rate for people whose melanoma is detected and treated before it spreads to the lymph nodes is 98 percent.25-26
The five-year survival rate for melanoma that spreads to nearby lymph nodes is 64 percent. The five-year survival rate for melanoma that spreads to distant lymph nodes and other organs is 23 percent.25-26, 30
The annual cost of treating skin cancers in the U.S. is estimated at $8.1 billion — about $4.8 billion for NMSC and $3.3 billion for melanoma.22
Want to know what dermatologists tell their patients about managing conditions that affect the skin, hair, or nails? You’ll find their expertise and insight in Diseases & conditions.
1Bickers DR, Lim HW, Margolis D, Weinstock MA, Goodman C, Faulkner E et al. The burden of skin diseases: 2004 a joint project of the American Academy of Dermatology Association and the Society for Investigative Dermatology. Journal of the American Academy of Dermatology 2006;55:490-500.
2Bhate K, Williams HC. Epidemiology of acne vulgaris. The British journal of dermatology 2013;168:474-85.
3Holzmann R , Shakery K. Postadolescent acne in females. Skin pharmacology and physiology 2014;27 Suppl 1:3-8.
4Khunger N , Kumar C. A clinico-epidemiological study of adult acne: is it different from adolescent acne? Indian journal of dermatology, venereology and leprology 2012;78:335-41.
5Tanghetti EA, Kawata AK, Daniels SR, Yeomans K, Burk CT , Callender VD. Understanding the Burden of Adult Female Acne. The Journal of Clinical and Aesthetic Dermatology 2014;7:22-30.
6American Academy of Dermatology/Milliman. Burden of Skin Disease. 2017. www.aad.org/BSD.
7Abuabara K, Magyari A, McCulloch CE, Linos E, Margolis DJ, Langan SM. Prevalence of Atopic Eczema Among Patients Seen in Primary Care: Data From The Health Improvement Network. Ann Intern Med. 2018. [Epub ahead of print ] doi: 10.7326/M18-2246.
8Eichenfield LF, Tom WL, Chamlin SL, Feldman SR, Hanifin JM, Simpson EL, et al. Guidelines of care for the management of atopic dermatitis: section 1. Diagnosis and assessment of atopic dermatitis. J Am Acad Dermatol. 2014 Feb;70(2):338-51.
9Beltrani VS, Boguneiwicz M. Atopic dermatitis. Dermatol Online J 2003;9(2):1.
10Rossi A, Anzalone A, Fortuna MC, Caro G, Garelli V, Pranteda G et al. Multi-therapies in androgenetic alopecia: review and clinical experiences. Dermatologic therapy 2016;29:424-32.
11Genetics Home Reference. National Institutes of Health U.S. Library of Medicine. https://ghr.nlm.nih.gov/condition/androgenetic-alopecia#statistics. Accessed March 30, 2018.
12Dainichi T , Kabashima K. Alopecia areata: What's new in epidemiology, pathogenesis, diagnosis, and therapeutic options? Journal of dermatological science 2017;86:3-12.
13Menter A, Gottlieb A, Feldman SR, Van Voorhees AS et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 1. Overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics. J Am Acad Dermatol 2008 May;58(5):826-50.
14Ranza R et al. Prevalence of psoriatic arthritis in a large cohort of Brazilian patients with psoriasis. J Rheumatol. 2015 May;42(5):829-34. doi: 10.3899/jrheum.140474
Acne Vulgaris Treatment & Management: Medical Care, Surgical Care, Consultations
Treatment should be directed toward the known pathogenic factors involved in acne. These include follicular hyperproliferation, excess sebum, Cutibacterium acnes (formerly Propionibacterium acnes) infection, and inflammation. The grade and severity of the acne help in determining which of the following treatments, alone or in combination, is most appropriate.
Current consensus recommends a combination of topical retinoid and antimicrobial therapy as first-line therapy for almost all patients with acne.
 The superior efficacy of this combination, compared with either monotherapy, results from complementary mechanisms of action targeting different pathogenic factors.
Retinoids reduce abnormal desquamation, are comedolytic, and have some anti-inflammatory effects, whereas benzoyl peroxide is antimicrobial with some keratolytic effects and antibiotics have anti-inflammatory and antimicrobial effects. 
Note the images below.
Acne with reactive hyperpigmentation; before treatment. Acne with reactive hyperpigmentation; after treatment.
Topical retinoids are comedolytic and anti-inflammatory. They normalize follicular hyperproliferation and hyperkeratinization.
Topical retinoids reduce the numbers of microcomedones, comedones, and inflammatory lesions.
 Topical retinoids should be initiated as first-line therapy for both comedonal and inflammatory acne lesions and continued as maintenance therapy to inhibit further microcomedone formation. 
The most commonly prescribed topical retinoids for acne vulgaris include adapalene, tazarotene, and tretinoin. These retinoids should be applied once daily to clean, dry skin, but they may need to be applied less frequently if irritation occurs.
Skin irritation with peeling and redness may be associated with the early use of topical retinoids and typically resolves within the first few weeks of use.  The use of mild, nonirritating cleansers and noncomedogenic moisturizers may help reduce this irritation.
 Alternate-day dosing may be used if irritation persists.
Topical retinoids thin the stratum corneum, and they have been associated with sun sensitivity.  Instruct patients about sun protection. Also see Sunscreens and Photoprotection.
Topical antibiotics are mainly used for their role against C acnes (formerly P acnes). They may also have anti-inflammatory properties. Topical antibiotics are not comedolytic, and bacterial resistance may develop to any of these agents. Commonly prescribed topical antibiotics for acne vulgaris include clindamycin, erythromycin, and, more recently, dapsone and minocycline.
Topical dapsone is a new sulfone antibiotic with anti-inflammatory properties that has been shown to be effective for mild-to-moderate acne, and it has a convenient once-daily application schedule.  It is available as 5% twice-daily and 7.5% once-daily formulations.
 The current American Academy of Dermatology guidelines preceded the FDA approval of the 7.5% formulation. Although no research has compared the efficacy of the 5% formulation with the 7.5% formulation, both have been separately shown to be efficacious and safe. The 7.
5% formulation has the additional compliance factor of once-daily application. [33, 38]
Minocycline topical foam 4% was evaluated in three 12-week phase 3 trials (n=2418) in patients aged 9 years or older. Each study demonstrated statistically significant disease improvement with minocycline topical compared with vehicle for the coprimary endpoint of absolute reduction of inflammatory lesions and investigator assessment. [39, 40]
Antibiotic resistance in C acnes (formerly P acnes) is common and is a significant threat to acne treatment.  Antimicrobials should be combined with a topical retinoids for greater clearing of lesions and to increase the potential for shortened antibiotic treatment.
They should be used with benzoyl peroxide to reduce the lihood of resistance.  Concurrent use of oral and topical antibiotics should be avoided and should not be used as monotherapy. If acne relapses, use the same antibiotic if it was previously effective.
It may also be helpful to use benzoyl peroxide for 5-7 days between antibiotic courses to reduce resistance in organisms on the skin. 
Benzoyl peroxide products are also effective against C acnes (formerly P acnes), and bacterial resistance to benzoyl peroxide has not been reported.  Benzoyl peroxide products are available over the counter and by prescription in a variety of topical forms, including soaps, washes, lotions, creams, and gels.
Benzoyl peroxide products may be used once or twice a day. These agents may occasionally cause a true allergic contact dermatitis. More often, an irritant contact dermatitis develops, especially if used with tretinoin or when accompanied by aggressive washing methods.
 If intensive erythema and pruritus develop, a patch test with benzoyl peroxide is indicated to rule out allergic contact dermatitis.
Systemic antibiotics are a mainstay in the treatment of moderate-to-severe inflammatory acne vulgaris.
 These agents have anti-inflammatory properties, and they are effective against C acnes (formerly P acnes). The tetracycline group of antibiotics is commonly prescribed for acne.
The more lipophilic antibiotics, such as doxycycline and minocycline, are generally more effective than tetracycline. 
Sarecycline is a new first-in-class tetracycline-derived antibiotic indicated for adults and children aged 9 years and older with non-nodular moderate-to-severe acne vulgaris.
Compared with currently available tetracyclines, it has a narrow spectrum of activity, including less activity against enteric gram-negative bacteria, and it also elicits anti-inflammatory effects. Clinical trials showed efficacy compared with placebo to be statistically significant.
Onset of efficacy, observed by improvement of inflammatory lesions, was evident at the first follow-up visit (ie, 3 weeks). 
Greater efficacy may also be due to less C acnes (formerly P acnes) resistance to minocycline. However, C acnes (formerly P acnes) resistance is becoming more common with all classes of antibiotics currently used to treat acne vulgaris.  C acnes (formerly P acnes) resistance to erythromycin has greatly reduced its usefulness in the treatment of acne. 
Subantimicrobial therapy or concurrent treatment with topical benzoyl peroxide may reduce the emergence of resistant strains.
 Comparing subantimicrobial 40-mg doxycycline, 100-mg doxycycline, and placebo, Moore et al found a comparable percentage of patients clear of acne between at the 40-mg and 100-mg doses, both significantly higher than placebo.
 Additionally, less drug-related adverse events were found with the 40-mg subantimicrobial dosing. Enteric-coated, delayed-release formulations of doxycycline can further reduce gastrointestinal adverse effects. 
Oral antibiotic use can lead to vaginal candidiasis; doxycycline can be associated with photosensitivity; and minocycline has been linked to pigment deposition of the skin, mucous membranes, and teeth. 
The emergence of antibiotic-resistant bacteria, other than C acnes (formerly P acnes), is a contentious debate. An early study by Miller et al found increased skin carriage of coagulase-negative staphylococci in not only acne patients with prolonged use of antibiotics, but also in their close contacts.
 On the contrary, a study by Fanelli et al found that Staphylococcus aureus remained sensitive to tetracycline even after prolonged use of that antibiotic for acne.
 This has significant ramifications when considering efforts to control the spread of methicillin-resistant S aureus (MRSA), because tetracycline group antibiotics are currently one of the primary options for outpatient treatment of MRSA infection.
Other antibiotics, including trimethoprim alone or in combination with sulfamethoxazole, and azithromycin, reportedly are helpful. [49, 50]
Some hormonal therapies may be effective in the treatment of acne vulgaris. Estrogen can be used to decrease sebum production. Additionally, it reduces ovarian production of androgens by suppressing gonadotrophin release.
 Oral contraceptives also increase hepatic synthesis of sex hormone–binding globulin, resulting in an overall decrease in circulating free testosterone.
Combination birth control pills have shown efficacy in the treatment of acne vulgaris. 
Spironolactone may also be used in the treatment of acne vulgaris.  Spironolactone binds the androgen receptor and reduces androgen production. Adverse effects include dizziness, breast tenderness, and dysmenorrhea.  Dysmenorrhea may be lessened by coadministration with an oral contraceptive.
In two 2017 retrospective studies, spironolactone has been shown to be effective in reducing inflammatory lesions in multiple areas of the body with minimal adverse effects.
[53, 54] Currently, more high-powered randomized controlled trials are needed to assess the efficacy of spironolactone monotherapy in treating acne, but spironolactone should be considered in recalcitrant acne, in women who do not tolerate or have contraindications to oral contraceptives, and to prevent antibiotic resistance.
 A 2015 large retrospective study of healthy women aged 18-45 years confirms potassium monitoring is unnecessary for these patients while taking spironolactone.
 Pregnancy must be avoided while taking spironolactone because of the risk of feminization of the male fetus, and spironolactone is not recommended for males because of the potential for gynecomastia. [35, 53] While a black box warning regarding possible cancer risk was placed on spironolactone many years ago after rats fed high doses of the medication developed both benign and malignant tumors, several large retrospective and longitudinal studies have found no association with cancer. 
Isotretinoin is a systemic retinoid that is highly effective in the treatment of severe, recalcitrant acne vulgaris.  Isotretinoin causes normalization of epidermal differentiation, depresses sebum excretion by 70%, is anti-inflammatory, and even reduces the presence of C acnes (formerly P acnes). 
Isotretinoin therapy should be initiated at a dose of 0.5 mg/kg/d for 4 weeks and increased as tolerated until a cumulative dose of 120-150 mg/kg is achieved.  Coadministration with steroids at the onset of therapy may be useful in severe cases to prevent initial worsening.
 Some patients may respond to doses lower than the standard recommendation dosages. A lower dose (0.25-0.4 mg/kg/d) may be as effective in clearing acne as the higher dose given for the same period and with greater patient satisfaction. However, the benefit of prolonged remission is not as great with such therapy as with standard doses.
 Lower intermittent dosing schedules (1 wk/mo) are not as effective. 
Some patients only require one course of oral isotretinoin for complete acne remission, while others require additional courses of isotretinoin therapy.
A study found 38% of the patients had no acne during 3-year follow up, and, among the remaining patients, 17% were controlled with further topical therapy, 25% with topical and oral antibiotics, and 20% with second course of isotretinoin.  Relapse is more ly in younger or female patients. 
Isotretinoin is a teratogen, so pregnancy must be avoided. Contraception counseling is mandatory, and two negative pregnancy test results are required prior to the initiation of therapy in women of childbearing potential.
The baseline laboratory examination should also include cholesterol and triglyceride assessment, hepatic transaminase levels, and a CBC count. Pregnancy tests and a lipid panel and liver enzyme examination should be repeated monthly during treatment while dosing is changing.
Once a level dose is used and the lipids, liver enzymes, and CBC count are normal, these tests may be discontinued.  Other adverse effects include dry skin, lips, and eyes; muscle aches; and headaches.
Patients experiencing severe headaches, decreased night vision, or adverse psychiatric events should stop taking isotretinoin immediately. 
Acne-associated mood changes and depression have also been reported during treatment, but a 2017 meta-analysis involving 1411 cases found no increased risk of depression with isotretinoin use.
 Some of the studies that reported a positive causal relationship between isotretinoin and depression included a dose-response relationship with depression of up to 3 mg/kg/day of isotretinoin; however, this high of a dose is not usually prescribed for acne.
 Other studies have described new-onset depression in both isotretinoin and antibiotic groups, suggesting depression is associated with acne, regardless of treatment.  Therefore, it is important to consider the risk of depression among all patients with acne.
Inflammatory bowel diseases (IBDs) have also been controversially linked to isotretinoin use. A number of case reports have linked isotretinoin with the onset of IBD, with a wide variety of severity of acne, dose of isotretinoin, and duration of treatment prior to the development of IBD.
 Subsequent case-control and cohort studies had conflicting results, with some suggesting no association between isotretinoin and IBD and others suggesting an association between isotretinoin and ulcerative colitis but not Crohn disease [64, 65, 66, 67] Finally, a 2016 large meta-analysis, indexing more than 9 million cases to reduce effects of selection bias and confounding factors, showed isotretinoin is not associated with an increased risk of Crohn disease or ulcerative colitis.  A US Food and Drug Administration(FDA)–mandated registry is now in place for all individuals prescribing, dispensing, or taking isotretinoin. For more information on this registry, see iPLEDGE. This registry aims to further decrease the risk of pregnancy and other unwanted and potentially dangerous adverse effects during a course of isotretinoin therapy.
While using isotretinoin, the patient is considered at high risk for abnormal healing and the development of excessive granulation tissue following procedures.  Many dermatologists delay elective procedures, such as dermabrasion or laser resurfacing (eg, with carbon dioxide laser or erbium:YAG laser), for up to 1 year after completion of therapy.
10 Potential Natural Remedies for Acne + Risk Factors and Conventional Treatments
Acne is one of the most common disorders in the Western world, where it is estimated to affect 50-95% of teenagers. Learn about how acne forms and the research behind many popular complementary treatments.
Why Does Acne Form?
The skin contains oil glands that produce an oily substance called sebum as well as hair follicles from where hair grows .
Acne occurs when these hair follicles on the skin become plugged with oil (sebum) and dead skin cells. This blockage creates an environment that is prone to bacterial infection, which can cause further inflammation .
The face, neck, chest, back and shoulder areas are most commonly affected .
Who is at Risk for Acne?
Acne is most common in teenagers and young adults, but people of all ages can be affected.
According to some estimates, about 80% of people have experienced acne at some point in their life .
Acne appears to be more common in Western societies and in more urban environments .
A number of factors can contribute to acne, some of which include :
- Increased oil production, which can be caused by hormonal changes, increased CRH, increased IGF-1, and lack of Vitamin-D 
- Bacterial infection, especially by the species Cutibacterium acnes (formerly known as Propionibacterium acnes)
- Inflammation, caused by the body’s inflammatory response to bacterial infection, which contributes to redness and swelling
- Genetics, a family history of acne can increase the risk of having acne 
- Diet may contribute to acne, foods that are associated with acne include dairy milk and foods high in carbohydrates 
- Smoking may worsen acne symptoms 
- Certain medications can cause acne, such as testosterone, corticosteroids, and lithium
- Pressure on the skin can worsen acne, such as wearing hats, helmets, and backpacks
- Contact with oily or greasy substances, such as from working in kitchens or using greasy skin products
Stress is often believed to cause or worsen stress, but clinical research has revealed conflicting results. It’s not entirely clear how much stress contributes to acne .
Treatments for Acne
If you suffer from persistent or severe acne, you may want to talk to your doctor about your options. Many of the medications used for acne require a prescription from a doctor.
There are a number of treatments for acne, which generally work by :
- Reducing oil production
- Reducing inflammation
- Eliminating bacterial infections
- Increasing skin cell turnover
- Altering hormone levels
Acne treatments typically take some time before results are seen, sometimes up to four to eight weeks. Treatment choice can depend on the type and severity of acne, the age of the patient, and other health conditions the patient may have .
Some common conventional treatments for acne include :
- Benzoyl peroxide, an over-the-counter topical product with antimicrobial effects that is generally the first choice for mild to moderate acne
- Antibiotics (in topical or pill form), such as clindamycin, erythromycin, or doxycycline
- Retinoids (in topical or pill form), which help reduce inflammation and oil (sebum) production, some examples include isotretinoin adapalene, and retinol
- Hormone medications such as oral birth control can improve acne symptoms
Different treatments are sometimes combined if treatment with one agent is ineffective.
Research on Complementary Treatments
In the following sections, we’ll discuss the research behind some of the complementary treatments commonly used for acne. Talk to your doctor before taking any of these treatments. They should never be used as a replacement for approved medical therapies.
1) Fish Oil
The omega-3 fatty acids in fish oil (DHA and EPA) have anti-inflammatory effects. There is some evidence that fish oil supplementation may also help inflammation associated with acne.
limited clinical evidence, fish oils are possibly effective for reducing acne symptoms.
For example, a 12-week study of 13 people found that fish oil supplementation improves overall acne severity, especially for those with moderate-to-severe acne .
Another randomized controlled clinical trial with 45 participants suggests that supplementation with 2,000 mg of EPA and DHA significantly reduces acne .
Oral supplementation with fish oils is considered to be ly safe when taken in appropriate doses .
2) Alpha Hydroxy Acids (AHAs)
Alpha hydroxy acids (AHAs) are a class of chemical substances that can naturally be found in certain foods or synthetically produced. They are common ingredients in cosmetic products .
Certain types of AHAs are possibly effective for acne.
For example, a randomized placebo-controlled trial of 120 patients with mild acne looked at the effects of glycolic acid, a type of AHA. Researchers found that a 10% glycolic acid topical product improves acne symptoms .
Another randomized placebo-controlled study of 26 subjects suggests that a 40% glycolic acid skin peel is effective for moderate acne .
In a clinical trial with 150 participants, a gluconolactone (another AHA) solution was as effective as 5% benzoyl peroxide lotion for mild-to-moderate acne .
A product containing a specific mix of AHAs (Hyseac AHA cream) reduced acne severity in mild-to-moderate acne, according to an open study of 248 patients .
In addition, several clinical trials have found that glycolic acid skin peels may improve the appearance of acne scars [16, 17, 18].
Generally speaking, topical AHA products are ly safe when used appropriately. However, high concentrations (greater than 10%) may cause skin burns .
Research shows that people with low zinc levels are more ly to have more severe forms of acne. Oral zinc supplementation is possibly effective for acne .
A number of small clinical trials suggest that taking zinc supplements (either zinc sulfate or zinc gluconate) can improve acne when compared to placebo .
However, there are also some studies that found oral zinc supplementation was ineffective for acne. In addition, research on topical zinc treatments has revealed conflicting results [21, 22, 23].
The use of zinc supplements is ly safe as long as doses do not exceed the upper limit of 40 mg per day (for adults) .
4) Tea Tree Oil
Tea tree oil has antimicrobial properties and is possibly effective for acne .
A randomized placebo-controlled trial of 60 patients with mild-to-moderate acne found that a 5% topical tea tree oil gel may reduce the severity of acne .
A different randomized clinical trial of 124 patients found that a 5% topical tea tree oil product reduced acne similar to a 5% benzoyl peroxide lotion, although tea tree oil appeared to work slower .
research, tea tree oil is possibly safe when used topically. However, it is unsafe when ingested .
Several studies have explored the use of probiotics for acne, although there is currently insufficient evidence to determine if probiotics are effective for this purpose.
A randomized open-label trial with 45 women found that a probiotic containing Lactobacillus acidophilus, Lactobacillus bulgaricus, and Bifidobacterium bifidum may reduce the number of acne lesions .
Oral supplementation with probiotics is considered to be ly safe when taken appropriately .
6) Aloe Vera
There is insufficient evidence to rate the effectiveness of topical aloe for acne.
However, one randomized study did find that an aloe vera topical gel in combination with tretinoin cream may be more effective for acne than either treatment alone .
Aloe gel is ly safe when used topically.
There is insufficient evidence to determine if guggul is an effective treatment option for acne.
However, there is one randomized study of 20 patients that found that oral guggul supplements may be as effective oral tetracycline (an antibiotic) for the treatment of nodulocystic acne, a severe form of acne .
Taking guggul supplements by mouth is possibly safe, limited clinical research .
8) Green Tea
According to a preliminary 8-week randomized trial with 35 patients, a 5% EGCG (a compound found in green tea) topical solution may help reduce acne .
However, overall there is insufficient evidence to rate green tea’s effectiveness for acne.
When used topically, green tea or EGCG is possibly safe, mostly due to limited clinical research .
Resveratrol is a plant compound with antioxidant and anti-inflammatory properties. It can be found in grapes, red wine, and some types of berries .
There is insufficient evidence to evaluate the effectiveness of resveratrol for acne.
However, there is one pilot study that found that a resveratrol-containing gel may help reduce the number of acne lesions on the face .
Resveratrol is ly safe when consumed in the amounts typically found in food. However, there is insufficient evidence to determine the safety of topical forms of resveratrol.
Honey has antibacterial properties, but research suggests that topical honey is possibly ineffective for the treatment of acne .
In a randomized controlled trial with 136 participants, a topical product containing 90% medical-grade kanuka honey did not improve acne more than control groups .
It’s unclear how safe topical honey is due to a lack of research.