What is acne vulgaris?
Acne vulgaris or common acne is a chronic inflammation of the pilosebaceous units, that is the hair follicles and their associated sebaceous glands .
Acne appear as red, white or black and sometimes itchy or tender blemishes on the face, neck, shoulders, upper arms, upper back or chest .
Acne most commonly appears in teenagers–boys and girls–usually after age of 12, but sometimes as early as at age of 8–and mostly disappears by the age of 25 [2,100]. Adult acne can persist over the age of 40, though.
Picture 1. Acne vulgaris on the forehead: papules and pustules (pimples)
(source: Wikimedia, Creative Commons licence)
Picture 2. Severe acne on the back
(source: Wikimedia, Creative Commons licence)
Acne forms :
- A whitehead or closed comedone appears as a white bump, 2-4 mm in size.
- A blackhead or open comedone appears as a black dot (1-2 mm); the black color is not from dirt but from the oxidation of oil when it comes in the contact with air; white greasy material can be squeezed out without popping.
- A papule appears as a flat red bump (2-4 mm).
- A pustule (pimple) appears as a white pus-filled blister surrounded by reddened skin.
- A nodule or a cyst appears as a tender lump–5 mm or larger–under the skin.
Picture 3. Acne vulgaris: a blackhead and whitehead
(source: Wikimedia, Creative Commons licence)
Picture 4. Nodular acne on the face
(source: Wikispaces, Creative Commons licence)
Acne is not an infection, so it is not contagious. A similar condition–bacterial folliculitis–is contagious, though.
Pathophysiology: How does acne develop?
Acne develops when oil and dead skin cells build up in the sebaceous glands and clog them. The following mechanisms are likely involved :
- Increased activity of the androgen (male sex) hormones, such as testosterone and dehydroepiandrosterone (DHEA) in the skin resulting in the increased excretion of oil by the sebaceous glands (in both sexes) [5,68]; NOTE: the blood levels of the androgen hormones in most individuals with acne are normal, but can be increased in individuals with various hormonal disorders and acne.
- Increased shedding of the cells (keratocytes) in the hair follicles 
- Colonization of the hair follicles by the bacteria Propionibacterium acnes, which are normally present on the skin
- Inflammation in the sebaceous glands 
Mild acne are noninflammatory acne, which include open comedones (blackheads) and closed comedones (whiteheads) limited to the face.
Moderate acne are inflammatory acne, which include papules (red bumps) and pustules (white blisters) on the face or trunk.
Severe acne are inflammatory acne, which include nodules or, rarely, cysts, which both appear as underskin lumps.
Acne conglobata and acne fulminans are very severe types of acne, which mainly occur in adolescent males. Painful, crusty and bleeding acne suddenly appear on the back, chest and neck; other symptoms can include joint pain, fever, enlarged liver and spleen . Possible triggers include drugs, such as testosterone, anabolic steroids and a reaction to oral isotretinoin .
Acne can be further infected by the bacterium Staphylococcus aureus; the condition called bacterial folliculitis, which may look similar to acne, appears as itchy, tender red bumps with white pus-filled centers. The infection can heal spontaneously in few weeks, but you can speed up recovery by applying an ointment containing the antibiotic mupirocin.
When acne heal, they sometimes leave dark red spots (hyperpigmentation), which may need several months or years to disappear .
Acne cysts and nodules, but sometimes also mild acne, can leave permanent scars . The risk of scars increases with early-onset acne and acne popping .
Early treatment with isotretinoin decreases the risk of scars but it does not treat formed scars . There is INSUFFICIENT EVIDENCE about the long-term effectiveness of skin needling, chemical peeling, laser therapy or injectable fillers in the treatment of scars . Some scars can be reduced by plastic surgery.
What causes acne?
The exact cause of acne is not known but the risk factors can include [1,2]:
- Genetic predisposition
- Seborrheic dermatitis or other causes of oily skin; but people with dry skin also get acne
- Apert, SAPHO, Behçet and PAPA syndrome 
- Increased blood levels of the androgen hormones (see hormonal acne)
- Hormonal drugs (see hormonal acne)
- Other drugs and supplements :
- Antidepressants: lithium, amoxapine
- Antiepileptics: carbamazepine, phenytoin, phenobarbital
- Antituberculous drugs: ethionamide, isoniazid, rifampicin
- Epidermal growth factor receptor inhibitors
- Halogens: iodides, chlorides, bromides, halothane
- TNF alpha inhibitors (etanercept, adalimumab, infliximab)
- Vitamins B6 and B12
In susceptible individuals, the following may trigger acne [2,4,5,6]:
- Psychological stress, such as before school exams [70,71], and conflicts in relationships associated with anxiety, anger and frustration
- Oil-based and other occlusive cosmetics (certain moisturizers, foundation and pomades) and sunscreens and other products that irritate the skin
- Pressure of the clothes or skin scrubbing
- Sun exposure
- High humidity or air pollution
- Premenstrual syndrome (within the week before the period)
Although, there seems to be insufficient evidence, several studies suggest the following dietary factors may aggravate acne:
- Irregular dietary patterns 
- High-glycemic load diets (soda, sweets, deserts and other foods high in sugar, white bread, biscuits and other bake goods made from white flour, white rice, potatoes); they stimulate insulin, IGF-1 and androgen hormone release and can thus trigger acne [15,60,61,62,65,67,73,87]; but some studies have found no harmful effect [66,85]
- Dairy products, such as milk [64,67,86], ice cream , cheese [60,84] or protein-calorie supplements (whey) [63,81,83] may trigger acne because they contain the growth hormone, insulin-like growth factor (IGF-1) and steroid hormones; they also raise the blood insulin levels, which all stimulate oil secretion by the sebaceous glands [60,61].
There is less evidence about the following possible triggers of acne:
- Iodine (in salt, milk and seaweeds) 
- High-protein diets, especially animal protein high in the amino acid leucine 
- Diet high in saturated and trans fats and low in polyunsaturated omega-3 fats [60,74]
- Chocolate (milk or dark) [64,67,88,89]
- Nuts 
- Pork and poultry 
- “Junk food” or fast food (pizza, French fries) [60,64]
- Cigarette smoking [112,113]
The following probably does not trigger acne [2,3,5]:
- Greasy foods
- Caffeine (in coffee and tea)
- Excessive sweating
- Poor skin hygiene
A doctor can usually make a diagnosis of acne by a simple inspection.
High blood levels of androgen or other hormones can reveal the underlying disorder.
The notable difference between acne and other conditions is the absence of blackheads in the later :
- Angiofibromas are small (1-3 mm) flesh-colored bumps on the nose and cheeks.
- Bacterial folliculitis (an inflammation of the hair follicles usually caused by Staphylococcus aureus) can cause red pimples anywhere on the body, including the face, inside of the nose or ear, scalp, trunk, buttocks, genitalia and limbs.
- Bumpy hives appears as an allergic reaction to foods or other irritants; pink itchy bumps appear and disappear within several hours.
- Chloracne can appear after inhalation, ingestion or contact with dioxin as a sudden eruption of skin-colored bumps and underskin cysts on the face and neck.
- Dermatitis herpetiformis appears in some individuals with celiac disease as very itchy red blisters on the elbows, knees, back, buttocks and scalp, mainly in adults.
- Facial demodicosis, caused by Demodex mites, appears as red bumps on the face.
- Hidradenitis suppurativa or acne inversa is an inflammation in armpits, groin or below the breasts with underskin bumps covered by red rash, which can ooze pus.
- Hot tub folliculitis caused by the bacterium Pseudomonas aeruginosa appears as red bumps on the skin areas covered by the swimming suit.
- Ingrown hair (folliculitis barbae, razor bumps) appears as red bumps on the shaved areas.
- Insect bites can cause red itchy and tender bumps.
- Keratosis pilaris (thickened hair follicles filled with skin cells) appears as skin-colored, red or brown non-itchy bumps, mainly on the upper arms or thighs.
- Leprosy is a rare bacterial infection that appears with skin-colored bumps and lumps.
- Milia–collections of dead skin cells in the skin–appear as small white bumps on the nose, cheeks and around the eyes, mainly in infants, but also in adults.
- Molluscum contagiosum is a viral infection that appears as small (2-3 mm) red fleshy bumps anywhere on the skin.
- Oil folliculitis is an inflammation of the hair follicles due to exposure to oils.
- Perioral dermatitis is a skin inflammation with red bumps around the mouth (limited to the chin and nasolabial folds).
- Pityrosporum folliculitis appears as red bumps as a reaction to the fungi Malassezia furfur.
- Ringworm (a fungal infection) can present with red or brownish scaly rash in the form of circular patches and occasional pus-filled bumps anywhere on the skin.
- Rosacea appears in flares with flushing or constant redness and occasional pus-filled bumps on the nose, cheeks, chin and forehead or, rarely, on neck and chest; it occurs after 30 and can be triggered by stress, alcohol or hot foods.
- Sebaceous hyperplasia is a sebaceous gland overgrowth that appears as yellowish or skin colored bumps on the face in middle aged or older people.
- Sebaceous or epidermoid cyst or other skin cyst
- Seborrheic dermatitis (skin inflammation by Malassezia fungi) appears as yellow greasy scales on the scalp, face and upper trunk.
- Sweat rash, prickly heat or miliaria (sweat gland clogging triggered by heat) appears as red itchy bumps in the armpits, groin or face.
- Syringoma are small benign tumors of the sweat glands that appear as clusters of skin-colored bumps, mainly below the eyes.
1. Lifestyle Changes: Diet and Coping With Stress
Stress is a possible trigger of acne. If your life is disorganized, it can help you clear acne, if you adopt regular eating, working and sleeping pattern.
It has been often proposed that foods high in sugar and quickly absorbable carbohydrates (soda, sweets, white bread, white rice, potatoes) and milk can aggravate acne. It can help you if you limit these or any other foods you suspect they trigger acne in your case–the most probable candidates are those foods you think are not really necessary for you or make you feel uncomfortable or ashamed when you eat them.
Total fasting for few weeks can decrease the production of sebum by the sebaceous glands by 40% . Recommending fasting to treat acne would be an exaggeration, but decreasing calorie intake (by overweight individuals) or avoiding very high calorie foods (by anyone) might help clear cane.
2. Over-The-Counter Products, Supplements, Herbs and Home Remedies
OTC topical medicines are available in the form of gels, lotions, creams, soaps or pads. They can contain one or more medicines mentioned below. Those that are effective should help within 4-8 weeks [1,2].
Benzoyl peroxide destroys the bacteria Propionibacterium acnes in the skin. There is some WEAK EVIDENCE that benzoyl peroxide is effective in the treatment of mild and moderate acne [18,20,31,33,42,43,47,118]. Gels with 2.5%, 5% and 10% benzoyl peroxide seem to be equally effective . According to one study review, 5.3% benzoyl peroxide in a foam form (to leave on) is effective in treatment of mild to moderate back acne  and according to another review, benzoyl peroxide 6-8% wash (to apply and rinse) can be effective in the treatment of inflammatory and noninflammatory facial acne .
There is some WEAK EVIDENCE about the effectiveness of tee tree oil [15,26,27,28,29] and bee venom  in the treatment of mild acne.
There is INSUFFICIENT EVIDENCE about the effectiveness in treatment of acne for aloe vera [23,36], alpha hydroxy acid , antioxidants (vitamin A or retinol [31,36,79,87], beta carotene , vitamin C , vitamin E ), Ayurvedic or Chinese herbs , basil oil , bovine cartilage , brewer’s yeast [23,106], essential oils (chamomile, cinnamon, grapefruit, ginger, hibiscus, jasmine, lavender, lemon, mint, rose, thyme) [107, 108], fish oil (omega-3 fatty acids) [72,73], hydrogen peroxide , linoleic acid , nicotinamide (vitamin B3) , Nigerian Toto , oligosaccharides from seaweed , pantothenic acid (by mouth) , prebiotics , probiotics , pyroxidine , resorcinol , salicylic acid (0.5-5%) [47,118], sulfur , resveratrol gel , tannins in herbal extracts (beard moss or usnea, Cannabis sativa, eucalyptus, green tea, licorice, mountain grapes, old man banksia, purple coneflower, rosemary, St.John’s-wort, witch hazel) , turmeric [101,102,107], vitex (for pre-menstrual acne) [106,107], zinc (topical or oral) [23,31,32,35] or yeasts, such as Saccharomyces bulderi .
There seems to be NO EVIDENCE about the effectiveness of the following home remedies in the treatment of acne when applied on the skin: apple cider vinegar, aspirin tablet, bacon, baking soda, banana peels, coconut oil, egg whites, honey, lemon juice, neem oil , orange peels, papaya, saliva, sea salt bath, steam cleaning, strawberries, tomatoes or toothpaste.
3. Prescribed Ointments
Prescribed ointments are intended for the treatment of moderate and severe acne.
Azelaic acid. There is some WEAK EVIDENCE about its effectiveness [39,40,41].
Salicylic acid (prescription-strength, 5-30%) is used as a chemical peel [1,5,37]. There is INSUFFICIENT EVIDENCE about the long-term effectiveness of chemical peels in the treatment of acne .
Retinoids (vitamin A derivatives) include tretinoin, isotretinoin, adapalene and tazarotene. Tretinoin seems to be most effective . Retinoids reduce sebum production, inflammation, shedding of the keratinocytes and bacterial colonization in the sebaceous glands .
Antibiotics, such as tetracycline, minocycline, doxycycline, erythromycin, trimethoprim, clindamycin, sulfacetamide or dapsone are intended for the treatment of inflammatory acne; they are probably not effective in mild noninflammatory acne (whiteheads and blackheads) . They should always be used in combination with benzoyl peroxide, a topical retinoid or azelaic acid. They do not seem to be more effective than benzoyl peroxide alone . There seems to be no clear differences in effectiveness among different antibiotics . Long-term antibiotic use can result in bacterial resistance .
Common side effects of acne ointments are skin dryness, redness, itching, burning, peeling, swelling and–with retinoids–initial worsening of acne, increased risk of sunburn and skin thinning [33,94,95]. An allergic reaction with severe itch and sudden appearance of pinkish bumpy or patchy hives may occur in sensitive individuals.
4. Drugs by Mouth
Oral drugs for moderate or severe acne [2,4,5]:
Antibiotics, such as doxycycline, erythromycin, minocycline, tetracycline or trimethoprim/sulfamethoxazole, may help in inflammatory acne. There seems to be no clear benefit of antibiotic-zinc combination over antibiotics alone . Tetracycline can cause yellow discoloration of the skin and (in children younger than 8 years of age) teeth and increases the risk of systemic lupus erythematosus, especially in women . Minocycline can cause liver damage .
Isotretinoin is considered very effective in the treatment of moderate to severe acne [33,99]. It can also prevents the formation of scars . It usually prescribed for 15-20 weeks. After the start of the treatment, acne may temporarily worsen.
Isotretinoin can have quite some side effects, such as cracked lips, mouth sores, dry or itchy skin, changes in skin color, skin peeling, hair loss, rash, excessive sweating, nosebleeds, voice changes, chest pain, depression, drowsiness, seizures, ringing in the ears, excessive thirst, frequent urination, difficulty breathing, fever, tiredness, diarrhea, blood in the stool and elevated triglyceride levels . Symptoms of overdose include flushing, headache, vomiting, dizziness and loss of coordination . You should not buy isotretinoin via the internet and always use it under the doctor’s supervision.
In the United States, women who want to use oral retinoids need to get involved into the Food and Drug Administration (FDA)-approved monitoring program iPLEDGE, which includes regular pregnancy tests and use of contraceptive pills in order to prevent birth defects.
Do not take isotretinoin if you are or can become pregnant, you are breastfeeding or taking tetracycline antibiotics or you are allergic to isotretinoin .
A common current approach to acne treatment with medicines [17,33]:
- Mild acne: OTC ointments containing benzoyl peroxide
- Moderate acne: topical retinoids plus topical antibiotics plus benzoyl peroxide or azelaic acid
- Severe acne: oral retinoids and oral antibiotics plus benzoyl peroxide
NOTE: You should continue with any acne treatment for at least 2 or 3 months before deciding if it works or not . A combination of various medicines is usually more effective than any single medicine. Discuss with a dermatologist which combination is most appropriate for you.
5. Dermatologic Procedures
There is INSUFFICIENT EVIDENCE about the effectiveness of the following therapies for acne :
- Light therapy with blue or red light, photodynamic therapy or green or yellow laser [7,8,19]
- Chemical peels (using glycolic acid [36,111], lactic acid, salicylic acid, Jessner’s solution or trichloroacetic acid)
- Extraction of blackheads and whiteheads
- Drainage and extraction of large cysts
- Acupuncture [15,21]
- Cupping [15,21]
- Cryotherapy 
- Exposure to sun 
6. Treatment of Acne in Pregnancy
In women, acne can worsen in early in pregnancy–probably due to increased estrogen and testosterone levels–and tend to become milder in late pregnancy .
Preferably, pregnant women should not use any drugs to treat acne. The following is considered safe during pregnancy :
- Benzoyl peroxide
- Azelaic acid
- Glycolic acid
- Low-concentration salicylic acid preparations
- Light and laser therapy
DO NOT use the following in pregnancy [5,11]:
- Oral retinoids (isotretinoin can cause severe birth defects or miscarriage)
- Topical retinoids: tretinoin, isotretinoin and adapalene
- High-concentration (>5%) salicylic acid
- Antibiotics, especially tetracyclines (doxycycline, minocycline, lymecycline), cotrimoxazole or fluoroquinolones
The following may help [2,8]:
- Learn how to cope with stress.
- Regularly wash the face with warm (not hot) water.
- Do not pick, pop or squeeze acne and avoid touching your face with the hands.
- Regularly shampoo your hair.
- Use only alcohol-free cleansers. Apply the cleanser gently with the fingertips not by a cloth or sponge.
- Avoid oil-based cosmetics.
- Avoid tanning beds and exposure to strong sunlight.
- Avoid humid environments, like unventilated kitchens, saunas or vaccations in tropics.
Some studies suggest that avoiding high-glycemic index load diets (soda and other foods high in sugar, white bread and other goods made from white flour, white rice, potatoes) [60,61,62,65,67,73,87] and dairy products (milk [64,67,86], ice cream , cheese [60,84] or protein-calorie supplements (whey) [63,81,83] may help prevent acne.
There is INSUFFICIENT EVIDENCE about the effectiveness of the high-fiber [73,87] or vegetarian diet  in the prevention or treatment of acne.
Infantile and Childhood Acne
In infants and small children between 6 months and 3 years of age, most commonly in boys acne are usually caused by genetic factors rather than hormonal abnormalities. They are usually mild or moderate, they typically appear on cheeks and resolve in few months .
In children, 3-6 years of age, acne are more likely caused by increased levels of androgen hormones due to congenital adrenal hyperplasia, Cushing syndrome, 21-hydroxylase deficiency, precocious puberty or androgen-secreting tumors . Typical associated symptoms include excessive body hair, abnormal growth and premature genital and breast development.
Treatment is usually topical with benzoyl peroxide or erythromycin gel [12,22]. In severe acne, oral antibiotics, such as erythromycin and trimethoprim, or isotretinoin can be used [12,22].
Adult acne are either acne that persists from adolescence or new-onset acne after age of 20. They are more common in women than in men and can persist after age of 30 or even 40. Triggers can include psychological stress, cigarette smoking  and excessive alcohol drinking .
In women, acne can be associated with high levels of the hormone dehydroepiandrosterone sulfate (DHEAS), dihydrotestosterone (DHT), testosterone  or cortisol  and in men with cortisol [58,59], androstenedione, DHEAS [50,59] or estradiol . Other common symptoms in women with high levels of androgen hormones include excessive hair growth on the skin (hirsutism), hair loss on the scalp (alopecia) and abnormal menstruation.
Stress can increase androgen activity in the skin and thus acne in this way: stress >> increased release of corticotropin-releasing hormone (CRH) by the brain or by the nerves in the skin >> increased activity of androgen hormones >> increased sebum production and inflammation in the sebaceous glands [115,116,117].
Conditions with increased levels of androgen and other hormones that can cause acne :
- Obesity associated with insulin resistance and therefore increased blood levels of insulin; it is not clear if untreated diabetes type 2 is associated with acne, though 
- Acromegaly with increased levels of the growth hormone (GH), insulin-like growth factor (IGF-1)  and testosterone 
- Congenital adrenal hyperplasia (CAH) with increased secretion of androgen hormones in children or adults 
- Cushing syndrome, for example due to adrenal gland tumors with increased secretion of cortisol and androgen hormones [6,53,56]
- Polycystic ovary syndrome (PCOS) with increased levels of dehydroepiandrosterone sulfate (DHEA-S) 
- Pituitary adenoma with increased secretion of adrenocorticotropic hormone (ACTH) 
- Androgen-secreting tumors (in the ovaries or adrenal glands) in women 
- Hypothyroidism associated with an increased secretion of the hormone prolactin  and testosterone 
- High blood levels of free testosterone due to low levels of sex hormone binding globulin (SHBG) caused by progestin-containing contraceptives, including pills and intrauterine devices or IUDS (desogestrel, levonorgestrel, norethindrone, norgestimate, norgestrel), glucocorticoids, insulin or obesity 
Hormonal drugs that can cause acne :
- Steroids, such as prednisone
- Contraceptives: medroxyprogesterone injection, implanted or intrauterine progesterone and oral contraceptives which reduce circulating sex hormone binding globulin (SHBG)
- Dehydroepiandrosterone (DHEA)
- Anabolic steroids (danazol, stanozolol, nandrolone) used mainly by bodybuilders
Antiandrogens such as cyproterone acetate , spironolactone , finasteride, flutamide  and corticosteroids (prednisone, dexamethasone) in low doses are used in women with signs of increased androgen production, such as excessive body hair; they may need 3-6 months to show effects [2,5,96].
- According to one 2012 review, spironolactone may help reduce hormone-related acne that appear in women before menstrual period .
- There is INSUFFICIENT EVIDENCE about the effectiveness of finasteride  and spironolactone [14,17] in reducing acne in women with diseases with increased androgen hormone levels.
- Prednisone by mouth can help in severe acne (acne fulminans) .
Side effects, such as breast tenderness, stomach upset and severe liver damage, limit the usability of antiandrogens in treatment of acne in women . Antiandrogens are not convenient for treatment of acne in en, because of feminizing side effects, such as impotence and enlarged breasts .
You may be able to prevent or limit acne by:
- Adopting regular eating, working and sleeping patterns
- Reducing psychological stress by solving eventual relationship- and work-related conflicts
- Avoiding foods with high glycemic index (sugary drinks, potatoes, white rice, white bread) and milk.
The most effective medications for mild acne seem to be the ointments containing benzoyl peroxide (available without prescription) and for moderate and severe acne tretinoin ointments and isotretinoin capsules (by prescription).
You should not expect to get rid of acne fast or even overnight, but only about a month or two after the onset of treatment.
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