both polymorphous light eruption outbreaks and the acne aestivalis breakout response can be prevented by topical antioxidants combined with the application of a broad spectrum sunscreen. pathophysiology simplistic representation of the formation of acne comedones. hair follicle anatomy demonstrating a healthy hair follicle (pictured left), a whitehead or closed comedo (middle picture), and a blackhead or open comedo (pictured right) flowchart of the pathological sequence of events leading to acne acne vulgaris is a chronic skin disease of the pilosebaceous unit and develops due to blockages in the skin's hair follicles. these blockages occur as a result of the following four abnormal processes: increased oily sebum production (influenced by androgens), excessive deposition of the protein keratin leading to comedo formation, colonization of the follicle by cutibacterium acnes (c. acnes) bacteria, and the local release of pro-inflammatory chemicals in the skin. the earliest pathologic change is the formation of a plug (a microcomedone), which is driven primarily by excessive growth, reproduction, and accumulation of skin cells in the hair follicle. in healthy skin, the skin cells that have died come up to the surface and exit the pore of the hair follicle. in people with acne, the increased production of oily sebum causes the dead skin cells to stick together. the accumulation of dead skin cell debris and oily sebum blocks the pore of the hair follicle, thus forming the microcomedone. the c. acnes biofilm within the hair follicle worsens this process. if the microcomedone is superficial within the hair follicle, the skin pigment melanin is exposed to air, resulting in its oxidation and dark appearance (known as a blackhead or open comedo). in contrast, if the microcomedone occurs deep within the hair follicle, this causes the formation of a whitehead (known as a closed comedo). the main hormonal driver of oily sebum production in the skin is dihydrotestosterone. another androgenic hormone responsible for increased sebaceous gland activity is dhea-s. the adrenal glands secrete higher amounts of dhea-s during adrenarche (a stage of puberty), and this leads to an increase in sebum production. in a sebum-rich skin environment, the naturally occurring and largely commensal skin bacterium c. acnes readily grows and can cause inflammation within and around the follicle due to activation of the innate immune system. c. acnes triggers skin inflammation in acne by increasing the production of several pro-inflammatory chemical signals (such as il-1α, il-8, tnf-α, and ltb4); il-1α is essential to comedo formation. c. acnes' ability to bind and activate a class of immune system receptors known as toll-like receptors (tlrs), especially tlr2 and tlr4, is a core mechanism of acne-related skin inflammation. activation of tlr2 and tlr4 by c. acnes leads to increased secretion of il-1α, il-8, and tnf-α. the release of these inflammatory signals attracts various immune cells to the hair follicle, including neutrophils, macrophages, and th1 cells. il-1α stimulates increased skin cell activity and reproduction, which, in turn, fuels comedo development. furthermore, sebaceous gland cells produce more antimicrobial peptides, such as hbd1 and hbd2, in response to the binding of tlr2 and tlr4. c. acnes also provokes skin inflammation by altering the fatty composition of oily sebum. oxidation of the lipid squalene by c. acnes is of particular importance. squalene oxidation activates nf-κb (a protein complex) and consequently increases il-1α levels. additionally, squalene oxidation increases 5-lipoxygenase enzyme activity, which catalyzes the conversion of arachidonic acid to leukotriene b4 (ltb4). ltb4 promotes skin inflammation by acting on the peroxisome proliferator-activated receptor alpha (pparα) protein. pparα increases the activity of activator protein 1 (ap-1) and nf-κb, thereby leading to the recruitment of inflammatory t cells. c. acnes' ability to convert sebum triglycerides to pro-inflammatory free fatty acids via secretion of the enzyme lipase further explains its inflammatory properties. these free fatty acids spur increased production of cathelicidin, hbd1, and hbd2, thus leading to further inflammation. this inflammatory cascade typically leads to the formation of inflammatory acne lesions, including papules, infected pustules, or nodules. if the inflammatory reaction is severe, the follicle can break into the deeper layers of the dermis and subcutaneous tissue and cause the formation of deep nodules. the involvement of ap-1 in the aforementioned inflammatory cascade activates matrix metalloproteinases, which contribute to local tissue destruction and scar formation. along with the bacteria c. acnes, the bacterial species staphylococcus epidermidis (s. epidermidis) also takes a part in the physiopathology of acne vulgaris. the proliferation of s. epidermidis with c. acnes causes the formation of biofilms, which blocks the hair follicles and pores, creating an anaerobic environment under the skin. this enables for increased growth of both c. acnes and s. epidermidis under the skin. the proliferation of c. acnes causes the formation of biofilms and a biofilm matrix, making it even harder to treat the acne. diagnosis acne vulgaris is diagnosed based on a medical professional's clinical judgment. the evaluation of a person with suspected acne should include taking a detailed medical history about a family history of acne, a review of medications taken, signs or symptoms of excessive production of androgen hormones, cortisol, and growth hormone. comedones (blackheads and whiteheads) must be present to diagnose acne. in their absence, an appearance similar to that of acne would suggest a different skin disorder. microcomedones (the precursor to blackheads and whiteheads) are not visible to the naked eye when inspecting the skin and require a microscope to be seen. many features may indicate that a person's acne vulgaris is sensitive to hormonal influences. historical and physical clues that may suggest hormone-sensitive acne include onset between ages 20 and 30; worsening the week before a woman's period; acne lesions predominantly over the jawline and chin; and inflammatory/nodular acne lesions. several scales exist to grade the severity of acne vulgaris, but disagreement persists about the ideal one for diagnostic use. cook's acne grading scale uses photographs to grade severity from 0 to 8, with higher numbers representing more severe acne. this scale was the first to use a standardized photographic protocol to assess acne severity; since its creation in 1979, the scale has undergone several revisions. the leeds acne grading technique counts acne lesions on the face, back, and chest and categorizes them as inflammatory or non-inflammatory. leeds scores range from 0 (least severe) to 10 (most severe) though modified scales have a maximum score of 12. the pillsbury acne grading scale classifies the severity of the acne from grade 1 (least severe) to grade 4 (most severe). differential diagnosis many skin conditions can mimic acne vulgaris, and these are collectively known as acneiform eruptions. such conditions include angiofibromas, epidermal cysts, flat warts, folliculitis, keratosis pilaris, milia, perioral dermatitis, and rosacea, among others. age is one factor that may help distinguish between these disorders. skin disorders such as perioral dermatitis and keratosis pilaris can appear similar to acne but tend to occur more frequently in childhood. rosacea tends to occur more frequently in older adults. facial redness triggered by heat or the consumption of alcohol or spicy food is also more suggestive of rosacea. the presence of comedones helps health professionals differentiate acne from skin disorders that are similar in appearance. chloracne and occupational acne due to exposure to certain chemicals & industrial compounds, may look very similar to acne vulgaris. management many different treatments exist for acne. these include alpha hydroxy acid, anti-androgen medications, antibiotics, antiseborrheic medications, azelaic acid, benzoyl peroxide, hormonal treatments, keratolytic soaps, nicotinamide, retinoids, and salicylic acid. acne treatments work in at least four different ways, including the following: reducing inflammation, hormonal manipulation, killing c. acnes, and normalizing skin cell shedding and sebum production in the pore to prevent blockage. typical treatments include topical therapies such as antibiotics, benzoyl peroxide, and retinoids, and systemic therapies, including antibiotics, hormonal agents, and oral retinoids. recommended therapies for first-line use in acne vulgaris treatment include topical retinoids, benzoyl peroxide, and topical or oral antibiotics. procedures such as light therapy and laser therapy are not first-line treatments and typically have only an add on role due to their high cost and limited evidence. blue light therapy is of unclear benefit. medications for acne target the early stages of comedo formation and are generally ineffective for visible skin lesions; acne generally improves between eight and twelve weeks after starting therapy. people often view acne as a short-term condition, some expecting it to disappear after puberty. this misconception can lead to depending on self-management or problems with long-term adherence to treatment. communicating the long-term nature of the condition and better access to reliable information about acne can help people know what to expect from treatments. skin care in general, it is recommended that people with acne do not wash affected skin more than twice daily. the application of a fragrance-free moisturizer to sensitive and acne-prone skin may reduce irritation. skin irritation from acne medications typically peaks at two weeks after onset of use and tends to improve with continued use. dermatologists recommend using cosmetic products that specifically say non-comedogenic, oil-free, and will not clog pores. acne vulgaris patients, even those with oily skin, should moisturize in order to support the skin's moisture barrier since skin barrier dysfunction may contribute to acne. moisturizers, especially ceramide-containing moisturizers, as an adjunct therapy are particularly helpful for the dry skin and irritation that commonly results from topical acne treatment. studies show that ceramide-containing moisturizers are important for optimal skin care; they enhance acne therapy adherence and complement existing acne therapies. in a study where acne patients used 1.2% clindamycin phosphate / 2.5% benzoyl peroxide gel in the morning and applied a micronized 0.05% tretinoin gel in the evening the overwhelming majority of patients experienced no cutaneous adverse events throughout the study. it was concluded that using ceramide cleanser and ceramide moisturizing cream caused the favorable tolerability, did not interfere with the treatment efficacy, and improved adherence to the regimen. the importance of preserving the acidic mantle and its barrier functions is widely accepted in the scientific community. thus, maintaining a ph in the range 4.5 - 5.5 is essential in order to keep the skin surface in its optimal, healthy conditions. diet causal relationship is rarely observed with diet/nutrition and dermatologic conditions. rather, associations — some of them compelling — have been found between diet and outcomes including disease severity and the number of conditions experienced by a patient. evidence is emerging in support of medical nutrition therapy as a way of reducing the severity and incidence of dermatologic diseases, including acne. researchers observed a link between high glycemic index diets and acne. dermatologists also recommend a diet low in simple sugars as a method of improving acne. as of 2014, the available evidence is insufficient to use milk restriction for this purpose. benzoyl peroxide the common acne vulgaris treatment benzoyl peroxide cream benzoyl peroxide (bpo) is a first-line treatment for mild and moderate acne due to its effectiveness and mild side-effects (mainly skin irritation). in the skin follicle, benzoyl peroxide kills c. acnes by oxidizing its proteins through the formation of oxygen free radicals and benzoic acid. these free radicals likely interfere with the bacterium's metabolism and ability to make proteins. additionally, benzoyl peroxide is mildly effective at breaking down comedones and inhibiting inflammation. combination products use benzoyl peroxide with a topical antibiotic or retinoid, such as benzoyl peroxide/clindamycin and benzoyl peroxide/adapalene, respectively. topical benzoyl peroxide is effective at treating acne. side effects include increased skin photosensitivity, dryness, redness, and occasional peeling. sunscreen use is often advised during treatment, to prevent sunburn. lower concentrations of benzoyl peroxide are just as effective as higher concentrations in treating acne but are associated with fewer side effects. unlike antibiotics, benzoyl peroxide does not appear to generate bacterial antibiotic resistance. retinoids retinoids are medications that reduce inflammation, normalize the follicle cell life cycle, and reduce sebum production. they are structurally related to vitamin a. studies show dermatologists and primary care doctors underprescribe them for acne. the retinoids appear to influence the cell life cycle in the follicle lining. this helps prevent the accumulation of skin cells within the hair follicle that can create a blockage. they are a first-line acne treatment, especially for people with dark-colored skin. retinoids are known to lead to faster improvement of postinflammatory hyperpigmentation. topical retinoids include adapalene, retinol, retinaldehyde, isotretinoin, tazarotene, trifarotene, and tretinoin. they often cause an initial flare-up