Pathogenesis, clinical manifestations, and diagnosis of acne vulgaris

INTRODUCTION — Acne vulgaris is a common cutaneous disorder characterized by chronic or recurrent development of papules, pustules, or nodules on the face, neck, trunk, or proximal upper extremities (picture 1A-J). The pathogenesis of acne vulgaris involves the interaction of multiple factors that result in the formation of comedones and the development of inflammation.

Acne vulgaris is most frequent among adolescents and young adults but is not limited to these ages. The severity of skin involvement varies from minimal involvement to disfiguring and highly inflammatory presentations. Hyperpigmentation, scarring, and negative psychosocial effects are common complications.

The pathogenesis, clinical manifestations, and diagnosis of acne vulgaris will be reviewed here. Acne in children younger than adolescents is reviewed in greater detail separately. The treatment of acne vulgaris is also discussed separately.

●(See "Acne in infants, young children, and preadolescents".)

●(See "Acne vulgaris: Overview of management".)

●(See "Acne vulgaris: Management of moderate to severe acne in adolescents and adults".)

●(See "Oral isotretinoin therapy for acne vulgaris".)

●(See "Light-based, adjunctive, and other therapies for acne vulgaris".)

●(See "Management of acne scars".)

EPIDEMIOLOGY — Acne vulgaris is common and occurs most frequently in adolescents and young adults. Estimates of the prevalence of acne vulgaris in adolescents range from 35 to over 90 percent [1-3].

Acne often begins in the preadolescent period (ages 7 to 12 years) and resolves in the third decade, but may persist into adulthood or develop de novo in adulthood. Adolescent acne exhibits a male predominance; in contrast, postadolescent acne predominantly affects women [4]. (See "Postadolescent acne in women".)

The prevalence of acne decreases with increasing age. A survey of over 1000 adults in the United States found the following rates of self-reported acne in males and females [2]:

●20 to 29 years – 43 and 51 percent, respectively

●30 to 39 years – 20 and 35 percent, respectively

●40 to 49 years – 12 and 26 percent, respectively

●Ages 50 and older – 7 and 15 percent, respectively

Of note, studies using a clinical examination typically find a lower prevalence than survey studies that document self-reported acne.

Infantile acne, a variant of acne vulgaris, may begin in infancy. Mid-childhood acne (acne that develops in children ages one to six years) is uncommon and may be an indicator of an underlying condition warranting further evaluation. (See "Acne in infants, young children, and preadolescents", section on 'Classification' and "Acne in infants, young children, and preadolescents", section on 'Clinical manifestations'.)

PATHOGENESIS — Acne vulgaris is an inflammatory disorder of the pilosebaceous unit, which is comprised of the hair follicle and sebaceous gland. The pathogenesis of acne involves a complex interplay of host factors, such as androgen-mediated stimulation of sebaceous glands, dysbiosis within the microbiome of the pilosebaceous follicle, and innate and cellular immune responses, and may be influenced by factors such as genetics and, possibly, diet [5].

Lesion development — The microcomedo (a small, hyperkeratotic plug composed of corneocytes in the lower portion of the follicular infundibulum; plural "microcomedones") is considered the precursor for the clinical lesions of acne vulgaris, which include closed comedones (often colloquially called "whiteheads"), open comedones (often colloquially called "blackheads"), and inflammatory papules, pustules, and nodules. The process by which microcomedones develop and evolve into other acne lesions remains to be elucidated but may involve interaction of four main pathogenic factors:

●Follicular hyperkeratinization

●Increased sebum production by sebaceous glands

●Cutibacterium acnes (C. acnes, formerly Propionibacterium acnes), an anaerobic diphtheroid that is a normal component of skin flora

●Inflammation

The temporal sequence of events leading to formation of acne lesions is unknown. The following events have been proposed (figure 1):

●Accumulation of sebum and keratinous material converts a microcomedo into a closed comedo (picture 1B).

●The follicular orifice is opened with continued distension, forming an open comedo (picture 1C). Densely packed keratinocytes, oxidized lipids, and melanin contribute to the dark color of the open comedo.

●Immune responses to C. acnes contribute to the development of inflammatory papules and pustules. Follicular rupture releases bacteria, proinflammatory lipids, and keratin into the surrounding dermis, leading to exacerbation of inflammation and/or nodule formation (picture 1G, 1K).

Sebaceous glands and the role of androgens — Androgens contribute to the development of acne by stimulating the growth and secretory function of sebaceous glands, leading to increased sebum production. Increased sebum production is thought to provide a growth medium for C. acnes. C. acnes utilizes triglycerides in sebum as a nutrient source by hydrolyzing them into free fatty acids and glycerol. The anaerobic, lipid-rich environment in microcomedos allows these bacteria to thrive.

Most circulating androgens are produced by the adrenal gland and the gonads (figure 2). Androgen production also occurs within the sebaceous glands, which convert dehydroepiandrosterone sulfate (DHEAS), an adrenal androgen precursor, to testosterone via the action of several enzymes (table 1). Testosterone is subsequently converted to 5-alpha-dihydrotestosterone (DHT) via the action of type I 5-alpha reductase in the sebaceous gland.

The effects of androgens are mediated through androgen receptors. Androgen receptors that bind DHT and testosterone are present in the sebaceous glands and the outer root sheath keratinocytes of the follicular epithelium. DHT has greater affinity for androgen receptors than testosterone.

Clinical observations support the importance of androgens for the development of acne. Although the majority of patients with acne have normal androgen levels, androgen excess due to conditions such as polycystic ovarian syndrome, congenital adrenal hyperplasia, or adrenal or ovarian tumors can cause acne. In addition, acne typically does not develop prior to adrenarche (the prepubertal period in which levels of DHEAS rise), with the exception of infantile acne, a condition seen in infants that results from excess androgen production by immature adrenal glands or gonads. Moreover, men with androgen insensitivity do not produce sebum and do not develop acne [6]. (See "Definition, clinical features, and differential diagnosis of polycystic ovary syndrome in adolescents" and "Epidemiology, phenotype, and genetics of the polycystic ovary syndrome in adults" and "Diagnosis and treatment of nonclassic (late-onset) congenital adrenal hyperplasia due to 21-hydroxylase deficiency" and "Adrenal hyperandrogenism" and 'Infantile acne' below and "Pathogenesis and clinical features of disorders of androgen action".)

Cutibacterium acnes and inflammation — The ability of C. acnes, the prominent commensal bacteria within the microbiome of pilosebaceous follicles [7-9], to activate innate and adaptive immune responses may contribute to the inflammatory response observed in acne. Sequencing of the C. acnes genome has led to the identification of bacterial properties that may contribute to inflammation and virulence [10,11]. Critical factors may include virulence-associated genes in certain C. acnes strains, C. acnes production of enzymes that promote degradation of the follicular wall and follicular rupture, and C. acnes surface proteins that trigger humoral and cell-mediated immune responses.

Strains of C. acnes associated with either acne (phylotype IA) or healthy skin (phylotypes II and III) have been identified [12]. The acne-associated strains are more likely to carry genes associated with antibiotic resistance [8]. Acne-associated strains also have a greater propensity to stimulate TH17 cells to secrete interferon (IFN)-gamma and proinflammatory interleukin (IL) 17, whereas healthy skin-associated strains stimulate TH17 cells to produce anti-inflammatory IL-10 [13,14]. Vitamin A and vitamin D may play regulatory roles in the C. acnes-induced IL-17 response; in an in vitro study, C. acnes-mediated IL-17 induction was inhibited by exposure of peripheral blood mononuclear cells to vitamin A or vitamin D [13].

C. acnes activates the innate immune response to produce proinflammatory IL-1 via activation of the nod-like receptor P3 (NLRP3) inflammasome in human sebocytes and monocytes [15,16]. It also binds and activates toll-like receptor 2, located on perifollicular macrophages, and triggers the release of proinflammatory cytokines (including IL-8 and IL-12) [17,18]. These cytokines contribute to the attraction of neutrophils and the release of neutrophil lysosomal enzymes that promote follicular rupture (see "Toll-like receptors: Roles in disease and therapy"). Differences in the host inflammatory response to C. acnes or the pathogenicity of specific strains of C. acnes that colonize skin may contribute to the variation in the prevalence and severity of acne [12,19]. C. acnes may also form biofilms within follicles that could contribute to resistance to therapy [20].

Gene expression studies have been performed in the skin of patients with acne to further elucidate the inflammatory response. Upregulation of matrix metalloproteinases 1 and 3, inflammatory cytokines (IL-8), and antimicrobial peptides (human beta-defensin 4 and granzyme B) have been detected in inflammatory acne lesions [21]. In addition, human beta-defensin 2 immunoreactivity is highly upregulated in acne-affected skin, with human beta-defensin 1 also upregulated to a lesser degree [22].

Genetics — Individuals with close family members with acne are at increased risk for the disorder, supporting a genetic component to the disease [3,23-25]. Case-control studies have demonstrated a more than threefold risk among individuals with affected first-degree family members [23,25,26]. A large twin study of monozygotic and dizygotic twins also supported the heritable nature of acne [27]. An important role for genetics in mild acne is less certain due to the almost ubiquitous occurrence in young adolescents.

ASSOCIATED FACTORS — Proposed contributory factors for acne have included skin trauma, dietary habits, stress, insulin resistance, and body mass index.

Skin trauma — Repetitive mechanical trauma caused by scrubbing affected skin with soaps, detergents, astringents, or other agents may worsen acne by rupturing comedones, promoting the development of inflammatory lesions [28].

Diet — The role of diet in acne is an evolving concept [29-33]. Several studies suggest an association between acne and increased milk consumption and high glycemic load diets. Increased levels of insulin-like growth factor (IGF) related to dairy consumption or high glycemic load diets and natural hormonal components of milk or other bioactive molecules in milk are hypothesized to play a role [34-37] (see 'Insulin resistance' below):

●Milk consumption – A study of 47,355 women in the Nurses' Health Study that used retrospective data collection to determine diet during high school found an association between acne and intake of milk [34]. Two subsequent, large, prospective, cohort studies (one involving boys and the other involving girls) also reported an association of milk ingestion and acne [38,39]. All three studies were questionnaire-based, requiring subjects to recall their dietary intake and self-diagnose acne and disease severity.

A case-control study of 205 patients with clinician-confirmed moderate to severe acne and 358 controls with mild or nonexistent acne also found an association between milk consumption (more than three portions per week) and moderate to severe acne (odds ratio [OR] 1.78, 95% CI 1.22-2.59) [23]. Similar to the other studies, food intake history was assessed via a retrospective patient questionnaire.

A case-control study that used three 24-hour diet recall phone interviews to assess typical food intake in 120 teenagers (ages 14 to 19 years) with moderate facial acne and 105 teenagers without acne suggests that the association of acne with higher milk consumption may be limited to low-fat and skim milk [40]. The study did not find an association between acne and consumption of full-fat milk.

A longitudinal, questionnaire-based, population study of Norwegian adolescents demonstrated an association between high intakes of dairy products and acne in adolescence [41].

●High glycemic load diets – Glycemic load is a nutritional concept that refers to a measure of glycemic effect (glucose-raising potential) of dietary carbohydrates.

A 12-week, randomized trial that compared low and high glycemic load diets in 43 male patients with acne found a greater reduction in lesion counts with the low glycemic load diet [42]. However, the participants on that diet also lost more weight than those on the high glycemic load diet, so it is possible that the improvement in acne was due to changes in weight rather than the composition of the diet. Additionally, a study of 20 subjects with altered metabolic profiles, randomized to a low glycemic load diet and metformin versus control, resulted in statistically significant improvements in both acne and metabolic parameters in the intervention group [43].

●Other factors – Although it is a common assumption that chocolate consumption increases severity of acne, a relationship between chocolate consumption and the prevalence or severity of acne has not been proven [32].

Data on favorable effects of dietary factors, such as zinc, omega-3 fatty acids, antioxidants, vitamin A, and dietary fiber, on acne vulgaris are limited [44]. Further studies are necessary to determine the roles of these supplements in acne vulgaris.

Stress — Psychologic stress is often proposed as a potential exacerbating factor for acne [45,46]. Some studies have found an association between stress and increased acne severity.

A prospective cohort study in 94 secondary school students compared acne severity and sebum production at times of high stress (midterm examinations) and low stress (summer holidays) [47]. Sebum production did not appear to be related to stress, but increased acne severity, as assessed by an examiner blinded to the hypothesis of the study, did appear to be associated with stress, particularly in boys.

Similarly, a study of 22 university students found that greater acne severity appeared to correlate with increased perceived stress around the time of school examinations [48].

Insulin resistance — Insulin resistance may play a role in acne. Insulin resistance may stimulate increased androgen production and is associated with increased serum levels of insulin-like growth factor-1 (IGF-1), a finding linked to increased facial sebum excretion [49].

There is a normal rise in insulin resistance and IGF-1 during puberty, the typical time of onset of acne. In addition, some studies have found higher serum IGF-1 levels in women with postadolescent acne than in women without acne [50] or a positive correlation between serum IGF-1 levels and acne lesion counts in women [36]. Moreover, a cross-sectional study of 100 postadolescent males with acne found a higher prevalence of insulin resistance in males with acne than in 100 age-matched controls (22 versus 11 percent) [51].

Body mass index — Studies evaluating the relationship between acne vulgaris and weight have yielded varied results, resulting in uncertainty regarding the relationship between these conditions [23,52-56]. One of the largest studies, a population-based study of over 600,000 Israeli adolescents and young adults (mean age 19 years), found an inverse relationship between excess weight and acne. As body mass index (BMI) increased, risk for acne progressively decreased, with diagnoses of acne in 20 and 16 percent of underweight (BMI <18.5) males and females, respectively, compared with 13 and 11 percent of severely obese (BMI >35) males and females, respectively [55]. The adjusted OR for acne in severely obese individuals was 0.53 (95% CI 0.42-0.64) for males and 0.5 (95% CI 0.37-0.62) for females. Individuals with a BMI of 18.5 to 22 were defined as the reference group.

In contrast, a case-control study of approximately 200 adolescents and young adults (ages 10 to 24) with moderate to severe acne and approximately 350 controls with no acne or mild acne found a correlation between low BMI and a reduced risk for moderate to severe acne that was most evident among males [23]. In addition, a cross-sectional, survey-based study of approximately 3600 young adults (ages 18 and 19) in Norway found an association between rising BMI and increased risk for acne among females [53].

CLINICAL MANIFESTATIONS

Classic features — The typical distribution of acne vulgaris correlates with areas of the body with large, hormonally responsive sebaceous glands, including the face, neck, chest, upper back, and upper arms. One or more types of active lesions may be present, including:

●Closed comedones – Noninflammatory; <5 mm; dome-shaped; smooth; skin-colored, whitish, or grayish papules (picture 1B)

●Open comedones – Noninflammatory, <5 mm papules with a central, dilated, follicular orifice containing gray, brown, or black, keratotic material (picture 1C)

●Papulopustular acne – Inflamed, relatively superficial papules and pustules, typically <5 mm in diameter (picture 1A, 1G)

●Nodular acne – Deep-seated, inflamed, often tender, large papules (≥0.5 cm) or nodules (≥1 cm) (picture 1I, 1L)

Nodular acne is sometimes inaccurately referred to as "cystic" or "nodulocystic" acne. In reality, true cysts are rare.

Skin pigmentation may mask the characteristic erythema of inflamed lesions in patients with highly pigmented skin (picture 1I).

The extent and severity of skin involvement varies widely, ranging from the periodic appearance of a few small comedones to the chronic presence of numerous inflamed nodules involving the majority of skin in an affected region (picture 1L-M). Patient characteristics may influence the likelihood of certain presentations. Preadolescent and young adolescent patients often present with comedonal acne involving the T-zone (involving the forehead, nose, and chin). As the acne progresses, adolescents may develop inflammatory lesions (picture 1B, 1G). Adult women may present with acne involving the lower face and neck that is often associated with premenstrual flares (picture 1A, 1N) [57,58]. Premenstrual flares of acne appear to be more common in women over the age of 33 than in women aged 20 to 33 years [59]. (See "Postadolescent acne in women".)

Estimations of acne severity are patient-specific and depend on a number of factors. The clinical type of lesions, presence of scarring, presence of draining lesions or sinus tracts, lack of therapeutic response, and the psychologic impact of acne are some of the features taken into account [60]. As an example, patients with inflammatory, nodular acne are often considered to have severe acne. Similarly, a patient without nodules but who has numerous inflammatory papules and pustules and notable scarring could also be classified as having severe disease.

Common sequelae — Resolution of individual acne lesions may leave transient or permanent changes on the skin. Postinflammatory hyperpigmentation and scarring are common sequelae that can be highly distressing for patients.

Postinflammatory hyperpigmentation — As with other inflammatory skin conditions, acne vulgaris may lead to the development of hyperpigmentation at the site of an active or resolving lesion. The risk for hyperpigmentation increases with increasing baseline skin pigmentation and is particularly common in individuals with skin phototypes IV to VI (table 2). (See "Postinflammatory hyperpigmentation".)

Postinflammatory hyperpigmentation typically resolves spontaneously, but an individual hyperpigmented macule may persist for several months or longer without treatment. As a result, even patients with relatively mild, active acne can exhibit postinflammatory hyperpigmentation as a prominent disfiguring feature (picture 2C).

Scarring — Acne scarring is a common consequence of acne vulgaris that occurs in some patients. Inflammatory acne is considered more likely to result in scarring than noninflammatory acne. Why scarring occurs in some patients and not others despite similar manifestations of acne vulgaris is not clear. (See "Management of acne scars", section on 'Pathogenesis'.)

Various types of scars can result from acne vulgaris, including atrophic scars (ice pick scars, rolling scars, and boxcar scars), hypertrophic scars, and keloids (picture 2A-B). The features of acne scars are reviewed separately. (See "Management of acne scars", section on 'Classification'.)

Variants — Occasional variants of acne vulgaris include acne conglobata and acne excoriée.

Acne conglobata — Acne conglobata is a severe form of nodular acne that most often occurs in young males (picture 1M). Skin involvement tends to be most prominent on the back, chest, and buttocks but can also appear on the face or other sites. Large, draining lesions; sinus tracts; and severe scarring may occur. Sinus tracts manifest as fluctuant, linear lesions and are formed when nodules merge. Systemic symptoms are absent.

Acne conglobata is distinct from acne fulminans, an acute condition characterized by nodules, friable plaques, erosions, and ulcers. (See 'Acne fulminans' below.)

The treatment of acne conglobata is reviewed separately. (See "Acne vulgaris: Management of moderate to severe acne in adolescents and adults", section on 'Acne conglobata'.)

Acne excoriée — Acne excoriée typically presents with relatively mild acne comedones or inflammatory papules that are chronically and obsessively picked and excoriated, leading to erosions and scarring (picture 3). This condition is often, but not always, seen in young women. An underlying psychiatric disorder can be associated, and treatment may involve antidepressants and psychotherapy. (See "Skin picking (excoriation) disorder and related disorders".)

Infantile acne — Infantile acne typically begins between ages three to six months and results from elevated levels of androgens produced by the immature adrenal gland in girls and the immature adrenal gland and testes in boys. Androgen levels fall by age one to two and is accompanied by improvement in acne. (See "Vesicular, pustular, and bullous lesions in the newborn and infant", section on 'Infantile acne'.)

COMPLICATIONS — Potential complications of acne vulgaris include psychosocial dysfunction, gram-negative folliculitis, acne fulminans, and solid facial edema.

Psychologic effects — Acne vulgaris can contribute to significant psychologic morbidity and, rarely, to mortality due to suicide [61,62]. Embarrassment, anxiety, and lowered self-esteem related to the appearance of affected skin or disfiguring scars can impact the social lives and employment of affected individuals.

Gram-negative folliculitis — Patients with acne vulgaris who have been treated with long-term systemic antibiotics (usually tetracyclines) may develop gram-negative folliculitis. These patients exhibit an initial response to the oral antibiotic, followed by apparent resistance to the treatment and worsening of acne.

Inflammatory papules, pustules, and nodules typically appear on perinasal skin and the central face. A culture of lesions will yield gram-negative organisms, such as Enterobacter, Klebsiella, Pseudomonas, Proteus, or Escherichia species. (See "Infectious folliculitis", section on 'Bacterial folliculitis'.)

Acne fulminans — Acne fulminans is a disorder characterized by an acute eruption of large, inflammatory nodules and friable plaques with erosions, ulcers, and hemorrhagic crusts (picture 4). This rare condition primarily affects adolescent males with pre-existing acne vulgaris. Acne fulminans may be triggered by isotretinoin therapy or may occur spontaneously. The pathogenesis is unclear. Lesions usually involve the trunk but may be present elsewhere.

Acne fulminans may occur in association with systemic symptoms (eg, fever, malaise, bone pain, arthralgias), erythema nodosum, and laboratory and radiologic abnormalities [63]. Potential laboratory abnormalities include leukocytosis, anemia, and an elevated erythrocyte sedimentation rate or C-reactive protein. Radiographs may reveal osteolytic lesions of the bone, particularly in the sternum, clavicles, sacroiliac joints, or hips.

A proposed classification system for acne fulminans divides the condition into four variants [63]:

●Acne fulminans with systemic symptoms – Skin manifestations (abrupt, dramatic flare of inflammatory acne with erosions, crusts, ulcers, and hemorrhagic nodules or plaques) are accompanied by systemic symptoms, laboratory abnormalities, or osteolytic bone lesions.

●Acne fulminans without systemic symptoms – Skin manifestations are similar to acne fulminans with systemic symptoms, but systemic findings are absent.

●Isotretinoin-induced acne fulminans with systemic symptoms – Drug-induced form of acne fulminans with systemic findings; skin manifestations are similar to the other variants.

●Isotretinoin-induced acne fulminans without systemic symptoms – Drug-induced form of acne fulminans without systemic findings; skin manifestations are similar to the other variants.

Isotretinoin-induced acne fulminans without systemic symptoms is the most common type of acne fulminans [63].

The evaluation and treatment of patients with acne fulminans are reviewed separately. (See 'Additional tests' below and "Acne vulgaris: Management of moderate to severe acne in adolescents and adults", section on 'Acne fulminans'.)

Solid facial edema — Solid facial edema (Morbihan's disease) is a rare complication of acne that presents as facial soft tissue edema and erythema. The condition may wax and wane in severity but usually does not spontaneously resolve without treatment. Improvement with isotretinoin with or without ketotifen, systemic glucocorticoids, or clofazimine has been reported [64].

ASSOCIATED DISEASES — Hyperandrogenism, a condition that may occur in disorders such as polycystic ovarian syndrome, late-onset adrenal hyperplasia, and adrenal or ovarian tumors, may cause acne. Polycystic ovarian syndrome is the most common cause of hyperandrogenism in women. (See "Definition, clinical features, and differential diagnosis of polycystic ovary syndrome in adolescents" and "Epidemiology, phenotype, and genetics of the polycystic ovary syndrome in adults" and "Diagnosis and treatment of nonclassic (late-onset) congenital adrenal hyperplasia due to 21-hydroxylase deficiency" and "Adrenal hyperandrogenism" and "Pathogenesis and clinical features of disorders of androgen action".)

Examples of rare syndromes that may include acne as a feature include SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome and PAPA (sterile pyogenic arthritis, pyoderma gangrenosum, and acne) syndrome. Patients with SAPHO syndrome exhibit features of inflammatory arthritis or osteitis, particularly of the anterior chest wall. (See "SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome" and "The autoinflammatory diseases: An overview".)

DIAGNOSIS AND EVALUATION — The diagnosis of acne vulgaris is generally made based upon the physical examination. There are no laboratory tests that confirm a diagnosis of acne vulgaris. The need for laboratory or radiologic tests is generally limited to patients for whom the clinical evaluation suggests underlying hyperandrogenism or other specific conditions warranting additional testing. Skin biopsies are not typically necessary. (See "Acne vulgaris: Overview of management".)

History — The patient history is an important component of the evaluation. The history is particularly helpful for identifying patients with acne caused or exacerbated by an exposure (eg, drug-induced acne) or who may need further evaluation for associated disease (eg, hyperandrogenism, SAPHO [synovitis, acne, pustulosis, hyperostosis, and osteitis] syndrome, acne fulminans). Information gleaned from the patient history may also be helpful for guiding treatment. (See "Acne vulgaris: Overview of management", section on 'Pretreatment assessment'.)

Helpful information includes:

●Age of onset and current age

●Medication history (table 3)

●Menstrual history in females (frequency, association with acne flares)

●Medical history

●Family history of acne

●Signs of virilization in young children or females (hirsutism, male pattern hair loss, genital enlargement, deepening of voice)

●Joint, bone, or systemic symptoms in patients with severe acne

●Skin care regimen (use of occlusive or comedogenic products)

●Current and prior treatments and response

●Psychologic impact of acne

Physical examination — The diagnosis is based upon the recognition of characteristic lesions (closed comedones, open comedones, inflammatory papules, inflammatory pustules, inflamed nodules) in a characteristic distribution (eg, face, chest, shoulders, back, or upper arms) during the skin examination.

Helpful factors to assess on the skin examination include:

●Lesion type and distribution

●Lesion stages (monomorphous versus polymorphous)

●Signs of hyperandrogenism in young children and females (hirsutism, male pattern hair loss)

●Presence of sequelae of acne vulgaris, including postinflammatory hyperpigmentation and scarring

The identification of comedones with or without other lesion types strongly supports the diagnosis. In addition, acne lesions are generally in various stages of development and resolution, in contrast to some presentations of drug-induced acne, which exhibit the acute development of monomorphous lesions. Pityrosporum folliculitis, a condition in the differential diagnosis of acne vulgaris, also often presents with monomorphous inflammatory lesions. (See 'Trunk and extremities' below and "Infectious folliculitis", section on 'Fungal folliculitis'.)

Additional tests — Laboratory tests and radiologic imaging is not indicated for the vast majority of patients with acne vulgaris. Indications for testing are primarily limited to patients who exhibit signs of associated disease or acne fulminans.

Populations in whom testing is advised include:

●Patients with signs of hyperandrogenism – Assessment for hyperandrogenism is indicated for patients exhibiting additional signs suggestive of androgen excess, such as may occur in polycystic ovarian syndrome, congenital adrenal hyperplasia, and adrenal or ovarian tumors [65]. Clinical findings that support an evaluation include:

•Irregular or infrequent menses in females

•Hirsutism

•Signs of virilization in females or prepubertal males (male pattern hair loss, clitoromegaly, increased muscle mass, deepening of voice (picture 5))

•Development of mid-childhood acne (onset between one and six years of age)

•Abrupt onset of severe, atypical, recalcitrant acne

Other signs that may suggest androgen excess in prepubertal children include early-onset body odor, early development of axillary or pubic hair, accelerated growth, advanced bone age, and genital maturation [65]. An endocrinologic work-up is usually not necessary for children with preadolescent acne (ages 7 to 12 years) in the absence of other clinical signs of hyperandrogenism [66,67]. (See "Acne in infants, young children, and preadolescents", section on 'Diagnosis'.)

Recommendations for the evaluation for hyperandrogenism vary based upon the clinical presentation:

•Premenopausal adolescent or adult females with oligomenorrhea without virilization:

-(See "Diagnostic evaluation of polycystic ovary syndrome in adolescents", section on 'Basic diagnostic approach'.)

-(See "Diagnosis of polycystic ovary syndrome in adults", section on 'Evaluation'.)

•Premenopausal adolescent or adult females with hirsutism without oligomenorrhea or virilization:

-(See "Evaluation of premenopausal women with hirsutism", section on 'Hirsutism and normal menstrual cycles'.)

-(See "Evaluation and management of postmenopausal hyperandrogenism".)

•Premenopausal adolescent or adult females with virilization:

-(See "Evaluation of premenopausal women with hirsutism", section on 'Severe hyperandrogenism'.)

-(See "Evaluation of premenopausal women with hirsutism", section on 'Additional evaluation for severe hyperandrogenemia'.)

•Postmenopausal women with hirsutism or virilization:

-(See "Evaluation and management of postmenopausal hyperandrogenism".)

•Children with mid-childhood acne or features suggestive of androgen excess:

-(See "Acne in infants, young children, and preadolescents", section on 'Diagnosis'.)

The abrupt onset of severe, atypical, or recalcitrant acne should prompt consideration of hyperandrogenism induced by adrenal or ovarian tumors. Laboratory tests and radiologic imaging may be necessary. (See "Clinical presentation and evaluation of adrenocortical tumors", section on 'Diagnostic evaluation' and "Evaluation of premenopausal women with hirsutism" and "Evaluation and management of postmenopausal hyperandrogenism" and "Ovarian hyperthecosis" and "Sex cord-stromal tumors of the ovary: Epidemiology, clinical features, and diagnosis in adults".)

Patients in whom initial tests reveal abnormalities may be referred to endocrinology, gynecology, or other specialists, as needed.

●Patients with acne fulminans – The following evaluation is suggested for patients with clinical findings consistent with acne fulminans to assess for systemic involvement and in preparation for isotretinoin therapy [63]:

•Complete blood count with differential

•Liver function tests

•Erythrocyte sedimentation rate and C-reactive protein in patients with systemic findings

•Serum cholesterol and triglycerides

•Urine or serum pregnancy test (in women)

•Radiograph (if symptoms suggestive of bone or joint involvement are present)

●Patients with musculoskeletal symptoms suggestive of SAPHO syndrome – SAPHO syndrome should be suspected in patients in whom moderate to severe nodular acne is accompanied by symptoms of arthritis or osteitis, particularly when involving the chest wall. The assessment of patients with SAPHO syndrome is reviewed separately. (See 'Associated diseases' above and "SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome", section on 'Diagnosis'.)

DIFFERENTIAL DIAGNOSIS — Although acne vulgaris is a common and often easily diagnosed condition, the possibility of other disorders, including other skin diseases and acneiform eruptions, should always be considered. Important diagnoses to consider include other skin diseases that induce inflammatory or noninflammatory skin lesions and acneiform eruptions, nonacne disorders that closely resemble acne.

Inflammatory facial lesions — Examples of disorders in the differential diagnosis of facial inflammatory acne lesions include:

●Rosacea – Common features of rosacea include erythema, telangiectasias, and papules or pustules on the central face (picture 6). Acne vulgaris is distinguished from rosacea by the presence of comedones and the absence of telangiectasias (figure 3). (See "Rosacea: Pathogenesis, clinical features, and diagnosis".)

●Periorificial dermatitis – Periorificial dermatitis (also known as perioral dermatitis) is characterized by small, grouped, erythematous papules in a perioral (or occasionally perinasal or periorbital) distribution (picture 7A-B). When the perioral skin is involved, a rim of spared skin is usually seen around the vermilion border of the lip. (See "Perioral (periorificial) dermatitis".)

●Demodex folliculitis – Demodex folliculitis often presents as inflammatory papules and pustules on the face (picture 8). The diagnosis is often made when patients fail to respond to treatments for rosacea or acne. An oil preparation demonstrating multiple Demodex mites provides support for the diagnosis (picture 9). However, clinical correlation is necessary because Demodex mites can also be found on normal skin, and increased numbers of mites are associated with papulopustular rosacea and periorificial dermatitis. (See "Infectious folliculitis", section on 'Demodex folliculitis'.)

●Pseudofolliculitis barbae – Pseudofolliculitis barbae occurs most commonly in individuals with tightly curled hair. Inflammatory papules and pustules occur in the beard area and may result in keloidal scarring. It is thought that short, shaved or clipped hairs in the beard area curl back towards the skin, penetrate the skin, and cause a foreign body inflammatory reaction (picture 10A-B). (See "Pseudofolliculitis barbae" and "Keloids and hypertrophic scars".)

●Facial angiofibromas in tuberous sclerosis – Facial angiofibromas associated with tuberous sclerosis usually appear in childhood. These lesions commonly present as persistent, 1 to 3 mm, pink or red papules on the nose and medial cheeks (picture 11). (See "Tuberous sclerosis complex: Clinical features".)

Noninflammatory facial lesions — Examples of disorders in the differential diagnosis of facial noninflammatory acne lesions include:

●Sebaceous hyperplasia – Visible enlargement of sebaceous glands is termed "sebaceous hyperplasia." It most commonly occurs in adults with a history of oily skin. These growths are umbilicated, yellowish papules most commonly found on the forehead and cheeks (picture 12A-B). These lesions may resemble basal cell carcinomas. (See "Cutaneous adnexal tumors", section on 'Sebaceous hyperplasia'.)

●Nevus comedonicus – Nevus comedonicus appears at birth or in childhood and exhibits a grouped or linear arrangement of comedones (picture 13).

●Adnexal tumors – Benign follicular tumors, such as trichoepitheliomas, trichodiscomas, or fibrofolliculomas, typically present as flesh-colored facial papules. (See "Cutaneous adnexal tumors".)

●Favre-Racouchot syndrome – Favre-Racouchot syndrome is a condition resulting from cutaneous photodamage (sun damage) seen in middle-aged or older adults. Open and closed comedos are found in areas of photodamage, usually on the lateral upper cheeks (picture 14).

Trunk and extremities — Examples of disorders that may present with lesions resembling acne vulgaris on the trunk or extremities include:

●Folliculitis – Staphylococcal, eosinophilic, pseudomonal, or Pityrosporum folliculitis may mimic inflammatory acne (picture 15A-D). Comedos are absent, and lesions are usually monomorphous, unlike the polymorphous lesions in different stages of development that are typical of acne. (See "Infectious folliculitis".)

●Keratosis pilaris – In this common condition caused by keratotic, follicular plugging, patients typically present with small, follicular papules on the extensor surfaces of the upper arms or thighs (picture 16A-B). Erythema may be present. Lesions can also occur on the face, particularly in children. (See "Keratosis pilaris".)

●Hidradenitis suppurativa – Hidradenitis suppurativa is a chronic inflammatory skin disorder characterized by recurrent, inflamed nodules and abscesses with a predilection for intertriginous skin areas, such as the axilla, groin, perianal, perineal, and inframammary regions (picture 17). Additional features include comedones, sinus tracts, and scarring. (See "Hidradenitis suppurativa: Pathogenesis, clinical features, and diagnosis".)

●Steatocystoma multiplex – Steatocystoma multiplex is an autosomal dominant or sporadic genetic disorder in which multiple yellow or skin-colored, sebum-filled cysts are found on the trunk, upper arms, or chest (picture 18). (See "Overview of benign lesions of the skin", section on 'Steatocystoma multiplex'.)

Acneiform eruptions — There are multiple disorders in which acne-like eruptions occur, unassociated with true acne vulgaris. These include:

●Drug-induced acne – Drug-induced acne typically presents with a monomorphous, inflammatory, papular eruption (as opposed to the polymorphous eruption with lesions in varying stages seen with acne vulgaris) (picture 19A-B). Medications associated with drug-induced acne are listed in a table (table 3). Glucocorticoid-induced eruptions are also referred to as "steroid folliculitis." (See "Topical corticosteroids: Use and adverse effects", section on 'Cutaneous'.)

●Neonatal cephalic pustulosis – Neonatal cephalic pustulosis (previously called neonatal acne) presents with inflammatory papules and pustules on the face in the absence of comedones. Neonatal cephalic pustulosis is distinct from infantile acne. Neonatal cephalic pustulosis appears within the first few weeks of life (picture 20); infantile acne usually appears around three to six months of age. (See "Skin lesions in the newborn and infant", section on 'Neonatal cephalic pustulosis (neonatal acne)'.)

●Acne cosmetica – Cosmetic products that contain comedogenic ingredients can induce the formation of acne lesions. This type of acne has lessened as products designed to be less comedogenic have become widely available. Heavy, oil-based hair products are still commonly used and may contribute to the development of acne on the forehead (pomade acne).

Irritant reactions to cosmetic products can also produce eruptions that resemble acne vulgaris. Inflammatory papules or pustules may occur within hours after the application of the inciting product.

●Acne mechanica – Worn items, such as turtlenecks, bra straps, shoulder pads, orthopedic casts, and sports helmets, may irritate pilosebaceous follicles, stimulating comedo formation.

●Occupational acne and chloracne – Comedones, inflammatory papules, pustules, nodules, or cysts can occur in response to exposure to certain chemicals, including insoluble cutting oils, coal tar derivatives, and chlorinated hydrocarbons. "Chloracne" is the term used to describe acne that occurs with exposure to chlorinated hydrocarbons (eg, dioxin) via percutaneous contact, inhalation, or ingestion. Clinically, chloracne is characterized by large, monomorphic comedos with evolution into severely inflammatory and scarring lesions. Chloracne is most common on the face, neck, postauricular skin, axillae, and scrotum, although other sites may be involved.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Acne vulgaris".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Acne (The Basics)")

●Beyond the Basics topics (see "Patient education: Acne (Beyond the Basics)")

SUMMARY

●Overview – Acne vulgaris is a common skin condition in adolescents and young adults that may also occur at other ages. The clinical manifestations of acne vulgaris vary widely, and the psychologic impact can be significant. (See 'Epidemiology' above and "Acne in infants, young children, and preadolescents".)

●Pathogenesis – Acne vulgaris is a disorder of the pilosebaceous follicles (see 'Pathogenesis' above):

•Lesion development – Follicular hyperkeratinization, sebum production, Cutibacterium acnes, and inflammation are involved in the pathogenesis. The temporal sequence of events leading to the formation of acne lesions is unknown but likely involves both host factors and dysbiosis within the microbiome of the pilosebaceous follicle. (See 'Lesion development' above.)

•Role of androgens – Androgens induce sebum production and are an important factor in the development of acne vulgaris. Hyperandrogenism may cause acne, but most patients with acne vulgaris do not have androgen excess. (See 'Sebaceous glands and the role of androgens' above.)

•Role of diet – The role of diet in acne vulgaris is an evolving concept. A contributory effect of milk and high glycemic index diets has been proposed, but prospective trials are necessary to clarify the relationship between diet and acne. (See 'Diet' above.)

●Clinical manifestations – Typically, acne vulgaris occurs on areas of the body with hormonally sensitive sebaceous glands, including the face, neck, chest, upper back, and upper arms. Open comedones, closed comedones, and inflammatory papules, pustules, or nodules are the characteristic lesions (picture 1A-J). (See 'Clinical manifestations' above.)

●Sequelae and complications – Common sequelae of acne vulgaris include postinflammatory hyperpigmentation and scarring (picture 2A-C). Acne fulminans is a serious complication of acne vulgaris that may present as an acute eruption of inflamed nodules and friable plaques and systemic symptoms. Other cutaneous complications of acne vulgaris include gram-negative folliculitis and solid facial edema. (See 'Common sequelae' above and 'Complications' above.)

●Diagnosis – The diagnosis of acne vulgaris rests upon the patient's history and physical examination. Laboratory tests are not necessary for most patients. Patients with additional clinical findings suggestive of hyperandrogenism should be tested for androgen excess. (See 'Diagnosis and evaluation' above and "Acne in infants, young children, and preadolescents", section on 'Diagnosis'.)

●Differential diagnosis – Although acne vulgaris is often easily diagnosed, the differential diagnosis includes a wide variety of skin diseases and acneiform eruptions (figure 3). (See 'Differential diagnosis' above and "Acne in infants, young children, and preadolescents", section on 'Differential diagnosis'.)