pathogenesis, clinical manifestations, and diagnosis of acne vulgaris.pdf
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Pathogenesis, clinical manifestations, and diagnosis of acne vulgaris.pdfTRANSCRIPT
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Official reprint from UpToDate
www.uptodate.com2014 UpToDate
Authors
Diane Thiboutot, MDAndrea Zaenglein, MD
Section Editors
Robert P Dellavalle, MD, PhD, MSPHMoise L Levy, MDMark V Dahl, MD
Deputy Editor
Abena O Ofori, MD
Pathogenesis, clinical manifestations, and diagnosis of acne vulgaris
Disclosures
All topics are updated as new evidence becomes available and our peer review processis complete.Literature review current through:Feb 2014. | This topic last updated:Dec 9, 2013.
INTRODUCTION Acne vulgaris is the most common cutaneous disorder affecting adolescents and young adults.
Patients with acne can experience significant psychological morbidity and, rarely, mortality due to suicide [1,2]. The
psychological effects of embarrassment and anxiety can impact the social lives and employment of affected individuScars can be disfiguring and lifelong. In one prospective study of 90 patients with acne, a significant improvement in
esteem was found with treatment of the acne [3]. Thus, it is imperative that clinicians are familiar with acne vulgaris
its treatment.
The pathogenesis, clinical manifestations, diagnosis, and differential diagnosis of acne vulgaris will be reviewed here
The treatment of acne vulgaris is discussed elsewhere. (See "Treatment of acne vulgaris"and "Hormonal therapy fo
women with acne vulgaris"and "Oral isotretinoin therapy for acne vulgaris"and "Light-based, adjunctive, and other
therapies for acne vulgaris".)
EPIDEMIOLOGY Estimates of the prevalence of acne vulgaris in adolescents range from 35 to over 90 percent [4
Acne tends to resolve in the third decade, but it may persist into or develop de novo in adulthood. The exact prevale
in adults is uncertain, and studies using a clinical examination typically find a lower prevalence than surveys askin
patients to self-report acne.
Post-adolescent acne predominantly affects women, in contrast to adolescent acne which has a male predominance
In one survey of over 1000 adults, self-reported acne in men and women was documented as follows [5]:
The difference in the prevalence of acne in males and females was statistically significant in each age group.
PATHOGENESIS
Pilosebaceous follicles Acne vulgaris is a disease of pilosebaceous follicles. Four factors are involved (figure 1
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!
Follicular hyperkeratinization!
Increased sebum production!
Propionibacterium acnes (P. acnes) within the follicle!
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The sequence of events leading to the development of an acne lesion is not fully understood. The earliest change in
pilosebaceous unit was initially thought to be follicular hyperkeratinization, which is associated with both increased
proliferation and decreased desquamation of keratinocytes lining the follicular orifice. This results in partial obstructi
the follicle with sebum and keratin (the microcomedo). However, an influx of inflammatory cells in the perifollicular re
may precede the changes in keratinization [7]. Initiating factors for this inflammatory process are unknown.
Sebaceous glands enlarge with adrenarche (the prepubertal period in which levels of DHEA-S rise) and sebumproduction increases. Sebum provides a growth medium for P. acnes, an anaerobic diphtheroid that is a normal
component of skin flora. Microcomedones provide an anaerobic lipid-rich environment that allows these bacteria to
thrive; they utilize triglycerides in sebum as a nutrient source by hydrolyzing them into free fatty acids and glycerol.
Inflammation results from the proliferation of P. acnes. Sequencing of the P. acnes genome has led to the identificati
the following bacterial properties that may contribute to the inflammatory response [8,9]:
A component of the host innate immune system, the toll-like receptor, is also thought to play an important role in the
acnes mediated inflammatory response [10]. Toll-like receptor-2, located on perifollicular macrophages, binds to P.
acnes, and triggers the release of proinflammatory cytokines (including IL-8 and IL-12) [11]. These cytokines contrib
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 P. acnes or the
pathogenicity of specific strains of P. acnes that colonize skin may contribute to the variation in the prevalence and
severity of acne [12,13].
Types of acne lesions The microcomedo is considered the precursor for the clinical lesions of acne vulgaris,including closed comedos, open comedos, and inflammatory papules, pustules, and nodules. The process by which
microcomedones evolve into other acne lesions remains to be elucidated, but may involve the following:
Role of androgens Androgens contribute to the development of acne through stimulating the growth and secreto
function of sebaceous glands. Most circulating androgens are produced by the adrenal gland and the gonads (figure
Androgen production also occurs within the sebaceous glands, which convert dehydroepiandrosterone sulfate (DHE
S), 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.
Inflammation!
Enzymes produced by P. acnes may promote the degradation of the follicular wall and follicular rupture.!
P. acnes surface proteins may play a role in antigenicity, triggering humoral and cell-mediated immune respons!
Heat shock proteins, which promote inflammation via the innate immune system, are produced by P. acnes.!
Porphyrins produced by P. acnes may contribute to adjacent tissue damage and inflammation.!
Accumulation of sebum and keratinous material converts a microcomedo into a closed comedo (a whitehead)
(picture 2C).
!
The follicular orifice is opened with continued distension, forming an open comedo (a blackhead) (picture 1).
Densely packed keratinocytes, oxidized lipids, and melanin all contribute to the dark color of the open comedo
!
Follicular rupture contributes to the development of inflammatory lesions. Following follicular rupture,
proinflammatory lipids and keratin are extruded into the surrounding dermis, leading to inflammatory papule or
nodule formation (picture 2A-B).
!
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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. Men wit
androgen insensitivity (lacking androgen receptors) do not produce sebum and do not develop acne, suggesting an
important role of androgen receptors in the pathogenesis of acne [14].
Infantile acne (with typical onset at age three to six months) occurs as a result of elevated levels of androgens produ
by the immature adrenal gland in girls, and the immature adrenal gland and testes in boys. Androgen levels fall by a
one to two, and acne subsequently improves. (See "Benign skin and scalp lesions in the newborn and young infant"
section on 'Neonatal acne'and "Benign skin and scalp lesions in the newborn and young infant", section on 'Infantile
acne'.)
The onset of acne in children correlates with the rise in serum levels of DHEA-S that occurs as puberty approaches
(adrenarche). Higher serum levels of DHEA-S are found in prepubertal girls with acne than in those without [15]; tho
with the highest levels develop the most severe acne [16].
Although androgen excess due to a variety of conditions can cause acne, the majority of patients with acne have no
androgen levels. Conditions in which hyperandrogenism is seen include polycystic ovarian syndrome, congenital ad
hyperplasia, and adrenal or ovarian tumors. (See "Pathogenesis and causes of hirsutism", section on 'Etiology'.)
External factors Soaps, detergents, and astringents remove sebum from the skin surface but do not alter sebum
production. Repetitive mechanical trauma caused by scrubbing with these agents may worsen the disorder by ruptu
comedos, promoting the development of inflammatory lesions [17]. Thus, patients with acne should refrain from rubb
their faces or picking their skin.
Turtlenecks, bra straps, shoulder pads, orthopedic casts, and sports helmets may all cause acne mechanica, in whic
occlusion of pilosebaceous follicles leads to comedone formation. Pomade acne is associated with the use of occlus
oil-based hair products. (See 'Acne cosmetica'below.)
Diet A potential role for diet in acne is controversial [18-21]. A study of 47,355 women in the Nurses' Health Study
used retrospective data collection to determine diet during high school found an association between acne and intak
milk [22]. The authors suggested that natural hormonal components of milk or other bioactive molecules in milk coul
exacerbate acne [22,23]. Two subsequent large prospective cohort studies (one involving boys and the other involvigirls) also reported an association of milk ingestion and acne [24,25]. 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 a possible association between milk consumption (more than three portions per week)
moderate to severe acne (odds ratio [OR] 1.78, 95% CI 1.22-2.59) [26]. Similar to the other studies, food intake histo
was assessed via a retrospective patient questionnaire. No randomized trials have evaluated the relationship betwe
dairy products and acne.
Other studies have suggested that insulin-like growth factor (IGF) may play a role in acne [27,28]. Milk consumption
been associated with increased levels of serum IGF [29]. IGF is also increased by ingestion of high glycemic loads a
could potentially link diet and acne. A 12-week randomized trial that compared low and high glycemic load diets in 4
male patients with acne found a greater reduction in lesion counts with the low glycemic load diet [30]. However, the
participants on that diet also lost more weight than those on the high glycemic load diet, so it is possible that the res
were due to changes in weight rather than the composition of the diet.
There is no reliable evidence that ingestion of chocolate is associated with an increased prevalence or severity of ac
[21].
Data on favorable effects of dietary factors such as zinc, omega-3 fatty acids, antioxidants, vitamin A, and dietary fib
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on acne vulgaris are limited [31]. Further studies are necessary to determine the roles of these supplements in acne
vulgaris.
Family history Individuals with close family members with acne are at increased risk for the disorder [26,32,33].
Case-control studies have demonstrated a more than three-fold risk among individuals with affected first-degree fam
members [26,33,34], and a large twin study of monozygotic and dizygotic twins also supported the heritable nature o
acne [35]. In cases of very severe acne, there is often a positive family history; but the role of genetics in mild acne i
uncertain due to the almost ubiquitous occurrence in young adolescents.
Stress Patients and clinicians commonly believe that psychological stress can exacerbate acne [36,37]. A
prospective cohort study in 94 secondary school students compared acne severity and sebum production at times o
high stress (midterm examinations) and low stress (summer holidays) [38]. Sebum production did not appear to be
related to stress, but acne severity, as assessed by an examiner blinded to the hypothesis of the study, did appear to
associated with stress, particularly in boys.
Similarly, a study of 22 university students found that acne severity appeared to have some correlation with stress
around the time of school examinations [39].
Receptors for corticotropin releasing hormone (CRH), a hormone involved in the stress response, are present in hum
sebaceous glands [40]. Sebaceous gland cells exhibit stronger staining for CRH in acne-involved skin than in norma
uninvolved skin. Although additional studies are necessary, these findings suggest that the CRH system may partici
in the occurrence of stress-exacerbated acne.
Body mass index Few studies have evaluated the relationship between weight and acne vulgaris, and study res
vary on the connection between these factors [26,41-43]. Whereas a case-control study of adolescents and young a
(ages 10 to 24) found a correlation between low BMI and a reduced risk for acne that was most evident among male
[26], a cross-sectional, survey-based study of young adults (ages 18 and 19) found a statistically significant associa
between rising BMI and increased risk for acne only among females [42].
CLINICAL MANIFESTATIONS AND CLASSIFICATION Acne vulgaris typically affects those areas of the body th
have the largest, hormonally-responsive sebaceous glands, including the face, neck, chest, upper back, and upper a
In addition to the typical lesions of acne vulgaris (eg, open comedones, closed comedones, and inflammatory lesionscarring and postinflammatory hyperpigmentation can occur, which can be greatly distressing for patients.
Postinflammatory hyperpigmentation is most common in patients with darker complexions, and an individual
hyperpigmented macule may take several months or more to resolve without treatment. (See "Treatment of acne
vulgaris", section on 'Therapy for postinflammatory hyperpigmentation'.)
Adult women may present with acne involving the lower face and neck that is often associated with premenstrual fla
(picture 3) [44,45]. These women, in particular, seem to benefit from hormonal therapies for acne [44]. Premenstrua
flares of acne appear to be more common in women over the age of 33 than in women aged 20 to 33 years [46]. (Se
"Hormonal therapy for women with acne vulgaris".)
Classification There is no universal classification system for acne vulgaris; the extensive variety of clinical
presentations would make it challenging to develop and implement such a system. A description of the actual lesion
encountered will be most useful when considering management of acne.
Young adolescents often have primarily comedonal acne consisting of noninflammatory lesions (closed and/or open
comedones) involving the forehead, nose and chin. As the acne progresses, patients develop inflammatory lesions
(papules, pustules, and nodules (picture 2A-C)) Comedones can become extensive in some patients (picture 1).
Nodules are tender inflammatory acne lesions that are larger than 5 mm in diameter [47]. Nodular acne is sometime
inaccurately referred to as "cystic" or "nodulocystic" acne (picture 4A-B). In reality, true cysts are rare. Sinus tracts, w
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manifest as fluctuant linear lesions, are formed when nodules merge. These are seen in the most severe forms of ac
and are difficult to treat (picture 5). The presence of scarring or postinflammatory hyperpigmentation is also assesse
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 [47]. As an example, patients with inflammatory, nodular
acne are often considered to have severe acne. Similarly, a patient without nodules but who has numerous inflamma
papules and pustules and notable scarring could also be classified as having severe disease.
Acne variants Occasionally, patients with acne vulgaris may exhibit variants of the disease, some of which requir
aggressive treatment [44,48]. These variants are discussed below.
Acne fulminans The presence of fever and arthralgias with an acute eruption of large inflammatory nodules a
friable plaques with hemorrhagic crusts suggests the diagnosis of acne fulminans, a systemic disorder (picture 6). T
rare condition affects adolescent males primarily. Lesions usually involve the trunk, but may be present elsewhere. A
fulminans is associated with leukocytosis, an elevated erythrocyte sedimentation rate, proteinuria, and osteolytic les
Patients with acne fulminans can be treated with systemic glucocorticoids (0.5 to 1 mg/kg) plus oral isotretinoinor or
antibiotics [49]. Treatment regimens vary, but oral glucocorticoids should be initiated about four weeks prior to startin
low-dose oral isotretinoin to prevent a flare of the condition [49]. Oral isotretinoin is started at 0.5 mg/kg/day or less a
can be gradually increased. After several weeks of therapy, glucocorticoids are tapered as tolerated. In rare cases,
treatment of acne vulgaris with isotretinoin can precipitate an acne fulminans-like eruption.
Acne conglobata Acne conglobata is a severe form of nodular acne that is most commonly seen in young m
(picture 7A-B). Lesions are most prominent on the back, chest, and buttocks, but can also appear in other sites. Larg
draining lesions, sinus tracts, and severe scarring may occur. Systemic symptoms are absent. Treatments have incl
systemic antibiotics, intralesional glucocorticoids, systemic glucocorticoids, and surgical intervention [48]. Patients c
respond well to isotretinoin, although they may experience severe flares at the start of isotretinoin therapy. For this
reason, lower doses of isotretinoin (0.5 mg/kg/day or less) plus systemic glucocorticoids before or during isotretinoin
therapy are often required [48].
A few case reports have documented improvement in acne conglobata during treatment with biologic TNF-alphainhibitors (etanercept[50], adalimumab[51], and combination therapy with infliximaband isotretinoin[52]). However
further study is necessary before treatment with these agents can be recommended.
SAPHO syndrome The SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, and osteitis) is another
disorder (picture 8). This diagnosis also requires systemic therapy [53]. (See "Major causes of musculoskeletal ches
pain", section on 'Sternocostoclavicular hyperostosis (SAPHO syndrome)'.), and (see "Treatment of musculoskeleta
chest pain"and "Neutrophilic dermatoses", section on 'SAPHO syndrome').
PAPA syndrome PAPA syndrome (sterile pyogenic arthritis, pyoderma gangrenosum, and acne) is an autoso
dominant inflammatory disorder that is discussed separately. (See "Periodic fever syndromes and other
autoinflammatory diseases: An overview", section on 'PAPA syndrome'.)
Gram-negative folliculitis Patients with pre-existing 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. Inflammator
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. Patient
are treated with antibiotics with gram negative coverage. Recalcitrant cases are managed with oral isotretinoinfor fo
five months [44].
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Neonatal acne and infantile acne Neonatal acne (also called neonatal cephalic pustulosis) and infantile acn
distinct conditions. Neonatal acne appears within the first few weeks of life (picture 9); infantile acne usually appears
around three to six months of age. (See "Benign skin and scalp lesions in the newborn and young infant", section on
'Neonatal acne'and "Benign skin and scalp lesions in the newborn and young infant", section on 'Infantile acne'.)
Childhood acne Mid-childhood acne (acne that occurs in children ages one to six years) is uncommon. Affec
children usually present with a mixture of comedones and inflammatory lesions on the face. An endocrinology worku
evaluate for hyperandrogenism is indicated when acne develops in a child in this age group [54].
Unlike mid-childhood acne, pre-adolescent acne (acne in children aged 7 to 12 years) is common. Acne may be the
initial sign of puberty [15]. A predominance of comedones with relatively few inflammatory lesions is typically seen in
affected children. An endocrinologic work-up usually is not necessary for children with pre-adolescent acne in the
absence of other clinical signs of hyperandrogenism [54,55]. However, the possibility of polycystic ovarian syndrome
should be considered in girls with unusually severe acne, other signs of hyperandrogenism, or a poor response to
treatment [54]. (See "Adrenal hyperandrogenism", section on 'Clinical manifestations'and "Clinical features and
diagnosis of polycystic ovary syndrome in adolescents", section on 'Clinical features'.)
Acne excorie des jeunes filles This scarring acne condition is often, but not always, seen in young women
Relatively mild acne comedones or inflammatory papules are chronically and obsessively picked and excoriated, lea
to erosions and scarring (picture 10). An underlying psychiatric disorder can be associated, and treatment may invoantidepressants and psychotherapy.
Solid facial edema Solid facial edema (Morbihan's disease) is a rare complication of acne that presents as fa
soft tissue edema and erythema. The condition may wax and wane in severity, but usually does not spontaneously
resolve without treatment. Improvement with isotretinoinwith or without ketotifen, systemic glucocorticoids, or
clofazimine has been reported [48].
DIAGNOSTIC EVALUATION Particular attention to endocrine function is essential in the evaluation of acne vulga
A medication history should also be reviewed for acne-inducing drugs (table 2). Skin should be examined carefully, s
an assessment of the type and location of lesions is critical for determining the most appropriate treatments.
Hyperandrogenism In women, polycystic ovary syndrome (PCOS) is the most common cause of hyperandrogenThis disorder is characterized by menstrual irregularity, hirsutism, acne, ovarian cysts, and varying degrees of insulin
resistance and acanthosis nigricans (picture 11). (See "Clinical manifestations of polycystic ovary syndrome in adult
One study of 51 women with acne (ages 15 to 46) found that 39 percent had menstrual abnormalities and 37 percen
had PCOS [56]. These observations suggest that all women with the combination of acne and oligomenorrhea shou
evaluated for PCOS. (See "Diagnosis of polycystic ovary syndrome in adults".)
The rapid appearance of acne in conjunction with virilization suggests an underlying adrenal or ovarian tumor. Patie
with Cushing's disease or syndrome and late-onset congenital adrenal hyperplasia may also experience acne vulga
Evidence of virilization includes a deepening voice, decreased breast size, clitoromegaly, alopecia, oligomenorrhea,
hirsutism. These patients may require imaging studies of the adrenal glands and ovaries, and hormonal evaluation.
Referral to an endocrinologist should be considered in these cases. (See "Epidemiology and clinical manifestations
Cushing's syndrome"and "Adrenal hyperandrogenism".)
Recommendations for initial screening tests for hyperandrogenism vary. DHEA-S, total testosterone, and free
testosterone levels are reasonable initial tests. A 17-hydroxyprogesterone level may also be obtained to screen for la
onset congenital adrenal hyperplasia, in which elevated levels of DHEA-S may also be seen. Referrals to endocrino
and gynecology should be considered if abnormalities are noted. Patients should not be taking oral contraceptives
during testing for hyperandrogenism.
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Medications A complete list of medications, including vitamin supplements, should be obtained. Known causes o
acne or acneiform eruptions include glucocorticoids, phenytoin, lithium, isoniazid, epidermal growth factor inhibitors,
iodides, bromides, androgens, and other drugs (table 2) [57]. Vitamins B2, B6, and B12 may also cause drug-induce
acne. (See 'Drug-induced acne'below and 'EGFR inhibitor acneiform eruption'below and "Drug eruptions", section o
'Halogenoderma'.)
Physical examination The physical examination should focus upon the skin and in women, evidence of
hyperandrogenism. The type and location of lesions, scarring (picture 12and picture 13), and postinflammatory
pigmentary changes (picture 14) should be noted. The skin examination is essential for determining the best treatme
course for an individual patient. (See "Treatment of acne vulgaris", section on 'Patient assessment'and "Treatment o
acne vulgaris", section on 'Overview of treatment'.)
Hirsutism or virilization should prompt further laboratory and imaging studies or referral. (See "Evaluation of
premenopausal women with hirsutism".)
DIFFERENTIAL DIAGNOSIS Although acne vulgaris is a common condition that clinicians may feel they can
accurately diagnose, a variety of disorders need to be considered in the differential diagnosis. In addition, patients m
present with acneiform eruptions, which have similar features, but are unrelated to acne vulgaris.
Non-acne dermatoses Some of the conditions in the differential diagnosis of acne include:
Rosacea Acne vulgaris is distinguished from acne rosacea by the presence of comedones and the absence
telangiectasias. Common features of rosacea include erythema, telangiectasias, and papules or pustules on th
central face (picture 15). (See "Rosacea: Pathogenesis, clinical features, and diagnosis".)
!
Perioral dermatitis Perioral dermatitis (also known as periorificial dermatitis) is characterized by small,
grouped, erythematous papules in a perioral (or occasionally perinasal or periorbital) distribution (picture 16). W
the perioral skin is involved, a rim of spared skin is usually seen around the vermilion border of the lip. (See
"Perioral (periorificial) dermatitis".)
!
Sebaceous hyperplasia Visible enlargement of sebaceous glands is termed sebaceous hyperplasia. It mo
commonly occurs in adults with a history of oily skin. These growths are umbilicated yellowish papules are mos
commonly found on the forehead and cheeks (picture 17). These lesions may resemble basal cell carcinomas
!
Pseudofolliculitis barbae and acne keloidalis nuchae These two conditions occur most commonly in
individuals of African origin, and are likely related to the configuration of the hair follicle. It is thought that short
shaved or clipped hairs curl back towards the skin, penetrate the skin, and cause a foreign-body inflammatory
reaction. Inflammatory papules and pustules occur, which may result in keloidal scarring as the lesions heal
(picture 18A-C). The beard area (pseudofolliculitis barbae) and the nuchal area (acne keloidalis nuchae) are
typically involved. (See "Pseudofolliculitis barbae"and "Keloids".)
!
Folliculitis Staphylococcal, eosinophilic, or pseudomonal folliculitis may mimic inflammatory acne (picture 1
B). Comedones are absent, and lesions are usually monomorphous, unlike the polymorphous lesion in differen
stages of development that are typical of acne. (See "Folliculitis".)
!
Keratosis pilaris In this common condition, caused by keratotic follicular plugging, patients typically presen
with small follicular papules on the extensor surfaces of the upper arms or thighs (picture 20A-B). Erythema m
be present. Lesions can also occur on the face, particularly in children. (See "Approach to the patient with pust
skin lesions", section on 'Keratosis pilaris'.)
!
Favre-Racouchot syndrome Favre-Racouchot syndrome is a condition resulting from cutaneous photodam
(sun damage) seen in middle-aged or older adults. Open and closed comedones are found in areas of
!
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Acneiform eruptions There are multiple disorders in which acne-like eruptions occur, unassociated with true acn
vulgaris. These include the following:
Drug-induced acne Drug-induced acne typically presents with a monomorphous inflammatory papular erupti
(as opposed to the polymorphous eruption with lesions in varying stages seen with acne vulgaris) (picture 24).
Medications associated with drug-induced acne are listed in a table (table 2). Glucocorticoid-induced eruptions are areferred to as "steroid folliculitis." (see 'Medications'above).
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 availabl
Heavy, oil-based hair products are still commonly used and may contribute to the development of acne on the forehe
(pomade acne).
Irritant reactions to cosmetic products can also produce eruptions that resemble acne vulgaris. Inflammatory papule
pustules may occur within hours after the application of the inciting product.
EGFR inhibitor acneiform eruption Epidermal growth factor receptor (EGFR) inhibitors and other tyrosine
kinase inhibitors used to treat cancers are known to cause an inflammatory acneiform eruption involving the face, neand upper trunk in the majority of patients receiving these medications (picture 25). (See "Cutaneous complications
molecularly targeted therapy and other biologic agents used for cancer therapy".)
Occupational acne Comedones, inflammatory papules, pustules, nodules, or cysts can occur in response to
exposure to certain chemicals, including insoluble cutting oils, coal tarderivatives, and chlorinated hydrocarbons.
Chloracne is the term used to describe occupational acne that occurs with exposure to chlorinated hydrocarbons (eg
dioxin) via percutaneous contact, inhalation, or ingestion. Clinically, chloracne is characterized by large monomorph
comedones 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.
Tropical acne Tropical acne occurs upon exposure to elevated environmental temperatures, and may be see
tropical countries or other situations (eg, occupations) in which individuals are exposed to extreme heat. Large
inflammatory nodules are seen on the trunk and buttocks. Treatment involves avoidance of heat. Systemic antibiotic
may also be used.
Radiation acne Treatment with ionizing radiation can result in the appearance of comedones as acute radiati
dermatitis resolves. Ionizing radiation induces follicular epithelial metaplasia, creating follicular hyperkeratotic plugs.
Apert syndrome Apert syndrome (ie, acrocephalosyndactyly type I) is an autosomal dominant disorder
associated with synostoses of bone in the hands, feet, cranium, and vertebral bodies. A diffuse acneiform eruption o
photodamage, usually on the lateral upper cheeks (picture 21).
Nevus comedonicus A lesion presenting at birth or in childhood, in which grouped or a linear arrangement
comedones are noted.
!
Adnexal tumors Benign follicular tumors, such as trichoepitheliomas, trichodiscomas, or fibrofolliculomas
typically present as flesh-colored facial papules.
!
Steatocystoma multiplex Steatocystoma multiplex is an autosomal dominant or sporadic genetic disorder
which multiple yellow or skin-colored sebum-filled cysts are found on the trunk, upper arms, or chest (picture 2
!
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 23). (See "Tuberous sclerosis complex: Genetics, clinical features, and diagnosis".)
!
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the arms, buttocks, and thighs is seen. The acneiform eruption is difficult to treat. Isotretinoinhas been used with
success in some cases. (See "Craniosynostosis syndromes", section on 'Apert syndrome'.)
INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, The Basics and Bey
the Basics. The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, a
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 educ
pieces are longer, more sophisticated, and more detailed. These articles are written at the 10 to 12 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 topic
your patients. (You can also locate patient education articles on a variety of subjects by searching on patient info an
the keyword(s) of interest.)
SUMMARY
th th
th th
Basics topics (see "Patient information: Acne (The Basics)")!
Beyond the Basics topics (see "Patient information: Acne (Beyond the Basics)")!
Acne vulgaris is a common condition in adolescents that also affects adults. The psychological impact of acnevulgaris can be significant. (See 'Introduction'above and 'Epidemiology'above.)
!
Acne vulgaris is a disorder of the pilosebaceous follicles. Follicular hyperkeratinization, sebum production,
Propionibacterium acnes (P. acnes), and inflammation are involved in the pathogenesis. Follicular rupture, whic
releases proinflammatory lipids and keratin into the dermis, can intensify the inflammation seen in acne. (See
'Pathogenesis'above.)
!
Androgens induce sebum production, and are an important factor in the development of acne vulgaris.
Hyperandrogenism may cause acne in some patients, but most patients with acne vulgaris do not have androg
excess. (See 'Role of androgens'above.)
!
The role of diet and stress in acne vulgaris remain unclear. A contributory effect of milk and high-glycemic indediets has been proposed, but prospective trials are necessary to ascertain the relationship between diet and ac
(See 'Diet'above and 'Stress'above.)
!
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 papu
pustules, or nodules may be seen. The term "cystic acne" is a misnomer, as true cysts are rare in acne vulgaris
Adult women may present with lower face and neck acne associated with premenstrual flares. (See 'Clinical
manifestations and classification'above.)
!
A number of uncommon acne variants exist. Highly inflammatory conditions such as acne fulminans and acne
conglobata require aggressive therapy to prevent scarring. (See 'Acne variants'above.)
!
The diagnosis of acne vulgaris rests upon the patient's history and physical examination. If virilization, menstru
irregularity, or hirsutism is seen in women presenting with acne, evaluation for hyperandrogenism is indicated.
medication history should evaluate for the use of drugs that may cause acne or acneiform eruptions. (See
'Diagnostic evaluation'above.)
!
Although acne vulgaris is a common condition that is often easily diagnosed, clinicians should be mindful of ot
diagnostic possibilities, including acneiform eruptions. (See 'Diagnostic evaluation'above and 'EGFR inhibitor
acneiform eruption'above.)
!
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Topic 39 Version 10.0
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GRAPHICS
Pathogenesis of follicular distention, rupture, and
inflammation in acne vulgaris
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Acne is a disease of the follicular canal of a sebaceous folicle. A compact stratum
corneum and a thickened granular layer in the infrainfundibulum are the
beginning of the formation of a comedone. Microcomedones (A) and closed (B)
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and open (C) comedones form. Excessive sebum secretion occurs, and the
bacterium P. acnesproliferates. The organism produces chemotactic factors,
leading to neutrophil migration into the intact comedone. Neutrophilic enzymes
are released and the comedone ruptures, inducing a cycle of chemotaxis and
intense neutrophilic inflammation (D and E).
Reproduced with permission from: Rubin E, MD and Farber JL, MD. Pathology, 3rd
Edition. Philadelphia: Lippincott Williams & Wilkins, 1999. Copyright 1999 LippincottWilliams & Wilkins.
Graphic 57892 Version 1.0
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Mild acne
This 14-year-old girl has multiple closed comedones and scattered,
small inflammatory papules and pustules on the forehead.
Courtesy of Douglas Hoffman, MD, Dermatlas; http://www.dermatlas.org.
Graphic 62816 Version 4.0
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Noninflammatory acne
Numerous open comedones are present on the chin.
Reproduced with permission: Goodheart HP. Goodheart's Photoguide of
Common Skin Disorders, 2nd ed, Lippincott Williams & Wilkins, Philadelphia
2003. Copyright 2003 Lippincott Williams & Wilkins.
Graphic 80536 Version 3.0
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Inflammatory and noninflammatory acne
The face of this teenager shows open and closed comedones, papules,
and pustules.
Reproduced with permission: Goodheart, HP. Goodheart's Photoguide of
Common Skin Disorders, 2nd ed, Lippincott Williams & Wilkins, Philadelphia
2003. Copyright 2003 Lippincott Williams & Wilkins.
Graphic 68412 Version 1.0
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Inflammatory acne
Erythematous papules and pustules are present.
Reproduced with permission from: www.visualdx.com. Copyright Logical
Images, Inc.
Graphic 70809 Version 3.0
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Synthetic pathways for adrenal steroid synthesis
The first step in adrenal steroid synthesis is the combination of acetyl CoA and
squalene to form cholesterol, which is then converted into pregnenolone. The enclosed
area contains the core steroidogenic pathway utilized by the adrenal glands and
gonads.
17!: 17-alpha-hydroxylase (CYP17, P450c17); 17,20: 17,20 lyase (also mediated by CYP17);
3": 3-beta-hydroxysteroid dehydrogenase; 21: 21-hydroxylase (CYP21A2, P450c21); 11":
11-beta-hydroxylase; (CYP11B1, P450c11); 18 refers to the two-step process of aldosterone
synthase (CYP11B2, P450c11as), resulting in the addition of an hydroxyl group that is then
oxidized to an aldehyde group at the 18-carbon position; 17"R: 17-beta-reductase; 5!R: 5-
alpha-reductase; DHEA: dehydroepiandrosterone; DHEAS: DHEA sulfate; A: aromatase
(CYP19); SK: sulfokinase; SL: sulfotransferase.
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Androgen production in the sebaceous gland
Dehydroepiandrosterone sulfate (DHEA-S)
!Steroid sulfatase
Dehydroepiandrosterone (DHEA)
!3 -hydroxysteroid dehydrogenase
Androstenedione
!17 -hydroxysteroid dehydrogenase
Testosterone
!5!-reductase type I
Dihydrotestosterone (DHT)
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Postadolescent acne
Characteristic location of acne along the jaw line in a woman. Multiple
papules have been excoriated.
Reproduced with permission from: Goodheart, HP, MD. Goodheart's
Photoguide of Common Skin Disorders, 2nd ed. Lippincott Williams & Wilkins,
Philadelphia 2003. Copyright 2003 Lippincott Williams & Wilkins.
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Acne nodules
Severe nodular acne on the forehead.
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Nodular acne
Erythematous papules, pustules, and nodules are present on the face.
This patient also has postinflammatory hyperpigmentation and
scarring.
Reproduced with permission from: www.visualdx.com. Copyright Logical
Images, Inc.
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Acne sinus tract
Multiple sinus tracts in an adolescent male with severe nodular acne.
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