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Acne vulgaris Summary

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					Acne vulgaris
ID: 101
Type: Monograph Standard [en-gb]

Topic Synonyms
  •       Acne
  •       Acne lesion
  •       Acne simplex
  •       Acneiform eruption
  •       Comedone
  •       Common acne
  •       Simple acne
  •       Pimples
  •       AV

Related Topics
  •       Folliculitis
  •       Overview of dermatitis
  •       Acne rosacea

Categories
  •       Dermatology
  •       Paediatrics and adolescent medicine

Summary
Key Highlights
  •       Acne may affect any age group, but it is most common in adolescents.
  •       Lesions consist of non-inflammatory comedones (whiteheads and blackheads) and inflammatory
          papules, pustules, nodules, and cysts.
  •       Severity ranges from mild comedonal acne to severe nodulocystic acne, which can be permanently
          disfiguring.
  •       Systemic effects may also be present with acne fulminans, a rare variant.
  •       Treatments include topical retinoids, keratolytics, and antibiotics; more severe inflammatory lesions
          may require oral antibiotics; severe nodulocystic acne may require oral isotretinoin.

 History and Exam,                  Tests                Treatment Options
 Diagnostic Factors                   Other Tests        Ongoing
  Key Diagnostic Factors              to Consider          •   mild-to-moderate acne
      •     presence of risk            •   hormonal             •
            factors                         evaluation           • non-inflammatory
      •     skin lesions                •   bacterial                  • keratolytic (topical retinoid or salicylic
                                            culture                      acid)
  Other Diagnostic Factors                                       • inflammatory
      •     skin tenderness                                            • topical retinoid + topical antibiotic or
      •     depression, social                                           benzoyl peroxide
            isolation                                      •   moderate-to-severe hormone-related,
      •     systemic complaints                                non-nodulocystic acne
                                                                 • oral hormonal therapy




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                                                      •   moderate-to-severe hormone-related,
                                                          non-nodulocystic acne
                                                            •
                                                            • inflammatory
                                                                 • oral antibiotic + topical retinoid
                                                            • inflammatory
                                                                 • topical benzoyl peroxide
                                                      •   moderate-to-severe non-hormone-related,
                                                          non-nodulocystic acne
                                                            •
                                                            • non-inflammatory
                                                                 • topical retinoid
                                                            • inflammatory
                                                                 • oral antibiotic + topical retinoid
                                                            • inflammatory
                                                                 • topical benzoyl peroxide
                                                      •   severe nodulocystic acne or acne resistant to
                                                          standard treatment
                                                            • oral retinoid
                                                      •   severe nodulocystic acne or acne resistant to
                                                          standard treatment
                                                            • oral corticosteroids

Basics
Basics: Definition
Acne vulgaris is a skin disease affecting the pilosebaceous unit. It is characterised by comedones, papules,
pustules, nodules, cysts, and/or scarring, primarily on the face and trunk. Clinical manifestations range
from mild to severe with systemic symptoms. Acne is most common in adolescents, but may occur at any
age. In addition to the physical lesions, acne can have profound psychological and social impact on
patients.[1]

Basics: Classifications
 Commonly accepted
There is no single uniform, standardised, and reproducible grading system for severity of acne. Acne is
commonly classified by type (comedonal/papular, pustular/nodulocystic) and/or severity
(mild/moderate/moderately severe/severe). Skin lesions can be described as inflammatory or
non-inflammatory.

 Leeds technique[2]
Assessment of severity, used primarily for research, using grades 1 to 12 (mild to severe).

 Simplified classification[3]
  •   Mild acne: comedones are the main lesions. Papules and pustules may be present but are small and
      few in number (generally <10).
  •   Moderate acne: moderate numbers (10 to 40) of papules and pustules. Moderate numbers (10 to 40)
      of comedones are also present. Sometimes mild truncal disease.




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  •   Moderately severe acne: numerous papules and pustules (40 to 100), usually with many comedones
      (40 to 100) and the occasional (up to 5) larger, deeper nodular inflamed lesions. Widespread affected
      areas usually involving face, chest, and back.
  •   Very severe acne: nodulocystic acne and acne conglobata with severe lesions; many large, painful
      nodular/pustular lesions along with many smaller papules, pustules, and comedones.

 FDA global grade[4]
Used primarily for research purposes.
  • Grade 0: clear skin with no inflammatory or non-inflammatory lesions
  •   Grade 1: almost clear; rare non-inflammatory lesions with no more than 1 small inflammatory lesion
  •   Grade 2: mild severity; greater than grade 1; some non-inflammatory lesions with no more than a few
      inflammatory lesions (papules/pustules only, no nodular lesions)
  •   Grade 3: moderate severity; greater than grade 2; up to many non-inflammatory lesions and may
      have some inflammatory lesions, but no more than 1 small nodular lesion
  •   Grade 4: severe; greater than grade 3; up to many non-inflammatory and inflammatory lesions, but
      no more than a few nodular lesions.

Basics: Vignette
Common Vignette
A teenage boy presents with closed comedones and slightly tender erythematous papules and pustules
on his forehead, cheeks, chin, chest, and upper back. Small lesions developed several years ago as he
entered puberty, and they have progressively worsened over the last year. Previous lesions have left
residual red-brown hyperpigmentation.

Basics: Other Presentations
Acne conglobata is severe, nodulocystic acne without associated systemic manifestations.[5] Acne fulminans
is the most severe form of cystic acne, characterised by the acute onset of nodular and suppurative acne
associated with multiple systemic manifestations, including fever, arthralgias, myalgias, hepatosplenomegaly,
and osteolytic bone lesions.[5] Acne mechanica is caused by persistent mechanical obstruction, often by
clothing or sporting equipment, which occludes the pilosebaceous unit and results in comedones.[6] Acne
excoriee des jeunes filles typically occurs in girls who scratch and pick at comedones and inflammatory
papules. Acneiform eruptions can be caused by some medicines (e.g., androgens, topical corticosteroids,
oral corticosteroids) and occupational or environmental exposures (e.g., chloracne caused by dioxins).

Basics: Epidemiology
Acne vulgaris is a common inflammatory pilosebaceous disease; it is so common that it is often referred
to as a physiological condition. Research has shown that 85% of young people between the ages of 12
and 24 years have acne, and while it is most common in teenagers, acne affects 8% of adults aged 25 to
34 years and 3% of adults aged 35 to 44 years. Acne in young adults may represent continuation of
adolescent acne or development of late-onset disease.[7] Acne is more common in boys than girls during
adolescence, but the incidence is higher in women during adulthood. Nodulocystic acne has an increased
prevalence in white people compared to black people.[8] Prevalence varies greatly across the world, with
Western modernised civilisations demonstrating much higher rates of acne, whereas some non-industrialised
societies report no cases of acne.[9] Acne vulgaris affects 40 to 50 million people annually in the US.

Basics: Aetiology
Acne is polygenic and multi-factorial. Four main pathogenetic factors contribute to the disease:



Page 3
  •   Sebaceous gland hyperplasia and excess sebum production. Sebaceous follicle size and number of
      lobules per gland are increased in patients with acne.[10] Androgens stimulate sebaceous glands to
      enlarge and produce more sebum, which is most prevalent during puberty.
  •   Abnormal follicular differentiation. In normal follicles, keratinocytes are shed as single cells into the
      lumen and then excreted. In acne, keratinocytes are retained and accumulate due to their increased
      cohesiveness.[11]
  •   Propionibacterium acnes colonisation. These gram-positive, non-motile rods are found deep in follicles
      and stimulate the production of pro-inflammatory mediators and lipases. While there may be increased
      numbers of P acnes in acne, bacterial counts often do not correlate with acne severity.[12]
  •   Inflammation and immune response. Inflammatory cells and mediators efflux into the disrupted follicle,
      leading to the development of papules, pustules, nodules, and cysts.
External factors occasionally contribute to acne, including mechanical trauma, cosmetics, topical
corticosteroids, and oral medicines (corticosteroids, lithium, iodides, some antiepileptics). Endocrine
disorders resulting in hyperandrogenism may also predispose patients to developing acne. Acne fulminans
is a rare acne subtype that presents with variable systemic manifestations, including fever, arthralgias,
myalgias, hepatosplenomegaly, and osteolytic bone lesions.
Given the high prevalence of the disease, isolating specific genetic factors is difficult. However, the
concordance rate for the prevalence and severity of acne among identical twins is high.[13] One study
concluded that 81% of variance in acne was attributable to genetics and only 19% to environmental
factors.[14]

Basics: Pathophysiology
The initial step in the development of acne is the formation of the microcomedo.[15] Follicular keratinocytes
that exhibit increased cohesiveness do not shed normally, leading to retention and accumulation. Androgens
stimulate enlargement of sebaceous glands and increased sebum production, and the abnormal
keratinaceous material and sebum collect in the microcomedo. This leads to a build-up of pressure, and
whorled lamellar concretions develop. At this stage, a non-inflammatory comedo may be seen clinically.
This micro-environment allows the proliferation of P acnes, which is part of the normal flora of follicles.
This gram-positive rod has low virulence but is capable of metabolising triglycerides and releasing free
fatty acids. This metabolism, as well as its ability to activate complement, produces pro-inflammatory
mediators, including neutrophil chemo-attractants.[16]
With increased pressure and recruitment of inflammatory mediators, the microcomedo may rupture and
release immunogenic keratin and sebum, thus stimulating an even greater inflammatory response.
Depending on the specific inflammatory cells present, suppurative pustules or inflamed papules, nodules,
or cysts may develop. If a sufficient amount of inflammation and tissue damage results, post-inflammatory
hyperpigmentation and scarring may result.

Basics: Risk Factors
Strong
 age 12 to 24 years
  •   Research has shown that 85% of young people between the ages of 12 and 24 years have acne.[7]
 genetic predisposition
  •   The concordance rate for the prevalence and severity of acne among identical twins is high.[13] One
      study concluded that 81% of variance in acne was attributable to genetics, and only 19% to
      environmental factors.[14]
 greasy skin/increased sebum production



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  •   Sebaceous follicle size and the number of lobules per gland are increased in patients with acne.[10]
      Androgens stimulate sebaceous glands to enlarge and produce more sebum, which is most prevalent
      during puberty. Sebum production is fairly high during the first 6 months of life, declines and remains
      stable throughout childhood, and dramatically increases during puberty.

Weak
 endocrine disorders
  •   Patients with endocrine disorders such as polycystic ovary syndrome, hyperandrogenism, and
      precocious puberty are more likely to have severe acne.
 dietary factors
  •   Few studies have examined the role of diet in acne. Several studies focusing on chocolate consumption
      found no effect on acne.[17] [18] While Western diet has been associated with increased incidence
      of acne, these observations are limited by their ability to separate genetic factors from environmental
      and dietary influences.[19]
 female gender/oestrogens
  •   The role of oestrogen in acne is unclear, but oestrogen is known to decrease sebum production.
      Many women note worsening of their acne prior to menstruation, and oral contraceptives often help
      to mitigate this cyclical worsening. Suppression of sebum production requires higher doses of oestrogen
      than does suppression of ovulation.[20]
 obesity/insulin resistance
  •   Insulin and insulin-like growth factor (IGF) can stimulate keratinocytes and sebaceous glands. Elevated
      IGF-1 levels are found in women with post-adolescent acne,[21] and obesity has been found to be
      associated with an increased prevalence of acne in people aged 20 to 40 years. However, no
      association between obesity and acne was found in patients aged 15 to 19 years.[22]
 hyperandrogenism
  •   The rise in circulating androgens at the onset of puberty is associated with increased production of
      sebum and the development of comedonal acne, but most patients with acne have normal androgen
      levels. Rare cases may be associated with pathologically elevated androgen levels due to an underlying
      disorder, such as polycystic ovary disease.
 corticosteroid medicines
  •   Acneiform eruptions can be caused by some medicines, including androgens, topical corticosteroids,
      and oral corticosteroids.
 halogenated aromatic hydrocarbons exposure
  •   Occupational or environmental exposures to halogenated aromatic hydrocarbons exposure (e.g.,
      chlorinated dioxins and dibenzofurans) can cause chloracne.

Basics: Prevention
No preventative strategies have been identified. Diet and weight control are not effective in preventing
acne.
Secondary Prevention
General good skin care techniques should be emphasised. Patients should be recommended to use only
"non-comedogenic" products on skin; to not pick, squeeze, or scratch acne lesions; and to avoid getting
hair products on the face.




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Diagnosis
Diagnosis: Diagnosis Approach
Characteristic history and examination findings are usually sufficient to diagnose acne vulgaris.

History
Acne vulgaris classically begins as puberty commences, but the clinical course is highly variable. Women
may note a fluctuating course centred on their menstrual cycles. Acne fulminans is a rare acne subtype
that presents with variable systemic manifestations, including fever, arthralgias, myalgias,
hepatosplenomegaly, and osteolytic bone lesions.

Physical examination
Non-inflammatory acne manifests as whiteheads (closed comedones) and blackheads (open comedones).
Inflammatory lesions begin as microcomedones but may develop into papules, pustules, nodules, or cysts.
Both types of lesions are found in areas of dense sebaceous glands. [image] [image] Acne may affect only
the face, but the chest, back, and upper arms are often involved. Moderate-to-severe acne lesions may
leave post-inflammatory hyperpigmentation and/or atrophic scars. [image] Other individuals may form more
hypertrophic scars at areas of prior involvement.[23] Severe nodulocystic acne [image] presenting with
fever, arthralgia, myalgia, hepatosplenomegaly, and osteolytic bone lesions suggests acne fulminans.

Laboratory evaluation
Routine endocrinological testing is not indicated for the majority of patients with acne. In patients with acne
and evidence of hyperandrogenism, hormonal evaluation for free testosterone, dehydroepiandrosterone
sulphate (DHEA-S), LH, and FSH is done.[24]
Routine microbiological testing is unnecessary in the evaluation and management of patients with acne.
If lesions centred in the peri-oral and nasal areas are unresponsive to conventional acne treatments,
bacterial culture and sensitivities to evaluate for gram-negative folliculitis are considered.[24]

Diagnosis: History and Exam, Diagnostic Factors
Key Diagnostic Factors
 presence of risk factors (common)
  •   Key risk factors include age 12 to 24 years, genetic predisposition, and having a greasy skin type.
 skin lesions (common)
  •   Open and closed comedones represent the non-inflammatory acne lesions, while papules, pustules,
      nodules, and cysts are manifestations of inflammatory lesions. Post-inflammatory hyperpigmentation
      and scarring may also result.[23]

Other Diagnostic Factors
 skin tenderness (common)
  •   Inflammatory papules, pustules, cysts, and nodules may be tender to palpation.
 depression, social isolation (common)
  •   Acne may have a significant psychological impact, including anxiety, depression, and even suicide.[25]
 systemic complaints (uncommon)
  •   Acne fulminans subtype manifests with fever, arthralgias, myalgias, hepatosplenomegaly, and osteolytic
      bone lesions.




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Diagnosis: Tests
Other Tests to Consider
                                    Test                                                   Result
hormonal evaluation                                                            elevated total testosterone,
  •   Rarely required.                                                         DHEA-S, LH, and FSH
  •   Free testosterone is the most sensitive test to establish the presence
      of hyperandrogenism; ordered only when there is concern for
      hyperandrogenism.
  •   If laboratory tests are abnormal, referral to an endocrinologist is
      indicated.
bacterial culture                                                              positive culture of
  •   Rarely required.                                                         gram-negative bacteria
  •   Ordered only when standard treatments are not efficacious and there
      is clinical suspicion of gram-negative folliculitis.
  •   Sample should be collected from multiple inflammatory lesions and
      also from a pustule if present.
  •   Treatment based on isolation and sensitivities of bacteria.

Diagnosis: Differentials
   Condition                         Sign/Symptoms                              Differentiating tests
Acne keloidalis     •   Most often seen in black patients; lesions are     •   Clinical differentiation usually
nuchae                  typically localised to the posterior neck. They        suffices.
                        begin as papules and pustules and may
                        progress to confluent keloids.[26]
Acneiform           •   Possible aetiologies to consider include oral      •   Clinical diagnosis usually
eruptions               medicines, topical corticosteroids, contrast dye,      suffices.
                        testosterone, and cosmetic products.
                    •   Clinical clues include the abrupt onset of lesions
                        within days of exposure, widespread
                        involvement, atypical locations, atypical age,
                        and improvement with cessation of medicine or
                        exposure.
Chloracne           •   Comedones, pustules, and cysts are most        •       Clinical differentiation usually
                        commonly found behind the ears and in the              suffices.
                        axillae and groin.                             •       Consider laboratory tests such
                    •   Consider exposure to halogenated aromatic              as liver enzymes and lipid
                        hydrocarbons (e.g., chlorinated dioxins and            panel.
                        dibenzofurans). Patient may have systemic
                        complications such as ophthalmic, neuropathic,
                        hepatic, and lipoprotein abnormalities.[27]
Favre-Racouchot     •   Multiple open and closed comedones on the          •   Clinical differentiation usually
syndrome                peri-orbital and malar areas, usually on older         suffices.
                        people with significant chronic sun exposure.      •   Skin biopsy shows increased
                        Typically non-inflammatory.                            elastic tissue with thickened,
                                                                               tortuous fibres in the upper and
                                                                               mid-dermis.[28]




Page 7
Folliculitis       •   Common condition that manifests as                 •    Clinical differentiation usually
                       erythematous papules and pustules, which are            suffices.
                       follicularly based.                                •    Pustular lesions that do not
                   •   As opposed to acne, folliculitis often affects the      respond to typical acne
                       trunk and extremities.                                  antibiotics may be cultured.
Gram-negative      •   Occurs in patients with acne treated with        •      Lesions may be cultured to
folliculitis           long-term antibiotics who subsequently develop          isolate the gram-negative
                       pustules or nodules on the anterior nares, which        bacteria if acneiform lesions do
                       then spreads. Can also occur in people after            not respond to typical antibiotic
                       hot tub immersion, as well as in HIV patients.          regimen.
Lupus miliaris     •   Firm yellowish-brown or red smooth papules          •   Diascopy reveals
disseminatus           peri-orbitally and characteristically on the eyelid     yellowish-brown lesions. Skin
faciei                 skin.[29]                                               biopsy reveals caseating
                                                                               epithelioid cell granulomas.
Milia              •   White keratinaceous cysts that are found on the •       Skin biopsy shows small cysts
                       face, particularly on the eyelids. Lesions are          derived from the infundibulum
                       fixed and persistent.                                   of the vellus hair.
Peri-oral          •   Common peri-oral eruption of papules and         •      Clinical differentiation usually
dermatitis             pustules on an erythematous and/or scaling              suffices.
                       base, often the result of topical corticosteroid
                       use. Localised symmetrically around the mouth,
                       with a clear zone around the vermilion
                       border.[30]
Pyoderma faciale   •   Rapid onset of reddish or cyanotic erythema         •   Skin biopsy shows a grenz
                       with abscesses, cysts, and occasionally sinus           zone and mixed inflammatory
                       tracts. No comedones and no involvement of              infiltrate in the upper and
                       back or chest.[31]                                      mid-dermis, with extravasation
                                                                               of RBCs and haemosiderin
                                                                               deposition.
Rosacea            •   Typically affects older people than acne       •        Clinical differentiation usually
                       vulgaris, most often women aged 30 to 50                suffices.
                       years.
                   •   Various forms, but classically presents with
                       background erythema and telangiectasias, and
                       inflammatory papules and pustules occasionally
                       superimposed.
                   •   Environmental factors often act as triggers.
Syringoma          •   Non-inflammatory small papules that occur     •         Skin biopsy shows a dense
                       primarily on the eyelids and upper cheeks,              fibrous stroma with dilated
                       usually multiple.                                       cystic spaces that have small
                   •   Disproportionately more prevalent in Japanese           comma-like tails resembling
                       women.                                                  tadpoles.
Adenoma            •   Small, translucent, waxy papules distributed    •       Skin biopsy shows dermal
sebaceum               symmetrically over the central cheek, nose, and         fibrosis and vascular
(angiofibromas)        forehead.                                               proliferation and dilation.
                   •   Multiple lesions associated with tuberous
                       sclerosis.[32]




Page 8
Diagnosis: Diagnostic Criteria
 Simplified classification[7]
  •   Mild: comedones are the main lesions. Papules and pustules may be present but are small and few
      in number (generally <10).
  •   Moderate: moderate numbers (10 to 40) of papules and pustules. Moderate numbers (10 to 40) of
      comedones are also present. Sometimes mild truncal disease.
  •   Moderately severe: numerous papules and pustules (40 to 100), usually with many comedones (40
      to 100) and the occasional (up to 5) larger, deeper nodular inflamed lesions. Widespread affected
      areas usually involving face, chest, and back.
  •   Very severe: nodulocystic acne and acne conglobata with severe lesions; many large, painful
      nodular/pustular lesions along with many smaller papules, pustules, and comedones.


Treatment
Treatment: Treatment Approach
Because multiple factors influence acne development, combination therapy is the mainstay of treatment,
except in mild-to-moderate comedonal acne. It is generally agreed that topical retinoids should be considered
for inclusion in combination treatments of most patients; they can also prevent and improve
hyperpigmentation associated with inflammatory acne lesions, particularly in patients with darker skin.

Mild-to-moderate acne
Comedonal acne is especially responsive to topical retinoids. In mild, primarily comedonal acne, topical
retinoids are the treatment of choice and are used as monotherapy.[33] [e1]
Salicylic acid has been used for years for its keratolytic properties, but few well-designed trials of its safety
and efficacy are available.[34] It is considered a less effective comedolytic agent than topical retinoids.
For inflammatory acne, combination therapy is the mainstay of treatment. Topical retinoids (tretinoin,[e1]
adapalene,[35] [e6] and tazarotene) are prescribed in combination with benzoyl peroxide[e2] and/or topical
antibiotics (clindamycin,[e3] erythromycin,[e7]or dapsone).[36]
Adapalene-benzoyl peroxide is a novel combination treatment combining 2 known effective drugs for
treatment of comedonal and noncomedonal acne.[37]

Moderate-to-severe acne
Moderate-to-severe comedonal acne with minimal inflammation may respond to topical retinoids alone.[e1]
[e6] [e5] Moderate-to-severe inflammatory acne is best treated by a combination of an oral antibiotic[e4]
and a topical retinoid. These drugs should not be used alone, due to potential for developing antibiotic
resistance. If oral antibiotics are used for more than 2 months without significant improvement, then the
addition of benzoyl peroxide to the treatment regimen should be considered to reduce the chance of
resistance and to increase efficacy of the antibacterial treatment.[33]
Oral antibiotics are typically administered for at least 6 to 8 weeks and up to several months, although
some patients require indefinite antibiotic therapy. If repeat treatment is necessary, an antibiotic that was
effective in the past is prescribed again; otherwise, an alternative antibiotic can be prescribed. If 2 antibiotics
from different classes are ineffective, a culture could be performed to help guide antibiotic selection. It is
generally agreed that topical and oral antibiotics should not be used as monotherapy.[33]

Severe nodulocystic acne or resistant to standard treatment
For severe acne or acne unresponsive to other treatments, a course of oral isotretinoin for 5 to 6 months
is the treatment of choice. Patients often report that more standard acne treatments work better after a



Page 9
course of isotretinoin, but some patients may require a repeat course of isotretinoin. Adverse effects with
this drug can be severe, and regular monitoring during treatment is required.[33] Severe headaches,
decreased night vision, or signs of adverse psychiatric events are signs for prompt discontinuation.
Isotretinoin is teratogenic; therefore, women need to undergo pregnancy tests before starting isotretinoin,
and monthly while taking the drug.
Oral corticosteroids such as prednisolone may be considered as adjunctive treatment to calm the skin
down before initiating isotretinoin, or in conjunction with isotretinoin for patients with severe acne flare or
acne fulminans (a type of severe nodulocystic acne). In these instances, oral corticosteroids are generally
used for 1 to 4 months to avoid relapse.[5]

Acne in females with hormonal involvement
Hormonal therapy may be used in women who experience acne flares associated with menstrual periods.
It can also be helpful in patients with proven ovarian or adrenal hyperandrogenism and in patients with
polycystic ovary syndrome. Treatment options include combined oral contraceptives containing cyproterone
plus ethinyloestradiol, or anti-androgenic drugs including spironolactone. Treatment may require specialist
endocrinologist involvement.[38]

Treatment: Treatment Options
Ongoing
                        Treatment
    Patient Group          Line                                      Treatment
mild-to-moderate           asdf
acne
     non-inflammatory     1st       keratolytic (topical retinoid or salicylic acid)
                                      • It is important that patients apply the medicine to the whole treatment
                                         area (e.g., the entire face), not to specific acne lesions.
                                      • Topical retinoids include tretinoin,[e1] adapalene,[35] [e6] and
                                         tazarotene.
                                      • Most topical retinoids produce some degree of fine peeling and
                                         erythema, especially early in treatment. Patients are started with
                                         lower potency, increased to higher potency if skin irritation is minimal.
                                      • Salicylic acid is keratolytic, but is considered a less effective
                                         comedolytic agent compared to topical retinoids.

                                    Primary Options
                                      • tretinoin topical: (0.01 to 0.1%) children >12 years of age and adults:
                                        apply to the affected area(s) once daily before bedtime or on
                                        alternate days
                                      • adapalene topical: (0.1%) children >12 years of age and adults:
                                        apply to the affected area(s) every evening
                                           • Less likely to cause irritation than tretinoin.[39]

                                      •   tazarotene topical: (0.05 to 0.1%) children >12 years of age and
                                          adults: apply to the affected area(s) every evening
                                    Secondary Options
                                      • salicylic acid topical: (0.5 to 2%) consult product literature for
                                          guidance on dosage
         inflammatory     1st       topical retinoid + topical antibiotic or benzoyl peroxide
                                      • Combination therapy is the mainstay of inflammatory acne treatment.



Page 10
                             •   Topical retinoids include tretinoin,[e1] adapalene,[35] [e6] and
                                 tazarotene.
                             •   Topical retinoids should be considered in combination with topical
                                 antibacterial regimens. Patients are started with lower potency,
                                 increased to higher potency if skin irritation is minimal. Benzoyl
                                 peroxide[e2] products should be applied at a different time to topical
                                 retinoids to avoid inactivation of either or both drugs.[33] Topical
                                 adapalene is less likely to cause irritation than tretinoin.[39]
                             •   Adapalene-benzoyl peroxide is a novel combination treatment
                                 combining 2 known effective drugs for treatment of comedonal and
                                 noncomedonal acne.[37]
                             •   Topical antibiotics, which include clindamycin,[e3]
                                 erythromycin,[e7]and dapsone,[36] are not recommended as
                                 monotherapy because of potential for bacterial resistance.[33]
                             •   Topical antibiotics may be discontinued once improvement is noted;
                                 if no improvement is noted within 6 to 8 weeks, they are discontinued
                                 and alternate therapy considered.[33]
                             •   Azelaic acid is an antimicrobial with mild comedolytic and
                                 anti-inflammatory properties.[40] It can be helpful in reducing
                                 post-inflammatory hyperpigmentation.

                           Primary Options
                             • tretinoin topical: (0.01 to 0.1%) children >12 years of age and adults:
                                 apply to the affected area(s) once daily before bedtime or on
                                 alternate days or
                             • adapalene topical: (0.1%) children >12 years of age and adults:
                                 apply to the affected area(s) every evening or
                             • tazarotene topical: (0.05% or 0.1%) children >12 years of age and
                                 adults: apply to the affected area(s) every evening
                                  -- AND --
                             • benzoyl peroxide topical: (1 to 10%) consult product literature for
                                 guidance on dosage or
                             • clindamycin topical: (1% foam) children >12 years of age and adults:
                                 apply to the affected area(s) once daily; (1% gel, lotion, pledget or
                                 solution) children >12 years of age and adults: apply to the affected
                                 area(s) twice daily or
                             • erythromycin topical: (2%) children and adults: apply to the affected
                                 area(s) twice daily or
                             • dapsone topical: (5%) children >12 years of age and adults: apply
                                 to the affected area(s) twice daily; reassess if no improvement in 12
                                 weeks
                             • azelaic acid topical: (20%) children >12 years of age and adults:
                                 apply to the affected area(s) twice daily
                             • adapalene/benzoyl peroxide topical: children >12 years of age and
                                 adults: apply to the affected area(s) once daily
moderate-to-severe   1st   oral hormonal therapy
hormone-related,             • Hormonal therapy may be used in women experiencing acne flares
non-nodulocystic                 associated with menstrual periods; they should be pursued only if
acne                             other treatments are ineffective.[38]
                             • Hormonal therapy is helpful in patients with proven ovarian or adrenal
                                 hyperandrogenism and patients with polycystic ovary syndrome.



Page 11
                                    •   Treatment may require specialist endocrinologist involvement.[38]
                                    •   Treatment options include combined oral contraceptives containing
                                        cyproterone plus ethinyloestradiol, or anti-androgenic drugs including
                                        spironolactone.

                                 Primary Options
                                   • combined oral contraceptives: consult product literature for guidance
                                     on dosage
                                       • Initially for 3 months but can continue indefinitely if required.

                                 Secondary Options
                                   • spironolactone : 25-200 mg orally once daily for 3-6 months
                                       • Can continue indefinitely if required.[41]

moderate-to-severe       asdf
hormone-related,
non-nodulocystic acne

         inflammatory adjunct oral antibiotic + topical retinoid
                                • For best results, the combination of oral antibiotics and topical
                                    retinoids should be considered.Topical retinoids include tretinoin,[e1]
                                    adapalene,[35] [e6] and tazarotene. Patients are started with lower
                                    potency of a topical retinoid, increased to higher potency if skin
                                    irritation is minimal. Topical adapalene is less likely to cause irritation
                                    than tretinoin.[39]
                                • If oral antibiotics need to be used for >2 months, the addition of
                                    topical benzoyl peroxide[e2] should be considered.[33]
                                • Oral antibiotics are typically administered for at least 6 to 8 weeks
                                    and for up to several months, although some patients require
                                    indefinite antibiotic therapy.[e4] If re-treatment is necessary, an
                                    antibiotic that was effective in the past should be considered again;
                                    otherwise an alternative antibiotic can be prescribed. Doxycycline,
                                    minocycline, and tetracycline have been associated with
                                    photosensitivity.[33] [42] [43]

                                 Primary Options
                                   • tretinoin topical: (0.01 to 0.1%) children >12 years of age and adults:
                                     apply to the affected area(s) once daily before bedtime or on
                                     alternate days or
                                   • adapalene topical: (0.1%) children >12 years of age and adults:
                                     apply to the affected area(s) every evening or
                                   • tazarotene topical: (0.05% or 0.1%) children >12 years of age and
                                     adults: apply to the affected area(s) every evening
                                      -- AND --
                                   • tetracycline : adolescents and adults: 250-500 mg orally twice daily
                                     for 2-3 months, followed by 250-500 mg once daily for 1-2 months or
                                   • minocycline : adolescents and adults: 50-100 mg orally (regular
                                     release) twice daily for 2-3 months, followed by 50-100 mg once
                                     daily for 1- 2 months or




Page 12
                                  • doxycycline : 50-100 mg orally twice daily for 2-3 months, followed
                                    by 50-100 mg once daily for 1-2 months
                                Secondary Options
                                  • tretinoin topical: (0.01 to 0.1%) children >12 years of age and adults:
                                    apply to the affected area(s) once daily before bedtime or on
                                    alternate days or
                                  • adapalene topical: (0.1%) children >12 years of age and adults:
                                    apply to the affected area(s) every evening or
                                  • tazarotene topical: (0.05% or 0.1%) children >12 years of age and
                                    adults: apply to the affected area(s) every evening
                                     -- AND --
                                  • erythromycin base: 500 mg orally twice daily for 2-3 months, followed
                                    by 500 mg once daily for 1-2 months
                                       • Higher reported bacterial resistance limits use of this drug to
                                          children and pregnant women.

                                Tertiary Options
                                  • tretinoin topical: (0.01 to 0.1%) children >12 years of age and adults:
                                     apply to the affected area(s) once daily before bedtime or on
                                     alternate days or
                                  • adapalene topical: (0.1%) children >12 years of age and adults:
                                     apply to the affected area(s) every evening or
                                  • tazarotene topical: (0.05% or 0.1%) children >12 years of age and
                                     adults: apply to the affected area(s) every evening
                                      -- AND --
                                  • trimethoprim/sulfamethoxazole : 160/800 mg orally twice daily for
                                     2-3 months, followed by 160/800 mg once daily for 1-2 months
                                        • Used as a third-line agent for acne resistant to tetracyclines
                                           and macrolides.

                       adjunct topical benzoyl peroxide
                                 • Topical benzyl peroxide may be added to the treatment regimen if
                                     oral antibiotics need to be used for >2 months.[33] [e2] Benzoyl
                                     peroxide products should be applied separately from topical retinoids
                                     to avoid inactivation of either or both drugs.[33]

                                Primary Options
                                  • benzoyl peroxide topical: (1-10%) consult product literature for
                                    guidance on dosage
moderate-to-severe      asdf
non-hormone-related,
non-nodulocystic
acne
    non-inflammatory     1st    topical retinoid
                                  • For patients with primarily comedonal acne, topical retinoids may
                                      be used. These include tretinoin,[e1] adapalene,[35] [e6] and
                                      tazarotene.
                                  • It is important that patients apply the medicine to the whole treatment
                                      area (e.g., the entire face), not to specific acne lesions.




Page 13
                              •   Most topical retinoids produce some degree of fine peeling and
                                  erythema, especially early in treatment. Start with lower potency and
                                  increase to higher potency if skin irritation is minimal. Topical
                                  adapalene is less likely to cause irritation than tretinoin.[39]

                            Primary Options
                              • tretinoin topical: (0.01 to 0.1%) children >12 years of age and adults:
                                  apply to the affected area(s) once daily before bedtime or on
                                  alternate days
                              • adapalene topical: (0.1%) children >12 years of age and adults:
                                  apply to the affected area(s) every evening
                              • tazarotene topical: (0.05% or 0.1%) children >12 years of age and
                                  adults: apply to the affected area(s) every evening
       inflammatory   1st   oral antibiotic + topical retinoid
                              • For best results, the combination of oral antibiotics and topical
                                  retinoids should be considered.Topical retinoids include tretinoin,[e1]
                                  adapalene,[35] [e6] and tazarotene. Patients are started with lower
                                  potency of a topical retinoid, increased to higher potency if skin
                                  irritation is minimal. Topical adapalene is less likely to cause irritation
                                  than tretinoin.[39]
                              • If oral antibiotics need to be used for >2 months, the addition of
                                  topical benzoyl peroxide[e2] should be considered.[33]
                              • Oral antibiotics are typically administered for at least 6 to 8 weeks
                                  and for up to several months, although some patients require
                                  indefinite antibiotic therapy.[e4] If re-treatment is necessary, an
                                  antibiotic that was effective in the past should be considered again;
                                  otherwise an alternative antibiotic can be prescribed. Doxycycline,
                                  minocycline, and tetracycline have been associated with
                                  photosensitivity.[33] [42] [43]

                            Primary Options
                              • tretinoin topical: (0.01 to 0.1%) children >12 years of age and adults:
                                apply to the affected area(s) once daily before bedtime or on
                                alternate days or
                              • adapalene topical: (0.1%) children >12 years of age and adults:
                                apply to the affected area(s) every evening or
                              • tazarotene topical: (0.05% or 0.1%) children >12 years of age and
                                adults: apply to the affected area(s) every evening
                                 -- AND --
                              • tetracycline : adolescents and adults: 250-500 mg orally twice daily
                                for 2-3 months, followed by 250-500 mg once daily for 1-2 months or
                              • minocycline : adolescents and adults: 50-100 mg orally (regular
                                release) twice daily for 2-3 months, followed by 50-100 mg once
                                daily for 1- 2 months or
                              • doxycycline : 50-100 mg orally twice daily for 2-3 months, followed
                                by 50-100 mg once daily for 1-2 months
                            Secondary Options
                              • tretinoin topical: (0.01 to 0.1%) children >12 years of age and adults:
                                apply to the affected area(s) once daily before bedtime or on
                                alternate days or




Page 14
                                    •   adapalene topical: (0.1%) children >12 years of age and adults:
                                        apply to the affected area(s) every evening or
                                    •   tazarotene topical: (0.05% or 0.1%) children >12 years of age and
                                        adults: apply to the affected area(s) every evening
                                         -- AND --
                                    •   erythromycin base: 500 mg orally twice daily for 2-3 months, followed
                                        by 500 mg once daily for 1-2 months
                                           • Higher reported bacterial resistance limits use of this drug to
                                              children and pregnant women.

                                  Tertiary Options
                                    • tretinoin topical: (0.01 to 0.1%) children >12 years of age and adults:
                                       apply to the affected area(s) once daily before bedtime or on
                                       alternate days or
                                    • adapalene topical: (0.1%) children >12 years of age and adults:
                                       apply to the affected area(s) every evening or
                                    • tazarotene topical: (0.05% or 0.1%) children >12 years of age and
                                       adults: apply to the affected area(s) every evening
                                        -- AND --
                                    • trimethoprim/sulfamethoxazole : 160/800 mg orally twice daily for
                                       2-3 months, followed by 160/800 mg once daily for 1-2 months
                                          • Used as a third-line agent for acne resistant to tetracyclines
                                             and macrolides.

                         adjunct topical benzoyl peroxide
                                   • Topical benzyl peroxide may be added to the treatment regimen if
                                       oral antibiotics need to be used for >2 months.[33] [e2] Benzoyl
                                       peroxide products should be applied separately from topical retinoids
                                       to avoid inactivation of either or both drugs.[33]

                                  Primary Options
                                    • benzoyl peroxide topical: (1-10%) consult product literature for
                                        guidance on dosage
severe nodulocystic        1st    oral retinoid
acne or acne resistant              • Before treatment with oral isotretinoin, patients require counselling
to standard treatment                   about the potential adverse effects. Severe headaches, decreased
                                        night vision, or signs of adverse psychiatric events are signs for
                                        prompt discontinuation.
                                    • FBC, lipid panel, and LFTs are monitored regularly.
                                    • Isotretinoin is teratogenic; therefore, women undergo pregnancy
                                        tests before starting isotretinoin, and monthly while taking the drug.
                                    • In the UK, isotretinoin is prescribed under the Pregnancy Prevention
                                        Programme (PPP), while in the US, it can only be prescribed through
                                        the iPledge system.[w1] These programmes are aimed at decreasing
                                        the number of birth defects associated with this medicine.

                                  Primary Options
                                    • isotretinoin : children >12 years of age and adults: 0.5 to 1 mg/kg/day
                                      orally for a total of 5-6 months




Page 15
                                           •   May need a repeat complete course if acne not controlled with
                                               other regimens after discontinuation.

severe nodulocystic    adjunct oral corticosteroids
acne or acne resistant           • Corticosteroids may be used as an adjunct to isotretinoin or to calm
to standard treatment                skin down before initiating isotretinoin, typically for 1 to 4 months to
                                     avoid relapses.They are always used in acne fulminans. Dose needs
                                     careful tapering to discontinue.

                                   Primary Options
                                     • prednisolone : 40-60 mg/day orally

Treatment: Emerging Treatments
 Laser and light treatments
Various laser and light modalities have been utilised in the treatment of acne. The best-known light therapy
is blue light, which is thought to target Propionibacterium acnes. However, treatment with this technique
has produced inconsistent results.[44] [45] Treatment with the pulsed dye laser has also produced
inconsistent results.[46] [47] These therapies are still not routinely prescribed, and more research is needed
to evaluate their effectiveness and to determine any long-term adverse effects. [48] [49]

Treatment: Treatment Guidelines
 Advice on the safe introduction and continued use of isotretinoin in acne in the
UK 2010
View Guidelines
Published by: British Association of Dermatologists
Last Published: 2010
Summary
  •   Isotretinoin should not be given to patients with hypervitaminosis A, to those with uncontrolled
      hyperlipidaemia, or to patients who are pregnant or lactating. Care should also be taken when
      prescribing to patients with renal or liver disease. This guideline discusses in detail 2 specific adverse
      effects of isotretinoin that should be considered: risk of teratogenicity and mood change.
 Isotretinoin for severe acne
View Guidelines
Published by: Medicines and Healthcare products Regulatory Agency (MHRA)
Last Published: 2008
Summary
  •   Guidelines provide a summary of advice on the use of isotretinoin for the treatment of severe acne.
      Isotretinoin is an effective treatment for severe acne but should not be used by some patients, such
      as those who are pregnant or considering becoming pregnant.
 Management of acne
View Guidelines
Published by: Global Alliance to Improve Outcomes in Acne
Last Published: 2003




Page 16
Summary
  •   Discusses the pathophysiology involved in acne vulgaris, as well as details regarding the use and
      mechanism of topical retinoids, antimicrobial therapy, hormonal therapy, oral retinoids, and adjunctive
      therapies.
 Standard guidelines of care for acne surgery
View Guidelines
Published by: Khunger N, IADVL Task Force and Department of Dermatology, Safdarjung Hospital, New
Delhi, India
Last Published: 2008
Summary
  •   Guideline discusses the use of various surgical procedures for the treatment of post-acne scarring
      and as adjuvant treatment for active acne. Surgery is indicated both in active acne and post-acne
      scars.

Followup
Followup: Outlook
Acne typically improves as patients progress through adolescence, but it may persist into adulthood. Most
patients do not have long-term consequences from acne, but severe lesions may leave residual scarring
in previously involved areas. Fine peeling and dryness caused by topical treatments tend to improve with
continued use.

Followup: Complications
                                    Complication                                       LikelihoodTimeframe
scarring                                                                               medium long term
  •  Severe acne may leave residual atrophic or hypertrophic scars in previously
     involved areas. There are a number of treatments for scarring, including
     excision or breakdown of the scar area. Newer treatments include fractionated
     CO2 and resurfacing with fractional laser therapy.
dyspigmentation                                                                   medium           variable
  •   Dyspigmentation can occur, especially in patients with darker skin types. It
      tends to be transient. Post-inflammatory hyperpigmentation can last for months.
      Sun protection is the mainstay of treatment.

Followup: Recommendations
Monitoring
FBC, lipid panel, and LFTs are monitored regularly in all patients taking isotretinoin. Women also require
monthly pregnancy tests to continue treatment with isotretinoin.
Patient Instructions
Before starting therapy, it is important to discuss realistic expectations with patients. With any acne therapy,
it can take at least 4 to 8 weeks before a response is seen; the full effects of treatment may take several
months, and acne may actually flare slightly after initiating treatment. Patients need to remain compliant
even if they are not seeing an early response. Even with the best treatment, patients may get occasional
acne lesions.




Page 17
Before treatment with isotretinoin, patients require counselling about the possibility of adverse effects and
the need for regular blood tests. Dry skin and chapped lips are very common, and lip and skin moisturisers
may be considered. Severe headaches, decreased night vision, or signs of adverse psychiatric events
should prompt the patient to seek medical attention. Patients should be instructed not to donate blood
during treatment or 30 days thereafter. Women must be advised that isotretinoin causes birth defects; they
should undergo pregnancy tests before starting, and monthly while taking the drug.

Evidence Scores
e1.      Reduction in inflammatory and non-inflammatory lesions in mild-to-moderate acne: there is poor-quality
         evidence to suggest that, when compared with placebo, topical tretinoin reduced the number of
         inflammatory and non-inflammatory lesions at 8 to 12 weeks.Clinical Evidence: [link] Score: C
e2.      Reduction in total lesion count or number of inflammatory and non-inflammatory lesions in moderate
         acne: there is poor-quality evidence to suggest that topical benzoyl peroxide, when compared with
         placebo, reduced total lesion count or number of inflammatory and non-inflammatory lesions at 4 to
         12 weeks.Clinical Evidence: [link] Score: C
e3.      Reduction in number of inflammatory lesions in mild to severe acne: there is poor-quality evidence
         to suggest that, compared with placebo or vehicle agent, topical clindamycin 1% reduced the number
         of inflammatory lesions at 8 to 12 weeks.Clinical Evidence: [link] Score: C
e4.      Improvement in acne: there is poor-quality evidence to suggest that oral erythromycin and oral
         doxycycline reduced the number of pustules after 6 weeks of treatment. There was no significant
         difference found between the two at 6 weeks or between oral erythromycin and oral tetracycline.
         Medium-quality evidence also suggests that oral tetracyclines (doxycycline, lymecycline, minocycline,
         oxytetracycline, tetracycline) are beneficial in the treatment of acne. However, adverse effects result
         in a trade-off between harm and benefit.Tetracyclines should not be taken by pregnant or breastfeeding
         women due to the harm tetracyclines cause to bone and teeth in fetuses and infants.Clinical Evidence:
         [link] Score: C
e5.      Reduction in inflammatory and non-inflammatory lesions in mild-to-moderate acne: there is poor-quality
         evidence to suggest that, when compared with placebo, topical isotretinoin reduced the number of
         inflammatory and non-inflammatory lesions at 8 to 12 weeks.Clinical Evidence: [link] Score: C
e6.      Reduction in inflammatory and non-inflammatory lesions in mild-to-moderate acne: there is
         medium-quality evidence to suggest that, when compared with placebo, adapalene reduced the
         number of inflammatory and non-inflammatory lesions at 12 weeks. Adapalene has also been found
         to maintain improvement in lesion counts in those who had responded to prior oral doxycycline
         treatment.Clinical Evidence: [link] Score: B
e7.      Reduction in number of inflammatory lesions in mild to severe acne: there is poor-quality evidence
         to suggest that, compared with placebo, topical erythromycin reduced the number of inflammatory
         lesions at 8 to 12 weeks.Clinical Evidence: [link] Score: C

Key Articles
     •   Strauss JS, Krowchuk DP, Leyden JJ, et al. Guidelines of care for acne vulgaris management. J Am
         Acad Dermatol. 2007;56:651-663.[Abstract]
     •   Gollnick H, Cunliffe W, Berson D, et al. Management of acne: a report from a global alliance to improve
         outcomes in acne. J Am Acad Dermatol. 2003;49:S1-S37.[Abstract]

Other Online Resources
w1. iPledge system (for isotretinoin prescribing)

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Page 19
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      outcomes in acne. J Am Acad Dermatol. 2003;49:S1-S37.[Abstract]
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Page 20
Image Library




                                     Comedonal acne
                Source: University of Michigan Department of Dermatology




Page 21
                         Typical appearance of acne
          Source: University of Michigan Department of Dermatology




Page 22
                                Scarring acne
          Source: University of Michigan Department of Dermatology




Page 23
                                         Nodulocystic acne
                     Source: University of Michigan Department of Dermatology

Credits
Authors
Yolanda Rosi Helfrich
Assistant Professor
Department of Dermatology
University of Michigan
Ann Arbor
MI
Mark Naftanel
Dermatologist
Kaiser Permante
Falls Church
VA
YRH declares that she has no competing interests.



Page 24
MN declares that he has no competing interests.

Peer Reviewers
Gina Taylor
Resident
Department of Dermatology
SUNY Downstate Medical Center
New York
NY
GT declares that she has no competing interests.




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