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A Brief Review on Acne Vulgaris: Pathogenesis, Diagnosis and Treatment

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 Research & Reviews: Journal of Pharmacology
ISSN: 2230-9861 (online), ISSN: 2349-1299 (print)
Volume 4, Issue 3
www.stmjournals.com

A Brief Review on Acne Vulgaris: Pathogenesis,

Diagnosis and Treatment
Manoj A. Suva1*, Ankita M. Patel2, Neeraj Sharma1,
Chandrayee Bhattacharya1, Ravi K. Mangi1
1
Aksharpreet Institute of Pharmacy, Lakhabaval Road, Jamnagar, Gujarat, India
2
Shri Sarvajanik Pharmacy College, Mehsana, Gujarat, India

Abstract
Acne vulgaris is one of the most common dermatological disorders that afflict people in
their adolescence. Acne vulgaris or simply known as acne is a human skin disease
characterized by skin with scaly red skin (seborrhea), blackheads and whiteheads
(comedones), pinheads (papules), large papules (nodules), pimples and scarring. Acne
vulgaris is a disease of pilosebaceous unit characterized by the formation of open and
closed comedones, papules, pustules, nodules and cysts. Acne affects skin having dense
sebaceous follicles in areas including face, chest and back. Acne is not life threatening
but severe acne can affect psychological status and social activities. The present review
focuses on an epidemiology, etiology, pathogenesis, diagnosis, differential diagnosis and
management of acne with the pharmaceutical dosage forms of oral and topical
administrations. Various medicines for acne treatment includes benzoyl peroxide,
antibiotics, antiseborrheic medications, sulfur and sodium Sulphacetamide, anti-
androgen medications, salicylic acid, hormonal treatments, alpha hydroxy acid, retinoids,
azelaic acid, keratolytic soaps and nicotinamide. Currently laser and light devices and
minor subcision surgery have been also performed for acne treatment.

Keywords: Acne vulgaris, comedones, pilosebaceous unit, benzoyl peroxide,

antibiotics, laser treatment

*Author for Correspondence E-mail: manojsuva_0211@yahoo.co.in

INTRODUCTION nodulocystic [11]. The cystic acne occurs on

Acne vulgaris or simply known as acne is a
human skin disease characterized by skin with
scaly red skin (seborrhea), blackheads and
whiteheads (comedones), pinheads (papules),
large papules (nodules), pimples and scarring
[1]. Acne affects skin having dense sebaceous
follicles in areas including face, chest and
back [2]. Acne may be of inflammatory or
non-inflammatory forms [3]. Due to changes
in pilosebaceous units lesions are caused by
androgen stimulation. Acne occurs commonly
during adolescence, affecting about 80–90%
of teenagers in the Western world and lower
rate are reported in rural societies [4–7]. Acne
is usually caused by increase in androgens
level like testosterone mainly during puberty
in both male and female [8]. Acne reduces
over time and tends to disappear over the age
[9, 10]. The large nodules called as cysts and
severe inflammatory acne called as
buttocks, groin, armpit area, hair follicles and
perspiration ducts and affects deeper skin
tissue than common acne. Acne causes
scarring and psychological effects such as;
reduced self-esteem and in rare cases
depression or suicide [12, 13]. Reports showed
the incidence of suicidal tendency in patients
with acne as about 7.1% [14]. Acne usually
occurs during adolescence [15]. The word
acne refers to the presence of papules, scars,
comedones and pustules. The common form of
acne is known as acne vulgaris. Many
teenagers suffer from this type of acne. Acne
vulgaris shows the presence of comedones.
Acne rosacea is synonym for rosacea and
some persons not have acne comedones
associated with their rosacea, hence prefer the
term rosacea. Chloracne occurs due to
exposure to polyhalogenated compounds.

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Acne Vulgaris Review Suva et al.

EPIDEMIOLOGY
In 2010, it was reported that acne affects
approximately 9.4% of the population [16]. It
affects about 90% of people during teenage
years and sometimes in adulthood [5]. About
20% people have moderate and severe cases.
Acne rates are low in rural areas and it may
not occur in the non-westernized people of
Paraguay and Papua New Guinea [7]. It is
more common in females 9.8% compared to
males 9.0% [16]. In over 40 years old subjects
about 1% of males and 5% of females have Fig. 2: Acne on the Back [20].
problems [5]. It affects all ethnic groups'
people and it is not clear if race affects rates of
disease [17, 18]. Acne affects 40 to 50 million
people which is about 16% in the United
States and approximately 3 to 5 million people
which is about 23% in Australia [19]. In the
United States, it is more severe in Caucasians
than African descent people [2].

Signs and Symptoms of Acne

It includes papules, nodules (large papules),
seborrhea (increased oil-sebum secretion),
comedones, pustules and scarring (Figures 1–
3) [1]. The appearance of acne varies with skin
color and it is also associated with
psychological and social problems [5].
Fig. 3: Acne on the Chest [20].
Acne scars shows inflammation within the
dermis and it is created by the wound healing
resulting in collagen deposition at one spot
[21]. In Table 1 type of scars are presented.

ETIOLOGY
Acne develops due to blockage of follicles,
hyperkeratinization and keratin plug formation
and sebum (microcomedo). With increased
androgen production, sebaceous glands are
enlarged and sebum production is increased.
The microcomedo may enlarge to form an
open comedo (blackhead) or closed comedo.
Comedones occur as a result of clogging of
sebaceous glands with sebum, naturally
occurring oil and dead skin cells [2].
Fig. 1: Acne on the Face.

Table 1: Types of Scars.

Scars Characteristics

Box car scars Angular scars occur on cheeks and can be either superficial or deep similar to chickenpox scars

Ice pick scars Deep pits are most common, sign of acne scarring

Rolling scars Wave like appearance in skin

Hypertrophic scars Thickened or keloid scars

Pigmented scars True scars, Change in the skin’s pigmentation, As a result of nodular or cystic acne, inflamed red mark

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Research & Reviews: Journal of Pharmacology
Volume 4, Issue 3
ISSN: 2230-9861 (online), ISSN: 2349-1299 (print)
The naturally occurring commensal bacterium
Propionibacterium acnes can cause
inflammation and inflammatory lesions like
infected pustules or nodules and papules in the
dermis around the microcomedo or comedone
resulting in redness, scarring or
hyperpigmentation [2, 22].
Environmental Factors
It includes various factors like High-humidity,
Prolonged sweating, Increase in skin
hydration, Exposure to dirt or vaporized
cooking oil or certain chemicals like
petroleum derivatives.
Drug Use
Drugs like Phenytoin, Isoniazid,
Phenobarbital, Lithium, Ethionamide,
Steroids, Azathioprine, Quinine and Rifampin
causes acne [23].
Hormonal
Menstrual cycles and puberty may also causes
acne. During puberty, increase in androgens
level causes the enlargement of follicular
glands and sebum production is also increased
[2, 24]. Anabolic steroids produce similar
effect [25]. Several hormones are linked with
acne like the androgens testosterone,
dihydrotestosterone, dehydroepiandrosterone
sulfate and insulin like growth factor 1 (IGF
-I). In later years development of acne vulgaris
is uncommon but rosacea incidence will
increase which is having similar symptoms in
older age groups. Acne vulgaris in adult
women may be due to underlying condition
such as; pregnancy, Cushing’s syndrome,
hirsutism or polycystic ovary syndrome. Acne
climacterica refers to menopause associated
acne, occurs as production of the anti-acne
ovarian hormones estradiol and progesterone
allowing the acnegenic hormone testosterone
to continuously exert its effects.
Genetic
The genetics of acne susceptibility is
polygenic as the disease does not follow
classic Mendelian inheritance pattern.
There are multiple candidates for genes related
to acne which includes polymorphisms in
Tumor necrosis factor-alpha, Interleukin-1
alpha, CYP1A1 [4].
RRJoP (2014) 1-12 © STM Journals 2014. All Rights Reserved
Psychological
Studies shows that increased stress levels are
associated with increased acne severity [26].
The National Institutes of Health (USA) shows
that stress can cause acne flare [27]. In
Singapore, study of adolescents observed
positive correlation between stress levels and
acne severity [28].
Infectious
Propionibacterium acnes (P. acnes) are
anaerobic bacterium species that mainly
causes acne. Staphylococcus aureus has been
discovered to play an important role since
normal pores colonized only by
Propionibacterium acnes [29]. Specific clonal
sub strains of P. acnes are also associated with
normal skin health and long term acne
problems. These strains have the capability of
changing, perpetuating or adapting to the
abnormal cycle of inflammation, oil
production and inadequate sloughing activities
of acne pores. For at least 87 years, one
virulent strain of Propionibacterium acnes has
been circulating around Europe [30].
Antibiotics resistance has been continuously
increasing to P. acnes in vitro [31].
Diet
The relationship between acne and diet
remains unclear although high glycemic diet is
associated with worsening of acne [32–34].
There is a positive association between the
milk consumption and prevalence of acne
increases [33, 35, 36]. Reports showed that
consumption of chocolate and salt are not
associated with development of acne [33].
Chocolate contains large amount of sugar that
can lead to high glycemic load. It might be
possible that acne is linked with obesity and
insulin metabolism [37].
Parasitic
Acne is linked with the parasitic mite
Demodex but it is not clear whether Demodex
or Demodex associated bacteria causes the
effects [38–40].
PATHOGENESIS
Acne develops as a result of bacterial
overgrowth and inflammation in the
pilosebaceous units. The body’s hormone level
alter pilosebaceous gland function and causes
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Acne Vulgaris Review
acne. Follicular epithelial cells abnormally
differentiated and forms tighter intracellular
adhesions and shed less. That leads to the
development of microcomedones or
hyperkeratotic plugs which enlarge to form
noninflammatory open or closed comedones
[41]. Androgens are causative factors for acne
which induces sebum production leading to
Fig. 4: Basic Mechanisms Involved in the Acne Pathogenesis.
The acne spreading depends on pilosebaceous
gland density and morphology and it is
common in the face, chest, neck and back.
Non-inflammatory acne is characterized by the
formation of closed or open comedones. Open
comedones also known as blackheads shows
dark colored hyperkeratotic plugs within the
follicular opening which is related to the
melanin oxidation but not dirt, as it is a
common disbelief. Closed comedones also
known as whiteheads are white to flesh toned
in color and not have a central open pore [41].
Propionibacterium acnes a normal component
of the cutaneous flora, invade the
pilosebaceous unit using lipid rich sebum as a
nutrient source and grow in the presence of
increased sebum production leading to
inflammation via complement activation and
the release of metabolic byproducts, proteases
and neutrophil-attracting chemotactic factors
[41, 44]. When comedones ruptures, the
contents of the pilosebaceous unit spread into
the adjacent dermis and it leads to
development of inflammatory acne vulgaris
lesions such as; cysts, nodules, papules and
pustules [41, 45].
Sometime cysts may adhere to form channels
or draining sinuses. The acne vulgaris occurs
due to increased sebum secretion, ductal
keratinocyte hyperproliferation, excess growth
of acne-associated bacteria and host
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Suva et al.
the comedones development [42] (Figure 4).
Changes in the skin’s natural flora are linked
with androgen related sebum production.
Diseases like congenital adrenal hyperplasia,
polycystic ovarian syndrome and endocrine
tumors result in a high level of androgens in
body and associated with the development of
acne vulgaris [43].
inflammatory response. In lesion initiation,
abnormal proliferation and differentiation
leads to the occurrence of microcomedone in
the initial lesion [46–48].
This is followed by (i) the accumulation of
sebum in the follicle lumen, causing a plug,
either open or closed (ii) inflammatory
components leaking from a follicle to the
dermis. An acne lesion thus forms. A patient’s
immune sensitivity toward acne associated
antigens and skin integrity can affect the
initiation of acne lesions. According to the
genomic data of Propionibacterium acnes
publicly released in 2004, acne virulence
factors encoded in the genome can degrade
host tissue and trigger inflammation [49, 50].
There are several molecular cues that cause the
progression of acne virulence. One is the
presence of Christie, Atkins, Munch-Peterson
(CAMP) factor of Propionibacterium acnes
and a secretory protein with its co-hemolytic
activity of the host acid sphingomyelinase
(ASMase). CAMP and ASMase can be
utilized for the development of drugs to inhibit
or to suppress bacterial overgrowth to prevent
the acne progression.
The synergistic lysis of erythrocytes via the
CAMP reaction has been found in
Propionibacterium acnes [51,52]. The CAMP
reaction was described as sheep erythrocytes
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Research & Reviews: Journal of Pharmacology
Volume 4, Issue 3
ISSN: 2230-9861 (online), ISSN: 2349-1299 (print)
lysis by Staphylococcus aureus
sphingomyelinase C and CAMP factor
produced by some streptococcal species.
The sphingomyelin and phospholipids are
hydrolyzed by the enzyme followed by cell
lysis [53]. Propionibacterium acnes CAMP
factor can be utilized by Staphylococcus
aureus to enhance hemolysis in acne lesion
[54]. A mutagenesis method has been
developed to knock out the genes encoding
CAMP factors in P. acnes [55].
The sialidase bacterial cell wall anchoring
factor produced by Propionibacterium acnes
can catalyze the hydrolysis of sialic acid from
the surface of mammalian cells and lead to cell
death. The immunization of sebocytes with
recombinant sialidase has been found to
neutralize Propionibacterium acnes induced
toxicity in sebocytes and sialidase vaccinated
ICR mice showed reduced erythema on the
ears [56,57]. This innovative medicine could
be developed for acne treatment. The
Propionibacterium acnes genome encodes
Fig. 5: Propionibacterium Acne Role in Acne Pathogenesis [60].
RRJoP (2014) 1-12 © STM Journals 2014. All Rights Reserved
several extracellular hydrolases, such as;
sialidase, endoglycoceramidases and
hyaluronate lyase. Propionibacterium acnes
lipase is responsible for bacterial colonization
in sebaceous follicles [52]. Other
inflammatory reactions localized in the acne
lesion include chemo attractant molecules that
recruit polymorphonuclear leukocytes and
lymphocytes, the production of the
inflammatory cytokines, and the complement
activation [58]. The pathogenesis of acne can
be triggered by toll like receptor 2 which
regulates many immune response genes.
Propionibacterium acnes activate the
pilosebaceous unit and induce the production
of IL-12 and IL-8 of monocytes via the TLR2
pathway. TLR2 and TLR4 expression is
increased in the acne lesions of the epidermis.
This inflammation can lead to
hyperproliferation of the ductal epidermis. IL-
8 recruits neutrophils to the pilosebaceous unit
in which degradative enzymes ruptured the
follicular epithelium [59]. The role of
Propionibacterium acnes in the pathogenesis
of acne is shown in Figure 5.
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Acne Vulgaris Review
DIAGNOSIS
Scales used for grading the severity of acne
vulgaris are as follows:
a) Pillsbury scale: It give classification of the
acne based on severity ranging from 1
(least severe) to 4 (most severe).
b) Cook's acne grading scale: It utilizes
images to grade severity ranging from 0
(least severe) to 8 (most severe).
c) Leeds acne grading technique: It counts
and categorizes inflammatory and non-
inflammatory lesions grade ranging from 0
to 10 [61].
Fig. 6: Acne Grades and Severity [62].
(i) Acne, grade I; multiple open comedones
(ii) Acne, grade II; closed comedones (iii)
Acne, grade III; papulopustules (iv) Acne,
grade IV; multiple open comedones,
closed comedones, and papulopustules,
plus cysts (Figure 6).
Differential Diagnosis
a) Acne rosacea: It is commonly observed in
middle age or later in life.
b) Folliculitis and boils: It may present with
pustular lesions similar to acne.
c) Milia: It is small keratin cysts that may be
confused with whiteheads. They may be
RRJoP (2014) 1-12 © STM Journals 2014. All Rights Reserved
Suva et al.
whiter than acne whiteheads and most
commonly seen around the eyes.
d) Perioral dermatitis.
e) Pityrosporum folliculitis: It predominates
on the trunk [63].
MANAGEMENT
Various medicines for acne treatment includes
benzoyl peroxide, antibiotics, antiseborrheic
medications, sulfur and sodium
Sulphacetamide, anti-androgen medications,
salicylic acid, hormonal treatments, alpha
hydroxy acid, retinoids, azelaic acid,
keratolytic soaps and nicotinamide [64]. Laser
and light devices and minor subcision surgery
is also performed. Benzoyl peroxide is first
line treatment for mild and moderate acne due
to its effectiveness and mild side effects like
irritant dermatitis, dryness of the skin, redness
and peeling. It helps to prevent formation of
comedones caused by P. acnes bacterium and
has anti-inflammatory properties [2]. Topical
application increases sensitivity to the sun and
sunscreen is combined to prevent sunburn.
Benzoyl peroxide is often combined with
antibiotics. Benzoyl peroxide is found to be
equally effective as antibiotics at all
concentrations, although it does not produce
bacterial resistance [65].
Antibiotics
Antibiotics are used in more severe cases due
to their antimicrobial activity against P. acnes
along with anti-inflammatory properties. They
are becoming less effective with increasing
resistance of P. acnes worldwide [2, 65].
Antibiotics including clindamycin,
erythromycin and tetracyclines such as;
doxycycline, oxytetracycline, lymecycline and
minocycline are topically applied or orally
administered for treatment of acne (Table 2).
Antiseborrheic Drugs
Sulfur is used in concentrations varying from 1
to 10% and act as an antiseborrheic and mild
keratolytic but it produces bad odor and the
staining of clothes. Alcohol-ether in equal
parts and zinc sulfate also act as sebum
reducing agents [66].
Topical Sulfur and Sodium Sulphacetamide
Sulfur is used as a drying agent and
antibacterial agent. It is present in washes,
lotions, creams, foam formulations,
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Volume 4, Issue 3
ISSN: 2230-9861 (online), ISSN: 2349-1299 (print)
prescription and nonprescription masks. It can
be useful for treatment of rosacea and
seborrhoeic dermatitis. Sodium
Sulphacetamide is often combined with sulfur
and has anti-inflammatory properties. Sodium
Sulphacetamide can treat acne and used for the
sensitive skin acne patient [67].
Salicylic Acid
Salicylic acid has bactericidal and keratolytic
properties and hence lessens acne. Salicylic
acid open obstructed skin pores and promotes
shedding of epithelial skin cells but it causes
hyperpigmentation of the skin in individuals
with darker skin types [2].
Anti-androgen Treatment
In females acne can be treated with the use of
combined oral contraceptives [45]. Third or
fourth generation progestins such as
norgestimate, desogestrel or drospirenone
combination product may be more beneficial
[68]. Oestrogenic oral contraceptive is an
effective for acne [69]. Due to androgenic
properties of oral contraceptive norethisterone
is contradicted in acne [70]. Anti-androgen
cyproterone combined with 50 µg of
ethinylestradiol is available as Dianette®
which is most effective hormonal intervention
[71]. A combination of ethinylestradiol with
drospirenone available as Yasmin® has been
found to be effective [72]. Spironolactone has
Table 2: Current Medical Treatments of Acne Vulgaris [61].
Administration Drug or dosage form
Tetracycline, Doxycycline, Minocycline,
Oral
Isotretinoin (13-cis-retinoic acid)
Benzoyl peroxide, Clindamycin,
Topical Erythromycin, Tetracycline, Tretinoin,
Tazarotene, Green tea extracts
Liposomes, Solid lipid nanoparticles,
Particle-based Drug
Nanostructured lipid carriers, Micro
delivery system
emulsions
Light based Endogenous porphyrins (coproporphyrin administration and Drug delivery system, Light therapy
therapy** III), 5-aminolevulinic acid
* For particle-based Drug delivery system, **this therapy use either topical drugs or particle based drug delivery system
along with light irradiation.
Procedures
Comedo extraction may help patient with
comedones that are not treated with standard
treatment [74]. Corticosteroids are injected
into the acne comedone for immediate relief
RRJoP (2014) 1-12 © STM Journals 2014. All Rights Reserved
been shown to be effective for older women
[73].
Topical Retinoids
Topical retinoids possess anti-inflammatory
properties and act by normalizing the follicle
cell life cycle and prevent hyperkeratinization
of these cells that can create a blockage. It
includes tretinoin, adapalene and tazarotene.
They are related to vitamin A and similar to
isotretinoin and have much milder side effects
like skin irritation and flushing [2]. Retinol a
form of vitamin A has mild effects and is used
in many over the counter moisturizers and
other topical products.
Oral Retinoids
Isotretinoin is effective for treatment of
moderate and severe acne and after one to two
months of use improvement is seen. In about
80% of people, a single course reports
complete remission in more than 50% patients
and 20% of patients require a second course.
Adverse effects includes dry skin, nose bleeds,
muscle pains, increased liver enzymes and
increased lipid levels in the blood. There is a
high risk of fetal abnormalities during
pregnancy. There is no evidence that oral
retinoids increase the risk of adverse effects
like depression and suicide [5]. Chemical
peeling of the skin is used for the treatment of
acne and peeling is superficial.
Treatment features
Drugs should be taken daily, High patient compliance,
Adverse effects limit the use of the drugs
Local administration of drugs, Ease of termination of
drug action, Adverse effects limit the use of the drugs
Sustained release of drugs, More effective than topical
gel, Higher flux of drug across the skin, Effective for
follicular targeting
Fewer adverse effects than systemic/topical
alone or along with liposomal drugs reported, Not a
first line therapy for acne vulgaris
[2]. There is no report that microdermabrasion
is effective. As of 2012, report for light
therapy and lasers is insufficient for regular
use [74]. Light therapy is an expensive
treatment and provides short term benefit and
Page 7
Acne Vulgaris Review
there is a lack of long term outcome data in
patients with severe acne [2, 75]. Laser
surgery can be used to reduce the scars left
behind by acne [76]. Boils can be removed by
surgical lancing in patients with cystic acne
[12]. In a double blind, randomized study, a
comparison was done between alpha-hydroxy
(30% glycolic acid) versus beta-hydroxy (30%
salicylic acid) peels and it was found that both
peels were equally effective for acne treatment
[77]. Subcision is occasionally used to treat
acne scars. Subcision involves insertion of a
tri-beveled hypodermic needle through skin
surface puncture and maneuvering its edges to
break down subcuticular fibrotic strands to
release the skin from the underlying
connective tissue [78]. It appears to be equally
effective as collagen filler [79].
Laser and Light Devices
The reports showed that photodynamic
therapy, light emitting diode therapy and
combination of pneumatic energy and light has
been successfully used with traditional
therapies for treatment of acne [80]. For the
treatment of acne combination product
Isolaz™ (Aesthera, Pleasanton, CA, USA)
uses a vacuum with broad band light source
has been shown to be effective in 11 patients
treated at 3 week intervals and decreases
inflammatory and noninflammatory lesions
[81].
Alternative Medicine
Various natural products have been
investigated for treatment of acne [82].
Topically administered Azelaic acid (20%)
twice daily for six months has been shown to
be effective for treatment of mild to moderate
acne [83]. It is similar effective as 5% topical
benzoyl peroxide, 0.05% isotretinoin and 2%
erythromycin [84]. Sometimes azelaic acid
may cause skin irritation [85].
A topical application of tea tree oil is also
effective for acne treatment [86]. A vaccine
has been tested successfully against
inflammatory acne in mice but has not yet
been proven to be effective in humans [87]. In
2007, the first genome sequencing of a P.
acnes bacteriophage (PA6) occurred which
could enhance the development of a potential
bacteriophage therapy to treat acne and might
improve the problems associated with long
RRJoP (2014) 1-12 © STM Journals 2014. All Rights Reserved
Suva et al.
term antibiotic therapy and bacterial resistance
[88].
CONCLUSION
Acne vulgaris is most common skin disorders
that affect people in their adolescence. Acne
vulgaris is characterized by skin with
seborrhea, blackheads and comedones,
papules, papules, pimples and scarring.
Various scales used for grading the severity of
acne vulgaris are Pillsbury scale, cook's acne
grading scale and Leeds acne grading
technique. Various medicines for acne
treatment includes benzoyl peroxide,
antibiotics like erythromycin, clindamycin,
tetracyclines, antiseborrheic medications like
sulfur and sodium sulphacetamide, anti-
androgen medications like norgestimate,
desogestrel or drospirenone, Dianette®,
Yasmin®, salicylic acid, hormonal treatments,
alpha hydroxy acid, retinoids, azelaic acid,
keratolytic soaps and nicotinamide. Currently
laser and light devices and minor subcision
surgery have been also performed for acne
treatment. Recently genome sequencing of P.
acnes bacteriophage (PA6) identified which
could enhance the development of a potential
bacteriophage therapy to treat acne.
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