ACNE VULGARIS
Dr.Pranita Wankhede
Definition
Chronic , self-limiting, inflammatory disease of the pilosebaceous
units characterized by seborrhea and formation of polymorphic array of
lesions consisting of comedones,
erythematous papules and pustules.In more severe cases nodules, deep pustules
or pseudo cyst and scarring.
Epidemiology
Age
Usually they start in adolescence and resolve by
mid-twenties.A peak in prevalence and severity occurs between 14 and
17 years in females and 16 and 19 years in males.
Sex
More common and more severe in males than females. Mild
comedonal acne may be the first sign of pubertal maturation.
Genetic factors
High concordance between monozygotic twins
Patient with persistent acne have a strong family history
Decreased incidence of atopic dermatitis in patients with acne is
genetically determined
Association of severe acne with XYY Syndrome
Aetiopathogenesis
Factors involved in
pathogenesis
Seborrhea
Circulating sex hormones
Quantity and quality of sebum secretion
Alteration in the pattern of keratinization Comedogenesis
Colonization of intrafollicular duct by P. acnes
Inflammation
Environmental factors
Seborrhea
Role of circulating sex hormones
Increased androgen production → Increased target cell response mediated through conversion of
testosterone to more active DHT by high 5α-reductase-I activity as it
present abnormally high in acne prone regions and sebaceous gland.
Some endocrine disorders related with acne are
PCOD, Late-onset adrenal hyperplasia and Acromegaly.
Quality and quantity of sebum secretion
Sebum consists of mixture of squalene,
wax,sterol esters, cholesterol, polar lipid and triglycerides.
Bacterial hydrolase especially from P.
acnes convert the triglycerides to free fatty acids on the skin surface as
inflammatory process.
Alteration in the pattern of keratinization-Comedogenesis
Comedones are due to abnormality in the proliferation and
differentiation of ductal keratinocytes and their increased adhesion due to
persistence of desmosomes leading to retention
hyperkeratosis.
Stimulus for hyperkeratosis
Androgens
Low linoleate in sebum, increased squalene and
free fatty acids
Abnormality in apoptosis
External chemicals like isopropyl myristate,
propylene glycol and D and C red dyes
Relationship between P. Acnes and acne
Three main organisms are isolated from skin
surface and pilosebaceous duct of patients with acne –
P. acnes, Staph
epidermidis and Malassezia furfur.
Adolescence and seborrhea are associated with
a significant increase in P. acnes numbers.
Mediation of inflammation
Precise factors are unknown.
CD4+ T cells and macrophages infiltrate.
Release of IL-1α could
also be an initiating factor, causing up-regulation of vascular adhesion
molecule expression such as ICAM-1, VCAM, E-selectin and Elam- 1.
Ductal keratinocytes produce IL-6, IL-8, IL-12
and TNF-α
Sebaceous glands produce leukotriene B4 which
induce recruitment activation of neutrophils and monocytes.It also stimulate
the production of a number of pro inflammatory cytokines.
Environmental and physiological factors
- Hot and humid
climate aggravate acne → increased sweating causing ductal
hydration
- Premenstrual flare
- Occupational factors by providing conducive atmosphere
- Dietary habits:
Foods with high glycemic index induces hyperinsulinemia
- Androgen
synthesis
- Increases
the level of IGF and reduces IGF binding proteins-up regulated growth of
follicular epithelium that increase sebum production and synthesis of
androgen from gonads
- Milk
and dairy products contains IGF and androgen DHEA,5α reduced testosterone.
- Emotional stress and strain
- Smoking produces arachidonic acid and
polycyclic hydrocarbon which induce phospholipase mediated inflammatory
mediators
- External
application of oils, pomades and other comedogenic chemicals
Clinical features
- Comedones-
Plug of sebaceus and keratenous material lodged in opening of hair
follicle
- Black heads (open comedones)-
(1-2mm) dome shaped papules in which there are dilated follicular outlets filled with keratin. Black due to
melanin oxidation
- White heads (closed comedones) – Generally 1mm, skin coloured, no visible follicular opening
- Intermediate comedones –
Features of both open and closed comedones
- Sandpaper comedones –
Multiple very small whiteheads found mainly on forehead
- Submarine Comedones –
Large comedonal structures >0.5cm diameter.Occur deep in skin; source
of recurrent inflammatory nodular lesion
- Secondary comedones –
Produced after exposure to dioxins(chloracne) , topical steroid
Inflammatory lesions
Superficial
– Papules, pustules (5mm or less)
Deep
– Deep pustules, nodule
Sinus
formation between nodules and/or deep pustules
leads to disfigurement and scarring
Lesions are tender, chronic and resistant
Pyogenic
granuloma may develop
infrequently in patients with severe disease of trunk and in patients during
early phase of treatment with isotretinoin.
Inflammatory
and haemorrhagic nodules
are feature of acne conglobata.
Grading of acne based on clinical features
Grade 1(mild) - Comedones, occasional papules
Grade 2(moderate) – Comedones, many papules, few pustules
Grade 3(severe) - Predominantly pustules, nodules, abscess
Grade 4(severe nodular)-Mainly severe nodules or abscess, widespread
scarring
Complication
- Scarring
– 90% develop some degree of
scarring.
- Increase collagen > hypertrophic scar, keloid
- Loss of collagen > ice-pick scar, box scars, rolling
scars, depressed fibrotic scars, atrophic macules, perifollicular
elastolysis
- Persistent
post-inflammatory hyperpigmentation
- Calcification
is a rare complication of scarring
Psychosocial effects of acne
- Embarrassment,
anxiety, shame
- Body
dismorphic disorder
- Lack
of confidence
- Impaired
social interaction
- Significant
problem with unemployment
- Suicidal
tendencies
Treatment
Mild
acne – Topical therapy
Moderate
acne –Oral therapy +
topical
Severe
acne – Oral isotretinoin
unless
Contraindicated
Topical drugs are benzoyl peroxide, retinoid,
antibiotics and azelaic acid, either as monotherapy or in combination
Topical therapy
Topical retinoids- i) Tretinoin (0.01-0.05%) , ii) isotertinoin (0.05%), iii) adapelene
(0.1%) iv) tazarotene
Mechanism of action
Reduce hypercornification within the
follicular canal
Inhibit development of the microcomedo and
non-inflamed lesion.
Make the microenvironment less favourable for
the development of inflammation.Reduce rupture of the comedone into surrounding
skin which result in less inflammation
2) Benzoyl peroxide
Available as creams, gel,lotion in a strength varying from 2.5 to 10%
Mechanism of action
Benzoyl peroxide is a powerful antimicrobial, rapidly destroys both
surface and ductal P. acnes,yeasts.
Release free oxygen radicals with potent bactericidal activity in the
sebaceous follicles.It has anti-inflammatory action too.It is a peeling agent with mild comedolytic activity which also reduce the number of non-inflamed lesions by
decreasing follicular hyperkeratosis.
Azelic acid
Mechanism of action
Reduce the number and function of P. acnes and comedones by normalizing
the disturbed terminal differentiation of keratinocytes in the follicle
infundibulum.There is direct anti-inflammatory effect of it.
Topical nicotinamide
4% topical nicotinamide has anti-inflammatory actions and does not
induce P.acnes resistance.
Effective in inflammed lesions also.
Other topical therapies
- Topical
dapsone 5%
- Sulphur
- Resorcin
- Alpha
hydroxy acids- glycolic acid, lactic acid.
- Chemical
peels like glycolic acid (10-50%), trichloroacetic acid, salicylic acid (10-30%)
- Complementary
therapy- Tree tea oil
- Gluconalactone(obtained
from Saccharomyces bulderi)
Oral therapy
- Antibiotics
- Isotretinoin
- Dapsone
- Clofazimine
- Vitamin
A
- Oral
zinc
- Steroid
- Hormonal
therapy
Oral antibiotics
- Tetracycline
(oxytetracycline, doxycycline, lymecycline, minocycline)
- Azithromycin,
Erythromycin
- Trimethoprim
- Oral
Clindamycin (not used due to pseudomembranous colitis)
Indications
Moderate and severe acne
- Patient
with scarring or who are prone to scarring
- Patient
who are likely to develop post inflammatory pigmentation
- Acne
fulminans
- Patient
with body dysmorphic disorder
Dose
- Tetracycline-
1g/day; Doxycycline-100mg/day;
Minocycline-100mg/day
- Lymecycline-
150mg- 300mg/day; Trimethoprim-
400-600mg/day
- Azithromycin-
in pulse dosing – 250-500 mg for 3 days in a week
- Oral
therapy should be given in combination with topical therapy for a minimum
of 6 months
Oral isotretinoin
Indications
- Severe
acne (grade IV)
- Moderately
severe acne not responding to conventional treatment
- Difficult
acne - acne conglobata, adult onset acne, androgenic acne, severe infantile acne and SAPHO syndrome
Mechanism of action
- Targets
all the pathophysiologic factors of acne
- Decrease
sebum secretion
- Alteration
of intrafollicular lipid
- Decrease
P. acnes
- Anti-inflammatory
action by inhibiting chemotaxis and stimulating T-helper cells leading to
increase in immunoglobulin
- Alteration
in pattern of follicular keratinization
- Antiandrogenic–Competitive
inhibition of
- 3-alpha-hydroxysteroid oxidation by
retinol dehydrogenase
Dose
0.5 – 1mg/kg/day
The treatment can be continued till a cumulative dose of 120-150 mg/kg
has been achieved.
Hormonal treatment
Indications
- Female
patients with acne who have polycystic ovarian syndrome (PCOS), SAHA
syndrome, HAIR-AN syndrome or cutaneous
hyperandrogenism
- Adult/androgenic
acne
- In
refractory/difficult acne where isotretinoin is either contraindicated or
inadequate
- When
concomitant menstrual control or contraceptive and acne therapy is
required
- Specific
hormonal therapies may be divided into two groups.
Androgen receptors blockers - Also referred to as antiandrogens
E.g. - Cyproterone acetate, spironolactone,
drospirenone and flutamide.
Agents that decrease the androgen production by ovaries and adrenals.
E.g- Estrogen alone or with progesterone (oral contraceptives)
Estrogen is used in two or three weeks cycle
In combined oral contraceptives
Ethinylestradiol (EE) 35 µg plus cyproterone
acetate 200 mg (EE-CPA)
EE 20 µg and drospirenone 3 mg
EE 30 µg with 150 mg of desogestrel / 75 mg of
gestodene / norgestimate (3rd generation progestin)
Given on day 1 (if contraception is a
requirement) or day 5 for 21 days in a month.
Side effects
Nausea, weight gain, chloasma, breast tenderness, spotting,
thromboembolism
Cyproterone acetate
50 mg -100mg for first ten days of the EE-CPA cycle for 5-10 cycles
Spironolactone (50-100 mg/day)
Flutamide In a dose of 250 mg twice daily in combination with an oral
contraceptive useful in acne and hirsutism
Systemic corticosteroids
Combination corticosteroid (2.5mg prednisolone in morning and 5mg in
evening) and OCP is used in severe recalcitrant acne, acne fulminans and
pyoderma faciale
Low dose corticosteroids are also useful in women who have 11 or 21
hydroxylase block or in those with excess of androgens
Oral Zinc therapy
Zn gluconate 200mg/day anti-inflammatory activity; inhibition of PMNL
chemotaxis induced by decrease granulocyte Zn level
NSAIDs:
Ibuprofen, Benoxaprofen-Reduce inflamed lesion
5-Lipoxygenase inhibitors -Reduce inflamed lesion, seborrhoea
Clofazamine- Acne
fulminans
Dapsone – In
severe nodular acne in doses of 50-200mg/day
Oral Vitamin A
Treatment of scars
Excision
of scars
- Dermabrasion
- Laser
resurfacing
- Collagen
injection (purified bovine dermal collagen)
- Gelatin
matrix implant
- Iontophoresis
( with estradiol and tretinoin for atrophic acne scars)
Hypertrophic and keloid scars
- Steroid
topical or intralesional
- Silicon
gel
- Cryotherapy
- Laser
ablation
- Topical treatments for PIH
Hydroquinone, kojic acid, azelaic acid, retinoid Alpha hydroxy-acid
and chemical peel with glycolic acid,trichloracetic acid or salicylic acid.
Further
reading
South Paul, JE, Matheny SC, Levis E. Current diagnosis & treatment
Family Medicine. 3rd ed., McGraw Hill; 2011
