Acne vulgaris

Acne vulgaris is a disorder of pilosebaceous complex which predominantly affects the peripubertal population and clinically manifests as comedones (open- blackheads, closed- whiteheads), papules, nodules, pustules and cysts and heals with scars.

Pathogenesis

1. Occlusion of pilosebaceous orifice

• Pilosebaceous orifice in acne is occluded by a keratinous plug induced by: chemicals (cosmetics) and reduced levels of linoleic acid in sebum of acne patients.
• Results in retention of sebum, encouraging growth of microbes, triggering a vicious cycle.
• Distended follicle ruptures, releasing proinflammatory chemicals into the dermis, stimulating intense inflammation. 
• Ductal epithelium also produces cytokines and an inflammatory cascade is triggered.

2. Increased sebum production

• Sebaceous gland activity is controlled by androgens.
• Most patients have normal levels of circulating androgens, but their sebaceous glands are unusually sensitive to androgens due to an enhanced end organ sensitivity.
• This is due to increased activity in sebaceous glands of an enzyme 5 alpha-reductase, which converts testosterone to more potent 5 alpha-dihydrotestosterone, which binds to specific receptors in the sebaceous glands increasing sebum production.

3. Microbial colonization

• Organisms implicated: Propionibacterium spp. especially P. acnes, Malassezia furfur, Staph epidermidis.
• Role in pathogenesis: these organisms trigger a type 4 inflammatory response and produce extracellular enzymes, which attracts inflammatory cells.

3. Release of inflammatory mediators

• Distended follicles ruptures, releasing inflammatory chemicals into the dermis, stimulating intense inflammation.
• Ductal epithelium also produces cytokines, triggering an inflammatory cascade.
• Microbes also produces extracellulae enzymes, which attract inflammatory cells.

Factors modifying acne

1. Genetic predisposition

• Patients with severe cystic acne often have a positive family history of acne of similar severity.
• Identical twins have greater concordance of severity of acne.

2. Diet

• Some recent studies have incriminated a high glycemic diet.
• Nuts, oily foods, chocolates, an aerated drinks increases acne.

3. Cosmetics

• Acne is seen in women who use oil-based cosmetics for long period of time.
• Acne often follows facial massage.

4. Menstrual cycle

• About 70% of the female patients complain of premenstrual aggravation of acne, probably related to premenstrual edema of the pilosebaseous duct.

5. Psychological factors

• Severe acne is related to increased anger and anxiety.

Clinical Features

Morphology

• Most patients with severe acne have a greasy skin with patulous follicular openings (pores).
• Eruption is polymorphic, characterized by comedones, papules, pustules, nodules, and cysts, all seen in the same patient at the same time.
• Comedones: are the pathognomonic lesions of acne vulgaris. Two main types of comedones recognized are: 1. Open comedones (black heads): are due to plugging of the pilosebaceous orifice by keratin and sebum on the skin surface. 2. Closed comedones (white heads): are due to keratin and sebum accretions plugging pilosebaseous ducts below the skin surface. Some closed comedones are deep seated (submarine comedones) and are best seen by stretching the skin.
• Scars: Acne scars can be: 1. Depressed scars: Ice pick scars, Box car scars, Rolling scars. 2. Hypertrophic and keloidal scars.

Sites of predilection

• Lesions are seen predominantly on the face (foreheads, cheeks, and chin), shoulders, upper chest, and back.
• If acne-like lesions occurs at unusual sites, suspect an acneiform eruption due to drugs or occupation acne.

Associations

1. Seborrhea: Greasiness of face and patulous folicular openings.

2. Features of hyperandrogenism:

• Like hirsutism, virilism, irregular periods, and weight gain may be present in some women
• Such patients need to be investigated for androgen secreting pathology like polycystic ovary syndrome.

Varients

1. Acne conglobata

• A severe form of acne, characterized by intercommunicating abscesses, cysts, and sinuses loaded with serosanguinous fluid or pus.
• Comedones are typically multiporous.
• Lesions take months to heal and on healing leave behind deep pitted or hypertrophic scars, joined by keloidal bridges.
• Lesions are not only severe but also more extensive and may be associated with follicular occlusion syndrome.

2. Occupational acne

• Caused by exposure to industrial chemicals like tar, chlorinated hydrocarbons and cutting oils.
• Lesions are predominantly comedones, though sometimes inflammatory cystic lesions may be present.

3. Cosmetic acne

• Eruption frequently seen in women using cosmetics, especially oil-based ones.
• Almost always comedones.
• Lesions frequently on the chin.

4. Drug-induced acne

• Steroid, androgens, anabolic steroids, oral contraceptives, antitubercular drugs, iodides, bromides and anticonvulsants can cause an acneiform eruption.
• Lesions are monomorphic, consisting of papules and sometimes pustules. Comedions and scarring are unusual, especially when induced by steroids.
• Trunk especially back; face may be involved.

5. Infantile acne

• Due to presence of maternal hormones in the child.
• May present at birth and may last for up to 3 years.
• Lesions similar to those of adolescent.

6. Late onset acne

• Acne with onset after 25 years of age.
• Predominantly women.
• Presents as deep seated, persistent lesions on lower half of face.
• Exclude underlying androgen secreting pathology, especially polycystic ovarian syndrome.

7. Acne fulminans

• Acute onset
• Presents as crusted, ulcerated lesions
• Associated with fever, myalgia and arthralgia.

8. Acne with facial massage

• Facial massage may be followed (3-6 weeks later) by an acneiform eruption in about 30% of patients.
• Indolent deep seated nodules with very few comedones. Heal with hyperpigmentation after several weeks.
• Predominantly on cheeks, along the mandible. Less on chin.

Investigations

• No investigations are required for routine management of acne vulgaris.
• In women, who have late-onset acne associated with hirsutism, virilization and menstrual irregularities, investigations to exclude an androgen secreting pathology (polycystic ovaries) need to be done.

Diagnosis

Points for diagnosis

Diagnosis is based on:

• Adolescent patient.
• Background skin of face is greasy with prominent follicular openings.
• Polymorphic eruption of papules, pustules, nodules, and cysts; lesions heal with typical scarring.
• Presence of comedones.
• Typical distribution: face, shoulders, upper part of trunk and chest.

Differential diagnosis

• Rosacea
• Folliculitis

Acne vulgaris Treatment

Treatment modalities available include:

• General measures.
• Topical therapy.
• Systemic therapy.
• Physical therapy.

1. General measures

• Local hygiene: regular gentle cleansing with soap and water should encouraged. Application of oil-based cosmetics should be avoided as they aggravate acne, but water based cosmetics can be used.
• Diet: Some dermatologists have begun to restrict high glycemic diets.
• Stress: Acne induces stress and this needs to be handled. Stress itself may induce acne.

2. Topical therapy

A. Retinoids

Preparations available:

• Drugs: Retinoic acid (RA), adapalene, isoretinion and tazarotene.

Indications:

• In active disease: effective against both comedones and inflammatory acne.
• For maintenance: reduces formation of microcomedo.

Mode of action:

• Specially effective against comedones because it normalizes follicular keratinization by: Increasing epidermal cell turnover and increasing dehiscence of stratum corneum.
• Also effective against inflammatory lesions, especially adapalene.

Clinical use:

• Start with lowest concentration; gradually introducing higher concentration over period of weeks.
• Use only at night, it can cause photosensitivity. Adapalene can be used during day.
• Should be applied to all acne-prone area.
• Excessive dryness is to be avoided to ensure compliance.
• Can be combined with topical antibiotics.

Side effects:

• Irritation: More with tazarotene> retinoic acid> adapalene.
• Photosensitivity: frequent with RA, so use at night.

B. Benzoyl peroxide (BP)

Mode of action: 

• BP is a powerful antimicrobial, decresing population of P. acnes.
• Also has anti-inflammatory effect.

Indications:

• Mild acne, as stand alone therapy
• Always to antibiotic therapy, to reduce resistance.
• Moderate-severe acne as topical adjuvant to systemic therapy.

Clinical use:

• Used in both inflammatory and non-inflammatory acne.
• Initially used in lower concentration for short duration (1-2 h); increases over period of time to higher concentration and over longer periods of time.

Side effects:

• Irritation.
• Bleaching of hair.

C. Topical antibiotics

• Most frequently used topical antibiotics are clindamycin (1-2%) and erythromycin (2-4%).

Mode of action: Suppress P.acnes and its mediators of inflammation and so are more effective against inflammatory acne.

Clinical use: Useful in inflammatory acne but must always be combined with topical retinoic acid or benzoyl peroxide.

Side effects: Resistance of microorganisms to antibiotics is a major problem, so should be combined with topical retinoids or benzoyl peroxide.

Other agents

• Alpha-hydroxy acids: e.g., glycolic acid (6-12%)
• Azelaic acid (10-20%): Also reduces postacne hyperpigmentation.

3. Systemic treatment

A. Antibiotics

Drugs used: 

• Doxycycline and minocycline are frequently used. Less frequently, erythromycin and azithromycin.

Mode of action:

• Inhibits growth of P. acnes and its metabolism.
• Direct anti-inflammatory effect.

Indications:

• Moderately severe acne
• Mild acne, if acne is affecting patient's quality of life.
• Severe acne, if oral retinoids cannot be used.

Regimens:

• Tetracycline (1g), doxycycline (100 mg), minocycline (100 mg), Erythromycin (1g) daily. Or azithromycin (250 mg), 3-4 times a week  (up to 3-6 months).
• Tetracycline and doxycycline should be taken empty stomach. Absorption decrease by milk, antacids and metal salts.
• Oral antibiotics should always be combined with topical agents.
• Minocycline concentrates in sebaceous glands and is more effective than tetracycine.

Adverse events:

• Gastrointestinal side effects: include nausea.
• Cutaneous side effects: Long term administration of minocycline may cause grayish pigmentation of skin, mucosae, and nails.
• Teratogenicity: tetracycline should be avoided in pregnant women and in children under 8 years of age.
• Infections: vaginal candidiasis.
• Resistance of P. acnes to antibiotics: more frequent with macrolides, so their use should be limited.

B. Hormones

Mode of action: 

• Antiandrogens act by decreasing sebum secretion rate.

Indications: Only in females.

• Late onset acne.
• Women with menstrual irregularities.

Treatment schedules: Need to be used for long periods of time (6-24 months)

• Cyproterone acetate: is available as combination of 2 mg cyproterone acetate and 35 microgram estradiol.
• Spironolactone: 50-100 mg daily.

C. Isotretinoin

• Isotretinoin (13-cis-retinoic acid), a retinoid has revolutionized management of severe intractable acne.

Mode of action:

• Inhibits sebum secretion
• Decreases P. acne counts
• Reduces inflammation.

Indications: 

• Severe acne, acne conglobata.
• Moderately severe acne not responds to conventional therapy.
• Any grade of acne which is causing distress.

Treatment schedule:

• Used in a dose of 0.5-1 mg/kg body weight daily.
• Higher dose required for truncal acne.
• Is given for the period of 12-16 weeks.

Side effects:

• Dryness of eyes, dry skin, cheilitis, hair loss and nose bleeds.
• Should not be used in pregnant women because of teratogenicity.
• Myalgia, vertebral hyperostosis and altered night vision.
• Patient should not to donate blood during treatment and for 1 month thereafter.
• Pseudotumor cerebri

4. Physical therapy

Intralesional corticosteroids

• Active disease: Inj. of long acting steroid (triamcinolone acetonide 10 mg/ml) into nodules results in dramatic resolution of lesions.
• Hypertrophic scars: Inj. of long acting steroid (triamcinolone acetonide 10 mg/ml) into recalcitrant hypertrophic scars/ keloids result in slow resolution of lesions.

Cryotherapy

• Freezing with liquid nitrogen hasten resolution of recalcitrant nodulocystic lesions.
• Scars also responds.

Laser thereapy

• Laser skin resurfacing has been used to treat acne scars.
• Laser used is carbon dioxide laser.

Photodynamic treatment

• Uses: Red light and a photosensitizer like aminolevulinic acid (ALA)
• Response: moderate

Dermabrasion

• Superficial dermabrasion helps in reducing scars
• Occasionally leaves behind unsightly hyperpigmentation and may cause photosensitivity.

Fillers

• Injection of fillers to augment tissue defects are of limited benefit. 
• Treatment is expensive and needs to be repeat every 6 months.