TOPICAL THERAPY

1) RETINOIDS

Retinoids have both comedolytic and anti-inflammatory properties

Available preparations – Tretinoin, Isotretinoin, adapalene, and tazarotene

Anti-acne Actions of Topical Retinoids :

1. Inhibit the formation of and reduce the number of microcomedones (precursor lesions).

2. Reduce mature comedones.

3. Reduce inflammatory lesions.

4. Promote normal desquamation of follicular epithelium.

5. Anti-inflammatory.

6. Likely to enhance penetration of other drugs.

7. Likely to maintain remission of acne by inhibiting microcomedone formation.

2) Benzoyl Peroxide

• The most common topical medication prescribed; also readily available over-the-counter; available in creams, lotion, gels, washes, and pledgets in strength 2.5% - 10%.

• A powerful antimicrobial agent through decreasing both the bacterial population and the hydrolysis of triglycerides.

• Can produce significant dryness and irritation - Allergic contact dermatitis.

• Of significance, bacteria are unable to develop resistance to benzoyl peroxide, making it the ideal agent for combination therapy.

3) Topical Antibiotics

• Erythromycin and clindamycin - the most commonly used; also been used in combination with benzoyl peroxide.

• The development of resistance is less likely in patients who are treated with a combination of benzoyl peroxide/erythromycin or clindamycin

• MOA – Bacteriostatic to P. acnes; anti-inflammatory by suppressing PMNL

• Indications – inflammatory lesions of mild to moderate acne

a. Clindamycin – as phosphate and hydrochloride in concentration of 1% as gel, lotion, foam, pledget, or solution; also available in combination with adapalene or BPO.

b. Erythromycin – in 2-3% as gel, solution, pledget or oitment; can cause burning, peeling, dryness and erythema.

c. Nadifloxacin – 1% cream inhibits enzyme DNA gyrase of P.acnes involved in DNA synthesis and replication.

• Azelaic Acid - available by prescription in cream or gel of 10 – 20%. Transient burning can occur. It is safe in pregnancy.

• Salicylic acid - it is a common ingredient of over-the-counter products in concentrations 0.5% to 10%; most commonly used as 2% wash and clenaser; lipid soluble ?-hydroxy acid has comedolytic properties; also causes exfoliation of the stratum corneum though decreased cohesion of the keratinocytes

SYSTEMIC THERAPY

1) Antibacterial Agents

Tetracyclines (doxy-, mino-, tetra-, and lymecycline) – preferred choice, on the basis of efficacy, safety and bacterial resistance

Others – macrolides ( azithromycin and erythromycin) and sulfamethoxazole (SMX) + trimethoprim (TMP)

Mechanism of action –

• Antibacterial – bacteriostatic action on P. acnes by interfering with protein synthesis

• Anti-inflammatory – by decreasing concentrations of FFAs, inhibiting macrophage action such as PMNL, chemo taxis, production of cytokine (IL-6 and TNF) and inhibiting inflammatory granuloma formation

• Immunomodulatory actions – modulating host response

• Indications – in moderate to severe acne and generally well tolerated; takes about 4 – 8 weeks to show clinical improvement

• The dose can gradually be tapered or the drug can be withdrawn once the inflammatory acne have decreased or stopped appearing while maintaining remission with topical retinoids

• Minimum duration of therapy – 6 – 8 weeks and maximum of 12 – 16 weeks

2) Oral Retinoids

The use of the oral retinoid, isotretinoin, has revolutionized the management of treatment-resistant acne

• Targets all pathophysiologic factors in acne with direct action on reduction of sebum secretion by reducing the size (up to 90%), by normalizing follicular keratinization, by anti-inflammatory action and indirect action by decreasing P. acnes population by changing the follicular milieu

• It also blocks skin androgen receptors in acne patients

Indications of Isotretinoin

• Severe nodulocystic acne lesions

• Severe acne variants like Gram – negative folliculitis, acne fulminans, and pyoderma faciale

• Failure of conventional therapy

• Moderate to severe acne relapsing frequently

• Acne with severe psychological distress

• Inflammatory acne with scarring

• Approved dose – 0.5 – 2.0 mg/kg/day and drug is given over a 20 week course until a cumulative dose of 120 – 150 mg/kg body weight is achieved; therapeutic effects may take 1 -3 months to be visible.

3) Hormonal Therapy

• The goal of hormonal therapy is to counteract the effects of androgens on the sebaceous gland.

• This can be accomplished with the antiandrogens, or agents designed to decrease the endogenous production of androgens by the ovary or adrenal gland, including oral contraceptives, glucocorticoids, or gonadotropin-releasing hormone (GnRH) agonists.

Indications for Hormonal Therapy :

• Patients with signs of peripheral hyperandrogenism like SAHA syndrome.

• Patients with late onset acne (acne tarda) or persistent acne.

• Patients with proven ovarian or adrenal hyperandrogenism.

• Sometimes as an alternate to repeated courses of isotretinoin.

• Acne resistant to conventional therapies.

• Perimenstrual flares.

• Prominence of xacne on lower face and neck.

Oral Contraceptives

• 3 OCP – currently FDA approved for the treatment of acne: (1) Ortho Tri-Cyclen, (2) Estrostep, and (3) Yaz.

• In an effort to reduce the estrogenic side effects of oral contraceptives, preparations with lower doses of estrogen (20 ?g) - for the treatment of acne.

1. Physical Modalities

• Comedo Removal – useful for removing comedones resistant to other therapies and helps to improve the patient’s appearance .

• Chemical Peeling –with 10-70% glycolic acid, Jessner’s solution and 10-30% salicylic acid; repeated peeling for acne scars and cystic lesions.

• Cryotherapy - Used for acne and scars – cause erythema and desquamation of the skin.

Solid carbon dioxide is mixed with acetone to form a slush, which is brushed lightly over the skin.

Liquid nitrogen and cryo-spray can also be used.

For nodulocystic acne – refrigerant is directly applied on the skin.

• Phototherapy

1. Ultraviolet (UV) light - beneficial in the treatment of acne; The sunlight has a biologic effect on the pilosebaceous unit and P. acnes.

UVB can also kill P. acnes in vitro; UV radiation has antiinflammatory effects by inhibiting cytokine action.

Twice-weekly phototherapy sessions are needed for any clinical improvement.

1. Red light - penetrates deeper into the dermis; has greater anti-inflammatory properties à the combination of blue and red light may prove the most beneficial.

Treatments - be given twice weekly for 15-minute sessions for the face alone, and 45 minutes for the face, chest, and back.

• Photodynamic Therapy - The topical application of aminolevulinic acid (ALA) 1 hour prior to exposure to a low-power light source (include the pulsed dye laser, intense pulsed light, or a broadband red light source)

• LASERS

1. The pulsed KTP laser (532 nm) - a 35.9?crease in acne lesions when used twice weekly for 2 weeks; lower sebum production even at 1 month

2. The pulsed dye laser (585 nm) - used at lower fluences to treat acne. Instead of ablating blood vessels and causing purpura, a lower fluence can stimulate procollagen production by heating dermal perivascular tissue. The beneficial effects of a single treatment can last 12 weeks.

3. Some of the nonablative infrared lasers, such as the 1,450 nm and 1,320 nm laser - helpful in improving acne; work by causing thermal damage to the sebaceous glands; 1,320 nm Nd:Yag and the 1,540 erbium glass lasers - improve acne.

ACNE SURGERY

-Removal of closed comedones – requires prior opening of their orifice with a small bore needle

-Cysts – require incision

-Atrophic acne scars - surgical management

1. Punch excision – up to subcutaneous level is mainly used for ice pick scars.

2. Elliptical excision is used for scar which require a punch larger than 3.5mm.

3. Skin grafting – in case of sinus tract or de-roofing a wide-based lesion.

4. Punch elevation – treatment of choice for depressed boxcar scar.

5. Subcision – treatment of choice for rolling or depressed scars. It works by breaking the fibrous strands that bind the papillary dermis to the deeper tissues, creating a controlled trauma leading to wound healing.

6. Chemical peels – superficial, medium and deep peels.

7. Microdermabrasion – mostly used for superficial scars. Can be performed with either aluminum oxide crystals or diamond tipped abrasive devices.

8. Percutaneous Collagen induction by microneedling – stimulates neocollagenesis and angiogenesis

9. Dermabrasion – works best for superficial scars; postoperative hypo- or hyperpigmentation may occur.

10. Combination therapy – using subcision, microneedling, & 15% TCA peel performed alternately at 2 week interval.

11. Tissue augmentation – Xenografts, autografts and homografts can be used. Injections of highly purified bovine dermal collagen have been used to correct defects caused by scars; Recollagenation.

12. Lasers and light therapy

• Ablative lasers – Ablative CO2 laser; Erbium: yttrium laser.
• Nonablative lasers – 532nm KTP, 1064nm Nd: Yag laser.