1. Treatment of Acne-II

2. Classification of Acne
Grade of Acne
Qualitative Description
Quantitative Description I
Comedonal acne
Comedones only, < 10 on face, none on trunk, no scars, noninflammatory lesions only II
Papular acne
10-25 papules on face and trunk, mild scarring, inflammatory lesions < 5 mm in diameter
III
Pustular acne
More than 25 pustules, moderate scarring, size similar to papules but with visible purulent core IV
Severe persistent pustulocyctis acne
Nodules or cysts, extensive scarring, inflammatory lesions > 5 mm in diameter -
Recalcitrant severe cystic acne
Extensive nodules/cysts
A primary care provider must direct suppressing or altering hormonal activity, correcting disfiguring effects, and using prescription drugs to treat acne..
The patient should not add OTC medications to prescribed regimens unless recommended by the prescriber

3. Exclusion for Self-Treatment
Grades II-IV acne: papules, pustules, nodules, cysts and/or scarring
Severe, recalcitrant acne (extensive nodules/cysts)
Exacerbating factors (e.g. comedogenic drugs)
Possible rosacea
(If acne lesions persist beyond mid-20s or develop in the mid-20s or later, the symptoms may signal rosacea rather than acne vulgaris)

4. Comedonal acne - topical treatment appropriate:
Pustular - an oral antibiotic would be best:
Comedonal acne - topical treatment appropriate:

5. Severe acne treated with Isotretinoin:
A) Before treatment:
B) After 5 months

6. Prescription Medication for acne:
Retinoic acid & Derivatives
Isotretinoin
Azelaic Acid
Antibiotics (topical or systemic)
Hormonal therapy

7. Retinoic Acid & Derivatives
Retinoic acid (tretinoin) is the acid form of vitamin A
13-cis-retinoic acid (isotretinoin) is analog of retinoic acid effective when given orally
Retinoic acid insoluble in water; susceptible to oxidation and ester formation particularly when exposed to light;
Topically applied retinoic acid remains chiefly in the epidermis (< 10% absorbed)

8. Retinoic Acid & Derivatives
The small quantities absorbed following a topical application are metabolized by the liver and excreted in bile and urine;
Retinoic acid has several effects on epithelial tissues (lysosomes, PG-E2, cAMP, cGMP and RNA polymerase)
Action in acne: (1) decreased cohesion between epidermal cells (2) increased epidermal cell turnover.
This results in expulsion of open comedones and transformation of closed comedones into open ones

9. Retinoic Acid & Derivatives
Retinoic acid is applied initially in a concentration sufficient to induce slight erythema with mild peeling
If too much irritaion is produced, decrease concentration or frequency of application;
During the first 4-6 weeks of therapy, comedones not previously evident may appear
However, with continued therapy, the lesions will clear, and in 8-12 weeks optimal clinical improvement should occur
(Retin-A Micro): timed release formulation with tretinoin containing microspheres. Less irritating

11. Retinoic Acid & Derivatives
Prolonged use of tretinoin promotes :
(1) dermal collagen synthesis
(2) new blood vessel formation
(3) thickening of the epidermis
Which helps diminish fine lines and wrinkles
Renova (0.05% cream): specially formulated for this purpose

12. Retinoic Acid & Derivatives
The most common adverse effects (topical):
erythema, dryness: first few weeks of use, but resolve with continued therapy;
May increase tumerogenic potential of UV radiation (in animals). Thus, patients are advised to minimize or avoid sun exposure and use protective sunscreen
Allergic contact dermatitis: rare

13. Retin-A dryness and irritation

14. Adapalene (Differin)
A derivative of naphathoic acid that resembles retinoic acid in structure and effects
Applied 0.1% gel once daily
Unlike tretinoin:
1. photochemically stable
2. less irritating
Most effective: mild to moderate acne vulgaris
Pregnancy-Adapalene has not been studied in pregnant women. It is not recommended for use during pregnancy. Adapalene in large doses has been shown to cause some bone problems in the fetuses of some animals. Before using this medicine, make sure your doctor knows if you are pregnant or if you are trying to become pregnant.
Breast-feeding-It is not known if adapalene passes into breast milk.

15. Treatment with Adpalene gel
DRUG CLASS AND MECHANISM: Adapalene is a gel used for the treatment of acne vulgaris (pimples). The exact mechanism of action is not known. Scientists believe that when adapalene is applied to the skin, it affects the growth of skin cells and thereby reduces the formation of pimples.

16. Tazarotene (Tazorac) Acetylenic retinoid 0.1% gel
Treatment of mild to moderately severe facial acne
Should not be used by pregnant women (pregnancy risk factor=X)
Contraceptive counseling in women of childbearing age.

17. Isotretinoin (Accutane)
A synthetic retinoid currently restricted to the treatment of severe cystic acne that is recalcitrant to standard therapies;
Well absorbed to circulation, extensively bound to plasma albumin,
elimination half-life of 21 hrs (parent drug), hrs (metabolite)
MOA: inhibits sebaceous gland size and function ….details
Isotretinoin prevents the formation of new comedos and resultant inflammatory lesions by decreasing the size and secretions of the sebaceous glands, normalizing follicular keratinization, and exerting anti-inflammatory effects. Sebum production is reduced by at least 90% through competitive inhibition of retinol dehydrogenase-4, the enzyme that mediates the skin's production of dihydrotestosterone and androstenedione.

18. MOA- isotretenoin:
Isotretinoin prevents the formation of new comedos and resultant inflammatory lesions by:
decreasing the size and secretions of the sebaceous glands,
normalizing follicular keratinization, and
exerting anti-inflammatory effects.
Sebum production is reduced by at least 90% through competitive inhibition of retinol dehydrogenase-4, the enzyme that mediates the skin's production of dihydrotestosterone and androstenedione.

19. Isotretinoin (Accutane)
Dose:
0.5-2 mg/kg/day, given orally in two divided doses daily for 4-5 months;
If severe cystic acne persists following this initial treatment, a second course of therapy may be initiated after 2 months;
The skin would be sensitive during treatment. Patient is at high risk for abnormal healing and development of excessive granulation following procedures (e.g. piercing, tatoos, epilation)
The effect of oral isotretinoin in severe nodulocystic acne can be dramatic. Most patients respond to a single four- to six-month therapeutic course. In general, pustules clear more rapidly than do papules or nodules. Lesions on the face, upper arms, and legs tend to respond more quickly than do truncal lesions. Results are generally not evident for one to two months after initiating therapy; therapeutic benefits continue for several months after drug discontinuation.8

20. Isotretinoin is available in 10-, 20-, and 40-mg soft gelatin capsules for oral administration.
Isotretinoin capsules should always be taken with food to maximize absorption

21. Isotretinoin (Accutane)
Adverse Effects
Common adverse effects (resemble hypervitaminosis A):
Dryness and itching of skin and mucous membranes
Less common: Headache, corneal opacities, pseudotumpr cerebri inflammatory bowel disease, anorexia, alopecia, muscle and joint pains
These effects are all reversible on discontinuation of therapy.
Mucocutaneous Dose-Related Effects
Dry lips and chelitis seen in virtually 100% of patients
Dry skin in ~70% of patients
Skin and nail fragility, scaling, loss of eyebrows and lashes, hair thinning
Adverse Impact on Lipid Profile (% of patients experiencing change)
Elevated triglycerides (66% acitretin; 25% isotretinoin)
Elevated cholesterol (33% acitretin; 7% isotretinoin)
Decreased HDL-C (40% acitretin; 15% isotretinoin)
Hepatotoxicity
Elevated AST, ALT, GGT, LDH (15% incidence with isotretinoin therapy; seen in 33% of acitretin-treated patients; hepatitis-related deaths have occurred)
Ophthalmologic Effects
Decreased night vision, dry eyes, decreased tolerance to contact lenses, corneal opacities (isotretinoin)
Psychiatric Symptoms
Depression, aggressive-violent behavior, self-injurious behavior, thoughts of suicide, suicide
Pseudotumor Cerebri
May occur with monotherapy; increased incidence with concomitant tetracycline ingestion
Pancreatitis
May occur in the absence of elevated lipids; more common in the presence of hypertriglyceridemia, hypercholesterolemia
Cardiovascular Disease
Associated with abnormal lipid profile

22. Isotretinoin (Accutane)
Adverse Effects
Skeletal hyperostosis has been observed in patients receiving isotretinoin
Premature closure of epiphyses noted in children treated with this medication
Lipid abnormalities (triglycerides, HDL) are frequent
Depression, psychosis, aggressiveness or violent behavior & rarely suicidal thoughts (discontinuation MAY NOT be sufficient)
Teratogenecity
Bone Abnormalities
Hyperostosis of spine, knees, ankles; alterations of bone mineral density, osteoporosis, bone fractures, delayed bone healing with isotretinoin
Hypervitaminosis A
Associated with use of vitamin A supplements in doses exceeding the recommended dietary allowance for vitamin A
Transient Worsening of Condition
During initial therapy, systemic retinoids may worsen acne or psoriasis
Hearing Impairment
Reported with isotretinoin; may persist after therapy is discontinued
Inflammatory Bowel Disease (IBD)
Reported in patients with no previous history of IBD who used isotretinoin
Hypersensitivity/Anaphylaxis
Patients can be allergic to retinoids or any dosage form excipients
<radiology> Idiopathic, increased cerebrospinal fluid production, increased intracranial pressure, papilledema, CT: slit-like ventricles, treatment: steroids

23. Teratogenecity
the skull, ears, and eyes and include facial dysmorphia and cleft palate.
Internal abnormalities affecting the thymus gland, central nervous system, cardiovascular system, and parathyroid gland (hormone deficiency) are recognized.
In some cases, these abnormalities have resulted in fetal death.
Nursing mothers should not receive isotretinoin.
Documented external abnormalities in babies whose mothers were exposed to isotretinoin during pregnancy involved the skull, ears, and eyes and include facial dysmorphia and cleft palate.6 Internal abnormalities affecting the thymus gland, central nervous system, cardiovascular system, and parathyroid gland (hormone deficiency) are recognized. In some cases, these abnormalities have resulted in fetal death.6 Nursing mothers should not receive isotretinoin.6

24. Facial dysmorphism

25. Cleft palate

26. Isotretinoin (Accutane)
Teratogenecity
Women of childbearing age must use an effective form of contraception for at least 1 month before; throughout isotretinoin therapy, and for one or more menstrual cycles following discontinuance of therapy
A serum pregnancy test must be obtained within 2 weeks before starting therapy
Therapy should be initiated only on the second or third day after the next normal menstrual period

27. Isotretinoin (Accutane)
Monitoring parameters:
CBC with differential & platelet count, baseline sed. rate, glucose,
Pregnancy tests
Lipids: prior to treatment & at weekly or biweekly intervals until response to treatment is established
Liver function tests: prior to treatment & at weekly or biweekly intervals until response to treatment is established
Creatine Phosphokinase
Blood Glucose
Suggested Laboratory Monitoring for Patients REceiving Systemic Retinoid Therapy
Pregnancy Testing Negative results from two urine or serum pregnancy tests sensitive to at least 25 mIU/mL before receiving initial prescription. A screening test should be performed initially; a confirmation test should be performed within the first five days of the menstrual cycle immediately preceding initiation of therapy or at least 11 days after the last act of unprotected sexual intercourse in patients with amenorrhea. Monthly pregnancy testing should be conducted throughout treatment.
Lipid Profiles Triglycerides, total cholesterol, LDL-C (fasting): pretreatment and then weekly or biweekly until patient's lipid response has stabilized (usually within four to eight weeks)
Liver Function Tests AST, ALT, and LDH: pretreatment and then weekly or biweekly until patient's response has stabilized (usually within four to eight weeks)
Blood Glucose Obtain baseline and follow-up values as needed, as new cases of diabetes mellitus have been diagnosed during retinoid therapy
Creatine Phosphokinase Rhabdomyolysis has been associated with strenuous physical activity in patients taking isotretinoin

28. Azelaic Acid (Azelex)
Straight chain saturated dicarboxylic acid; effective in the treatment of acne vulgaris;
Its mechanism of action not fully determined. However, studies shown:
Antimicrobial activity against P acnes
In vitro inhibition of the conversion of testosterone to dihydrotestosterone
Initial therapy: once daily application of 20% cream to affected areas for 1 week. Then twice daily thereafter
Mild irritation with redness and dryness of the skin during the first week of treatment
Clinical improvement 6-8 weeks of continuous therapy

29. Topical Antibiotics
Commonly prescribed: erythromycin and clindamycin alone or in combination with benzoyl peroxide
MOA: (1) bactericidal activity against P acnes. (2) may also have anti-inflammatory effect
Topical antibiotics are not comedolytic,
Bacterial resistance may develop to any of these agents.
The development of resistance is lessened if topical antibiotics are used in combination with benzoyl peroxide

30. Systemic Antibiotics
Tetracycline and congeners (minocycline and doxycycline)
Erythromycin, azithromycin
Trimethoprim alone or in combination with sulfamethoxazole
MOA: (1) P acnes; (2) Anti-inflammatory
Minocycline is more effective than tetracycline and bacteria has less resistance to this agent

31. Systemic Antibiotics
Bacterial resistance to these agents may be reduced by combining them with topical retinoids and/or topical benzoyl peroxide
Most common side effects:
phototoxicity from tetracycline group, especially doxycycline
Vertigo-like dizziness>> minocycline
Stevens-Johnson syndrome>> trimethoprim-sulfamethoxazole
All oral antibiotics predispose to Candida infections, particularly vaginitis

32. Stevens Johnsons Syndrome

35. Hormonal Therapy
MOA: estrogens are responsible for maintenance of the normal structure and function of the skin and blood vessels
Acne may be exacerbated by agents containing androgen-like progestins (e.g. norethindrone, lynestrenol, norethynodrel), whereas agents containing large amounts of estrogen usually cause marked improvement in acne

36. Progestational Activity (relative to 1 mg of norethindrone)
Progestin
Progestational Activity (relative to 1 mg of norethindrone)
Androgenic Activity (relative to 1 mg of norethindrone)
norethindrone 1 mg
1.0
norethrindrone acetate 1 mg
1.2
1.6
ethynodiol diacetate 1 mg
1.4
0.6
levonorgestrel 1 mg
5.3
8.3
dl-norgestrel 1 mg
2.6
4.2
norgestimate 1 mg
1.3
1.9
norelgestromin 1 mg
desogestrel 1 mg
9.0
3.4
drospirenone 1 mg
1.5
0.0

37. Ethinyl estradiol + Drospirenone

38. Hormonal Therapy FDA approved a triphasic, combination OCP:
Ortho-Tri-Cyclen: Ethinyl estradiol (0.035 mg) + Norgestimate:
Days 1-7 ……… mg
Days 8-14……… mg
Days 15-21………0.25 mg

39. Hormonal Therapy
A study showed that this OC reduced acne lesion counts by more than 50% in female subjects, compared with lesion reductions of about 26% in controls
Acne improvement during treatment with Ortho-Tri Cyclen may take 3-4 months to become apparent;
Main limitation of anti-androgen therapy for acne is that it cannot be used with male patients