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Acne Vulgaris Megan D. P. Cooper, RPh, PharmD Spring 2016 Lecture Objectives • • • • • • Describe the etiology, exacerbating factors, and pathophysiology of acne vulgaris Describe the clinical presentation of acne vulgaris Discuss the pharmacology, side effects, drug interactions, and proper dosing of commonly used medications for acne vulgaris Given a patient case, select an appropriate treatment regimen, monitoring parameters and patient related consultation recommendations considering the patient's diagnosis and unique characteristics Assess a patient’s pharmacotherapeutic regimen for safety and efficacy using clinical signs, symptoms and laboratory data Counsel patients on non-pharmacologic modalities to treat acne vulgaris Definition of disease: Chronic inflammatory disorder of the pilosebaceous unit Most notable for open and closed comedones and inflammatory lesions (papules, pustules, nodules) Etiology FOUR primary factors involved in the formation of acne lesions: 1. Increased sebum production o Sebum production in the sebaceous glands is primarily driven by androgenic activity, and the acne affected pilosebaceous units seem to have a hyper-responsiveness to circulating androgens. o Testosterone is the predominant androgen, is increased in acne and capable of enhancing sebaceous gland activity (androgen stimulation is enhanced at puberty) 2. Follicular hyperproliferation and abnormal desquamation o Follicular hyperkeratinization and abnormal corneocyte desquamation lead to follicular obstruction. This, in combination with the androgen-stimulated increase in sebum production, promotes the formation of the microcomedo, the earliest stage of acne. 3. Bacterial growth o Propionibacterium acnes: a gram-positive anaerobe, resides in the follicle as normal flora, however the mix of “trapped” keratinocytes and sebum provide an environment for overgrowth 4. Inflammation o May be a consequence of increased sebum production, keratinocyte sloughing and bacterial growth o P.acnes may trigger inflammatory acne lesions by producing biologically active mediators and promoting proinflammatory cytokine release Pathophysiology: Follicular canal contents include keratinocytes, P.acnes, and free fatty acids The microcomedo enlarges to form a comedo as lipids, bacteria, and desquamated corneocytes accumulate. P. acnes can proliferate in this environment The comedo “plugs” the pilosebaceous follicle → the follicular canal widens and an increase in cell production is seen → sebum mixes with excess loose cells in the follicular canal to form a keratinous plug, which results in a “blackhead” or open comedo. The open comedo has a brown or black appearance due to melanin accumulation. Inflammation or trauma to the follicle may lead to formation of a “whitehead” or closed comedo. Closed comedones are important clinically because they can become larger, inflammatory lesions secondary to P. acnes activity. Exacerbating factors or Risk Factors: Genetic predisposition Oil based cosmetics or skin creams Occlusive hair dyes Repetitive mechanical trauma by over-scrubbing skin Occlusive clothes (bras, helmets, turtlenecks, shoulder pads, etc) Excessive rubbing of skin or picking at skin High humidity Heavy sweating Diet – controversial; not scientifically proven – high glycemic index vs low glycemic index diet Psychological stress – proven scientifically Occupational exposures to dirt, vaporized cooking oils or grease Androgens Azathioprine Barbituates Corticosteroids Corticotropin Cyclosporine Medications known to cause acne: Disulfiram Isoniazid Lithium Phenytoin Psoralens Vitamins B2, B6, B12 Additional Testing Usually not necessary unless attempting to rule out causes for acne-like lesions or patients with suspected hyperandrogenism o Endocrinologic testing: o Testosterone, free o Dehydroepiandrosterone sulfate o Leutinizing hormone o Follicle-stimulating hormone Clinical Presentation: Lesions typically occur on the face, back, upper chest & shoulders because this is where sebaceous glands are most predominant. Usually present with a mixture of lesions in various stages of development, and may include noninflammatory and inflammatory lesions, scars, and residual hyperpigmentation. The presence of 5-10 comedones is usually diagnostic: o Comedones o Pustules o Papules o Nodules o Cysts Non-inflammatory lesions: consist of open and closed comedones o Open comedo (blackhead): plug of sebum, keratinocytes, and microorganisms blocking a dilated hair follicle opening o Closed comedone (whitehead): a similar plug blocking a closed hair follicle opening Inflammatory lesions: consist of papules, pustules and maybe nodules Scars are a common result of inflammatory acne lesions Acne Severity Mild Moderate Severe Predominant Lesions Non-inflammatory lesions consisting of few to numerous open and closed comedones Inflammatory papules and pustules with some non-inflammatory lesions described above Inflammatory and noninflammatory lesions described above with scarring usually present Papules Possible Pustules Possible Nodules None Numerous Numerous Few Extensive Extensive Scarring None Possible Extensive Extensive Treatment Patient Considerations Deciding on the appropriate course of treatment for an individual patient requires a comprehensive assessment that includes: Nonpharmacological and Alternative therapies None has proven drastically effective Herbal and alternative therapies (primarily tea tree oil) is well tolerated and effective but has slower onset of action than other topical therapies Dietary restriction has not demonstrated benefit Cleanse skin with noncomedogenic soap twice daily Avoid vigorously scrubbing lesions Do not pick or squeeze lesions Avoid occlusive clothing or head gear, resting face on hands, oil based cosmetics Pharmacologic Treatment Most treatments reduce or prevent new eruptions, and during the first few weeks of therapy acne may worsen existing lesions It takes _____ weeks for a microcomedo to mature. Thus, any therapy must be continued beyond this duration in order to assess efficacy. Initial treatment is aimed at reducing lesion count and duration of therapy varies depending on severity and treatment response o Oily skin – use gels, solutions, lotions o Normal skin – use gels, solutions, lotions, creams o Dry skin – use lotions and creams o Solutions can be drying but are useful for use over large areas of skin o Foams are good for hair-bearing areas Topical therapy is primarily used in mild to moderate acne Systemic therapy is required in patients with moderate to severe acne TOPICAL THERAPY (mild to moderate acne) Topical retinoids (TRs): tretinoin (Atralin™; Avita®; Renova®; Retin-A® Micro; Retin-A®; Tretin-X™) adapalene (Differin® XP; Differin®) tazarotene (Avage™; Tazorac®) COMBO PRODUCTS: adapalene 0.1% + benzoyl peroxide 2.5% gel (Epiduo®) tretinoin 0.025% + clindamycin 1.2% gel (Veltin®, Ziana®) Safety “Photosensitivity” and sunburn risk Tazarotene Category X; the others are C Tolerability All agents cause skin irritation, dryness, flaking of skin, but microsphere formulations of tretinoin and 3rd generations are more tolerable Efficacy Generally recommended as first line agents for comedogenic and mild to moderate inflammatory acne Preferred agents for acne maintenance to minimize antibiotic use Reduces follicular occlusion and halts microcomedo formation Effective as monotherapy but synergistic when used in combo with topical antibiotics and benzoyl peroxide with minimal to no increased side effects May take up to 3 months to see an effect, and therapy should be continued until no new lesions develop Accelerates resolution of post-inflammatory hyperpigmentation May enhance penetration of other topical acne meds Comparative trials do not definitively advocate for one agent over another, however adapalene tends to be the best tolerated; tazarotene may be more effective but is most irritating Preference/Pearls Transient worsening of symptoms initially but usually resolves within 24 weeks with continued treatment Many dosage forms available: gels, creams, solutions; microsphere formulation and liquid polymer forms are less irritating Simplicity/Dosing Once daily application in the evening due to photoliability (except adapalene) Patient counseling points/additional info Due to preventative effect of TRs on acne, counsel patients to apply to entire face, not as spot treatment of individual lesions. Skin should be dry at time of application Use at least SPF 15 sunscreen for outdoor activities Skin becomes extremely sensitive to weather extremes (wind, cold) Counsel appropriately when using concomitantly with other photosensitizing meds Benzoyl Peroxide 2.5%-10% (BPO) Safety Photosensitivity and sunburn risk Tolerability Skin irritation, erythema, scaling, peeling, xerosis, stinging, tightening sensation, burning, swelling, pruritus Can bleach hair, skin, and clothing Efficacy Efficacy seen with 2.5% and 5% concentrations with only minimal benefit when increased to 10%. Increasing concentration leads to higher incidence of side effects with minimal benefit. Useful for both comedonal and inflammatory acne Bactericidal against P.acnes, increases epithelial sloughing, comedolytic Comparable efficacy to antibiotics without causing bacterial resistance Recommended as one of the first line agents for acne Useful as monotherapy but more effective when used in combo with other topical agents Preference/Pearls Available Rx and OTC; many dosage forms available: gels, lotions, creams, pads, masks, cleansers, solutions, soap When used in combo with oral or topical antibiotics, decreases and prevents antibacterial resistance BPO is most cost effective agent in acne management Simplicity/Dosing Twice daily application Patient counseling points/additional info Advise patient to wash away drug after a few hours when first initiating therapy to help skin grow to tolerate it Do not use simultaneously with topical tretinoin and tazarotene because BPO oxides them and makes them less effective. If using both agents, use BPO in the morning, and TR at night. Apply to dry skin to minimize irritation Azelaic acid Azelex®--20% Cream---FDA approved for acne vulgaris Finacea®--15% Gel----FDA approved for acne rosacea Safety Avoid contact with eyes or mucous membranes Tolerability Skin irritation is reported in a few individuals Isolated reports of hypopigmentation with use Efficacy Possesses antimicrobial, comedolytic and mild anti-inflammatory properties Can improve acne induced post-inflammatory hyperpigmentation Effective for both mild-moderate inflammatory acne and comedonal acne Preference/Pearls Considered second or third line agent in the treatment of mild to moderate inflammatory acne and comedonal acne in patients who cannot tolerate benzoyl peroxide or topical retinoids Has a hypopigmentation effect that may be effective in treating postinflammatory hyperpigmentation resulting from acne Has no likelihood of bacterial resistance, systemic adverse effects or photosensitivity Simplicity/Dosing Once daily application is just as effective as twice daily application Use in combo with other agents is more effective than using it alone Patient counseling points/additional info Apply to clean dry skin Dapsone 5% gel (Aczone®) Safety Increased risk of hemolytic anemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency taking ORAL dapsone, but this is not a problem when used TOPICALLY Testing for G6PD deficiency is NOT necessary if using topical form Questionable decrease in hemoglobin with topical use—caution in those with anemia---monitor Photosensitivity Tolerability Temporary yellow to orange skin and hair discoloration may occur if used concurrently with BPO; if both agents are needed, apply one in the morning and the other in the evening and wash face between applications Skin oiliness, peeling, dryness, erythema Efficacy Mechanism not entirely understood, but has anti-inflammatory and antimicrobial properties Useful for mild-moderate inflammatory and comedonal acne Greatest improvement is seen in inflammatory lesions Preference/Pearls Is a sulfone derivative, NOT sulfonamide—therefore topical dapsone is NOT contraindicated in patients with sulfa allergy Is a newer agent, and is still undergoing studies evaluating long-term efficacy as monotherapy and safety when combined with other agents Simplicity/Dosing Twice daily application for at least 12 weeks Patient counseling points/additional info Apply small (pea-size) amount to skin and gently rub in Patients may notice gritty appearance to particles after application Salicylic Acid Safety Risk of salicylate toxicity with repeated widespread use on highly permeable (inflamed or abraded) skin Tolerability Mild skin irritation Efficacy Keratolytic, comedolytic, anti-inflammatory, bacteriostatic and fungistatic properties Considered 2nd line agent because comedolytic properties are less potent than TRs and BPO; generally used when patients cannot tolerate TRs or BPO due to skin irritation Preference/Pearls Simplicity/Dosing Many dosage forms: cloths, cleansers, cream, foam, gel, liquid, lotions, soaps Available OTC and Rx Dosed once to three times daily depending on product Effective concentrations for acne are 0.5%-2% Patient counseling points/additional info Apply to clean dry skin If using cleanser, medication is only active as long as product is on skin. Topical Antibiotics (clindamycin or erythromycin) Erythromycin 2% gel, solution Clindamycin 1% gel, solution, lotion, foam, pledget COMBO PRODUCTS: Clindamycin 1.2% + BPO 2.5% gel (Acanya®) Clindamycin 1% + BPO 5% gel (BenzaClin®) Clindamycin 1.2% + BPO 5% gel (Duac®) Clindamycin 1.2% + tretinoin 0.025% gel (Veltin®, Ziana®) Erythromycin 3% + BPO 5% gel (Benzamycin®) Safety Pseudomembranous colitis and hypersensitivity reactions have been rarely reported (<1%) in patients using topical clindamycin Tolerability Dry skin, erythema, itching, scaling or peeling Efficacy Directly suppresses P.acnes MUST use in combination with BPO to minimize/prevent resistance; use as a single agent is not recommended Efficacy is also increased with combined with BPO or TR Preference/Pearls Recommended 2nd line because of concerns of increasing resistance to these agents Simplicity/Dosing Both agents are available in a combo product with BPO Clindamycin is available in combo with tretinoin Many dosage forms: gels, solution, foam, lotions Apply once or twice daily after facial cleansing Patient counseling points/additional info If using topical clindamycin foam, dispense the dose into the cap or onto a cool surface and then administer small amounts to the affected area Other miscellaneous topical agents Sulfur and resorcinol have been used for years but evidence from peer-reviewed literature supporting efficacy is lacking Aluminum chloride possesses antibacterial activity, but there is controversial evidence as to its efficacy Topical zinc alone – ineffective Sulfacetamide – a topical antibiotic used in acne; data regarding effectiveness is limited; cannot be used in sulfa-allergic patients TOPICAL THERAPY: SUMMARY & CLINICAL PEARLS Topical therapy is a standard of care in mild to moderate acne treatment Due to their high effectiveness, TRs are recommended 1st line for treatment and maintenance BPO is also recommended as a first line agent and is the most cost effective due to OTC status Combination of topical agents are more effective than any agent used alone Topical abx are effective but must be used in combo with BPO to prevent bacterial resistance; generally reserved for inflammatory acne Salicylic acid is moderately effective in the treatment of acne (less effective than TRs and BPO) Azelaic acid has usefulness in postinflammatory hyperpigmentation It’s very effective to use multiple topical agents that affect different aspects of acne pathogenesis, but be aware of compatibility between agents SYSTEMIC THERAPY (moderate to severe acne) Oral antibiotics Tetracycline 250-500 mg po BID on empty stomach Doxycycline 100-200 mg po daily (without regard to meals) Minocycline 50mg po BID without regard to meals Solodyn® extended release minocycline dosed 1mg/kg/day Erythromycin 500mg po BID with food Clindamycin 150-300 mg po daily Trimethoprim-sulfamethoxazole 1 DS tab po BID Safety Tooth discoloration, enamel hypoplasia, and reduced bone growth in children <8yo and pregnant women (tetracyclines) Fetal and infant toxicity (tetracyclines and sulfamethoxazole/TMP) Bone marrow suppression, SJS, TEN (sulfamethoxazole/TMP) Bacterial resistance, GI upset, pseudomembranous colitis (erythromycin, clindamycin) Photosensitivity Tolerability Nausea, vomiting, diarrhea, vaginal candidiasis Efficacy Minocycline, doxycycline, tetracycline, erythromycin, clindamycin, azithromycin, sulfamethoxazole/TMP are all efficacious for treating acne Place in therapy—reserve for treatment resistant inflammatory acne AAD recommends reserving oral Abx for moderate to severe acne and limiting duration of use when possible (experts recommend limiting use to 12-18 weeks) Improvement is generally seen in 6-10 weeks Preference/Pearls Use BPO in combo with oral abx to decrease bacterial resistance Can also use oral abx in combo with TR to increase efficacy and to minimize use of abx Minocycline appears more efficacious, followed by doxycycline and tetracycline, respectively (CONTROVERSIAL) Minocycline is the least photosensitizing of the three tetracyclines but can cause vertigo, skin discoloration, and lupus-like syndrome Save erythromycin for patient who are recommended against using tetracyclines (pregnancy, <8yo) Very high bacterial resistance to erythromycin----for this reason not used preferentially Sulfamethoxazole/TMP or TMP alone may be used for patients who cannot use the above-mentioned abx (used rarely) Simplicity/Dosing Once or twice daily dosing, depending on agent Oral abx are less expensive than other agents typically used for moderate to severe acne Patient counseling points/additional info May try probiotics or yogurt to minimize occurrence of vaginal candidiasis Tetracycline absorption is inhibited by food, dairy products, antacids and iron; and must be taken on an empty stomach. Patients should take one hour prior to eating or two hours after a meal Doxycycline and minocycline can be taken with food and drink (although still separate with divalent cations), and doing so may reduce the GI side effects Isotretinoin (Amnesteem®, Claravis™, Absorica®, Myorisan®, Zenatane®) Safety Highly teratogenic (pregnancy category X)— iPLEDGE™ program Suicidal ideations Pancreatitis Pseudotumor cerebri Relative contraindications: Hyperlipidemia, diabetes mellitus, severe osteoporosis Significant adverse effects are numerous, frequent, and often dose related: Drying of the oral, nasal, and ocular mucosa – VERY common Chelitis and skin desquamation Elevated cholesterol & triglycerides – reversible upon dose reduction or drug d/c Dose is better absorbed with fatty good because it is a vitamin A derivative, but the overall diet needs to be healthier because of the hyperlipidemia concern Elevation of CPK, glucose Photosensitivity Pseudotumor cerebri Excess granulation tissue, scarring Hepatomegaly with increased LFTs Bone abnormalities – decreased BMD, impairment of growth Arthralgias, myalgias, muscle stiffness and headaches Significant mood changes, depression, suicidal ideation and completed suicides Alopecia Hearing & vision impairment IBD Efficacy Effectively reduces inflammatory lesions and acne cysts—the most effective sebosuppressive agent Reserved for severe nodulocystic acne, treatment resistant acne, or acne resulting in physical or psychological scarring Preference/Pearls All AB rated in Orange Book EXCEPT Absorica BX Participation in iPLEDGE™ program a must for all patients Requires monthly pregnancy tests and commitment to use 2 forms of contraception Any and all pregnancies need to be referred to a reproductive toxicity specialist for evaluation Treat for up to 20 weeks and discontinue sooner if acne resolution is 70% or greater Can only be prescribed by prescribers knowledgeable in its administration and monitoring and must be registered with iPLEDGE program Relapse usually occurs within the first 3 years and is highest in those with truncal acne and those receiving lower than the total recommended cumulative dose Acne may worsen initially during the first few weeks of treatment but can be managed with short course of steroids Cannot donate blood during treatment or within one month of stopping the drug Simplicity/Dosing/Monitoring parameters: Twice daily dosing Weight-based dosing (0.5 mg/kg/day in divided doses for first month, then increased to 1 mg/kg/day in divided doses) Requires monthly monitoring of various adverse events (neurologic, ophthalmologic, GI, metabolic) Monitor LFTs & lipids at baseline and at weeks 4 & 8. Must screen for psychiatric disorders and depression before and during treatment Monitor CPK, glucose, CBC with diff Patient counseling points/additional info Participating in iPLEDGE™, avoiding pregnancy, regular/routine monitoring should be continually reinforced Prescriptions should only be for 1-month supply and should be filled within 7 days of Rx date Oral retinoids carry same risk of sunburn than topical retinoids, so recommend sunscreen for all patients during outdoor activities Do not use with tetracyclines or tigecycline – increases chance of pseudotumor cerebri Increases clearance of carbamazepine Decreases effectiveness of oral contraceptives (hence the need for two forms of birth control) More info about iPLEDGE™ Program: www.ipledgeprogram.com o o o o o ALL patients (male and female), prescribing physicians, dispensing pharmacies, and wholesalers & manufacturer must be registered Pregnancy test (for all female patients of childbearing potential): Two negative tests prior to beginning therapy (the second performed at least 19 days after the first test and performed during the first 5 days of the menstrual period immediately preceding the start of therapy); monthly tests to rule out pregnancy prior to refilling prescription. Pregnancy tests must be done in CLIA certified lab and results must be submitted to iPLEDGE™ before prescription authorization Two forms of contraception must be used: initiated at least 1 month prior to therapy, during the entire treatment course and continued for up to 1 month after discontinuing treatment Physicians must certify expertise in the diagnosis and treatment of acne, and knowledge of the risk and severity of birth defects with isotretinoin ACNE IN SPECIAL POPULATIONS & MISC ACNE TREATMENTS: Post-inflammatory hyperpigmentation: o DOC – TRs or Azelaic acid o Alternative: Hydroquinone (Esoterica®, Lustra®---many brand name products) Available in 2% formulations OTC Available in 3-4% formulations as Rx o Depigmenting agent that acts by inhibiting melanin production o Dosed BID o May cause grayish discoloration of skin at sites of application (uncommon) Pregnancy o Consider risk vs benefit o Isotretinoin and tazarotene Category X!!! Absolute contraindication! o Clindamycin, erythromycin, azelaic acid---Category B o Benzoyl peroxide—Category C Pediatrics/Adolescents o Preadolescent acne (7-12 years) is common and may precede other signs of pubertal maturation o Pathogenesis and treatment is similar to older adolescents and adults o General approach is to use the least aggressive regimen that is effective while avoiding regimens that encourage the development of bacterial resistance. Nonpharmacologic measures and twice daily cleaning regimens OTC products including low strength BPO, salicylic acid, sulfur, resorcinol, sodium sulfacetamide as possible ingredients TRs—clinical trials include 12-18 yrs old Tretinoin gel 0.05% (Atralin®) FDA approved in >10yrs old Adapalene and BPO (Epiduo®) indicated for ages 9 and older Adapalene gel, tretinoin gel, tretinoin microsphere gel have been investigated in both open label and blinded studies in children < 12 yrs (currently are used offlabel in this age group) AAD endorses use of TRs for all types and severities of acne in children and adolescents of all ages Topical Abx OK if used in combo with BPO Reserve oral Abx for moderate to severe inflammatory acne: prefer doxycycline or minocycline UNLESS < 8yrs old Isotretinoin for severe, scarring, and/or refractory acne in adolescents (>13-Grade A recommendation); preadolescents (Grade C) Reserve use of oral contraceptives for acne not associated with endocrinologic pathology until 1 year after onset of menses Oral contraceptives Safety/Considerations VTE risk, breast CA history/family history, cerebrovascular disease, smoking in patients >35yo Tolerability Abnormal vaginal bleeding, cycle disruption Headaches Abdominal cramping Nausea, weight gain, bloating, breast tenderness, lower extremity edema, decreased libido, increased appetite Efficacy Reduces severity of inflammatory and comedonal acne Can take up to 3-6 months to see a significant effect Preference/Pearls Low to moderate dose of ethinyl estradiol (20-35 mcg) appears to be target dose Good choice in women with excess production of androgen, severe seborrhea, androgenic alopecia, late-onset acne Use 2nd or 3rd generation progestins, as they have the least androgenic activity (norgestimate, norethindrone acetate, desogestrel) DO NOT use 2nd generation progestins (levonorgestrel or norgestrel) as these have the MOST androgenic activity. Drosperinone has antiandrogenic activity Simplicity/Dosing Once daily dosing May be used to treat other conditions including dysmenorrhea, PCOS, menorrhagia May be used to prevent pregnancy in those taking isotretinoin, and can help acne at same time Patient counseling points/additional info Patients need to have annual physical exams while using OCs, including PAP smear and breast exams Smoking cessation counseling for patients who use cigarettes infrequently Oral spironolactone Safety Hyperkalemia- must monitor potassium Monitor blood pressure Caution in renal impairment Tolerability Gynecomastia in men In women, menstrual irregularity, breast tenderness, headache, fatigue Efficacy Anti-androgen that blocks androgen receptors at higher doses May require 3-6 months to see significant effect Preference/Pearls Typically reserved for patients with hyperandrogenism or PCOS Simplicity/Dosing Dosed at 50-200 mg per day Patient counseling points/additional info Counsel on importance of monitoring BP and potassium levels Caution in concomitant use of other meds that increase potassium Oral corticosteroids o Limited data to support effectiveness but may be of temporary benefit in those with severe inflammatory acne; only use very short bursts of high dose o Good choice for those with adrenal hyperandrogenism; use low doses o Generally used to reduce flare ups, especially when associated with tretinoins and isotretinoin SYSTEMIC THERAPY: SUMMARY & CLINICAL PEARLS Systemic therapy is typically reserved for moderate to severe acne when topical therapies in combination have failed Because of bacterial resistance concerns, BPO should always be used in combination with oral antibiotics, and duration of use should be limited to 12-18 weeks Combining oral antibiotics with TRs improves efficacy and limits duration of abx use Estrogen containing OCs can be useful in some women (regardless of acne severity) Oral antiandrogens such as spironolactone can be useful in the treatment of acne, especially in those patients with hyperandrogenism There is limited data supporting the use of oral corticosteroids, but there is consensus expert opinion that steroids offer temporary benefit in patients who have severe inflammatory acne, well-documented adrenal hyperandrogenism, and to reduce flare-ups associated with TRs and oral isotretinoin. TREATMENT ALGORITHM Mild comedonal acne Mild to moderate inflammatory acne Moderate to severe inflammatory acne Severe nodular acne 1. Topical retinoid + oral Abx + benzoyl peroxide (1st line option) (combos more effective than monotherapy) 1. Topical Retinoids (TR) or 2. Benzoyl peroxide (BPO) or 3. Topical Salicylic acid or azelaic acid (2nd line agents) Generally monotherapy will suffice 2. Consider adding oral isotretinoin if <50% improvement after 6 months of tx with oral Abx 3. OR consider adding antiandrogen or corticosteroid in select patients or those unwilling to take oral isotretinoin Any combination of topical therapies (combos more effective than monotherapy) 1. TR + BPO (1st line agents) 2. Topical Abx + BPO +/- TR 1. Oral isotretinoin 2. Oral Abx + topical retinoid + benzoyl peroxide (but not as effective as the above) If any combination topical therapy is ineffective, consider oral antibiotics For acne maintenance: TR for mild acne TR +/- BPO for moderate-severe acne For women, regardless of severity who desire contraception: antiandrogenic oral contraceptives For hyperandrogenic patients: consider spironolactone or corticosteroids (in add’n to standard therapy) For TR and isotretinoin flare, or highly inflammatory acne: corticosteroids For post-inflammatory hyperpigmentation: TR or azelaic acid Resources: Eichemfield LF, Krakowski AC, Piggott C, Del Rosso J, Baldwin H. et al. Evidence-Based Recommendations for the Diagnosis and Treatment of Pediatric Acne. Pediatrics 2013; 131;S163 DOI: 10.1542/peds.2013-0490B Strauss JS, Krowchuk DP, Leyden JJ, Lucky AW, et al. Guidelines of care for acne vulgaris management. J Am Acad Dermatol, 2007;56:651-63 DOI: 10.1016/j.jaad.2006.08.048 www.fda.gov for drug information