Acne Vulgaris Lecture Notes PDF

Acne Vulgaris Dermal Therapeutic  Objectives Explain pathophysiology and etiology of acne Identify the typical symptoms and variations of acne vulgaris Recommend initial steps for the evaluation and treatment of acne vulgaris Demonstrate understanding the range of sev...

Acne Vulgaris Dermal Therapeutic  Objectives Explain pathophysiology and etiology of acne Identify the typical symptoms and variations of acne vulgaris Recommend initial steps for the evaluation and treatment of acne vulgaris Demonstrate understanding the range of severity of acne vulgaris Demonstrate understanding common differential diagnoses of acne Recount the range of treatment options for acne vulgaris Select the most appropriate treatment options for acne vulgaris depending on the severity and  Introduction Acne vulgaris is a common chronic skin disease involving blockage and/or inflammation of pilosebaceous units (hair follicles and their accompanying sebaceous gland). Acne can present as non-inflammatory lesions, inflammatory lesions, or a mixture of both, affecting mostly the face but also the back and chest. Risk factors include genetics, the menstrual cycle, anxiety and stress, hot and humid climates, using oil-based makeup, and squeezing pimples.  Epidemiology Acne is the most common skin disease in the US and affects 80% of the population at some point in life. It begins at adolescence and the diseases gradually subsides by the age of 23–25 years. In some cases it may persists till middle-age. Teenagers or adulthood are the most common age groups having acne with the prevalence of 68.5% for males and 66.8% for females. On the other hand, acne incidence above 50 years is the least common having the prevalence of 7.3% for males and 15.3% for females. Cont. Epidemiology Acne epidemiology; percentage reported by decade. Adapted from Collier et al.(2008).  Etiology Acne is a multifactorial disease. Genetic, racial, hormonal, dietary, and environmental factors have been implicated in its development. Its psychologic impact can be severe. The role of heredity in acne has not been clearly defined; however, there is a significant tendency toward more serious involvement if one or both parents had severe acne during their youth. Cont. Etiology Four major etiologic factors are involved in the development of acne: 1. Increased sebum production, due to hormonal influences. 2. Alteration in the keratinization process and hyperproliferation of ductal epidermis. 3. Bacterial colonization of the duct with Propionibacterium acnes. 4. Production of inflammation with release of inflammatory mediators in  Cont. Etiology The most common triggers are:  Puberty During puberty, surges in androgens stimulate sebum production and hyperproliferation of keratinocytes.  Hormonal changes that occur with pregnancy or the menstrual cycle.  Occlusive cosmetics, cleansers, lotions, and clothing.  High humidity and sweating.  Some studies suggest a possible association with milk products and high glycemic diets.  Acne may abate in summer months because of sunlight has anti inflammatory effects.  Some drugs ( eg , corticosteroids, lithium, phenytoin, isoniazid) worsen acne or cause acneiform eruptions.  Pathophysiology Pathophysiology of Acne vulgaris is a multifactorial process , occurs through the interplay of 4 major factors: 1. Follicular plugging with sebum and keratinocytes 2. Excess sebum production 3. Colonization of follicles by Cutibacterium acnes (formerly Propionibacterium acnes), a normal human anaerobe. 4. Release of multiple inflammatory mediators Cont. Pathophysiology  Types of Acne Lesion Type: Acne Vulgaris Can Be Noninflammatory or Inflammatory  Noninflammatory acne is characterized by open and closed comedones that develop from the subclinical microcomedo.  Inflammatory acne is traditionally characterized as having papulopustular and/or nodular lesions, which may arise from the microcomedo or from noninflammatory clinically apparent lesions  Cont. Types of Acne There are 6 main types of spot caused by acne: 1. Blackheads (Open comedones): Approximately 2 to 5 mm, darktopped with contents extruding, and relatively stable. Not filled with dirt, but are black because the inner lining of the hair follicle produces pigmentation (coloring ) 2. Whiteheads (Closed comedones): have a similar appearance to blackheads, but may be firmer and won't empty when squeezed. Visible as a 1 to 2 mm whitehead most easily seen when the skin is stretched. It is often inconspicuous with no visible follicular opening Is the first clinical sign of acne Has a tendency to rupture  Cont. Types of Acne 3. Papules : Small red bumps that may feel tender or sore. 4. Pustules : Similar to papules, but have a white tip in the center , caused by a build up of pus. Formed from a superficial aggregation of neutrophils. Appears as a raised white lesion filled with pus, usually less than 5 mm in diameter Superficial pustules usually resolve within a few days without scarring  Cont. Types of Acne 5. Nodules: Large hard lumps that build up beneath the surface of the skin and can be painful. Produced through deeper, dermal, inflammatory infiltration. Is the most severe variant of acne Appears as warm, tender, firm lesions, with a diameter of 5 mm or greater May be suppurative or hemorrhagic within the dermis, may involve adjacent follicles and sometimes extend down to fat 6. Cysts: large pus filled lumps that look similar to boils and carry the greatest risk of causing permanent scarring. Cystic acne may show double comedones, resulting from prior inflammation and fistulous links between neighboring sebaceous units  Diagnosis The diagnosis of acne is based on the history and physical examination. Lesions most commonly develop in areas with the greatest concentration of sebaceous glands, which include the face, neck, chest, upper arms, and back. Diagnosis of Acne Vulgaris needs assessment for contributing factors (eg , hormonal, mechanical, or drug related) and differential diagnosis. Determination of severity (mild, moderate, severe). Assessment of psychosocial impact. Cont. Diagnosis How severe your acne is will determine where you should go for treatment and what treatment you should have. The severity of acne is often categorized as: A. Mild mostly whiteheads and blackheads, with a few papules and pustules. B. Moderate more widespread whiteheads and blackheads, with many papules and pustules. C. Severe lots of large, painful papules, pustules, nodules or cysts; you might also have some scarring. Cont. Diagnosis Acne in women If acne suddenly starts in adult women, it can be a sign of a hormonal imbalance, especially if it's accompanied by other symptoms such as: 1. Excessive body hair (hirsutism). 2. Irregular or light periods. The most common cause of hormonal imbalances in women is polycystic ovary syndrome (PCOS). PCOS can be diagnosed using a combination of ultrasound scans and blood tests.  Differential Diagnosis Acne vulgaris is rarely misdiagnosed. The conditions most commonly mistaken for acne vulgaris include: Rosacea, Perioral dermatitis, Gram-negative folliculitis, and Drug-induced acne.  Acne Vulgaris Treatment The first step in determining a safe and efficacious treatment regimen for acne vulgaris is to establish desired outcomes for the patient, regarding both short and long term goals. There are two governing principles: the chronic nature warrants early and aggressive treatment, and maintenance therapy is often needed for optimal outcomes. Treatment for acne depends on how severe it is. It can take several months of treatment before acne symptoms improve. This must be stressed with the patient to encourage adherence to lengthy treatment regimens, which address management of current symptoms and signs and preventive measures.  Desired Outcomes (Goals of Treatment) Basic goals of treatment include:  Alleviation of symptoms by reducing the number and severity of lesions (objective and subjective grading) and  Improving appearance,  Slowing progression,  Limiting duration and recurrence,  Prevention of longterm disfigurement associated with scarring and hyperpigmentation, and  Avoidance of psychologic suffering. Cont. Goal of Therapy The primary aim of acne treatment is to prevent or minimize scarring, once scarred the skin will never return to normal. The treatment can be topical or systemic. In some cases physical modalities such as comedone extraction or intra-lesional injection may be required. The patients should be told that the treatment of acne is long-term, and the response to treatment is slow. They should not expect a spontaneous cure.  General Approach to Treatment The approach to acne management is largely determined by: Severity index. Lesion type: predominantly non inflammatory or inflammatory. Treatment preferences including patient choices. Cost implications. Skin type and/or ethnic group. Patient age. Adherence. Response to previous therapy. Presence of scarring. Psychologic effects. Family history of persistent acne.  TREATMENT GENERAL APPROACH Patient education about goals, realistic expectations, and dangers of overtreatment is important to optimize therapeutic outcomes. Treatment regimens are targeted to types of lesions and acne severity. Mild acne usually is managed with topical retinoids alone or with topical antimicrobials, salicylic acid, or azelaic acid. Moderate acne can be managed with topical retinoids in combination with oral antibiotics and, if indicated, benzoyl peroxide. Severe acne is often managed with oral isotretinoin. Cont. TREATMENT Initial treatment is aimed at reducing lesion count and may last from a few months to several years; chronic indefinite therapy may be required to maintain control in some cases. Topical treatment forms include creams, lotions, solutions, gels, and disposable wipes. Responses to different formulations may depend on skin type and individual preference. Antibiotics such as tetracyclines and macrolides are the agents of choice for papulopustular acne. Oral isotretinoin is the treatment of choice in severe papulopustular acne and nodulocystic/ conglobate acne. Hormonal therapy may be an effective alternative in female patients. GENERAL APPROACH  NONPHARMACOLOGIC THERAPY Surface skin cleansing with soap and water has a relatively small effect on acne because it has minimal impact within follicles. Skin scrubbing or excessive face washing does not necessarily open or cleanse pores and may lead to skin irritation. Use of gentle, nondrying cleansing agents is important to avoid skin irritation and dryness during some acne therapies.  NONPHARMACOLOGIC THERAPY Diet : It is unclear what role diet plays in worsening acne. Scientists have found that people who consume a diet that offers a good supply of vitamins A and E and of zinc may have a lower risk of severe acne. But suggests that a diet with a low glycemic load may help.  Cleansers Mild acne may respond well to simple measures such as cleansing the skin with proprietary keratolytics ; these dissolve the keratin plug of the comedones. Cleansers need to be used with care as they can cause considerable dryness and scaling of the skin.  Moisturizers These can soothe the skin, especially in people who are using acne treatment such as isotretinoin, say researchers. Moisturizers containing aloe vera at a concentration of at least 10 percent can have a soothing and possibly anti inflammatory effect.  Avoid exacerbators Avoid: Harsh soaps, Strong sunlight, Oil- based make up and spicy food  Topical Therapy Topical therapy is the standard of care for mild to moderate acne. Those with moderate to severe acne will require systemic therapy. Topical treatments work only where applied. To reduce new lesion development, they must be applied to the entire affected area rather than individual spots. Most cause initial skin irritation, which may result in nonadherence or discontinuation. Irritation can be minimized by starting with lower strengths and gradually increasing frequency or dose. Where irritation persists, changing formulation from alcoholic solutions to washes, gels, or more moisturizing creams or lotions might help. Cont. Topical Therapy Topical treatment falls into two categories: keratolyticsfor non-inflammatory lesions and the topical antibiotics for inflammatory lesions. Targeting the micro-comedoneis essential in the treatment of acne. This would prevent the development of other lesions. The retinoids are the major agents used to target the microcomedones. Current consensus recommends a combination of topical retinoid and antimicrobial therapy as first-line therapy for almost all patients with acne.  Topical Keratolytic agents They are more effective in the non-inflamed lesions of acne. Topical retinoids are comedolytic; these can be continued as maintenance therapy to inhibit further micro-comedone formation. Topical retinoids normalize the altered pattern of follicular keratinization. The common topical retinoids are tretinoin 0.01, 0.025, 0.05% isotretinoin 0.05%, and adapelene 0.1%.  Cont. Topical Keratolytic agents.. The side effects of topical retinoids include: Dryness and burning sensation, they are also sensitive to sunlight. Isotretinoin and adapalene are less irritating. Combined preparation of retinoids and topical antibiotics are better tolerated. Benzoyl peroxide is a comedolytic and anti- bacterial agent, available in strengths of 2.5, 5 and 10%. It is important to explain to the patient that treatment with retinoids and benzoyl peroxide will dry the skin and cause local irritation. In order to reduce the irritation patients should initially use these preparations two to three times a week then gradually increase the frequency of applications. Sulphur, resorcinol and salicylic acid are also keratolytics. Salicylic acid is available as an over the counter preparation as a mild comedolytic agent.  Topical Antibacterial agents These are more effective in the inflamed lesions of acne. Commonly used topical antibiotics include 2% erythromycin, 1% clindamycin. Antibacterial resistance to Propionibacterium acnes is a problem with topical erythromycin. Topical antibiotics should be given for 3month period to prevent resistance. For prolonged use, benzoyl peroxide alone is preferable to avoid antibiotic resistance.  Other Topical Agents Other topical preparations are 20% azelaic acid:  It reduces comedones and normalizes the altered follicular keratinization of the pilosebaceous follicles.  The antimicrobial action and a direct influence on follicular hyperkeratosis are assumed to be the basis for the therapeutic efficacy of azelaic acid in acne.  Systemic Treatment The systemic treatment can be antibacterial or hormonal. Systemic therapy is an add-on therapy to topical treatment in moderate to severe acne with nodules and cysts, acne not responding to topical therapy, and active acne with scarring.  Antibiotics  Hormonal Therapy  Oral retinoids (Isotretinoin)  Systemic Antibiotics Antibiotics that concentrate in the pilosebaceous apparatus are preferred for acne therapy. These include tetracyclines, erythromycin, azithromycin, co-trimoxazole, trimethoprim and flucloxacillin. Several weeks are required to obtain maximum clinical response; usual duration of treatment is 4–6months. It is usual to start with 500mg tetracycline twice daily. When the acne is under control the dose should then be tapered to 250–500mg daily. Side effects are rare after a prolonged treatment with tetracycline. Tetracyclines should not be given to pregnant women and children below the age of 12years.  Cont. Systemic Antibiotics If acne is not responding to tetracycline then we can use one of the following:  Erythromycin 500mg twice daily,  Azithromycin 250mg three times a week,  Trimethroprim300mg twice daily. Oral antibiotics are generally prescribed for moderate- to-severe acne for 4–6months. The duration of therapy depends upon the clearance of acne. Longer period of treatment may be necessary if the lesions are not fully under control. Once the acne is well controlled, topical regimen should be continued as maintenance therapy. The antibiotic course could be repeated in the future if needed. If the patient does not respond to two groups of antibiotics, especially if scarring is noted then isotretinoin therapy should be considered.  Cont. Systemic Antibiotics The other tetracycline that can be used is: Lymecycline 408mg daily. Its compliance is good, and bacterial resistance is less than with first generation tetracyclines Doxycycline 100mg daily, doxycycline can occasionally cause a photosensitive eruption. Minocycline 50–100mg twice daily is another alternative, it has good tissue penetration and greater antimicrobial activity, but it is associated with an increased risk of systemic lupus erythematosus like syndrome (SLE) (generally not used because of this side- effect).  Hormone Therapies These include certain types of oral contraceptives (OCPs) that increase sex hormone-binding globulin and consequently reduce free testosterone levels. These are generally OCPs that have higher oestrogen and lower androgen potential (such as Yasmin®). Antiandrogen treatment alone can be teratogenic and therefore is given to women in the form of a contraceptive that contains cyproterone acetate with ethinyloestradiol (Dianette®). Long-term safety data are available up to 5 years. Dianette® may also help diminish mild hirsutism.  Oral retinoids Isotretinoin has revolutionised the treatment of severe acne, but it is usually reserved for resistant disease unresponsive to other oral therapies. This is because of its side-effect profile. should be warned that there is a potential risk of mood swings and depression and to stop the medication immediately if they experience problems. A modern approach to isotretinoin dosing is to begin patients on a low dose for the first 1–2 months (20–40 mg daily) and then increase to 1 mg/kg/day to minimise initial xerosis. The cumulative target dosage for isotretinoin is 120–150 mg/kg based on studies showing that acne is likely to be ‘cured’ if a full treatment course is taken. Occasionally, patients require a second or even third course of isotretinoin treatment, and some patients (particularly males with very severe acne) may require long-term treatment with very low doses such as 20 mg/week.  Cont. Isotretinoin Isotretinoin (Accutane) decreases sebum production, changes sebum composition, inhibits P. acnes growth within follicles, inhibits inflammation, and alters patterns of keratinization within follicles. It is the treatment of choice for severe nodulocystic acne. It can be used in patients who have failed conventional treatment as well as those who have scarring acne, chronic relapsing acne, or acne associated with severe psychological distress. Dosing guidelines range from 0.5 to 1 mg/kg/day, but the cumulative dose taken during a treatment course may be the major factor influencing long term outcome. Optimal results are usually attained with cumulative doses of 120 to 150 mg/kg. A 5-month course is sufficient for most patients. Alternatively, an initial dose of 1 mg/kg/day for 3 months, then reduced to 0.5 mg/kg/day and, if possible, to 0.2 mg/kg/day for 3 to 9 more months may optimize the therapeutic outcome.  Cont. Isotretinoin Adverse effects are frequent and often dose related. About 90% of patients experience mucocutaneous effects; drying of the mouth, nose, and eyes is most common. Cheilitis and skin desquamation occur in more than 80% of patients. The conjunctiva and nasal mucosa are affected less frequently. Systemic effects include transient increases in serum cholesterol and triglycerides, increased creatine kinase, hyperglycemia, photosensitivity, pseudotumor cerebri, excess granulation tissue, hepatomegaly with abnormal liver injury tests, bone abnormalities, arthralgias, muscle stiffness, headache, and a high incidence of teratogenicity. Patients should be counseled about and screened for depression during therapy, although a causal relationship to isotretinoin therapy is controversial. Because of teratogenicity, contraception is required in female patients beginning 1 month before therapy, continuing throughout treatment, and for up to 3 months after discontinuation of therapy. All patients receiving isotretinoin must participate in the iPLEDGE program, which requires pregnancy tests and assurances by prescribers and pharmacists that they will follow required procedures. Questions? Thank You