Medicine for acne: Tretinoin

Tretinoin
Tretinoin (Retin-A), also known as retinoic acid, is the agent of choice for noninflammatory acne consisting of open and closed comedones. It is available in various preparations: Retin-A solution (0.05%) is the strongest and most irritating. Retin-A gel (0.025% and 0.01%) is drying and is for oily skin. Retin-A cream (0.1%, 0.05%, and 0.025%) is lubricating and is for dry skin

Mechanism of action
Tretinoin, an oxidation product of vitamin A, initiates increased cell turnover in both normal follicles and comedones and reduces the cohesion between keratinized cells. It acts specifically on microcomedones (the precursor lesion of all forms of acne), causing fragmentation and expulsion of the microplug, expulsion of comedones, and conversion of closed comedones to open comedones. New comedone formation is prevented by continued use. Inflammation may occur during this process, temporarily making acne worse. Continual topical application leads to thinning of the stratum corneum, making the skin more susceptible to sunburn; sun damage; and irritation from wind, cold, or dryness. Irritants such as astringents, alcohol, and acne soaps will not be tolerated as they were previously. The incidence of contact allergy is very low. Because of the direct action of tretinoin on the microcomedone, many clinicians believe tretinoin is appropriate for all forms of acne

Combination therapy: synergism
Tretinoin enhances the penetration of other topical agents such as topical antibiotics and benzoyl peroxide. The enhanced penetration results in a synergistic effect with greater overall drug efficacy and a faster response to treatment

Application techniques
The skin should be washed gently with a mild soap (e.g., Purpose, Basis) no more than two to three times each day, using the hands rather than a washcloth. Special acne or abrasive soaps should be avoided. To minimize possible irritation, the skin should be allowed to dry completely by waiting 20 to 30 minutes before applying tretinoin. Tretinoin is applied in a thin layer once daily. Medication is applied to the entire area, not just to individual lesions. An amount the size of a pea is enough for a full facial application. Patients with sensitive skin or those living in cold, dry climates may start with an application every other or every third day. The frequency of application can be gradually increased to as often as twice each day if tolerated. The corners of the nose, the mouth, and the eyes should be avoided; these areas are the most sensitive and the most easily irritated. Tretinoin is applied to the chin less frequently during the initial stages of therapy; the chin is sensitive and is usually the first area to become red and scaly. Sunscreens should be worn during the summer months if exposure is anticipated.

Response to treatment

One to four weeks
During the first few weeks, patients may experience redness, burning, or peeling. Those with excessive irritation should use less frequent applications (i.e., every other or every third day.) Most patients adapt to treatment within 4 weeks and return to daily applications. Those tolerating daily applications may be advanced to a higher dosage or to the more potent solution.

Three to six weeks
New papules and pustules may appear because comedones become irritated during the process of being dislodged. Patients unaware of this phenomenon may discontinue treatment. Some patients never get worse and sometimes begin to improve dramatically by the fifth or sixth week

After six weeks
Most patients improve by the ninth to twelfth week and exhibit continuous improvement thereafter. Some patients never adapt to tretinoin and experience continuous irritation or continue to worsen. An alternate treatment should be selected if adaptation has not occurred by 6 to 8 weeks. Some patients adapt but never improve. Tretinoin may be continued for months to prevent appearance of new lesions

Medicine for acne: Oral antibiotics: Minocycline

Minocycline.
Minocycline (50-mg and 100-mg capsules and scored tablets) is a tetracycline derivative that has proved valuable in cases of pustular acne that have not responded to conventional oral antibiotic therapy. Minocycline is very expensive; generic forms are now available. One study comparing minocycline (50 mg three times a day) with tetracycline (250 mg four times a day) revealed that minocycline resulted in significant improvement in patients who did not respond to tetracycline. Patients who responded to tetracycline had significantly advanced improvement when switched to minocycline. The inhibitory effect on gastrointestinal absorption with food and milk is significantly greater for tetracycline than for minocycline. Food causes a 13% inhibition of absorption with minocycline and a 46% inhibition with tetracycline, milk a 27% inhibition with minocycline and a 65% inhibition with tetracycline. The simpler regime and early onset of clinical improvement are likely to result in better patient compliance. There is therefore justification for the use of minocycline as first-line oral therapy.
DOSING.
The usual initial dosage is 50 to 100 mg twice each day. The dosage is tapered when a significant decrease in the number of lesions is observed, usually in 3 to 6 weeks.
ADVERSE EFFECTS.
Minocycline is highly lipid-soluble and readily penetrates the cerebrospinal fluid, causing dose-related ataxia, vertigo, nausea, and vomiting in some patients. In susceptible individuals, central nervous system (CNS) side effects occur with the first few doses of medication. If CNS adverse reactions persist after the dosage is decreased or after the capsules are taken with food, alternative therapy is indicated. A blue-gray pigmentation of the skin, oral mucosa, nails, and thyroid gland has been found in some patients, usually those taking high dosages of minocycline for extended periods. Skin pigmentation has been reported in depressed acne scars, at sites of cutaneous inflammation, as macules resembling bruises on the lower legs, and as a generalized discoloration suggesting an off-color suntan. Pigmentation may persist for long periods after minocycline has been discontinued. The consequences of these deposits are unknown. Tooth staining (lasting for years) located on the incisal one half to three fourths of the crown has been reported in adults, usually after years of minocycline therapy. In contrast, tooth staining produced by tetracycline occurs on the gingival third of the teeth in children treated before age 7.

Medicine for acne: Oral antibiotics: Tetracycline

Tetracycline.
Tetracycline is the most widely prescribed oral antibiotic for acne. One major disadvantage is the requirement that tetracycline not be taken with food (particularly dairy products), certain antacids, and iron, all of which interfere with the intestinal absorption of the drug. Failure to adhere to these restrictions accounts for many of the reported therapeutic failures of tetracycline.
DOSING.
Efficacy and compliance are obtained by starting tetracycline administration at 500 mg twice each day and continuing this dosage until a significant decrease in the number of inflamed lesions occurs, usually in 3 to 6 weeks. Thereafter the dosage may be decreased to 250 mg twice each day or oral therapy may be discontinued in favor of topical antibiotics. Patients with severe pustular and cystic acne or those who do not respond to 1 gm/day might respond to a higher dosage of tetracycline (1.5 to 3.0 gm/day). These higher dosages may not be tolerated by some patients. Patients who do not respond after 6 weeks of adequate dosages of oral tetracycline should be introduced to an alternative treatment. For unknown reasons a significant number of patients who take tetracycline exactly as directed do not respond to high dosages, whereas others respond very favorably to 250 mg once a day or once every other day and flare when attempts are made to discontinue treatment.
ADVERSE EFFECTS.
The incidence of photosensitivity to tetracycline is low, but it increases when higher dosages are used. All females should be warned about the increased incidence of Candida albicans vaginitis that occurs while taking antibiotics. The package labeling of oral contraceptives warns that reduced efficacy and increased incidence of breakthrough bleeding may occur with tetracycline and other antibiotics. Although this association has not been proven, it is prudent to inform patients of this potential risk. Pseudotumor cerebri, a self-limited disorder in which the regulation of intracranial pressure is impaired, is a rare complication of tetracycline treatment. Increased intracranial pressure causes papilledema and severe headaches. Increased intraocular pressure can lead to progressive visual impairment and eventually blindness.

Medicine for acne : Benzoyl peroxide

Benzoyl peroxide

The primary effect of benzoyl peroxide is antibacterial, therefore it is most effective for inflammatory acne consisting of papules, pustules, and cysts, although many patients with comedone acne respond to it. Benzoyl peroxide is less effective than vitamin A acid at disrupting the microcomedo. Benzoyl peroxide and isotretinoin significantly reduce noninflamed lesions in 4 weeks. In one study, benzoyl peroxide had a more rapid effect on inflamed lesions with significant reductions at 4 weeks, whereas the use of isotretinoin showed a significant improvement at 12 weeks.

Preparations.

Benzoyl peroxide is available over the counter and by prescription. Some examples of benzoyl peroxide preparations are water-based gel (Benzac AC 2.5%, 5%, and 10%), alcohol-based gel (Benzagel 5% and 10%), and acetone-based gel (Persa-gel 5% and 10%) (see the Formulary). Water-based gels are less irritating, but alcohol-based gels, if tolerated, might be more effective. Benzoyl peroxide is also available in a soap base in strengths from 2.5% to 10%.

Mechanism of action.

Benzoyl peroxide produces a drying effect that varies from mild desquamation to scaliness, peeling, and cracking. Patients should be reassured that drying does not cause wrinkles. It causes a significant reduction in the concentration of free fatty acids via its antibacterial effect on P. acnes. This activity is presumably caused by the release of free radical oxygen, which is capable of oxidizing bacterial proteins. Benzoyl peroxide seems to reduce the size of the sebaceous gland, but whether sebum secretion is suppressed is still unknown. Patients should be warned that benzoyl peroxide is a bleaching agent that can ruin clothing.

Principles of treatment.

Benzoyl peroxide should be applied in a thin layer to the entire affected area. Most patients experience mild erythema and scaling during the first few days of treatment, even with the lowest concentrations, but adapt in a week or two. It was previously held that vigorous peeling was necessary for maximum therapeutic effect; although many patients improved with this technique, others became worse. Recent studies show that an adequate therapeutic result can be obtained by starting with daily applications of the 2.5% or 5% gel and gradually increasing or decreasing the frequency of applications and strength until mild dryness and peeling occur.

Allergic reaction.

Approximately 2% of patients develop allergic contact dermatitis to benzoyl peroxide and must discontinue its use. The sudden appearance of diffuse erythema and vesiculation suggests contact allergy to benzoyl peroxide.

Medicine for acne : Corticosteroids

Corticosteroids.
Corticosteroids can be considered in recalcitrant cases of acne not responsive to oral contraceptives or spironolactone and for patients with elevated DHEAS. Corticosteroids can be used alone or in combination with oral contraceptives and antiandrogens. Elevated DHEAS indicates adrenal androgen overproduction. Either dexamethasone (0.125 to 0.5 mg at bedtime) or prednisone (2.5 to 7.5 mg at bedtime and 2.5 mg on waking) is prescribed. Low-dose steroids administered at bedtime prevent the pituitary from producing extra ACTH and thereby reduce the production of adrenal androgens. Dexamethasone may be the more rational choice for adrenal suppression with its longer duration of action. The drug is given at bedtime so that effective levels will be present during the early morning hours when ACTH secretion is most active. Initial dosage should be dexamethasone 0.25 mg or prednisone 2.5 mg, and the dosage should be increased to dexamethasone 0.5 mg or prednisone 5.0 to 7.5 mg if the DHEAS level has not been lowered after 3 to 4 weeks of treatment. Therapy is continued for 6 to 12 months, but the benefits may persist beyond that. This low dosage produces a clinical improvement and suppresses DHEAS levels. At these dosages, few patients experience shutdown of the adrenal-pituitary axis or other adverse effects of the drug. ACTH stimulation tests or early morning cortisol levels may be performed every few months to make sure that there is no adrenal suppression. Not all patients respond.

Medicine for acne: Oral contraceptives

Oral contraceptives.
Ovarian hypersecretion of androgens can be suppressed with oral contraceptives. Most oral contraceptives contain combinations of estrogens and progestational agents. Oral contraceptives with estrogen (ethynyl estradiol or mestranol) and progestins of low androgenic activity are the most useful. Higher dose estrogen pills are more effective but not as safe.
Most synthetic progesterones have some degree of androgenic activity, which is undesirable in patients who already have signs of androgen excess. Oral contraceptives that appear to be useful in androgenic disorders and acne include Demulen, Ovcon 35, Modicon, Brevicon, and Ortho-Novum 7/7/7. The progesterone ethynodiol diacetate in Demulen is a relatively low androgenic progesterone. Norethindrone is more androgenic, but the low doses contained in Ovcon-35, Modicon, and Brevicon make these pills relatively nonandrogenic. Triphasil, containing levonorgestrel, and Diane (available outside the United States), containing cyproterone acetate, produced a 72% reduction in acne.
The estrogenic and androgenic activity of various oral contraceptives are listed in the Formulary. In many instances acne flares after the use of oral contraceptives is discontinued. Selection of an appropriate agent may provide the benefit of effective acne therapy for women who have chosen an oral contraceptive for birth control. Women in their thirties and forties without risk factors such as smoking or a family history of premature cardiovascular disease can safely use low-dose oral contraceptives to reduce ovarian androgen secretion.
Drugs that may reduce the effectiveness of oral contraceptives
Antibiotics
ampicillin, amoxicillin, isoniazid, metronidazole, penicillin, rifampin, tetracycline
Anticonvulsant drugs
barbiturates, carbamazepine, ethosuximide, phenytoin, primidone
Sedatives and hypnotics
barbiturates, benzodiazepines, chloral hydrate
Others
antacids, antimigraine preparations, clofibrate

Medicine for acne: Antiandrogen therapy

The majority of patients with acne do not have serum androgen abnormalities. The profound sebum suppression produced by isotretinoin has to a large extent eliminated the need for antiandrogenic therapy. Antiandrogenic therapy is reserved for patients with acne who have clinical signs of androgen excess and for those in whom other treatments have failed.
Patient population.
There is a group of women with treatment-resistant, late-onset, or persistent acne. Some of these women have signs suggesting hyperandrogenism, such as hirsutism, irregular menses, or menstrual dysfunction, but others are normal. Serum androgens may or may not be elevated.
Ovulation abnormalities.
Ovulation disturbances have been found in 58.3% of women acne patients, with a prevalence of anovulation in juvenile acne and of luteal insufficiency in late-onset/persistent acne. Women affected by late-onset or persistent acne have a high incidence of polycystic ovary disease. Polycystic ovaries are not necessarily associated with menstrual disorders, obesity, or hirsutism. The presence of polycystic ovaries in acne patients does not correlate with acne severity, infertility, menstrual disturbance, hirsutes, or biochemical endocrinologic abnormalities.
Androgens.
A combination of the effects of circulating androgens and the effects of their metabolism at the hair follicle modulates sebum production and acne severity. Androgens (free testosterone [fT], dehydroepiandrosterone sulfate [DHEAS]) are the most important hormones in the pathogenesis of acne. Plasma-free testosterone is the active fraction of testosterone and determines plasma androgenicity.
Diagnosis--serum androgen levels.
fT and DHEAS are the most practical ways of evaluating hormonal influences in the female. DHEAS is the best index of adrenal androgen activity.
Treatment
Three options.
There are three options for treating acne systemically with hormone manipulation. Estrogen suppresses ovarian androgen, glucocorticoids suppress adrenal androgen, and antiandrogens (spironolactone) act at the peripheral level (hair follicle, sebaceous gland).

Medicine for acne: Isotretinoin Side effects

Isotretinoin Side effects
Side effects occur frequently, are dose-dependent, and are reversible shortly after discontinuing treatment. Patients with side effects can be managed at a lower dosage for a period long enough to reach the 120 mg/kg cumulative dose level. Explain to patients that the long-term benefit is related to the cumulative dosage, not to the duration of therapy.
The incidence of side effects was documented in a large study. Patients in that study stopped isotretinoin for the following reasons: mucous/skin effects (2.5), elevated triglyceride levels (2.0), musculoskeletal effects (1.3), headaches (1.1), elevated liver enzyme levels (0.6), amenorrhea (0.4), and other (0.5).
Teratogenicity--pregnancy prevention program.
Isotretinoin is a potent teratogen primarily involving craniofacial, cardiac, thymic, and central nervous system structures. A number of physicians inadvertently prescribed isotretinoin to pregnant women, which resulted in birth defects. For this reason the FDA considered withdrawing isotretinoin in 1988. Roche Laboratories designed the pregnancy prevention program; as a result, isotretinoin is still available.
The pregnancy prevention program is available from Roche Laboratories in a box containing a qualification checklist for patients, information about treatment, contraception counseling and serum pregnancy testing information, an optional referral form for expert counseling on contraception and patient self-evaluation, consent forms, and a follow-up survey.
Women should be educated about the risks to the fetus and the need for adequate contraception. Sexually active women should have a pregnancy test and postpone therapy until their next normal menstrual period. Some physicians will not prescribe isotretinoin to women of child-bearing age unless they are taking oral contraceptives. Others withhold isotretinoin if abortion is not an option. Isotretinoin is not mutagenic, nor is it stored in tissue. It is recommended that contraception be continued for 1 month after stopping isotretinoin. Patients can be reassured that conception is safe after this 1-month period. One study showed that from the fourth month of treatment onward, a statistically significant increase in the mean sperm density, sperm morphology, and motility were not affected. One year after treatment there was no evidence of any negative influence of 6 months of treatment with isotretinoin on spermatogenesis.
Plasma lipid abnormalities.
Accutane therapy induces an elevation of plasma triglycerides. In one study of patients (ages 14 to 40 years) treated for 20 weeks with 1 mg/kg/day, the maximum mean triglyceride levels rose 46.3 mg/dl in men and 52.3 mg/dl in women. In that study, 2 of 53 patients had a triglyceride elevation over 500 mg/dl, and 8 had elevations of 200 to 500 mg/dl. Triglyceride levels rise after 6 weeks of therapy and continue to rise while therapy continues. Age, sex, and weighted dose do not appear to be risk factors for triglyceride elevations. Overweight subjects are 6 times more likely to develop significant elevations in serum triglyceride, and subjects with elevated baseline triglyceride levels are 4.3 times more likely to develop significant elevations. Plasma lipid and lipoprotein levels return to baseline by 8 weeks after treatment. Liver and lipid abnormalities rarely necessitate dosage reduction and the need for repeat laboratory tests after initial normal values has been questioned.
Hyperostoses.
Asymptomatic hyperostoses (spurs) of the spine and extremities can be documented radiographically in some patients but do not seem to be of concern with a standard course of isotretinoin therapy.
Cheilitis.
Cheilitis is the most common side effect, occurring in virtually all patients. Application of emollients should be started with the initiation of therapy to minimize drying.
Approximately 40% of patients develop an elevated sedimentation rate during treatment. Isotretinoin does not specifically affect skeletal or myocardial muscles, 28% of patients complain of musculoskeletal symptoms. Accutane contains the preservative parabens; those patients with a proven allergy to parabens cannot receive Accutane. Exuberant granulation tissue may occur at the sites of healing acne lesions and is more likely to develop in patients who have preexisting crusted, draining, or ulcerated lesions. Granulation tissue can be controlled with intralesional steroid injections or silver nitrate sticks. Severe dry skin or eczema commonly occurs on the backs of the hands. Routine use of moisturizers and infrequent washing is recommended.

Medicine for acne: Isotretinoin Therapy (2)

Isotretinoin therapy.
Patients are seen frequently during the course of therapy (e.g., every 4 weeks). Isotretinoin is given in two divided doses daily, preferably with meals. Many patients experience a moderate to severe flare of acne during the initial weeks of treatment. This adverse reaction can be minimized by starting at 10 to 20 mg twice each day and gradually increasing the dosage during the first 4 to 6 weeks. Treatment is discontinued at the end of 16 to 20 weeks, and the patient is observed for 2 to 5 months. Those with persistently severe acne may receive a second course of treatment after the posttreatment observation period.
Response to therapy.
At dosages of 1 mg/kg/day, sebum production decreases to approximately 10% of pretreatment values and the sebaceous glands decrease in size. Maximum inhibition is reached by the third or fourth week. Within a week, patients normally notice drying and chapping of facial skin and skin oiliness disappears quickly. These effects persist for an indefinite period when therapy is discontinued.
During the first month, there is usually a reduction in superficial lesions such as papules and pustules. New cysts evolve and disappear quickly. A significant reduction in the number of cysts normally takes at least 8 weeks. Facial lesions respond faster than trunk lesions.
Resistant patients.
Younger patients (14 to 19 years of age) and those who have severe acne relapse more often. [acne relapses more often than facial acne. A return of the reduced sebum excretion rate to within 10% of the pretreatment level is a poor prognostic factor. with microcystic acne (whiteheads) and women with gyneco-endocrinologic problems are resistant to treatment. Women who do not clear after a total cumulative dose of 150 mg/kg need laboratory and clinical evaluation of their endocrinologic status. They may benefit from antiandrogen therapy.
Psychosocial implications.
Patients successfully treated with isotretinoin have significant posttreatment gains in social assertiveness and self-esteem. There is also a significant reduction in anxiety and depression.
Patients with minimal facial acne but with symptoms of dysmorphophobia (inappropriate depression and/or anxiety response to mild acne) are often treated with long-term antibiotic therapy with no perceived improvement. These patients respond to isotretinoin in that they are satisfied with the cosmetic results achieved. The incidence of relapse is greater than that of other acne patients and often requires additional therapy in the form of antibiotics or further isotretinoin.
Laboratory studies.
Pregnancy tests, triglyceride tests, complete blood counts, and liver function tests are performed on patients taking isotretinoin.

Medicine for acne: Isotretinoin Therapy (1)

Dosage.
The severity of the side effects of isotretinoin is proportional to the daily dose. Start with lower dosages and progressively increase the dosage in accordance with the tolerance.
The cumulative dose may be more important than the duration of therapy. A cumulative dose of greater than 120 mg/kg is associated with significantly better long-term remission. This dosage level can be achieved by either 1 mg/kg/day for 4 months or a smaller dosage for a longer period. The therapeutic benefit from a total cumulative dose of more than 150 mg/kg is virtually nonexistent. Analysis of 9 years of experience demonstrated that 1 mg/kg/day of isotretinoin for 4 months resulted in the longest remissions. Relapse rates in patients receiving 0.5 mg/kg/day were approximately 40% and those receiving 1.0 mg/kg/day were approximately 20%. Younger patients, males, and patients with truncal acne derive maximum benefit from the higher dosages. In these patients, dosages less than 0.5 mg/kg/day for a standard 4-month course are associated with a high relapse rate. Treat older patients with facial acne with a dosage of 0.5 mg/kg/day. Double the dosage if there is no response at the end of 2 months. Side effects depend on the dosage and can be controlled through reduction.
Duration of therapy.
A standard course of isotretinoin therapy is 16 to 20 weeks. Approximately 85% of patients are clear at the end of 16 weeks; 15% require longer treatment. Side effects are related to the dosage. Treat for a longer duration at a lower dosage if mucocutaneous side effects become troublesome. Patients with large, closed comedones may respond slowly and relapse early with inflammatory papules. Another ill-defined group responds slowly and requires up to 9 months until the condition begins to clear.
Relapse and repeat courses of isotretinoin.
Approximately 39% of patients relapse and require oral antibiotics (23%) or additional isotretinoin (16%). Relapse usually occurs within the first 3 years after isotretinoin is stopped; most often during the first 18 months after therapy. Some patients require multiple courses of therapy. The response to repeat therapy is consistently successful, and side effects are similar to those of previous courses. Repeat courses of isotretinoin seem to be safe.

Medicine for acne: Isotretinoin (Accutane)

Isotretinoin (Accutane 10-, 20-, 40-mg capsules)
Isotretinoin (13-cis retinoic acid), an oral retinoid related to vitamin A, is a very effective agent for control of acne and in the induction of long-term remissions, but it is not suitable for all types of acne. Isotretinoin affects all major etiologic factors implicated in acne. It dramatically reduces sebum excretion, follicular keratinization, and ductal and surface Propionibacterium acnes counts. These effects are maintained during treatment and persist at variable levels after therapy. A number of side effects occur during treatment. Isotretinoin is a potent teratogen; pregnancy must be avoided during treatment. Isotretinoin is not mutagenic; female patients should be assured that they may safely get pregnant but should wait for at least 1 month after stopping isotretinoin. Age is not a limiting factor in patient selection.
Indications
Severe, recalcitrant cystic or nodular and inflammatory acne.
A few patients with severe disease respond to oral antibiotics and vigorous drying therapy with a combination of agents such as benzoyl peroxide and sulfacetamide/sulfur lotion. Those who do not respond after a short trial of this conventional therapy should be treated with isotretinoin to minimize scarring.
Moderate acne unresponsive to conventional therapy.
Moderate acne usually responds to antibiotics (e.g., tetracycline or erythromycin 500 mg twice daily) plus topical agents. Change to a different antibiotic (e.g., minocycline 100 mg twice daily) if response is poor after 3 months. Change to a third antibiotic (e.g., ampicillin, a cephalosporin, or trimethoprim/sulfamethoxazole) if response is poor after 3 months on the second antibiotic. Change to isotretinoin if response is unsatisfactory after three consecutive 3-month courses of antibiotics. Patients who have a relapse during or after three courses of antibiotics are also candidates for isotretinoin.
Patients who scar.
Any patient who scars should be considered for isotretinoin therapy. Acne scars leave a permanent mark on the skin and psyche.
Excessive oiliness.
Excessive oiliness is disturbing and can last for years. Antibiotics and topical therapy may provide some relief, but isotretinoin's effect is dramatic. Relief may last for months or years; some patients require a second or third course of treatment.
Severely depressed or dysmorphophobic patients.
Some patients, even with minor acne, are depressed. Those who do not respond to conventional therapy are candidates for isotretinoin. They respond well to isotretinoin, although some may relapse quickly and require repeat courses.

Medicine for acne: Spironolactone

Spironolactone (SPL) has antiandrogenic properties and is used to treat acne. Men do not tolerate the high incidence of endocrine side effects, therefore it is only used in women. SPL decreases steroid production in adrenal and gonadal tissue. In women, total serum testosterone decreases and dehydroepiandrosterone sulfate is either decreased or remains unchanged. Free testosterone levels are unchanged or decreased. SPL acts as an antiandrogen peripherally by competitively blocking cytosol receptors for dihydrotestosterone in the sebaceous glands.
Indications.
Spironolactone can be used with antibiotics or oral contraceptives or as a single drug therapy. Therefore it can be used when the source of androgen is either adrenal or ovarian or when screening for serum androgens is normal. Cyproterone acetate has similar effects (available outside the United States). A formulation of cyproterone acetate, in combination with 50 or 35 mug of estradiol, is available outside the United States. These drugs (Diane and Dianette) serve as an oral contraceptive and as an inhibitor of androgen receptors.
Usage in Acne:
Spironolactone causes a significant reduction in sebum secretion and a decrease in the lesion counts of patients. Studies show that SPL at a dosage of 200 mg/day suppresses sebum production by 75% and can reduce lesion counts by up to 75% over a 4-month period.
Adverse reactions.
Side effects are dose related. The incidence is high, but the severity is generally mild and most women tolerate treatment. Menstrual irregularities (80%) such as amenorrhea, increased or decreased flow, midcycle bleeding, and shortened length of cycle occur. Oral contraceptives reduce the incidence and severity of menstrual irregularities. Breast tenderness or enlargement and decreased libido are infrequent. Other effects include mild hyperkalemia, headache, dizziness, drowsiness, confusion, nausea, vomiting, anorexia, and diarrhea. There are no documented cases of spironolactone-related tumors in human beings. The safety of spironolactone use during pregnancy is unknown.

Medicine for acne pictures

Each diagram illustrates commonly used medicines. Oral and topical forms are included together with dosages and side effects.

Acne tips

• Essentials of Diagnosis
• Often occurs at puberty, though onset may be delayed until the third or fourth decade
• Open and closed comedones the hallmarks
• Severity varies from comedonal to papular or pustular inflammatory acne to cysts or nodules
• Face, neck, upper chest, and back may be affected
• Pigmentary changes and severe scarring can occur
• Differential Diagnosis
• Acne rosacea, perioral dermatitis, folliculitis, and tinea.
• Trunk lesions may be confused with folliculitis or miliaria.
• May be induced by topical, inhaled, or systemic steroids, oily topical products, and anabolic steroids.
• Foods neither cause nor exacerbate acne.
• In women with resistant acne, hyperandrogenism should be considered; may be accompanied by hirsutism and irregular menses.
• Treatment
• Improvement usually requires 4--6 weeks
• Topical retinoids very effective for comedonal acne but usefulness limited by irritation
• Topical benzoyl peroxide agents
• Topical antibiotics (erythromycin combined with benzoyl peroxide, clindamycin) effective against comedones and mild inflammatory acne
• Oral antibiotics (tetracycline, doxycycline, minocycline) for moderate inflammatory acne; erythromycin is an alternative when tetracyclines contraindicated
• Low-dose oral contraceptives containing a nonandrogenic progestin can be effective in women
• Diluted intralesional corticosteroids effective in reducing highly inflammatory papules and cysts
• Oral isotretinoin useful in some who fail antibiotic therapy; pregnancy prevention and monitoring essential
• Surgical and laser techniques available to treat scarring
• Advice:
Don't waste time continuing failing therapies in scarring acne; treat
aggressively if needed to prevent further scars.

What is acne?

Acne
Acne is a common inflammatory disease of a sebaceous gland associated with a hair follicle, called the pilosebaceous unit. There are two types of acne: inflammatory and non-inflammatory. Both types of acne are characterized by excessive sebum production. The excess sebum accumulates in the follicle, causing the follicle to swell.
In inflammatory acne, the follicle becomes blocked by the sebum and a type of acne-specific bacterium, Propionibacterium acnes, proliferates in the canal. Eventually, the follicle ruptures and the sebum and bacteria are released into the dermis, causing inflammation of the dermal tissue. In non-inflammatory acne, the follicle does not burst but remains dilated. The sebum either moves to the skin surface (a blackhead) or the canal remains blocked (a whitehead).
Acne is commonly seen in teenagers and young adults, beginning with the onset of puberty. Although both boys and girls suffer from acne, it is especially severe and common in boys. Adults, especially women, may have a recurrence of acne.
Causes of Acne
Sebum production is stimulated by androgens, especially testosterone. The sharp increase in androgens seen in both girls and boys during puberty is largely responsible for the onset and severity of acne. There is little research support for traditional biases that diet or lack of facial cleansing contributes to acne, although P. acne infection of the obstructed follicle may be worsened by poor nutrition. Instead, there is a strong genetic influence over the development of acne that may be related to oversensitivity of the sebaceous glands to androgen or the presence of an environment favorable to the proliferation of bacteria. Other contributors to acne may be important and vary for any given individual. Protective against acne is estrogen, which opposes the action of androgen on the sebaceous glands and reduces the development of acne. In adult women, the development of acne may be related to other systemic conditions or
may occur as the level of testosterone relative to estrogen begins to rise in the early perimenopausal years.
Acne rosacea is a condition of the skin that develops in middle-aged adults of both sexes and is characterized by redness (erythema), papules, and pustules, especially on the forehead, nose, cheeks, and chin. Although no specific cause of acne rosacea has been identified, it is associated with heightened sensitivity to the sun. The condition may come and go and is typically exacerbated by hot drinks and alcohol. It may result in hypertrophy of the sebaceous glands, with thickening of the nose (rhinophyma), a permanent development. Eye irritation, including conjunctivitis, may be present. There is also a genetic tendency to develop rosacea, with light-skinned populations especially susceptible.
Clinical Manifestations
Acne may present with a variety of lesions on one individual. Lesions can include blackheads, whiteheads, nodules, pustules, cysts, and scars. Lesions are commonly over the face, back, and shoulders.
In women, acne may increase before or during the menstrual period when estrogen levels are lowest.
With rosacea, the face may turn bright red with even limited sun or alcohol exposure, and papules and pustules may develop.
Complications
Scarring may occur in severe cases of acne.
Self-esteem may be affected even with less severe conditions.
Rhinophyma may occur with rosacea.
Treatment
Topical agents such as benzoyl peroxide and retinoic acid (vitamin A, Retin A) are used to dry and to peel the skin. This effect increases cell turnover and opens the follicles and facilitates the movement of sebum to the skin. Benzoyl peroxide also works to eliminate P. acnes. Retin A may lead to excessive drying and redness of the skin, and individuals using Retin A must avoid unprotected sun exposure. Pregnant women are advised to avoid using Retin A.
Antibacterial soap may reduce bacterial contamination of the skin.
Topically applied antibiotics, often in combination with benzoyl peroxide, may be prescribed for use once or twice a day. Topical antibiotics, usually tetracycline, erythromycin, or clindamycin, work to reduce P. acnes proliferation. Treatment with this regimen typically takes at least 4 weeks to induce notable improvement.
Oral low-dose antibiotic therapy (e.g., tetracycline, doxycycline) may be administered to reduce bacterial proliferation in the follicle. Antibiotic therapy requires several weeks to be effective and may induce photosensitivity. Oral tetracycline damages developing teeth; therefore, it is
contraindicated in pregnant women or women planning to get pregnant. Tetracycline is also a drug of choice for rosacea.
Birth-control pills containing estrogen can reduce sebum production. They may be used to treat acne in girls and women.
Systemic 13-cis-retinoic acid (isotretinoin) may be used for severe nodular cystic acne. This drug can cause severe birth defects and should not be used by young women who are or may get pregnant. Males likewise should avoid impregnating a partner while on isotretinoin