The Treatment of Cystic Acne

M. G. Davis, MD, FRCPC
Department of Medicine, University of Toronto, Toronto, Canada

The Disease

Cystic acne is characterized by the formation of cysts enclosing a mixture of keratin and sebum in varying proportions. It is the most severe of the four main types of acne, which are comedonal, papular, pustular, and cystic. A patient with cystic acne usually has more than one type of lesion (polymorphous morphology) and these lesions vary in degree and severity. Conglobate acne is a severe cystic acne with nodules and suppurative lesions, and if associated with systemic symptoms is called acne fulminans.

Adolescents are especially affected by severe acne. Cystic acne may result in low self-esteem, restriction of daily activity, and could lead to clinical depression. That is why it is important to treat cystic acne aggressively when starting therapy. The goal of treatment is not only to improve the patient’s appearance, but to reduce the risk of permanent scarring.

The Cause

Acne begins with microcomedone formation. This can progress, depending on the amount of inflammation, into papular, pustular, and cystic lesions. Intrinsic factors, such as adolescence, genetic predisposition, and hormonal changes (either normal or disease-related) may cause or aggravate the problem. Extrinsic factors, such as drugs, hormones, and other environmental factors (extremes of humidity, working conditions, cosmetics, sunscreens, etc.) may also play a role in the aggravation of this disorder and therefore should be considered in the course of treatment.

Patient History

A detailed history is important since the avoidance or removal of causative factors is imperative for successful treatment. The following factors should be considered:

Age and Sex

• Adolescent patients may not require any further investigation.
• In adults, look for cofactors that may aggravate the acne.
• For female patients, menstrual history is important, especially regarding the regularity or absence of periods. Clues for polycystic ovarian syndrome (PCOS) must be sought.

Environmental Factors

• Patients who spend a lot of time swimming may be harder to treat.
• Occlusive sports clothing (e.g., helmets or other body padding) may aggravate the acne.
• Cosmetic use

Complete Drug History or History of Chemical Exposure

• Hormones, such as androgens or contraceptives, as well as systemic steroids
• Antiepileptic drugs (e.g., phenytoin (Dilantin®), as well as iodides, bromides, or chlorinated hydrocarbons)

Clinical Appearance

• The morphology of the lesion (i.e., comedones, cysts, scars, and pits)
• Look for other signs of androgen stimulation, especially in females, such as hirsutism, alopecia, oily hair, and oily complexion.
• The distribution of the acne may help determine whether clothing or equipment is a factor.

Laboratory Investigation

With the suspicion of androgen excess, check:

• Dehydroepiandrosterone sulphate (DHEAS)
• Free and total testosterone
• Luteinizing hormone (LH)
• Follicle stimulating hormone (FSH)
• Androstenedione

The Treatment:

Extrinsic Factors:

These causative factors must be removed or avoided to achieve successful treatment.

Topical Therapy:

While topical agents (i.e., benzoyl peroxides, topical antibiotics, and topical retinoids) will not penetrate deeply enough to affect change, they may still play a role in treatment, especially when there is a polymorphous morphology. Because topical antibiotics alone are frequently associated with the development of resistance, combinations of topical antibiotics and benzoyl peroxides are recommended.

Systemic Therapy:

Systemic therapy is necessary for clinical improvement because topical agents do not penetrate deeply enough to affect change. The three primary groups of drugs used to treat cystic acne are systemic antibiotics, systemic hormonal or antiandrogen therapy, and systemic retinoids.

Systemic Antibiotic Treatment

For years antibiotics were the most common treatment for cystic acne. Unfortunately, because of their overuse, there is a higher degree of resistance to these drugs and a lower degree of effectiveness. By suppressing the population of Propionibacterium acnes, they reduce the inflammatory factors that cause the formation of papules, pustules, and cysts. Two main groups of antibiotics are used: tetracyclines and erythromycins.

Dose

With regard to tetracycline or its derivatives doxycycline or minocycline, proper dosing is imperative. In most adults or fully grown teens, the proper dose should be:

• Tetracycline – 250mg, one b.i.d.
• Doxycycline – 100mg, one daily or one b.i.d.
• Minocycline – 100mg, one b.i.d.

For patients under 50kg, the dose may be lower, but if too low, it is ineffective.

Patients require treatment for 6 months–1 year or until natural remission occurs. It is also important not to reduce it from the initial full dose. (Many physicians will start tetracycline at the proper dose of 1000mg/day and will decrease to 500mg/ day by the 3rd or 4th week.) The full dose should be maintained until there is complete clearing and then the drug may be stopped after clearing has been maintained for at least 1 month. It can then be restarted for flares.

Side-Effects

Potential side-effects include photosensitivity and interactions with other drugs, such as oral contraceptives. Check for liver function periodically and advise female patients to avoid pregnancy. Erythromycins may be as effective as tetracyclines but cause no photosensitivity. They do cause more gastrointestinal upset, which may severely limit their usefulness.

Systemic Hormonal Therapy Treatment (for Women)

• Hormonal therapy can be used whether or not hormonal abnormalities have been demonstrated. The progestational antiandrogen-containing contraceptives, i.e., 2mg cyproterone acetate and 0.35ìg ethinyl estradiol (Diane-35^®), or 3.0mg drospirenone and 0.030mg ethinyl estradiol (Yasmin^®) work best. The side-effect profile is similar to other OCPs.
• Spironolactone (Aldactone^®), at a dose of 100mg daily, works well as an antiandrogen, but must be used in combination with oral contraceptives in women of childbearing age.

Side-effects for Spironolactone are rare but may include menstrual irregularities, breast tenderness, dizziness, and fatigue. Hypokalemia is extremely rare in patients who are not taking concurrent diuretics.

Systemic Retinoids (Isotretinoin) Treatment

Isotretinoin (Accutane^®) is the gold standard for treating cystic acne and the only drug that may produce a prolonged remission. Retinoids have been available for over 20 years in Canada and have a remarkable safety profile if guidelines are strictly followed and patients are monitored properly. Unfortunately, this is a drug that many family practitioners may be reluctant to prescribe, but a familiarity with the side-effects and monitoring schedules make it as simple to use as other systemic agents.

Dose

• Dosing is proportional to the patient’s weight (usually 1mg/kg of body weight per day) for generally 20 weeks.
• The ideal total dose is 120–150mg/kg.
• For patients with severe cystic acne, it is better to start at half the normal dose for 2–3 weeks and increase to the full dose over a 2–4 week period.
• The majority of patients will respond well to one course, but approximately 15%–20% will require a second course.

Side-Effects

• Serious side-effects are rare. Common side-effects, such as dry skin and eczema, are controllable with emollients or corticosteroid creams. Cheilitis may be treated with lip balms.
• Teratogenic. In Canada there is a pregnancy prevention program that must be followed just before, during, and after therapy with this drug.
  • For female patients, it is imperative to get a negative pregnancy test before starting treatment, and then have monthly tests while taking the medication, and again 1 month after stopping.
• Liver function and lipids must be checked monthly.

Communication

• It is important to sit with patients and review the information booklets in detail and then obtain written consent.
• The pregnancy prevention program must be fully discussed.