Primary Care Visit Report
A 34-year-old female with no prior medical history presented with acne on her face. The patient was put on oral contraceptive (OCP) at the age of 16 for cystic acne and remained on OCP for the following 17 years, during which time her acne was well controlled. She discontinued OCP 1 year prior to visit because she wanted to get pregnant. Her acne flared about 8 months later. The acne was around her jawline, on her back, posterior neck, and behind her ears. She had not been using any acne medication as she found it dried her skin and made it flakey.
Vitals were normal. On exam, there was cystic acne on the patient’s lower jaw and upper back.
She was treated with combination benzoyl peroxide/clindamycin gel (Benzaclin) 1–5 % twice daily. Retinoids were avoided due to the patient’s desired pregnancy. The patient followed up 3 weeks later and her acne was improving on the Benzaclin; however, she noted her skin was drying and she had one additional pustular acne outbreak while on the medication. The patient was continued on Benzaclin only due to her desired pregnancy.
Discussion from Dermatology Clinic
Differential Dx
• Acne vulgaris
• Perioral dermatitis
• Folliculitis
• Rosacea
Favored Dx
Patient age and lesion distribution along the chin and jawline are suggestive of mild to moderate adult-onset, hormonal dominant acne.
Overview
Acne vulgaris is the medical term for common acne. It describes an extremely common condition affecting the pilosebaceous unit which consists of hair, hair fol-licle, arrector pili muscles, and sebaceous gland—a gland which secretes a lubri-cating oily matter called sebum into the hair follicle. Acne occurs when these hair
follicles become clogged and represents a broad spectrum of lesions and severity. Its cause is multifactorial, with genetic predisposition, hormonal concentrations, change in quantity and quality of sebum secretion, colonization by the bacteria Propionibacterium acnes, and disrupted desquamation of keratinocytes all playing a role in its pathogenesis.
Acne is one of the most common dermatological complaints, with more than 80 % of adolescents and adults developing acne at some point in their lives [1]. Teenage acne is more common in males than females; however, in age groups of 20 years and older, females are more often affected [2]. Recent data suggest that adult acne is becoming more common [2–4].
Presentation
The first presentation of acne usually coincides with the onset of puberty when androgens, especially testosterone and DHEA, stimulate sebaceous activity [5]; however, preadolescent acne is not uncommon. During adolescence, mixed come-dones (whiteheads and blackheads) tend to initially appear in the centrofacial area (forehead, nose, chin), and later may spread to areas of high sebaceous gland activ-ity, such as the remainder of the face, the upper arms, and the upper trunk.
A variety of lesions may present with acne and are classified as inflammatory or noninflammatory type. The precursor to all lesions is the microcomedone, which occurs when desquamated keratinocytes and sebum accumulate and clog pores (representing hair follicles). Microcomedones can unclog on their own, or evolve to become visible comedones. Comedones are noninflammatory lesions that are clas-sified as open (“blackheads”) when they are pigmented due to oxidation of cellular debris, or closed (“whiteheads”), which contain unoxidized material.
When comedones are left untreated, bacterial and hormonal factors, and poor exfoliation can lead to the proliferation of inflammatory lesions such as pustules, papules, cysts and nodules. Papules are inflamed comedones, pustules feature visible pus, cysts are large, inflamed pus-filled lesions, and nodules are large, firm bumps. Inflammation commonly occurs due to the colonization of follicles by Propionibacterium acnes, with the degree of inflammation variable depending on individuals’ immuno-sensitivity to the pathogen. Additionally, inflammatory lesions occur when the follicle wall ruptures and the surrounding tissue becomes inflamed.
Lesions with severe inflammation carry the biggest risk of scarring, dyspigmen-tation, keloid formation, and development of true cysts.
Workup
Acne is diagnosed by clinical presentation. Blood tests to check for hormone levels (especially hyperandrogenism) are only indicated if patients demonstrate signs of an endocrine disorder (e.g., polycystic ovary syndrome most commonly, or
Cushing’s syndrome), for example excessive body hair (hirsutism), or irregular/infrequent menstrual periods. The recommended blood panel includes testosterone (free and total), LH, FSH, DHEA, and 17-hydroxyprogesterone. Abnormal test results warrant a referral to an endocrinologist.
Clinical assessment of acne should include severity grading. Although there is no standard scale to measure acne severity, some consensus has been achieved as to important aspects for consideration. When evaluating severity, physicians should consider the number and type of lesions, extent of distribution and involvement on facial and extrafacial sites, severity of inflammation, presence of pigmentary changes and scarring, and psychosocial effects on patient [5, 6]. These factors should help to classify an individual’s acne as mild (i.e., minimal number of indi-vidual lesions), moderate (i.e., widespread whiteheads and blackheads with few cysts or nodules), or severe (i.e., scarring, nodules and/or cysts). It is important to ascertain from the patient whether the acne at the time of visit represents an average day, or whether they are experiencing a flare, as that may help dictate treatment.
Treatment
Acne medications account for 12.6 % of the total cost of treating skin disorders globally [7]. Perhaps for that reason many different medications, including combi-nation therapies, have been developed to treat acne. Left untreated, acne may spon-taneously improve during late teenage years and early adulthood [2]; however, this carries a risk of scarring and is not always the case as acne can present for the first time, or persist, into adulthood. Treatment should focus on preventing the appear-ance of new lesions.
Acne can be treated with topical, systemic, and laser therapies. Topical treatments aim to decrease sebum production and reduce bacterial colonization, calm inflamma-tion, and normalize the keratinization process [8]. Topicals generally fall into broader categories of antimicrobials (nonspecific activity against microbes), antibiotics (targeted activities against specific bacteria), and retinoids. Topical benzoyl peroxide (BPO) is a cornerstone of acne treatment that has antimicrobial, anti- inflammatory, and keratolytic effects. This can be used in combination with topical antibiotics or retinoids if monotherapy is inadequate; however, patients should be closely monitored for any irritation if both BPO and retinoids are used. Prescription azelaic acid gel or cream, and sodium sulfacetamide are further examples of antimicrobials that are use-ful in acne treatment, with the latter providing additional anti- inflammatory proper-ties. All of the above topical treatments have demonstrated efficacy in treating mild acne [1, 8].
Topical retinoids are a class of medications that have been successful in treating comedonal acne. These include tretinoin, tazarotene, and adapalene. They have comparable efficacies; however, tazarotene demonstrates superiority in additionally reducing the number of inflammatory lesions and treating post-inflammatory hyper-pigmentation [8]. Providers should note that tretinoin is rendered inactive in the presence of UV light, or oxidative products like benzoyl peroxide. When initiating retinoids, patients should be advised of potential irritation and initiate therapy slowly, by using the products every other day for the first week or 2. Although the systemic absorption of topical retinoids is minimal, they are strongly contraindi-cated in pregnancy. When retinoids alone are insufficient treatment, they can be used in conjunction with benzoyl peroxide (with BPO applied in the morning and retinoid at night in order to avoid retinoid inactivation by BPO), or topical antibiotics.
The primary topical antibiotic that is used in treating acne is clindamycin. Bacterial resistance has rendered the use of topical and oral erythromycin obsolete. Still, clindamy-cin should not be used as a monotherapy, and should be used in conjunction with ben-zoyl peroxide or retinoids in order to improve efficacy and minimize resistance.
Systemic therapies for acne include oral antibiotics, hormonal treatments, and isotretinoin. If topical treatments are not well tolerated, producing inadequate results, or if inflammatory lesions are numerous and severe, oral antibiotics can be prescribed. Doxycycline and minocycline are best tolerated and preferred over tetracycline due to decreased bacterial resistance [9]. A more recent approach with some demonstrated efficacy has been the use of subantimicrobial doses of doxycycline (20 mg twice daily for 6 months) with decreased bacterial resistance observed [9, 10].
Hormonal treatment for female acne includes oral contraceptives and spirono-lactone. Oral contraceptives that contain moderate to high levels of estrogen, e.g., Ortho Tri-Cyclen, Yasmin, and Estrostep, minimize sebaceous gland activity and can help control acne after 3–4 months of use [1, 9]. Spironolactone is an anti- androgen that is effective in 25–200 mg dosing [1, 7, 9]. Our practice generally prescribes doses of 50–100 mg daily, and 25 mg is sufficient for patients with milder cases of acne. Spironolactone is trialed in adult female patients with typical presentations of cystic acne along the jawline, as a treatment for the acne. If blood tests are performed and indicate abnormal hormone levels, they are referred to an endocrinologist for treatment of the hormone imbalance.
Oral isotretinoin is FDA-approved for severe, recalcitrant, nodular acne that has failed a more conservative treatment approach. It is the only known possible cure for acne, with cure rates up to 40 % [1, 9]. Isotretinoin is a known teratogen and thus patients in the USA need to be registered through the federally regulated iPledge program. Due to strict oversight of management, patients requiring isotretinoin therapy should be referred to a dermatologist for administration.
Laser and photodynamic therapy are increasingly popular alternatives to topical and oral acne treatment as they can help avoid some unwanted side effects. Fractional CO2 lasers have been found to show up to 83 % improvement for some acne scars [11, 12], and pulsed dye lasers can improve inflammatory acne and reduce lesion counts [13].
In addition to the various treatment options reviewed above, any discussion of acne treatment warrants a mention of the historically controversial role of diet in acne. Randomized controlled studies on the topic are lacking, although recent research suggests foods with a high glycemic index, such as sugars and simple carbohydrates, and dairy (particularly skim milk) may play a role in its exacerbation [4, 14]. It should also be noted that smoking and stress can worsen acne as well [1, 3, 7].
Out of the treatment options discussed, the most appropriate course for the patient in this case was continuation of Benzaclin, as she was trying to become pregnant.
Follow-Up
Patients should be advised that most acne treatments require weeks to provide nota-ble improvement, generally between 5 and 6 weeks to 3 months [7, 8]. Providers should follow up with patients after 4 weeks to assess improvement, as well as to discuss any unwanted side effects like dryness, or irritation. Treatment can be scaled back to every other day if there is excessive dryness or irritation. Alternatively medications like topical retinoids may be applied with moisturizer to help counter some of the side effects. If topical retinoids are well tolerated, dosages can be increased incrementally. If no improvement is noted on topical medications alone, patients can trial the addition of oral antibiotic therapy.
Questions for the Dermatologist
– What is the first line of treatment for acne?
First line therapy for acne would be an antimicrobial medication, most commonly an over-the-counter product that contains benzoyl peroxide. A first line prescription would be topical clindamycin. There are also prescription products that combine both benzoyl peroxide and clindamycin, which would make a good initial therapy.
– Which acne treatments are safe during pregnancy?
There are only two Category B medications available for acne treatment that are generally regarded as safe for use in pregnancy. Those are topical azelaic acid and clindamycin. There are mixed opinions about the use of benzoyl peroxide because animal studies have not been conducted; our practice doesn’t recommend its use in pregnancy.
– Which treatments are definitely not safe if a patient is trying to conceive?
Our practice would not start a patient who is actively trying to get pregnant on oral isotretinoin therapy. For other oral medications, patients should stop immediately once they learn they are pregnant. We discontinue all oral medications upon conception rather than avoid these entirely.
– Are there specific birth control pills that are better at treating acne?
Estrogen-dominant oral contraceptives are preferred for treating acne.
– What are the different kinds of acne and how are they best described?
The main classification of acne is inflammatory versus noninflammatory. Inflammatory acne features red, juicy pimples (also known as pustules), or red nodules. This type of acne is best treated with antimicrobial medications. Noninflammatory acne features open and closed comedones, which are blackheads and whiteheads, respectively. These are best treated with the retinoid family of medications.
References
1. Nguyen TT. Acne treatment: easy ways to improve your care. J Fam Pract. 2013;62(2):82–9.
2. Collier CN, Harper JC, Cafardi JA, Cantrell WC, Wang W, Foster KW, Elewski BE. The prev-alence of acne in adults 20 years and older. J Am Acad Dermatol. 2008;58(1):56–9.
3. Albuquerque RGR, Rocha MAD, Bagatin E, Tufik S, Andersen ML. Could adult female acne be associated with modern life? Arch Dermatol Res. 2014;306:683–8.
4. Mahmood SN, Bowe WP. Diet and acne update: carbohydrates emerge as the main culprit. J Drugs Dermatol. 2014;13(4):428–35.
5. Webster GF. Clinical presentation of acne. In: Zeichner J, editor. Acneiform eruptions in der-matology: a differential diagnosis. New York: Springer Science + Business Media; 2014.
6. Tan J, Wolfe B, Weiss J, Stein-Gold L, Bikowski J, Delrosso J, Webster GF, Lucky A, Thiboutot D, Wilkin J, Leyden J, Chren MM. Acne severity grading: determining essential clinical com-ponents and features using Delphi consensus. J Am Acad Dermatol. 2012;67:187–93.
7. Howard DM. Adult acne: overview and case study. Nurse Pract. 2014;39(8):12–5.
8. Kober MM, Bowe WP, Shalita AR. Topical therapies for acne. In: Zeichner J, editor. Acneiform eruptions in dermatology: a differential diagnosis. New York: Springer Science + Business Media; 2014.
9. Kardos Garshick M, Kimball A, Drake L. Systemic therapies for acne. In: Zeichner J, editor. Acneiform eruptions in dermatology: a differential diagnosis. New York: Springer Science + Business Media; 2014.
10. Skidmore R, Kovach R, Walker C, Thomas J, Bradshaw M, Leyden J, Powala C, Ashley
R. Effects of subantimicrobial-dose of doxycycline in the treatment of moderate acne. Arch Dermatol. 2003;139(4):459–64.
11. Majid I, Imran S. Fractional CO2 laser resurfacing as monotherapy in the treatment of atrophic facial acne scars. J Cutan Aesthet Surg. 2014;7(2):87–92.
12. Bhate K, Williams HC. What’s new in acne? An analysis of systematic reviews published in 2011–2012. Clin Exp Dermatol. 2014;39(3):273–7.
13. Erceg A, de Jong EM, van de Kerkhof PC, Seyger MM. The efficacy of pulsed dye laser treat-ment for inflammatory skin diseases: a systematic review. J Am Acad Dermatol. 2013; 69(4):609–15.
14. Burris J, Rietkerk W, Woolf K. Acne: the role of medical nutrition therapy. Acad Nutr Diet. 2013;113(3):416–30.