Etiology And Pathogenesis

An appreciation of the pathogenesis of acne facilitates a better understanding of targeted treatments. Acne develops in the pilosebaceous unit (Figure 125-1). There are four primary factors involved: abnormal keratinization, increased sebum production, proliferation of Propionibacterium acnes bacteria, and inflammation. With the onset of adrenarche, there is an increase in androgen production and a resultant increase in sebum secretion. Each sebaceous gland has a different threshold of androgen sensitivity, effecting an individually unique response to puberty. Simultaneously, there is increased proliferation of keratinocytes and decreased desquamation. The accumulation of sebum and keratinocytes leads to the formation of the microcomedo, the precursor to acne lesions. P. acnes, a normal skin inhabitant, thrives in this lipid-rich environment. The organisms release chemotactic factors, setting up an inflammatory response. Depending on the contribution of each primary factor, a microcomedo can evolve into a closed comedo (whitehead), open comedo (blackhead) (Figure 125-2), or an inflammatory pustule, papule, or nodule if the sebum, keratin, and microorganisms, with the accumulation of inflammatory cells, rupture into the dermis.

Figure 125-1 Pilosebaceous unit.

Figure 125-2 Acne.

Extrinsic factors can exacerbate acne. Although many patients erroneously believe that acne is caused by not keeping the skin clean, cleansing the face helps clear the skin of surface lipids but does not help prevent acne. Furthermore, aggressive cleansing with washcloths or loofahs as well as manipulation and squeezing of lesions can aggravate them by provoking an inflammatory response and can also lead to scarring. Additionally, cosmetics, hair preparations, and occlusive clothing can all worsen facial and body acne. Stress can also lead to an increase in androgenic hormones and thus exacerbate acne.

There is little evidence to show that particular foods worsen acne. One study has shown an increased self-reported rate of acne during adolescence with consumption of milk. However, this relationship was thought to be secondary to acnegenic hormones and bioactive molecules in milk. Further study is needed in this area to prove or disprove any possible association.

Climate also seems to affect acne, with summer attenuating symptoms, yet this correlation is confounded by the fact that summertime generally harbors less stress, which has been associated with acne flares.

Clinical Presentation

Acne is a disease that can be seen in the first year of life, early childhood, the prepubertal period, and puberty. Neonatal cephalic pustulosis, formerly referred to as neonatal acne, appears in the first 3 months after birth and usually resolves in 1 to 3 months. In neonates, it is extremely important to exclude other bacterial, viral, or fungal causes, but a physician should also consider milia, erythema toxicum neonatorum, transient neonatal pustulosis, and sebaceous gland hyperplasia. Infantile or toddler acne is less common and usually presents between 3 and 6 months of life and can last 1 to 2 years. This is not typically associated with precocious puberty or a hormonal imbalance but needs to be considered in conjunction with a thorough history and physical examination. See Table 125-1 for a comparison of acne seen in neonates and toddlers. Acne can present in any location where there are sebaceous glands. In addition to the face, it is frequently found on the neck, upper chest, shoulders, and back (see Figure 125-2). There are multiple classification systems used to talk about acne, but a description of the lesions and their locations is most helpful. The resolution of acne may leave postinflammatory changes that usually resolve themselves but may take weeks to months, especially in darker pigmented patients. Moderate and severe acne can leave permanent scars.

The diagnosis of acne is relatively straightforward. Typical acne includes comedones, papules, pustules, and nodules in the distribution of the face, upper back, and chest. Acne that begins at an abnormal age, particularly severe acne, acne accompanied by an abnormal growth history or virilization, or acne that is recalcitrant to treatment, should be further evaluated. The physician may want to consider an underlying disorder, such as premature adrenarche, precocious puberty, Cushing’s syndrome, congenital adrenal hyperplasia, and gonadal or adrenal tumors, or an alternative diagnosis if the lesions are not typical (Box 125-1). Perioral dermatitis and facial angiofibromas are shown in Figure 125-3.

Figure 125-3 Perioral dermatitis and facial angiofibromas.

Management

The initial evaluation of a patient with acne begins with a complete history. Most patients have no relevant history of systemic disease, but particular attention must be paid to a history or physical examination that is consistent with signs of endocrine dysfunction in patients with an atypical age of presentation and lesion morphology. Hyperandrogenism can cause abnormal weight gain, menstrual irregularities, hirsutism, and signs of insulin resistance such as acanthosis nigricans. Elevated cortisol levels can cause hypertension, striae, or a buffalo hump. Signs of virilization such as decreased breast size, alopecia, and clitoromegaly can be attributable to an underlying adrenal or ovarian tumor. In addition, acne-associated spondyloarthropathies have been associated with severe acne, including acne fulminans, PAPA (pyogenic arthritis, pyoderma gangrenosum, and acne), and SAPHO (synovitis, acne, pustulosis, hyperostosis, osteomyelitis) syndrome. A complete medication history must also be taken. The physical examination should focus on the type and location of the lesions, postinflammatory changes, and scarring. In cases with red flags for an underlying systemic disease, laboratory evaluation may include measuring levels of free and total testosterone, DHEA-S (dehydroepiandrosterone sulfate), follicle-stimulating hormone, luteinizing hormone, 17 α-hydroxyprogesterone, and prolactin. Some experts also recommend an adrenocorticotropic hormone (ACTH) stimulation test. Bone age is a useful radiologic study for hyperandrogenism. A referral to an endocrinologist is also appropriate.

Treatment of acne should begin with good skin hygiene. Patients should be instructed to use nonirritating, noncomedogenic cleansers, which should be applied gently without scrubbing or using any harsh washing materials, as well as noncomedogenic moisturizers and sunscreen. Patients should be counseled that acne takes weeks to clear, and close follow-up should be arranged to assess the efficacy of treatment, side effects, and barriers to compliance. Often, teenagers will give up too early on therapy that would have been successful if they had been counseled that it will take weeks for full effect.

In general, when choosing a topical treatment, the vehicle should complement the patient’s skin type and be realistic for its distribution of placement. For example, whereas gels may provide some drying action, creams are less likely to dry but more likely to leave a white film in dark-skinned patients.

See Figure 125-4 for an acne treatment algorithm for the initial management strategies for the treatment of acne.

Figure 125-4 Acne treatment algorithm.

Future Directions

Determining the pathophysiology of acne has led to targeted therapies. Further understanding the molecular mechanisms of acne can lead to the development of new treatments, such as medication targeting toll-like receptors on the membranes of inflammatory cells, activated by P. acnes, and using vitamin D analogues to control sebum production. Additionally, the role of laser and light therapy in the treatment of acne is currently being studied. However, successful application of these technologies relies on a therapeutic doctor-patient relationship, individualized therapy, and adherence to treatment. Promoting adherence with medication reminders via text messages, self-monitoring with diaries, support groups, and telephone follow-up is another aspect being investigated to contribute to the successful management of acne.