Section 6. Disorders of the Sebaceous and Apocrine Glands

Acne vulgaris is the most common skin disorder in adolescents. It is a multifactorial disease characterized by chronic inflammation of the pilosebaceous units of certain areas (face and trunk) that manifests as comedones, papules, nodules, cysts, or papulopustules, often but not always followed by scars.

Insight

Neonatal acne (presenting between the age of 2 weeks and 3 months of life) is common and self-limited. Infantile acne (presenting between 3 and 6 months of age) may foreshadow more severe acne later in life.

Epidemiology

Age Typically begins at puberty.

Gender M > F, and males tend to be more severely affected.

Prevalence Approximately 85% of 12- to 24-year-old patients have some form of acne. Forty to fifty million people in the United States have acne annually.

Drugs Systemic corticosteroids, iodides, bromides, anticonvulsants (phenytoin and trimethadione), and antidepressants (lithium) can exacerbate acne in susceptible patients.

Genetic Aspects Family history may be a predictor of acne severity.

Other Factors Emotional stress, lack of sleep, and menses can cause exacerbations. Pressure or rubbing of skin can cause local outbreaks (acne mechanica). Androgen excess can also lead to severe refractory cases.

Pathophysiology

The lesions of acne (comedones) are the result of genetics (increased number and size of sebaceous glands), hormones (androgens), bacteria (Propionibacterium acnes), and the inflammatory response in the pilosebaceous unit. Androgens stimulate sebaceous glands to produce larger amounts of sebum; bacteria contain lipase that converts lipids into fatty acids. Both excess sebum and fatty acids cause the corneocytes to block the pilosebaceous unit and comedones are formed. If the comedo is open to the skin surface, the oxidized keratin protrudes and darkens in color (blackheads). Closed comedones may break under the skin and the contents (sebum, lipid, fatty acids, keratin) enter the dermis, provoking inflammation (papules, pustules, nodules). Rupture plus intense inflammation may lead to scarring.

History

Duration of Lesions Weeks to months.

Season Worse in fall and winter.

Symptoms Itching or pain in lesions (especially nodulocystic type).

Physical Examination

Skin Lesions

Type

• Comedones: open comedones are “blackheads,” closed comedones are “whiteheads” (Fig. 6-1A).
• Papules with or without inflammation, pustules (Fig. 6-1B).
• Nodules, noduloulcerative lesions, 2 to 5 cm in diameter.
• Postinflammatory hyperpigmentation.
• Scars. Atrophic depressed (often pitted) or hypertrophic (keloid) scars.

Shape Round; nodules may coalesce to form linear plaques.

Arrangement Isolated single lesion (e.g., nodule) or scattered discrete lesions (papules, cysts, nodules).

Sites of Predilection Face, chest, back, shoulders.

Differential Diagnosis

Acne has many morphologies and thus has a large differential including milia, miliaria, candidal infections, pustulosis, sebaceous hyperplasia, appendageal tumors, folliculitis, keratosis pilaris, and rosacea.

Course and Prognosis

Acne may have a mild self-limited course or a protracted recurrent course that may persist into adulthood.

Laboratory Studies

Persistent acne may be a result of XYY chromosomal genotype or endocrine disorders such as polycystic ovarian syndrome, hyperandrogenism, hypercortisolism, or precocious puberty. Patients suspected of hyperandrogenism should have screening tests including serum levels of total and free testosterone (to detect ovarian excess androgen), detects adrenal excess androgen (DHEAS), and 17-hydroxyprogesterone (detects adrenal excess androgen). Patients suspected of hypercortisolism should have an AM serum cortisol checked.

Management

Patients and parents should be educated on factors that may aggravate acne:

1. 1. Repeated pressure, leaning, touching, or scrubbing acne-prone areas.

   2. Occlusive garments such as headband, chinstraps, helmets, and hats.

   3. Oil and grease in moisturizers, face creams, makeup, or hair products.

   4. Greasy-air-filled environments in fast-food kitchens.

   5. Squeezing or popping pimples can lead to scarring.

   6. Certain medications taken for other problems (e.g., oral contraceptives, lithium, hydantoin, topical, and systemic steroids).

   7. Emotional stress.

   8. Hormonal changes with menses.

   9. Foods typically do not play a major role, but some people find specific foods trigger their acne and are helped by avoiding them.

Mild

1. 1. Topical antibiotics such as clindamycin or erythromycin help decrease bacterial load and inflammation.

   2. Topical benzoyl peroxide also suppresses P. acnes and microbial resistance has not been reported.

   3. Topical salicylic acid or α-hydroxy acid preparations can help slough the outer layer of skin preventing follicular blockage.

   4. Topical retinoids (tretinoin, adapalene, tazarotene) are effective, but require detailed instructions and gradual increases in concentration. Retinoids help the skin turn over more rapidly to decrease possible follicular blockage and rupture.

   5. Topical sulfur is antimicrobial and keratolytic.

Moderate to Severe

1. 1. Oral antibiotics such as tetracycline (25–50 mg/kg/d divided bid not to exceed 3 g/d), erythromycin (30–50 mg/kg/d divided bid, not to exceed 2 g/d), doxycycline (5 mg/ kg/d divided qid–bid, not to exceed 200 mg/d), or minocycline (2 mg/kg/d, not to exceed 200 mg/d) are probably the most effective and can be tapered to lower doses once the acne is under good control. Minocycline, tetracycline, and doxycycline should only be used in children older than 8 years because of potential permanent staining of growing teeth. Erythromycin should not be taken with astemizole, terfenadine, or cisapride, and can also increase theophylline levels. All oral antibiotics also theoretically interfere with the efficacy of oral contraceptives (OCP) and backup contraceptive methods should be used.

   2. In females, acne can be controlled with oral contraceptives. Three OCPs are currently FDA-approved for the treatment of acne:

   • (1) A triphasic OCP with norgestimate (preogestin)-ethinyl estradiol 35 μg (Estrostep).
   • (2) Graduated ethinyl estradiol (20–35 μg) with norethindrone acetate (Ortho-tri-cyclin).
   • (3) 20 mg of ethinyl estradiol with 3 μg drospirenone (Yaz or Yasmin).

   In Europe and Canada, 2 mg cyproterone (a progestational antiandrogen) with ethinyl estradiol (35 or 50 μg) is available (Diane-35) and highly effective.

   3. Oral spironolactone blocks androgen receptors and 5α-reductase. Doses or 50 to 100 mg daily can reduce sebum production and improve acne. Patients taking spironolactone should be cautioned regarding hyperkalemia and hypotension side effects.

   4. Oral 13-cis-retinoic acid (isotretinoin) is highly effective for cystic acne. As retinoids are teratogenic, it is necessary that female patients have a pretreatment pregnancy test and they must be on two forms of birth control at least 1 month prior to beginning treatment, throughout treatment, and for 1 month after treatment is discontinued. Furthermore, a patient must have a negative serum pregnancy test within the 2 weeks prior to beginning treatment. Dosage: 0.5 to 2 mg/kg/d with meals for a 15- to 20-week course, which is usually adequate. Approximately 30% of patients require a second course. Careful monitoring of the blood is necessary during therapy, especially in patients with elevated blood triglycerides before therapy is begun. Currently, isotretinoin use is regulated by the iPLEDGE program which requires prescriber, patient, and pharmacist to sign off electronically on a monthly basis during treatment.

   Common side effects of isotretinoin include xerosis, dry oral and nasal mucosa, xerophthalmia, myalgias, and skeletal hyperostoses. Serious side effects include idiopathic intracranial hypertension (pseudotumor cerebri), depression, suicidal ideation, and teratogenicity.

   5. Incising and expressing comedones can improve cosmetic appearance transiently.

   6. Intralesional steroids for deep and inflamed lesions can quickly help them resolve.

   7. Acne scarring can be treated with dermabrasion, laser resurfacing, chemical peels, filler substances, or punch grafting.

Infantile acne is acne that appears when the infant is 3 to 4 months or older. Unlike neonatal acne, which is short-lived and self-resolving, infantile acne can be more long-standing, refractory to treatment, and predictive of a more severe resurgence of acne at puberty.

Epidemiology

Age 3 to 4 months or <8 years.

Gender M > F.

Genetics More common in children with a family history of acne.

Physical Examination

Skin Findings

Type Comedones (closed and open), papules, pustules, and occasional cystic nodules (Fig. 6-2).

Distribution Face.

Course and Prognosis

Infantile acne has a variable course. In some individuals, it clears spontaneously after a few weeks. In others, especially cases with earlier onset and a family history of acne, the course is more protracted and severe with likely resurgence at puberty. Persistent severe infantile acne should be worked up for an endocrine abnormality, and an elevated level (>0.5 μg) of 17-ketosteroids in a 24-hour urine collection is suggestive of gonadal and adrenal hyperactivity.

Management

Infant skin is usually very sensitive, and mild cases of infantile acne can be managed with gentle cleansing. More severe cases may require topical medications, but they should be used sparingly and in low doses to the affected areas qid–bid to avoid overdrying and irritating the skin. Topical medications include:

1. 1. Topical antibiotics such as clindamycin or erythromycin help decrease bacterial load and inflammation.

   2. Topical benzoyl peroxide also suppresses P. acnes with no risk of resistance.

   3. Topical sulfur is antimicrobial and keratolytic.

   4. Topical salicylic acid, hydroxy acid preparations, or retinoids are effective, but may be too irritating in this age group.

Periorificial dermatitis is an acnelike eruption on the perioral, periocular, or rarely anogenital skin characterized by discrete erythematous papules that often coalesce, forming inflammatory plaques.

Insight

Unlike acne, periorificial dermatitis lacks true comedones (blackheads and whiteheads) and can be thus differentiated.

Epidemiology

Age Any age. Seen in both young children and adults, aging from 15 to 40 years.

Gender F > M.

Etiology Unknown.

Other Factors May be precipitated or markedly aggravated by potent topical (fluorinated) corticosteroids, inhaled or nebulized corticosteroids, and/or cosmetics.

History

Duration of Lesions Weeks to months.

Skin Symptoms Occasional itching or burning.

Physical Examination

Skin Lesions

Type Initial lesions are erythematous papules. Confluent plaques may appear eczematous with erythema and scale (Fig. 6-3).

Color Pink to red.

Size 1- to 2-mm papules coalescing into larger plaques.

Arrangement Papules are irregularly grouped.

Distribution Initial lesions usually around mouth and nasolabial folds, rarely in the anogenital area.

Differential Diagnosis

The diagnosis of periorificial dermatitis is made clinically and needs to be differentiated from contact dermatitis, atopic dermatitis, seborrheic dermatitis, rosacea, acne vulgaris, and sarcoidosis.

Course and Prognosis

Appearance of lesions is usually subacute over weeks to months. Periorificial dermatitis is, at times, misdiagnosed as an eczematous or seborrheic dermatitis and treated with a fluorinated corticosteroid preparation, which worsens the condition. Untreated, periorificial dermatitis fluctuates in activity over months to years. With treatment for several months, mild recurrences can occur but clear easily.

Management

Treatment should begin by eliminating any topical agents that may be aggravating or precipitating the condition, such as fluorinated corticosteroids, toothpaste with fluoride, or cosmetics. Often, just by eliminating the offending agent, the rash will clear. More refractory cases may require topical medications sparingly to the affected areas:

1. 1. Topical antibiotics such as clindamycin, erythromycin, or metronidazole can help decrease inflammation.

   2. Topical benzoyl peroxide is antimicrobial.

   3. Topical sulfur preparations are antimicrobial and keratolytic.

   4. Topical salicylic acid, hydroxy acid, or retinoids can help but must be used sparingly to avoid irritation.

   5. Many cases require a course of oral antibiotics such as a macrolide or tetracycline.

Hidradenitis suppurativa is a chronic disease of apocrine-gland-bearing skin (typically the axillae, inguinal folds, and anogenital region) that results in recurrent suppurative nodules (boils), draining sinus tracts, and cribriform scarring of the involved areas.

Insight

Incision and drainage of these lesions is almost completely unhelpful save for temporary pain and pressure relief; they tend to refill immediately upon healing.

Synonyms Apocrinitis, hidradenitis axillaris, acne inversa, Verneuil’s disease, pyoderma fistulans significa.

Epidemiology

Age Develops at or soon after puberty.

Gender F:M 5 3:1.

Race Affects blacks more than whites.

Incidence Affects 1% of the population.

Etiology Predisposing factors: Obesity, genetic predisposition to acne, occlusion of the follicular infundibulum, follicular rupture, and secondary bacterial infection.

Pathophysiology

Sequence of changes: (1) keratinous plugging of the apocrine duct, (2) dilatation of apocrine duct and hair follicle, (3) severe inflammatory changes limited to a simple apocrine gland, (4) bacterial growth in dilated duct, (5) ruptured duct/gland results in extension of inflammation/infection, (6) extension of suppuration/tissue destruction, and (7) ulceration and fibrosis, sinus tract formation.

History

Intermittent pain, abscess formation in axilla(e), and/or inguinal area. The area under the breast may also be affected, and associated severe cystic acne of the face, chest, and back is also seen. The “follicular occlusion tetrad” labels the common association of hidradenitis suppurtiva with acne congloblata, dissecting cellulitis of the scalp, and pilonidal sinus.

Physical Examination

Skin Findings

Type of Lesion Inflammatory nodule or abscess that drains purulent or seropurulent material. Eventually, sinus tracts form and result in fibrosis and “bridge,” hypertrophic, and keloidal scars (Fig. 6-4).

Size 0.5- to 1.5-cm nodules.

Color Erythematous nodules.

Palpation Lesions moderately to exquisitely tender. Pus may be expressed from abscesses.

Distribution of Lesions Axillae, under breasts, inguinal folds, anogenital areas.

General Findings

Often associated with obesity. Associated with severe cystic acne of the face (acne conglobata), chest, or back.

Differential Diagnosis

The diagnosis of hidradenitis suppurativa is made clinically by the characteristic distribution of the rash and by the resultant cribriform scarring. Early disease may be confused with furunculosis, lymphadenitis, ruptured tricholemmal cysts, cat scratch disease, or tularemia. Late disease can resemble lymphogranuloma venereum, donovanosis, scrofuloderma, actinomycosis, or the sinus tracts and fistulae associated with ulcerative colitis and regional enteritis.

Laboratory Examinations

Bacteriology Staphylococcus aureus or streptococci are organisms that commonly secondarily infect skin lesions; usually cultures of the lesions or pus reveal normal skin flora.

Dermatopathology Early: keratin occlusion of apocrine duct and hair follicle, ductal/tubular dilatation, and inflammatory changes. Late: abscesses followed by destruction of apocrine/eccrine/pilosebaceous apparatus, fibrosis, and scarring.

Course and Prognosis

Spectrum of disease is very broad. Many patients have mild involvement. The disease sometimes undergoes a spontaneous remission with age (more than 35 years). In some individuals, the course can be relentlessly progressive, with marked morbidity related to chronic pain, draining sinuses, and scarring.

Treatment

1. 1. Weight reduction and methods of decreasing friction and moisture are helpful. Loose clothing/undergarments, absorbent powders).

   2. Antibacterial soaps and topical clindamycin has been useful to reduce S. aureus carriage and secondary infection.

   3. Intralesional triamcinolone (3–5 mg/mL) into early inflammatory lesions can hasten resolution and decrease pain.

   4. Systemic steroids, cyproterone acetate, ethinyl estradiol, isotretinoin, acitretin, finasteride, cyclosporine, TNF-α, and TNF-botox have been used in refractory severe cases with limited success.

   5. With extensive, chronic disease, complete excision or CO2 laser ablation of involved axillary tissue or inguinal area may be required.