80 - ACNE VARIANTS AND ACNEIFORM ERUPTIONS Flashcards
Neonatal acne can occur in up to 20% of healthy newborns. Lesions usually appear around 2 weeks of age and resolve spontaneously within 3 months. Typically, small, inflamed papules congregate over the nasal bridge and cheeks (Fig. 80-1). Because comedo formation is absent, the pathogenesis of neonatal acne may be different than acne vulgaris. It has been shown that sebum excretion rates in newborns are transiently elevated in the perinatal period. 1 Additionally, Malassezia sympodialis, a normal commensal on human skin, may also play a role. Some reports have demonstrated positive cultures of the pustules with Malassezia spp. and improvement with ketoconazole cream.2 Although there appears to be a strong association between Malassezia spp. and neonatal acne, definite causality has not yet been proven. 3 Neonatal cephalic pustulosis presents with similar but widespread papulopustular lesions over face, scalp, upper chest and back, and shoulders.
Infantile acne presents at 3 to 6 months of age classically with open and closed comedones over the cheeks and chin. (Fig. 80-2). Papules, pustules, and nodules can also present on the face. Pitted scarring may occur even with relatively mild disease. Infantile acne is caused in part by the transient elevation of dehydroepiandrosterone (DHEA) produced by the immature adrenal gland. 4 Additionally, during the first 6 to 12 months of life, boys may also have an increased level of luteinizing hormone (LH) that stimulates testosterone production. Around 1 year of age, these hormone levels begin to stabilize until they surge again during adrenarche. As a result, infantile acne usually resolves around 1 to 2 years of age. Treatment generally consists of topical retinoids and benzoyl peroxide. Oral therapy with erythromycin, azithromycin, trimethoprim, or isotretinoin can be used in severe or refractory cases.
MIDCHILDHOOD ACNE
Mid-childhood acne is defined as appearing between 1 and 7 years of age. 5 Typically, acne is very rare in this age group because the adrenal and gonadal production of androgens should be quiescent. Therefore, any child with acne in mid-childhood should be evaluated for other signs of hyperandrogenism (pubic or axillary hair, testicular enlargement or breast development). In addition, the child’s growth chart should be compared with the bone age to determine if child’s growth is accelerated as well. If any additional abnormalities are noted, further laboratory workup for hyperandrogenism is warranted with the input of a pediatric endocrinologist.
DESCRIBE LESIONS OF ACNE CONGLOBATA
This severe form of nodular acne is most common in teenage males but can occur in either sex and into adulthood. Acne conglobata (conglobate means shaped in a rounded mass or ball) is a mixture of comedones, papules, pustules, nodules, abscesses, and scars arising in a more generalized pattern over the back, buttocks, chest, and, to a lesser extent, on the abdomen, shoulders, neck, face, upper arms, and thighs (see Fig. 78-4). The comedones often have multiple openings. The inflammatory lesions are large, tender, and dusky colored. Draining lesions discharge a foul-smelling serous, purulent, or mucoid material. Subcutaneous dissection with the formation of multichanneled sinus tracts is common. Healing results in an admixture of depressed and keloidal scars. The management of these patients is challenging. The use of isotretinoin is highly effective in these patients. However, because severe flares may occur when isotretinoin is started, the initial dose should be 0.5 mg/kg/day or less, and systemic glucocorticoids are often required either before initiating isotretinoin therapy or as concomitant therapy. Systemic tetracyclines, intralesional glucocorticoids, systemic glucocorticoids, surgical debridement, surgical incision, and surgical excision may also be required to effectively control acne conglobata.
most severe form of acne and may occur with or without systemic symptoms
Acne fulminans (also known as acute febrile ulcerative acne)
The sudden appearance of inflammatory, tender, oozing, friable plaques with hemorrhagic crusts characterizes this extreme presentation. The lesions predominate on the chest and back (Fig. 80-3) and rapidly become ulcerative and heal with scarring. The disease is reported to occur primarily in teenage boys. Systemic symptoms are often present. The patients are febrile; have a leukocytosis of 10,000 to 30,000/mm 3 white blood cells; and usually have polyarthralgia, myalgia, hepatosplenomegaly, and anemia. Bone pain is common, especially at the clavicle and sternum. Radiologic examination may demonstrate lytic bone lesions. Occasionally, there is accompanying erythema nodosum. Although this disease is often classified with acne conglobata, there are basic differences. The onset of acne fulminans is more explosive; nodules and polymorphous comedones are less common; the face is not involved as frequently, and the neck is usually spared; ulcerative and crusted lesions are unique; and systemic symptoms are more common.
Systemic glucocorticoid therapy, along with intralesional glucocorticoids, is first-line treatment for acne fulminans. Systemic glucocorticoids (prednisone 0.5–1.0 mg/kg/day) are started before isotretinoin for 2 to 4 weeks, depending on the severity of systemic symptoms, and continued during the first few weeks to months of isotretinoin therapy. The initial dosing of isotretinoin should be quite low (0.1 mg/kg/day) during the initial weeks of therapy until the inflammation is controlled. 6 The daily dose of glucocorticoids should be slowly decreased as tolerated over weeks to months. Alternately, 0.5 mg/kg/day of isotretinoin started immediately with 10 mg of prednisolone three times daily has been recommended. 7 Dapsone in conjunction with isotretinoin has been reportedly beneficial in the treatment of acne fulminans associated with erythema nodosum. 8 Cyclosporine, anakinra, and tumor necrosis factor (TNF) inhibitors have also been used in difficult cases of acne fulminans.9-11
ISOTRETINOININDUCED ACNE FULMINANS
In contrast to the de novo version, isotretinoin-induced acne fulminans arises after starting isotretinoin therapy for acne. An explosive flare of tender, oozing, friable plaques with hemorrhagic crusts occurs with or without associated systemic symptoms. The flaring typically arises within the first month of treatment but may occur later. The pharmacomechanism of this unfortunate adverse reaction is not fully understood. Patients with severe inflammatory acne in particular are at risk. Lower starting doses of isotretinoin (0.3 to 0.5 mg/kg/day) and the concomitant addition of systemic corticosteroids may prevent flaring. If isotretinoin-induced acne fulminans does occur, the isotretinoin dose should be lowered or discontinued and prednisone therapy immediately started, following the guidelines for the management of acne fulminans above.
What is SAPHO SYNDROME
SAPHO syndrome is manifested by synovitis, acne, pustulosis, hyperostosis, and osteitis. It is predominantly associated with hyperostosis of the anterior chest, palmoplantar pustulosis, hidradenitis suppurativa, and acne fulminans. Its cause is unknown. Reported successful treatments for SAPHO syndrome include nonsteroidal antiinflammatory drugs, sulfasalazine, infliximab, adalimumab, methotrexate. 12 Paradoxically, worsening of SAPHO skin manifestations can be seen with anti-TNF agents. 13,14 The bisphosphonates are beneficial for treating the associated bone pain.
What are PAPA, PASH, AND PAPSH SYNDROME
PAPA (pyogenic arthritis, pyoderma gangrenosum and acne), PASH (pyoderma gangrenosum, acne and hidradenitis suppurativa) and PAPASH (pyogenic arthritis, acne, pyoderma gangrenosum and hidradenitis suppurativa) are a group of systemic autoinflammatory disorders resulting from dysregulation of the innate immune system and over production of interleukin (IL)-1. 16 Patients with these disorders have a variable combination of sterile neutrophilic skin lesions, including acne, pyogenic granuloma, and hidradenitis suppurativa, and pyogenic arthritis. They may also give a history of inflammatory bowel disease and pancytopenia after administration of sulfacontaining medications. Mutations in the protein serinethreonine phosphatase interacting protein (PSTPIP1) results in an increase in IL-1β production. 17 There have been reports of successful treatment with cyclosporine, dapsone, infliximab, and anakinra.18,19
ACNE EXCORIÉE
Acne excoriée (or acne excoriée des jeunes filles) is a variant of skin-picking disorder. Often quite mild acne is systematically and neurotically excoriated, leaving crusted erosions that may scar. It is more common in females. Acne excoriée and skin-picking disorder are now recognized as excoriation disorders by the American Psychiatric Association in the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5). 20 They are categorized under obsessive-compulsive disorders and as such should be comanaged with psychiatry to address both the acne and the underlying psychogenic excoriation. That said, many patients are lost to followup, and there is a low rate of referral to mental health providers.21
ACNE MECHANICA
Acneiform eruptions have been observed after repetitive physical trauma to the skin such as pressure, friction, or rubbing. Two types of reactions result, either a flare in acne with comedones and inflammatory papules (“acne mechanica”) or follicular inflammatory lesions (“folliculitis mechanica”). 22 This can occur from clothing (belts and straps), sports equipment (football helmets and shoulder pads), and with crutches and prosthetics. 23,24 A classic example of acne mechanica is “fiddler’s neck,” produced where the violin pad repetitively rubs against the player’s lateral neck. 25 The pathogenesis of these reactions are not fully understood. Alterations in the barrier function, microbiome, and activation of innate immune system, as well as keratinocyte disruption and increase in IL-1a are purposed to play a role.22,26
ACNE WITH SOLID FACIAL EDEMA
A rare and disfiguring variant of acne vulgaris is acne with solid facial edema, also known as Morbihan disease. There is a woody edema of the mid third face with accompanying erythema and acne. Similar changes have been reported with rosacea and Melkerson-Rosenthal syndrome. There may be fluctuations in the severity of the edema, but spontaneous resolution does not occur. Diagnosis can be made clinically. The histology of solid facial edema is nonspecific with dermal edema, fibrosis, dilated blood vessels, and a mixed inflammatory infiltrate.27 Oral antibiotic treatment in acne with solid facial edema is typically ineffective. Treatment with lowdose isotretinoin (0.2–0.5 mg/kg/day) alone or in combination with oral glucocorticoids, ketotifen (1–2 mg/day), or clofazimine for 4 to 5 months has been reported to be beneficial.28-30
ACNE WITH ASSOCIATED ENDOCRINOLOGY ABNORMALITIES
Although the majority of cases of acne vulgaris occur in patients without endocrinologic disturbances, there are specific populations whose acne is driven or worsened by endocrine abnormalities. As mentioned previously, it is important to screen patients for such abnormalities by taking a thorough history. In females, in addition to the presence of acne, hyperandrogenism may be marked by irregular menstrual cycles, a deepened voice, increased libido, and hirsutism. Laboratory work can help define an endocrinologic problem causing acne.
POLYCYSTIC OVARIAN SYNDROME
Polycystic ovarian syndrome (PCOS) occurs in roughly 5% to 10% of women. Hyperandrogenism, acne, insulin resistance, and acanthosis nigricans are clinical markers of this syndrome. PCOS should be suspected in women with any combination of oligomenorrhea, clinical or biochemical hyperandrogenism, or polycystic ovaries on ultrasound scan. 31 Premenarchal women with acne and hirsutism should be screened for PCOS with a serum free testosterone level. 32,33 Additional testing may be indicated if the result is abnormal. In typical cases, testing should be deferred until 2 years after menarche because of the lack of established laboratory norms and inherent irregularity of menstrual cycles in this age group. 34 Women with PCOS are at increased risk of infertility, impaired glucose tolerance, type 2 diabetes, dyslipidemia, endometrial cancer, and cardiovascular disease. Combined oral contraceptives with spironolactone can be helpful in controlling acne and hirsutism. 35,36 The addition of metformin can also beneficial. 37 Additional treatment consists of weight management, lipid control, regulation of insulin resistance, and fertility assistance.32
CONGENITAL ADRENAL HYPERPLASIA
Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder caused by varying enzyme defects in the cortisol production pathway. 21β-hydroxylase, deficiency can result in both a classic severe type and as a nonclassic mild type. Neonates are screened at birth for the classic type and typically present with ambiguous genitalia and salt wasting. The nonclassic type is not identified at birth and can present throughout childhood and adolescence. The prevalence of the nonclassic type in the white population is 0.1%. Patients with this type of CAH have normal cortisol levels but increased androgens. Female patients present with findings similar to PCOS, including precocious puberty, irregular menses, polycystic ovaries, hirsutism, and acne. 38 Values of dehydroepiandrosterone sulfate (DHEAS) in the range of 4000 to 8000 ng/mL are suggestive of CAH. Findings of CAH in males are often subtle and acne may be the only sign. CAH should be considered in patients who do not respond to treatment. 39 Treatment of patients with CAH consists of low-dose replacement of glucocorticoids, as well as oral contraceptives, spironolactone, or flutamide in females.
STEROID FOLLICULITIS
As early as 2 weeks after initiation of systemic glucocorticoids or corticotropin, folliculitis may appear. Similar lesions may follow the prolonged application of topical glucocorticoids to the face or with inhaled steroids for asthma. The pathology of steroid acne is that of a focal folliculitis with a neutrophilic infiltrate in and around the follicle. This type of acne clearly differs from acne vulgaris in its distribution and in the type of lesions observed. The lesions, which are usually all in the same stage of development, consist of small pustules and red papules. In contrast to acne vulgaris, they appear mainly on the trunk, shoulders, and upper arms, with lesser involvement of the face. Postinflammatory hyperpigmentation may occur, but comedones, cysts, and scarring are unusual. Steroid folliculitis is uncommon in younger children. Treatment consists primarily of stopping any corticosteroid use. Typical acne treatments such as topical retinoids and antibiotics may also be helpful.
DRUGINDUCED ACNE
In addition to glucocorticoids, other medicines can also cause a monomorphic, diffuse papular eruption that mimics steroid folliculitis. Such drugs include phenytoin, lithium, isoniazid, high doses of vitamin B complexes, halogenated compounds, and certain chemotherapy medications (Table 80-1). Halogenated compounds containing either bromides or iodides are often found in cold and asthma remedies, sedatives, radiopaque contrast material, kelp, and other vitamin and mineral combinations. With iodides, in particular, inflammation may be marked. 40,41 The iodine content of iodized salt is low and; therefore, it is extremely unlikely that enough iodized salt could be ingested to cause this type of acne.
EPIDERMAL GROWTH FACTOR RECEPTOR INHIBITOR ASSOCIATED ERUPTION
Epidermal growth factor receptor (EGFR) inhibitors may also cause a follicular-based eruption. EGFR inhibitors are primarily used to treat non–small-cell lung cancer, colorectal cancer, and breast cancer. Some of the EGFR inhibitors include the monoclonal antibodies cetuximab, panitumumab, necitumumab, pertuzumab, and small-molecule tyrosine kinase inhibitors gefitinib, erlotinib, afatinib, osimertinib, and lapatinib. A frequent side effect of the EGFR inhibitors is a perifollicular, papulopustular eruption distributed on the face and upper torso. The eruption occurs in up to 86% of patients treated with EGFR inhibitors. 42 An associated lateral paronychia may also occur. Histopathological sections of lesional skin show a noninfectious perifolliculitis. The cause of the acneiform eruption is not clear, but it may occur because EGFR is highly expressed in the basal cell layer of the epidermis, follicular keratinocytes, and the sebaceous epithelium. The presence and severity of the eruption correlates with a positive treatment response. 42,43 If the eruption is absent, dosing may be inadequate, or the patient’s tumor may be unresponsive to EGFR inhibitor therapy. Treatment consists of managing pruritus with systemic antihistamines, γ-aminobutyric acid agonists, or aprepitant. 44 Management of the rash is based on the severity. The National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE) grades the rash using a 1 to 5 scale based on body surface area involved, associated symptoms, and concomitant infection. For mild disease, topical hydrocortisone 2.5% cream or clindamycin 1% lotion is suggested. For more severe disease, higher strength topical steroids, doxycycline or minocycline, or low-dose isotretinoin is recommended.45
PSEUDOACNE OF THE NASAL CREASE
The transverse nasal crease is an anatomic variant that appears as a transverse linear groove across the middle of the nose. Preadolescent patients develop comedones, milia, and acneiform red papules within the nasal crease (Fig. 80-4). It can be familial or associated with the “allergic salute.” Histologic examination of the papules reveals keratin granulomas that may be derived from ruptured, inflamed milia. Because of its similarity in clinical appearance to acne but deviation from acne histologically, it has been termed “pseudoacne of the nasal crease.”54
The facial Afro-Caribbean eruption (FACE) is another variant of periorificial dermatitis characterized by uniform, granulomatous sarcoidal papules distributed over the typical periorificial areas. 60 (Fig. 80-6) Distinguishing features include involvement of the upper eyelids and helices of the ears. 61 Histology is similar to granulomatous perioral dermatitis.
