A 5-year-old boy presents with complaints of a facial rash. The lesions began around his mouth 3 months ago, at which time his mother treated them with topical 1% hydrocortisone cream. At first the lesions improved, but they soon recurred and spread to his nose and around his eyes. The boy denies any associated pain or itch. Examination of the skin reveals monomorphic erythematous papules with a few papulopustules on the bilateral cheeks, and on perinasal, perioral, and periorbital skin. His mother inquires if he has acne.
Acneiform eruptions are common skin diseases resembling acne vulgaris. Whereas acne vulgaris is usually easily recognized, the differential diagnosis of acneiform eruptions is broad and largely depends on the age of onset and the morphology and location of the lesions.
Acne vulgaris is a very common skin condition characterized by comedones, papules, pustules, nodules, and cysts on sebum-rich areas of the body such as the face and trunk. Likewise, lesions of acneiform eruptions can be papulopustular, nodular, or cystic. The differential diagnosis of acneiform eruptions from true acne relies on absence of comedones. The comedone is the sine qua non of acne—it is always present. Comedones can be open or closed and appear as papules with black or white centers, respectively.
Acneiform eruptions that present during childhood should be differentiated from childhood acne and from one another. In this review, we focus on the morphologic presentation of acneiform eruptions in children, including neonatal acne and cephalic pustulosis, periorificial dermatitis (perioral dermatitis), acneiform drug eruptions, facial angiofibromas, and childhood rosacea. A basic approach to clinical management is also presented.
Neonatal Acne and Neonatal Cephalic Pustulosis
Acne that is present at birth or appears during the first 4 weeks of life (ie, the neonatal period) is referred to as acne neonatorum. Neonatal acne is common and has been estimated to occur in approximately 20% of newborns, with a mean age of onset of 3 weeks.1
Morphologically, neonatal acne is characterized mainly by facial eruptions of inflammatory and noninflammatory lesions. The presence of inflammatory papules and pustules, the typical absence of comedonal lesions, and a distribution limited to the face, and particularly the cheeks, are diagnostic (Figure 1 and Table 1). Some make a distinction between neonatal acne, which is thought to be related to hormonal stimulation of sebaceous glands, and neonatal cephalic pustulosis, which is thought to be associated with the Malassezia species of yeast on neonatal skin.2 Neonatal cephalic pustulosis tends to be composed mainly of pustules and may extend to the upper chest (Figure 2).
Neonatal acne. This infant had clear skin until age 4 weeks, at which time she experienced a sudden onset of small erythematous papules and pustules on the cheeks and forehead (pictured). Photo courtesy of Bridget Beck, MD (Denver, CO) (used with permission).
Key Findings in a Patient Presenting with Acneiform Eruption
Neonatal cephalic pustulosis. This infant had multiple small erythematous pustules on the forehead, cheeks, and chin with extension of lesions on to the upper chest.
Neonatal acne and cephalic pustulosis must be differentiated from other dermatoses occurring in the neonatal period (Table 2). Sebaceous hyperplasia occurs in many healthy neonates and presents as transient yellow papules on the cheeks, nose, and forehead.3 Acne neonatorum can appear similar to miliaria rubra, also known as heat rash. Miliaria is a common finding in newborns, particularly in warm climates. Miliaria rubra is characterized by small groups of erythematous papules and pustules. In addition to facial involvement, the distribution often includes the trunk and intertriginous skin, areas that are spared in neonatal acne. The entity is caused by obstructed sweat leaking into the dermis of the skin and resulting in a localized inflammatory response.3 Miliaria is rarely present at birth and usually develops in association with a warm environment. Lesions resolve rapidly when the infant is placed in a cooler environment.
Differential Diagnoses for Pediatric Acneiform Eruptions
The course of neonatal acne and neonatal cephalic pustulosis is typically mild and transient, usually resolving within weeks (but sometimes lasting up to 4 months) without scarring.2 The mainstay of treatment consists of once or twice daily use of a mild cleanser and water. Topical imidazole antifungal agents such as ketoconazole might hasten resolution in some cases of cephalic pustulosis.2
Periorificial Dermatitis (Perioral Dermatitis)
Periorificial dermatitis, sometimes termed perioral dermatitis (POD), is a common acneiform eruption of unknown origin that can be diagnosed by clinical history and physical examination. It is most often found in women between the ages of 16 and 45 years but also commonly occurs in children between the ages of 7 months and 13 years.2,4 POD presents as papules, pustules, or vesicles periorally, but may include similar eruptions periorbitally or perinasally (Figure 3 and Table 1). Typically, the vermilion border of the lip is spared. The presence of pruritus, general irritation, or a burning sensation is variable.5,6 About one-fifth of patients experience pruritus.6 The term “dermatitis” in the name perioral dermatitis suggests an eczematous condition, but there may or may not be fine scaling present. POD in children most frequently occurs before the age of 5 years but has been documented in infants as young as age 6 months.6 Girls may be more likely to develop POD than boys.6 Childhood granulomatous periorificial dermatitis (CGPD) is a rare clinical variant of POD that typically occurs in prepubertal children, predominantly in African Americans and other dark-skinned individuals.7,8 CGPD can be clinically differentiated from POD by the presence of yellow-brown papules rather than erythematous papules and pustules. Biopsy may aid in the diagnosis of CGPD.
Periorificial dermatitis. This 4-year-old girl had small erythematous papules and pustules around the mouth and nose.
The etiology of POD is not well understood but deficiencies of skin barrier function and features of atopy have been detected at increasing rates in affected patients.9 Previous topical corticosteroid use or use of inhaled corticosteroids is frequently reported in association with POD.10 Typically, the eruption may improve initially with the use of topical corticosteroids, but worsens with continued use and with abrupt discontinuation of therapy.6,10 One theory is that corticosteroid use damages the skin barrier function.
Many other skin disorders present with inflammatory eruptions around the mouth, nose, or eye (Table 2). POD can be differentiated from acne vulgaris based on the absence of comedones. Rosacea shows a predilection for the cheeks rather than the periorificial sites of POD. Seborrheic dermatitis lacks the presence of papules, and presents with erythema and scale on the perinasal skin as well as on the scalp, eyebrows, and nasolabial folds. Seborrheic dermatitis spares the perioral skin. The lesions of allergic contact dermatitis are typically papules or vesicles with weeping or crusting. Unlike POD, intense pruritus is commonly present. Irritant contact dermatitis presents with a burning sensation rather than the pruritus seen with allergic contact dermatitis, and it tends to lack papules and pustules. The patient history in such cases should be helpful in revealing the irritant cause of the disorder.
The course of POD is self-limited and scarring is absent in most cases. Mild cases may resolve within a few months without pharmacologic therapy in some patients, whereas in others it may persist for several years and be refractory to topical therapies.6,10–13 A generally well-accepted approach to therapy involves the discontinuation of topical corticosteroids and the avoidance of skin care products that may irritate or occlude the skin. The skin should be cleansed with water alone with only as-needed application of a non-occlusive moisturizer. Pharmacologic therapy with anti-inflammatory agents can accelerate resolution of the lesions. Topical calcineurin inhibitors and topical metronidazole have been shown to be beneficial in mild to moderate POD. When topical therapy alone is not effective, the addition of oral medication can be considered. Oral erythromycin for 4 to 6 weeks is the standard systemic treatment for patients age 8 years and younger. The oral tetracyclines can be used in patients age 9 years or older.6,7,11,12
Multiple Facial Angiofibromas
Multiple facial angiofibromas, formerly called adenoma sebaceum, are a rare but important cause of acneiform eruptions in adolescents. These are hamartomas of the skin that are often initially misdiagnosed as acne because of the distribution on the nasolabial folds, cheeks, and chin. Careful inspection will reveal that the lesions are usually pink or skin-colored dome-shaped papules with tiny telangiectatic vessels, and that comedones are absent (Figure 4). The presence of multiple facial angiofibromas prior to adulthood is almost always indicative of a diagnosis of tuberous sclerosis,14 but can also be seen in the setting of multiple endocrine neoplasia (MEN) type I.15 By the time patients with tuberous sclerosis reach age 9 years, 75% of them will have multiple facial angiofibromas.16 They usually become apparent by age 5 years and become more prominent with advancing age.16
Multiple facial angiofibromas. This prepubertal child had multiple small, firm pink papules on bilateral cheeks and nose. Examination confirmed a diagnosis of tuberous sclerosis. Photo courtesy of Kristen Hook, MD (University of Minnesota Medical School) (used with permission).
Angiofibromas are differentiated from acne vulgaris by the presence of telangiectasia and the absence of comedones and pustules. Histologically, angiofibromas show atrophic sebaceous glands with dermal fibrosis and some capillary dilation. Fibroblasts are quite large and have a stellate shape giving the lesion a glial appearance. Elastic tissue is characteristically absent.
If one suspects this diagnosis, it is reasonable to obtain a biopsy or refer to those with expertise in pediatric dermatologic disease. In the past, most available treatments for facial angiofibromas were procedural in nature, with pulsed dye laser therapy showing the most promise, especially when lesions had a prominent vascular component. Topical rapamycin is an off-label treatment for facial angiofibromas that has shown some success.14 Everolimus is a rapamycin-derivative and also demonstrates promise as a topical treatment option.17
Drug-Induced Acneiform Eruptions
Drug-induced, or iatrogenic, acneiform eruptions are typically composed of monomorphic papulopustules located predominantly on the trunk and extremities that appear after the administration of an inciting drug (Table 1).18 A variety of pharmacologic agents are associated with acne-like eruptions (Table 3). Steroid-induced eruptions are also known as steroid acne or steroid folliculitis. Diagnosis is based on several characteristics that support a relationship between drug ingestion and acneiform lesions.18 Whereas acne vulgaris tends to be polymorphous with lesions in varying stages, acneiform drug eruptions tend to have monomorphic lesions with a temporal relationship to medication administration. Comedones are typically absent, and the lesions may extend beyond the sebaceous areas, with lesions on the trunk and upper arms. The eruption may be resistant to conventional acne treatments, but anti-inflammatory medications might be helpful. Treatment includes the discontinuation of the inciting drug when appropriate.
Major Causes of Drug-Induced Acne
Epidermal growth factor receptor (EGFR) inhibitors and other tyrosine kinase inhibitors used to treat malignancy deserve mention because a common, even expected, side effect of these agents is an inflammatory acneiform eruption often involving the face, neck, and upper trunk. The onset of the eruption typically occurs within the first 2 weeks of therapy but has been documented to occur up to 2 months after starting treatment.19 This effect is generally not considered a contraindication to use of the EGFR agent, and partial or complete resolution has been seen in a few patients even with continued therapy with the offending medication.19 After the discontinuation of the drug, resolution typically occurs within 1 month.20
Rosacea is a disorder of vasomotor instability characterized by centrofacial erythema including the forehead, cheeks, nose, perioral, and periocular skin (Table 1). Its etiology is unknown, but it is associated with several known predisposing and exacerbating factors.11 Accurate incidence data are not available but it is known that rosacea affects both sexes, typically presents after age 30 years, and disproportionately affects persons of fair-skinned European and Celtic origin.21 Although rosacea is quite common in adults, it is relatively rare in childhood. In one study, 20% of children with rosacea were found to have a history of rosacea in their immediate families, although this number may be underestimated because only one parent of each patient was examined.22
In children, rosacea presents as facial flushing, commonly in response to stress (either emotional or environmental). Most cases of rosacea in children consist of episodes of bright-red facial flushing that last longer than normal physiologic flushing. Children may also report irritation or a burning sensation with these episodes.11 Less commonly, the presence of papules and pustules overlying an erythematous base with telangiectasias are noted.11 Eye involvement can occur in children, with meibomian gland inflammation and keratitis being the most common findings. In contrast to adult rosacea, the phymatous reaction (enlargement of the nose) of chronic disease has not been reported in children.
Rosacea is a clinical diagnosis; there is no specific histologic change unique to rosacea. The presence of papulopustular lesions with rosacea may be confused with similar lesions of acne vulgaris, perioral dermatitis, and lupus erythematosus. Rosacea can be differentiated from acne vulgaris based on the absence of comedones. Attention to the distribution of the facial lesions and the history of flushing in response to stress allow for the differentiation of the conditions (Table 2). Patients with perioral dermatitis or granulomatous perioral dermatitis do not exhibit flushing or telangiectasias.11 The erythema and telangiectasias seen in the butterfly or malar rash of systemic lupus erythematosus can be confused with rosacea. Biopsy and immunofluorescence may be useful in confirming a diagnosis of cutaneous lupus.11
Treatment of rosacea in childhood begins with avoidance of identified triggers to prevent flares. All topical steroids, even low potency, over-the-counter preparations should be avoided because they have been shown to exacerbate the condition.22 The most useful topical therapy is metronidazole, but topical sulfonamide and azelaic acid may also be helpful. Options for systemic therapy include metronidazole and the macrolide and tetracycline classes of antibiotics, with avoidance of tetracyclines in children younger than age 9 years.7,11,23
Case Presentation: Wrap Up
Because of the distribution of the child’s rash and the lack of comedones, you reassure the parent that this is not acne but instead is consistent with periorificial dermatitis. You recommend cessation of hydrocortisone, use of gentle cleansers and moisturizers, and a topical calcineurin inhibitor twice daily. At a follow-up visit 6 weeks later, the eruption is almost completely resolved.
Acneiform eruptions in childhood, ranging from common conditions such as neonatal acne and periorificial dermatitis to rare diseases such as childhood rosacea, may be difficult to diagnose. Special attention should be given to the differing morphologic presentations to identify the most likely diagnosis. We present key findings that aid in diagnosis, including patient history, physical examination with attention to the presence or absence of comedones, histologic examination, and the history of drug therapy. The goals of pharmacotherapy are to reduce inflammation, improve or accelerate healing, and prevent complications. Treatment varies with the particular acneiform eruption suspected. For entities resistant to therapy, it is reasonable to obtain a biopsy or collaborate with those who have expertise in pediatric skin disease.
- Katsambas A, Katoulis A, Stavropoulos P. Acne neonatorum: a study of 22 cases. Int J Dermatol. 1999;38(2):128–130. doi:10.1046/j.1365-4362.1999.00638.x [CrossRef]
- Paller A, Mancini A. Hurwitz Clinical Pediatric Dermatology. 3rd ed. Philadelphia, PA: Elsevier Saunders; 2006.
- Bolognia J, Jorizzo J, Schaffer J. Dermatology. 3rd ed. Philadelphia, PA: Elsevier Saunders; 2012.
- Hafeez Z. Perioral dermatitis: an update. Int J Dermatol. 2003;42(7):514–517. doi:10.1046/j.1365-4362.2003.01852.x [CrossRef]
- Mihan R, Ayres S. Perioral dermatitis. Arch Dermatol. 1964;89:805–805. doi:10.1001/archderm.1964.01590300031010 [CrossRef]
- Nguyen V, Eichenfield L. Periorificial dermatitis in children and adolescents. J Am Acad Dermatol. 2006;55(5):781–785. doi:10.1016/j.jaad.2006.05.031 [CrossRef]
- Tarm K, Creel N, Krivda S, Turiansky G. Granulomatous periorificial dermatitis. Cutis. 2004;73(6):399–402.
- Frieden I, Prose N, Fletcher V, Turner M. Granulomatous perioral dermatitis in children. Arch Dermatol. 1989;125(3):369–373. doi:10.1001/archderm.1989.01670150059008 [CrossRef]
- Dirschka T, Tronnier H, Folster-Holst R. Epithelial barrier function and atopic diathesis in rosacea and perioral dermatitis. Br J Dermatol. 2004;150(6):1136–1141. doi:10.1111/j.1365-2133.2004.05985.x [CrossRef]
- Lipozencic J, Hadzavdic S. Perioral dermatitis. Clin Dermatol. 2014;32(1):125–130. doi:10.1016/j.clindermatol.2013.05.034 [CrossRef]
- Lacz N, Schwartz R. Rosacea in the pediatric population. Cutis. 2004;74(2):99–103.
- Tempark T, Shwayder T. Perioral dermatitis: a review of the condition with special attention to treatment options. Am J Clin Dermatol. 2014;15(2):101–113. doi:10.1007/s40257-014-0067-7 [CrossRef]
- Weber K, Thurmayr R. Critical appraisal of reports on the treatment of perioral dermatitis. Dermatology. 2005;210(4):300–307. doi:10.1159/000084754 [CrossRef]
- Jacks S, Witman P. Tuberous sclerosis complex: an update for dermatologists. Pediatr Dermatol. 2015; [Epub ahead of print]. doi:10.1111/pde.12567 [CrossRef].
- Asgharian B, Turner M, Gibril F, Entsuah L, Serrano J, Jensen R. Cutaneous tumors in patients with multiple endocrine neoplasm type 1 (MEN1) and gastrinomas: prospective study of frequency and development of criteria withhigh sensitivity and specificity for MEN1. J Clin Endocrinol Metab. 2004;89(11):5328–5336. doi:10.1210/jc.2004-0218 [CrossRef]
- Jozwiak S, Schwartz R, Janniger C, Michalowicz R, Chmielik J. Skin lesions in children with tuberous sclerosis complex: their prevalence, natural course, and diagnostic significance. Int J Dermatol. 1998;37(12):911–917. doi:10.1046/j.1365-4362.1998.00495.x [CrossRef]
- Dill P, De Bernardis G, Weber P, Lösch U. Topical everolimus for facial angiofibromas in the tuberous sclerosis complex. A first case report. Pediatr Neurol. 2014;51(1):109–113. doi:10.1016/j.pediatrneurol.2014.02.016 [CrossRef]
- Du-Thanh A, Kluger N, Bensalleh H, Guillot B. Drug-induced acneiform eruption. Am J Clin Dermatol. 2011;12(4):233–245. doi:10.2165/11588900-000000000-00000 [CrossRef]
- Jacot W, Bessis D, Jorda E, et al. Acneiform eruption induced by epidermal growth factor receptor inhibitors in patients with solid tumours. Br J Dermatol. 2004;151(1):238–241. doi:10.1111/j.1365-2133.2004.06026.x [CrossRef]
- Li T, Perez-Soler R. Skin toxicities associated with epidermal growth factor receptor inhibitors. Target Oncol. 2009;4(2):107–119. doi:10.1007/s11523-009-0114-0 [CrossRef]
- Wilkin J, Dahl M, Detmar M, et al. Standard classification of rosacea: report of the National Rosacea Society Expert Committee on the classification and staging of rosacea. J Am Acad Dermatol. 2002;46(4):584–587. doi:10.1067/mjd.2002.120625 [CrossRef]
- Weston W, Morelli J. Steroid rosacea in prepubertal children. Arch Pediatr Adolesc Med. 2000;154(1):62–64.
- Kroshinsky D, Glick S. Pediatric rosacea. Dermatol Ther. 2006;19(4):196–201. doi:10.1111/j.1529-8019.2006.00075.x [CrossRef]
Key Findings in a Patient Presenting with Acneiform Eruption
||Area of Involvement
||Face, chest, back
||Comedones, papules, pustules, nodules, and cysts
|Neonatal acne, cephalic pustulosis
||First 4 weeks of life
||Inflammatory papules and pustules
||Children, young women
||Perioral, periorbital, perinasal
||Papules, pustules, or vesicles on erythematous base; sparing of skin around the vermillion border of the lip
|Granulomatous periorificial dermatitis
||Perioral, perinasal, periorbital, and/or extrafacial
||Dome-shaped erythematous, yellow-brown papules (lack of pustules)
||Age 5 years or older
||Nasolabial folds, cheeks, chin
||Pink or skin-colored dome-shaped papules with tiny telangiectatic vessels
|Drug-induced acneiform eruption
||Trunk and extremities
||Rare in childhood, adult
||Flushing ± papules, pustules, and telangiectasias
Differential Diagnoses for Pediatric Acneiform Eruptions
|Neonatal acne (neonatal cephalic pustulosis)
|Periorificial dermatitis (perioral dermatitis)
Allergic contact dermatitis
Irritant contact dermatitis
|Childhood granulomatous periorificial dermatitis
Lupus disseminatus faciei
Basal cell carcinoma
|Drug-induced acneiform eruptions
Granulomatous periorificial dermatitis
Systemic lupus erythematosus
Major Causes of Drug-Induced Acne
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