Acneiform Eruptions

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Background

Acneiform eruptions are dermatoses that resemble acne vulgaris. Lesions may be papulopustular, nodular, or cystic. While acne vulgaris typically consists of comedones, acneiform eruptions (such as acneiform drug eruptions) usually lack comedones clinically. See the image below.



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Acneiform eruption. Courtesy of DermNet New Zealand (http://www.dermnetnz.org/assets/Uploads/doctors/quizzes/48/case6.jpg).

Acnelike eruptions develop as a result of infections, hormonal or metabolic abnormalities, genetic disorders, and drug reactions.

Those entities included in this discussion are nevus comedonicus, eruptive hair cysts, tuberous sclerosis,[1, 2] amineptine acne, steroid acne, chloracne, acneiform drug eruptions, gram-negative folliculitis, eosinophilic pustular folliculitis, Pityrosporum folliculitis, coccidioidomycosis, secondary syphilis,[3, 4] sporotrichosis,[5] rosacea, and perioral dermatitis.

Etiology

See Physical Examination.

Patient Education

For patient education resources, see the Skin, Hair, and Nails Center; Teen Health Center and Sexually Transmitted Diseases Center, as well as Acne and Syphilis.

History

Patients with acneiform eruptions present with acnelike lesions such as papulonodules, pustules, and cysts. They typically do not present with comedones, which is a distinguishing factor. The physical location may be outside of the area in which acne vulgaris occurs. Acneiform eruptions can be distinguished from acne vulgaris by a history of sudden onset, monotonous lesion morphology, and development of the eruption at an age outside the range typical of acne vulgaris. In the case of drug-induced acneiform eruptions, the eruption resolves with discontinuation of the medication.

Physical Examination

Nevus comedonicus (NC) is an infrequent developmental anomaly manifesting as aggregated open comedones. It consists of dilated follicular or eccrine orifices plugged with keratin. Also known as comedone nevus and nevus acneiformis unilateralis, it may be solitary, congenital, or, less frequently, can occur later in life as a result of occupational exposure. The differential diagnosis of NC includes familial dyskeratotic comedones and linear comedone formations usually linked with acne vulgaris or chronically sun-damaged skin (Favre-Racouchot disease). Infrequently, multiple comedones in other unusual contexts may raise NC as a possible consideration. Treatment of NC is generally surgical, through excision or carbon dioxide laser ablation of the involved skin. Medical therapy with topical retinoids may be of some benefit. For more information, see Nevus Comedonicus.

The eruptive vellus hair cysts[6] manifest as flesh-colored papules found usually on the face, chest, neck, thighs, groin, buttocks, and axillae. They represent an anomaly of the vellus hair follicles and may be hereditary. Histopathology reveals a mid dermal epithelial cyst containing vellus hairs and keratinous material. These cysts may undergo spontaneous regression, form a connection to the epidermis, or undergo degradation with a resultant foreign body granulomatous formation. Treatment is often difficult. Incision and drainage of individual lesions carries the risk of subsequent scarring, and modalities such as carbon dioxide laser ablation are difficult to use over large surface areas. Topical retinoids and 12% lactic acid preparations have proven useful in some instances. For more information, see Eruptive Vellus Hair Cysts.

Steroid acne[7, 8] is observed as monomorphous papulopustules located predominantly on the trunk and extremities, with less involvement of the face. Characteristically, it appears after the administration of systemic corticosteroids, including intravenous therapy. Topical or inhaled corticosteroids may cause an acneiform eruption of the area of skin under which the topical preparation is applied or in around the nose or mouth in the case of inhaled steroids. The eruption usually resolves after discontinuation of the steroid and, in addition, may respond to the usual treatments of acne vulgaris. For more information, see Acne Vulgaris.

Exposure to halogenated aromatic hydrocarbon compounds, such as chlorinated dioxins and dibenzofurans, by inhalation, ingestion, or direct contact of contaminated compounds or foods induces a cutaneous eruption of polymorphous comedones and cysts referred to as chloracne. Other associated skin findings may include xerosis and pigmentary changes. Internal changes involving the ophthalmic, nervous, and hepatic systems may also occur, and some chloracnegens can be oncogenic. Treatment is difficult because chloracne may persist for years, even without further exposure. Chemicals that contain iodides, bromides, and other halogens can also induce an acneiform eruption similar to that of steroid acne; however, the iodide-induced eruption may be more extreme.

Antibiotics may induce an acute generalized pustular eruption. Penicillins and macrolides are the greatest offenders. Patients usually are febrile with leukocytosis, and the eruption does not usually involve comedones. Other implicated antibiotics include co-trimoxazole, doxycycline, ofloxacin, and chloramphenicol. Other types of medications can also produce an acnelike eruption, including corticotropin, nystatin, isoniazid, itraconazole, hydroxychloroquine, naproxen, mercury, amineptine,[9, 10, 11] the antipsychotics olanzapine and lithium, chemotherapy drugs, and epidermal growth factor receptor inhibitors.[12, 13, 14, 15, 16, 17, 18, 19] For more information, see Drug Eruptions.

Various infections may also display an acneiform pattern. Gram-negative folliculitis, a persistent papulopustular eruption, may be a complication in patients on prolonged treatment with oral antibiotics for acne vulgaris or rosacea. Antibiotic use, such as those of the tetracycline class, can alter the normal skin flora of the skin allowing for growth of gram-negative organisms in the nares of the nose. These gram-negative organisms are typically spread to the skin of the upper lip, chin, and jawline whether they cause a folliculitis. Culture of the papulopustules grows gram-negative bacilli and gram-negative rods, including Escherichia coli and Klebsiella, Enterobacter, and Proteus species. Typical history is a patient with a sudden acne flare despite no change in treatment or a patient unresponsive to traditional therapies. Oral isotretinoin is considered standard of care. For more information, see Gram-Negative Folliculitis, Acne Vulgaris, and/or Rosacea.

Pityrosporum folliculitis is another infectious folliculitis that is presumably caused by a host reaction to the yeast Malassezia furfur, previously named Pityrosporum ovale, a normal human skin commensal organism. It appears primarily on the trunk and upper extremities of late adolescents and young adults. Unlike acne vulgaris, it is pruritic, does not contain comedones, and responds to empiric antifungal therapy rather than antibiotics. Diagnosis is typically made clinically, although the yeast and hyphae can be observed in biopsy specimens in the widened follicular ostia along with keratinous material, and occasionally, rupture of the follicular wall may occur. Patients may be treated with topical leave-on, wash-off, or systemic antifungal therapy. For more information, see Pityrosporum Folliculitis.

Eosinophilic pustular folliculitis (EPF) is a disease of unclear etiology, thought to be an allergic hypersensitivity. It appears as a recurrent pruritic papulopustular eruption on the face, trunk, and extremities. Histopathology reveals a predominantly perifollicular infiltration of eosinophils with some mononuclear cells and subcorneal pustules composed of eosinophils. Three main types exist, (1) infantile form, (2) HIV associated, and (3) classic Ofuji disease in immunocompetent patients, typically Japanese patients. Patients may also demonstrate blood eosinophilia and leukocytosis. Treatment modalities and results vary greatly. Options include topical and systemic corticosteroids, oral antibiotics, dapsone, isotretinoin, and pulsed ultraviolet phototherapy (PUVA). Indomethacin is the treatment of choice for classic Ofuji disease. For more information, see Eosinophilic Pustular Folliculitis.

Several infectious diseases may result in acneiform eruptions, as follows:

Rosacea appears similarly to acne vulgaris with papulopustules on the face, but in addition, patients may also have facial flushing and telangiectasias. Patients with rosacea, however, lack comedones. Four subtypes of rosacea exist: (1) erythematotelangiectatic, (2) papulopustular, (3) phymatous, and (4) ocular.

Rosacea is more common in the white population and in women in the third and fourth decades of life. Men, however, more commonly develop sebaceous hyperplasia of the nose, known as rhinophyma. Associated eye findings are variable but include blepharitis, conjunctivitis, iritis, iridocyclitis, hypopyon iritis, and even keratitis. Although the definitive etiology is unknown, weather extremes, hot or spicy foods, alcohol, and Demodex folliculorum mites can trigger and exacerbate this condition. Acne rosacea has also been associated with the ingestion of a high-dose vitamin B6 supplement.[20]

Histopathology of rosacea skin reveals granulomatous inflammation. Treatment primarily includes skin barrier sunscreens and topical antibiotics such as metronidazole, retinoids, and oral tetracyclines.

Perioral dermatitis, also a disorder of unclear etiology, is mainly observed in the young, white, female population as papulopustules with erythematous base. The eruption is predominantly perioral in location, characteristically sparing the vermilion border of the lip, but it may also include the perinasal and periorbital areas. A variant known as periocular dermatitis affects the skin around the eyes. The eruption is thought to be a variant of rosacea, as biopsies show changes similar to those of rosacea.

Causative agents are theorized to be prior use of topical corticosteroids, but neither duration of use nor steroid strength have been shown to be clearly related. Demodex mites,[21] moisturizers, fluorinatced compounds, and contact irritants or allergens have also been implicated as causes of eruption.

Therapy typically includes cessation of topical steroids or other offending agents and topical anti-inflammatory treatments such as topical metronidazole, topical pimecrolimus cream, azelaic acid, as well as oral anti-inflammatory dose antibiotics such as doxycycline. For more information, see Perioral Dermatitis.

Lymphoma has been reported as a cause of acneiform eruptions.[22]

Laboratory Studies

The workup of acneiform eruptions varies greatly, reflecting the wide variety of diseases. This can include skin biopsies, cultures and sensitivities, serologic tests, and empiric trials of drug withdrawal (see Physical Examination).

Histologic Findings

Depending on the eruption, biopsies may demonstrate suppurative folliculitis, eosinophilic folliculitis, keratosis pilaris, or granulomatous dermatitis.[23]

Medical Care

Treatment varies with the particular disease suspected and consists of a wide range of methods, including excision, laser ablation, topical/oral antibiotics, topical/oral retinoids, and drug withdrawal. Please review individual topics in Physical Examination for greater detail.

Medication Summary

The goals of pharmacotherapy are to reduce inflammation, eliminate infection if present, reduce morbidity, and prevent complications.

Treatment varies with the particular disease suspected and consists of a wide range of methods, including excision, laser ablation, topical/oral antibiotics, topical/oral retinoids, and drug withdrawal. Please review individual topics in Physical Examination for greater detail.

Ciclopirox (Loprox)

Clinical Context:  Ciclopirox interferes with DNA, RNA, and protein synthesis by inhibiting the transport of essential elements in fungal cells.

Econazole (Spectazole)

Clinical Context:  Econazole is effective in cutaneous infections. Ii interferes with RNA and protein synthesis and metabolism. Econazole disrupts fungal cell wall permeability, causing fungal cell death.

Ketoconazole (Extina, Xolegel)

Clinical Context:  Ketoconazole is an imidazole broad-spectrum antifungal agent; it inhibits the synthesis of ergosterol, causing cellular components to leak and resulting in fungal cell death.

Class Summary

Antifungals are used in the first-line therapy of Pityrosporum folliculitis. The use of topical agents has few adverse effects besides an allergic reaction to the active agent or inactive component. The mechanism of action usually involves the inhibition of pathways (eg, enzyme, substrate, transport) that are necessary for sterol and/or cell membrane synthesis, or the permeability of the cell membrane (polyenes) of the fungal cell is altered.

Indomethacin (Indocin)

Clinical Context:  Indomethacin is a potent inhibitor of cyclooxygenase, which may decrease the local production of arachidonic acid derived chemotactic factors for eosinophils present in sebum (eg, 12-L-hydroxy-5,8,10-heptadecatrienoic acid and/or prostaglandin).

Class Summary

Because the etiology and the pathogenesis of eosinophilic pustular folliculitis have not been fully elucidated, no established treatment schemes exist. A number of options have been tried with various results; however, no controlled treatment trials have been performed for this condition. Oral indomethacin consistently appears to be most beneficial, at least in the classic form of the disease.

Cyproheptadine

Clinical Context:  Cyproheptadine is used for the symptomatic relief of allergic symptoms caused by histamine released in response to allergens and skin manifestations.

Hydroxyzine (Vistaril)

Clinical Context:  Hydroxyzine antagonizes H1 receptors in the periphery. It may suppress histamine activity in the subcortical region of the CNS.

Class Summary

These agents may alleviate itching in some HIV-associated cases of eosinophilic pustular folliculitis. Sedating forms may be more effective (especially for nocturnal pruritus).

Cyclosporine (Gengraf, Neoral, Sandimmune)

Clinical Context:  Cyclosporine is a cyclic polypeptide that suppresses some humoral immunity and, to a greater extent, cell-mediated immune reactions. It suppresses mRNA expression of Th2 cytokines (interleukins 4 and 13) in peripheral blood mononuclear cells.

Pimecrolimus cream (Elidel)

Clinical Context:  Pimecrolimus cream is used for short-term treatment or for intermittent, long-term treatment in unresponsive or intolerant cases. It is available in a 1% cream.

This was the first nonsteroid cream approved in the United States for mild to moderate atopic dermatitis. It is derived from ascomycin, a natural substance produced by the fungus Streptomyces hygroscopicus var. ascomyceticus. Pimecrolimus cream selectively inhibits the production and release of inflammatory cytokines from activated T cells by binding to cytosolic immunophilin receptor macrophilin-12. The resulting complex inhibits phosphatase calcineurin, thus blocking T-cell activation and cytokine release. Cutaneous atrophy was not observed in clinical trials, a potential advantage over topical corticosteroids. Pimecrolimus cream is indicated only after other treatment options have failed.

Class Summary

Treatment with oral cyclosporine might successfully control eosinophilic pustular folliculitis refractory to indomethacin.

Dapsone (Aczone)

Clinical Context:  Dapsone prevents bacterial use of para-aminobenzoic acid (PABA) for folic acid synthesis by acting as a competitive inhibitor.

Tetracycline

Clinical Context:  Tetracycline inhibits bacterial protein synthesis by binding with 30S and, possibly, 50S ribosomal subunit(s). Tetracycline has anti-inflammatory activity. It can be administered at 250-500 mg orally twice daily.

Doxycycline (Doryx, Adoxa, Monodox, Vibramycin)

Clinical Context:  Doxycycline is a broad-spectrum antibiotic with excellent gram positive cover, including most resistant staph organisms. It inhibits protein synthesis and, thus, bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria. Doxycycline may block the dissociation of peptidyl t-RNA from ribosomes, causing RNA-dependent protein synthesis to arrest.

Metronidazole (MetroCream, MetroGel)

Clinical Context:  Metronidazole is active against various anaerobic bacteria and protozoa. It appears to be absorbed into the cells; the intermediate metabolized compounds that are formed bind DNA and inhibit protein synthesis, causing cell death.

Class Summary

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of this clinical setting. Antibiotic treatments for rosacea include tetracyclines and metronidazole. Dapsone is used in the treatment of eosinophilic pustular folliculitis.

Topical tretinoin (Retin-A Micro, Atralin, Tretin-X Avita)

Clinical Context:  Topical tretinoin inhibits microcomedo formation. It decreases the cohesiveness of keratinocyesin sebaceous follicles, which allows for easy removal. It has anti-inflammatory properties. Topical tretinoin is available as creams and gels.

Adapalene (Differin)

Clinical Context:  Adapalene inhibits microcomedo formation. It decreases the cohesiveness of keratinocyesin sebaceous follicles, which allows for easy removal. It has anti-inflammatory properties and is available as creams and gels.

Tazarotene (Tazorac)

Clinical Context:  Tazarotene inhibits microcomedo formation. It decreases the cohesiveness of keratinocyesin sebaceous follicles, which allows for easy removal. It has anti-inflammatory properties and is available as creams and gels.

Isotretinoin (Claravis, Amnesteem, Sotret, Myorisan)

Clinical Context:  Isotretinoin is an oral retinoid indicated for recalcitrant, nodulocystic acne. It addresses all four pathogenic factors involved the development of acne: follicular hyperkeratinization, inflammation, sebum production, and Cutibacterium acnes (formerly Propionibacterium acnes)growth. Treatment is weight-based, usually dosed initially 0.5 mg/kg and increased to 1 mg/kg in 2 divided doses for 15-20 weeks. Once-daily dosing is not recommended. One may adjust the dose to administer up to 2 mg/kg/day. Patients must be registered into government regulated iPledge program in order to receive the medication.

Class Summary

These agents stimulate cellular retinoid receptors and help normalize keratinocyte differentiation and are comedolytic. In addition, they have anti-inflammatory properties. Oral isotretinoin also reduces sebum production in the skin. Retinoids are classified into 3 generations. The first comprises topical tretinoin and systemic isotretinoin. Acitretin is a second-generation retinoid used to treat psoriasis. The third-generation retinoids include topical adapalene and tazarotene.

Salicylic acid acne (Benzac Blemish Clearing Hydrator 0.5%, Benzac Intensive Spot Treatment 2%, Benzac Skin Balancing Foaming Cleanser 0.5%)

Clinical Context:  Salicylic acid is a comedolytic agent. It inhibits the formation of comedones resulting from oil and skin cells that become trapped in the pore. Its lipophilic characteristics facilitate the peeling of the exterior layer of the dermis and opens follicles that are plugged. This leads skin cells to renew their cell cycle of proliferation and differentiation. Salicylic acid can interfere with the arachidonic acid cascade of the inflammatory process. This action results in the reduction of inflammatory acne lesions.

Benzoyl peroxide (BenzEFoam, PanOxyl, Neutrogena On The Spot, Invisible Acne Treatment)

Clinical Context:  Benzoyl peroxide is an oxidizing agent that possesses antibacterial properties and is comedolytic. The antibacterial activity results from the release of active or free-radical oxygen that can oxidize bacterial proteins. Benzoyl peroxide is oxidized into benzoic acid with contact to the skin. It is available OTC and by prescription.

Azelaic acid (Azelex, Finacea)

Clinical Context:  Azelaic acid has been shown to help reduce inflammation and may aid in treatment of postinflammatory hyperpigmentation. Apply it twice daily. Improvement may be seen within 4 weeks.

Erythromycin and benzoyl peroxide (Benzamycin)

Clinical Context:  This agent contains erythromycin, which is a macrolide antibiotic, as well as benzoyl peroxide. Benzoyl peroxide, in addition to being an antibacterial agent, is a keratolytic and desquamative agent. With benzoyl peroxide, free-radical oxygen is released upon administration, oxidizing bacterial proteins in sebaceous follicles and decreasing the number of anaerobic, bacterial, and irritating free fatty acids. It has keratolytic and comedolytic effects.

Erythromycin is indicated for infections caused by susceptible strains of microorganisms.

The combination drug may be applied topically twice daily.

Class Summary

Acne products are used for the treatment of mild to moderate acne vulgaris. These agents may have antibacterial and comedolytic properties. In severe cases, the agents may be used as an adjunct in therapeutic regimens.

What are acneiform eruptions?Which clinical history findings are characteristic of acneiform eruptions?What is nevus comedonicus (NC) and how is it treated?What are eruptive vellus hair cysts (EVHS) and how are they treated?What is steroid-induced acne?What is chloracne and how is it treated?What is the role of antibiotics in the etiology of acneiform eruptions?What is the role of infection in the etiology of acneiform eruptions?What is rosacea and how is it treated?What is perioral dermatitis and how is it treated?What are the differential diagnoses for Acneiform Eruptions?Which tests are performed in the workup of acneiform eruptions?Which histologic findings are characteristic of acneiform eruptions?How are acneiform eruptions treated?What is the role of medications in the treatment of acneiform eruptions?Which medications in the drug class Acne Agents, Topical are used in the treatment of Acneiform Eruptions?Which medications in the drug class Retinoid-Like Agents are used in the treatment of Acneiform Eruptions?Which medications in the drug class Antibiotics, Other are used in the treatment of Acneiform Eruptions?Which medications in the drug class Immunosuppressants are used in the treatment of Acneiform Eruptions?Which medications in the drug class Antihistamines, First Generation are used in the treatment of Acneiform Eruptions?Which medications in the drug class Nonsteroidal Anti-inflammatory Drugs (NSAIDs) are used in the treatment of Acneiform Eruptions?Which medications in the drug class Antifungals, Other are used in the treatment of Acneiform Eruptions?

Author

Julianne H Kuflik, MD, Assistant Clinical Professor of Dermatology, Department of Dermatology, Rutgers New Jersey Medical School

Disclosure: Nothing to disclose.

Coauthor(s)

Robert A Schwartz, MD, MPH, Professor and Head of Dermatology, Professor of Pathology, Professor of Pediatrics, Professor of Medicine, Rutgers New Jersey Medical School

Disclosure: Nothing to disclose.

Specialty Editors

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Dirk M Elston, MD, Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Disclosure: Nothing to disclose.

Additional Contributors

Joshua A Zeichner, MD, Assistant Professor, Director of Cosmetic and Clinical Research, Mount Sinai School of Medicine; Chief of Dermatology, Institute for Family Health at North General

Disclosure: Received consulting fee from Valeant for consulting; Received grant/research funds from Medicis for other; Received consulting fee from Galderma for consulting; Received consulting fee from Promius for consulting; Received consulting fee from Pharmaderm for consulting; Received consulting fee from Onset for consulting.

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Acneiform eruption. Courtesy of DermNet New Zealand (http://www.dermnetnz.org/assets/Uploads/doctors/quizzes/48/case6.jpg).

Acneiform eruption. Courtesy of DermNet New Zealand (http://www.dermnetnz.org/assets/Uploads/doctors/quizzes/48/case6.jpg).