An acneiform drug eruption is an atypical form of acne seen in association with numerous pharmacological agents, such as antimicrobials, corticosteroids, and many immunomodulating/chemotherapeutic drugs. The clinical presentation includes a papulopustular rash accompanied by pruritus, usually within a few days after administration of the mentioned medications. The typical presence of comedones prior to the development of these lesions in acne is absent, which is one of the main distinguishing features from acne. Clinical assessment, potentially supported by a histopathological examination, is crucial in order to make the diagnosis.
Presentation
An acneiform drug eruption is considered to be an important cutaneous drug-induced adverse effect. It has been described in patients taking both topical and systemic drugs [1], with the most involved classes being antimicrobials (tetracycline, streptomycin, isoniazid, clofazimine, and antimycotics), central nervous system (CNS)-acting agents (lithium, phenobarbital, and hydantoin derivatives such as phenytoin), chemotherapeutics (epidermal growth factor receptor - EGFR inhibitors such as cetuximab, erlotinib, and gefitinib, but also cyclosporin A), interferon (IFN), gold salts, etc. [1] [2] [3] [4]. Corticosteroids, in topical as well as systemic formulations, are particularly associated with an acneiform drug eruption in women [1]. The typical signs are characterized by the onset of skin lesions within several days after the introduction of drugs [5]. Erythematous follicular papules are the hallmark of an acneiform drug eruption [1] [3] [5] [6]. These lesions develop on the face, but also on the extremities, particularly on the forearms and buttocks, whereas the shoulders, the retroauricular area, and the superior portion of the trunk might serve as additional locations [1] [3] [5] [6]. The papules are further differentiated from acne vulgaris by the formation of punctiform vesicles in the center, followed by vesiculopustular progression [1]. Additional findings that exclude acne vulgaris are the absence of comedones that should normally precede the formation of acne, the older age of the patient (acne are primarily seen in adolescence), accompanying signs of systemic drug toxicity (eg. fever or malaise), and resolution of lesions after discontinuation of the drug [1] [5].
Entire Body System
- Pathologist
Tissue pathways for urological pathology The target primary users of the tissue pathway are trainee and consultant cellular pathologists. These recommendations will also be of value to trainee/qualified biomedical scientists involved in... [evidence.nhs.uk]
Drug-induced skin reactions: a pathologist viewpoint. Cutan Ocul Toxicol 2016; 35: 67–79. DOI: 10.3109/15569527.2015.1015725. Journal Ocvirk J, Heeger S, McCloud P, Hofheinz RD. [dermnetnz.org]
Cardiovascular
- Hypertension
[…] urticaria–like skin lesions to painful oral ulcers with widespread bullous skin lesions (see Erythema Multiforme and Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis ) Penicillin, barbiturates, sulfonamides (including derivatives used to treat hypertension [merckmanuals.com]
Eyes
- Photophobia
There may also be eye symptoms like redness, tearing, dryness, a sensation of foreign bodies in the eyes and photophobia. It can be triggered by the sun, wind, weather extremes, drinking alcohol, eating hot and spicy foods. [skinspecialistsonline.com]
- Blepharitis
Associated eye findings are variable but include blepharitis, conjunctivitis, iritis, iridocyclitis, hypopyon iritis, and even keratitis. [emedicine.medscape.com]
Musculoskeletal
- Myalgia
[…] immune complex vasculitis Chlorothiazide, meprobamate, anticoagulants Serum sickness–type drug reaction A type III immune complex reaction Acute urticaria and angioedema more common than morbilliform or scarlatiniform eruptions Possibly polyarthritis, myalgias [merckmanuals.com]
The most prevalent clinical findings of DIL are musculoskeletal (e.g., arthralgias, myalgias, arthritis) and constitutional (e.g., fever, malaise, anorexia, weight loss) symptoms. 17,18 Certain agents are more closely linked with specific clinical findings [uspharmacist.com]
Skin
- Acneiform Eruption
Drug-Induced Acneiform Eruptions T2 - Drug-induced Acneiform Eruptions AU - Do, Ha K. [indiana.pure.elsevier.com]
Follicular acneiform eruption induced by imatinib. J Eur Acad Dermatol Venereol. 2006;20:1368–70. PubMed Google Scholar 46. Lee JE, Lee SJ, Lee HJ, Lee JH, Lee KH. Severe acneiform eruption induced by cetuximab (Erbitux). [link.springer.com]
Some sources consider acne vulgaris part of the differential diagnosis for an acneiform eruption. [4] Other sources classified acne vulgaris under acneiform eruption. [5] MeSH explicitly excludes perioral dermatitis from the category of "acneiform eruptions [en.wikipedia.org]
What Are Acneiform Eruptions? Acneiform eruptions are skin lesions that are similar to those acne vulgaris. What Causes Acneiform Eruptions? Causes of acneiform eruptions include: 1. [skinspecialistsonline.com]
- Acne Vulgaris
Additional findings that exclude acne vulgaris are the absence of comedones that should normally precede the formation of acne, the older age of the patient (acne are primarily seen in adolescence), accompanying signs of systemic drug toxicity (eg. fever [symptoma.com]
Acne vulgaris is a polymorphic infl ammatory skin disease, clinically characterized by mixture of comedones, superficial and deep infl amed papules, pustules, and nodules. It is a chronic infl ammation of the pilosebaceous unit. [indiana.pure.elsevier.com]
Patient discussion about acne vulgaris Q. what is the best treatment for acne vulgaris A. [medical-dictionary.thefreedictionary.com]
Some sources consider acne vulgaris part of the differential diagnosis for an acneiform eruption. [4] Other sources classified acne vulgaris under acneiform eruption. [5] MeSH explicitly excludes perioral dermatitis from the category of "acneiform eruptions [ipfs.io]
How is acne vulgaris treated? There are many safe and effective acne treatments. [dermcoll.edu.au]
- Photosensitivity
It may be idiopathic or result from either endogenous photosensitizers or exogenous causes, such as drugs. 5,13-16 Photosensitivity reactions may manifest as either a photo-allergic or phototoxic reaction. [uspharmacist.com]
Photosensitivity is not an immunological reaction. It may be caused by production of free radicals or reactive oxygen species. There is an excessive sensitivity to sunburn. The phenothiazines and doxycycline are often involved. [patient.info]
Vertigo caused by high-dose minocycline, demethylchlortetracycline-related photosensitivity reactions, and irritant reactions from topical retinoids are examples. [plasticsurgerykey.com]
[…] to painful oral ulcers with widespread bullous skin lesions (see Erythema Multiforme and Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis ) Penicillin, barbiturates, sulfonamides (including derivatives used to treat hypertension and diabetes) Photosensitivity [merckmanuals.com]
The most commonly associated drugs are antibiotics (ampicillin, penicillin, cephalosporins), the sulphonamides, isoniazid, phenytoin and carbamazepine, NSAID, gold, thiazides and allopurinol Photosensitive eruptions Figure 5 Refer to the chapter on Photodermatoses [pcds.org.uk]
- Skin Rash
Skin rash A rash is an area of irritated or swollen skin. [icdlist.com]
A review of the treatment options for skin rash induced by EGFR targeted therapies: Evidence from randomized clinical trials and meta-analysis. Radiol Oncol 2013; 47: 166–175. DOI: 10.2478/raon-2013-0014. [dermnetnz.org]
Patients presenting with a skin rash or skin lesions should be thoroughly assessed for the possibility of such a relationship and, if one is found, should be treated (if necessary) and educated regarding the drug-induced skin disorder ( TABLE 2 ). [uspharmacist.com]
- Alopecia
alopecia : Pseudopelade of Brocq Central centrifugal cicatricial alopecia Pressure alopecia Traumatic alopecia Tumor alopecia Hot comb alopecia Perifolliculitis capitis abscedens et suffodiens Graham-Little syndrome Folliculitis decalvans ungrouped: Triangular [en.wikipedia.org]
Other physical manifestations include acneiform papules and pustules where comedones are absent, alopecia, tenderness and redness on the palms and soles, target lesions seen in erythema multiforme, tender, erythematous nodules seen in erythema nodosum [aocd.org]
Alopecia Alopecia may occur with angiotensin-converting enzyme (ACE) inhibitors, allopurinol, anticoagulants, azathioprine, bromocriptine, beta-blockers, cyclophosphamide, hormones (especially those with androgenic effects), indinavir, NSAIDs, phenytoin [patient.info]
Workup
The diagnosis of an acneiform drug eruption rests on the ability of the physician to identify the key findings and establish the underlying cause. For this reason, a thorough patient history and a detailed physical examination are main steps in order to raise suspicion toward this entity. Recent administration of the previously mentioned pharmacological agents is perhaps the crucial piece of information that can be obtained. Other patient details, such as age, the presence of underlying disorders for which these drugs are used, and the pattern of rash distribution are equally important for making a presumptive diagnosis. Recognition of an acneiform drug eruption is mainly based on clinical grounds, but a biopsy with subsequent histopathological examination can be performed. Typical findings include spongiosis, disruption of the follicular epithelium and a nonspecific inflammatory reaction with both lymphocytes and neutrophils [5], whereas a suppurative follicular inflammation with a dense neutrophilic infiltrate is reported by other authors [6].
Treatment
It provides dermatologists with the most recent developments in the treatment of acne and associated disorders. [books.google.com]
Treatment consists of discontinuing the glucocorticoid or protecting the skin from the inhaled product. Initial treatment includes topical antibiotics and sulfur preparations. [ime.acponline.org]
There are many safe and effective acne treatments. [dermcoll.edu.au]
Topical therapy is usually the best place to start treatment. 12 If tolerated, benzoyl peroxide is the simplest and most cost-effective treatment. Bacterial resistance to benzoyl peroxide has not been noted. [clinicaladvisor.com]
Etanercept was subsequently discontinued and the patient was started on ustekinumab for treatment of psoriasis and psoriatic arthritis as well as minocycline (100 mg twice daily) for treatment of nodulocystic acne. [mdedge.com]
Prognosis
Prognosis Most cases resolve without complications but it may take 10-14 days for the rash to disappear. Patients with exanthematous eruptions will have mild desquamation as the rash resolves. [patient.info]
Etiology
Perioral dermatitis, also a disorder of unclear etiology, is mainly observed in the young, white, female population as papulopustules with erythematous base. [emedicine.medscape.com]
[…] of comedones or any apparent infectious etiology, acne vulgaris is characterized by the presence of sebum and comedones. 2-4 Like EGFR, HER-2 receptors have been shown to play a role in keratinocyte differentiations in the skin 5 ; hence, the observed [jhoponline.com]
(Etiology) Drug-Induced Acne occurs as an adverse reaction of the body to certain medications that are taken for various conditions. [dovemed.com]
Other cutaneous eruptions that may superficially resemble acne vulgaris but that are not thought to be related to it etiologically are due to infection (e.g. gram-negative folliculitis) or unknown causes (e.g. acne necrotica or acne aestivalis). [karger.com]
Epidemiology
Epidemiology [ 2 ] Hospital Episode Statistics from 1996 to 2000 logged 62,000 hospital admissions in England each year due to drug allergies and adverse drug reactions. [patient.info]
Drug-induced skin pigmentation: epidemiology, diagnosis and treatment. Am J Clin Dermatol. 2001;2:253-262. To comment on this article, contact [email protected] [uspharmacist.com]
Pathophysiology
Steroid-induced acneiform eruption Member Rated 0 Patient case no. 10804 Date added 02 June 2010 Patient details Age Adult Location India Localisation Head / face Primary Lesions Comedones Erythema papules Pustule Pathophysiology inflammatory skin appendage [dermquest.com]
The pathophysiology of acneiform eruption is poorly understood. [e-ijd.org]
Clinical signs, pathophysiology and management of skin toxicity during therapy with epidermal growth factor receptor inhibitors. Ann Oncol. 2005;16:1425–33. PubMed Google Scholar 56. Sladden MJ, Clarke PJ, Mitchell B. [link.springer.com]
Pharmacotherapy: A Pathophysiologic Approach. 8th ed. New York, NY: The McGraw Hill Companies, Inc; 2008:1661-1672. 7. Chia FL, Leong KP. Severe cutaneous adverse reactions to drugs. Curr Opin Allergy Clin Immunol. 2007;7:305-309. 8. [uspharmacist.com]
Prevention
How can Drug-Induced Acne be Prevented? Currently, it may not be possible to prevent Drug-Induced Acne. Stopping the medication causing the condition as early as possible is important. [dovemed.com]
Prevention of acneiform rash caused by EGFR inhibitors includes topical corticosteroids (hydrocortisone 2.5%, alclometasone) and oral antibiotics (minocycline, doxycycline, or antibiotics covering skin flora) twice daily for at least the first 6 weeks [ascopost.com]
This is also known as a comedolytic treatment (“comedolytic” is the term used to describe a product or medication that prevents the formation of comedones such as whiteheads and blackheads). [dermcoll.edu.au]
All patients should be educated to avoid the offending agent to prevent further complications. [aocd.org]
Etanercept works by acting as a decoy receptor for TNF-α, thereby preventing it from binding cell surface receptors and subsequently decreasing inflammation. [mdedge.com]
References
- Rosa DJ, Matias FAT, Cedrim SD, Machado RF, Sá AA, Silva VC. Acute acneiform eruption induced by interferon beta-1b during treatment for multiple sclerosis. An Bras Dermatol. 2011;86:336–338.
- Du-Thanh A, Kluger N, Bensalleh H, Guillot B.Drug-induced acneiform eruption. Am J Clin Dermatol. 2011;12(4):233-245
- Pontello Junior R, Kondo RN. Drug-induced acne and rose pearl: similarities. An Bras Dermatol. 2013;88(6):1039-1040.
- Plewig G, Jansen T. Acneiform dermatoses. Dermatology. 1998;196(1):102-107.
- Segaert S, Van Cutsem E. Clinical signs, pathophysiology and management of skin toxicity during therapy with epidermal growth factor receptor inhibitors. Ann Oncol. 2005;16:1425–1433.
- Lee JE, Lee SJ, Lee HJ, Lee JH, Lee KH. Severe acneiform eruption induced by cetuximab (Erbitux) Yonsei Med J. 2008;49:851–852