Acute Localized Exanthematous Pustulosis
A Cutaneous Drug Reaction in a Dental Setting
Jennifer L. Vickers, BS,
Ryan J. Matherne, MD,
Elgene G. Mainous, DDS and
Brent C. Kelly, MD
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ABSTRACT
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Background. Acute generalized exanthematous pustulosis is a severe cutaneous eruption caused most commonly by antibiotics. Rarely, a localized variant of this pustular reaction called "acute localized exanthematous pustulosis" has been described.
Case Description. A 29-year-old woman sought treatment at the authors’ dermatology clinic for an outbreak of numerous superficial, nonfollicular pustules with an underlying erythematous base that was accompanied by subjective fever. The lesions appeared two days after the patient began taking amoxicillin prescribed for endocarditis prophylaxis before she underwent a dental cleaning. Cultures were negative for bacteria, and the eruption resolved within four days after the patient discontinued the drug therapy.
Clinical Implications. Newly revised guidelines for antibiotic prophylaxis for endocarditis indicate that adverse reactions far outweigh the benefits in most cases. It is important that general dentists and oral surgeons recognize this rare pustular eruption, because antibiotics, particularly amoxicillin, are the primary inciting agents. In addition, health professionals should make clinical choices based on evidence, weigh the risks of any treatment plan against its benefits and practice caution when prescribing any drug.
Key Words: Acute generalized exanthematous pustulosis; acute localized exanthematous pustulosis; amoxicillin; endocarditis prophylaxisAbbreviations: AAOS: American Academy of Orthopedic Surgeons. • ADA: American Dental Association. • AGEP: Acute generalized exanthematous pustulosis. • AHA: American Heart Association. • ALEP: Acute localized exanthematous pustulosis.
Acute generalized exanthematous pustulosis (AGEP) is an uncommon but well-known cutaneous drug reaction characterized by the eruption of dozens to hundreds of scattered pustules following drug administration. Acute localized exanthematous pustulosis (ALEP) is a less common form of pustular drug eruption in which lesions are consistent with the characteristics of AGEP but are localized typically to the face, neck or chest. It is important that general dentists and oral surgeons recognize this rare pustular eruption, because antibiotics, particularly amoxicillin, are the primary inciting agents. We present a case of a woman with a cutaneous drug reaction consistent with ALEP that occurred subsequent to prophylactic administration of amoxicillin in a dental setting.
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CASE REPORT
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A 29-year-old Latin-American woman with a history of acne rosacea sought treatment at our clinic in the Department of Dermatology at the University of Texas Medical Branch, Galveston, for an outbreak of numerous pustules in the area of the nose, perioral region, chin and, to a lesser extent, the cheeks (Figure 1
). The pustules were scattered, superficial and nonfollicular, with an underlying erythematous base (Figure 2). The pustules began two days after the patient initiated a course of amoxicillin therapy prescribed by her dentist for endocarditis prophylaxis during a routine dental cleaning. She reported subjective fever and fatigue but no nausea or vomiting. She returned to her dentist because of concerns regarding a drug reaction. The dentist thought the pustules most likely represented a flare of her rosacea and subsequently referred her to the dermatology clinic. Cultures of a pustule were negative for bacteria. The patient’s pustule eruption rapidly resolved, accompanied by desquamation, within four days of discontinuing the amoxicillin treatment.
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DISCUSSION
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The pustules associated with AGEP are nonfollicular and sterile and often coalesce on an edematous, erythematous base. The eruption can be accompanied by fever and neutrophilic leukocytosis. Onset is abrupt and usually begins in skin folds or on the face before spreading to the trunk and extremities.1,2 Although lesions typically appear within a few days after drug administration, the time of first appearance can vary from two days to three weeks. Resolution, which is accompanied by generalized desquamation, occurs approximately four to 10 days after discontinuation of the medication.2 The major histologic feature of AGEP is spongiform, subcorneal pustules.Although the literature reports cases of AGEP caused by a wide range of drugs, it is most commonly associated with antimicrobials, particularly macrolides, betalactams and terbinafine.1 The pathophysiology of the condition is not well-known. However, clinicians have used patch tests and lymphocyte transformation tests to aid in the diagnosis of AGEP, and several patients with a history of AGEP have demonstrated a drug-specific lymphocyte proliferation response measured in vitro. These findings strongly suggest T lymphocyte involvement.3
Prange and colleagues4 first defined ALEP. They described a woman whose symptoms fit the criteria of AGEP and whose lesions were localized to the face. To our knowledge, investigators have reported ALEP in six separate case reports.5–10 These reports describe patients with lesions that are consistent with the characteristics of AGEP but are localized typically to the face, neck or chest. Two cases occurred following administration of amoxicillin-clavulanic acid,5,6 three occurred following administration of amoxicillin only7–9 and one occurred after administration of levofloxacin.10 Two cases, in addition to our case, are known to have occurred when prophylactic antibiotics were given in a dental setting.6,9
Previously, the American Heart Association (AHA) and the American Dental Association (ADA) recommended that patients with certain heart conditions take antibiotics before undergoing dental procedures to prevent infective endocarditis. The AHA, in conjunction with the ADA, revised the guidelines originally published in 1997 and published the revisions in the October 2007 issue of AHA’s journal Circulation and the January 2008 issue of The Journal of the American Dental Association (JADA).11,12 The new guidelines are based on a growing body of scientific evidence that shows the risks of taking preventive antibiotics outweigh the benefits for most patients. The risks include adverse reactions to antibiotics that range from mild to potentially severe and, very rarely, can result in death. Inappropriate use of antibiotics also can lead to the development of drug-resistant bacteria. The guidelines now recommend that many of the patients for whom clinicians previously prescribed prophylactic antibiotics no longer need short-term antibiotics for the prevention of infective endocarditis. The recommendations indicate that only patients who are most likely to experience an adverse outcome if they develop a heart infection—such as those with artificial heart valves, a history of infective endocarditis, certain severe congenital heart conditions or a cardiac transplant that develops a problem with a valve—should receive prophylactic antibiotics for routine dental procedures.11,12
Before prescribing any antibiotic regimen, all health care professionals should consider the existing balance between the perceived benefit of the drug and the risks of adverse reactions.
Likewise, the ADA and the American Academy of Orthopedic Surgeons (AAOS) published their first advisory statement on antibiotic prophylaxis for dental patients with prosthetic joints in 1997; these organizations revised and published updated guidelines in the July 2003 issue of JADA.13 The revised guidelines now indicate (as did the AHA’s) that, on the basis of the evidence, it is more likely that spontaneous bacteremias result from daily activities, such as brushing or flossing, than from dental treatments, and the risk of adverse reactions to antibiotics, as well as the risk of developing bacterial resistance, is far greater than the benefit achieved from the use of prophylactic antibiotics. Clinicians should implement vigorous treatment with antibiotics only in patients who have acute orofacial infections and who have undergone total joint prosthesis placement. There is no scientific evidence to support the use of antibiotics in dental patients who have plates or screws or the routine use of antibiotics in patients who have had total joint replacement.13
In this case report, the indication for administration of antibiotics is unclear given that the patient had no known heart or joint conditions. In addition, the clinician prescribed a 10-day course of amoxicillin, which does not correspond with the AHA-recommended regimen of a single dose of 2 grams of amoxicillin administered 30 to 60 minutes before a dental procedure.11,12 Given the temporal correlation of the onset and resolution of the lesions with, respectively, the administration and discontinuation of the antibiotic therapy, we suggest that the administration of the antibiotic therapy caused this patient’s outbreak. Because of the patient’s history, acne rosacea or acne vulgaris should have been considered in the differential diagnosis; however, with the extremely abrupt onset of lesions, the patient’s report of subjective fever, the resolution of symptoms with discontinuation of the antibiotic treatment and healing accompanied by desquamation rather than scarring and pigmentation, the diagnosis of acne is unlikely. In addition, the pustules were superficial and nonfollicular, which is not the appearance of acne rosacea or acne vulgaris. In light of the patient’s clinical presentation and its similarity to previously published case reports, we believe this to be a case of ALEP secondary to amoxicillin administration.
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CONCLUSIONS
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Dental care professionals should be aware of this rare reaction to antibiotics and of the updated practice guidelines outlined by the AHA, the ADA and the AAOS regarding the administration of antibiotics. Before prescribing any antibiotic regimen, particularly one that is prophylactic in nature, all health care professionals should consider the existing balance between the perceived benefit of the drug and the risks of adverse reactions and potential for development of bacterial resistance. Clinicians should prescribe prophylactic antibiotics only for patients whose medical histories are congruent with the criteria as delineated in the revised practice guidelines, and the prescribed regimen should follow the described treatment regimen appropriate for the individual patient. Health care professionals also should keep in mind that, in general, the formerly widely used practice of prescribing prophylactic antibiotics as reinforcement despite the lack of any true indication no longer is thought to be practical or prudent. Health care professionals should make evidence-based choices and practice caution when faced with the decision of whether to prescribe a drug.
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FOOTNOTES
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Ms. Vickers is a fourth-year medical student in the School of Medicine, University of Texas Medical Branch, Galveston.
Dr. Matherne is a resident in the Department of Dermatology, University of Texas Medical Branch, Galveston.
Dr. Mainous is a professor and the chief of the Department of Oral and Maxillofacial Surgery, University of Texas Medical Branch, Galveston.
Dr. Kelly is an assistant professor in the Department of Dermatology, University of Texas Medical Branch, 301 University Boulevard, Galveston, Texas 77555-0783, e-mail "bckelly{at}utmb.edu". Address reprint requests to Dr. Kelly.
Disclosure. The authors did not report any disclosures.
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REFERENCES
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ABSTRACT
CASE REPORT
