Jpn. J. Infect. Dis., 54, 2001

Laboratory and Epidemiology Communications
Skin EmptlOn 8 Days a洗er a Single Dose ofEfavirenz‑Containlng Combination Therapy
Hirohisa Yazaki, Yoshimi Kikuchi and Shinichi Oka*AIDS Clinical Center, International Medical Center ofJapan,
Toyama 1‑21‑1, Shinjuku‑ku, Too,0 162‑8655
Communicated by Hiroshi Yoshikura(Accepted January 1 5, 2002)

A 24‑yeaト01d woman visited our clinic on 14 August 2001

because of a generalized skin eruptlOn and fever of 37. loC.
The eruptlOn had appeared on the preceding night on her lower
extremities and had extended to her whole body within 1 day.
A photograph of her fわrearms is shown in Fig. 1. Examina‑tion showed erythematous discrete papules surrounded bywhite skin, causlng Severe itching. These features resembled

those of eruptions induced by efavirenz (EFV). Written
informed consent was obtained from this subject to report
this unusual emptlOn and to include her photograph.
The husband, a 3トyear‑old hemophilia A patient, wasinfected with HIV‑1 following infusion of a contaminatedblood product befわre 1985. He had been treated with 40 mg

bid stavudine (d4T), 150 mg bid lamivudine (3TC), and 600
mg q.d. EFV since Febmary 2000. The couple got ma汀ied inDecember 2000. At the time orpresentation, a blood sample
taken from the husband showed a CD4 count of >400 cells/
LIL and viral load <50 copies/mL. After sexual intercourse
without uslng a COndom on the night of4 August 2001, thewife decided to take 40 mg d4T, 150 mg 3TC, and 600 mg
EFV only once the next momlng aS pOSteXpOS∬e prophylaxis.

Fig. 1. A photograph of the forearms of the affected patient taken on 14

She reported not taking any other or repeat dose of the above

August 2001. EmptlOmS Were itchy, erythematous discrete papulcs

prophylaxis thereafter. She had been well until the eruptlOnsurrounded by white skin, and measured 1‑5 mm in diameter. The

appeared on 1 3 August and had never previously taken anti‑

appearance of the skin lesion and the clinicalcourse was qulte Simト

tar to that orEFV‑induced lesions.

HIVl drugs. An antihistamine was used f♭r 2 days f♭r thetreatment of emptlOnS, Which resulted in a gradual disappear‑

ance of eruptlOnS Within 1 week without scamng. No otherwith EFV. The EFV‑induced eruptlOn Often appears aroundclinical symptoms, including fever, Were noted during theclinical course. Blood tests on 14 August revealed no abnor‑

10 days after commencement or therapy and sometimes

mahties, including a WBC of4,200/LIL with normal differen‑

improves spontaneously without medication within 1 week,

tial count, hemoglobin 12.5 g/dL, platelets 1 8.6/LIL, aspartateeven when the same therapy lS COntinued at the same dose.

aminotransferase 1 3 U/L, lactate dehydrogenase 1 33 U/L, andThe skin eruptlOnS Seen in our patient also appeared 8 days

C‑reactive protein 0.20 mg/dL. Immunoglobulin G (IgG)

after taking d4T, 3TC, and EFV and improved within 1 week.

antibodies to measles, rubella, and cytomegalovirus wereThus, the clinical presentation and course were very similar.

already positive, and lgM antibodies to these viruses wereHowever, the striking difference between this case and othernegative at presentation. All of the anti‑HIV‑ 1 antibody tests

HIVI cases of EFV‑induced emptlOn Was that our patientperf♭med on 14 August, 5 October, and 8 November weretook the drugs only once, while a full course of treatment isnegative. HIVI RNA in plasma was also negative on 8

usually taken by HIV 1 patients. EruptlOn induced by EFV isNovember. The patient had no histories offTood or drug allergleS

usually considered to be an allerglC reaction to the drug, lnand denied eatlng eXCePt10nal food or taking any medica‑

which hypersensitivlty lS evoked during therapy. However,tions fわr at least 1 week befわre the emptlOn.

the usual resolution of eruptlOnS Without discontinuation of

The skin eruptlOn in our patient was very similar to thethe same therapeutic dose argues agalnSt drug‑induced

skin rash occasionally observed in patients treated with EFV;

hypersensitivity. For example, trimethoprim/su胞methoxazole

which has a very unlque appearance and can easily be distin‑(T/S)‑induced hypersensitivity is successfully desensitized byguished from other eruptlOnS Caused by drugs commonly used

restarting a very low dose ofT/S (1). In some cases, most if
not all of the causative drugs or their metabolites can have*Corresponding author: Tel/Fax: +8 1 ‑3‑527315 1 93, E‑mail: oka@

toxic effects, which could manifTest as skin eruptions. However,in our case, drugs or their metabolites had already been

imcj.hosp.goJP

246

Jpn. J. Infect. Dis., 54, 200l
excreted at the onset. We丘rst thought that the enlption was aREFERENCES

clinical manifestation of acute viral infection. However, We
were able to exclude various acute viral infections often

1. Yoshizawa, S., Yasuoka, A., Kikuchi, Y., Honda, M.,

associated with generalized erythematous papules, including

HIV‑1 infection, by clinical, biochemical, and serologlCal

Gatanaga, H., Tachikawa, N., Hirabayashi, Y. and Oka,
S. (2000): A 5‑day course of oral desensitization toexaminations, although very rare viral infections could nottrimethoprim/sulfamethoxazole (T/S) in patientswith

be ruled out. Ifthe skin emptlOn in our patient was actuallyhuman immunodeficiency virus type‑1 infection who

caused by EFV the mechanism of EFV‑induced emptlOn must

were previously lntOlerant to T/S. Ann. Allergy Asthma
lmmuno1., 85, 241‑244.

be considered to be more heterogeneous than previously
thought.

2. Centers f♭r Disease Control and Prevention (2001):

EFV is likely to be used widely in the future as a post‑

Updated U.S. Public Health Service guidelines fわr theexposure prophylaxis, including after needle injury, aS it has

management of occupational exposures to HBV; HCV andHIV and recommendations fわr postexposure prophylaxis.

proved itself useful in the?xpanded therapeutic regimen (2)･
severe complications of the central nervous system a洗er theMorbid. Mortal. Wkly. Rep., 50, RR‑1 1.
3. Marzolini, C., Telenti, A., Decosterd, LA., Greub, G.,

first few doses (3), a possible occurrence of skin eruptions

Biollaz, J. and Buclin, T. (2001 ): Efavirenz plasma levels

should also be monitoredfrom the start of therapy, and suchcan predict treatment failure and central nervous system

individuals should be followed for at least 2 Weeks afterside effects in HIV‑1‑infected patients. AIDS, 15, 71‑75.

While its continued use is Impossible fb∫ those who develop

discontinuation of therapy.

247