A case of paracetamol-induced acute generalized exanthematous pustulosis in a pregnant woman localized in the neck region.

Abstract

A 32-year-old woman, 18 weeks pregnant, presented to the gynecologic emergency room with an acute fine pustular eruption on her neck and back. There was no history of medical problems. She had had one normal pregnancy that ended with the delivery of a healthy baby and one pregnancy that was aborted because of fetal anomalies. The present third pregnancy had been induced by clominophene and was proceeding normally. During the past 8 weeks, the woman had been taking vitamin B complex and iron sulfate regularly. She developed a fever of 38°C following a routine amniocentesis, for which she was treated with 1 g paracetamol. Several hours later, a mild asymptomatic eruption developed symmetrically on her upper back and sides of the neck consisting of scores of pustules on an erythematous base with a nonfollicular distribution (Figure 1). There was no involvement of mucoses, nails, or peripheral joints. Laboratory investigations showed leukocytosis (10,000/mm3 ) with marked neutrophilia (84%); normal blood and urine chemistry; negative results for blood, amnion fluid, and pustular culture for bacteria, viruses, and fungi; negative blood serologies for Epstein Barr Virus, adeno, and entero viruses; and negative standard patch tests. Histology investigation showed an intraepidermal pustule located subcorneally, with perivascular mixed infiltrate and a few interstitially scattered eosinophiles (Figures 2 and 3). There were no areas of parakeratosis or proliferation of capillaries in the papillary dermis. Paracetamol was stopped, and the eruption resolved within a week with the appearance of a fine desquamation. A definite diagnosis of acute exanthematous pustulosis was made based on the presence of most of the clinical and histologic criteria recently delineated: typical pustules in a typical distribution, acute onset and acute resolution, low-grade fever and neutrophilia, and representative subcorneal spongiform pustules. The main differential diagnosis in this case was with pustular psoriasis, with its special variant of pregnancy impetigo herpetiformis. It was ruled out, however, because of no personal or family history of psoriasis, the absence of other symptoms or signs favoring psoriasis in the physical examination, and normal blood chemistry with no hypocalcemia. Acute generalized exanthematous pustulosis is associated in most cases with antimicrobial drugs, mainly β lactams and macrolides. There is, however, a long list of other drugs that have been reported as possible inducers of this pustular reactive rash, including a few reports on paracetamol.1-4 Skin tests or challenge tests with suspected drugs in this pregnant patient were not performed, but an in vitro interferon-gamma release test with the three suspected drugs (paracetamol, vitamin B complex, and iron sulfate) was conducted 1 month after resolution of the rash, using a previously described method.3 Briefly, the patient's lymphocytes were cultured for 24 hours in test tubes containing phytohemagglutinin and each drug or with medium alone (10% fetal calf serum). Unmodified drugs dissolved in the appropriate solvents. Following incubation, the supernatants were collected for the detection of interferon-gamma release using the ELISA technique (Biotest, Enco Diagnostics, Petach Tikvah, Israel). Interferon-gamma release was measured by the percentage of its increase calculated by an accepted formula.3 A remarkable increase of interferon (94%) was observed following in vitro challenge of the patient's lymphocytes with paracetamol, but not with iron sulfate or B complex. In vitro challenge of lymphocytes from a control patient who had taken paracetamol without developing an adverse reaction with the drug failed to induce an increase in interferon (Table). These findings point, without doubt, to paracetamol as the drug responsible for inducing acute generalized exanthematous pustulosis in this case. Figure 1Open in figure viewerPowerPoint A fine pustular eruption, located on the (A) upper back and (B, C) sides of the neck, consisting of numerous nonfollicular pustules on an erythematous base Table .. Results of In Vitro Interferon-Gamma Release Test in the Patient With Acute Generalized Exanthematous Pustulosis (AGEP) and in the Control Patient Patient Drug Interferon-Gamma Without Drug(pg/ml) Interferon-Gamma with Drug(pg/ml) Interferon-Gamma Increase(%) AGEP Paracetamol Vitamin B complex 552 552 1074 542 94 No increase Iron sulfate 552 522 No increase Control Paracetamol 962 930 No increase Vitamin B complex 962 961 No increase Iron sulfate 962 949 No increase