A 66-year-old male patient was admitted to the hospital with abnormal speech and behavior over 3 days. The patient had a history of hypertension and long-term heavy alcohol consumption (> 50 years). There was no history of liver disease. On admission, the patient had a low-grade fever (100.4 F). In addition, his other vital signs were stable. Physical examination revealed no generalized lymphadenopathy or hepatosplenomegaly. Neurological examination was unremarkable, and the patient was negative for meningism. Computed tomography (CT) of the chest revealed chronic bronchitis with bilateral lung infections (Figure 1). Abdominal CT showed no significant abnormalities. Screens for human immunodeficiency virus (HIV), syphilis, tuberculosis (TB) IgG antibodies, and hepatitis A, B, and C viruses were all negative. Cerebrospinal fluid (CSF) analysis showed no significant abnormality. Furthermore, culture results were negative. Laboratory test results showed an elevated white blood cell (WBC) count, 15.18 x 109/L; high neutrophil percentage, 77%; and high urinary amylase, 1,118 U/L. His serum lactate dehydrogenase, liver transaminases, and bilirubin levels were normal.
Pip/Taz 4.5 g intravenous (IV) q12h empirical anti-infective therapy was initiated on admission according to the Pip/Taz instructions of the "National Centralized Drug Procurement" policy. Treatment was effective. Seventy-two hours after treatment, the PCT level was at 0.08 ng/mL. The patient's respiratory symptoms improved, and his body temperature normalized. However, on day 10 after Pip/Taz treatment, the patient developed a fever of 104.7 F with chills and his PCT levels began to gradually increase. Therefore, we made dose adjustments based on the patient's response to treatment. Pip/Taz treatment was adjusted to 4.5g IV q8h. Additionally, blood, urine, and sputum samples were collected for analysis. Laboratory test results showed low WBC, 2.72 109/L; normal neutrophil percentage, 48.8%; and high lymphocyte percentage, 43.8%, indicating relative lymphocytosis. Serum PCT was persistently elevated (Figure 2). D-dimer was 40.19 ug/mL. In addition, lactate dehydrogenase was high at 560 U/L. Serum levels of eosinophils, hepatic transaminase, bilirubin, and amylase, were all normal. The antibiotic treatment was switched to meropenem (1 g IV q8h), considering the possibility of exacerbated or drug-resistant bacterial infection.
Seventy-two hours after meropenem treatment, the patient again developed high a fever of 105.4 F. On examination, a generalized, pruritic non-blanching rash was observed. Although a chest CT scan showed no obvious lung lesions (Figure 1), it revealed multiple enlarged lymph nodes in the mediastinum and bilateral axillae. Blood culture results of blood, urine, and sputum specimens were all negative. A test for the protozoal parasite Plasmodium vivax was also negative. Laboratory test results showed high WBC, 15.9 x 109/L; neutrophil percentage, 65.8%; and serum PCT, 4.11 ng/mL. These results also showed persistently elevated eosinophils,1.69 x 109/L (Figure 2); B-type natriuretic peptide (BNP), 1,575 pg/mL; IL-6, 9.45 pg/ml; IL-10, 26.51 pg/ml; and interferon-gamma (IFN-gamma), 116.17 pg/ml. Furthermore, cytomegalovirus IgG was elevated to 531 AU/mL. Levels of herpes simplex virus type I (HSV-I) IgG and herpes simplex virus type II (HSV-II) IgG were 339 AU/ml and 27 AU/ml, respectively. Serum creatinine, liver bilirubin, and transaminase levels were normal.
The patient experienced no significant discomfort during the fever. Several subspecialties assessed the patient for a non-infectious cause. Pip/Taz and meropenem-induced DRESS was considered based on elevated eosinophils, fever, almost universal non-blanching rash, lymphadenopathy, and organ involvement, all of which met DRESS diagnostic criteria (Table 1).
Meropenem treatment was discontinued, and methylprednisolone 500 mg IV daily was started for 3 days for shock therapy and tapered, along with concomitant anti-allergic treatment (specifically: intravenous calcium gluconate, oral ebastine, and topical calamine lotion). The patient's fever rapidly resolved, levels of eosinophils and PCT decreased and the generalized rash gradually subsided. However, BNP levels remained abnormal. Following discharge, the patient was prescribed prednisone (40 mg po daily for 2 weeks and then tapered over a 3-week period). Monthly telephone follow-ups were conducted. Five months following discharge, no further fever was reported, and the generalized rash was reported to have subsided.