A 36-Year-Old Woman With Recurrent High- Grade Fevers, Hypotension, and Hypertriglyceridemia RICHARD C. CHOU, 1 CHARLES A. DINARELLO, 2 JUDITH A. FERRY, 1 AND PAOLA DAL CIN 3 INITIAL CLINICAL PRESENTATION Chief symptom A 36-year-old white woman was transferred for evaluation of a 6-month history of recurrent high-grade fevers and episodic hypotension. History of the present illness The patient had been admitted 6 months earlier to an outside hospital with a high-grade fever, an erythematous rash on her lower extremities, and pain in her legs. She had a history of bipolar disorder and schizoaffective dis- order, and had been treated with the antipsychotic medi- cations ziprasidone and quetiapine fumarate. An initial evaluation for infections was negative, and broad- spectrum antibiotics failed to relieve the fever. The pa- tient’s fevers were attributed to the neuroleptic malignant syndrome (Table 1). Her fevers continued unabated to temperatures as high as 103°F, despite discontinuation of her antipsychotic medications and treatment with bro- mocriptine. She was transferred to another hospital for further evaluation and management. At the transfer hospital, the patient exhibited a transient increase in her creatine kinase level to 1,389 units/liter (normal value 240). Assays for antinuclear antibodies, antibodies to double-stranded DNA, and extractable nu- clear antigens (Ro, La, Sm, and RNP) were negative, as were anti–Jo-1 antibodies. A magnetic resonance image of the lower leg showed muscle edema with localized infarc- tion. A muscle biopsy showed perivascular inflammatory infiltrates consistent with an inflammatory myopathy. Prednisone 60 mg/day was started and azathioprine was considered, but the patient’s localized rash and leg pain resolved spontaneously before treatment with azathio- prine was started. The patient was prescribed a tapering course of prednisone for presumed dermatomyositis, and did not experience recurrent episodes of fever, rash, or leg pain while receiving glucocorticoids (Table 1). No photo- graphic record of the patient’s original rash exists. Within one week of discharge, the patient developed recurrent fevers and was readmitted to a third hospital. Her dose of prednisone at that time was unknown. She was later found to have a urinary tract infection caused by Escherichia coli and was treated with trimethoprim/sulfa- methoxazole. Despite antibiotic treatment, the patient con- tinued to have intermittent high-grade fevers and episodes of hypotension, with blood pressure as low as 70/40 mm Hg (Table 1). She was transferred to a fourth hospital. Upon transfer, the patient had a temperature of 104°F, sinus tachycardia (140 –160 beats/minute), hypotension, and a hematocrit of 20%. There was no rash despite the development of intermittent high-grade fever. Multiple cultures were negative for infection. The pa- tient underwent a bone marrow biopsy that showed a hypercellular marrow, and a peripheral smear showed some dysplastic myeloid forms and blasts. These were interpreted as being consistent with reactive changes as- sociated with anemia of chronic disease. A second muscle biopsy finding showed mild perivascular inflammatory infiltrates in the endomysium, consistent with an inflam- matory myopathy. However, further analysis by electron microscopy and immunohistochemical staining demon- strated no definitive evidence of such a condition. Anti- bodies against the membrane attack complex of comple- ment, the major histocompatibility complex, CD20, CD3, laminin , Brown-Brenn stain, and NADH reductase were negative. The final interpretation of the muscle biopsy finding was nonspecific and possibly the result of trauma or ischemia at needle entry sites. The patient continued receiving prednisone without a 1 Richard C. Chou, MD, PhD (current address: Dartmouth- Hitchcock Medical Center, Lebanon, New Hampshire), Ju- dith A. Ferry, MD: Massachusetts General Hospital, Har- vard Medical School, Boston, Massachusetts; 2 Charles A. Dinarello, MD: University of Colorado School of Medicine in Denver, Aurora; 3 Paola Dal Cin, PhD: Brigham and Wom- en’s Hospital, Harvard Medical School, Boston, Massachu- setts. Address correspondence to Richard C. Chou, MD, PhD, Section of Rheumatology, Department of Medicine, Dart- mouth-Hitchcock Medical Center, 1 Medical Center Drive, Lebanon, NH 03756. E-mail: Richard.C.Chou@hitchcock. org. Submitted for publication January 29, 2009; accepted in revised form September 14, 2009. Arthritis Care & Research Vol. 62, No. 1, January 15, 2010, pp 128 –136 DOI 10.1002/acr.20024 © 2010, American College of Rheumatology CLINICOPATHOLOGIC CONFERENCE 128