A 74-Year-Old Woman with Abdominal Pain and Fever
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A SELF-TEST IM BOARD REVIEW DAVID L. LONGWORTH, MO, JAMES K. STOLLER, MD, EDITORS OF CLINICAL PETER MAZZONE, MD CRAIG NIELSEN, MD RECOGNITION Department of Pulmonary and Critical Department of General Internal Care Medicine, Cleveland Clinic Medicine, Cleveland Clinic A 74-year-old woman with abdominal pain and fever 74-YEAR-OLD WOMAN was transferred pulmonary embolism, and a subsequent pul- from a local hospital for further evalua- monary angiogram was read as normal. A tion and management of abdominal pain with chest CT scan did not reveal anything other fever. than the small bilateral pleural effusions seen The patient had presented to the local on the chest radiograph. A thoracentesis hospital 11 days before with a 1-day history of revealed transudative fluid only. Intravenous bilateral upper-quadrant abdominal pain. She heparin was discontinued. described the pain as a constant ache with Past history. The patient had had essen- intermittent sharper pains accompanied by tial thrombocythemia for 5 years, for which nausea, but she could not identify any precip- she took hydroxyurea until 2 months before itants of the pain. She was also constipated. admission. Hydroxyurea was restarted at the A few days after being admitted to the local hospital because her platelet count was local hospital, the patient had developed a high at 750 x 109/L (normal 150-400 x fever and mild shortness of breath. She was 109/L), but it was stopped 3 days later because treated empirically for a possible pulmonary of mucositis. More than 30 years ago, the infection with a variety of antibiotics (ceftri- patient had been diagnosed with "pernicious Her platelet axone, ticarcillin-clavulanate, erythromycin, anemia. count dropped metronidazole, cefazolin, and vancomycin). Family history was unremarkable. The Blood, urine, and sputum cultures remained patient lived with her husband on a farm, had from 750 to negative throughout her hospitalization. two healthy children, and had not recently 272 x 109/L At the local hospital she had also under- traveled. gone an upper gastrointestinal (GI) series, a in only a few small bowel follow-through, a barium enema, Physical examination days and computed tomography (CT) of the On presentation to our hospital the patient abdomen. These revealed colonic diverticulo- was experiencing diffuse abdominal pain, nau- sis and a dilated gallbladder with no gall- sea, vomiting, fatigue, and sweats. stones. A hepato-iminodiacetic acid scan was On physical examination, the patient reported as suspicious for acute cholecystitis. appeared ill. Her temperature was 38.2°C, CT-guided aspiration of the gall bladder heart rate 102/minute and regular, blood revealed "non-purulent fluid." Cultures of the pressure 123/67 mm Hg, respiratory rate fluid from the gallbladder were negative. A 16/minute, and oxygen saturation 96% by chest radiograph revealed only small bilateral pulse oximetry while receiving oxygen at pleural effusions. 2 L/minute per nasal cannula. She had mild During the barium enema the patient had oral mucositis, decreased basal breath sounds become hypoxic, requiring supplemental oxy- bilaterally, and a grade 2/6 systolic ejection gen and transfer to the intensive care unit. murmur (reported in the past). Her Her physicians started intravenous heparin abdomen was soft with diffuse tenderness therapy empirically while investigations were but without palpable organomegaly or peri- performed. A ventilation-perfusion scan was toneal signs. Her stool was negative for interpreted as showing a low probability of occult blood. She had no focal neurologic CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 66 • NUMBER 8 SEPTEMBER 1999 469 Downloaded from www.ccjm.org on October 6, 2021. For personal use only. All other uses require permission. IM BOARD REVIEW MAZZONE AND NIELSEN TABLE 1 At this point our patient had had an upper The patient's laboratory values CI series, a small bowel follow-through, a bar- ium enema, CT scans of the chest and at the time of admission abdomen, a hepato-iminodiacetic acid scan, aspiration and later removal of her gallbladder, TEST VALUE UNITS NORMAL RANGE a pulmonary angiogram, a bone marrow aspi- White blood cell count 4.07 X 109/L 4.2-5.4 ration, and multiple cultures, none of which Hemoglobin 9.2 g/dL 12.0-16.0 provided an adequate explanation for her Platelet count 272 x 109/L 150-400 symptoms and fever. Sodium 135 mmol/L 132-148 Potassium 4.5 mmol/L 3.5-5.0 • FEVER OF UNKNOWN ORIGIN Chloride 108 mmol/L 98-110 Carbon dioxide 22 mmol/L 24-32 Which of the following choices is not part Blood urea nitrogen 11 mg/dL 8-25 of the standard definition of fever of Creatinine 1.0 mg/dL 0.7-1.4 1 unknown origin? Glucose 112 mg/dL 65-110 • Temperature greater than 38.3 °C • Fever for at least 3 weeks deficits, TABLE 1 shows her laboratory values at • Fever that defies diagnosis after 1 week of the time of admission. Coagulation studies inpatient investigation were normal. • Fever that cannot be suppressed by Her medications on transfer included antipyretics ticarcillin-clavulanate and heparin in prophy- lactic, subcutaneous doses. The standard definition of fever of unknown origin has been a temperature higher than • HOSPITAL COURSE 38.3 °C for at least 3 weeks that defies diagno- sis after 1 week of inpatient investigation. The Fever of We continued to give ticarcillin-clavulanate, ability of antipyretics to suppress the fever is unknown origin performed bone marrow aspiration to assess not part of the definition. the patient's essential thrombocythemia and A new classification scheme divides fever has a new set to look for a cause of her fever, and obtained a of unknown origin into four categories: classic, of criteria general surgery consult. The surgeons believed nosocomial, neutropenic, and HIV-associated. that the patient might have acute cholecysti- In each, the definition differs somewhat from tis and so scheduled her for a laparoscopic the older, standard definition. cholecystectomy the following day. The Classic fever of unknown origin (an patient tolerated the operation well. The ini- unexplained temperature higher than tial pathology study suggested an acute exac- 38.3 °C for at least 2 weeks, or three outpa- erbation of chronic cholecystitis. tient visits, or 3 days in the hospital). There Two days passed, but the patient's condi- are many potential causes. Infectious causes tion did not change significantly. She contin- are numerous (tuberculosis being the most ued to spike fevers with temperatures as high common). If a typical infection cannot be as 39°C and complained of nausea, vomiting, found, occult infections must be considered abdominal pain, and weakness. Blood, urine, (eg, abscesses, osteomyelitis, endocarditis, and sputum cultures remained negative, and prostatitis), as should viral infections (eg, her laboratory values remained about the cytomegalovirus, Epstein-Barr virus) and same. She noted some swelling of her right infections with less common organisms such lower extremity. A duplex ultrasound scan as fungi, Plasmodium (the agents of malaria), revealed a popliteal deep venous thrombosis, or Rickettsia. Some neoplastic diseases can which we monitored by serial duplex ultra- cause fever; the most common being lym- sound examinations. Her bone marrow aspira- phomas, leukemias, renal cell carcinoma, tion results were consistent with the prior and hepatomas. Collagen vascular diseases, diagnosis of essential thrombocythemia. granulomatous disorders, and miscellaneous 470 CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 66 • NUMBER 8 SEPTEMBER 1999 Downloaded from www.ccjm.org on October 6, 2021. For personal use only. All other uses require permission. causes such as drug fever, gout, cirrhosis, TABLE 2 recurrent pulmonary emboli, and metabolic Causes of primary adrenal disorders round out the list. insufficiency Nosocomial fever of unknown origin (an unexplained temperature higher than Anatomic destruction 38.3°C in a hospitalized patient in whom Idiopathic Autoimmune fever was not present at admission; there Adrenoleukodystrophy must be at least 3 days of investigation with Infections 2 days of culture incubation). Investigation Tuberculosis should focus on sites where occult infec- Fungal Viral tions might be sequestered, such as intravas- Infiltration cular lines, sinuses (with nasogastric tubes), Metastatic disease prosthetic devices, acalculous cholecystitis, Amyloid and Clostridium difficile colitis. Drugs and Sarcoid transfusion-related fevers must also be con- Hemorrhage sidered. Waterhouse-Friderichsen syndrome Neutropenic fever of unknown origin (a Antiphospholipid syndrome temperature higher than 38.3 °C in a patient Heparin-induced thrombocytopenia with a neutrophil count lower than 500/pL Metabolic failure Congenital adrenal hyperplasia after 3 days of investigation with 2 days of cul- Cytotoxic agents ture incubation). All types of infections, Drugs including fungal, viral, and gram-positive and gram-negative bacterial organisms, must be considered. A cause of the fever is often not found. In general, patients do well with sup- • ADRENAL INSUFFICIENCY portive care, including empiric antimicrobial Which of the following laboratory find- therapy, while awaiting a rise in the neu- 2 ings is consistent with a diagnosis of pri- trophil count. mary adrenal insufficiency? In spite of HIV-associated fever of unknown origin persistent (a temperature higher than 38.3°C for more • Increased serum sodium than 4 weeks for outpatients or 3 days of in- • Increased serum chloride vomiting,