IM Board Review

Fever after recent travel

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A 28-year-old man developed fever, night sweats, nausea, headache, reduced appetite, skin rash, and hemoptysis 2 weeks after returning to the United States from Mexico.

The patient had fistulizing Crohn disease and had been taking the tumor necrosis factor alpha (TNF-alpha) blocker adalimumab for the past 3 months. He had no risk factors for human immunodeficiency virus infection, and he had stopped smoking 1 year previously. Chest radiography and a tuberculin skin test before he started adalimumab therapy were negative. While in Mexico, he did not drink more than 1 alcoholic beverage a day.

He had presented recently to his local hospital with the same symptoms and had been prescribed ciprofloxacin, metronidazole, ceftriaxone, vancomycin, and ampicillin, which he was still taking but with no improvement of symptoms. Blood cultures drawn before the start of antibiotic therapy had been negative. Urinalysis, a screen for infectious mononucleosis, and lumbar puncture were also negative. Results of renal function testing were normal except for the anion gap, which was 20.8 mmol/L (reference range 10–20).

INITIAL EVALUATION

On presentation to this hospital, the patient was afebrile but continued to have temperature spikes up to 39.0°C (102.2°F). His heart rate was 90 per minute, blood pressure 104/61 mm Hg, respiratory rate 18 per minute, and oxygen saturation 95% on 2 L of oxygen via nasal cannula.

At presentation, the patient had a sparse, erythematous, macular, nonblanching rash on the lower and upper limbs.
Figure 1. At presentation, the patient had a sparse, erythematous, macular, nonblanching rash on the lower and upper limbs.
Respiratory examination revealed decreased air entry bilaterally, with fine bibasilar crepitations. The abdomen was tender without guarding or rigidity, and splenomegaly was noted. A sparse erythematous macular nonblanching rash was noted on the lower and upper limbs (Figure 1). The rest of the physical examination was unremarkable.
Laboratory testing results
Table 1 shows the results of initial laboratory testing at our facility, as well as those from a recent presentation at his local hospital. Results of a complete blood cell count were:
  • White blood cell count 10.0 × 109/L (reference range 4.0–10.0 × 109/L)
  • Lymphocyte count 6.1 × 109/L (1.2–3.4)
  • Hemoglobin level 13.6 g/dL (14.0–18.0)
  • Platelet count 87 × 109/L (150–400), reaching a nadir of 62 on hospital day 23
  • Albumin 47 g/L (35–50)
  • Total bilirubin 48 µmol/L (2–20)
  • Alkaline phosphatase 137 U/L (40–135)
  • Alanine aminotransferase 22 U/L (9–69)
  • Aspartate aminotransferase 72 U/L (5–45).

He continued to have temperature spikes. His alkaline phosphatase level plateaued at 1,015 U/L on day 30, while his alanine aminotransferase and aspartate aminotransferase levels remained stable.

The patient’s ceftriaxone was continued, and the other antibiotics were replaced with doxycycline. Fluconazole was added when sputum culture grew Candida albicans. However, these drugs were later discontinued in view of worsening results on liver enzyme testing.

The evaluation continues

Sputum cultures were negative for acid-fast bacilli on 3 occasions.

Serologic testing was negative for:

  • Hepatitis B surface antigen (but hepatitis B surface antibody was positive at > 1,000 IU/L)
  • Hepatitis C virus antibody
  • Cytomegalovirus immunoglobulin (Ig) G
  • Toxoplasma gondii IgG
  • Epstein-Barr virus viral capsid antigen IgM
  • Rickettsia antibodies
  • Antinuclear antibody
  • Antineutrophil cytoplasmic antibody
  • Antiglomerular basement membrane antibody.

Chest radiography showed blunting of both costophrenic angles and mild prominence of right perihilar interstitial markings and the right hilum.

Computed tomography of the chest, abdomen, and pelvis showed a subpleural density in the lower lobe of the right lung, small bilateral pleural effusions, right hilar lymphadenopathy, and splenomegaly with no specific hepatobiliary abnormality.

A white blood cell nuclear scan found no occult infection.

Abdominal ultrasonography showed a prominent liver and spleen. The liver parenchyma showed diffuse decreased echogenicity, suggestive of hepatitis.

Transesophageal echocardiography showed no vegetations or valvular abnormalities.

Bronchoscopy showed normal airways without evidence of pulmonary hemorrhage. No foci of infection were obtained. A focus of granuloma consisting of epithelioid histiocytes in tight clusters was seen on washings from the right lower lobe, but no malignant cells were seen.

Sections of pathologically enlarged right hilar and subcarinal lymph nodes obtained with transbronchial needle aspiration were sent for cytologic analysis and flow cytometry.

Cultures for tuberculous and fungal organisms were negative.

Repeat chest radiography showed a new right basilar consolidation with a small effusion (arrow).
Figure 2. Repeat chest radiography showed a new right basilar consolidation with a small effusion (arrow).
Repeat chest radiography showed a new right basilar consolidation with a small effusion (Figure 2).

A clue. On further inquiry, the patient said he had gone swimming in the natural pool, or cenote, under a rock formation at Cenote Maya Park in Mexico.

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