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Case 19 – A 27-year-old woman with fever and cough

A 27-year-old woman presents to her physician because of 5 days of fever and cough. She has no significant past medical history but has been “fighting colds” for the past 3 months, which she attributed to the winter season. She began having low-grade fevers as well as a dry cough 5 days ago. She has also become increasingly short of breath over the past 2 days. Her temperature is 38.7°C (102°F), heart rate is 110/min, respiratory rate is 24/min, blood pressure is 110/70 mm Hg, and oxygen saturation is 90% on room air. Physical examination reveals pallor and oral thrush. Lung auscultation is significant for bilateral crackles and rhonchi throughout. The remainder of her examination is unremarkable. She lives with her husband, who is HIV-positive but is currently asymptomatic. She has no pets and no recent travel history. X-ray of the chest reveals diffuse bilateral interstitial infiltrates.

What is the most likely diagnosis?

The patient’s respiratory symptoms, oral thrush, and radiographic findings are most concerning for Pneumocystis carinii pneumonia (PCP) (now called Pneumocystis jiroveci). PCP is an important cause of pneumonia in immunocompromised hosts and is a leading cause of opportunistic infection, morbidity, and mortality in patients with HIV. The fact that this patient’s husband is HIV positive makes her chance of also being HIV positive very likely.

What is the next step in diagnosis?

Specific diagnosis of PCP requires documentation of the organism in respiratory specimens. Conventional stains such as toluidine blue O, methenamine silver, or Giemsa can be used to identify the organism. Immunofluorescent staining is the most common technique currently in use.

What is the most appropriate management for this patient?

Trimethoprim-sulfamethoxazole (TMP-SMX), which acts by inhibiting folic acid synthesis, is considered the drug of choice for all forms of pneumocystosis. Therapy is continued for 14 days in non-HIV-infected patients and for 21 days in persons infected with HIV. In patients with severe PCP, corticosteroids given in conjunction with anti-Pneumocystis therapy, decreases the incidence of mortality and respiratory failure.

What findings would one expect to see on high-resolution computed tomography (HRCT)?

A patchy or nodular ground-glass appearance is the most common finding of PCP on HRCT. HRCT has a high sensitivity for PCP among HIV-positive patients.

What prophylactic therapy should this patient use for her condition?

Indications for prophylaxis of PCP in HIV-positive patients include:

1. History of PCP
2. CD4 cell count <200/mm³
3. History of oropharyngeal candidiasis

Oral trimethoprim-sulfamethoxazole (TMP-SMX) is the preferred prophylactic regimen. Other options include pentamidine, dapsone, and atovaquone. Oral TMP-SMX is also useful in preventing toxoplasmosis and bacterial infections.

By Jessica Kagen Hart, Resident, Department of General Pediatrics, Children’s Hospital of Philadelphia; in association with Le TT, Schabelman E, Shivaram A, and Klein J, eds: First Aid Cases for the USMLE Step 2 CK. New York: McGraw-Hill, 2007.

Case 18 – A 60-year-old man with significant bleeding

A 60-year-old man presents to the emergency department complaining of a persistent nosebleed. His nose began bleeding spontaneously about 3 hours ago, and he has not been able to get it to stop despite direct pressure and ice packs. He denies trauma, blood disorders, cancer, or a family history of hematologic or oncologic problems. He has gastroesophageal reflux disease, for which he recently increased his dose of cimetidine, and atrial fibrillation, for which he takes metoprolol and warfarin. His temperature is 37.0°C (98.6°F), blood pressure is 120/80 mm Hg, heart rate is 90/min, and respiratory rate is 10/min. Physical examination is notable for crusted blood around his left nasal ala and slowly oozing bright red blood from his left nostril. He also has small conjunctival hemorrhages and a large bruise on his knee. The remainder of his physical examination is unremarkable, including a regular heart rate and rhythm and normal chest, abdominal, and neurologic examinations. Laboratory tests show:

WBC count: 6000/mm³
Hemoglobin: 13.5 g/dL
Hematocrit: 40%
Platelet count: 350,000/mm³
International Normalized Ratio: 12.5
Prothrombin time: Normal

What conditions should be included in the differential diagnosis?

The differential diagnosis of clinically significant hemorrhage includes trauma and disorders of hemostasis, specifically problems with platelet quantity (thrombocytopenia) and quality or clotting factor deficiency. Inherited (hemophilia, von Willebrand’s disease) and acquired (hematologic malignancy, bone marrow dysfunction, liver disease, medication, autoimmune) diseases may have identical clinical presentations, albeit frequently in different patient populations.

What is the most likely diagnosis?

This patient has clinically significant, persistent bleeding (epistaxis and other hemorrhagic phenomena) in the context of an International Normalized Ratio (INR) of 12.5 while receiving warfarin therapy. Although he may have an underlying malignancy or inherited bleeding disorder, his entire clinical presentation can be explained by his medications. Cimetidine inhibits the cytochrome P450 (CYP450) system of drug metabolism (a hepatic enzymatic system that metabolizes drugs for excretion), and warfarin is metabolized by this system. Thus, a recent increase in cimetidine dosage in a patient who takes warfarin could easily lead to dangerously high warfarin levels, evidenced in this patient by severe bleeding and a high INR.

What other risk factors are associated with this condition?

Medications and other compounds that induce the CYP45 system include:

1. Alcohol
2. Barbiturates
3. Carbamazepine
4. Dexamethasone
5. Griseofulvin
6. Phenytoin
7. Quinidine
8. Rifampin

Medications and other compounds that inhibit the CYP45 system include:

1. Cimetidine
2. Clarithromycin
3. Erythromycin
4. Grapefruit juice
5. Isoniazid
6. Ketoconazole
7. Ritonavir

What is the most appropriate management for this patient?

In patients with either severe bleeding or an INR >20 (risk factor for intracranial hemorrhage), immediate cessation of warfarin and CYP450 inhibitors is crucial. This patient should also receive nasal packing, as well as admission for observation and serial neurologic exams (for intracranial hemorrhage monitoring), INR assessments, and hemoglobin levels. Finally, this patient should be counseled to use a different histamine blocker for his gastroesophageal reflux disease, such as ranitidine, to avoid this complication in the future.

By Brian Ash, MD, Resident in Anesthesia and Perioperative Care, University of California, San Francisco Medical Center; in association with Le TT, Schabelman E, Shivaram A, and Klein J, eds: First Aid Cases for the USMLE Step 2 CK. New York: McGraw-Hill, 2007.