Patient Presentation A 35-year-old man presented to Mulago Hospital in Kampala, Uganda, with shortness of breath and right upper

quadrant abdominal pain.

History The patient described 2 months of increasing shortness of breath and dyspnea on exertion. He noted a decreased exercise tolerance, as he previously was able to walk long distances without limitation, but at the time of presentation could walk only a few steps before becoming short of breath. He also complained of increasing orthopnea and paroxysmal nocturnal dyspnea over the preceding 2 months, and at presentation could sleep only if sitting upright in bed. He denied cough, hemoptysis, chest pain, or lower extremity edema. He denied having any contact with persons who were sick or known to have tuberculosis (TB). He described his abdominal pain as dull, constant, right upper quadrant pain that did not radiate. The pain did not vary with eating. He denied nausea, vomiting, or diarrhea. He had not noted any melena or bright red blood in his stool. He also denied any increase in his abdominal girth. He noted a 30-pound weight loss over the previous 2-3 months, with subjective fevers and night sweats. He denied any past trauma to his chest or abdomen. His HIV status was unknown. His medical history was notable for "drainage of fluid around the heart," approximately 1 year prior to presentation. He had never received anti-TB therapy in the past. He was not taking any medications and denied any allergies. The patient worked as a carpenter in a rural area of northern Uganda, and denied any work in or near a body of fresh water such as the Nile River. He was single and sexually active with women only. He had a history of sex with multiple partners and typically did not use any method of protection during intercourse. He denied any injection drug or tobacco use. He occasionally drank alcohol. His family history was notable for 4 siblings who had died of AIDS.

Physical Exam General: Cachectic man in respiratory distress, sitting bolt upright in bed and speaking in 2- and 3-word sentences. Vital signs: Temperature 38.0C, pulse 110 beats per minute, blood pressure 100/60, respiratory rate 30 breaths per minute, oxygen saturation of 98% on room air. Head: Notable for temporal wasting, anicteric sclera, pale conjunctiva, moist mucous membranes, and no oral thrush. Neck: Shotty anterior cervical lymphadenopathy was present. Jugular venous pulsations were visible to the angle of the jaw when the patient was sitting upright, and did not vary with respiration.

Chest: Lungs were clear to auscultation bilaterally. Heart: Point of maximal impulse (PMI) was nondisplaced. Auscultation showed tachycardia with a regular rhythm, a II/VI systolic ejection murmur at the base, and no S3 heart sound, pericardial rub, or diastolic knock. An exam for pulsus paradoxus revealed a drop in systolic pressure of 8 mm of mercury during inspiration. Abdomen: Liver was enlarged and pulsatile with the liver edge palpated at 4 cm below the costal margin. Palpation elicited mild right upper quadrant tenderness, but abdomen was soft, nondistended, with normal active bowel sounds, and without masses or splenomegaly. Extremities: No lower extremity edema. Radial and dorsalis pedis pulses were normal. Neurologic exam was normal.

Initial Studies Laboratory tests: None. An HIV test was ordered. Electrocardiogram: Not performed. Chest X ray: Markedly enlarged cardiac silhouette, with a cardiothoracic ratio of approximately 75%. No pulmonary infiltrates, effusions, or hilar lymphadenopathy were seen.

Differential Diagnosis Shortness of breath: 1. Chronic pericarditis with pericardial effusion causing tamponade: This was considered the most likely cause of the patient's symptoms, given his history of "fluid around the heart," the physical exam findings of an enlarged, pulsatile liver with elevated jugular venous pressure, no S3 heart sound, a nonpalpable PMI, normal breath sounds, and the chest X-ray finding of an enlarged cardiac silhouette. The different etiologies of pericarditis with pericardial effusion that were considered in this patient included: a. Infectious etiologies: TB (the most common cause of pericardial disease in sub-Saharan Africa and therefore the most likely cause of chronic pericardial effusion),(1,2) virus (HIV, cytomegalovirus), pyogenic effusion (although a more acute time course would be expected), fungal disease (eg, histoplasmosis, cryptococcosis), syphilis, and parasitic diseases (eg, toxoplasmosis, amebiasis). b. Malignancy: particularly lymphoma or Kaposi sarcoma, or possibly lung carcinoma.

c. Uremia. d. Autoimmune disease: systemic lupus, rheumatic heart disease. e. Other: trauma, myxedema, hemopericardium, medication effects (eg, drug-induced lupus), postsurgery or postradiation developments, or idiopathic causes. Most of these etiologies of pericardial effusion could be excluded on the basis of the patient's history and presentation. Other common causes of shortness of breath were considered, including: 1. Bacterial pneumonia: However, his lungs were clear with no consolidation on X ray, and the duration of his symptoms (2 months) was not consistent with the presentation of a typical bacterial pneumonia. 2. Pulmonary TB: His symptoms of weight loss, low-grade fever, and night sweats in a TB-endemic area raised suspicion of TB, but more likely as the cause of pericardial disease rather than pulmonary disease given the normal-appearing lung parenchyma on chest X ray, and his lack of cough. 3. Pneumocystis jiroveci pneumonia (PCP): Given the patient's risk factors for HIV, PCP was considered in the differential and he was tested for HIV. However, he had normal oxygen saturation and a normal-appearing lung parenchyma. The duration of his symptoms (2 months) also made PCP less likely. 4. Congestive heart failure: Causes of heart failure in a young man in Uganda include TB pericarditis, dilated cardiomyopathy from HIV, myocarditis from other viral diseases (eg, Coxsackie), and restrictive cardiomyopathy. Of note, TB pericarditis is one of the most common causes of clinical heart failure in sub-Saharan Africa.(3) 5. Pulmonary hypertension: Causes of pulmonary hypertension in Uganda include HIV, schistosomiasis, and rheumatic heart disease. 6. Anemia: The patient did appear anemic, with pale conjunctiva, and high-output cardiac failure was considered. However, given his chest X-ray findings, pericardial disease was considered more likely.

Conclusive Studies 1. The patient underwent a bedside echocardiogram with a portable ultrasound machine the morning after admission that showed a massive pericardial effusion with fibrin strands. 2. Although no pulsus paradoxus was present, the severity of his dyspnea, along with tachycardia at rest, was consistent with a high risk of impending tamponade. Personnel at Mulago Hospital performed a therapeutic and diagnostic pericardiocentesis, which yielded 1.5 liters of bloody pericardial fluid. 3. The pericardial fluid was sent for acid-fast bacilli (AFB) smear, which was negative, and a white blood cell count, which showed 10,000 cells/L, mostly lymphocytes. The fluid was not cultured. 4. HIV serology was positive.

Diagnosis A presumptive diagnosis of TB pericarditis was made.

Treatment and Clinical Course Symptoms improved dramatically following pericardiocentesis. Exercise tolerance increased markedly. A repeat echocardiogram revealed no reaccumulation of pericardial fluid. A presumptive diagnosis of TB pericarditis was made, and the patient was started on empiric 4-drug anti-TB therapy (rifampicin, isoniazid, pyrazinamide, and ethambutol) and adjunctive prednisolone. He was discharged from the hospital on these medications, with outpatient follow-up scheduled at the Infectious Diseases Institute (IDI) in Kampala to establish ongoing HIV care and evaluate response to TB therapy.

Learning Points TB pericarditis is the most common cause of pericardial disease in subSaharan Africa, and its incidence is particularly high in HIV-infected individuals. As a result, treatment for TB pericarditis often is begun empirically before a definitive diagnosis can be made. Close follow-up for response to therapy should be maintained and an alternative diagnosis should be considered if response is inadequate. HIV testing is a readily available and important part of the diagnostic evaluation for pericardial disease due to the increased incidence of TB pericarditis in HIV-infected individuals. Echocardiography is not always available in resource-limited environments. In these settings, chest X ray can provide important diagnostic information. Cardiomegaly, evidence of active pulmonary TB, and the absence of mediastinal lymphadenopathy each are consistent with the diagnosis of TB pericarditis. Blind pericardiocentesis carries a higher risk of complications than echocardiography-guided pericardiocentesis but may be the only available option and is an important tool for both diagnostic and therapeutic indications. AFB culture of the pericardial fluid, if available, has higher sensitivity than AFB staining, which usually is negative in TB pericarditis.