Differential Diagnosis for Shortness of Breath, Fever, Elevated Liver Enzymes, and Thrombocytopenia

Single Most Likely Diagnosis

• Severe COVID-19: This diagnosis is considered the most likely due to the combination of symptoms such as shortness of breath, fever, and the potential for COVID-19 to cause secondary effects like elevated liver enzymes and thrombocytopenia. The global pandemic has made COVID-19 a common cause of these symptoms.

Other Likely Diagnoses

• Pneumonia: Bacterial or viral pneumonia can cause shortness of breath and fever. Elevated liver enzymes and thrombocytopenia can occur due to severe infection or sepsis.
• Sepsis: A systemic infection that can lead to multi-organ dysfunction, including respiratory distress, fever, elevated liver enzymes, and thrombocytopenia.
• Hemophagocytic Lymphohistiocytosis (HLH): A rare but potentially life-threatening condition characterized by an overactive and inappropriate immune response, which can cause fever, thrombocytopenia, and elevated liver enzymes, along with shortness of breath if there is pulmonary involvement.

Do Not Miss Diagnoses

• Pulmonary Embolism (PE): Although less likely to cause fever and elevated liver enzymes directly, a large PE can lead to acute right heart failure, which might result in liver congestion and thus elevated liver enzymes. Thrombocytopenia can be seen in conditions associated with PE, such as cancer or antiphospholipid syndrome.
• Endocarditis: Infective endocarditis can cause fever, thrombocytopenia, and elevated liver enzymes due to embolic phenomena or systemic infection. Shortness of breath can occur due to heart failure or pulmonary emboli.
• Malaria: In areas where malaria is endemic, it can cause fever, thrombocytopenia, and elevated liver enzymes. Shortness of breath can occur in severe cases due to anemia or acute respiratory distress syndrome (ARDS).

Rare Diagnoses

• Lymphoma: Certain types of lymphoma can cause systemic symptoms like fever, night sweats, and weight loss, along with specific symptoms like shortness of breath if there is pulmonary involvement, and thrombocytopenia or elevated liver enzymes due to liver or bone marrow involvement.
• Ehrlichiosis/Anaplasmosis: Tick-borne illnesses that can cause fever, thrombocytopenia, and elevated liver enzymes. Shortness of breath is less common but can occur in severe cases.
• Toxicity or Drug-Induced Conditions: Certain drugs or toxins can cause a combination of these symptoms, including shortness of breath, fever, elevated liver enzymes, and thrombocytopenia, due to allergic reactions, direct toxicity, or idiosyncratic reactions.