Every Nook and Cranny

In addition to basic laboratory studies and a chest radiograph, multiple sets of blood cultures should be obtained, along with a transthoracic echocardiogram and a ferritin level. The evidence to support leptospirosis and scrub typhus is strong enough to justify empiric use of doxycycline once the blood cultures are obtained, especially given the difficulty in definitively diagnosing these diseases in a timely fashion.

Laboratory analysis revealed a total leukocyte count of 13,600/uL (85% neutrophils), hemoglobin 10 g/dL, and platelet count 35,000/uL. Absolute eosinophil count was 136/uL. Serum chemistry showed sodium of 145 meq/L, potassium 4.1 meq/L, blood urea nitrogen 80 mg/dL, creatinine 1.6 mg/dL, aspartate transaminase (AST) 44 U/L (normal, 0-40), alanine transaminase (ALT) 81 U/L (normal, 0-40), direct bilirubin 3 mg/dL, and indirect bilirubin 3 mg/dL. Lactate dehydrogenase, alkaline phosphatase, albumin, and coagulation studies were normal. Erythrocyte sedimentation rate (ESR) was 42 mm (normal, 0-25) and highly sensitive C-reactive protein was 42 mg/L (normal, 0-10). Arterial blood gas on ambient air revealed a pH of 7.52, PaCO2 24 mm Hg, PaO2 55 mm Hg, and bicarbonate 20 meq/L. Urinalysis was normal. Blood cultures were obtained. Electrocardiogram (ECG) showed regular narrow complex tachycardia with incomplete left bundle branch block. Old ECGs were not available for comparison. Chest radiograph showed bilateral air space opacities with evidence of vein cephalization. Abdominal and pelvis ultrasonography showed pericholecystic fluid and mild hepatomegaly, but no free fluid, pleural effusion, or evidence of cholecystitis. Point of care immunochromatographic rapid malarial antigen detection test (detects Plasmodium falciparum, Plasmodium vivax, Plasmodium malaria, and Plasmodium ovale) was negative.

Most of the findings described are commonly observed in both scrub typhus and leptospirosis, including cytopenias, parenchymal infiltrates, hepatomegaly, elevated transaminases and bilirubin, cardiac involvement, fever, and rash. The rash described is more consistent with scrub typhus than with leptospirosis. The absence of a headache and joint findings argue modestly against these diagnoses. Likewise, HLH provides an adequate explanation for most of the patient’s symptoms, signs, and test results. These include fever, lung involvement, rash, hepatomegaly, elevated bilirubin, and cytopenias; however, leukocytosis and cardiac involvement are less characteristic. SLE also provides a satisfactory explanation for much of the symptoms, although the rash characteristics, normal urinalysis, and leukocytosis make this diagnosis less likely.

Additional testing that should be performed includes serum antinuclear antibody (ANA) and ferritin, since the latter may be markedly elevated in the setting of HLH. Bone marrow aspirate and biopsy should be performed looking specifically for evidence of hemophagocytosis. Finally, a transthoracic echocardiogram (TTE) should be performed to assess evidence of myocardial dysfunction as it may alter the therapeutic approach, although the results will be unlikely to differentiate between the preceding considerations.

Troponin I was negative, but N-terminal probrain natriuretic peptide was elevated at 20,000 pg/mL (normal, 0-900). D-dimer was negative. TTE showed left ventricular ejection fraction (LVEF) of 35% with global left ventricular hypokinesis. On three separate examinations, the peripheral blood smear did not show malarial parasites, atypical lymphocytes, or schistocytes. Three sets of blood cultures, testing for bacteria and fungi, were sterile. A throat culture was sterile. Widal test, as well as Leptospira and Mycoplasma serologies, were negative. Serology for Legionella pneumophila was positive, but the urinary antigen testing was negative. Antibodies to HIV 1 and 2 and anti-hepatitis C virus (HCV) antibody were negative. Dengue IgM ELISA (qualitative) returned positive.

Despite the absence of arthralgias, myalgias, headache, and retro-orbital pain, a positive dengue IgM ELISA supports acute dengue infection, provided the patient did not experience an unexplained febrile illness in the previous months. Most of his presentation may be explained by dengue, including fever, rash, liver abnormalities, myocardial dysfunction, and thrombocytopenia. The bilateral airspace opacities seen on chest radiograph also fit reasonably provided these actually reflect pulmonary edema. Leukocytosis (as opposed to leukopenia) is highly unexpected in dengue, but its presence could be an outlier.