It's All in the Granules: Capnocytophaga Vs. APL
Authors: Ormond Sean , Simon Alyssa , Norton Dustin , Burkart Madelyn , Krishnamurthy Sarada 
Published: December 2024

Intracellular inclusion bodies coupled with disseminated intravascular coagulation (DIC) often reflect a diagnosis of acute promyelocytic leukemia (APL). In this case we present a patient with Capnocytophaga canimorsus bacteremia with initial concern for APL.

A previously healthy 40-year-old male presented to the emergency department with two days of progressive abdominal pain, dyspnea, and subjective fevers. Medical history was notable only for an uncomplicated arthroscopic right partial medial meniscectomy two days prior to presentation. Social history was remarkable for a recently obtained puppy and occasional alcohol use. On arrival, the patient was normotensive, afebrile, and tachycardic. On exam, he was ill-appearing with diffuse abdominal pain and clean arthroscopic incisions of the right knee. Initial laboratory workup was notable for lactic acidosis, pancytopenia, and coagulation studies indicative of DIC. Imaging did not reveal a clear source of sepsis, notable only for scattered peribronchovascular and peripheral nodular opacities on chest CT. He was started on broad spectrum antibiotics and transferred to the medical intensive care unit (ICU).

Over the next several hours, the patient developed rapidly progressive shock and encephalopathy requiring intubation. Skin changes became evident with mottling of bilateral lower extremities which progressed to purpura fulminans. Bedside ultrasound revealed new, severe systolic dysfunction which was later confirmed by echocardiography. Initial differential diagnoses included APL, thrombotic thrombocytopenic purpura (TTP), and bacterial, viral or tick-borne illness complicated by DIC and progressive shock. A peripheral blood smear ruled out TTP given a lack of schistocytes. It also showed rounded neutrophilic intracellular inclusion bodies consistent with bacilliform organisms coupled with toxic granulation and vacuolization and a notable absence of promyelocytes with bilobed nuclei. Ultimately, empiric all-trans retinoic acid (ATRA) was started for possible APL given the still unclear clinical picture and its relatively benign side effect profile. Flow cytometry of peripheral blood did not demonstrate any aberrant populations of blasts or promyelocytes, so ATRA was discontinued. Blood cultures grew Capnocytophaga canimorsus after six days and his antibiotics were de-escalated to ceftriaxone. He was extubated and successfully weaned off vasopressors after five days. Long-term sequelae of his acute illness included anuric renal failure requiring dialysis and lower extremity ischemic necrosis necessitating bilateral below-knee-amputations.

In summary, intracellular inclusion bodies are seen in many conditions including bacterial, tick-borne and viral infections, autoimmune diseases, and hematologic malignancy. Several characteristics of this case pointed away from APL and towards Capnocytophaga canimorsus bacteremia. His recent arthroscopic procedure coupled with a new pet dog, who it should be noted had tugged at his bandages, did place him at risk for infection as this pathogenic strain of Capnocytophaga can be transmitted via the saliva of canines through an open wound. The blood smear demonstrated neutrophils with intracytoplasmic rods consistent with phagocytosed bacteria, as seen in other case reports of Capnocytophaga infection. Lack of azurophilic staining of the inclusion bodies typical of Auer rods, absence of promyelocytes in the peripheral blood, and neutrophils with toxic granulation and vacuolization with a left shift spoke toward a diagnosis of sepsis and against APL. This case presents just one example of the wide array of pathology which generates neutrophilic intracellular inclusion bodies and the importance of history taking, careful review of blood smear, and keeping a wide differential in the face of multi-organ failure.