A stray adult male Boxer was presented to the referring veterinarian by a Good Samaritan for evaluation. Physical examination disclosed mild preputial and cutaneous trauma, and mild cachexia (body condition score 2/5). Dirofilaria immitis (heartworm) antigen testing1 documented heartworm infection, and the patient was treated with prednisolone (0.5 mg/kg q24h PO), doxycycline (5 mg/kg q12h PO), and a single dose of moxidectin2 (2.5 mg/kg topically) for 1 month before 2-step melarsomine adulticide treatment. One week after beginning treatment, the dog began coughing excessively and furosemide (1 mg/kg q12h PO) and pimobendan (0.25 mg/kg q12h PO) were prescribed. One month after beginning treatment, the dog was observed to cough up fresh blood several times. Inspection of the sputum revealed several long worms in the hemorrhagic sputum. The worms were collected, fixed in 10% formalin, and submitted to Cornell University College of Veterinary Medicine for parasitologic analysis. The cough resolved with exercise restriction, cefodoxime (10 mg/kg q24h), and hydrocodone syrup (5 mg q6h PO as required).
Analysis of the worms consisted of visual morphologic examination by a veterinary parasitologist (DDB), and genotypic identification by polymerase chain reaction (PCR). The PCR was performed using previously described filarial primers and cycling conditions, and amplicons were analyzed by gel electrophoresis on a 1% agarose gel. Both morphologic evaluation and PCR analysis confirmed that the worms were D. immitis.
A search of the Veterinary Information Network (VIN) discussion database identified 5 additional cases in which dogs with advanced heartworm disease (based on radiographic evidence and heartworm antigen testing) suffered bouts of hemoptysis in which single or multiple worms were observed in the expectorated blood. Two of these cases had insufficient information for inclusion in this report. A 5th case was identified by a veterinarian who contacted the primary author after learning through discussions on VIN that the primary author was interested in cases of dirofilarial hemoptysis.
A female spayed mixed-breed dog, adopted from a shelter 4 months before presentation where it tested positive for heartworm infection by an antigen test (brand unknown), was examined for coughing. Heartworm prophylaxis3 was dispensed, and the dog was scheduled for adulticide treatment for several months. One month after the initial examination, the dog presented to the veterinarian after a coughing episode during which it coughed up mucus, blood-tinged foam, and a long worm. The veterinarian prescribed fenbendazole (50 mg/kg × 14 days) and prednisolone (0.5 mg/kg q12h × 5 days then q24h × 5 days PO). Coughing progressed over the next 6 weeks and another worm was coughed up. The worm was submitted to the veterinary parasitology department of the regional veterinary college and morphologically identified as D. immitis (Fig 1A). Doxycycline (5 mg/kg q12h × 30 days) was prescribed, and the coughing subsided.
A 2-year-old male neutered mixed-breed dog (12 kg) was diagnosed with heartworm disease and treated with doxycycline (10 mg/kg q24h) and moxidectin.2 Two weeks later, the dog was presented to the referring veterinarian for evaluation of incessant coughing. The dog was hospitalized, treated with dexamethasone acetate (1 mg/kg IM), furosemide (1 mg/kg SQ), and placed in an oxygen cage. Approximately 10 minutes after administering the medications, the dog coughed out a worm measuring approximately 20 cm, the coughing ceased immediately and did not recur for the remainder of the day. The worm was submitted for genotyping, and PCR analysis of the worm DNA (as described above) confirmed the identity as D. immitis.
A 5-year-old female spayed German Shepherd (38 kg) was presented to the referring veterinarian after an episode of hemoptysis. Several worms were noticed in the bloody sputum. A heartworm antigen test4 was positive. A routine CBC and serum biochemistry profile were performed and disclosed regenerative anemia (RBC, 4.01 × 106/μL; Hb, 9.5 g/dL; hematocrit, 30.9%; corrected reticulocyte count, 7.8%), eosinophilia (1600/μL), and hypoalbuminemia (2.0 g/dL). Evaluation of thoracic radiographs identified marked pulmonary artery enlargement, consistent with dirofilariasis. The dog was treated with ivermectin3 272 μg PO monthly, prednisolone 1 mg/kg q24hr PO for 2 weeks, and doxycycline 6 mg/kg q24hr PO for 2 weeks. The worms were examined by the veterinarian, and were considered to be consistent with D. immitis (Fig 1B).
A 6-year-old intact female 5-kg Boston Terrier was presented to the referring veterinarian for dyspnea and coughing for 2 days. The dog was not receiving heartworm prophylaxis at the time of presentation, and demonstrated mild hemoptysis during the examination. Evaluation of thoracic radiographs indicated evidence of heartworm disease (ie, enlarged pulmonary arteries, increased caudal lung lobe opacity). A heartworm antigen test4 was positive. The dog was hospitalized and treated with dexamethasone sodium phosphate (0.5 mg/kg IV) and diphenhydramine (3 mg/kg IM) and placed in an oxygen cage for 3 hours. Prednisone (1 mg/kg PO) was administered approximately 8 hours after presentation, along with a single dose of doxycycline (20 mg/kg PO). The dog stabilized over the next 24 hours, but then suddenly decompensated, with severe hemoptysis and dyspnea. One worm was coughed up during decompensation, and the dog was euthanized at owner's request (Fig 1C). A 2nd worm was retrieved from the dog's airways during postmortem examination. The worms were identified as D. immitis.
Two of the dogs ultimately underwent routine adulticide treatment5 with resolution of dirofilarial infection and hemoptysis. The 3rd dog underwent adulticide treatment approximately 4 months after the initial diagnosis, but died approximately 3 weeks after the third injection. The 4th dog was maintained on moxidectin and doxycycline. The 5th dog was euthanized during the initial presentation.
Hemoptysis (expectoration or coughing up of blood) has been reported as a consequence of severe heartworm infection in dogs,[2-6] although it remains a relatively uncommon finding. Even fewer reports exist of dogs coughing up or vomiting up adult heartworms.[2, 7] This case series is the 1st report of expectoration of adult D. immitis in the bloody sputum of a series of dogs with heartworm disease. Our findings suggest that although uncommon, clinicians should be aware of such manifestations of canine heartworm disease.
The pathophysiology of filarial hemoptysis remains unclear. Adult D. immitis worms reside in the pulmonary arteries. The clinical presentation in all of these dogs suggests that these worms were not present in the airways as a consequence of aberrant larval migration and maturation, but as a result of pulmonary artery rupture and subsequent extravasation. Given the size of the arteries in which adult worms are found, such rupture would most likely be para-bronchial rather than alveolar or bronchiolar. Whether vigorous coughing predisposed these dogs to arterial rupture is unknown. Similarly, whether exceptionally high pulmonary artery pressures might contribute to rupture is also unknown; however, none of the dogs in this case series had right-sided congestive heart failure, and other diseases resulting in severe pulmonary arterial hypertension do not result in arterial rupture and hemoptysis. This suggests that the presence of worms in the arteries is somehow instrumental in the rupture.
Verminous expectoration has been reported in humans infected with Syngamus (Mammomonogamus) laryngeus,[8, 9] and with ascarid larvae during pulmonary-intestinal migration. However, in such cases, the worms reside within or are migrating through the large airways. In contrast, D. immitis resides within the pulmonary vasculature and therefore does not have direct access to the outside environment via the airways. The authors could find no reports of adult Angiotrongylus vasorum (another intravascular nematode) being identified in sputum (hemorrhagic or otherwise) of infected dogs with coughing, or of A. vasorum infection resulting in hemoptysis independent of coagulopathic hemorrhagic diathesis. Thus, this phenomenon appears to be restricted to D. immitis.
The sudden cessation of or improvement in coughing in several of the dogs described here suggests that coughing and acute dyspnea were more likely a consequence of intrapulmonary hemorrhage and the presence of the worm within the bronchi, than related to underlying chronic heartworm disease (ie, pneumonitis and parenchymal inflammation).
In 4/5 cases in this report, and in contrast with the report by Turk et al, the hemoptysis was not fatal. Several of the dogs underwent successful adulticide treatment with resolution of clinical signs, whereas 1 dog died acutely during adulticide treatment several months after the episode of hemoptysis. However, 1 of the dogs in this report was euthanized during the presenting episode. Thus, although distressing, alarming, and potentially fatal, the sequelae of hemoptytic manifestations of heartworm disease are not necessarily always fatal.
This case series highlights an uncommon manifestation of canine heartworm disease and provides initial insights into potential outcomes of this phenomenon.
Conflict of Interest: Mark Rishniw has consulted for Merial on heartworm-related issues. Dwight Bowman has consulted for Bayer, Pfizer, Merial, Ciba, Elanco, Novartis, and IDEXX on heartworm-related issues.
Vetscan Canine Heartworm Rapid Test, Abaxis North America, Union City, CA