JAVMA, Vol 243, No. 11, December 1, 2013 Vet Med Today: Pathology in Practice 1545

History

An adult captive male Harris hawk (Parabuteo unicinctus) with a puncture wound to the head was treat-ed by a referring veterinarian. Doxycycline, meloxicam, and trimethoprim-sulfamethoxazole were prescribed. After 1 week of treatment by the owner at home, the wound resolved, but the hawk developed respiratory tract signs including coughing, wheezing, head shaking, and episodes of open-mouthed breathing. On physical examination at the University of Tennessee College of Veterinary Medicine, the hawk had yellow crusty mate-rial adhered to the opening of the glottis and respiratory wheezes were detected via auscultation. The hawk was treated with oxygen and placement of a cannula in the

This report was submitted by Aniela M. Nelson,† DVM; Michael P. Jones, DVM, DABVP; and Linden Craig, DVM, PhD, DACVP; from the Departments of Biomedical and Diagnostic Sciences (Nelson, Craig) and Small Animal Clinical Sciences (Jones), College of Vet-erinary Medicine, University of Tennessee, Knoxville, TN 37996.

Address correspondence to Dr. Craig (linden@utk.edu).†Deceased.

Pathology in Practice

In cooperation with

left caudal thoracic air sac. The owner was told to dis-continue administration of doxycycline and meloxicam, and the hawk was discharged from the hospital with the air sac cannula in place. One week later, the referring veterinarian replaced the left air sac cannula with a can-nula in the right caudal thoracic air sac. The hawk was found dead the next morning.

Gross Findings

At necropsy, the hawk weighed 700 g (1.54 lb) and was in good body condition. There were 1- to 2-mm, slightly raised, yellow plaques lining the oral cavity. There was a slightly raised rough yellow circumferential plaque covering the mucosa of the middle to distal portion of the trachea and major bronchi (Figure 1). Similar plaques lined the air sacs. The cannula was in the subcutis of the right side but did not communicate with an air sac.

Formulate differential diagnoses from the history, clinical findings, and Figure 1—then turn the page →

Figure 1—Photograph of the longitudinally bisected trachea of a Harris hawk (Parabuteo unicinctus) that was referred for evaluation of respiratory tract signs, which developed after 1 week of treatment for a puncture wound. The hawk died 1 week after the referral examination and placement of an air sac cannula (2 weeks after initiation of treatment). Notice the yellow, rough plaque covering the tracheal mucosa. Bar = 1 cm.

1546 Vet Med Today: Pathology in Practice JAVMA, Vol 243, No. 11, December 1, 2013

Histopathologic Findings

Specimens of the trachea and lung tissues underwent histologic examination. The tracheal mucosa was diffusely ulcerated and replaced by a thick layer of fibrin with epi-thelioid macrophages, multinucleated giant cells, eosino-phils, heterophils, and mucus (Figure 2). Macrophages and multinucleated giant cells frequently contained and surrounded birefringent, pale yellow to colorless crystals (Figure 3). There were multifocal areas of necrosis. The lung tissue had similar changes, along with foci of granu-lation tissue and bronchial squamous metaplasia. The air sacs were thickened with fewer macrophages and multi-nucleated giant cells containing the crystals.

Morphologic Diagnosis and Case Summary

Morphologic diagnosis: severe ulcerative and granulo-matous tracheitis and bronchitis with intralesional crystals.

Case summary: doxycycline aspiration in a hawk.

Comments

The trachea of the hawk of the present report was still patent, but the bronchi were obstructed by foreign material and associated inflammation. At the time of necropsy, the air sac cannula was in the subcutis and did not communicate with the air sac; therefore, the cause of death was likely hy-poxia due to airway obstruction. The grossly bright yellow color of the material combined with the crystalline histologic appearance was most consistent with aspiration of doxycy-cline. None of the other prescribed drugs were yellow.

Doxycycline is a crystalline salt that is available in multiple forms for administration. The oral forms avail-able for animals are tablets, capsules, and an oral suspen-sion. The tablets are compressed doxycycline hyclate, which is yellow and has an acidic pH. The oral suspen-sion is doxycycline monohydrate salt, a less acidic pink powder that is reconstituted prior to administration.1

Doxycycline hyclate has been implicated in drug-induced esophageal injury in humans and cats. The irritant na-ture of doxycycline can be attributed to its acidic pH.

In humans, doxycycline has been associ-ated with esophageal ulceration, but in cats, the injury is often not detected until there is stricture formation.2 The stricture formation and fibrosis are presumed to be sequelae to ulceration and inflammation that develop as a result of doxycycline dissolving in the esophagus. Following pill administration, it is recommended that cats ingest food or undergo a lavage procedure. In contrast to humans, inges-tion of food does not substantially affect the bioavailability of the drug in cats.2

The anatomic features of the oral cavity of birds predispose them to aspira-tion of administered liquids. The esoph-agus is caudal to the glottal mound; thus, medications need to be directed over this mound of tissue during administra-tion. To avoid inadvertent aspiration, the medications can be administered into the crop through a gavage system. Most avian species, excluding owls, possess a small crop.3 In the case described in the

Figure 2—Photomicrograph of a cross section of the trachea from the hawk in Figure 1. Notice the thick plaque of fibrin (arrow) and marked inflammation (asterisk). H&E stain; bar = 200 µm.

Figure 3—Photomicrographs of a section of a secondary bronchus from the hawk in Figure 1. A—Intralesional crystals are visible by plain light microscopy. B—The same crystals are birefringent and pale yellow to colorless when viewed with polarized light. H&E stain; bar = 100 µm.

JAVMA, Vol 243, No. 11, December 1, 2013 Vet Med Today: Pathology in Practice 1547

present report, the medications had been administered into the hawk’s oral cavity by the owner and were not administered via gavage.

For birds, the recommended forms of doxycycline for oral administration are the oral suspension or the hyclate salt mixed with food.4 The mixing of medica-tion with food is oriented toward seed-eating birds, and the bioavailability is uncertain when medications are injected into dead prey for administration to meat-eating birds. Avian species with a crop can be given medication through a gavage system. The lesions in the hawk of the present report were consistent with administration and aspiration of a slurry made from doxycycline tablets (supported by the lack of food in the trachea); aspiration of the drug exposed the deli-cate respiratory tract epithelium to the low drug pH, accounting for the profuse inflammation and squa-mous metaplasia.

Doxycycline monohydrate for oral suspension is difficult to obtain, is expensive, and precipitates out of solution readily.a Some veterinary pharmacists recom-mend the oral syrup (doxycycline calcium [a less caus-

tic formulation]) for administration to birds: however, this too is difficult to obtain.a Nevertheless, doxycycline hyclate tablets are caustic and their administration to birds as an oral slurry is not recommended because of the risk of aspiration; if there is no better option avail-able, use of a gavage system is recommended.

a. Stevens T, College of Veterinary Medicine, University of Tennessee, Knoxville, Tenn: Personal communication, 2012.

References1. TEVA Pharmaceuticals USA Inc. DOXYCYCLINE—doxycycline

powder, for suspension (archived drug label). Available at: dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=54526. Accessed Sep 7, 2011.

2. German AJ, Cannon MJ, Dye C, et al. Oesophageal strictures in cats associated with doxycycline therapy. J Feline Med Surg 2005;7:33–41.

3. Redig PT, Cruz-Martinez L. Raptors. In: Tully TN, Dorrestein GM, Jones AK, eds. Handbook of avian medicine. 2nd ed. Phila-delphia: WB Saunders Co, 2009;209–242.

4. Plumb D. Plumb’s veterinary drug handbook. 7th ed. Stockholm, Wis: Pharmavet Inc, 2011;365.