Bicavitary eosinophilic effusion in a dog with coccidioidomycosis

Abstract This is a case of coccidioidomycosis in a dog, examined for vomiting and labored breathing. Physical examination and thoracic and abdominal imaging revealed pleural and peritoneal effusions, both of which exhibited neutrophilic inflammation with a substantial eosinophilic component. The dog had positive IgM and IgG coccidioidomycosis titers at initial evaluation. The eosinophilic component of the inflammation was attributed to coccidioidomycosis. The dog underwent approximately 6 months of fluconazole treatment, with both effusions and clinical signs improving after 6 weeks. Three months after cessation of antifungal treatment, the dog developed a mid‐diaphyseal lytic and proliferative lesion in the left radius caused by Coccidioides spp. This case illustrates the importance of consideration of coccidioidomycosis when an eosinophilic cavitary effusion is present in dogs that live in or have traveled to endemic regions.


| INTRODUCTION
Coccidioidomycosis is the most common systemic fungal disease in the southwestern United States, and is caused by the dimorphic, saprophytic fungus Coccidioides immitis or Coccidioides posadasii. 1 These organisms are endemic in dry climates of Arizona, California, Texas, New Mexico, and Central and South America. 2 The incidence of pulmonary infection in people in endemic areas has substantially increased over the last 10 to 20 years. 3,4 In addition, there is a significant correlation between the rate of coccidioidomycosis in humans and a risk map for coccidioidomycosis in dogs in California. 5 Thus, it is also likely an emerging infectious disease in dogs.
In people with coccidioidomycosis, peripheral eosinophilia can occur with acute pulmonary infections, with a higher degree of eosinophilia seen in more severe, disseminated, infections. 6 An increased number of eosinophils in tissues is less common. 7 There is an association between fungal and allergic disease in people, and fungal exposure and sensitization promote and worsen the clinical progression of allergic disease. 8 Thus, in some cases, increased numbers of tissue eosinophils due to fungal disease might in part be related to hypersensitivity.
Eosinophilic effusions because of coccidioidomycosis occur in humans, are most commonly found in the pleural cavity, and are thought to result from direct invasion from a lung parenchymal lesion. 9 Eosinophilic effusions are uncommon in animals, with most cases being secondary to underlying neoplasia. 10 This report describes coccidioidomycosis-related bicavitary eosinophilic effusion in a dog. In addition to neoplasia, coccidioidomycosis should also be considered Abbreviations: AFAST, abdominal focused assessment with sonography for trauma; ALP, alkaline phosphatase; RI, reference interval; TFAST, thoracic focused assessment with sonography for trauma. as a differential diagnosis for eosinophilic effusions, particularly if the dog lives in or has traveled to an endemic area.  [10][11][12][13][14][15][16][17] In both dogs and cats, certain infectious agents, such as Dirofilaria immitis, peritoneal cestodiasis, sarcocystosis, and lungworms, can cause an eosinophilic effusion. 11,[18][19][20] Other causes of eosinophilic effusions in dogs and cats include hypersensitivity, congestive heart failure, pneumothorax, interstitial pneumonia, disseminated eosinophilic granulomatosis, and Dacron implants (Dacron arterial conduit: USCI Division, C.R. Bard Inc, Billerica, Massachusetts), and can present as a single cavitary or as bicavitary effusion. 10,11,21 Other documented causes of bicavitary effusion in animals include disseminated carcinomatosis, liver lobe torsion, and visceral mast cell neoplasia. 16,22,23 Compared to people, cases of coccidioidomycosis in dogs are relatively underreported. In addition, the clinical course of the disease is also different between species, with dogs developing more subclinical, chronic infections. 24 Although not uncommon in endemic areas, pleural effusion in dogs with coccidioidomycosis is rarely reported in the literature except in association with disseminated disease involving the pericardium. 25  Eosinophilic pleural effusion associated with coccidioidomycosis occurs in people, with approximately 15% (22/146) of patients hospitalized for coccidioidomycosis infection having pleural effusion. 9 All fluids in this study were exudates with a mean pleural eosinophil count of 10.3%, which is similar to the eosinophil percentage within this dog's peritoneal effusion. 9 The dog's pleural effusion had a comparatively higher eosinophil percentage of 30, and this could be reflective of disease differences between humans and dogs.

| CASE DESCRIPTION
Peritoneal effusions related to coccidioidomycosis infection are rare, with few cases documented in the human literature. [26][27][28][29][30] These cases include coccidioidomycosis with gastrointestinal involvement, and in a case of a liver transplant. 27,29,30 In some cases, hematogenous spread from primary pulmonary infections and ingestion of pulmonary secretions have been proposed as the underlying pathogenesis. 26 It is possible that the dog had Coccidioides spp. granulomas in the abdominal viscera, particularly in light of the ultrasonographic finding of hyperechoic pancreatic mesenteric nodules that could have contributed to the development of peritoneal effusion. In addition, the markedly increased serum ALP enzyme activity, and mild hypercholesterolemia at initial presentation could lend support to mild pancreatitis possibly secondary to infection. Thus, although rare, this case illustrates that the presence of an eosinophilic effusion should prompt clinicians for investigation of possible coccidioidomycosis infection in dogs that live in or have visited endemic regions.
Although concurrent neoplasia cannot be entirely excluded from consideration in the case presented here, it was considered unlikely.
The dog had complete resolution of effusions in both body cavities as well as clinical improvement after prolonged fluconazole treatment.
Relapse of clinical disease after cessation of successful antifungal treatment is documented in human medicine, with relapse in approximately 29% of 34 patients, with a mean time to relapse of 7.3 months. 31 Similarly, relapse is also common in dogs after cessation of the recommended course of antifungal treatment, and it is unclear if resolution of infection offers lifelong immunity to the organism. 32,33 Complete recovery rates generally vary with disease severity, but an overall rate of 60% has been accepted. 32 Thus, relapse of clinical disease in the dog presented here is not an unusual occurrence.

CONFLICT OF INTEREST DECLARATION
Authors declare no conflict of interest.

OFF-LABEL ANTIMICROBIAL DECLARATION
Authors declare no off-label use of antimicrobials.

INSTITUTIONAL ANIMAL CARE AND USE COMMITTEE (IACUC) OR OTHER APPROVAL DECLARATION
Authors declare no IACUC or other approval was needed.

HUMAN ETHICS APPROVAL DECLARATION
Authors declare human ethics approval was not needed for this study.