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Veterinary Forum May 2009 (Vol 26, No 5)

Case Report — Disseminated Aspergillosis Presenting as a Spinal Cord Lesion

by Rebecca Spivack, VMD, Aaron Wehrenberg, DVM, Kent Stauffer, DVM, MS, DACVS, DABVP

    Buddy, a 6-year-old, neutered beagle, presented to the Veterinary Specialty Center of Indiana with a 2-month history of thoracolumbar pain. Buddy's neurologic condition was severe, progressive, and accompanied by muscle atrophy and ataxia of the pelvic limbs. Initially, he had been partially responsive to an antiinflammatory course of prednisone at 0.8 mg/kg PO q12h, but his condition began to deteriorate despite this treatment.

    The dog also had a recent history of hematuria and prostatitis, which resolved with orchidectomy and antibiotics. In addition, he had recently traveled from his home in Indiana to the coast of South Carolina.

    On presentation, palpation revealed significant thoracolumbar pain, pelvic limb ataxia, and conscious proprioceptive deficits in both pelvic limbs. Cranial nerves, cervical palpation, and thoracic limb reflexes were within normal limits. These findings were consistent with a T3-L3 spinal cord lesion.

    Medical workup and diagnosis

    A complete blood count, serum biochemistry profile, and thoracic radiography revealed no significant abnormalities. Proteinuria at +3 and a urine pH of 8.0 were found on urinalysis, with a negative urine culture. Brucellosis titers were negative. Survey spinal radiography showed signs of osteoproliferative disease from T12 to L7, with similar lesions present on the right ilial body (Figure 1). Sublumbar lymphadenopathy was apparent but was not sonographically appreciable. Abdominal ultrasonography was generally unremarkable except for solitary, sonolucent nodules in the spleen and on the right psoas muscle. Fine-needle aspiration of the spleen and psoas muscle revealed lymphoid hyperplasia and normal skeletal muscle.

    An infectious cause was strongly considered on the differentials list for the patient's T3-L3 myelopathy. Neoplasia could not be ruled out. Spinal radiography revealed an organized pattern of periosteal reaction that appeared to be less aggressive than the typical changes seen in patients with bacterial osteomyelitis. A computed tomography (CT) scan of the thoracolumbar spine showed a bony reaction that extended beyond the central vertebrae, involving the dorsal laminae and transverse processes, as well as both ilial wings (Figure 2). All diagnostic imaging was reviewed by a board-certified radiologist.

    Specimens of the L6 and L7 transverse processes and articular facets, as well as a sample of the right ilial wing, were obtained by biopsy. Histopathology revealed periosteal proliferative bone with no evidence of infectious organisms or neoplasia. Bone marrow aspirations of the ilium were unremarkable. Possible causes that were considered at this stage included toxoplasmosis, neosporosis, hepatozooan infection, fungal infection, and unidentified foreign body reaction.

    The patient was started on clindamycin at 11.8 mg/kg PO q12h while fungal cultures were pending and additional diagnostic tests were being considered. Buddy also received tramadol at 2.0 mg/kg PO q12h for analgesia during this time.

    Approximately 10 days after referral, the cause was confirmed by abundant growth of Aspergillus organisms on fungal culture of bone near the lumbar spine. A long-term course of systemic antifungal medication was indicated, and the prognosis for clinical improvement was guarded to poor. The owners declined treatment, and Buddy was kept comfortable on tramadol at 2.0 to 3.9 mg/kg PO q8-12h until he was euthanized 2 months after diagnosis.

    Discussion

    Although fungal osteomyelitis is a relatively uncommon cause of T3-L3 spinal cord pathology, disseminated fungal infections with bony involvement are widely reported in small animals.1 Diagnostic differentials include but are not limited to aspergillosis, histoplasmosis, candidiasis, coccidioidomycosis, and blastomycosis, as well as systemic infections of Geomyces, Exophiala, or Phialemonium spp.2,3

    Fungal osteomyelitis is often diagnosed through cytology and histopathology, which typically reveal pyogranulomatous inflammation and fungal hyphae.1 A pyogranulomatous response alone is not sufficient to diagnose systemic mycoses because viral infection, mycobacteriosis, or foreign body reaction may produce a similar response.

    A complete blood count and serum chemistry screen may reveal monocytosis, hyperglobulinemia, increased alkaline phosphatase in cases of bony remodeling, and azotemia with involvement of the urinary tract.1 Urinalysis may reveal active sediment with hyphae visible on microscopic analysis.1

    Available serologic testing includes ELISA, counterimmunoelectrophoresis (CIE), agar gel immunodiffusion (AGID), immunofluorescent antibody (IFA), and polymerase chain reaction (PCR), although results may be difficult to interpret for a ubiquitous pathogen.1 Fungal cultures may be warranted to confirm the presence of fungal infection, which in Buddy's case was the most specific diagnostic test.

    Aspergillus is a saprophytic fungus that is ubiquitous in the environment. Disseminated aspergillosis is considered a disease of immunocompromised individuals and is most commonly seen in young to middle-aged dogs, with overrepresentation among German shepherds.1 The most common route of entry is the respiratory tract, through which the organism then spreads hematogenously.1 The urogenital tract is a less likely but feasible point of entry for fungal infections.1 It is not possible to determine whether Buddy's history of urogenital disease was a salient factor in the development of disseminated aspergillosis.

    Immunoglobulin A (IgA) deficiencies have been implicated in the development of disseminated Aspergillus infections, which can lead to compromise in local immune mechanisms within the respiratory tract.1 Administration of systemic corticosteroids is another potential risk factor that may facilitate the transition from local to systemic mycoses by decreasing immune function.1

    Although Buddy initially had been placed on a course of steroids to treat thoracolumbar pain, whether this exacerbated his condition is unclear. Based on the onset of clinical signs, it is likely a fungal infection had already been established at the time of this treatment. Buddy had no other obvious reason to be immunocompromised, although IgA levels were not measured in the workup.

    If medical therapy had been pursued, the main considerations for systemic antifungals would have been itraconazole and amphotericin B (Table 1).1 Itraconazole is a synthetic imidazole that is a broad-spectrum antifungal agent.4 It has been shown to have greater efficacy against Aspergillus organisms than any other imidazole, although its failure rate has been up to 50% even with long-term treatment.4 Relapse is common once therapy is discontinued, which may be related in part to the immunocompromised state of the individual. Because clinical improvement often precedes complete eradication of the organism, an endpoint in treatment should be established by repeating cytology and culture of affected tissues, as well as evidence of radiographic resolution.1

    Although itraconazole does not penetrate the cerebrospinal fluid as easily as fluconazole does, it is more efficacious than fluconazole in the treatment of disseminated aspergillosis, so it is the drug of choice.4 The most common side effect of itraconazole is gastrointestinal signs, such as nausea and vomiting, although these are often controlled by giving the drug with a meal.4 Dose-dependent hepatotoxicity has been documented in humans, dogs, and cats but is a greater concern in patients with preexisting liver impairment.4 Drug eruption and vasculitis also have been reported but are uncommon.4

    In addition, amphotericin B was considered because of its excellent activity against Aspergillus spp, but in the case of Buddy, its administration was less practical because of parenteral administration and because of the significant nephrotoxicity associated with its use.4 In humans, voriconazole has been recently used to treat disseminated aspergillosis but has not been used widely in domestic species.5

    1. Greene CE (ed). Infectious Diseases of the Dog and Cat, ed 3. St. Louis, Mo.: Elsevier; 2006:620-627.

    2. Earne JB, Walker MC, Alleman AR. Systemic infection with Geomyces organisms in a dog with lytic bone lesions. JAVMA 2007;230(4):537-540.

    3. Smith AN, Spencer JA, Vygantas KR, Welch JA. Disseminated infection with Phialemonium ovatum in a German shepherd dog. JAVMA 2000;216(5):708-712.

    4. Boothe DM (ed). Small Animal Clinical Pharmacology and Therapeutics. Philadelphia: WB Saunders; 2001:222-234.

    5. Sheehan DJ, Hitchcock CA, Sibley CM. Current and emerging azole antifungal agents. Clin Microbiol Rev 1999;12:40-79.

    References »

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