Patellar Blastomycosis in a Dog

Introduction

Stifle joint disorders constitute the most frequent cause of hind-limb lameness in the dog. Stifle lameness secondary to patellar disease consists most commonly of a congenital luxation.¹ Patellar injuries are uncommon and usually result from direct trauma. Traumatic injuries may result in fractures and dislocations of the patella.^2,3 Other pathological conditions include bone cysts, osteomyelitis and neoplasia of primary origin, metastasis, or invasion from adjacent structures.^4–6 Osteomyelitis, defined as an inflammation of the bone and its bone marrow contents, can occur by primary contamination or hematogenous spread.⁷ Most infections are bacterial in origin, although fungi may occasionally be involved.⁸ Osteomyelitis secondary to parasites and viruses has rarely been reported. The objective of this paper is to report the diagnosis, treatment, and outcome of patellar blastomycosis causing stifle joint disease in a dog. To the authors’ knowledge, this is the first case of patellar blastomycosis reported in the dog.

Case Report

A 4-year-old, 11.1-kg, spayed female, mixed-breed dog was referred to the University of Illinois Veterinary Teaching Hospital (VTH) for evaluation of nonweight-bearing, left hind-limb lameness of 6 months’ duration. The referring veterinarian treated the dog initially with analgesics and exercise restriction for 1 month. When the dog failed to improve, a presumptive diagnosis of cranial cruciate ligament disease was made. An arthrotomy was performed, and the stifle was stabilized with an extra-capsular lateral fabella suture.

When the dog was admitted to the VTH, it had a grade V/V, left hind-limb lameness with severe muscle atrophy. The stifle was markedly painful and thickened with severe soft-tissue swelling, preventing accurate palpation of the patella and patellar ligament. Tibial compression and cranial drawer tests, performed while the dog was sedated, were negative; however, the affected stifle range of motion was markedly decreased when compared to that of the right stifle.

The results of a complete blood cell count, serum biochemical profile, and urinalysis were within reference ranges. Radiographs made by the referring veterinarian at the onset of the lameness were reviewed, and a radiolucent lesion consistent with lysis of the patella was visible on the lateral radiograph of the left stifle [Figure 1]. Additional caudocranial and mediolateral radiographs of the left stifle were made while the dog was sedated. The patella appeared progressively lytic and medially displaced, with a well-defined periosteal response on its cranial surface [Figure 2].

Differential diagnoses included infectious (bacterial or fungal) and neoplastic (primary, metastatic, or invasion from adjacent soft tissues) diseases of the patella. Thoracic radiography and abdominal ultrasonography were performed to evaluate the dog for other signs of neoplastic disease. Right lateral, left lateral, and ventrodorsal thoracic radiographs, made while the dog was sedated, were normal. On abdominal ultrasonography, the left medial iliac lymph node was enlarged; it measured 17.3 mm × 9 mm and had a hypoechoic echotexture. Results of cytological analysis of ultrasound-guided fine-needle aspirates of this node included hemodilution and scattered lymphoid cells predominated by small lymphocytes, with rare lymphoblasts and intermediate lymphocytes. Results of cytological examination of joint fluid aspirated from the affected stifle were consistent with severe suppurative inflammation and hemodilution. No microorganisms were observed, and mucin content was adequate.

The day after the dog was presented to the VTH, an exploratory arthrotomy was performed via a lateral para-patellar approach. The joint capsule was markedly thickened. Mild osteophytosis was present on both trochlear ridges of the distal femur. The patellar articular cartilage was intact, but the outer rim of the articular surface was lined by tissue resembling granulation tissue. The patellar ligament was markedly thickened and appeared infiltrated with the same tissue. Both cruciate ligaments and visible portions of the menisci were intact. The previously placed, extracapsular lateral fabellar suture was not removed. Synovium and samples of the joint capsule were harvested with Mayo scissors. Samples of the patellar bone were obtained with Jamshidi bone biopsy needles and Lempert rongeurs. The body of the patella was soft and brittle. Samples were submitted for histopathological evaluation, bacterial culture, and sensitivity testing. An interlocking loop suture using 0 (3.5 metric) monofilament nylon was placed from the tendon of insertion of the quadriceps on the patella, over the patella, and into the patellar ligament; this was intended to relieve tension during weight bearing and to prevent postoperative fracture of the weakened patella or avulsion of the patella tendon from the patella.

The dog recovered uneventfully from the surgical procedure. Bacterial culture results were negative. Microscopic examination of the biopsied tissues revealed severe, locally extensive, pyogranulomatous, and proliferative synovitis with intralesional yeast and moderate, locally extensive, pyogranulomatous osteomyelitis. The morphology of the organisms was suggestive of Blastomyces dermatitidis [Figure 3].

Although no evidence of respiratory system involvement was seen, a blood gas analysis was performed following diagnosis to rule out occult respiratory insufficiency from possible pulmonary blastomycosis. A fundoscopic examination also was performed to rule out ocular blastomycosis. Results of both tests were normal. The dog was treated with itraconazole (5 mg/kg body weight, per os [PO] q 12 hours) starting 3 days postoperatively. Carprofen (2.2 mg/kg body weight, PO q 12 hours for 2 weeks) also was dispensed to provide postoperative analgesia.

The dog was reexamined 3 weeks after surgery. Pain and lameness (grade IV/V) were improved. Results of a serum biochemical profile submitted to monitor for potential hepatotoxicity from the itraconazole were within reference ranges. Radiographs of the left stifle were made and evaluated [Figure 4]. The lytic lesions of the patella appeared slightly more severe than before surgery, most likely as a result of the biopsy. Although the radiographic evidence of periosteal response on the patella and stifle effusion remained essentially unchanged, the soft-tissue swelling surrounding the patella had resolved.

The dog was admitted for 10 days of intensive physical rehabilitation to encourage use of the left hind limb. The physical rehabilitation protocol consisted initially of land treadmill exercises, supplemented with massage and passive range of motion. Underwater treadmill exercises were introduced 1 week into rehabilitation. At the time of discharge, the dog’s lameness had improved to a grade II/V, and the range of motion of the left stifle joint appeared well improved.

Itraconazole therapy was continued at 5 mg/kg q 12 hours for a total of 90 days, during which time the dog had no reported adverse reaction to the drug. When the dog was evaluated 1 month after discontinuation of the antifungal medication, 4 months after presentation at the VTH, the lameness had resolved and muscle mass appeared restored. No difference in range of motion could be appreciated between the two stifles. Partial remineralization of the patella was noted on radiographic evaluation, along with remodeling of the patellar periosteal response [Figure 5]. Swelling surrounding the patella and patellar tendon was resolved. The enthesiophyte on the tibial plateau appeared smaller; however, this finding may have resulted from a difference in positioning between consecutive radiographs. Results of a serum liver biochemical profile were within reference ranges. No recurrence of lameness was reported at the time of submission of this article (40 months postoperatively).

Discussion

Blastomyces dermatitidis is a soil-borne, dimorphic fungus that causes systemic infection. Blastomycosis is endemic in the Mississippi, Missouri, and Ohio River valleys, as well as in Wisconsin and the central Atlantic states.^9,10 At room temperature (25°C), the organism is found in the mycelial (i.e., hyphal) form and produces conidia. Infection occurs when conidia are inhaled, deposited in the lungs, and incubated at body temperature (37°C). During incubation, the infective conidia assume the yeast phase. The host may successfully eliminate the infection, or the organism may disseminate by hematogenous or lymphatic routes to lymph nodes, eyes, skin, subcutaneous tissue, bone, liver, external nares, the reproductive tract, or to the central nervous system—with or without persistence of a pulmonary infection.^11,12

Pulmonary infection is reported in the majority (85%) of affected dogs.¹³ The organism rarely causes a focal lesion when directly inoculated in a wound. Osseous and cutaneous blastomycoses without other sites of involvement have been reported in human patients and are usually a result of direct inoculation of the organism or by dog bites.^14–17 Solitary bone lesions have been reported in 10% to 15% of dogs with blastomycosis, presumably secondary to local inoculation or wound contamination.^18,19

The mode of infection in the case described here remains unclear. Intraoperative contamination during the arthrotomy performed by the referring veterinarian is unlikely since osteolytic lesions were present on radiographs obtained prior to this surgery. Local inoculation, wound contamination, or extension from the joint is most likely because of the lack of clinical signs in any other body tissue and the historical free access to the outdoors afforded the dog at home. Hematogenous spread—typical of most fungal osteomyelitis—is much less likely because of the dense and relatively a vascular nature of the patella. To the authors’ knowledge, this is the first case report of isolated patellar blastomycosis in a dog.

Clinical signs of infection with blastomycosis depend on the organs affected. In human patients and dogs, the most common clinical signs include respiratory abnormalities and weight loss.¹³ Fungal osteomyelitis typically results in lameness. Pain and swelling are usually noted over epiphy-seal regions of bones below the elbow or stifle joints. Single lesions are more common than multiple lesions. Fungal mono- or polyarthritis is considered a rare cause of lameness. ²⁰

The diagnosis of blastomycosis is made based on results of radiography, cytology, serology, and histopathology. In cases involving bone, osteolysis typically occurs in the metaphyses or epiphyses of long bones. The forelimbs are affected more commonly than hind limbs, with most lesions localizing below the elbow or stifle.²⁰ Periosteal proliferation and soft-tissue swelling are noted in approximately 50% of cases.²⁰

Though nonspecific, scintigraphy can be used to determine the extent of dissemination of the disease and to detect occult lesions. Identification of the organism on cytopathology or histopathology strengthens the diagnosis of blastomycosis. Histological lesions are typically purulent to pyogranulomatous, with neutrophils, macrophages, and multinucleated giant cells. Yeast bodies are often identified in these lesions.²¹ Culture allows definitive identification of Blastomyces dermatitidis. Mycelia may take 1 to 4 weeks at 37°C to grow on Sabouraud’s dextrose agar, whereas yeast will grow on blood or brain-heart infusion agar in 1 to 2 weeks at 25°C. The microbiology laboratory should be made aware of cases suspected of blastomycosis, because viable cultures of Blastomyces dermatitidis are a potential hazard for laboratory personnel.²²

If the organism cannot be identified, fungal titers may be measured. The agar gel immunodiffusion test is used to detect antibodies to the A-antigen of Blastomyces dermatitidis and has a reported sensitivity range of 41% to 90%.^13,23–26 However, titers may be negative in the early phase of the disease and currently are not recommended as the sole test for confirming a diagnosis of blastomycosis in dogs.²³

Antigen detection is a more sensitive test for diagnosis of blastomycosis than antibody detection using the agar gel immunodiffusion test.²⁷ A radioimmunoassay for the WI-1 antigen of Blastomyces dermatitidis has been described and is reported to have a higher sensitivity (92%) than the agar gel immunodiffusion test.²⁴ The MVista Blastomyces antigen enzyme immunoassay has also been evaluated in dogs. Its sensitivities for detection of the antigen in urine and serum were 93.5% and 87%, respectively.²⁷ Both antigen tests, however, are not currently available for clinical use. Although less accurate, serological testing along with clinical signs and suggestive radiographic findings are supportive of blastomycosis and may be substituted for identification of the organism to diagnose blastomycosis.

Therapeutic administration of amphotericin B, alone or in combination with ketoconazole, is effective in approximately 75% of all dogs with blastomycosis.^28,29 Treatment with ketoconazole alone is effective in about 33% of dogs, with relapses occurring in about 33% of these cases.^29,30 Fluconazole has low protein binding, is only slightly hydrophobic, and therefore is distributed widely in body fluids. Fluconazole reaches high concentrations in the cerebrospinal fluid, urine, and ocular fluid.^31,32 Its use is preferred in cases with infection at these sites.^33–35

Itraconazole has recently gained popularity for the treatment of canine blastomycosis because of its ease of administration and low toxicity.^36,37 It has been shown to be more effective against isolates of Blastomyces dermatitidis than fluconazole or ketoconazole in vitro.³⁸ Itraconazole is now considered the treatment of choice for dogs with blastomycosis. Recommended doses vary from 5 to 10 mg/kg once daily for 60 to 90 days or for 2 to 4 weeks beyond clinical resolution. Both doses were found to be effective, with similar cure and relapse rates; but adverse effects were less common with the lowest dose.³⁶ Recurrence is reported in 20% of dogs treated with a 60-day course of itraconazole; the majority of these recurrences were within 426 days of antifungal therapy.³⁶ Dogs that relapse usually respond to a second course of itraconazole.²⁵ The dog in this report responded to an extended course of itraconazole without any adverse reaction to the medication and without recurrence during a 40-month follow-up period.

Conclusion

Blastomycosis should be considered as a differential diagnosis for osteolytic patellar diseases and secondary arthritis of the stifle joint. Definitive diagnosis may require histological evaluation of a surgical biopsy. Management with surgical debridement and joint lavage followed by oral itraconazole treatment and physical rehabilitation successfully resolved the clinical signs in this dog.