Pathology in Practice

Lara M. Tomich 1Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois, Urbana, IL 61802.

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Jason B. Pieper 1Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois, Urbana, IL 61802.

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Adam W. Stern 1Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois, Urbana, IL 61802.
2Veterinary Diagnostic Laboratory, University of Illinois, Urbana, IL 61802.

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History

An approximately 1-year-old 4.1-kg (9.0-lb) castrated male domestic shorthair cat was evaluated because of a 3-month history of nonhealing wounds on the ventral aspect of the abdomen. The lesions were first noted when the cat was captured for neutering at an animal shelter and subsequent adoption. The wounds were thought to be attributable to trauma and were debrided and closed with placement of Penrose drains during bilateral orchiectomy. The cat was treated with ampicillin (dose unknown, SC, once), robenacoxib (2 mg/kg [0.9 mg/lb], SC, once and PO, q 24 h for the following 2 days), and amoxicillin–clavulanic acid (15.3 mg/kg [7.0 mg/lb], PO, q 12 h for 10 days). The drains were removed, and a second debridement with closure of the wounds was performed 10 days after the initial surgery; the aforementioned treatment regimen with ampicillin, robenacoxib, and amoxicillin–clavulanic acid was repeated. Wound closure was unsuccessful despite 2 additional attempts over the following month. In the 2 months after the unsuccessful attempts at closure, several antimicrobials including clindamycin, enrofloxacin, doxycycline, and rifampin were administered to the cat because of suspected atypical mycobacterial infection. There was no improvement in the cat's condition, and referral to a dermatology service was recommended. At the time of the referral evaluation, the cat was being treated with enrofloxacin (5 mg/kg [2.3 mg/lb], PO, q 24 h), doxycycline (10 mg/kg [4.5 mg/lb], PO, q 24 h), and rifampin (15 mg/kg [6.8 mg/lb], PO, q 24 h).

Clinical and Gross Findings

At the referral evaluation, the cat was febrile with a rectal temperature of 40.1°C (104.1°F). The caudoventral portion of the abdomen was partially shaved, and numerous erythematous to purpuric macules, erosions, and ulcerations were observed. There were 2 large cavernous and communicating draining tracts extending into the musculature (Figure 1). The lesions and the draining tracts were covered by a serous exudate. Palpation of the affected caudal ventral portion of the abdomen appeared to cause the cat some discomfort.

Figure 1—
Figure 1—

Photograph of the ventral aspect of the abdomen of a 1-year-old cat that was referred for evaluation of multiple draining tracts that had not responded to treatment. Notice the large cavernous draining tracts that connect deeply.

Citation: Journal of the American Veterinary Medical Association 257, 5; 10.2460/javma.257.5.503

Physical examination findings were otherwise normal, and the cat was eating, drinking, urinating, defecating, and behaving normally at the shelter. Cytologic examination of an impression smear of the lesions (stained with a commercially available Romanowsky stain variant) revealed evidence of pyogranulomatous inflammation but no observable infectious agents. Skin biopsy specimens were collected and submitted to the hospital's veterinary diagnostic laboratory for histologic examination, aerobic and anaerobic microbial cultures, 18S rRNA fungal PCR assay, 16S rRNA mycobacterial PCR assay, and mycobacterial culture.

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

Histopathologic and Microbiological Findings

Histologic examination of sections of skin revealed large numbers of macrophages and neutrophils diffusely within the dermis and panniculus admixed with aggregates of lymphocytes and plasma cells (Figure 2). There was dermal and subcuticular edema and scattered fibrosis. Large aggregates of macrophages and neutrophils rarely surrounded radiating colonies of tangled filamentous bacteria that were gram positive and acid-fast positive (Figure 3).

Figure 2—
Figure 2—

Photomicrographs of a section of skin from the cat in Figure 1. A—Notice the pyogranulomatous inflammation with a cluster of tangled bacteria within the subcutaneous fat. H&E stain; bar = 100 μm. B—Branching, beaded filaments have fragmented into pleomorphic rods. H&E stain; bar = 10 μm.

Citation: Journal of the American Veterinary Medical Association 257, 5; 10.2460/javma.257.5.503

Figure 3—
Figure 3—

Photomicrograph of another section of skin from the cat in Figure 1. Notice the acid-fast cluster of tangled bacteria. Fite stain; bar = 50 μm.

Citation: Journal of the American Veterinary Medical Association 257, 5; 10.2460/javma.257.5.503

Both aerobic microbial and mycobacterial cultures of the skin biopsy specimens yielded growth of Nocardia sp, which was most closely related to Nocardia brasiliensis (as determined from results of matrix-assisted laser desorption-ionization–time-of-flight mass spectrometry). Results of anaerobic microbial culture, 18S rRNA fungal PCR assay, and mycobacterial PCR assay were negative. The organism was susceptible to amikacin, amoxicillin–clavulanic acid, cefovecin, chloramphenicol, doxycycline, gentamicin, ticarcillin–clavulanic acid, and trimethoprim-sulfamethoxazole.

Morphologic Diagnosis and Case Summary

Morphologic diagnosis: marked, chronic, diffuse, pyogranulomatous dermatitis and panniculitis with intralesional gram-positive and acid-fast–positive bacteria consistent with Nocardia sp.

Case summary: dermatitis and panniculitis associated with Nocardia infection in a domestic shorthair cat.

Comments

For the cat of the present report, the dosage of doxycycline was increased to 10 mg/kg, PO, every 12 hours, and treatment with amoxicillin–clavulanic acid was restarted at a dosage of 20 mg/kg (9.1 mg/lb), PO, every 12 hours. Administration of rifampin and enrofloxacin was discontinued. Rapid improvement in the cat's condition was noted in the following 1 to 2 weeks, and the lesions resolved completely within 1 month. Antimicrobial treatment was continued for 2 weeks after resolution of clinical signs. The abdominal lesions recurred 6 months after cessation of antimicrobial treatment, and administration of doxycycline and amoxicillin–clavulanic acid was restarted with subsequent slower resolution of clinical signs. At 2.5 months after restarting the antimicrobial treatments, a subcutaneous nodule remained that was surgically excised and submitted for histologic examination, which revealed numerous bacterial aggregates within the nodule.

Cutaneous nocardiosis closely resembles infections of other higher-order bacteria such as Mycobacterium spp, Rhodococcus spp, Corynebacterium spp, Actinomyces spp, and Dermatophilus spp. Because of the similarities between the clinical features of nocardiosis and those of other pyogranulomatous bacterial infections, results of cytologic or histologic examination and microbial culture and antimicrobial susceptibility testing of appropriate specimens are crucial for accurate diagnosis and effective treatment. Nocardia spp appear as nonstaining filamentous bacteria in cytologic preparations after a modified Romanowsky stain variant is applied and are gram positive, as are Rhodococcus spp, Corynebacterium spp, Actinomyces spp, and Dermatophilus spp. Mycobacterium spp are also gram positive but may resist this staining. Nocardia spp are partially acid-fast positive, whereas Corynebacterium spp, Actinomyces spp, and Dermatophilus spp are all acid-fast negative. Rhodococcus spp are variably and weakly acid-fast positive. Mycobacterium spp are strongly acid-fast positive.1–4 When an infection with Nocardia spp is suspected, microbial cultures are best incubated at 37°C, and a period of 72 hours to 2 weeks may have to elapse before detectable growth of the organisms is achieved.1,5

Nocardia spp are ubiquitous saprophytes from the environment and are not part of the normal flora of mammals, unlike Actinomyces spp. They are aerobic, gram-positive, partially acid-fast–positive, filamentous bacteria that typically cause infection by inoculation of soft tissue via penetrating wounds or inhalation of aerosols containing the organisms. Infection with Nocardia spp causes acute or chronic, suppurative or granulomatous disease in many species, including cats, dogs, humans, cattle, horses, pigs, and birds.1

Pathogenic strains of Nocardia spp are facultative intracellular organisms that survive within phagocytic vacuoles by use of superoxide dismutase and inhibition of lysosomal enzymes. Cutaneous and subcutaneous abscess formation is the most common clinical sign in cats.1 Less commonly, pulmonary and disseminated forms of nocardiosis may develop in cats.6 Rarely, nocardiosis has been associated with osteomyelitis and sinorhinitis.5,7,8

Nocardia-induced abscesses often develop into nonhealing wounds with discharge. Lesions tend to spread circumferentially through the development of contiguous lesions or through the lymphatic vessels. Draining sinus tracts are a common sequela. Among cats with nocardiosis, males are overrepresented likely because of their comparatively increased propensity for roaming, fighting, and sustaining penetrating injuries.5 Some affected cats may have a predisposing underlying disorder, such as renal transplantation, retroviral infection, or glucocorticoid administration, whereas others may be immunocompetent.9 The most common pathogenic species of Nocardia that affects cats are Nocardia cyriacigeorgica, N brasiliensis, Nocardia otitidiscaviarum, and Nocardia nova complex.7 Molecular techniques that involve amplification and sequencing of 16S RNA and 65-kDa heat shock protein genes are important for distinguishing among species.5,7,8 Traditionally, trimethoprim-sulfonamide, aminoglycosides, and late-generation β-lactam drugs are the antimicrobials of choice for treatment of feline nocardiosis.7 Results of microbial culture and antimicrobial susceptibility testing can be very helpful in determining all antimicrobial options because treatment is generally long term, and safer, better-tolerated alternatives to trimethoprim-sulfonamide are welcomed. For example, in the case described in the present report, bacterial culture and antimicrobial susceptibility testing showed that the isolate was susceptible to amoxicillin–clavulanic acid and doxycycline; treatment with these drugs was chosen over administration of trimethoprim-sulfonamide because they were less likely to cause serious adverse effects such as bone marrow suppression. Although monotherapy has been reported to be efficacious in vitro, clinical cases of nocardiosis often require a combination treatment. Duration of drug administration should be at least 3 to 6 months; shorter periods of treatment often result in recurrence of lesions. In humans with nocardiosis, the best outcomes are achieved with combined surgical excision and debridement and long-term antimicrobial treatment. For cats with Nocardia infection, prognosis should be considered guarded; however, early diagnosis and appropriate intervention with a combination treatment may somewhat improve prognosis.10 Among affected cats that have an underlying predisposing condition and delayed diagnosis and are given inappropriate treatment, the mortality rate is high.

Acknowledgments

The authors thank Sandra Grable for assistance with sample collection.

References

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