Pyogranulomatous panniculitis in a cat associated with infection by the Mycobacterium fortuitum/peregrinum group

Abstract

A 6-year-old, spayed female, American domestic shorthair was presented with a 10-month history of nodules on the dorsum. Diagnosis of pyogranulomatous panniculitis caused by Mycobacterium fortuitum/peregrinum group was achieved by using tissue culture, chromatography, and histopathologic examination. Pathological findings, diagnosis, and clinical management of the condition are discussed.

A 6-year-old, spayed female, American domestic shorthair was presented to the Ontario Veterinary College Teaching Hospital (OVC-VTH) with a 10-month history of subcutaneous nodules on the dorsum, which had been diagnosed originally as bite wounds. These lesions had been unresponsive to treatment with amoxicillin and clavulanic potassium (Clavamox; Pfizer Canada, Animal Health Group, London, Ontario) and had progressively worsened, extending down the flanks and developing purulent discharge from several draining tracts.

The referring veterinarian had taken skin biopsies, which were routinely fixed and stained with hematoxylin and eosin, Gram, and periodic acid-Schiff (PAS) stains. A histopathological diagnosis of pyogranulomatous nodular deep dermatitis was made; no organisms were seen. On presentation to the OVC-VTH, the cat had large, irregular, coalescing nodules extending from the dorsum down both flanks. The skin overlying these masses was mottled blue with several crusted draining tracts. Dyspnea was pronounced, and the owner stated that this was the result of an ongoing cardiac problem, which was being treated by the referring veterinarian. Due to the severity of the dyspnea, it was decided to take multiple biopsies for histopathologic examination and tissue culture, as the first and least traumatic procedure. Based on our presumption that Actinomyces or Nocardia spp. were the most likely pathogens, the cat was treated with a combination of erythromycin (Novo-Rythro; Novopharm, Toronto, Ontario) and ampicillin (Novoampicillin; Novopharm, Toronto, Ontario) at doses of 20 mg/kg body weight (BW), PO, q12h, each, until culture results were available. Two skin biopsies were cultured on blood, MacConkey's agar, and Sabouraud dextrose agar for routine detection of pathogens. Occasional gram-positive bacilli were seen on direct microscopic examination. Fungal cultures yielded no significant fungal organisms, but a few pinpoint, dry, white colonies were observed on blood agar in pure culture after 48 h. Staining these white colonies with Ziehl-Neelsen revealed acid-fast bacilli. A presumptive identification of a rapidly growing Mycobacterium sp. was therefore made. The Mycobacterium fortuitum/peregrinum group was identified (Ontario Ministry of Health, Central Public Health Laboratory, Etobicoke, Ontario) by high-performance liquid chromatography (HPLC) in cultures obtained from the skin biopsies. This group is one of 4 taxa that are closely related to and include M. fortuitum (formerly M. fortuitum bv: fortuitum), M. peregrinum (formerly M. fortuitum bv: peregrinum), M. fortuitum third biovariant complex sorbitol-positive, and M. fortuitum third biovariant complex sorbitol-negative (1). These taxa have minimal differences in susceptibility to antimicrobial agents and produce similar clinical disease. The 4 taxa can be separated only by carbohydrate utilization, which is done by only a few laboratories (2,3).

Histologically, the lesion was a pyogranulomatous panniculitis. Many small, well-defined granulomas were found in the deep dermis. These granulomas consisted of relatively large vacuolated macrophages mixed with neutrophils. Most of these granulomas had large central vacuoles, which represented lipocysts (Figure 1). Sections stained with PAS, Gram, and acid-fast stains for Mycobacterium spp. and Nocardia spp. were examined. A few short, gram-positive, beaded bacilli were found in one granuloma located within the central lipocyst (Figure 2). Some bacilli showed weak positive staining on acid-fast stain. When M. fortuitum was identified in culture, the antibiotic regimen was changed to doxycycline (NovoDoxylin; Novopharm) 5 mg/kg BW, PO, q12h, and enrofloxacin (Baytril; Bayer Inc., Toronto, Ontario) 5 mg/kg BW, PO, q24h. Moderate improvement was seen with treatment, but the lesions failed to resolve. Several months later, worsening signs of heart failure prompted a request by the owner for the cat to be euthanized. A request for necropsy was denied.

Figure 1. Pyogranulomatous panniculitis as indicated by presence of extensive aggregation of macrophages and neutrophils (A) with centrally located lipocyst (B). Hematoxylin and eosin stain; bar = 100 μm.

Figure 2. Gram-positive filamentous bacteria (arrow) in the center of a lipocyst. Gram stain; bar = 50 μm. Inset: bar = 20 μm.

Unfortunately, mycobacterium antimicrobial susceptibility testing was not performed; therefore, its resistance profile is unknown. Diagnosis at the species level is important, as potentially useful antibiotics may be chosen based on known susceptibility patterns (4). For example, M. fortuitum and M. smegmatis are usually susceptible to high doses of fluoroquinolones (ciprofloxacin, enrofloxacin, ofloxacin), whereas M. chelonae is not (5,6). Mycobacterium chelonae is usually susceptible only to clarithromycin (7). Other drugs found useful both in vitro and in vivo are gentamicin, amikacin, kanamycin, doxycycline, trimethoprim-sulfonamide, chloramphenicol, clofazimine, and cefuroxime. Opportunistic mycobacteria are usually resistant to antituberculosis drugs (4).

The genus Mycobacterium is the only genus in the family Mycobacteriaceae. These organisms are mycolic acid-producing bacteria, like Rhodococcus and Nocardia. A division occurs between slowly and relatively rapidly growing species of mycobacteria. Fast growers require less than 7 d to produce easily seen colonies (3). Mycobacterium fortuitum is one of the numerous saprophytic, nontuberculous, nonlepromatous, nonchromogenous species that cause opportunistic or atypically rapid growing mycobacterial infections (4). Others in this group include M. smegmatis, M. abscessus, and M. chelonae. Rapidly growing opportunistic mycobacteria have been isolated from many cats, humans, and dogs with cutaneous lesions, as well as from different systemic infections (4,8).

To our knowledge, this is the first reported case of pyogranulomatous panniculitis associated with M. fortuitum/peregrinum infection in a cat in Canada. The cutaneous lesions in cats are most commonly multiple, subcutaneous pyogranulomas with fistulous tracts associated with purulent or serosanguineous drainage (4,8). In this cat, the clinical picture, microscopic lesions, and the location of the bacteria within lipocysts are typical of M. fortuitum infection in cats (4,9). Unlike the organisms of tuberculosis and leprosy, bacteria of this group are ubiquitous in nature, especially in water and wet soil (4). Mycobacterium fortuitum is not pathogenic for animals under normal circumstances and is usually acquired after traumatic introduction (4,5,10). A history of bite wounds was reported in this case. In humans, sporadic cases of cutaneous and systemic lesions due to M. fortuitum infection are reported. In these cases, postsurgical contamination is by far the most common method of infection (11).

The prognosis for M. fortuitum infection and other opportunistic mycobacterioses in cats is guarded and depends mainly on early diagnosis and long-term treatment. Mycobacterium fortuitum is usually susceptible to high dosages of fluoroquinolones (4,5,10). Parenteral enrofloxacin is potentially retinotoxic to some cats in high dosages, and may result in acute and diffuse retinal degeneration (12). Although some cats have been cured with fluoroquinolone therapy alone, others require life-long treatment, and lesions may recur after complete resolution. In this case, the fluoroquinolone treatment was started 10 mo after the appearance of the clinical signs. Delayed proper diagnosis and the poor health condition of this cat due to complicated cardiomyopathy led to the poor prognosis and the decision for euthanasia.

Diagnosis of opportunistic mycobacteriosis is not always easy, and a diligent search for the organism in biopsies is usually required. Organisms are usually not identified on acid-fast-stained tissue sections in these infections (9,10). Frozen section biopsy specimens have improved staining capacity (4). Bacterial culture of deep tissue samples is essential for definitive diagnosis. Analysis of mycobacterial cell wall fatty acid composition by HPLC is recognized as a useful tool for the identification of mycobacteria (3). Mycolic acids are high-molecular weight fatty acids that are present in the cell wall of these bacteria. After several preparatory steps, these mycolic acid esters are separated and detected by ultraviolet (UV) spectrophotometry. Reproducible chromatogenic patterns are used for the identification. Pattern recognition is performed by visual comparison of sample results with mycolic acid patterns from reference species of known mycobacteria. Differential diagnoses should include nocardiosis, blastomycosis, and foreign body reaction.