JPC SYSTEMIC PATHOLOGY
SIGNALMENT (JPC# 4069782): 3-month-old miniature horse filly
HISTORY: This filly presented with a one week history of non-resolving respiratory congestion. High fever and increased respiratory rate were noted and (unspecified) treatment was initiated. The patient was initially responsive to care, but subsequently had two seizures and died
HISTOPATHOLOGIC DESCRIPTION: Effacing approximately 40% of the normal pulmonary parenchyma there are multiple pyogranulomas (up to 11mm) composed of a central core of necrosis with numerous degenerate neutrophils and macrophages, admixed with necrotic cellular debris, fibrin and scattered mineral, surrounded by epithelioid macrophages, fewer multinucleated giant cells, and low numbers of lymphocytes and plasma cells. Macrophages and multinucleated giant cells are often packed with numerous 1-2um basophilic coccobacilli. Similar inflammatory cells (including macrophages packed with coccobacilli), necrotic debris and fibrin fill remaining bronchioles, infiltrating through the bronchiolar epithelium/wall to fill adjacent alveoli and efface alveolar septa (necrosis). There is multifocal type II pneumocyte hyperplasia. Bronchiolar epithelial cells are multifocally necrotic with sloughing into the lumen. In less affected areas, alveolar septa are expanded up to 4 times normal by fibrin, edema and low numbers of macrophages. There are multifocal areas of mild hemorrhage and a few hemosiderin-laden macrophages are present. The pleura and interlobular septa are expanded up to 5 times normal by fibrin and edema. Multifocally, vascular walls contain mild neutrophilic infiltrate and are rimmed by moderate perivascular edema.
MORPHOLOGIC DIAGNOSIS: Lung: Pneumonia, pyogranulomatous and necrotizing, multifocal-to-coalescing, chronic-active, severe, with numerous intrahistiocytic coccobacilli, miniature horse, equine.
ETIOLOGIC DIAGNOSIS: Rhodococcal pneumonia
CAUSE: Rhodococcus equi
- Rhodococcus equi is a common, facultative intracellular gram-positive bacterium
- Proliferates in macrophages and multinucleated giant cells
- Causes two primary forms of disease, typically in foals 1-6 months old:
- Pyogranulomatous bronchopneumonia
- Ulcerative enterocolitis
- Can also cause ulcerative typhlitis with granulomatous or suppurative inflammation of mesenteric and/or colonic lymph nodes, polysynovitis, septic arthritis, osteomyelitis and other secondary manifestations
- Worldwide distribution with highest incidence in dry, dusty, manure-contaminated environments during summer months
- Cell wall contains complex lipids similar to Mycobacterium and Nocardia sp.; increases resistance to chemicals, dehydration, oxidative stress and lowered pH.
- Normally inhabits soil and gastrointestinal tract of herbivores
- Transmission via inhalation of Rhodococcus equi-contaminated dust
- Virulent forms of equi contain a 80-90 Kbp plasmid containing a vapA gene (virulence associated protein A) encoding 15-17 kDa cell surface lipid proteins that elicit an intense humoral response and allow bacteria to survive within macrophages
- Other factors encoded by the plasmid (VapC through VapI, VapX) are dispensable; VapB and VapN can increase virulence in some nonequine species
- Other factors in virulence: Cholesterol oxidase, choline phosphohydrolase, lecithinase, cell wall mycolic acids, capsular polysaccharide, rhequichelin
- In the absence of opsonization of bacteria or activation of macrophages by IFN-gamma, fusion of the phagosome-lysosome is inhibited: Bacteria replicate within and eventually rupture macrophage, releasing more bacteria
- A strong TH-1 response is necessary to clear an established infection, as CD4+ T-cells produce IFN-gamma to activate macrophages and CD8+ T-cells lyse infected macrophages
- Neutrophils can kill equi, but also effect significant tissue damage
- Young foals are at increased risk due to waning passive humoral immunity and an underdeveloped cell-mediated immune response; most infected by 2-weeks of age
- Failure of passive transfer of colostral immunoglobulins is a predisposing factor; hyperimmune plasma protects against development of disease
TYPICAL CLINICAL FINDINGS:
- Fever, cough, nasal discharge and increased respiratory rate
- Diarrhea and weight loss
- Sudden death (subacute form)
- Lameness or reluctance to walk
- Subcutaneous abscesses
- Leukocytosis with neutrophilia and monocytosis
- Increased plasma fibrinogen (an indicator of inflammation)
TYPICAL GROSS FINDINGS:
- Lung: Multiple 1-100 mm diameter, coalescing, firm, pyogranulomatous foci predominantly in the cranioventral lung lobes
- Gastrointestinal tract: Ulcerative enterocolitis, often located over Peyer’s patches in the ileum, and irregular well-defined ulcers in the large intestine occur in more than 50% of foals with pneumonia; these often appear as raised along the periphery with a depressed ulcerated center (“volcano ulcers”)
- Tracheobronchial and mesenteric lymph nodes: Swollen, pale, and edematous, often with pyogranulomatous lymphadenitis. Mesenteric LN infections can progress to large abscesses
- Joints: Polysynovitis, especially of the tibiotarsal and stifle joints
- Bone: Osteomyelitis
- Eye: Uveitis, panophthalmitis
- Misc: Pericarditis, endocarditis, cellulitis, subcutaneous abscesses, guttural pouch empyema, pleuritis, sinusitis, myositis, stomatitis, pyometra, omphalitis, peripheral lymphadenopathy
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Lung: Pyogranulomatous pneumonia (can start as abscesses); alveolar lumina contain abundant macrophages and giant cells containing many cytoplasmic bacteria; septal necrosis and atelectasis; usually no distinct fibrous capsule around necrotic debris
- Intestine: Pyogranulomatous inflammation of lymphoid tissue; fibrinonecrotic ulceration of overlying epithelium
- Lymph nodes: Pyogranulomatous lymphadenitis
- Joints: can cause a septic arthritis or a nonseptic, mononuclear, probably immune mediated polysynovitis
ADDITIONAL DIAGNOSTIC TESTS:
- Bacterial culture and/or PCR amplification combined with cytologic examination of transtracheal aspiration
- +/- Weakly acid fast (Fite)
- Radiographic evidence of lung abscesses, ultrasonography
- Rhodococcus equi: Most common
- Although fungal pneumonias are uncommon in horses, possible etiologies include Aspergillus fumigatus, Histoplasma capsulatum, Blastomyces dermatitidis, Coccidioides immitis, and Cryptococcus neoformans
- Mycobacterium: Rare in horses
- Foreign body
- Streptococcus zooepidemicus: Most common cause of bacterial pleuropneumonia in foals and a common cause of pleuropneumonia in older horses
- Embolic pneumonia caused by Streptococcus equi, Actinobacillus equuli, Pasteurella multocida, Bordatella bronchiseptica, Escherichia coli, Bacteroides , Salmonella sp., and Chlamydophila psittaci; can be differentiated on bacterial culture
- Equine viral rhinopneumonitis (EVR) (Family Herpesviridae): Intranuclear inclusions; mild transient bronchointerstitial pneumonia
- Equine influenza virus (Family Orthomyxoviridae): Mild self-limiting bronchopneumonia
- Rhinovirus (Family Picornaviridae): Typically affects the upper respiratory system, but not the lungs
- Adenoviral pneumonia (Family Adenoviridae): Necrotizing pneumonia; intranuclear inclusions; usually in CID foals
- Equine viral arteritis (Genus Arterivirus): Interstitial pneumonia with arteritis and edema
- Pneumocystis carinii: Interstitial pneumonia, usually in immunocompromised foals; may occur as a co-infection with equi; silver-stained sections
- Mice: Classification of R equi as virulent (vapA positive), intermediately-virulent (vapB positive) or avirulent (no virulence plasmid) is based on behavior of isolate in mice.
- Cattle: Metritis; tubercle-like lesions in lymph nodes; pneumonia in calves; new plasmid virulence factor (vapN) isolated from some cattle strains
- Sheep: Caseous bronchial lymphadenitis
- Goats: Pyogranulomatous lesions in the liver and lungs; osteomyelitis of the vertebra and skull; fibrinous enterocolitis
- Pigs: Pyogranulomatous lesions in submaxillary and cervical lymph nodes; disseminated disease caused by vapB positive strains
- Cats: Pyogranulomatous skin lesions; usually vapA positive
- Dogs: Suppurative pleuropneumonia, endophthalmitis, endocarditis, vaginitis, tracheitis, osteomyelitis, myositis, hepatitis in mostly immunocompromised dogs
- Camelids: Suppurative to necrotizing pneumonia; also involvement of liver, spleen and mediastinal lymph nodes
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