JPC SYSTEMIC PATHOLOGY
Signalment (JPC# 1795578): A horse
HISTORY: This animal had purulent nasal discharge and a chronic cough. The nasal mucosa and skin were ulcerated, and there was thickening of the superficial lymphatics and abscesses in the superficial lymph nodes.
HISTOPATHOLOGIC DESCRIPTION: Lung: Effecting 20% of the section there are multifocal, random, variably sized nodules of pyogranulomatous inflammation with a central area of eosinophilic cellular and karyorrhectic debris and hemorrhage (necrosis), surrounded by viable and degenerate neutrophils, macrophages, lymphocytes, plasma cells, and rare multinucleated giant macrophages. Inflammatory cells often extend into adjacent, congested alveolar septa and alveoli where they are admixed with homogenous eosinophilic material (edema), polymerized fibrin, necrotic debris and hemorrhage. Multifocally, there are peribronchiolar and perivascular aggregates of lymphocytes, plasma cells, fewer macrophages, rare neutrophils and edema. The pleural and underlying subpleural connective tissue is expanded up to 0.5mm by edema, fibrin, graunulation tissue, and low numbers of previously described inflammatory cells.
MORPHOLOGIC DIAGNOSIS: Lung: Pneumonia, pyogranulomatous and necrotizing, multifocal, random, moderate, with hemorrhage, and pleural edema, breed unspecified, equine.
ETIOLOGIC DIAGNOSIS: Burkholderial pneumonia
CAUSE: Burkholderia mallei (formerly Pseudomonas mallei)
CONDITION: Glanders (Farcy for cutaneous disease)
- Highly contagious and zoonotic disease primarily of horses, donkeys, and mules that is characterized by cutaneous, nasal and pulmonary lesions
- Small, straight to slightly curved, blunt ended, non-motile, unencapsulated, non-spore forming, weakly gram-negative bacillus
- Historically important disease; now eradicated except in parts of North Africa, Eastern Europe, the Middle East, Asia and South America
- In horses, the disease is usually chronic and debilitating with organisms confined to the lesions and discharges; exudates from nasal and cutaneous ulcers are the most infective
- Acute disease primarily affects donkeys, mules and humans with organisms distributed in most tissues; organism may be excreted in feces, urine, saliva and tears
- Virulence factors: capsular polysaccharides; glycocalyx biofilm, resistance to membrane attack complex (MAC), and phago-lysosome fusion
- Ingestion/inhalation of infective excretions and discharges (esp. skin and nasal mucosa) > invasion of bacteria through pharyngeal and intestinal mucosa > septicemia (acute)/bacteremia (chronic) > localization to lungs, possibly skin and nasal mucosa > hematogenous spread to many organs including the spleen, lymph nodes and testes
TYPICAL CLINICAL FINDINGS:
- Mucopurulent nasal discharge
- Rapidly spreading ulcers on the nasal mucosa
- Nodules on the skin of the lower limbs or abdomen
- Nasal lesions on the lower parts of the turbinates and cartilaginous nasal septum
- Nodules eventually ulcerate and become confluent
- Unilateral serous nasal discharge, which becomes purulent and bloodstained
- Cutaneous ulcers discharging a dark honey-colored serum that may become fistulous tracts
- Swollen and painful joints
TYPICAL GROSS FINDINGS:
- Generalized petechial hemorrhages
- Severe catarrhal bronchopneumonia with enlarged bronchial lymph nodes
- Pulmonary nodules with caseous or calcified centers surrounded by zones of inflammation: 2-cm diameter pyogranulomatous nodules throughout the lung
- Ulceration and pyogranulomatous inflammation of mucosa in the nose, trachea, larynx, bronchi
- Nasal lesions: Often unilateral, with copious, purulent, green-yellow exudates
- Nodules and ulcers in the skin, notably on the medial aspect of the limbs with cord-like thickening of lymphatics “farcy pipes or farcy buds” (nodules or ulcers that follow lymphatic vessels = purulent lymphangitis with leukocyte necrosis)
- A characteristic stellate scar replaces healing ulcers on the lower parts of the mucosa of the turbinates and nasal septum
- Abundant unilateral yellow-green nasal exudate
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Fibrinohemorrhagic exudate
- Granulomatous inflammation with a central core of degenerate neutrophils
- Exudative and proliferative
- Mature lesions have central areas of liquefactive or caseous necrosis, surrounded by epithelioid macrophages, multinucleated giant cells and lymphocytes, which blend with an outer layer of granulation tissue
- With time, fibrosis and re‑epithelialization of the ulceration results in scar formation
- Hematogenous spread to the spleen and, less commonly, to other organs
- Bacteria measure 0.5 x 2 um
ADDITIONAL DIAGNOSTIC TESTS:
- Mallein test: This involves intradermal injection of a glycoprotein produced by mallei, which is similar to tuberculin and elicits a local or systemic hypersensitivity; the usual site for injection is the palpebra, with swelling and pus‑forming inflammation of the conjunctiva indicating a positive test
- Serological tests: Complement fixation (most accurate), agglutination and hemagglutination
- Laboratory animal inoculation: "Straus" reaction involves intraperitoneal injection of guinea pigs; subsequent purulent peritonitis and orchitis within 2‑4 days indicates a positive test
- Bacterial culture: Blood agar
- In advanced clinical cases of glanders, the typical lymphangitis in the cutaneous form (Farcy) and the nasal ulcers in the pneumonic form are highly suggestive
Cutaneous form (Farcy):
- Epizootic lymphangitis (Histoplasma capsulaturm farciminosum): Disease of the tropics/subtropics; high numbers of yeast in lesions
- Ulcerative lymphangitis (Corynebacterium pseudotuberculosis): Gram‑positive, small, pleomorphic rods, nonmotile
- Sporothrix schenkii : Uncommon mycosis; cutaneous nodules that often ulcerate and fistulate
- Pythiosis: Hyphae with eosinophilic and granulomatous inflammation
- Strangles (Streptococcus equi): Cervical lymphadenitis with chronic nasal discharge; pulmonary and visceral involvement with “bastard” strangles
- Tuberculosis: Typical pulmonary tubercles with acid fast organisms (uncommon in horses)
- Equine viral rhinopneumonitis and equine influenza virus
- Rhodococcal pneumonia
- Melioidosis: pseudomallei causes disease in rodents, dogs, cats and horses; suppurative acute lesions; granulomatous chronic lesions; embolic pneumonia
- Man is highly susceptible; infection from contact with infected animals, food or equipment; potential biological weapon
- Syrian hamsters (Mesocricetus auratus) and BALB/c mice: Highly susceptibility to infection and have been used as animal models
- Goats, sheep, dogs, cats, zoo carnivores and reported in dromedaries: Susceptible to natural infection; usually fatal
- Cattle, pigs and birds are very resistant to natural disease
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- Caswell JL, Williams KJ. Respiratory system. In: Maxie ME, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 2. 6th ed. Philadelphia, PA: Elsevier; 2016:573.
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- Radostits OM, Gay CC, Blood DC, Hinchcliff KW. Veterinary Medicine. 10th ed., London, England: Harcourt Publishers; 2007:1083-1085.
- Stundick MV, Albrecht AT, Houchens CR, Pierce Smith A, Dreier TM, Larsen JC. Animal Models for Francisella tularensis and Burkhoderia Species: Scientificc and Regulatory Gaps Toward Approval of Antibiotics Under the FDA Animal Rule, Vet Pathol. 2013 Sep;50(5):877-92.
- US Animal Health Assn: Glanders. In: Foreign Animal Diseases. 7th ed., Boca Raton, FL: Boca Publications Group, Inc.; 2008:281-286.
- Wernery U, Wernery R, Joseph M, Al-Salloom F, Johnson B, Kinne J, et al. Natural Burkholderia mallei infection in dromedary, Bahrain. Emerg Infect Dis 2011;17(7). http://dx.doi.org/10.3201/eid1707.110222. Accessed August 25, 2014.