JPC SYSTEMIC PATHOLOGY
SIGNALMENT: (JPC #2237297) Tissue from a dog.
HISTORY: None provided.
CBC Range Chemistry Range Urinalysis
WBC 23.1 (5-14.1) Phos 12.7 (2.9-5.3) S.G. 1.020
Segs 84% BUN 159 (8-28) pH 6.5
Lymphs 6 % AST 186 (13-15) Protein 952 mg/dl
Monos 7% Creatinine 6.7 (0.5-1.7) Creatinine 73 mg/dl
Bands 1% Cholesterol 340 (135-278) Blood 3+
Eos 2% T.P. 5.1 (5.4-7.5)
Alb 2.1 (2.3-3.1)
HISTOPATHOLOGIC DESCRIPTION: Kidney: Diffusely, glomeruli vary in size, and are either expanded, measuring up to 400 um in diameter, or are atrophied with mild expansion of the urininferous space (glomerulocystic atrophy). Multifocally glomeruli contain one or more of the following changes: hypercellularity with the presence of few neutrophils and scattered eosinophilic and karyorrhectic cellular debris (necrosis); thickening of glomerular capillary loops up to three times normal; expansion of glomerular mesangium by variable amounts of eosinophilic fibrillar material and thickening of glomerular basement membranes. Other glomerular changes include: hypertrophy and hyperplasia of parietal and visceral epithelium; adhesions between glomerular tufts and Bowman's capsule (synechiae); expansion of the uriniferous space by hypereosinophilic homogenous material (proteinaceous fluid) and/or fibrin (glomerular crescent); and periglomerular fibrosis and mineralization. Multifocally, tubules are ectatic, up to 150 um in diameter, and have one or more of the following changes: expansion of the lumen by eosinophilic proteinaceous fluid; attenuation of epithelium; necrosis characterized by shrunken hypereosinophilic epithelial cells with pyknotic nuclei; hypertrophied epithelial cells with vacuolated cytoplasm (degeneration); regeneration characterized byepithelium that is piled up with increased cytoplasmic basophilia; filling of tubule lumina by sloughed epithelial cells admixed with cellular debris. Multifocally and extensively, tubule epithelial cell cytoplasm contains brown globular pigment (hemosiderin or lipofuscin). Multifocally, within the cortical interstitium, there are many lymphocytes and plasma cells that often surround glomeruli and vessels.
MORPHOLOGIC DIAGNOSIS: Kidney: Glomerulonephritis, membranoproliferative, chronic, global, diffuse, moderate, with tubular degeneration, necrosis, regeneration, and lymphoplasmacytic interstitial nephritis, breed unspecified, canine.
ETIOLOGIC DIAGNOSIS: Borrelial glomerulonephritis
CAUSE: Borrelia burgdorferi
CONDITION: Lyme disease, Lyme borreliosis, Lyme nephritis
- burgdorferi is a gram-negative, pathogenic spirochete that is transmitted by an Ixodes tick and can infect humans, dogs, cats, cattle, and other animals
- In dogs, burgdorferi causes fever, shifting leg lameness, polyarthritis, and anorexia; less commonly, lymphadenopathy, malaise, and protein-losing glomerulopathy, and rarely, meningitis and myocarditis have been reported May cause rapidly progressive membranoproliferative glomerulonephritis (MPGN)
- Labrador and Golden retrievers breeds are over-represented in the incidence of renal disease
- Ixodes ticks have a 2-year life cycle: eggs are laid in the spring > develop into larvae which feed on small mammals/reptiles in summer > then adults feed on deer/large mammals in fall and maintain the disease through overwintering of infected nymphs; Birds disperse infected ticks to new areas
- After being ingested by an Ixodes tick during a blood meal, Borrelia burgdorferi localizes in the gut via outer surface protein A (Osp A); when the tick attaches to a new host and begins a blood meal, there is an increase in temperature within the tick which causes a change in expression of outer surface proteins from Osp A to Osp C; Osp C allows the spirochete to localize to the salivary glands within 48 hours of tick attachment; The spirochete then enters the host through the tick’s mouthparts.
- Exact mechanism of renal damage is unclear; glomerular disease is likely the primary injury which leads to a decreased glomerular filtration rate with resulting tubular necrosis; it is NOT the result of direct damage by spirochetes or immune mediated tubular destruction
- Disease thought to be driven by immune complexes containing a variety of antigens, including OspA, OspB, and/or flagellin
- burgdorferi is a persistent pathogen that can evade immune clearance and organisms are NOT frequently found in the kidney; clinical illness results from the host's inflammatory response
TYPICAL CLINICAL FINDINGS:
- Most common signs in dogs: anorexia, lethargy, lameness with fever and lymphadenopathy
- Occasionally, signs of acute, progressive renal failure - uremia, azotemia, proteinuria, peripheral edema, body cavity effusions
- Arthritis (typically intermittent and involves one or more joints) is a common feature in animals, with myocarditis and nephritis in dogs, ocular disease and encephalitis in horses, and abortion in cattle
TYPICAL GROSS FINDINGS:
- Typically light tan (occasionally red-brown ‘golden kidney’) renal cortex, multifocal red pinpoint foci, diffuse bulging of the medulla on section
TYPICAL LIGHT MICROSCOPIC FINDINGS:
Classic triad of lesions:
- Diffuse membranoproliferative glomerulonephritis with periglomerular fibrosis and glomerular synechiae to Bowman's capsule; variable crescent formation (fibrin, inflammatory cells within uriniferous space)
- Multifocal tubular necrosis and regeneration, cortical tubular dilation, and luminal protein casts
- Lymphoplasmacytic interstitial nephritis
- Multifocal electron-dense subendothelial deposits along the glomerular basement membrane (GBM) with visceral epithelial cell foot process fusion
- Expansion, folding, and splitting of the GBM
- Increase in mesangial matrix
- Swelling and vacuolization of parietal cell cytoplasm
ADDITIONAL DIAGNOSTIC TESTS:
- Validated IHC is not available
- Lyme borreliosis serology against outer surface proteins (Osp) C and F or recombinant protein C6
- Silver or Romanovsky-type stains (Giemsa, Wright’s)
- Dark field examination to demonstrate spirals and motility
- Canine Lyme nephritis can be distinguished from most other causes of renal disease by the simultaneous presence of both diffuse glomerulonephritis and tubule epithelial cell necrosis and regeneration with concurrent lymphoplasmacytic interstitial nephritis
- Fowl: anserina causes avian borreliosis/fowl spirochetosis of chickens, turkeys, geese, ducks, and other avian species; spread by Argas persicus
- Non-human primates: Meningitis
- Cats: Arthritis and meningitis
- Horses: Polyarthritis and neuroborreliosis (chronic necrosuppurative to nonsuppurative perivascular to diffuse meningoradiculoneuritis); Borrelia-associated cutaneous pseudolymphoma reported in one horse: benign self-limiting lymphoproliferative condition in skin causing papular to nodular asymptomatic lesions
- Cattle: Abortions; theileri causes mild febrile anemia in cattle
- Cianciolo RE, Mohr FC. Urinary system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals 6th ed. vol 2. St. Louis, MO: Elsevier; 2016: 411-412.
- Craig LE, Dittmer KE, Thompson KG. Bones and joints. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals 6th ed. vol 1. St. Louis, MO: Elsevier; 2016: 152.
- Dambach DM, Smith CA, Lewis RM, Van Winkle TJ. Morphological, immunohistochemical, and ultrastructural characterization of a distinctive renal lesion in dogs putatively associated with Borrelia burgdorferi infection: 49 cases (1987-1992). Vet Pathol 1997; 34(2):85-96.
- Fulton RM. Bacterial diseases. In: Boulianne M, ed. Avian Disease Manual. 7th ed. Jacksonville, FL: American Association of Avian Pathologists, Inc; 2013: 132-133.
- Goldstein RE, Cordner AP, Sandler JL, Bellohusen BA, Erb HN. Microalbuminuria and comparison of serologic testing for exposure to Borrelia burgdorferi in nonclinical Labrador and Golden Retrievers. J Vet Diagn Invest. 2007;19(3):294-297.
- Greene CE, Straubinger RK, Levy SA. Borreliosis. In: Green, CE, ed. Infectious Diseases of the Dog and Cat 4th ed. St. Louis, MO: Elsevier Saunders; 2012: 447-465.
- Imai DM, Barr BC, Daft B, Bertone JJ, Feng S, Hodzic E, et al. Lyme neuroborreliosis in 2 horses. Vet Pathol. 2011:48(6) 1151-1157.
- LeFebvre RB. Spiral-curved organisms I: Borrelia. In: McVey DS, Kennedy M, Chengappa MM, eds. Veterinary Microbiology, 3rd ed. Ames, IA: Wiley-Blackwell; 2013:155-157.
- McAdam AJ, Milner DA, Sharpe AH. Infectious Diseases. In: Kumar V, Abbas AK, Aster JC, eds. Robbins and Cotran Pathologic Basis of Disease 9th ed. Philadelphia, PA: Elsevier Saunders; 2015: 381-382.