JPC SYSTEMIC PATHOLOGY
SIGNALMENT (JPC# 1752289): Dog
HISTORY: This dog had splenomegaly and hepatomegaly.
HISTOPATHOLOGIC DESCRIPTION: (H-P07a) Spleen: Diffusely splenic red pulp is effaced by numerous macrophages, moderate numbers of plasma cells, fewer lymphocytes, and occasional neutrophils that fill and expand the cords and red pulp vascular spaces, and replace and obscure the white pulp, trabeculae, and capsule. Macrophages are up to 40 um in diameter and contain numerous 2-4 um, ovoid, intracytoplasmic amastigotes with an eccentric, round to ovoid, basophilic nucleus and a <1 um, linear, basophilic, kinetoplast. Multifocally, there are scattered random areas of karyorrhectic and cellular debris (lytic necrosis) containing numerous viable and degenerate neutrophils admixed with variable amounts of an eosinophilic beaded to fibrillar fibrin. There is multifocal histiocytic erythrophagocytosis and hemosiderosis, and rare megakaryocytes.
(H-P07a) Liver: Diffusely sinusoids, portal and periportal areas, and vessels are expanded by numerous macrophages, lymphocytes, plasma cells, and fewer neutrophils. Most macrophages are filled with protozoal organisms as previously described in the spleen. Diffusely, there is centrilobular to midzonal disruption, attenuation and loss of hepatic cords. In these areas hepatocytes are rarely degenerate or necrotic, there are increased numbers of hemosiderin laden Kupfer cells, and central veins occasionally contain fibrin thrombi.
(H-P07b) Price Giemsa: Intracytoplasmic amastigotes have bright blue nuclei, purple kinetoplasts and light blue cytoplasm.
- Spleen: Splenitis, histiocytic and plasmacytic, subacute, diffuse, severe, with multifocal necrosis and numerous intrahistiocytic protozoal amastigotes, breed unspecified, canine.
- Liver: Hepatitis, histiocytic, subacute, diffuse, moderate, with multifocal hepatocellular degeneration, necrosis and loss, and numerous intrahistiocytic protozoal amastigotes.
ETIOLOGIC DIAGNOSIS: Splenic and hepatic leishmaniasis
CAUSE: Leishmania spp. (differentials include L. infantum/chagasi, L. donovani)
CONDITION: Visceral leishmaniosis
SYNONMYNS: Kala-azar, Dum dum fever
- A zoonotic, vector-borne disease caused by an obligate intracellular (intrahistiocytic) diphasic protozoan
- Class: Kinetoplasta; Family: Trypanosomatidae
- L. infantum (chagasi) most common; also L. donovani, L. braziliensis
- Endemic in Mediterranean countries, parts of Africa, India, Central and South America, Texas, Oklahoma and Ohio
- Can infect a wide variety of domestic animals and wildlife; dogs common
- Susceptible breeds: Boxer, Cocker spaniel, Rottweiler, German shepherd
- Resistant: Ibizan hound
- Three forms of disease: Cutaneous, mucocutaneous, and visceral
- Dogs usually have cutaneous and visceral manifestations
- Cutaneous leishmaniasis
- L. infantum, L. tropica, L. mexicana, L. braziliensis
- Sandfly bites around muzzle, ears, eyes
- Long standing lesions have “typical” granulomas
- Mucocutaneous leishmaniasis
- L. braziliensis
- Central America
- Animals not frequently infected in nature
- Nodular mucosal leishmaniasis affecting the oral cavity, tongue, nose and penis have been reported in the dog
- Visceral leishmaniasis
- L. infantum (L. chagasi), L. donovani
- Wide geographic distribution
- Mimics histoplasmosis
- Canine leishmaniasis used to be a sporadic disease in U.S.; it is now considered endemic because, since 1999, there have been outbreaks of infantum (chagasi) primarily in foxhounds in U.S. and Canada
- German shepherd dogs, boxers, Dobermans and long-coated cocker spaniels may be predisposed; collie breeds and Ibizian hounds may be resistant
- Skin lesions occur in >80% of dogs with visceral involvement
- Cutaneous leishmaniasis
- Leishmania amastigotes have been reported in: fibrosarcoma, T-cell lymphoma, adrenocortical adenoma and TVT
- Other possible concomitant infections (possibly due to immunosuppression) include: Ehrlichia, Babesia, Anaplasma, Hepatozoon, Trypanosoma, Dirofilaria, Demodex, Sarcoptes, Spirocerca
- Female sandfly injects promastigotes and saliva (saliva has potent vasodilating, anticoagulant, anesthetic and immunomodulatory properties) to host skin > promastigotes phagocytized by macrophages via CD35 and ICD11b/CD18 > multiply and form non-flagellated amastigotes within phagolysosomes> evasion of innate immune system via remodeling of phagosome and interference with signaling pathways > macrophages rupture (a mechanical consequence of proliferation) > freed amastigotes penetrate additional host cells and disseminate primarily through hemolymphatic system> sandfly takes a blood meal from infected host > ingests mononuclear cells containing amastigotes> transform into flagellated promastigotes
- Severity of disease is determined by the host immune response, genetics and concurrent disease; usually a mixed Th1/Th2 response is present in both sick and asymptomatic dogs:
- Predominant cell-mediated immune response: resistance to infections (TH1 dependent (IL-2, IFN-gamma, TNF-alpha)
- Predominant humoral response: susceptible to infection; TH2 (IL-4); humoral response increases in parallel with the worsening of clinical signs
- inefficient killing with higher parasitic burden; +/- antigen:antibody complexes (type III hypersensitivity)> glomerulonephritis (+/- polyarthritis, vasculitis, uveitis)
- Autoantibody production: Polymyositis
- Leading cause of death is chronic proteinuric nephritis (may progress to end-stage kidney, nephrotic syndrome, or systemic hypertension)
- Epistaxis typically associated with rhinitis, but may also be due to thrombocytopathy, increased serum viscosity due to hyperglobulinemia or vasculitis
TYPICAL CLINICAL FINDINGS:
- Systemic signs: Fever, lethargy, cachexia, poor body condition, rough hair coat, diarrhea, lymphadenomegaly, splenomegaly, hepatomegaly
- Non-painful, non-pruritic, generalized, dry exfoliative dermatitis (most common cutaneous manifestation) with alopecia, recurrent oculonasal discharge, nasal crusting , epistaxis
- Most common laboratory finding is hyperproteinemia characterized by hypergammaglobulinemia and hypoalbuminemia; also proteinuria, azotemia, elevated ALP and ALT, mild non-regenerative anemia, lymphopenia, thrombocytopenia
- Skin lesions occur in over 80% of dogs with visceral involvement
TYPICAL GROSS FINDINGS:
- Visceral: Generalized lymphadenopathy, hepatosplenomegaly
- Nodular granulomas (liver, kidney); erosion/ulceration (oral, nasal, GI mucosa, mucocutaneous junction, skin, synvoiae); soft red bone marrow
- Cutaneous: Alopecia, ulcerative or exfoliative dermatitis, nasodigital hyperkeratosis, onychogryposis
- Most severe on muzzle, periorbital (“periocular lunettes”), and aural regions (where sandflies feed); nodular mucosal leishmaniasis is also reported
- Less common: Masticatory myositis, anterior uveitis, keratoconjunctivitis sicca, epistaxis (uni- or bilateral), polyarthritis, glossitis/stomatitis, myocarditis, meningoencephalomyelitis, orchitis/epididymitis/prostatitis
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Initially hemic-lymphatic hypertrophy with macrophage proliferation & focal pyogranulomas> widespread plasmacytic, lymphohistiocytic inflammation, most severe in spleen, liver, lymph nodes, bone marrow
- Intrahistiocytic amastigotes: ovoid to round, 2-3 um, with a clear halo, a round, basophilic nucleus with rod-like kinetoplast adjacent nucleus; occasionally within other leukocytes, endothelial cells, fibroblasts or neoplastic cells
- Membranoproliferative glomerulonephritis
- Skin: granulomatous to lymphoplasmacytic perifolliculitis and perivascular dermatitis
- Lymphoplasmacytic or granulomatous myocarditis (especially right atrial), myocardial necrosis and increased interstitial collagen, are prevalent in dogs with leishmaniasis
- Ocular inflammation: Conjunctiva, limbus, ciliary body, iris, cornea, sclera/iridocorneal angle, choroid, optic nerve sheath
- CNS: Intramedullary spinal cord mass, meningoencephalomyelitis, vasculitis
- Ovoid amastigote with a double membrane-bound nucleus, often within parasitophorous vacuole
- Flagellum in a flagellar pocket near nucleus
ADDITIONAL DIAGNOSTIC TESTS:
- Cytology; immunohistochemistry
- Cell-block technique on bone marrow aspirates
- Serology (IFA, ELISA)
- Intradermal leishmanin injection = “Montenegro test”
- Sarcoptic/demodectic mange, seborrhea, pemphigus foliaceus, SLE, bacterial infection, superficial necrolytic dermatitis, Zn-responsive dermatitis, neoplasia
- Trypanosoma cruzi (tissue phase/amastigote form): most often found within cardiomyocytes
- Histoplasma capsulatum: 2-5um, narrow-based budding; predominantly histiocytic inflammation
- Toxoplasma gondii: 2-6um tachyzoites; necrosis
- Neospora caninum: 4-7um tachyzoites
- Sporothrix schenckii: 4-10um, oval to cigar shaped yeast
- Neorickettsia helminthoeca – intracellular; gram negative; organisms are 0.3-2.0 um, pleomorphic cocci or rods
- Dogs: myocarditis, myositis (esp. masticatory), crusting at mucocutaneous junctions, nails, pinna tips, splenomegaly, lymphadenopathy, bone marrow suppression, nodular dermatitis, glossitis, immune-complex deposition, osteomyelitis, epistaxis, anterior uveitis, keratoconjunctivitis sicca, orchiepididymitis, meningoencephalomyelitis, polyarthritis, weight loss.
- Visceral leishmaniasis (caused by infantum, typically found in the Mediterranean) detected in foxhounds from a hunt club in New York in 1999; L. infantum antibody has since been detected in multiple kennels in North America
- Cats: Mexicana (endemic in Texas) has cutaneous tropism; only 5 of 8 cases in this report stained with Giemsa; pinnae most frequent site of nodule formation
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