Session #2000

Introduction

Pathology of reptiles and amphibians is a major component of reptile medicine and has provided critical tools to better understand the significance and clinical relevance of many infectious agents and the pathogenesis of non-infectious diseases. Pathology is the necessary complement of the clinical suspicion and of a growing array of ancillary examinations. Accordingly, the absence of the pathology investigation is often associated with an incomplete or incorrect diagnosis. Pathology investigation in reptiles and amphibians is even more relevant than in other species, given the notorious limited and non-specific array of clinical signs shown by poikilotherms when disease occurs. Here we will provide a concise summary of the main pathologic findings associated with some of the most relevant infectious and not infectious diseases of amphibians and reptiles.

Infectious Diseases

Adenovirus

Adenoviruses are a large group of DNA viruses, which have been documented in several reptile taxa, although predominantly in lizards and snakes. More recently, a growing number of reports in chelonians have been documented, although associated lesions have been clearly demonstrated only in a very limited number of cases. In lizards, adenoviruses are characterized by necrotizing lesions. Histologically characteristic findings include large, prominent intranuclear basophilic inclusions associated with cellular necrosis, more commonly observed in the liver, along with a characteristic biliary duct proliferation. In snakes, it is not unusual to observe proliferative lesions mainly restricted to the gastrointestinal tract. In chelonians, during the most severe outbreak reported, adenovirus infection was associated with a multisystemic disease.

Herpesvirus

Herpesviruses are relatively common infectious agents in chelonians and, to a minor extent, in lizards. Snakes and crocodilians are relatively unusual hosts. The associated pathology is relatively characteristic, with integumentary lesions (tumor proliferations or necrosis) or multisystemic lesions in sea turtles, stomatitis and glossitis in tortoises, and liver necrosis in freshwater turtles. In lizards, the disease presentation spans from the presence of predominant visceral lesions to marked oral disease. In snakes, it has repeatedly been reported as an infection of the venom glands. The histological lesions find their hallmark in the presence of eosinophilic intranuclear inclusions in the epithelial cells of the affected organs, along with an alternative association of proliferative or necrotizing lesions. Herpesviruses are notorious for undergoing latency, a dormant stage, which is characterized by the absence of clinical disease. Accordingly, the characteristic lesions might not be clinically detectable in infected animals, which have survived the acute phase of the disease. However, the clinical disease and the associated lesions may reemerge anytime in a totally unpredictable manner, although events leading to immune suppression are major predisposing conditions.

In amphibians, at least four herpesviruses have been characterized to date. Three of them have been associated with either benign or malignant proliferative lesions, affecting the integument and kidney, respectively. Ranid herpesvirus 1 was the first amphibian herpesvirus to be characterized and it has been demonstrated to be the causative agent of the Lucké renal adenocarcinoma in leopard frogs (Lithobates pipiens). Ranid herpesvirus 2 was isolated from frogs affected by kidney tumors, but it was shown not to have any role in the tumor occurrence. The latest two amphibian herpesviruses characterized to date are Ranid herpesvirus 3 and Bufonid herpesvirus 1, both shown to be associated with a prominent proliferative skin disease in the common frog (Rana temporaria) and common toad (Bufo bufo), respectively.

Paramyxovirus (Ferlavirus)

Paramyxoviruses are RNA viruses, relatively commonly detected in reptiles and, in particular, in snakes and lizards, with a relatively minor incidence in chelonians. Paramyxoviruses are often associated with respiratory disease in snakes, which is characterized by lesions proliferative in nature and, more specifically, with a proliferative interstitial pneumonia. Similar tissue changes have been observed as well in lizards, although the incidence of overt disease in this taxon is markedly lower than that observed in snakes. A similar proliferative pneumonia is seen in snakes infected with serpentovirus, another emerging RNA virus. Both these agents should be considered in the differential diagnosis when similar lesions are observed. A virus, originally included within the family Paramyxoviridae, and later on recognized as part of a new virus family, the Suniviridae, was shown to be associated with both pneumonia and central nervous system (CNS) disease in the affected snakes.

Reptarenavirus

Reptarenaviruses are RNA viruses, which are strong candidates as etiologic agents of inclusion body disease of boid snakes, a disease, which for several decades has been an elusive condition, originally believed to be caused by a retrovirus. The disease leads to a progressive wasting condition and finds its hallmark in relatively pleomorphic, eosinophilic to basophilic, intracytoplasmic inclusions. These inclusions can be found in a restricted or large number of organs according to the affected snake group and, more specifically, with mainly CNS distribution in pythons and multisystemic in boids. Occasionally, inclusions can be observed in circulating mononuclear cells. The diagnosis for a long time has essentially relied on the detection of the characteristic inclusion bodies in specific simply targetable organs such as the liver and the esophageal tonsils. The discovery of reptarenaviruses as candidate agents has allowed a wider use of molecular testing complementing the histopathologic diagnosis.

Mycoplasma

Mycoplasma agassizii and M. testudineum are significant pathogens of chelonians, which have been shown to be causatively linked to a life-threatening condition called upper respiratory tract disease, which is considered one of the presumptive contributors to the decline of the free-ranging population of Agassiz’s desert tortoises (G. agassizii) in Southern California. The disease is proliferative in nature and is associated with a progressive subversion of the characteristic tissue architecture of the respiratory and olfactory epithelium of the nasal cavities of the affected tortoises. Conjunctivitis is also relatively commonly observed in the affected animals. Histologically, there is loss of the submucosal glands of the nasal mucosa and a heterophilic to mononuclear inflammatory infiltration, consistently with a classic proliferative nature. More recently, a growing number of mycoplasmas distinct from M. agassizii and M. testudineum, have been detected in several species of chelonians, both terrestrial and aquatic (freshwater turtles); however, their clinical significance is unclear, especially in the absence of specific transmission studies.

Ranavirus

Ranavirus is a genus of DNA viruses, within the family Iridoviridae. Ranaviruses include strains able to infect any vertebrate poikilotherm, namely, reptiles, amphibians, and fish. Ranavirus infection is often fatal and associated with a multisystemic disease, which is histologically characterized by the presence of characteristic small basophilic intracytoplasmic inclusions, necrosis, and a common fibrinoid vascular necrosis affecting vessels of several organs, but characteristically more common in the spleen. In chelonians, Ranavirus infection can be associated with a similar stomatitis and glossitis observed with herpesvirus, although the incidence of stomatitis secondary to herpesvirus is much higher, at least in tortoises. In lizards, Ranavirus can cause skin disease, whereas its incidence in snakes is relatively limited.

In amphibians, Ranavirus can cause severe ulcerative skin disease with hemorrhages and fibrinoid vascular necrosis with secondary hemorrhages. The classic basophilic intracytoplasmic inclusions can be observed in infected amphibians as well.

Chytrid Fungi

Chytrid fungi are among the most significant infectious agents of amphibians and are considered a major contributor to the extinction and extirpation of local populations. Two main chytrid fungi are known, Batrachochytrium dendrobatidis and B. salamandrivorans. The first was the earliest to be discovered and has been shown to cause severe skin disease, leading to skin necrosis and secondary fatal infection. The fungus is keratinophilic and accordingly causes disease mainly in post-metamorphosed amphibians. Gross lesions include skin hemorrhages and reddening along with abnormal skin shedding. Some of these lesions are overlapping with those seen in Ranavirus-infected amphibians. The second chytrid characterized to date is B. salamandrivorans and it has been shown to be a deadly agent, especially in common salamanders (Salamandra salamandra), where it causes a fatal ulcerative skin disease.

Not Infectious Diseases

Metabolic Bone Diseases (MBD-Fibrous Osteodystrophy)

Metabolic bone disease is a general term to indicate a dysmetabolism leading to the progressive weakening of the bones, with a progressive replacement of the osteoid matrix with cartilage and fibrous tissue in the most common of its possible clinical manifestation (fibrous osteodystrophy). The disease can be observed in both reptiles and amphibians and is characterized by three stages, with a preclinical one, when the progressive bone demineralization occurs in absence of detectable clinical signs. The following stage includes a more severe demineralization with bone deformation, pathologic fracture, and reduction of the mobility of the affected animal. In the third stage, more frequently observed in animals which are capable of preserving some degree of mobility, the classic fibrous-cartilaginous proliferation replacing the cortical bone and compressing the progressively atrophic regional skeletal muscles are observed. Macroscopically the cross section of the long bones is dramatically increased by soft tissue.

Gout

Gout is another dysmetabolism affecting, in this case, the excretory function. Any condition, which leads to a reduction of the excretion of uric acids or a disproportional increase of its production, may lead to gout. The pathologic expression of the disease is the precipitation of urate crystals (tophi) which are normally observed in the lumen of the renal tubules, which may undergo significant damage until they are completely replaced by fibrous tissue. In chronic conditions, a large portion of the kidney can be completely replaced by fibrous tissue with a progressive loss of renal function. Differently from gout, pseudo gout is characterized by the precipitation of calcium crystals.

Renal Degeneration

Additionally to gout, a number of pathologic conditions may affect the reptilian kidney and, in particular, in lizards. The pathogenesis is not clear and given the chronicity of the conditions, which are normally observed, the original etiology is unlikely to be found. The affected animals show a mix of tissue changes, which can be present with a distinct degree of severity. Common degenerative changes include tubular degeneration and loss with fibrosis, membranous, and membranous-proliferative glomerulopathy, glomerulonephritis, and glomerulosclerosis. Anecdotal reports consider as potential predisposing of inciting conditions, a number of management issues ranging from diet, lighting, temperature, and supplementation.

References

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