Definition
A group of conditions of diverse cause in which extracellular deposition of insoluble fibrillar proteins (amyloid) in various organs and tissues compromises their normal function.
Pathophysiology
- Patients usually affected by systemic reactive amyloidosis; tissue deposits contain AA, which is a fragment of an acute-phase reactant protein called SAA.
- Phases of amyloid deposition:
- Predeposition phase: SAA concentration is high but without amyloid deposits; colchicine administration during this phase may prevent development of the disease.
- Deposition phase (rapid portion): amyloid deposits increase rapidly; colchicine administration delays but does not prevent tissue deposition of amyloid; DMSO may promote resolution of amyloid deposits and a persistent decrease in SAA concentration.
- Deposition phase (plateau portion): net deposition of amyloid changes little; neither DMSO nor colchicine is beneficial.
- Clinical signs in dogs and cats usually are associated with amyloid deposition in the kidneys.
- Dogs-amyloid deposits usually found in the glomeruli leading to proteinuria and nephrotic syndrome.
- Cats-amyloid deposits usually found in the medullary interstitium but may occur in glomeruli.
- Some Chinese shar-pei dogs with familial amyloidosis have medullary amyloidosis without glomerular involvement.
- Siamese and Oriental shorthair cats with familial amyloidosis have hepatic amyloidosis.
- A different type amyloid, pancreatic islet amyloid polypeptide, or amylin, deposits in the pancreas of old cats. Amylin is a hormone secreted along with insulin by the pancreatic beta cells. Chronic increased stimulus for secretion of amylin by beta cells (e.g., states of insulin resistance) lead to pancreatic islet cell amyloidosis.
Systems Affected
Renal/Urologic-predilection for renal AA deposition. Liver, spleen, adrenal glands, pancreas, tracheobronchial tree, and gastrointestinal tract also may be affected.
Genetic
(See “Breed Predilections.”) No genetic involvement is clearly established; familial amyloidosis occurs in Chinese shar-pei, English foxhound, and beagle dogs, and in Abyssinian, Oriental shorthair, and Siamese cats.
Incidence/Prevalence
Uncommon, occurs mostly in dogs; rare in cats, except Abyssinians.
Signalment
Species
Dog and cat
Breed Predilections
- Dog-Chinese shar-pei, beagle, collie, pointer, English foxhound, and walker hound; German shepherd dog and mixed breeds are at lower risk.
- Cat-Abyssinian, Oriental shorthair, and Siamese.
Mean Age and Range
- Cats-mean age at diagnosis 7 years; range 1–17 years.
- Dogs-mean age at diagnosis is 9 years; range 1–15 years. Chinese shar-Pei dogs-median age at diagnosis is 5 years; range 3.6–17 years.
- Prevalence increases with age.
- Abyssinian cats-range <1–17 years.
- Chinese shar-pei dogs-usually <6 years of age when signs of renal failure develop.
- Siamese cats with familial amyloidosis of the liver and thyroid gland usually develop signs of liver disease when 1–4 years old.
Predominant Sex
Dogs and Abyssinian cats-females at a slightly higher risk (<2:1). Female-to-male ratio is higher in Chinese shar-pei dogs (∼ 2.5:1).
Signs
General Comments
- Depend on the organs affected, the amount of amyloid, and the reaction of the affected organs to amyloid deposits.
- Usually caused by kidney involvement; occasionally, hepatic involvement may cause signs in Chinese shar-pei dogs and Oriental shorthair and Siamese cats.
Historical Findings
- No clear history of a predisposing disorder in most (∼75%) cases.
- Anorexia, lethargy, polyuria and polydipsia, weight loss, vomiting.
- Ascites and peripheral edema in animals with nephrotic syndrome.
- Chinese shar-pei dogs may have a history of previous episodic joint swelling and high fever that resolves spontaneously within a few days.
- Beagle dogs with juvenile polyarteritis may have a history of fever and neck pain that persist for 3–7 days.
- Oriental shorthair and Siamese cats may present with spontaneous hepatic hemorrhage leading to acute collapse and hemoabdomen.
Physical Examination Findings
- Related to renal failure-oral ulceration, emaciation, vomiting, and dehydration; kidneys usually small, firm, and irregular in affected cats; they may be small, normal-sized, or slightly enlarged in affected dogs.
- Signs of nephrotic syndrome (e.g., ascites, subcutaneous edema).
- Related to the primary inflammatory or neoplastic disease process.
- Thromboembolic phenomena-may occur in up to 40% of affected dogs; signs vary with the location of the thrombus; patients may develop pulmonary thromboembolism (e.g., dyspnea) or iliac or femoral artery thromboembolism (e.g., caudal paresis).
- Chinese shar-pei dogs and Oriental shorthair and Siamese cats may have signs of hepatic disease (e.g., jaundice, cachexia, and spontaneous hepatic rupture with intraperitoneal bleeding).
Causes
- Neoplasia and chronic infectious and non-infectious inflammatory conditions can be found in 30–50% of dogs with reactive amyloidosis.
- Chronic inflammation-systemic mycoses (e.g., blastomycosis, coccidioidomycosis), chronic bacterial infections (e.g., osteomyelitis, bronchopneumonia, pleuritis, steatitis, pyometra, pyelonephritis, chronic suppurative dermatitis, chronic suppurative arthritis, chronic peritonitis, nocardiosis, chronic stomatitis), parasitic infections (e.g., dirofilariasis, leishmaniasis, hepatozoonosis), and immune-mediated diseases (e.g., systemic lupus erythematosus). Amyloid deposits can be found in up to 35% of FIV-positive cats.
- Neoplasia (e.g., lymphoma, plasmacytoma, multiple myeloma, mammary tumors, testicular tumors).
- Familial (e.g., Chinese shar-pei, English foxhound, and beagle dogs; Abyssinian, Siamese, and Oriental shorthair cats).
- Others-cyclic hematopoiesis in gray collies; juvenile polyarteritis in beagles.
