Immunological Conditions Flashcards
Immune-mediated Polyarthropathy (IMPA)
OVERVIEW
- aka: idiopathic nonerosive noninfectious arthritis
- leading cause of FUO
- can affect single joints, but polyarticular is most common
- most commonly large breed dogs 1-6yo, purebreds overrepresented (Goldens, GSD)
- TYPE I: idiopathic (most common)
- TYPE II: associated with infection
- TYPE III: associated with GI or hepatic dz
- TYPE IV: associated with neoplastic causes
CLINICAL SIGNS
- cyclic fever (not responsive to abx)
- lethargy
- stiff gait
- lameness
- spinal pain
- immobility
- less common: generalize muscle atrophy, joint swelling, lymphadenopathy, anorexia
DIAGNOSIS
- CBC: signs of general inflammation with neutrophilia and leukocytosis
- chem: normal
- limb rads: soft tissue swelling
- arthrocentesis/FLUA: sterile inflammation
TREATMENT
- supportive care, immunosuppressive
- single agent immunosuppression with steroid most common, however second agent may be needed
- approx 30-50% will suffer relapse
- most cases require treatment for 3-6 months
Immune-mediated Hemolytic Anemia (IMHA)
OVERVIEW
- primary (most common) or secondary
- RBCs marked as foreign, results in attachment of Abs (IgG or IgM), which results in RBCs being partially or completely cleared from the bloodstream by the mononuclear phagocyte system (extravascular hemolysis)
- in some cases Abs can also fix complement resulting in formation of membrane attach complex that leads to intravascular hemolysis
CLINICAL SIGNS
- lethargy
- hyporexia
- vomiting/diarrhea
- PE = signs of anemia (tachypnea, tachycardia, pale MM, systolic murmur)
- yellow-orange discoloration to feces and hematuria consistent with hemolysis
RULE OUTS/DIFFERENTIAL DIAGNOSES
- zinc toxicity
- genetic diseases (PK deficiency)
- microangiopathic disease (hemangiosarcoma, hemolytic uremic syndrome [HUS])
DIAGNOSIS
- CBC: anemia (often severe; preregenerative common initially, then will become strongly regenerative), if thrombocytopenic consider Evan’s Syndrome or consumption from DIC, elevated WBC from inflammation or bone marrow activation, auto-agglutination (saline agglutination or blood film review), spherocytosis
- chem: hypoalbuminemia (2nd to marked inflammation), hyperbilirubinemia (hemolysis, higher bili = poorer outcome), elevated LE (initially via hypoxia injury, then 2nd to corticosteroids)
- UA: bilirubinuria, hemoglobinuria
- Coombs (DAT): when IMHA is suspected but not confirmed by slide agglutination, Coombs tests for anti-RBC Abs on the RBCs themselves
- coags: thrombocytopenia WITH prolonged PT/aPTT indicates DIC
- rule out reasons for secondary IMHA (AUS for neoplasia, vector-borne dx testing, TXR/AXR, recent vx or admin of cephalosporins, trimethoprim-sulfa, etc)
TREATMENT
- supportive nursing care
- pRBC transfusion PRN
- monitor for PTE or other clots (esp. if DIC)
- thromboprophylactics (clopidogrel)
- immunosuppression with glucocorticoids and likely second agent (leflunomide, mycophenolate, cyclosporine)
- IVIg, vincristine
Immune-mediated Thrombocytopenia (ITP, IMT, IMTP)
OVERVIEW
- aka idiopathic thrombocytopenic purpura
- primary and secondary
- platelets marked as foreign, Abs bind to platelet surface and results in destruction by immune system
- Abs against epitopes on the platelet GPIIb/IIIa, the fibrinogen receptor, have been identified in dogs with ITP
- regulation T cells (Treg) may be causally associated with the onset of primary ITP
- secondary: neoplasia (lymphoma, hemangiosarcoma, histiocytic sarcoma), paraneoplastic (increased consumption 2nd to bleeding tumor, DIC, splenic sequestration, decreased production 2nd to myelophthisis) sulfonamides/cephalosporines, Ehrilichia canis, Anaplamsa phagocytophilium, Babesia spp, Leptospira spp, Leishmania infantum, inflammatory dz (chronic hepatitis, pancreatitis, SIRS)
CLINICAL SIGNS
- lethargy
- anorexia
- weakness
- collapse
- hematuria
- hemorrhages
- epistaxis
- melena
- GI bleeding
- PE = petechiae, ecchymosis, epistaxis, melena, oral hemorrhage, signs of anemia if severe hemorrhage
DIAGNOSIS
- ensure not spurious (traumatic venipuncture, clot in tube, etc)
- often severe thrombocytopenia
- PLT <50K = risk of spontaneous bleeding
- rule out secondary ITP (AXR/TXR, AUS, vector-borne testing, hx of recent sulfa/cephalosporins, vx, etc)
- primary ITP a diagnosis of exclusion
- platelet surface-associated immunoglobulin (PSAIg) is sensitive but not specific for ITP, so false positives are major disadvantage
TREATMENT
- supportive nursing care
- no jug sticks
- soft food diet
- pRBC transfusion PRN (if secondary anemia)
- PRP, lyophilized platelets (in life-threatening cases); lifespan of transfused platelets relatively short due to increased consumption and destruction
- immunosuppression with glucocorticoids and likely second agent (leflunomide, mycophenolate, cyclosporine)
- IVIg, vincristine
Pemphigus
OVERVIEW
- Pemphigus foliaceus
- most common auto-immune skin dz in dogs and cats
- autoantibodies that disrupt adhesions between keratinocytes, and induce subcorneal pustules
- Desmocollin-1 major target Ag in dogs
- Akita, Chows, English Bulldogs, Doberman, Collies, Aussies; no breed predisposition in cats
CLINICAL SIGNS
- subcorneal pustule, progress rapidly into secondary erosions and crusts, which may represent the only clinical finding on exam
- lesions on nasal planum, dorsal nose, periocular, concave pinnae; more than half will progress to generalized phenotype involving trunk, paw pads; cats: facial lesions as well as ungual (nail bed) and nipples
- pesticide-triggered PF = corresponds with recent flea prevention and is always present in between scapulae, at site of topical flea preventative application
- lesions appear bilaterally symmetrical
DIAGNOSIS
- combination of 1) skin lesion type and distribution, 2) exclusion of an infection, 3) supportive histopathologic findings
- histopath/cytology: acantholytic keratinocytes mixed with non-degenerated neutrophils and/or eosinophils
TREATMENT
- immunosuppressive doses of glucocorticoids
- +/- second agent (azathioprine, chlorambucil, cyclophosphamide)
Systemic Lupus Erythematosus (SLE)
OVERVIEW
- with SLE immune system dysregulation leading to immune complex formation is thought to induce tissue damage (type III hypersensitivity); however direct antibody-mediated cytotoxicity (type II hypersensitivity) and cell-mediated autoimmunity (type IV hypersensitivity) also occur
- SLE produces a wide range of Abs directed against nuclear, cytoplasmic, and cell membrane molecules; autoantibodies can cause damage through the formation of immune complexes, opsonization of target cells, and interference with cellular physiology
- T cells cause direct tissue damage; dermatologic and renal lesions associated with cytotoxic T cell-mediated damage
CLINICAL SIGNS (most common to least common)
- IMPA
- fever
- renal disorders
- dermatologic lesions
- lymphadenopathy/spleen omega lymph
- leukopenia
- hemolytic anemia
- thrombocytopenia
- myosin is
- CNS disorders
- neuropathy
DIAGNOSIS
- demonstration of at least two separate manifestations of autoimmunity along with a positive ANA titter
- patients with three or more manifestations may also be considered to have SLE despite negative ANA
- DOGS: IMPA, immune-mediated skin dz, glomerulonephritis, IMHA and/or ITP
- CATS: similar to dogs, however CNS signs may be more common
- CBC, chem, UA, imaging, arthrocentesis, skin bx, serum ANA titer, vector-borne disease testing, fungal testing (cats = add FeLV/FIV) needed to prove immune disease
- skin bx should avoid erosions or ulcers, intact skin needed to substantiate dx; erythematous areas adjacent to lesions are most useful
- dx in cats less defined
- ANA preferred over LE (lupus erythematosus) test due to higher sensitivity of ANA
TREATMENT
- avoid sunlight if photosensitization
- immunosuppression with corticosteroids, then tapered to lowest effective dose in less severe cases
- second agent (mycophenolate) often more effective
- cats: pred + chlorambucil
- if proteinuria treat with protein-restricted diet supplemented with O3FA, enalipril, and aspirin (using caution if steroids are being administered)
Systemic Inflammatory Response Syndrome (SIRS)
OVERVIEW
SIRS: a clinical syndrome caused by systemic inflammation of infectious (i.e. sepsis) or noninfectious origin. In dogs, the diagnosis of SIRS is based on fulfillment of at least 2 or 4 criteria: tachycardia, tachypnea, hypo- or hyperthermia, and either leukocytosis, leukopenia, or >5% bands
SEPSIS: 1. Systemic inflammatory response to infection or 2. Life-threatening organ dysfunction caused by a deregulated host response to infection
SEVERE SEPSIS: this terminology has fallen out of favor and is generally not used
SEPTIC SHOCK: 1. The systemic inflammatory response to infection with hypotension despite adequate fluid resuscitation along with the manifestations of hypoperfusion or 2. Subset of sepsis in which underlying circulatory and cellular/metabolic abnormalities are profound enough to substantially increase mortality. Generally, this is sepsis with either persisting hypotension requiring vasopressin’s to maintain a MAP > 65 mmHg or a serum lactate > 2mmol/L despite adequate volume resuscitation in people
MULTIPLE ORGAN DYSFUNCTION SYNDROME (MODS): altered function of 2 or more organs secondary to SIRS such that homeostasis cannot be maintained without intervention
ACUTE RESPIRATORY DISTRESS SYNDROME (ARDS): a pulmonary inflammatory disorder characterized by noncardiogenic pulmonary edema (NCPE), neutrophilic inflammation, and hypoxemia
PATHOPHYSIOLOGY
- with normal tissue injury/infection proinflammatory and antiinflammatory elements are released simultaneously to balance tissue repair and healing
- endothelium responsible for initiating inflammatory process; endothelium regulates blood vessel tone and vascular permeability and, in response to injury, will allow local vasodilation and therefore increase microvascular permeability, which results in localized edema
ENDOTHELIUM
— regulates blood vessel tone, vascular permeability
— allows local vasodilation in response to injury —> therefore increased microvascular permeability —> results in localized edema
— regulates WBC activity —> attract leukocytes to local area of injury —> phagocytosis ensues
— when macrophages invade bacteria cytokines and proinflammatory mediators are activated —> results in injury to endothelial cell and underlying tissues
— apoptosis and formation of O2 free radicals within endothelial cells result in localized removal of damaged tissue —> creates gaps between cells —> extravasation of tissue fluids and cellular materials to interstitial space —> edema
— in sepsis: localized regulation become dysfunctional and inflammatory process continues systemically
SEPTIC SHOCK
— shock: disturbance of function
— consumed O2 > delivered O2
— blood carries nutrients, oxygen, hormones to all tissues, aids in fluid balance; system dependent on cardiac output (heart rate x stroke volume); if cardiac function and perfusion are impaired neurohormonal responses —> inflammatory mediators —> decompensation
— during initial stages of shock cellular hypoxia causes energy deficit (mitochondria unable to produce ATP) —> anaerobic metabolism —> metabolic acidosis —> acute compensatory sympathetic response causes major arteries/veins to constrict —> initially, capillaries constrict (decreased perfusion to tissues) —> progresses and blood flows into capillaries while outflow restricted —> causes volume shift of blood accumulating in venules —> fluid/protein leak into surrounding tissues (increasing viscosity) —> prolonged vasoconstriction results in loss of blood flow to vital organs (some/peripheral tissues overperfused while others/vital organs suffer ischemic damage)
— pulmonary vascular blood flow becomes disrupted, leads to pulmonary edema, may lead to ARDS
CLINICAL SIGNS
- hyper- or hypodynamic response during sepsis
- hyperdynamic: fever, brick red MM, tachycardia, bounding pulses; progresses to hypodynamic
- hypodynamic: pale MM, hypothermia
- GI or resp signs associated with endotoxemia
- hyper- or hypoglycemia
- hypoalbuminemia
- azotemia
- hyperbilirubinemia
- increased ALT and/or ALP
- leukocytosis, neutrophilia w/ left shift, or leukopenia
- anemia
- thrombocytopenia
- coagulopathies (decreased protein C and antithrombin, prolonged PT/aPTT, increased D-dimer)
- myocardial dysfunction
- vasodilation —> hypotension
- metabolic acidosis
- CATS: similar to dogs except bradycardia, hypothermia, abdominal pain are frequent and feline-unique findings; hyperdynamic phase not often recognized in cats
DIAGNOSIS
- demonstration of evidence of infection and systemic inflammation (SIRS) via culture, cyto, histology, serology
- sample collection from blood, urine, wound exudate, peritoneal fluid, BAL, synovial fluid, etc. based on clinical presentation/findings
- sample collection should be prior to abx administration
- peritoneal fluid glucose concentration AT LEAST 20 mg/dL lower than concurrent BG diagnostic for septic peritoneal effusion
TREATMENT
1. initial hemodynamic stabilization
- CVP = 8-12 mmHg
- MAP = > 65 mmHg
- UOP = > 0.5 ml/kg/hr
- superior vena cava oxygen saturation >70% or mixed venous oxygen saturation > 65%
- resuscitation targeted to normalize lactate
- fluid resuscitation: bolus crystalloids or colloids, then maintenance tailored to patient (consider ongoing losses, third spacing, pulmonary edema, etc); colloids may help prevent interstitial edema in addition to crystalloids
- vasopressors only when necessary: positive inotropes (dobutamine) increase CO without vasoconstriction; vasopressors as next step if ongoing hypotension
2. alleviating the inciting cause
- antimicrobial therapy
- wound debridement, etc.
3. intensive supportive care
- early initiation of enteral or parenteral feeding (including feeding tubes) help maintain GI barrier function and reduce risk of GI bacterial translocation (carefully monitor for hyperglycemia, esp. w/ parenteral nutrition)
- GI protectants (omeprazole, famotidine, sucralfate)
- close monitoring of ventilation, acid-base, PCV, organ function to avoid MODS
- once MODS recognized: specific therapy to maintain homeostasis, may require peritoneal or hemodialysis, plasma or blood transfusion, positive inotropic agents, mechanical ventilation
- patient comfort: analgesia (NO MORPHINE - augments inflammatory response to endotoxin, detrimental to MAP, increases mortality in endotoxemic rats), catheter maintenance, bladder/bowel care, PROM/turning
- immunomodulation has been proposed as novel therapy for sepsis; many therapies evaluated in human med with little success; only successful trial in dogs used polymyxin E - binds to endotoxin from gram- bacteria, prevents interaction between endotoxin and immune system
Myasthenia Gravis (Acquired)
Myasthenia Gravis (Congential)
Hypersensitivity Reactions
Vaccine
Transfusion
