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Basics ⬇

Outline

BASICS

Definition!!navigator!!

  • A regulated elevation in the thermal set point. Body temperature is actively maintained at this new set point by the body's thermoregulatory mechanisms. Hyperthermia is differentiated from fever as it involves a loss of thermoregulation, resulting in an unregulated rise in body temperature
  • Normal rectal temperature—adult 99.1–100.5°F (37.3–38°C); foal 100–102°F (37.8–39°C)

Pathophysiology!!navigator!!

  • A physiologic reaction involving communication between the periphery and the central nervous system
  • Involves complex interactions between cytokines, acute-phase reactants, and the neuroendocrine system
  • Induced by endogenous (including cytokines that are released from cells of the immune system in response to infectious, inflammatory, neoplastic, traumatic, or immunologic stimuli) or exogenous (bacterial products, foreign antigens) pyrogens
  • Endogenous pyrogens act on the organum vasculosum laminae terminalis (cluster of neurons surrounded by the anterior hypothalamus and preoptic nucleus) to stimulate the production of prostaglandins within the central nervous system. Prostaglandin E2 initiates a cascade that results in an increase in the set point for thermoregulation. Toll-like receptors bind exogenous pyrogens resulting in a similar intracellular cascade

Systems Affected!!navigator!!

All body systems can be affected.

Genetics!!navigator!!

Certain breeds are predisposed to associated disorders—Fell Ponies (Fell Pony syndrome), Arabians (severe combined immunodeficiency).

Signalment!!navigator!!

Nonspecific

Signs!!navigator!!

Historical Findings

Investigate recent exposure to new animals, recent travel, vaccination history, health of in-contact animals, diet, housing, previous medical history, medication administration, and course.

Physical Examination Findings

  • Thorough physical examination is essential, including oral, rebreathing, rectal, and neurologic examinations as well as lymph node palpation and gait analysis
  • Nonspecific signs such as lethargy, anorexia, and weight loss, or physical examination may identify a suspected source

Causes!!navigator!!

Infectious

Respiratory

  • Upper respiratory tract—EHV-1, EHV-4, equine influenza virus, Streptococcus equi
  • Guttural pouch empyema—secondary to upper respiratory tract infection or retropharyngeal lymph node abscessation, S. equi, Streptococcus zooepidemicus
  • Retropharyngeal lymph node abscessation—S. equi, S. zooepidemicus, Corynebacterium pseudotuberculosis, Actinobacillus, Mycobacterium avium
  • Sinusitis—primary (bacterial, fungal, mixed); secondary to dental disease, trauma, neoplasia
  • Lower respiratory tract—S. zooepidemicus, S. equi, Streptococcus pneumoniae, Pasteurella, Escherichia coli, Klebsiella, Pseudomonas, Bacteroides spp., Mycoplasma, Aspergillus, phycomycetes, Pneumocystis carinii, Coccidioides immitis, Histoplasma capsulatum, Cryptococcus neoformans, EHV-5 (equine multinodular pulmonary fibrosis), African horse sickness, M. avium, Mycobacterium bovis, Mycobacterium tuberculosis, Nocardia asteroides, adenovirus, Hendra virus
  • Pleuropneumonia—S. zooepidemicus, Pasteurella, Actinobacillus, E. coli, Klebsiella, Bacteroides
  • Foals—Rhodococcus equi, S. zooepidemicus, S. equi, Staphylococcus epidermidis, Pasteurella, P. carinii

Gastrointestinal

  • Peritonitis—primary: Actinobacillus equuli; secondary: gastrointestinal trauma, perforation, ischemia or vascular compromise; abdominal abscess rupture, common variable immunodeficiency
  • Colitis—Salmonella spp., Clostridium difficile, Clostridium perfringens, Neorickettsia risticii, equine coronavirus, cyathostomiasis. Foals—Salmonella spp., C. perfringens, C. difficile, rotavirus, Cryptosporidium, R. equi
  • Duodenitis—proximal jejunitis
  • Abdominal abscessation—S. equi, R. equi, C. pseudotuberculosis
  • Vesicular stomatitis

Neurologic

  • Cerebrum/brainstem—EEE, WEE, VEE, WNV, rabies, bacterial meningitis, brain abscess, mycotic encephalitis, listeriosis, hyperammonemia (enteric disease)
  • Spinal cord disease—EHV-1, vertebral osteomyelitis (R. equi, Streptococcus spp., Staphylococcus spp., Actinobacillus, Aspergillus, Brucella abortus)
  • Otitis media/interna—Actinobacillus, Salmonella spp., Enterobacter, Pseudomonas, Streptococcus spp., Staphylococcus spp., Aspergillus

Hepatic

  • Cholelithiasis—associated with Salmonella spp., E. coli, Aeromonas, Citrobacter, group D Streptococcus
  • Cholangiohepatitis—Gram-negative enteric bacteria (Salmonella spp., E. coli, Citrobacter), Aeromonas, Acinetobacter
  • Infectious necrotic hepatitis
  • Tyzzer disease
  • Chronic active hepatitis
  • Liver abscess

Musculoskeletal

  • Clostridial myonecrosis—Clostridia spp.
  • Streptococcus-associated rhabdomyolysis
  • Osteomyelitis/septic arthritis (bacterial, fungal)
  • Fistulous withers

Integument

  • Cellulitis—Staphylococcus spp., Streptococcus spp., Clostridia spp.
  • Dermatophilosis—Dermatophilus congolensis
  • Subcutaneous abscess—C. pseudotuberculosis, foreign body, S. equi
  • Urticaria—equine Getah virus

Hematologic

Anemia—equine infectious anemia, piroplasmosis.

Cardiovascular

  • Vasculitis—equine viral arteritis, equine infectious anemia, Anaplasma phagocytophilum
  • Phlebitis—thrombophlebitis (Streptococcus spp., Staphylococcus spp., Pasteurella, Actinobacillus, E. coli, Klebsiella pneumoniae)
  • Omphalophlebitis—many organisms can be involved, i.e. E. coli, Proteus, Streptococcus spp.
  • Endocarditis—Streptococcus spp., A. equuli, R. equi, Pasteurella spp., Candida parapsilosis, Erysipelothrix rhusiopathiae, Staphylococcus aureus
  • Pericarditis—idiopathic
  • Septic—A. equuli, Enterococcus faecalis, Streptococcus faecalis, C. pseudotuberculosis
  • African horse sickness

Renal

Pyelonephritis—Gram-negative infections common.

Reproductive

Abortion—bacterial and viral causes.

Systemic

Septicemia

Inflammatory

Respiratory

  • Smoke inhalation
  • Acute respiratory distress syndrome

Gastrointestinal

  • Ulcerative duodenitis (foals)
  • Right dorsal colitis (NSAID toxicity)
  • Sterile peritonitis (uroperitoneum)

Hepatic

  • Chronic active hepatitis—etiology unknown
  • Idiopathic acute hepatitis disease (Theiler disease)

Integument

  • Purpura haemorrhagica—secondary to viral disease, bacterial disease, drug administration, or toxin exposure. Most commonly associated with S. equi
  • Thermal burns
  • Generalized granulomatous disease
  • Pemphigus foliaceus—autoantibody formation against a desmosomal glycoprotein
  • Bullous pemphigoid—autoantibody formation against epithelial basement membrane
  • Systemic lupus erythematous—type III hypersensitivity reaction
  • Panniculitis—trauma, infection, autoimmune disease, vasculitis

Hematologic

  • Immune-mediated hemolytic anemia—primary; secondary (associated with drugs, infection, neoplasia)
  • Neonatal isoerythrolysis
  • Transfusion reaction—immunologic; nonimmunologic—due to contamination of donor product during collection, storage, or administration

Cardiovascular

Myocarditis—inflammation secondary to viral, bacterial, or parasitic disease.

Systemic

Systemic inflammatory response syndrome—can occur secondary to many diseases and injuries.

Nutritional

  • Nutritional myodegeneration—vitamin E and selenium deficiency (cardiac and skeletal forms)
  • Hyperlipemia

Neoplasia

With any form of neoplasia.

Iatrogenic

  • Myelogram (e.g. pneumonia, septic or aseptic meningitis)
  • Transport (respiratory infections)
  • Transfusion reactions
  • Adverse drug reaction
  • Antibiotic-associated colitis
  • Thrombophlebitis

Trauma

Traumatic inflammation.

Immunodeficiency

  • Result of increased susceptibility to infection
  • Severe combined immunodeficiency
  • Selective immunoglobulin M deficiency
  • Transient hypogammaglobulinemia
  • Agammaglobulinemia
  • Fell Pony syndrome
  • Common variable immunodeficiency

Toxins

  • Fescue toxicosis
  • Blister beetle toxicosis (cantharidin)
  • Snake bite
  • Castor bean toxicity (Ricinus communis)
  • Arsenic
  • Mercury
  • Chlorinated hydrocarbons
  • Dinitrophenol
  • Trichloroethylene extracted feed
  • Propylene glycol
  • Algae
  • Pyrrolizidine alkaloid
  • Water hemlock (Cicuta spp.)
  • Jimson weed
  • Mycotoxicosis

Risk Factors!!navigator!!

  • Exposure to infected animals
  • Poor biosecurity/husbandry/management
  • Transportation
  • Immunodeficiency
  • Intense exercise

Diagnosis ⬆ ⬇

Outline

DIAGNOSIS

Differential Diagnosis!!navigator!!

In 1 retrospective study of fever, cause was—43% infectious, 22% neoplastic, 6.5% immune mediated, 19% miscellaneous; 9.5% cause was not identified.

Further Diagnostics!!navigator!!

Depending on the abnormalities identified on initial clinical evaluation, ancillary testing will likely be required.

CBC/Chemistry/Urinalysis!!navigator!!

  • Hematology—fibrinogen and serum amyloid A: markers of infection/inflammation (fibrinogen >1000 mg/dL often indicates abscess, osteomyelitis, pyelonephritis)
  • White blood cell count/differential—increases often with bacterial infections or decreases with severe acute infections
  • Blood smear—A. phagocytophilum in neutrophil cytoplasmic vacuoles, red blood cell parasites, and assess cell morphology
  • Packed cell volume and total protein—assess for evidence of hemoconcentration, anemia, hypoproteinemia, or hyperproteinemia
  • Serum chemistry—specific organ compromise
  • Urinalysis—identifying renal protein loss, urinary tract infection, and hematuria/hemoglobinuria; cantharidin toxin and leptospirosis

Other Laboratory Tests!!navigator!!

  • Blood culture (bacteremia, fungemia)
  • Immunoglobulin levels (neonates)
  • Coggins test (equine infectious anemia)
  • Direct Coombs test (hemolytic anemia)
  • Antinuclear antibody test
  • Virus isolation (from blood, nasopharynx)
  • Serology—paired titers most useful
  • Fungal serology
  • PCR—S. equi, Neorickettsia, A. phagocytophilum, piroplasmosis
  • Vitamin E level—whole blood levels in suspected nutritional myodegeneration

Imaging!!navigator!!

Ultrasonography

  • Thorax—assess effusion, consolidation, pleural masses
  • Abdomen—assess internal organs, intestinal wall thickness, peritoneal fluid, lymph nodes
  • Jugular veins (thrombosis)
  • Heart—assess valves (endocarditis), pericardium (effusion)
  • Abscess/mass—useful to assess nature and extent of unidentified masses

Radiography

  • Thorax—useful in cases of pneumonia, neoplasia, pleural effusion, masses
  • Abdomen—limited usefulness, especially in adults; can do contrast studies to assess swallowing and gastric emptying
  • Skull—sinusitis, masses
  • Musculoskeletal—assess physitis, osteomyelitis, osteosarcoma, vertebral body abscessation

Endoscopy

  • Upper respiratory tract—assess guttural pouches, pharyngeal region, nasomaxillary opening
  • Lower respiratory tract—identify tracheitis, abnormalities in distal airways
  • Gastroscopy—assess esophageal and gastric mucosa for ulceration, masses, biopsy (gastric, duodenal)
  • Other—cystoscopy, sinoscopy, rectum

Nuclear Scintigraphy

  • Identify regions of active inflammation
  • Can perform with radiolabeled white cells or radiolabeled albumin

MRI/CT

Perform studies of head in cases of suspected intracranial or brainstem disease or in cases of otitis interna/media or sinusitis.

Other Diagnostic Procedures!!navigator!!

  • Transtracheal wash—culture, cytology, Gram stain: lower respiratory tract disease suspected
  • Bronchoalveolar lavage—cytology, Gram stain: diffuse lower airway disease suspected
  • Guttural pouch lavage—culture, cytology, PCR
  • Abdominocentesis—culture, cytology, Gram stain: peritonitis, bowel compromise, or neoplasia
  • Thoracocentesis—culture, cytology, Gram stain
  • Sinocentesis—culture, Gram stain, cytology
  • Cerebrospinal fluid analysis—assess nucleated cell count, protein, culture, cytology, and specific disease testing
  • Lymph node aspiration—culture, Gram stain, cytology
  • Abscess aspiration—culture, Gram stain, cytology
  • Fecal assessment—Salmonella PCR/culture, C. perfringens toxin assay, C. difficile toxin assay, rotavirus ELISA/latex agglutination, fecal egg count. Perform similar cultures and toxin assays on gastric reflux
  • Biopsy—lung (parenchymal disease), liver, skin, muscle (immunofluorescent stain for S. equi), lymph nodes, bone
  • Synoviocentesis—cytology, cell count, total protein level, culture
  • Pericardiocentesis—cytology and culture
  • Bone marrow aspirate/biopsy—assess progenitor cells in selected cases of anemia, thrombocytopenia, or leukogram abnormalities

Pathologic Findings!!navigator!!

Dependent on cause.

Treatment ⬆ ⬇

Outline

TREATMENT

  • Target at known source. Supportive nursing care, rest, temperature-controlled environment, food and water
  • IV fluid therapy
  • Enteral or parenteral nutritional support. Pyrexia is a catabolic state and weight loss should be closely monitored

Client Education!!navigator!!

  • Identify clinical signs in contact horses
  • Monitor horses’ temperature daily
  • Biosecurity

Surgical Considerations!!navigator!!

Exploratory laparotomy may be indicated. Surgery may be necessary as an adjunct to medical therapy in some disease processes, i.e. sinusitis secondary to tooth root abscessation, septic arthritis.

Medications ⬆ ⬇

Outline

MEDICATIONS

There is some debate as to whether treatment of fever is beneficial.

Drug(s) of Choice!!navigator!!

NSAIDs

Weigh benefits, disadvantages, and potential side effects.

Corticosteroids

  • Anti-inflammatory agents, and at higher doses immunosuppressive agents (dexamethasone, prednisolone, and prednisolone sodium succinate). These drugs can be useful in the treatment of selected nonseptic inflammatory and immune-mediated diseases. Occasionally used as a powerful anti-inflammatory in the presence of infections (R. equi pneumonia and acute respiratory distress syndrome)
  • Other anti-inflammatory drugs that are in use include azathioprine, cyclophosphamide, aurothioglucose, and pentoxifylline

Antimicrobials

  • Ideally, the source of fever and etiologic agent should be identified before antimicrobial therapy is initiated. Bacterial sources of fever should be treated with antibiotics based on culture and sensitivity results. The location of infection must be taken into consideration with appropriate antimicrobials chosen to target this location. In circumstances where empirical treatment must be initiated without the benefit of culture and sensitivity results, broad-spectrum antimicrobial cover should be initiated
  • Local therapy may be more appropriate than systemic therapy (i.e. intra-articular and regional administration in septic joints/osteomyelitis)
  • Fungal disease can be difficult to treat in the horse due to the lack of availability of antifungal agents and the expense of treatment. Therapy should ideally be initiated based on culture and sensitivity results
  • Parasitism should be treated with institution of a comprehensive deworming program based on the needs and facilities of the individual horse and property. It is important to monitor for development of resistance and to treat for encysted cyathostomes and tapeworms
  • Viral disease rarely has directed therapeutic options and care normally involves supportive therapy. Acyclovir (aciclovir) has been used in treatment of the neurologic form of EHV-1, and interferon therapy has been tried in the treatment of WNV

Precautions!!navigator!!

NSAIDs

Can result in nephrotoxicity, right dorsal colitis, gastric ulceration. Side effects are more common in dehydrated or hypovolemic animals, and when administered concurrently with other nephrotoxic agents such as aminoglycosides, tetracyclines, and amphotericin B.

Corticosteroids

  • Can induce hypothalamic–pituitary–adrenal system suppression or immunosuppression
  • Have been associated with development, or worsening, of laminitis

Antimicrobials

  • Can result in antibiotic-induced colitis. Aminoglycosides, oxytetracycline, and amphotericin B are potentially nephrotoxic. Aminoglycoside therapeutic drug monitoring is recommended
  • Itraconazole—use with care in cases with hepatic impairment

Possible Interactions!!navigator!!

  • Care should be taken in using multiple drugs that are potentially nephrotoxic in patients that are dehydrated or hypovolemic
  • α2-Agonist drugs (e.g. xylazine, detomidine) may induce tachypnea and nostril flaring in horses with pyrexia

Follow-up ⬆ ⬇

Outline

FOLLOW-UP

Patient Monitoring!!navigator!!

Therapeutic efficacy should be monitored by assessing clinical abnormalities on a regular basis (i.e. fibrinogen, ultrasonographic or radiographic findings). While receiving medications, monitoring should be used to assess for side effects; i.e. monitor total protein, albumin, and creatinine while undergoing NSAID treatment.

Prevention/Avoidance!!navigator!!

  • Follow simple biosecurity rules when working with horses
  • Maintain current vaccination status on all horses

Possible Complications!!navigator!!

  • Many disease processes that cause fever have been associated with a risk for the development of laminitis
  • Many horses with severe infectious disease such as colitis or pleuropneumonia have subclinical coagulopathies and are at risk for jugular thrombophlebitis and disseminated intravascular coagulopathy
  • Anorexia can predispose horses, ponies, and donkeys to hyperlipemia

Miscellaneous ⬆ ⬇

Outline

MISCELLANEOUS

Age-Related Factors!!navigator!!

  • Neonates are immunodeficient prior to receiving colostrum
  • Foals
    • Increased susceptibility to disease when maternal immunity wanes
    • R. equi—signs of disease are seen between 1 and 6 months of age
  • Racehorses
    • Transportation and exercise can both contribute to compromised immune function. Populations are often transient, with constant exposure to new horses occurring
    • Pleuropneumonia
    • Viral respiratory disease
  • Older horses—neoplasia

Zoonotic Potential!!navigator!!

  • Rabies
  • Salmonella spp.
  • Brucellosis
  • Leptospirosis
  • EEE, WEE, VEE
  • Anthrax
  • Cryptosporidium
  • C. difficile
  • R. equi (immunocompromised individuals)
  • Hendra virus

Pregnancy/Fertility/Breeding!!navigator!!

Fever and the associated inflammatory response can be detrimental to pregnancy; fetal evaluations should be performed in febrile pregnant mares. Foaling should be attended and the foal carefully assessed for signs of in utero compromise. Drug therapy should be carefully considered in the late term mare to ensure there are no contraindications.

Synonyms!!navigator!!

Pyrexia

Abbreviations!!navigator!!

  • CT = computed tomography
  • EEE –Eastern equine encephalitis
  • EHV = equine herpesvirus
  • ELISA = enzyme-linked immunosorbent assay
  • MRI = magnetic resonance imaging
  • NSAID = nonsteroidal anti-inflammatory drug
  • PCR = polymerase chain reaction
  • VEE = Venezuelan equine encephalitis
  • WEE = Western equine encephalitis
  • WNV = West Nile virus

Suggested Reading ⬆ ⬇

Dinarello CA. Infection, fever, and exogenous and endogenous pyrogens: some concepts have changed. J Endotoxin Res 2004;10:201–222.

Greisman LA, Mackowiak PA. Fever: beneficial and detrimental effects of antipyretics. Curr Opin Infect Dis 2002;15:241–245.

Author(s) ⬆

Author: Michelle Abraham Linton

Consulting Editor: Ashley G. Boyle

Acknowledgment: The author and editor acknowledge the prior contribution of Julie Ross.