What is horse serum allergy

English, Swedish, Spanish


Scientific Contributions presented at meetings and congresses

  • Gamma-glutamyltransferase (GGT): Membrane bound induced enzyme; liver specific
  • Diffuse mild fibroplasia primarily in portal areas
  • Ferrándiz R. Tropical mite allergens. Magic Lite VIP Meeting, Hørsholm, Denmark, 1995.
  • Cause of hepatocellular loss unknown; recent study identified Theiler’s disease-associated virus (TDAV) a Flaviviridae member that appears to be a plausible candidate viral cause of this disease
  • Brown DL, Van Wettere AJ, and Cullen JM.

    Hepatobiliary System and Exocrine Pancreas. In: McGavin MD, Zachary JF, eds. PathologicBasisofVeterinaryDisease. 6th ed. St. Louis, MO: Elsevier; 2017:456.

  • Common cause of acute hepatic failure in horses
  • Casas R, Ferrándiz R. Estudio comparativo de extractos alergénicos de ácaros del polvo. Interasma’ 88, La Habana, Cuba, 1988.
  • Hepatic encephalopathy: Restlessness, hyperexcitability, compulsive walking and head pressing, apparent blindness, ataxia, muscle tremors, seizures, and sudden death
  • Extensive bile pigment deposits in hepatocytes and Kupffer cells
  • Ferrándiz R.

    Mites and mite crossreactivity. Studies from Cuba and Sweden. Årsmöte i Svensk Förening för Allergologi. Linköping, Sweden, Mars 1996.

  • Casas, R, R. Ferrándiz, B. Björkstén. Presence of free Fel d 1 and immune complexes with allergen in the serum of cat allergic children. International Congress of Allergy and Clinical Immunology, ICACI´97, Cancún, Mexico. Allergy and Clin Immunol Int. Suppl. 4:11.
  • Becquer A, Ferrándiz R. Comportamiento de las poblaciones de Cerosipha gossypii en plantaciones de Cucurbita moschata. III Seminario Cientifico Inst. Ciencias Agrícolas, La Habana, 1981.
  • Incubation period of 42-60 days (sometimes as endless as 90 days) after receiving injections of equine-origin biologics, including tetanus antitoxin, equine encephalomyelitis antiserum, pregnant mare serum gonadotropin, African horse sickness antiserum, anthrax antiserum, and plasma
  • Acute hepatic insufficiency secondary to loss of hepatocytes
  • Casas R, Ferrándiz, R, Dreborg S.

    Sensitization of Cuban asthmatic adolescents by skin tests and specific IgE. Annual Congress European Society of Pediatric Allergy and Clinical Immunology, Rome, Italy, November 1995.

  • Casas R, Abdo A, Ferrándiz R. Valoración de la eficacia terapéutica del extracto alergénico D. pteronyssinus en el asma bronquial. IX Conferencia Científica CIMEQ, La Habana, 1993.
  • Ferrándiz R. La transmisión de virus por los insectos. Asociación de Profesores de Carazo, Carazo, Nicaragua, 1983.

  • Ferrándiz R, Casas R, Einarsson R, Dreborg S. Crossreactivity between D. siboney and other domestic mites. XVI European Congress of Allergology and Clinical Immunology, Madrid, Spain, June 1995.
  • Ferrándiz, R. Exposure and avoidance of inhalant allergens. ALK Satellite Symposium. International Congress of Allergy and Clinical Immunology, ICACI´97, Cancún, Mexico, Oct. 21.
  • Casas, R, S. Garriga, N. Martinez, B. Fernández, R. Ferrándiz, S. Dreborg. Sensitization to inhalant allergens in Cuban asthmatics. International Congress of Allergy and Clinical Immunology, ICACI´97, Cancún, Mexico.

    Allergy and Clin Immunol Int. Suppl. 4:136.

  • Clinical pathology: Leukocytosis (neutrophilia, lymphocytopenia), hypoglycemia, hyperbilirubinemia, hyperammonemia, increased serum bile acids, prolonged one-stage prothrombin time (OSPT), increased liver enzymes:
    1. Sorbitol dehydrogenase (SDH): Hepatocellular leakage enzyme; liver specific
    2. Ferrándiz R. Allergenic characterization of the home dust mite Dermatophagoides siboney. KFC Meeting, Loka Brun, 4-5 Sept. 97
    3. Possible equine DNA virus (equine parvovirus) another potential causative agent (has fulfilled Koch’s postulates in n=2 experimental trial)
    4. Etiology not known; infectious etiology suspected because of sporadic occurrence in horses that own not received equine biological products; there are reports of in-contact non-treated horses developing the disease
    5. Liver: Shrunken and flaccid “dish-rag liver” (classic lesion); stained by bile pigments; mottled appearance; enhanced lobular pattern because of necrosis of hepatocytes in centrilobular areas with congestion
    6. Equine hepatic necrosis:
      1. Acute toxic hepatitis: Generally centrilobular necrosis with minimal inflammation; biliary hyperplasia; fibrosis with chronicity; +/- photosensitization
      2. Mildly affected animals: Afebrile, depression, anorexia, excessive yawning, icterus, +/- type II photosensitization
      3. Henricson K., Andræ S., Gromell A., Ferrandiz R., Effect of therapeutic silk in the treatment of children with atopic eczema.

        A report of 11 cases in Sweden. Allergy, 2007; 62 (Suppl.83):322.

      4. Chandriani S, Skewes-Cox P, et al.

        What is horse serum allergy

        Identification of a previously undescribed divergent virus from the Flaviviridae family in an outbreak of equine serum hepatitis. Proc Natl Acad Sci USA.

        What is horse serum allergy

        2013; 110(15):E1407-15.

      5. Casas, R, J-Å. Wihl, B. Fernández, R. Ferrándiz, S. Dreborg. Biological standardization (BS) of Dermatophagoides siboney (Ds), D. pteronyssinus (Dp), D. farinae (Df) and Blomia tropicalis (Bt) in exposed and non-exposed mite allergic individuals. International Congress of Allergy and Clinical Immunology, ICACI´97, Cancún, Mexico. Allergy and Clin Immunol Int. Suppl. 4:137.
      6. Icterus, ascites, +/- splenic congestion and petechial hemorrhages
      7. Hyperammonemia linked to hepatic encephalopathy
      8. Ferrándiz R. El cultivo de protoplastos y su utilización en la fitopatología. Reunión Científica Comisión Agropecuaria, La Habana, 1987.

      9. Hepatitis B virus causes similar lesions in human beings
      10. Dreborg S, Felix K, Ferrándiz R, Einarsson R. Allergens of horse dander. Comparison between breeds and individual animals using immunoblotting. 52nd Annual Meeting of American Academy of Allergy Asthma and Immunology, New Orleans, USA, March 1996.
      11. Ferrándiz R. Un sistema experto de inteligencia artificial sobre la transmisión de virus por áfidos. I Seminario Internacional de Sanidad Vegetal, La Habana, 1987.
      12. Cullen JM, Stalker MJ.

        Liver and Biliary system. In: Maxie MG, ed. Jubb, Kennedy and Palmer’s Pathology of Domestic Animals. Vol 2. 6th ed. St. Louis, MO: Elsevier Ltd; 2016:313-314.

      13. Pyrrolizidine alkaloid toxicity: Chronic; hepatocyte necrosis; megalocytosis; centrilobular fibrosis; bile duct proliferation and fibrosis
      14. Ferrandiz RF, Persson Å, Bruzelius L. Effect of bed encasing on mite allergic children. A survey of 97 children in Sweden. J Allergy Clin Immunol 2008; 121(2):s295.
      15. Ferrándiz R, Casas R, Dreborg S. Sensitization to Dermatophagoides siboney, Blomia tropicalis and other domestic mites in asthmatic patients. 52nd Annual Meeting of American Academy of Allergy Asthma and Immunology, New Orleans, USA, March 1996.

      16. Aspartate aminotransferase (AST): Hepatocellular leakage enzyme; not liver specific, found in liver, muscle and erythrocytes
      17. Ferrándiz R, Dreborg S. Analysis of individual crossreacting allergens between Dermatophagoides siboney and other mites by immunoblot inhibition. 21st Collegium Internationale Allergologicum, September 1996, Schloß Fuschl, Salzburg, Austria. Int. Arch Allergy and Immunol 1997, 1-3:238-239.
      18. Casas R, Bonachea I, Labrada A, Ferrándiz R. Caracterización in-vitro de extractos alergénicos de ácaros del polvo del género Dermatophagoides. I Congreso Nacional de Alergología,
      19. Fernández B, Labrada A, Casas R, Ferrándiz R.

        Determinación del contenido de Der p I, alergeno mayor de Dermatophagoides pteronyssinus en diferentes extractos alergénicos. II Congreso Nacional Alergología, La Habana, 1993.

      20. Few surviving swollen and vacuolated periportal hepatocytes or sometimes finish depletion of parenchymal cells (lesion appears older than clinical symptoms suggest)
      21. Fernández T, Ferrándiz R. Influencia de diferentes aislados del virus del mosaico severo del caupí sobre los distintos componentes del rendimiento de la soya. II Simposium Internacional sobre Sanidad Vegetal en la Agricultura Tropical, Havana, 1986.
      22. Divers TJ and Barton MH. Disorders of the Liver. In: Reed SM, Bayly WM, and Sellon DC, eds.

        Equine Internal Medicine. 4th ed. St. Louis, MO: Elsevier Ltd; 2018: 865-866.

      23. Ferrándiz R, Gutierrez F. Desarrollo y reproducción de Myzus persicae. II Jornada Científica, Inst. Inv.

        What is horse serum allergy

        Fund. Agr. Tropical, Habana, 1979.

      24. Ferrándiz R, Casas R. Dreborg S. Characterization of allergens from home dust mite Dermatophagoides siboney. Purification of Der s 1 and Der s 2 allergens. XV International Congress of Allergology and Clinical Immunology, Stockholm, Sweden, June 1994.
      25. Prolonged incubation period and a extremely rapid clinical course; acute hepatic failure with death occurring within 6 to 24 hours
      26. Becquer A, Ferrándiz R. Dinamica de las poblaciones de áfidos en plantaciones de frijol. 3 Conferencia de Ciencias Agropecuarias, Universidad Central de Las Villas, 1980.

      27. Ferrándiz, R. Specific IgE analysis with Magic Lite using solid phases prepared by the customers. Vårmöte i klinisk kemi, 21-23 april, Malmö, Sweden.
      28. Aflatoxicosis: At low doses, resembles pyrrolizidine alkaloid toxicity; at high doses, periacinar hepatocytes vanish and are replaced by a mixture of inflammatory cells, fibroblasts, and primitive vascular channels
      29. Ferrándiz R, Casas R, Dreborg S. The differences and similarities between Dermatophagoides siboney and other mite species. 53 Annual Meeting of American Academy of Allergy Asthma and Immunology, San Francisco, USA, 21-26 February 1997; JACI Vol.99(1) part 2: 346.

      30. Equine infectious anemia (equine lentivirus): Subacute; centrilobular fatty degeneration and hepatocellular loss; increased numbers of sinusoidal Kupffer cells; portal infiltration by lymphocytes and plasma cells extremely characteristic
      31. Severe macrovesciular fatty change; may coalesce and form fatty cysts; dilated sinusoids and condensed reticulin framework
      32. Ferrándiz R. Exposure and avoidance of inhalant allergens. European Society of Pediatric Allergy and Clinical Immunology/ERPA Join Meeting, Odense, Denmark, May 1996.
      33. “Serum sickness” – a Type III hypersensitivity approximately 10 days after istration of antiserum or certain medications, characterized by generalized vasculitis with erythema, edema and urticaria of the skin, neutropenia, joint swelling and proteinuria
      34. No hemorrhage; acute necrosis typically not seen, instead hepatocyte loss is the main feature with collapsed or distortion of reticulin framework; prominent inflammation not a feature
      35. Sewer, M, O.

        Jorge, M. Labrada, R. Ferrándiz, M. González, M.A. Coca, A. Labrada. Generation of monoclonal antibodies against Der s 1, a major allergen of Dermatophagoides siboney. International Congress of Allergy and Clinical Immunology, ICACI´97, Cancún, Mexico. Allergy and Clin Immunol Int. Suppl. 4:135.

      36. Labrada A, Fernández B, Casas R, Ferrándiz R. Equilibración de potencia de extractos alergénicos por ELISA inhibición. Congreso de Biotecnología, La Habana, 1994.
      37. Divers TJ, Tennant BC, et al. New parvovirus associated with serum hepatitis in horses after inoculation of common biological product.

        Emerg Infect Dis. 2018; 24(2):303-310.

Skin hypersensitivities (allergies) in horses are often diagnosed using clinical signs only. Intradermal testing or serological assays are diagnostic options to confirm the allergic nature of the disease and to identify the allergen(s). Our objective was to develop an allergen-specific enzyme-linked immunosorbent assay (ELISA) using a monoclonal antibody specific for horse IgE and to examine its potential for allergen detection in serum in comparison to intradermal testing.

Intradermal testing with 61 allergen extracts was performed on 10 horses affected with skin hypersensitivity. Their sera were analyzed by ELISA for IgE antibodies to the same allergens. The kappa test of concordance was used for comparison of the results of both tests. Out of 61 allergen extracts, only two (Timothy and Quack) had kappa values greater than 0.60, suggesting a substantial agreement between skin testing and IgE ELISA. The statistical comparison of the remaining 59 allergens showed little or no concordance between the tests beyond chance.

What is horse serum allergy

To identify parameters that may influence the sensitivity of the ELISA, the assay was modified to detect allergen-specific IgGb and IgG(T) in serum, and the protein content in every allergen extracts was sure by SDS-PAGE. The commercial allergen extracts revealed a high variation in detectable protein. High concentrations of allergen-specific IgG in horse serum were found to compete with IgE for binding to the plates. In conclusion, an ELISA using whole serum and crude allergen preparations provides limited diagnostic information in horses.

The dependable diagnosis of allergens in equine skin hypersensitivity is essential to improve allergen-specific treatments, such as hyposensitization, or the development of allergy vaccines.

JPC SYSTEMIC PATHOLOGY
DIGESTIVE SYSTEM
September 2018
D-M06

SIGNALMENT (AFIP #1431298): 6-month-old Appaloosa foal

HISTORY: The foal was vaccinated 2 weeks prior to death for tetanus, Eastern equine encephalitis and Western equine encephalitis.

Clinical findings included blindness, incoordination, constipation, head pressing, icterus, AST=1800 (205-555 U/L), bilirubin=12 (0.1-1.9 mg/dl).

HISTOPATHOLOGIC DESCRIPTION: Liver: There is diffuse hepatic necrosis affecting the centrilobular and midzonal regions characterized by loss of hepatocytes, stromal collapse, distortion of the reticulin framework and replacement by eosinophilic cellular and karryohectic debris. Remaining adjacent periportal hepatocytes are often individualized, degenerate with swollen, pale, vacuolated cytoplasm; necrotic, with shrunken hyper eosinophilic cytoplasm and pyknotic nuclei; or occasionally contain large, distinct, clear intracytoplasmic vacuoles (vacuolar change, lipid type).

Hepatic cords are disrupted and hepatocytes are individualized and separated by multifocal areas of hemorrhage, there are increased numbers of Kupffer cells which often contain phagocytosed erythrocytes and minimal amounts of globular brown pigment (hemosiderin or bile), and scattered lymphocytes and plasma cells. Portal areas are mildly expanded by clear space (edema) and contain mildly increased amounts of fibrous connective tissue, few lymphocytes, plasma cells, macrophages, and rare neutrophils.

MORPHOLOGIC DIAGNOSIS: Liver: Hepatocellular necrosis and hepatocyte loss, submassive, diffuse, severe, with stromal collapse, hemorrhage, and biliary ductular reaction, Appaloosa, equine.

ETIOLOGIC DIAGNOSIS: Unknown (flavivirus suspected)

CONDITION: Equine serum hepatitis

SYNONYMS: Theiler»s disease, idiopathic acute hepatic disease (IAHD), post-vaccinal hepatitis

GENERAL DISCUSSION:

  1. Etiology not known; infectious etiology suspected because of sporadic occurrence in horses that own not received equine biological products; there are reports of in-contact non-treated horses developing the disease
  2. Common cause of acute hepatic failure in horses
  3. Incubation period of 42-60 days (sometimes as endless as 90 days) after receiving injections of equine-origin biologics, including tetanus antitoxin, equine encephalomyelitis antiserum, pregnant mare serum gonadotropin, African horse sickness antiserum, anthrax antiserum, and plasma

PATHOGENESIS:

  1. Acute hepatic insufficiency secondary to loss of hepatocytes
  2. Possible equine DNA virus (equine parvovirus) another potential causative agent (has fulfilled Koch’s postulates in n=2 experimental trial)
  3. Cause of hepatocellular loss unknown; recent study identified Theiler’s disease-associated virus (TDAV) a Flaviviridae member that appears to be a plausible candidate viral cause of this disease
  4. Hyperammonemia linked to hepatic encephalopathy

TYPICAL CLINICAL FINDINGS:

  • Prolonged incubation period and a extremely rapid clinical course; acute hepatic failure with death occurring within 6 to 24 hours
  • Mildly affected animals: Afebrile, depression, anorexia, excessive yawning, icterus, +/- type II photosensitization
  • Hepatic encephalopathy: Restlessness, hyperexcitability, compulsive walking and head pressing, apparent blindness, ataxia, muscle tremors, seizures, and sudden death
  • Clinical pathology: Leukocytosis (neutrophilia, lymphocytopenia), hypoglycemia, hyperbilirubinemia, hyperammonemia, increased serum bile acids, prolonged one-stage prothrombin time (OSPT), increased liver enzymes:
    1. Sorbitol dehydrogenase (SDH): Hepatocellular leakage enzyme; liver specific
    2. Aspartate aminotransferase (AST): Hepatocellular leakage enzyme; not liver specific, found in liver, muscle and erythrocytes
    3. Gamma-glutamyltransferase (GGT): Membrane bound induced enzyme; liver specific

    TYPICAL GROSS FINDINGS:

    1. Liver: Shrunken and flaccid “dish-rag liver” (classic lesion); stained by bile pigments; mottled appearance; enhanced lobular pattern because of necrosis of hepatocytes in centrilobular areas with congestion
    2. Icterus, ascites, +/- splenic congestion and petechial hemorrhages

    TYPICAL LIGHT MICROSCOPIC FINDINGS:

    1. Extensive bile pigment deposits in hepatocytes and Kupffer cells
    2. Diffuse mild fibroplasia primarily in portal areas
    3. Few surviving swollen and vacuolated periportal hepatocytes or sometimes finish depletion of parenchymal cells (lesion appears older than clinical symptoms suggest)
    4. Severe macrovesciular fatty change; may coalesce and form fatty cysts; dilated sinusoids and condensed reticulin framework
    5. No hemorrhage; acute necrosis typically not seen, instead hepatocyte loss is the main feature with collapsed or distortion of reticulin framework; prominent inflammation not a feature

    DIFFERENTIAL DIAGNOSIS:

  • Equine hepatic necrosis:
    1. Acute toxic hepatitis: Generally centrilobular necrosis with minimal inflammation; biliary hyperplasia; fibrosis with chronicity; +/- photosensitization
    2. Equine infectious anemia (equine lentivirus): Subacute; centrilobular fatty degeneration and hepatocellular loss; increased numbers of sinusoidal Kupffer cells; portal infiltration by lymphocytes and plasma cells extremely characteristic
    3. Pyrrolizidine alkaloid toxicity: Chronic; hepatocyte necrosis; megalocytosis; centrilobular fibrosis; bile duct proliferation and fibrosis
    4. Aflatoxicosis: At low doses, resembles pyrrolizidine alkaloid toxicity; at high doses, periacinar hepatocytes vanish and are replaced by a mixture of inflammatory cells, fibroblasts, and primitive vascular channels

    COMPARATIVE PATHOLOGY:

    1. Cullen JM, Stalker MJ.

      Liver and Biliary system. In: Maxie MG, ed. Jubb, Kennedy and Palmer’s Pathology of Domestic Animals. Vol 2. 6th ed. St. Louis, MO: Elsevier Ltd; 2016:313-314.

    2. Brown DL, Van Wettere AJ, and Cullen JM. Hepatobiliary System and Exocrine Pancreas. In: McGavin MD, Zachary JF, eds. PathologicBasisofVeterinaryDisease. 6th ed.

      What is horse serum allergy

      St. Louis, MO: Elsevier; 2017:456.

    3. “Serum sickness” – a Type III hypersensitivity approximately 10 days after istration of antiserum or certain medications, characterized by generalized vasculitis with erythema, edema and urticaria of the skin, neutropenia, joint swelling and proteinuria
    4. Chandriani S, Skewes-Cox P, et al. Identification of a previously undescribed divergent virus from the Flaviviridae family in an outbreak of equine serum hepatitis. Proc Natl Acad Sci USA. 2013; 110(15):E1407-15.
    5. Divers TJ and Barton MH. Disorders of the Liver. In: Reed SM, Bayly WM, and Sellon DC, eds. Equine Internal Medicine.

      4th ed. St. Louis, MO: Elsevier Ltd; 2018: 865-866.

    6. Hepatitis B virus causes similar lesions in human beings
    7. Divers TJ, Tennant BC, et al. New parvovirus associated with serum hepatitis in horses after inoculation of common biological product. Emerg Infect Dis. 2018; 24(2):303-310.

    REFERENCES:

    Skin hypersensitivities (allergies) in horses are often diagnosed using clinical signs only. Intradermal testing or serological assays are diagnostic options to confirm the allergic nature of the disease and to identify the allergen(s).

    Our objective was to develop an allergen-specific enzyme-linked immunosorbent assay (ELISA) using a monoclonal antibody specific for horse IgE and to examine its potential for allergen detection in serum in comparison to intradermal testing. Intradermal testing with 61 allergen extracts was performed on 10 horses affected with skin hypersensitivity. Their sera were analyzed by ELISA for IgE antibodies to the same allergens.

    The kappa test of concordance was used for comparison of the results of both tests. Out of 61 allergen extracts, only two (Timothy and Quack) had kappa values greater than 0.60, suggesting a substantial agreement between skin testing and IgE ELISA. The statistical comparison of the remaining 59 allergens showed little or no concordance between the tests beyond chance. To identify parameters that may influence the sensitivity of the ELISA, the assay was modified to detect allergen-specific IgGb and IgG(T) in serum, and the protein content in every allergen extracts was sure by SDS-PAGE.

    The commercial allergen extracts revealed a high variation in detectable protein. High concentrations of allergen-specific IgG in horse serum were found to compete with IgE for binding to the plates. In conclusion, an ELISA using whole serum and crude allergen preparations provides limited diagnostic information in horses. The dependable diagnosis of allergens in equine skin hypersensitivity is essential to improve allergen-specific treatments, such as hyposensitization, or the development of allergy vaccines.

    JPC SYSTEMIC PATHOLOGY
    DIGESTIVE SYSTEM
    September 2018
    D-M06

    SIGNALMENT (AFIP #1431298): 6-month-old Appaloosa foal

    HISTORY: The foal was vaccinated 2 weeks prior to death for tetanus, Eastern equine encephalitis and Western equine encephalitis.

    Clinical findings included blindness, incoordination, constipation, head pressing, icterus, AST=1800 (205-555 U/L), bilirubin=12 (0.1-1.9 mg/dl).

    HISTOPATHOLOGIC DESCRIPTION: Liver: There is diffuse hepatic necrosis affecting the centrilobular and midzonal regions characterized by loss of hepatocytes, stromal collapse, distortion of the reticulin framework and replacement by eosinophilic cellular and karryohectic debris. Remaining adjacent periportal hepatocytes are often individualized, degenerate with swollen, pale, vacuolated cytoplasm; necrotic, with shrunken hyper eosinophilic cytoplasm and pyknotic nuclei; or occasionally contain large, distinct, clear intracytoplasmic vacuoles (vacuolar change, lipid type).

    Hepatic cords are disrupted and hepatocytes are individualized and separated by multifocal areas of hemorrhage, there are increased numbers of Kupffer cells which often contain phagocytosed erythrocytes and minimal amounts of globular brown pigment (hemosiderin or bile), and scattered lymphocytes and plasma cells. Portal areas are mildly expanded by clear space (edema) and contain mildly increased amounts of fibrous connective tissue, few lymphocytes, plasma cells, macrophages, and rare neutrophils.

    MORPHOLOGIC DIAGNOSIS: Liver: Hepatocellular necrosis and hepatocyte loss, submassive, diffuse, severe, with stromal collapse, hemorrhage, and biliary ductular reaction, Appaloosa, equine.

    ETIOLOGIC DIAGNOSIS: Unknown (flavivirus suspected)

    CONDITION: Equine serum hepatitis

    SYNONYMS: Theiler»s disease, idiopathic acute hepatic disease (IAHD), post-vaccinal hepatitis

    GENERAL DISCUSSION:

    1. Etiology not known; infectious etiology suspected because of sporadic occurrence in horses that own not received equine biological products; there are reports of in-contact non-treated horses developing the disease
    2. Common cause of acute hepatic failure in horses
    3. Incubation period of 42-60 days (sometimes as endless as 90 days) after receiving injections of equine-origin biologics, including tetanus antitoxin, equine encephalomyelitis antiserum, pregnant mare serum gonadotropin, African horse sickness antiserum, anthrax antiserum, and plasma

    PATHOGENESIS:

    1. Acute hepatic insufficiency secondary to loss of hepatocytes
    2. Possible equine DNA virus (equine parvovirus) another potential causative agent (has fulfilled Koch’s postulates in n=2 experimental trial)
    3. Cause of hepatocellular loss unknown; recent study identified Theiler’s disease-associated virus (TDAV) a Flaviviridae member that appears to be a plausible candidate viral cause of this disease
    4. Hyperammonemia linked to hepatic encephalopathy

    TYPICAL CLINICAL FINDINGS:

  • Prolonged incubation period and a extremely rapid clinical course; acute hepatic failure with death occurring within 6 to 24 hours
  • Mildly affected animals: Afebrile, depression, anorexia, excessive yawning, icterus, +/- type II photosensitization
  • Hepatic encephalopathy: Restlessness, hyperexcitability, compulsive walking and head pressing, apparent blindness, ataxia, muscle tremors, seizures, and sudden death
  • Clinical pathology: Leukocytosis (neutrophilia, lymphocytopenia), hypoglycemia, hyperbilirubinemia, hyperammonemia, increased serum bile acids, prolonged one-stage prothrombin time (OSPT), increased liver enzymes:
    1. Sorbitol dehydrogenase (SDH): Hepatocellular leakage enzyme; liver specific
    2. Aspartate aminotransferase (AST): Hepatocellular leakage enzyme; not liver specific, found in liver, muscle and erythrocytes
    3. Gamma-glutamyltransferase (GGT): Membrane bound induced enzyme; liver specific

    TYPICAL GROSS FINDINGS:

    1. Liver: Shrunken and flaccid “dish-rag liver” (classic lesion); stained by bile pigments; mottled appearance; enhanced lobular pattern because of necrosis of hepatocytes in centrilobular areas with congestion
    2. Icterus, ascites, +/- splenic congestion and petechial hemorrhages

    TYPICAL LIGHT MICROSCOPIC FINDINGS:

    1. Extensive bile pigment deposits in hepatocytes and Kupffer cells
    2. Diffuse mild fibroplasia primarily in portal areas
    3. Few surviving swollen and vacuolated periportal hepatocytes or sometimes finish depletion of parenchymal cells (lesion appears older than clinical symptoms suggest)
    4. Severe macrovesciular fatty change; may coalesce and form fatty cysts; dilated sinusoids and condensed reticulin framework
    5. No hemorrhage; acute necrosis typically not seen, instead hepatocyte loss is the main feature with collapsed or distortion of reticulin framework; prominent inflammation not a feature

    DIFFERENTIAL DIAGNOSIS:

  • Equine hepatic necrosis:
    1. Acute toxic hepatitis: Generally centrilobular necrosis with minimal inflammation; biliary hyperplasia; fibrosis with chronicity; +/- photosensitization
    2. Equine infectious anemia (equine lentivirus): Subacute; centrilobular fatty degeneration and hepatocellular loss; increased numbers of sinusoidal Kupffer cells; portal infiltration by lymphocytes and plasma cells extremely characteristic
    3. Pyrrolizidine alkaloid toxicity: Chronic; hepatocyte necrosis; megalocytosis; centrilobular fibrosis; bile duct proliferation and fibrosis
    4. Aflatoxicosis: At low doses, resembles pyrrolizidine alkaloid toxicity; at high doses, periacinar hepatocytes vanish and are replaced by a mixture of inflammatory cells, fibroblasts, and primitive vascular channels

    COMPARATIVE PATHOLOGY:

    1. Cullen JM, Stalker MJ.

      Liver and Biliary system. In: Maxie MG, ed. Jubb, Kennedy and Palmer’s Pathology of Domestic Animals. Vol 2. 6th ed. St. Louis, MO: Elsevier Ltd; 2016:313-314.

    2. Brown DL, Van Wettere AJ, and Cullen JM. Hepatobiliary System and Exocrine Pancreas. In: McGavin MD, Zachary JF, eds. PathologicBasisofVeterinaryDisease.

      What is horse serum allergy

      6th ed. St. Louis, MO: Elsevier; 2017:456.

    3. “Serum sickness” – a Type III hypersensitivity approximately 10 days after istration of antiserum or certain medications, characterized by generalized vasculitis with erythema, edema and urticaria of the skin, neutropenia, joint swelling and proteinuria
    4. Chandriani S, Skewes-Cox P, et al. Identification of a previously undescribed divergent virus from the Flaviviridae family in an outbreak of equine serum hepatitis. Proc Natl Acad Sci USA. 2013; 110(15):E1407-15.
    5. Divers TJ and Barton MH.

      Disorders of the Liver. In: Reed SM, Bayly WM, and Sellon DC, eds. Equine Internal Medicine. 4th ed. St. Louis, MO: Elsevier Ltd; 2018: 865-866.

    6. Hepatitis B virus causes similar lesions in human beings
    7. Divers TJ, Tennant BC, et al. New parvovirus associated with serum hepatitis in horses after inoculation of common biological product. Emerg Infect Dis. 2018; 24(2):303-310.

    REFERENCES:

    • Cullen JM, Stalker MJ. Liver and Biliary system. In: Maxie MG, ed.

      Jubb, Kennedy and Palmer’s Pathology of Domestic Animals. Vol 2. 6th ed.

      What is horse serum allergy

      St. Louis, MO: Elsevier Ltd; 2016:313-314.

    • Divers TJ and Barton MH. Disorders of the Liver. In: Reed SM, Bayly WM, and Sellon DC, eds. Equine Internal Medicine. 4th ed. St. Louis, MO: Elsevier Ltd; 2018: 865-866.
    • Chandriani S, Skewes-Cox P, et al. Identification of a previously undescribed divergent virus from the Flaviviridae family in an outbreak of equine serum hepatitis. Proc Natl Acad Sci USA. 2013; 110(15):E1407-15.
    • Brown DL, Van Wettere AJ, and Cullen JM. Hepatobiliary System and Exocrine Pancreas.

      In: McGavin MD, Zachary JF, eds. PathologicBasisofVeterinaryDisease. 6th ed. St. Louis, MO: Elsevier; 2017:456.

    • Divers TJ, Tennant BC, et al. New parvovirus associated with serum hepatitis in horses after inoculation of common biological product. Emerg Infect Dis. 2018; 24(2):303-310.

    Maybe it's the name that amplifies the dread horse people tend to feel when the grapevine rumors a neighborhood infection. Certainly, no one who's had to nurse a horse through to recovery wants a repeat experience, and anyone who's read John Steinbeck's The Red Pony about a young boy's first exposure to death and loss can't assist but expect the worst of the disease.

    Yes, strangles has a terrible name and a worse reputation. Horses who come below with a Streptococcus equi infection get an ugly helpful of ill, and they seem to be knocked out of training forever.

    "People own definitely gotten more panicked about strangles over the years," says George Sengstack, manager of Callithea Farm, a 60-horse boarding stable in Potomac, Maryland. "Fourteen years ago, before we had horses trailering in and out, I had a horse who got strangles. We kept him away from the other horses in a circular pen and were really careful [about using separate equipment]. He got better, and it wasn't a large ordeal."

    Sengstack's experience with strangles is more the norm than Steinbeck's fatal scenario, but the highly contagious disease can be a genuine blight on a stable of susceptible horses.

    Also called equine distemper, the infection typically begins 10 to 12 days after exposure to S. equi.

    First the horse experiences a high fever, depression, appetite loss and enlargement of the lymph nodes between the jawbones. Copious amounts of thick, yellow pus start draining from the nostrils, and before three weeks are up, the abscessed nodes at the throat may burst open to drain. The disease's descriptive name comes from the "strangling" noise produced as severely affected horses struggle to draw breaths into their obstructed airways. Aside from observing the obvious physical signs in diagnosis, veterinarians can run cultures of the nasal drainage to see if it contains the streptococcal organism.

    Exposure often occurs when a new horse, who's shedding the S.

    equi bacterium without visible signs of sickness, is introduced into a herd. The organisms spread from horse to horse through direct contact, such as touching muzzles, environmental contamination and shared equipment, such as feed buckets and bridles. Strangles spreads rapidly, producing large outbreaks in herds not previously exposed or vaccinated. The infection is especially aggressive in populations of foals and young horses. Most horses recover, but fatalities do happen, primarily from secondary pneumonia that takes hold in debilitated or immune-compromised animals. And every now and again, S.

    equi infect lymph nodes deeper within the body, producing a more dangerous condition called bastard strangles.

    Isolation is the single most effective means of controlling the spread of the disease. Infected horses generally show signs within two weeks of exposure, so preventing contact between potential carriers and a healthy herd for at least that endless should reduce contagion. Three- to four-week quarantine periods for newcomers or exposed horses are generally enough to slow or stop the spread of the disease.

    In textbook terms, then, strangles isn't really a large deal.

    It hardly ever kills or causes lasting damage to horses, and it's easily controlled by physical separation, the most basic of medical precautions. Yet the fact that strangles isn't effectively prevented or treated by the same means applied to other common equine diseases gives it a rather sinister cast. It must be some sort of super infection, correct, if treatment is iffy and vaccines aren't reliable? Well, not exactly. The myths and misconceptions surrounding strangles tend to overplay the current gaps in scientific knowledge about the disease. Given recent genetic advances in characterizing the strangles organism, truly effective prevention is no longer a pipe dream.

    Maybe it's the name that amplifies the dread horse people tend to feel when the grapevine rumors a neighborhood infection.

    Certainly, no one who's had to nurse a horse through to recovery wants a repeat experience, and anyone who's read John Steinbeck's The Red Pony about a young boy's first exposure to death and loss can't assist but expect the worst of the disease. Yes, strangles has a terrible name and a worse reputation. Horses who come below with a Streptococcus equi infection get an ugly helpful of ill, and they seem to be knocked out of training forever.

    "People own definitely gotten more panicked about strangles over the years," says George Sengstack, manager of Callithea Farm, a 60-horse boarding stable in Potomac, Maryland.

    "Fourteen years ago, before we had horses trailering in and out, I had a horse who got strangles. We kept him away from the other horses in a circular pen and were really careful [about using separate equipment]. He got better, and it wasn't a large ordeal."

    Sengstack's experience with strangles is more the norm than Steinbeck's fatal scenario, but the highly contagious disease can be a genuine blight on a stable of susceptible horses. Also called equine distemper, the infection typically begins 10 to 12 days after exposure to S. equi.

    First the horse experiences a high fever, depression, appetite loss and enlargement of the lymph nodes between the jawbones.

    Copious amounts of thick, yellow pus start draining from the nostrils, and before three weeks are up, the abscessed nodes at the throat may burst open to drain. The disease's descriptive name comes from the "strangling" noise produced as severely affected horses struggle to draw breaths into their obstructed airways. Aside from observing the obvious physical signs in diagnosis, veterinarians can run cultures of the nasal drainage to see if it contains the streptococcal organism.

    Exposure often occurs when a new horse, who's shedding the S. equi bacterium without visible signs of sickness, is introduced into a herd.

    What is horse serum allergy

    The organisms spread from horse to horse through direct contact, such as touching muzzles, environmental contamination and shared equipment, such as feed buckets and bridles. Strangles spreads rapidly, producing large outbreaks in herds not previously exposed or vaccinated. The infection is especially aggressive in populations of foals and young horses. Most horses recover, but fatalities do happen, primarily from secondary pneumonia that takes hold in debilitated or immune-compromised animals. And every now and again, S. equi infect lymph nodes deeper within the body, producing a more dangerous condition called bastard strangles.

    Isolation is the single most effective means of controlling the spread of the disease.

    Infected horses generally show signs within two weeks of exposure, so preventing contact between potential carriers and a healthy herd for at least that endless should reduce contagion. Three- to four-week quarantine periods for newcomers or exposed horses are generally enough to slow or stop the spread of the disease.

    In textbook terms, then, strangles isn't really a large deal. It hardly ever kills or causes lasting damage to horses, and it's easily controlled by physical separation, the most basic of medical precautions. Yet the fact that strangles isn't effectively prevented or treated by the same means applied to other common equine diseases gives it a rather sinister cast.

    It must be some sort of super infection, correct, if treatment is iffy and vaccines aren't reliable? Well, not exactly. The myths and misconceptions surrounding strangles tend to overplay the current gaps in scientific knowledge about the disease. Given recent genetic advances in characterizing the strangles organism, truly effective prevention is no longer a pipe dream.


    Scientific Contributions and papers

    • Ferrándiz R, Molina M, Enriquez C, Jarquin L. Introducción al estudio de los áfidos (Homoptera:Aphididae) de Nicaragua. Cienc Agr 1985;22:10-15.
    • Ferrándiz R, Gutierrez F.

      Conducta de prueba del áfido M. persicae sobre plantas infectadas con el virus del grabado del tabaco. Cienc Agr 1985;24:23-29.

    • Casas R, Djerf P, Häggström P, Ferrándiz R, Björkstén B. Fel d 1 and Fel d 1 — immune complexes in the serum of cat allergic children. Clin Exp Allergy,1998, 28,1258-63
    • Ferrándiz R, Casas R. Dreborg S, Einarsson R, Bonachea I, Chapman MD. Characterization of allergens from home dust mite Dermatophagoides siboney. Purification of Der s 1 and Der s 2 allergens. Clin Exp Allergy 1995;25:922-928
    • Ferrándiz R. Reseña bibliográfica sobre las especies de áfidos Aphis gossypii y Rhopalosiphon maidis.

      Cienc Agr 1981;8:39-57.

    • Ferrándiz R, Casas R, Dreborg S. Sensitization to Dermatophagoides siboney, Blomia tropicalis and other domestic mites in asthmatic patients. Allergy 1996;51:501-505.
    • Ferrandiz R. Allergenic characterization of the domestic mite Dermatophagoides siboney. Linköping University Medical Dissertation No.532. 1997.
    • Ferrándiz R, Gutierrez F. Adquisición e inoculación del virus del grabado del tabaco por Myzus persicae. Cienc Agr 1986;27:55-60.
    • Ferrándiz R, Gutierrez F. Effect of bell pepper plant age on tobacco etch virus transmission by M.

      persicae. Capsicum Newsletter 1985;4:71-72.

    • Henricson K., Andræ S., Gromell A., Ferrandiz R., Effect of therapeutic silk in the treatment of children with atopic eczema. A report of 11 cases in Sweden. Allergy, 2007; 62 (Suppl.83):322.
    • Larsson, I., Ferrandiz, R. Klarmajoritet av läkemedelskommittéer rekommenderar Anapen. Läkartidningen 2008; 105:2865.
    • Felix K, Ferrándiz R, Einarsson R, Dreborg S. Allergens of horse dander. Comparison between breeds and individual animals using immunoblotting. J Allergy Clin Immunol 1996:98:169-71.
    • Ferrándiz, R. Dreborg, S. Kvalster i husdamm orsakar dammallergin.

      Incitament 1996, 1-2:23-26.

    • Ferrándiz R, Casas R, Dreborg S, Einarsson R, Fernández B. Crossreactivity between Dermatophagoides siboney and other home dust mite allergens in sensitized asthmatic patients. Clin Exp Allergy 1995;25:929-934
    • Ferrandiz R. Missvisande rubrik om kvalsterallergiprevention. Läkartidningen 2007; 104(nr 1–2):59.
    • Ferrándiz R, Casas R, Dreborg S. Crossreactivity between Dermatophagoides siboney and other domestic mites. II. Analysis of individual cross-reacting allergens after SDS-PAGE and western blotting inhibition.

      Int Arch Allergy Immunol 1998; 116:206-214.

    • Ferrándiz R, Dreborg S. Analysis of individual crossreacting allergens between Dermatophagoides siboney and other mites by immunoblot inhibition. Int Arch Allergy Immunol 1997, 113:238-239.
    • Casas R, Ferrándiz R, Wihl Jan-Åke, Fernández B, Dreborg S. Biological activity of Dermatophagoides siboney and Blomia tropicalis on exposed and non-exposed individuals. Effect of patient selection on the standardization of mite extracts. Allergy, 1999,54:392-96
    • Larsson, I., Ferrandiz, R. Liten smärta och tillförlitlighet viktigt i livshotande situationer.

      Läkartidningen 2008; 105:2865.

    • Ferrandiz, R. Specialsilke vid atopiskt eksem. Läkartidningen 2007; 104:405.
    • Ferrándiz R, Becquer A. Reproducción y desarrollo de la forma áptera de Myzus persicae. Cienc Agr 1984;18:39-46.
    • Ferrandiz, R. Medicinskt silke är ett komplement. Läkartidningen 2007; 104:1530.
    • Ferrándiz R. Estudios de la transmisión de virus en el cultivo del pimiento. Reporte final de proyecto PPE 051, 1985.
    • Ferrándiz R, Gutierrez F. Reproducción y desarrollo de Aphis gossypii bajo condiciones controladas.

      Cienc Agr 1986;27:51-54.

    • Becquer A, Ferrándiz R. Poblaciones de Dactynotus ambrosiae sobre Parthenium hysterophorus. Cienc Agr 1981;15:7-14.
    • Ferrándiz R, Becquer A. Estudios de los principales insectos de la familia Aphididae vectores de virus que afectan los cultivos. Reporte final de proyecto PPE 04, 1981, 45 pp.
    • Caballero R, Suarez O, Ferrándiz R. Movimiento de la larva de Heliothis virescens sobre plantas de tabaco.

      Cienc Agr,

    • Ferrandiz RF, Persson Å, Bruzelius L. Effect of bed encasing on mite allergic children. A survey of 97 children in Sweden. J Allergy Clin Immunol 2008; 121(2):s295.
    • Becquer A, Ferrándiz R. Dinámica de las poblaciones de áfidos en plantaciones de frijol. Cienc Agr 1981;8:23-28.
    • Ferrándiz R, Casas R, Dreborg S. Purification and IgE binding capacity of Der s 3, a major allergen from Dermatophagoides siboney.

      Clin Exp Allergy 1997, 27:700-704.

    • Ferrándiz R, Becquer A. Nuevo reporte de plantas hospedantes para la especie Aphis craccivora en Cuba. Cienc Agr 1979;4:177-178. 32. Ferrándiz R, Becquer A. Reproducción y desarrollo de la forma áptera de Rhopalosiphon maidis bajo condicines controladas. Cienc Agr 1979;4:145-155.


    Professional and istrative experience

    2015 Medeca Pharma AB: General Manager

    2005-2015 Medeca Pharma AB: Product Manager and medical manager.

    1998-2005 Pharmaceutical company ALK Sverige AB: Sales representative

    1994-1997 University of Linköping: Researcher at Department of Pediatrics

    1986-1994 Pharmaceutical industry BioCen: Head of the Department of Allergens at the National Middle for Bioproducts (BioCen)

    1976-1986 Research Institute INIFAT, Academy of Sciences: Researcher at the Institute of Fundamental Investigation on Tropical Agriculture (INIFAT), Academy of Sciences: Investigations on virus transmission, plant virology and physiol­ogy of viral infection.

    Head of three diverse research projects. Head of the Department of Entomology. Head of the Plant Protection Department. PhD at the Academy of Science.



    Rafael Ferrandiz

    High resolution image

    Tel. +46 (0)70-256 34 32, Email: (first name).(last name)@medeca.se

    Born 1953.


    Education

    Ph.D at  Linköping Medical dissertation, Linköping, Sweden, November 1997.

    Ph.D.

    at Academy of Sciences, Havana, 1986.

    School of Biological Sciences, University of Havana, Cuba (1971-1975)


    Patents

    Ferrándiz R, Casas R, Labrada A. Production of allergenic extracts for diagnostics and immunotherapy. ONITEM, Havana, Cuba

    Ferrándiz R, Casas R , Dreborg S. Purification of major proteins from the home dust mite Dermatophagoides siboney. ONITEM, Havana, Cuba


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