• View in gallery

    Photomicrograph of a hepatic biopsy sample from an African gray parrot (Psittacus erithacus) with iron overload disease. The artifactual changes observed are due to the small size of the biopsy sample and slight crushing of the tissue. H&E stain; bar = 100 µm.

  • View in gallery

    Photomicrograph of a follow-up hepatic biopsy sample obtained after 14 months of treatment that consisted of feeding a low-iron, low-vitamin C diet, adding a black tea supplement to the bird's water, and administering deferoxamine. The artifactual changes observed are due to the small size of the biopsy sample and slight crushing of the tissue. H&E stain; bar = 100 µm.

  • 1.

    Sandmeier P, Clauss M, Donati OF, Chiers K, Kienzle E, Hatt JM. Use of deferiprone for the treatment of hepatic iron storage disease in three hornbills. J Am Vet Med Assoc. 2012;240:7581.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2.

    Rupley AE. Common diseases and treatments. In: Rupley AE, ed. Manual of Avian Practice. WB Saunders Co; 1997:264309.

  • 3.

    Trupkiewicz J, Garner MM, Juan-Salles C. Passeriformes, caprimulgiformes, coraciiformes, piciformes, bucerotiformes, and apodiformes. In: Mcaloose D, Terio KA, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. Elsevier; 2018:793818.

    • Search Google Scholar
    • Export Citation
  • 4.

    Eid R, Arab NT, Greenwood MT. Iron mediated toxicity and programmed cell death: a review and re-examination of existing paradigms. Biochim Biophys Acta Mol Cell Res. 2017;1864:399430.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5.

    Lumeij JT. Hepatology. In: Ritche BW, Harrison GJ, Harrison LR, eds. Avian Medicine: Principles and Applications. Wingers Publishing Inc, 1994;522537.

    • Search Google Scholar
    • Export Citation
  • 6.

    Koutsos E, Gelis S, Echols MS. Advancements in nutrition and nutritional therapy. In: Speer BL, ed. Current Therapy in Avian Medicine and Surgery. Elsevier; 2016:142176.

    • Search Google Scholar
    • Export Citation
  • 7.

    Garner M, West G, Talcott P. Five lorikeets with hemochromatosis associated with high concentrations of dietary iron. In: Proceedings Annual Conference of Association of Avian Veterinarians. Association of Avian Veterinarians; 2000:215216.

    • Search Google Scholar
    • Export Citation
  • 8.

    Rasidi EK, Xie S, Hsu C. Iron storage disease in a blue and gold macaw (Ara ararauna). In: Proceedings of Exoticscon. Exoticscon; 2019:384.

    • Search Google Scholar
    • Export Citation
  • 9.

    Rupiper DJ, Read DH. Hemochromatosis in a hawk-head parrot (Deroptyus accipitrinus). J Avian Med Surg. 1996;10:2427.

  • 10.

    O'Connor MR, Garner MM. Iron storage disease in African grey parrots (Psittacus erithacus) exposed to a carnivorous diet. J Zoo Wildl Med. 2018;49:172177.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11.

    Barton JC, Edwards CQ, eds. Hemochromatosis: Genetics, Pathophysiology, Diagnosis and Treatment. Cambridge University Press; 2000.

  • 12.

    Beutler E. Hemochromatosis: genetics and pathophysiology. Annu Rev Med. 2006;57:331347.

  • 13.

    Macwhirter P. Passeriformes. In: Ritche BW, Harrison GJ, Harrison LR, eds. Avian Medicine: Principles and Applications. Wingers Publishing Inc; 1994:11721199.

    • Search Google Scholar
    • Export Citation
  • 14.

    Rush EM, Wernick M, Beaufrere H, et al. Advances in clinical pathology and diagnostic medicine. In: Speer BL, ed. Current Therapy in Avian Medicine and Surgery. Elsevier; 2016:461530.

    • Search Google Scholar
    • Export Citation
  • 15.

    Matheson JS, Paul-Murphy JR, O'Brien RT, Steinberg H. Quantitative ultrasound, magnetic resonance imaging, and histologic image analysis of hepatic iron accumulation in pigeons (Columbia livia). J Zoo Wildl Med. 2007;38:222230.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16.

    Whiteside DP, Barker IK, Conlon PD, et al. Pharmacokinetics disposition of the oral iron chelator deferiprone in the domestic pigeon (Columba livia). J Avian Med Surg. 2007;21:121129.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17.

    Whiteside DP, Barker IK, Conlon PD, et al. Pharmacokinetics disposition of the oral iron chelator deferiprone in the white leghorn chicken. J Avian Med Surg. 2007;21:110120.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18.

    Hoefer HL, Orosz S, Dorrestein GM. The gastrointestinal tract. In: Altman RB, Clubb SL, Dorrestein GM, Quesenberry K, eds. Avian Medicine and Surgery. WB Saunders Co; 1997:412453.

    • Search Google Scholar
    • Export Citation
  • 19.

    Cornelissen H, Ducatelle R, Roles S. Successful treatment of a channel-billed toucan (Ramphastos vitellinus) with iron storage disease by chelation therapy: sequentual monitoring of the iron content of the liver during the treatment period by quantitative chemical and image analyses. J Avian Med Surg. 1995;9:131137.

    • Search Google Scholar
    • Export Citation
  • 20.

    Olsen GP, Russell KE, Dierenfeld E, Phalen DN. A comparison of four regimens for treatment of iron storage disease using the European starling (Sturnus vulgaris) as a model. J Avian Med Surg. 2006;20:7479.

    • Search Google Scholar
    • Export Citation
  • 21.

    Carpenter JW, ed. Exotic Animal Formulary. 5th ed. Elsevier; 2018:248252.

  • 22.

    Gancz AY, Wellehan JF, Boutette J, et al. Diabetes mellitus concurrent with hepatic haemosiderosis in two macaws (Ara severa, Ara militaris). Avian Pathol. 2007;36:331336.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23.

    West GD, Garner MM, Talcott PA. Hemochromatosis in several species of lories with high dietary iron. J Avian Med Surg. 2001;15:297301.

    • Search Google Scholar
    • Export Citation
  • 24.

    McDonald DL, Jaensch S, Harrison GJ, et al. Health and nutritional status of wild Australian psittacine birds: An evaluation of plasma and hepatic mineral levels, plasma biochemical values, and fecal microflora. J Avian Med Surg. 2010;24:288298.

    • PubMed
    • Search Google Scholar
    • Export Citation

Advertisement

Pathology in Practice

Stephanie Lamb DVM, DABVP1, Drury Reavill DVM, DABVP, DACVP2, and Ethan Biswell DVM, MS, DACVP3
View More View Less
  • 1 Arizona Exotic Animal Hospital, Mesa, AZ
  • | 2 Zoo/Exotic Pathology Service, Carmichael, CA
  • | 3 Zoetis Reference Laboratories, Louisville, KY

Abstract

In collaboration with the American College of Veterinary Pathologists

Abstract

In collaboration with the American College of Veterinary Pathologists

History

A 25-year-old male (determined by DNA testing) Congo African gray parrot (Psittacus erithacus) was presented for a wellness examination. The bird's diet consisted of a mixture of parrot pellets (Zupreem Fruit Blend Premium Daily Bird Food; Premium Nutritional Products Inc), seeds, and nuts combined with fresh table items the owner would provide daily. These items varied but could include various vegetables (peas, corn, lima beans, green beans, and squash), fruits (cantaloupe, apple, pear, and banana), eggs, fish, and pasta. Results of a physical examination were unremarkable. A CBC and serum biochemistry panel were performed.

Clinical and Clinicopathologic Findings

Results of the CBC were normal, but serum bile acids and cholesterol concentrations were high (Table 1). It was recommended that the patient be fed a more balanced diet for psittacines and that the seeds, eggs, and fish be removed from the diet. The owner was instructed to feed a commercially available pelleted feed (Adult Lifetime; Harrison's Bird Foods) as 80% of the diet, with the remaining 20% of the diet consisting of fresh table items, including vegetables and fruits. The owner was also instructed to encourage the patient to exercise and to feed a milk thistle supplement (Nature's Answer).

Table 1

Serum bile acids and cholesterol concentrations and lactate dehydrogenase (LDH) activity in a 25-year-old African gray parrot (Psittacus erithacus).

Date of testingBile acids (µmol/L)Cholesterol (mg/dL)LDH (U/L)
5/27/201691.6360293
6/30/201746.2388716
8/24/201774.1347254
8/31/2018115.4292630
11/6/2018296.3330220

The patient was presented for multiple follow-up examinations and repeated evaluations of the CBC and serum biochemistry profile over the next 30 months. The physical examination findings remained unchanged. Although it had been recommended that the patient receive the milk thistle supplement continuously, the owner had intermittently stopped and started administration over this time period. The owner had switched to the recommended commercially available parrot pellet and also gave the bird bread (Bird Bread Mix Original; Harrison's Bird Foods), a scrambled or hard-boiled egg daily, apple, cantaloupe, banana, frozen organic peas, corn, lima beans, and seeded toast with peanut butter. It was again recommended that the owner discontinue feeding the bird eggs.

Follow-up blood work over the 30-month time period revealed slight alterations in serum bile acids and cholesterol concentrations and lactate dehydrogenase activity (Table 1), with the general trend being toward increases in values indicative of altered hepatic function. Radiographs were obtained during this period, but no abnormalities were observed. Owing to the fact that birds are known to mask signs of illness, hepatic biopsy of the liver was recommended to help identify a cause for the increase in serum bile acids concentration.

For the hepatic biopsy, feathers were plucked over the caudal aspect of the coelom, and the surgical site was prepared with chlorhexidine and alcohol scrub. A ventral midline coeliotomy with a transverse incision to the left was made. The liver was identified, and a segment was collected for histopathologic evaluation. The incision was closed routinely, and recovery from surgery was uneventful.

Formulate differential diagnoses, then continue reading.

Histopathologic Findings

Multiple aggregates of Kupffer cells containing extensive accumulations of golden-brown cytoplasmic pigments were present throughout the liver (Figure 1). Individualized Kupffer cells with golden-brown cytoplasmic pigment were also seen diffusely in hepatic sinusoids, and moderate numbers of hepatocytes contained golden-brown or blue-gray cytoplasmic pigments. There was one area that was interpreted as mild fibroplasia that appeared to be associated with a portal triad. Results were consistent with iron overload. Examination of a section of the liver stained with Prussian blue stain revealed that the pigmented granules within hepatocytes and Kupffer cells were iron granules, confirming the diagnosis of iron overload disease.

Figure 1
Figure 1

Photomicrograph of a hepatic biopsy sample from an African gray parrot (Psittacus erithacus) with iron overload disease. The artifactual changes observed are due to the small size of the biopsy sample and slight crushing of the tissue. H&E stain; bar = 100 µm.

Citation: Journal of the American Veterinary Medical Association 259, S2; 10.2460/javma.21.04.0209

A portion of the hepatic biopsy sample was submitted to the Colorado State University Veterinary Diagnostic Laboratory for quantitative iron analysis by means of flame atomic absorption spectroscopy. A modified dry ash procedure was used for sample preparation. The iron content was 988 ppm.

Morphologic Diagnosis and Case Summary

Morphologic diagnosis and case summary: iron overload disease in an African gray parrot.

Comments

Iron overload disease is a condition characterized by accumulation of excessive amounts of iron within an organ, resulting in cellular damage. It most frequently affects the liver, with the most common lesions being hepatocellular degeneration or necrosis, hepatic cord disruption, periportal fibrosis, bile duct hyperplasia, nodular hyperplasia, and, with severe chronic disease, cirrhosis. Iron deposits in other tissues are usually not associated with cellular or architectural changes.13

Iron is a biologically essential element (especially in hemoglobin) and is a catalyst for chemical reactions that involve free radical formation, which can lead to cellular damage by inducing oxidative stress.4 Iron overload disease has been described in several captive avian species including mynahs and starlings (Sturnidae) and, most commonly, toucans (Rhamphastidae).1,2,5,6 In psittacines, it has been identified in lorikeets, a blue and gold macaw (Ara ararauna), a hawk-head parrot (Deroptyus accipitrinus), and African gray parrots (Psittacus erithacus).710

The etiology of iron overload disease is unknown. In mammals, genetics have been implicated, but in birds, excessive iron in the diet has been suggested to play a role.1,2,57,11,12 Iron is absorbed from the intestines and is transported hematogenously via transferrins to eventually be stored as hemosiderin or ferritin in hepatocytes and Kupffer cells in the liver, siderophages in the spleen, and cells in the bone marrow. The bioavailability of dietary iron and absorption from the intestines are increased by dietary vitamin C and reduced by dietary tannins and phytates.3 It is thought that species of birds susceptible to iron overload disease have evolved to eat foods that are low in iron. When iron is in greater supply in the diet, their ability to downregulate the absorption of iron is limited, and they will store absorbed iron in the liver in the form of hemosiderin.6 Other potential causes for iron overload disease have been postulated to be an inherited metabolic defect and altered intestinal absorption.2

Antemortem diagnosis of iron overload disease requires histopathologic evaluation of a hepatic biopsy sample. This sample can also be used for chemical analysis or quantitative image analysis with spectrometry to determine iron concentration.1,7,13,14 MRI has also been used to measure iron content in pigeons (Columba livia domestica) and hornbills.1,15 However, the small size of avian patients may make use of this diagnostic method challenging.1

In cases of early iron overload disease, treatment involves management with low-iron, low-vitamin C diets, addition of tannin to the water, phlebotomy, and administration of iron chelators. In cases of advanced disease when the patient has developed ascites, aspiration of fluid is necessary in addition to the previously mentioned treatments.2

Iron chelation agents can be either oral or injectable. Deferiprone is an oral iron chelator and has been studied in both chickens and pigeons at a dosage of 50 mg/kg, PO.16,17 Deferiprone has been reported to have been used in hornbills at a dosage of 75 mg/kg, PO, once daily for 3 months and in a blue and gold macaw at a dosage of 50 mg/kg, PO, once daily for 3 months.1,8

Deferoxamine is an injectable iron chelator that has been used in birds to treat iron overload disease.2,18,19 A channel-billed toucan (Ramphastos vitellinus) with this condition was treated with deferoxamine at a dosage of 100 mg/kg, SC, once daily for 4 months.19 In a study with starlings, deferoxamine was used at this same dosage along with a low-iron diet to treat high hepatic iron content. The mean nonheme iron content in the starlings’ livers decreased from 3,132 to 450 ppm.20 Other dosages and routes of administration exist for deferoxamine, with a dosage of 40 to 50 mg/kg, IM, every 12 hours for 14 days as one suggestion.21

Hepatic iron content can vary widely in birds. One report22 indicates a range of 60 to 300 ppm in chickens, and chemical analysis of formalin-preserved hepatic samples from lories yielded a range of 60 to 1,000 ppm.23 In a study24 involving 3 species of cockatoos, frozen liver samples from wild-caught birds evaluated by inductively coupled plasma spectrometry had hepatic iron content ranging from 110 to 1,030 ppm, with significant differences in hepatic iron content among species.

Treatments for the patient in the present report included feeding a low-iron, low-vitamin C diet and adding a black tea supplement (Iron Out; Greywood Manor Tea and Provisions) to the bird's water because of the supplement's tannin content. Phlebotomies were performed, with 10% of the blood volume removed every 2 weeks for 4 treatments. Treatment with deferoxamine was also initiated.

Fourteen months after the first biopsy, a second hepatic biopsy was performed on the same liver lobe to determine whether the patient's condition was improving. The histopathologic diagnosis was the same as for the first hepatic sample; however, the second sample had a reduced degree of fibroplasia (Figure 2). Quantitative analysis of iron content was performed as previously described, except that a larger sample was used, and the iron content this time was 8,930 ppm. This result was unexpected, because the histologic appearance had improved; however, the difference could be explained by the difference in sample size. The first sample weighed 0.11 mg, and the second sample weighed 2.58 mg. The method for quantitative iron analysis by flame atomic absorption spectroscopy has been validated for sample sizes of ≥ 10 mg. Therefore, the results that were obtained may not have been accurate, especially for the first sample.

Figure 2
Figure 2

Photomicrograph of a follow-up hepatic biopsy sample obtained after 14 months of treatment that consisted of feeding a low-iron, low-vitamin C diet, adding a black tea supplement to the bird's water, and administering deferoxamine. The artifactual changes observed are due to the small size of the biopsy sample and slight crushing of the tissue. H&E stain; bar = 100 µm.

Citation: Journal of the American Veterinary Medical Association 259, S2; 10.2460/javma.21.04.0209

Following the second hepatic biopsy, treatment with deferoxamine was continued, along with the previous diet and tea supplementation. Repeated blood work revealed normal hepatic biochemical results. Repeated biopsy of the liver was recommended but not permitted. Follow-up blood work was performed every 3 to 6 months for monitoring, and as of 24 months after deferoxamine treatment was initiated, no abnormally high hepatic biochemical results have been identified.

Acknowledgments

Dr. Reavill is deceased.

No external funding was used in this case. The authors declare that there were no conflicts of interest.

References

  • 1.

    Sandmeier P, Clauss M, Donati OF, Chiers K, Kienzle E, Hatt JM. Use of deferiprone for the treatment of hepatic iron storage disease in three hornbills. J Am Vet Med Assoc. 2012;240:7581.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2.

    Rupley AE. Common diseases and treatments. In: Rupley AE, ed. Manual of Avian Practice. WB Saunders Co; 1997:264309.

  • 3.

    Trupkiewicz J, Garner MM, Juan-Salles C. Passeriformes, caprimulgiformes, coraciiformes, piciformes, bucerotiformes, and apodiformes. In: Mcaloose D, Terio KA, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. Elsevier; 2018:793818.

    • Search Google Scholar
    • Export Citation
  • 4.

    Eid R, Arab NT, Greenwood MT. Iron mediated toxicity and programmed cell death: a review and re-examination of existing paradigms. Biochim Biophys Acta Mol Cell Res. 2017;1864:399430.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5.

    Lumeij JT. Hepatology. In: Ritche BW, Harrison GJ, Harrison LR, eds. Avian Medicine: Principles and Applications. Wingers Publishing Inc, 1994;522537.

    • Search Google Scholar
    • Export Citation
  • 6.

    Koutsos E, Gelis S, Echols MS. Advancements in nutrition and nutritional therapy. In: Speer BL, ed. Current Therapy in Avian Medicine and Surgery. Elsevier; 2016:142176.

    • Search Google Scholar
    • Export Citation
  • 7.

    Garner M, West G, Talcott P. Five lorikeets with hemochromatosis associated with high concentrations of dietary iron. In: Proceedings Annual Conference of Association of Avian Veterinarians. Association of Avian Veterinarians; 2000:215216.

    • Search Google Scholar
    • Export Citation
  • 8.

    Rasidi EK, Xie S, Hsu C. Iron storage disease in a blue and gold macaw (Ara ararauna). In: Proceedings of Exoticscon. Exoticscon; 2019:384.

    • Search Google Scholar
    • Export Citation
  • 9.

    Rupiper DJ, Read DH. Hemochromatosis in a hawk-head parrot (Deroptyus accipitrinus). J Avian Med Surg. 1996;10:2427.

  • 10.

    O'Connor MR, Garner MM. Iron storage disease in African grey parrots (Psittacus erithacus) exposed to a carnivorous diet. J Zoo Wildl Med. 2018;49:172177.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11.

    Barton JC, Edwards CQ, eds. Hemochromatosis: Genetics, Pathophysiology, Diagnosis and Treatment. Cambridge University Press; 2000.

  • 12.

    Beutler E. Hemochromatosis: genetics and pathophysiology. Annu Rev Med. 2006;57:331347.

  • 13.

    Macwhirter P. Passeriformes. In: Ritche BW, Harrison GJ, Harrison LR, eds. Avian Medicine: Principles and Applications. Wingers Publishing Inc; 1994:11721199.

    • Search Google Scholar
    • Export Citation
  • 14.

    Rush EM, Wernick M, Beaufrere H, et al. Advances in clinical pathology and diagnostic medicine. In: Speer BL, ed. Current Therapy in Avian Medicine and Surgery. Elsevier; 2016:461530.

    • Search Google Scholar
    • Export Citation
  • 15.

    Matheson JS, Paul-Murphy JR, O'Brien RT, Steinberg H. Quantitative ultrasound, magnetic resonance imaging, and histologic image analysis of hepatic iron accumulation in pigeons (Columbia livia). J Zoo Wildl Med. 2007;38:222230.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16.

    Whiteside DP, Barker IK, Conlon PD, et al. Pharmacokinetics disposition of the oral iron chelator deferiprone in the domestic pigeon (Columba livia). J Avian Med Surg. 2007;21:121129.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17.

    Whiteside DP, Barker IK, Conlon PD, et al. Pharmacokinetics disposition of the oral iron chelator deferiprone in the white leghorn chicken. J Avian Med Surg. 2007;21:110120.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18.

    Hoefer HL, Orosz S, Dorrestein GM. The gastrointestinal tract. In: Altman RB, Clubb SL, Dorrestein GM, Quesenberry K, eds. Avian Medicine and Surgery. WB Saunders Co; 1997:412453.

    • Search Google Scholar
    • Export Citation
  • 19.

    Cornelissen H, Ducatelle R, Roles S. Successful treatment of a channel-billed toucan (Ramphastos vitellinus) with iron storage disease by chelation therapy: sequentual monitoring of the iron content of the liver during the treatment period by quantitative chemical and image analyses. J Avian Med Surg. 1995;9:131137.

    • Search Google Scholar
    • Export Citation
  • 20.

    Olsen GP, Russell KE, Dierenfeld E, Phalen DN. A comparison of four regimens for treatment of iron storage disease using the European starling (Sturnus vulgaris) as a model. J Avian Med Surg. 2006;20:7479.

    • Search Google Scholar
    • Export Citation
  • 21.

    Carpenter JW, ed. Exotic Animal Formulary. 5th ed. Elsevier; 2018:248252.

  • 22.

    Gancz AY, Wellehan JF, Boutette J, et al. Diabetes mellitus concurrent with hepatic haemosiderosis in two macaws (Ara severa, Ara militaris). Avian Pathol. 2007;36:331336.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23.

    West GD, Garner MM, Talcott PA. Hemochromatosis in several species of lories with high dietary iron. J Avian Med Surg. 2001;15:297301.

    • Search Google Scholar
    • Export Citation
  • 24.

    McDonald DL, Jaensch S, Harrison GJ, et al. Health and nutritional status of wild Australian psittacine birds: An evaluation of plasma and hepatic mineral levels, plasma biochemical values, and fecal microflora. J Avian Med Surg. 2010;24:288298.

    • PubMed
    • Search Google Scholar
    • Export Citation

Contributor Notes

Corresponding author: Dr. Lamb (stephlovesbirds@hotmail.com)