Vitamin D Toxicosis in a Blue-Tongued Skink (Tiliqua scincoides) Presented with Epistaxis and Tongue Discoloration
Abstract
A 10-yr-old intact blue-tongued skink (Tiliqua scincoides) of unknown sex presented for epistaxis and dyspnea. On physical examination, dysecdysis, necrosis of the tip of the tail, and a pink discoloration of the proximal third of the tongue were noted in addition to epistaxis, dyspnea, and tachypnea. Clinical pathology findings included marked polychromatophilia, moderate heterophilia with signs of toxicity, a regenerative left shift, and moderate hyperglycemia. Because of the suspicion of an infectious etiology, antibiotics were prescribed. Meloxicam was also administered without clinical improvement. Swelling of the pharyngeal area was noted on whole-body computed tomographic and magnetic resonance imaging. Oro-pharyngeal endoscopic-guided biopsies were performed under general anesthesia. Histology was consistent with moderate erosion and goblet cell hyperplasia. Plasma 25-hydroxyvitamin D3 concentration was 768 nmol/L and was interpreted as possible vitamin D toxicosis. Prednisolone was prescribed to enhance calciuresis and treat potential vasculitis, but the skink was ultimately euthanized. Histopathologic examination was consistent with vitamin D toxicosis. The diet of this skink mostly consisted of greens dusted with a supplement containing calcium and vitamin D3. This case report describes the challenges associated with antemortem diagnosis of a vitamin D toxicosis, even with current imaging techniques. It highlights that specific reference intervals should be established for 25-hydroxyvitamin D3 and ionized calcium concentrations in various reptile species. Clinicians presented with a blue-tongued skink displaying a pink tongue or tail necrosis should consider vitamin D toxicosis in their differential diagnosis.
Case Report
A 10-yr-old intact blue-tongued skink (Tiliqua scincoides) of unknown sex presented for an acute onset of bilateral epistaxis and dyspnea over 6 h. The lizard's diet consisted of greens, such as spring mix, cucumbers, peas, carrots, and zucchinis, and a daily dusting (sprinkle) of a supplement containing calcium and vitamin D3 (ReptiVite with D3, ZooMed, San Luis Obispo, CA, USA). In addition, protein sources were provided every 2–3 days and included canned snails (Can'O snails, ZooMed), rarely canned Erionota trax caterpillars (Can'O pillars, ZooMed), occasional pinkie mice (less than once a month), cooked chicken eggs, fish meat, shrimp, and mussels. Occasionally, the owner also offered commercial powdered food (Repashy Crested Gecko Classic, Repashy Superfood, Saskatoon, SK, Canada). Table 1 summarizes guaranteed analyses of the commercial items included in this diet. The owner reported that the lizard had refused live insects for the past 2 yr, and this was attributed to discomfort while swallowing the prey. Ultraviolet B fluorescent lighting was provided, but the bulb had not been changed in the past year. The remainder of the environment was adequate for the species, including a warm spot at 35°C (95°F) and a cooler area at 25°C (77°F). Heat was provided by two ceramic heat lamps and an under-tank heating pad at the warm end. In addition, one heat lamp was installed at the cooler end of the terrarium. The terrarium temperature was measured continuously by a digital thermometer. The terrarium humidity was 40–50%. The substrate was aspen wood shavings (Aspen snake bedding, ZooMed).
On physical examination, abnormal findings included retained shed, coagulated blood on the nostrils, dyspnea, tachypnea (respiratory rate of 36 movements per minute), a discoloration of the tip of the tail, and a pink discoloration of the proximal third of the tongue (Fig. 1). The owner reported that the tongue and tail discoloration had been present for years and attributed the tail lesion to a previous episode of dysecdysis. Initial differentials included head trauma, ulcerative rhinitis or pharyngitis, an ulcerated mass within the respiratory tract, and a coagulation disorder or vasculitis. Retained shed were gently removed from the nostrils and oxygen was provided in an incubator (Snyder Manufacturing, Centennial, CO, USA) through a humidifier (Oxyvac Medical Instruments, Incheon, Korea) with a flow of 2 L/min and an FiO2 ranging from 30 to 38%. The dyspnea resolved within an hour, and the respiratory rate was 8 movements per minute at the time of discharge. Because of time constraints, the owner elected to come back for a recheck examination to perform hematology, plasma biochemistry, and a whole-body computed tomographic (CT) examination to evaluate the pulmonary parenchyma, bronchi, and bronchioles.
Citation: Journal of Herpetological Medicine and Surgery 30, 4; 10.5818/19-04-193.2
On recheck examination the following week, decreased appetite was reported. Blood was obtained from the ventral coccygeal vein. Marked polychromatophilia and moderate heterophilia (8.85 × 109/L; reference interval: 0.402–7.983 × 109/L; ZIMS Expected Test Results for Tiliqua scincoides, 2015) with toxicity and a regenerative left shift (non-segmented heterophils: 1.64 × 109/L) were detected on hematology. Moderate hyperglycemia (13.3 mmol/L [31.7 mg/dl]; reference interval: 4.3–11.2 mmol/L; ZIMS Expected Test Results for Tiliqua scincoides, 2015) was noted on the plasma biochemistry panel. Other parameters, including plasma creatine kinase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, total proteins, total calcium, phosphorus, uric acid, and bile acids, were unremarkable. Of note, the plasma total calcium concentration was 3.31 mmol/L (13.24 mg/dl; reference interval: 2.5–4.4 mmol/L; ZIMS Expected Test Results for Tiliqua scincoides, 2015) and the plasma phosphorus concentration was 1.08 mmol/L (3.27 mg/dl; reference interval: 0.77–2.92 mmol/L; ZIMS Expected Test Results for Tiliqua scincoides, 2015). The calcium-phosphorus solubility index was 3.6 mmol2/L2 (43 mg2/dl2).
A whole-body CT (GE Lightspeed 16, GE Healthcare, Mississauga, ON, Canada) was performed without sedation. No IV contrast was administered because of the possibility for vasculitis and the risk of worsening the necrotic distal tail lesion. Marked swelling of the pharyngeal wall resulted in a partial stenosis. To further evaluate the pharyngeal swellings, the images were compared with CT findings from a healthy blue-tongued skink (Fig. 2A, B) and to published anatomy (Baird, 1970). In addition, the auditory tubes had a narrowed diameter; otherwise, the pulmonary tissue was unremarkable. A scant amount of coelomic fluid was present, which displayed an attenuation of 4.5 Hounsfield units. This finding was compatible with a nonhemorrhagic coelomic effusion. Although rare mineralized foci were identified in both kidneys (Fig. 2D), no hepatic lesions were noted.
Citation: Journal of Herpetological Medicine and Surgery 30, 4; 10.5818/19-04-193.2
Dietary changes were recommended, including replacement of the vitamin supplement by a calcium supplement without vitamin D, and discontinuation of any dietary item that was not part of the natural diet. In particular, seafood products and fish meat were discontinued due to concerns about a high cholesterol content of the diet. The owner was also instructed to change the ultraviolet B light. Because of the suspicion of an infectious etiology (hematology results), a broad-spectrum antibiotic, ceftiofur at 11 mg/kg IM q 48 h (Excede, Pfizer, Saint-Laurent, QC, Canada) was administered for 8 days. The patient's condition worsened, and it was represented for anorexia. The owner was instructed to discontinue the ceftiofur treatment, and the lizard ate a large meal of snails on the following day.
A distal progression of the tongue discoloration was noted on subsequent examination 10 days later. The distal tail necrotic area was stable in length. Serous discharge was noted on the nares, and no recurrence of dyspnea was reported. Owing to the lack of clinical improvement, whole-body magnetic resonance imaging (MRI), followed by pharyngeal endoscopy and esophagoscopy, were planned in an attempt to localize a potential mass in the head region and to obtain tissue biopsies. Vitamin K1 (Veda-K1 injection 10-mg/ml solution, Vedco, Saint-Joseph, MO, USA) IM was administered at 0.5 mg/kg 2 days before the biopsy. Premedication with morphine 1 mg/kg (Morphine LP, Sandoz Canada, Boucherville, QC, Canada) IM was administered 3.5 h before the procedure, as described previously (Kehoe et al., 2016). Alfaxalone 10 mg/kg (Alfaxan, Jurox Animal Health, New South Wales, Australia) and midazolam 0.4 mg/kg (Midazolam, Sandoz Canada) were administered IM for induction. The lizard was intubated with a 2.0-mm uncuffed endotracheal tube, maintained on isoflurane 2–3% (Isoflurane, USP, Fresenius Kabi Animal Health, ON, Canada), and a whole-body MRI was acquired (GE Signa 1.5T HDxt, GE Healthcare). Again, no IV contrast was administered due to concerns for vasculitis. A persistent diffuse irregular pharyngeal wall thickening was noted (Fig. 2C). Hyperintense fluid compatible with secretions or acute hemorrhage was also noted on the T2-weighted images ventrally in the left tympanic cavity and in the pharynx near the esophageal entrance. No other lesion was detected in the head or the lungs. The lizard was determined to be a female based on the presence of ovarian follicles. Persistent scant coelomic effusion was also noted.
Pharyngeal endoscopy and esophagoscopy were performed with a 2.7-mm 30° angle rigid endoscope (Karl Storz Endoscopy Canada Ltd., Mississauga, ON, Canada). Diffuse symmetrical hypervascularization of the pharynx was noted (Fig. 3). Eight pharyngeal biopsies were obtained with a biopsy forceps (Elliptical cup, 5Fr, Karl Storz Endoscopy Canada Ltd.) through an operating shield, avoiding large vessels. Biopsy samples were fixed in formalin and processed routinely. The lizard recovered uneventfully. Subcutaneous lactated Ringer's solution (Baxter Corporation, Mississauga, ON, Canada) was administered at 15 ml/kg. Pending biopsy results, azithromycin 10 mg/kg PO q 48 h (Azithromycin Pediatric Suspension, Sandoz Canada) and meloxicam 0.2 mg/kg PO q 24 h for 5 days (Apo-meloxicam, Apotex Inc., Toronto, ON, Canada) were prescribed. The owner was instructed to offer additional syringe feeding with a liquid diet for omnivorous animals (Emeraid Omnivore Care, Lafeber Company, Cornell, IL, USA), with a calcium content of 1%. Daily baths in lukewarm water were performed to maintain hydration. Pharyngeal biopsies were consistent with moderate erosion with abundant mucus production of undetermined etiology.
Citation: Journal of Herpetological Medicine and Surgery 30, 4; 10.5818/19-04-193.2
On recheck examination 1 week later, a proximal progression of the tongue discoloration was noted. The owner reported continued anorexia but syringe fed the skink daily with a liquid diet. Based on the histopathology results, an infectious process was considered less likely. Further examination of the imaging findings, including mineralized foci in both kidneys, in conjunction with the historical diet, directed us to consider vitamin D toxicosis. A blood sample was obtained from the ventral coccygeal vein for recheck plasma biochemistry and serum vitamin D testing (Veterinary Diagnostic Laboratory, Michigan State University, East Lansing, USA). Plasma biochemistry values were within normal limits, except for a severe hyperglycemia of 31.7 mmol/L (576 mg/dl; reference interval: 4.3–11.2 mmol/L), which was attributed to a high-sugar meal given 12 h earlier (Repashy meal replacement powder, Repashy Superfood). The plasma total calcium concentration was 2.88 mmol/L (11.52 mg/dl; reference interval: 2.5–4.4 mmol/L), and the plasma phosphorus concentration was 1.49 mmol/L (4.52 mg/dl; reference interval: 0.77–2.92 mmol/L). The calcium-phosphorus solubility index was 4.3 mmol2/L2 (52 mg2/dl2).
The 25-hydroxyvitamin D concentration, measured by radioimmunoassay, was 768 nmol/L. There was no reference interval available for this species, but the laboratory did report a median concentration of 312 nmol/L for 27 blue-tongued skinks with various clinical histories that were tested in their laboratory (Michigan State University, personal communication). The ionized calcium was 1.68 mmol/L. Unfortunately, there is no reference interval for this species; however, this measure was higher than references for other lizards (e.g., green iguana [Iguana iguana], 1.47 ± 0.105 mmol/L; Dennis et al., 2001). Parathormone could not be measured, but this test has not been validated in lizards. Because of the suspicion of vitamin D toxicosis, the lizard was given a poor prognosis, but the owner declined hospitalization or euthanasia. Subcutaneous lactated Ringer's solution was administered at 15 ml/kg, and prednisolone at 0.5 mg/kg PO q 24 h was prescribed to increase calciuresis and to manage a potential vasculitis. Unfortunately, the skink continued to deteriorate, with a proximal progression of the tail necrosis and increasing lethargy. On a recheck examination 40 days after the initial presentation, a foul-smelling odor was found originating from the tail. Euthanasia and a complete necropsy were elected by the owner. After induction with midazolam, alfaxalone, and isoflurane as previously described, intracardiac injection of pentobarbital sodium (Euthansol, Merck Animal Health, Kirkland, QC, Canada) was performed. Cessation of heart beat was confirmed within 10 min.
On gross necropsy, the distal tip of the tongue showed a black discoloration, whereas the proximal part was pink. The caudal part of the tail presented a gray discoloration over 10 cm, separated from healthy tissue by a thin circumferential hemorrhagic zone. Serous liquid was noted surrounding the lung, which appeared edematous and congested. The liver appeared subjectively enlarged with rounded margins. Tissues were fixed and processed routinely.
On histopathologic examination, slight-to-moderate mineralization of the media of the large vessels at the heart base was noticed with Van Kossa stain (Fig. 4). A few ventricular cardiomyocytes appeared calcified. Multifocal calcifications and necrosis of skeletal and cardiac muscles were present, involving pharyngeal myocytes and myocytes of coccygeal muscles. This was associated with degenerescence and necrosis of the tail and tongue. Tongue vessels and adjacent tissues were markedly infiltrated by cocci, fibrin, heterophils, lymphoplasmacytic cells, and melanomacrophages. A slight heterophilic infiltration of the laryngeal lamina propria was also noted. No lesions were detected in the nasal cavities. Acute-to-subacute severe pulmonary hemorrhage was detected, and Prussian blue stain detected hemosiderophages, indicating antemortem bleeding. Hepatic lipidosis and hepatic thrombosis were present with a focal calcification surrounded by melanomacrophages. A few renal tubules contained mineralized material in their lumen or epithelium. Collecting ducts contained slightly basophilic filamentous material, and rare renal vessels were filled with fibrin and mineralized material. Overall, many of these lesions were compatible with the clinical diagnosis of vitamin D toxicosis.
Citation: Journal of Herpetological Medicine and Surgery 30, 4; 10.5818/19-04-193.2
Discussion
Vitamin D toxicosis was diagnosed in this blue-tongued skink presented for epistaxis, progressive dysorexia associated with uncomfortable food prehension, and pink discoloration of the tongue. In retrospect, the epistaxis likely arose from chronic bleeding in the respiratory tract and was associated with an underlying vascular injury. On CT, MRI, and necropsy, no lesion was noted in the nasal cavity. Therefore, blood most likely originated from the respiratory tract and reached the nasal cavity through the choana, causing epistaxis.
In lizards, calcium homeostasis is regulated by parathormone (source parathyroid glands), calcitonin (source ultimobranchial body), and vitamin D compounds (Klaphake, 2010). Calcitriol, or 1,25-dihydroxyvitamin D3, is the active form of vitamin D3 and is formed by the hydroxylation of cholecalciferol in the liver and kidney (Mellanby et al., 2005). Calcitriol increases gastrointestinal phosphorus and calcium absorption through increased calbindin in the enterocytes (Swenson and Bradley, 2013). It also enhances osteoclastic mobilization of osseous calcium stores, renal reabsorption of calcium, and phosphorus excretion (Klaphake, 2010). Once the calcium-phosphorus solubility index reaches a critical threshold, tissular metastatic calcification can occur (Swenson and Bradley, 2013).
Calcidiol, or 25-hydroxyvitamin D3, was measured in the present case, as it is the plasmatic storage form of vitamin D and has a longer half-life than calcitriol (Jones et al., 2015). Typically, hypercalcemia is expected to be present in cases of vitamin D toxicosis; however, in this case, total calcium was initially within normal limits. This has been reported previously in humans (Jacobus et al., 1992; Chakraborty et al., 2015) and birds (Swenson and Bradley, 2013). The human cases were attributed to genetic mutations affecting vitamin D receptors or to the mutation of vitamin D 24-hydroxylase, a key enzyme inactivating calcitriol. Although this mutation has not been investigated in reptiles, it should be noted that normocalcemia does not rule out hypervitaminosis D. In the case presented here, plasmatic total calcium and ionized calcium concentrations could not be accurately assessed due to the lack of published reference intervals for these tests in blue-tongued skinks. The calcium-phosphorus solubility index is also unknown in blue-tongued skinks. However, a solubility index value similar to that obtained on the recheck biochemistry has been reported in birds with confirmed vitamin D toxicosis (Swenson and Bradley, 2013). No attempt was made to measure calcitriol in this patient, as reference intervals are lacking in blue-tongued skinks. It is possible that temporary peaks in calcitriol were associated with the temporarily increased solubility index and tissue calcification, while total calcium had returned to normal at the time of initial measurement. An alternative explanation could be that the patient was hypoalbuminemic, contributing to an increased ionized calcium value, while total calcium concentration remained within normal limits. Plasma total protein was within normal limits in this case, but a plasma protein electrophoresis would have been necessary to measure a true albumin concentration. In addition, the albumin-to-globulin ratio, as measured, was within the normal reference range of 0.3 to 2 for healthy squamates (Laube et al., 2018). Ultimately, it was not possible to rule out an increased ionized calcium at initial presentation in this patient.
Vitamin D toxicity associated with vascular metastatic calcification has been previously reported in squamates (Borza et al., 2012). The pink discoloration of the tongue of this blue-tongued skink, as well as the distal tail necrosis, was likely secondary to vascular injury. Hypervitaminosis D was suspected antemortem given the high 25-hydroxy-vitamin D3 concentration and was confirmed by histopathology. Of note, no reference intervals are available for 25-hydroxyvitamin D3 concentration in blue-tongued skinks. This result was compared with published references values in squamates, including leopard geckos (Eublepharis macularius) (162–235 nmol/L; Gould et al., 2018), green iguanas (mean of 375 nmol/L; Ullrey and Bernard, 1999), eastern indigo snakes (Drymarchon couperi) (270–475 nmol/L; Knafo et al., 2016), corn snakes (Pantherophis guttatus) (196 ± 16.73 nmol/L; Acierno et al., 2008), and Burmese pythons (Python bivittatus) (39–244 nmol/L; Bos et al., 2018). These concentrations were markedly lower than the value measured for the skink in this case. Based on the findings, it is important that we establish reference intervals for 25-hydroxyvitamin D3 in other reptile species, given the risk of intoxication by this vitamin and the challenges for antemortem diagnosis, as exemplified by this case. Indeed, it was not possible to detect vessel calcification antemortem in this case despite using CT and MRI. Contrast may have aided in a diagnosis but was not used because of the concern for vasculitis. Deeper biopsy samples that included vessels might have also helped to reach a diagnosis; however, this was not attempted due to the risk of hemorrhage. In addition, it was not possible to perform cardiac ultrasound in this case due to the presence of osteoderms in the species (O'Malley, 2005). Given the history, it is likely that the daily administration of vitamin D3 through the calcium and vitamin supplement contributed to the intoxication. According to the manufacturer, this product should only be administered two to three times a week and “lightly dusted on greens.” However, specific quantitative recommendations for blue-tongued skinks are lacking. Other significant sources of vitamin D3 in the diet included fish meat, the powdered diet, eggs, and pinkies (Schmid and Walther, 2013). Although vitamin D3 is noted as part of the ingredient list of the powdered diet, vitamin D3 content of this diet could not be determined, despite contacting the manufacturer. Blue-tongued skinks are omnivorous and are reported to eat snails, insects, and carrion in the wild (Abbate et al., 2009). Insects can contain small amounts of vitamin D3 (Finke, 2013), but we could not find any information regarding vitamin D3 concentrations of caterpillars. Concentrations of vitamin D3 in snails are considered negligible (U.S. Department of Agriculture, Agricultural Research Service, 2019; #426). Although mussels and shrimp are not part of the natural diet of this Australian lizard, their vitamin D3 content is also negligible (Schmid and Walther, 2013). Thus, it is likely these supplemented invertebrates did not contribute to the lesions.
In mammals and birds, vitamin D toxicosis is typically associated with nephropathy and multifocal metastatic calcifications of the vascular walls of multiples organs, including the lungs, trachea, kidneys, myocardium, aorta, digestive tracts, skeletal muscle, choroid plexus, and bones (Morita et al., 1995; Swenson and Bradley, 2013). Lesions secondary to renal insufficiency may also be present, such as gouti tophi in birds (Swenson and Bradley, 2013). Renal lesions were mild in the case presented here, possibly because the skink was euthanized due to necrosis of the extremities, whereas previous cases reported in green iguanas and birds had died of vitamin D toxicosis (Wallach, 1966; Swenson and Bradley, 2013).
Calcification of the media layer of major vessels of the heart base was noted in this case. Lesions were difficult to locate without special stain but became evident once Van Kossa stain was used. In other reports of hypervitaminosis D in squamates, the media of arteries was also calcified (Wallach, 1966; Borza et al., 2012). Mineralized vessels were abundant in multiple organs of green iguanas with hypervitaminosis D (Wallach, 1966), whereas only the heart and blood vessels at the base of the heart were affected in veiled chameleons (Chamaeleo calyptratus) (Borza et al., 2012). Differentials for arterial mineralization should also include atherosclerosis, which has been previously reported in a bearded dragon (Pogona vitticeps) (Schilliger et al., 2010), neoplasia, and renal disease associated with soft tissue mineralization (Divers, 2019). In the present case, no cholesterol deposits were noted in the vessels, ruling out atherosclerosis (Wallach, 1966). In cases of leukemia-associated hyperviscosity syndrome, necrosis of the extremities can also occur. Therefore, hematology should be performed to rule out leukemia in similar cases. Finally, severe renal disease was ruled out at necropsy and uric acid was within normal limits in this case.
Severe pulmonary hemorrhage noted postmortem in the present case was partially attributed to euthanasia. It is suspected that pulmonary vascular lesions also caused hemorrhage antemortem and contributed to epistaxis, given the detection of hemosiderin in the lesions. However, the severity of pulmonary hemorrhage could not be confirmed due to euthanasia artifacts. Alternatively, metabolic acidosis could have contributed to tachypnea, as reported in cats with vitamin D toxicosis (Wehner et al., 2013).
Hepatic lipidosis was likely secondary to the active reproductive status of this female and associated dysorexia. Hepatic vascular lesions, including thrombosis, could also be secondary to hypervitaminosis D. Although hepatic disease was not detected on the biochemistry panel nor CT or MRI, it may have been a contributing factor to the anorexia. The precise cause of anorexia in this case remains undetermined. It seems more likely that the reluctance to eat was secondary to the swollen pharynx and associated inflammation, rather than to the tongue lesion. Indeed, in a case of glossectomy in a blue-tongued skink, the animal quickly resumed feeding after the tip of the tongue was amputated (Kehoe et al., 2016).
Initially, a lesion localized within the head region was suspected in this skink, based on the discoloration of the tongue and decreased appetite associated with painful food prehension. The tail lesion was overlooked and, in retrospect, should have been investigated further because a generalized vascular process should have been considered more likely. An infectious lesion was suspected due to the toxic changes and left shift noted on the hematology results. A broad-spectrum antibiotic was initially chosen empirically, and the dose was extrapolated from the pharmacokinetic studies published in green iguanas and bearded dragons (Churgin et al., 2014; Sadar et al., 2018). Because of the lack of clinical improvement, other infectious differentials were considered, especially cryptosporidiosis of the pharynx, as reported in green iguanas (Fitzgerald et al., 1998; Uhl et al., 2001). For this reason, azithromycin was prescribed pending biopsy results. Azithromycin has been shown to be effective for treating aural Cryptosporidium baileyi in owls (Molina-Lopez et al., 2010), but its effectiveness in reptiles is unknown. Alternatively, paromomycin, another antibiotic, has also been shown to be effective against lizard cryptosporidiosis (Grosset et al., 2011), but this drug is not absorbed systemically and would therefore not be appropriate for aural cryptosporidiosis. Regardless, infectious lesions were noted in the tongue on necropsy, which suggests minimal response to antibiotic therapy or relapse after azithromycin discontinuation.
Treatment of vitamin D toxicosis typically includes supportive care and palliative treatment for hypercalcemia in the form of fluid therapy and treatment enhancing calciuresis. Extrapolating from canine medicine, the optimal treatment would have been to place an intraosseous catheter, administer sodium chloride 0.9% at 1–2 ml/ kg/h for 24 h with ionized calcium, monitor the respiratory rate closely, and re-evaluate the patient every 24 h. In case of recurring epistaxis or dyspnea, the fluid rate should be decreased as needed. Calciuresis could be attempted using bisphosphonates and corticosteroids (Mellanby et al., 2005; Wehner et al., 2013). No dose of bisphosphonates has been described in reptiles to our knowledge. The ionized calcium measured in this case appeared to be high compared with a reference available in green iguanas (Dennis et al., 2001); therefore, prednisolone treatment was attempted but was unsuccessful. In addition, sucralfate could have been administered orally to decrease calcium absorption (Wehner et al., 2013), although the diet was modified to decrease calcium content in this case. Supportive care, including supplemental feeding and soaking, were also implemented to no avail. As metastatic calcification is irreversible, the prognosis is usually grave once clinical signs are noted. Being a liposoluble vitamin, vitamin D is stored in multiple tissues (e.g., fat and striated muscles) (Mawer et al., 1972) and can result in progressive release that contributes to elevated plasmatic vitamin D concentrations and long-lasting effects. Therefore, euthanasia was recommended due to poor quality of life and prognosis.
In summary, this case report describes the challenges associated with antemortem diagnosis of a vitamin D intoxication. It highlights that specific reference intervals should be established for 25-hydroxyvitamin D3 and ionized calcium concentrations in various reptile species. In addition, clinicians presented with a blue-tongued skink displaying a pink tongue or tail necrosis should consider hypervitaminosis D in their differential diagnosis. Finally, access to ultraviolet B lights should be preferred to oral vitamin D whenever available for captive reptiles.
Photographic image of the tongue of an anesthetized 10-yr-old female blue-tongued skink. The proximal part of the tongue is pink, whereas the distal part of the tongue is dark blue.
(A) Computed tomography (CT) of the pharyngeal area sectioned at the level of the middle ear showing the reduced pharyngeal lumen (asterisk) and the narrowed auditory tube (arrowheads). (B) CT of a healthy blue-tongued skink at the same level. at, auditory tube; ph, pharynx; pp, paroccipital process; rp, retroarticular process; t, trachea; tc, tympanic cavity. (C) Transverse T2-weighted fast spin echo MRI image of the pharynx (ph) of a 10-yr-old female blue-tongued skink at the level of the middle ear (top) and caudally (bottom), showing hyperintense fluid accumulation (white arrow on both images) in the ventral aspect of the left tympanic cavity (tc) and ventrally in the right side of the pharynx at the esophagus entrance. Low signal-to-noise ratio is due to patient size and the presence of osteoderms. (D) Dorsal plane reformatted CT image of the caudal coelomic cavity with mineralized foci in bilateral kidneys (white arrow).
Endoscopic images of the pharynx of a 10-yr-old blue-tongued skink: general view of the pharynx (A) and biopsy site (B).
Histopathology lesion noted at the level of the vessels of the heart base. (A) Hematoxylin phloxine saffron stain and (B) Van Kossa stain: mineralized tissues appear black. Magnification, ×200.
