Colchicine intoxication in a dog

293381704_5664537806890011_4414435878500424694_n    Dr Denica Djodjeva

        Sofia, Bulgaria

 

Abstract

Colchicine is extracted from Colchicum autumnale (autumn crocus, or meadow saffron) and Gloriosa superba (glory lily). It is a lipid-soluble alkaloid that is isolated from the plant and is one of the main agents used in the treatment of crystal arthropathy gout, immune-mediated disorders such as Behçet’s disease (characterized by vasculitis), familial Mediterranean fever (characterized by polyserositis and amyloidosis), and neutrophilic dermatoses.  Because colchicine stimulates enzymes called collagenases, which break down collagen protein and inhibit liver cells from making amyloid A, in dogs and cats colchicine is used off-label to reduce scarring processes such as liver cirrhosis, amyloidosis, Shar-Pei fever, fibrosis following placement of a glaucoma drainage device, to prevent granuloma formation following tracheal stent placement and to prevent urethral stricture formation. In birds, it has also been reportedly used to treat hyperuricemia.

Colchicine is rapidly absorbed after oral administration. The pharmacokinetics involves the intestines, liver, and kidneys.  Rapidly absorbed from jejunal and ileal enterocytes, colchicine is partially locally metabolized by enterocytes. The bulk of absorbed colchicine is further metabolized by the liver and excreted in bile. The time to peak concentration in humans is 0.5 to 2.0 h, decreasing rapidly within 2 h. Colchicine undergoes extensive enterohepatic recirculation before being fecally excreted and is distributed to all tissues in the body, where it binds to intracellular tubulin and has a dissociation half-life of 20–40 hours. The accumulation in the kidney, liver, spleen, gastrointestinal wall, and leucocytes may lead to toxicity.  Because of the high degree of tissue uptake, only 10% of a single dose is eliminated within 24 hours, and elimination from the body may continue for 10 days or more. The long half-life and enterohepatic recirculation explain colchicine’s prolonged effect. However, the severity and mortality rate of the poisoning is usually related to the dose ingested. The lowest lethal oral dose reported for dogs is 0.13 mg/kg. Fatalities in the first few days result from shock, respiratory or cardiac arrest, or rapidly progressive multiple organ failure. The most common side effects start 2-5 hours after ingestion and are associated with gastrointestinal upset, vomiting, and diarrhea and are very rare but colchicine can suppress neutrophil production and can cause bone marrow suppression.

Introduction

To date, there are only a few described cases in the veterinary literature of colchicine intoxication in a dog. The main symptoms associated with ingested medication are severe abdominal pain, diarrhea, nausea, vomiting, and in more severe cases, DIC and MODS. There is no specific antidote, and the therapy is symptomatic and supportive. If

colchicine ingestion is suspected, giving active charcoal or gastric lavage would be beneficial if too much time has not passed since ingestion.

Three clinical phases of intoxication are described, each of which is associated with the corresponding expected complications and symptoms.

  1. Gastrointestinal / 10-24 hours – characterized by abdominal pain, nausea, vomiting, and diarrhea. Hypovolemic state and hypotension due to severe dehydration, and peripheral leukocytosis.
  2. Multiorgan phase / 2 – 7 days – bone marrow hypoplasia with strong leukopenia and thrombocytopenia; oliguric renal failure; cardiac arrhythmias and arrest; electrolyte and metabolic disorders such as hyponatremia, hypocalcemia, hypokalemia, hypophosphatemia; changes in mental status, seizures; respiratory distress, hypoxia.
  3. Recovery, if death has not occurred/ after 7 days – leukocytosis; risk of alopecia.

Manifestations of Colchicine Toxicity reported in humans

Gastrointestinal: Abdominal pain; Nausea/vomiting; Diarrhea; Paralytic ileus; Hepatocellular damage; Pancreatitis
Respiratory: Respiratory distress; ARDS
Hematological: Leukocytosis (first stage); Bone marrow hypoplasia; Coagulopathy; Hemolytic anemia
Skin: Rash; Alopecia
Cardiovascular: Hypovolemia; Hypotension; Depressed myocardial contractility; Peripheral vasodilation; Arrhythmias; Myocarditis
Renal: Proteinuria/hematuria; Acute renal failure
Metabolic: Metabolic acidosis; Hyponatremia; Hypocalcemia; Hypophosphatemia; Hypomagnesemia
Fertility: Azoospermia; Sterility
Miscellaneous: Fever; Hypothermia
Neuromuscular: Mental status changes; Coma; Ascending paralysis; Seizures; Peripheral neuropathy; Rhabdomyolysis

 

The Case of Lady: A Pomeranian’s Struggle with Colchicine Toxicity

Lady’s clinical journey commenced when her owners discovered that she had ingested up to three tablets of colchicine, each containing 0.5 mg of the drug. The ingestion occurred less than 24 hours before her admission, and the rapid onset of clinical symptoms constitutes an emergency, requiring immediate veterinary intervention.

Upon evaluation, Lady presented with a constellation of acute gastrointestinal symptoms including diarrhea, nausea, vomiting, abdominal pain, fatigue, and a notable refusal to eat. Each of these symptoms indicates a severe systemic response, triggered by the colchicine overdose. Colchicine is known to affect multiple organ systems, primarily targeting the gastrointestinal tract, bone marrow, liver, and kidneys. The rapid decline in Lady’s health condition pretty good shows the nature of colchicine toxicity, which can escalate quickly if not addressed promptly.

The prognosis for Lady remains questionable due to the timing of her ingestion and the associated clinical signs. In veterinary practice, the prognosis in cases of colchicine toxicity is influenced by various factors, including the extent of ingestion, the duration since exposure, and the promptness of medical treatment. Given that less than one day has elapsed since the incident, there remains a crucial window of opportunity for effective medical intervention. Treatment protocols typically include decontamination procedures such as emesis induction and activated charcoal administration to reduce further absorption of the toxin but in a time manageable time after the ingestion. In this case, these procedures were not performed due to time elapsed since ingestion.   Supportive care, including intravenous fluids and anti-emetics, may be required to manage dehydration and electrolyte imbalances that commonly accompany gastrointestinal distress.

Test and Investigations:

In the realm of clinical diagnostics, the role of point-of-care (POC) examinations cannot be underestimated. For Lady, a range of POC exams were scheduled, including a complete blood count (CBC), basic metabolic panel (BH), and electrolytes, alongside imaging studies such as abdominal ultrasound and X-ray. Notably, Lady’s irregular vaccination status necessitated the inclusion of a CPV/CCV/G test, which ultimately returned negative results.

Laboratory findings highlighted evidence of dehydration, accompanied by increased liver enzyme levels—a possible reflection of hepatic distress or injury. These findings warrant immediate attention, as dehydration can exacerbate underlying conditions and complicate treatment protocols. Concurrently, the elevated liver enzymes may suggest an underlying metabolic or infectious process that requires further exploration.

The abdominal ultrasound provided crucial insights into Lady’s condition. Importantly, the examination did not reveal any free fluid, which often serves as a potential marker for various abdominal pathologies, such as perforation or significant intra-abdominal hemorrhage. However, the ultrasound did unveil a thickened intestinal wall and signs of inflammation in the small intestine, coupled with increased peristalsis. These findings are suggestive of an inflammatory condition, such as enteritis, which could stem from a variety of etiologies including infectious agents or inflammatory bowel disease.

Complementing the ultrasound findings, the X-ray examination corroborated the absence of any foreign body, thus eliminating a critical differential diagnosis that could account for Lady’s symptoms. The combination of these imaging modalities and laboratory tests contributes to a more comprehensive understanding of her moment health status.

Treatment and Problem-Solving Plan for Hemorrhagic Gastroenteritis due to colchicine intoxication

Hemorrhagic gastroenteritis is a serious condition characterized by inflammation and bleeding, which can lead to significant morbidity. Despite a few cases of colchicine intoxication described, Lady’s case presented a structured treatment and problem-solving plan implemented during the hospitalization and her critical condition. The approach utilized involved a combination of symptomatic therapies, intensive monitoring, nutritional support, and hygiene care tailored to address the complexities arising from her illness.

Upon admission, Lady exhibited clinical signs, including lethargy, refusal of food and water, and vital signs indicative of distress: arterial blood pressure at 150 sys (Doppler measurement), heart rate at 120 bpm, respiratory rate at 21/min, and hypothermia at 36,5 C°, MMC- pink, CRT>2sec. Immediate interventions commenced with symptomatic therapy, specifically the administration of antacids and antiemetics, complemented by antibiotics, supportive care, and warming. Regular monitoring of vital signs was imperative, enabling prompt detection of any deterioration in her condition.

The antibiotic regimen consisted of Ampicillin at a dosage of 20 mg/kg every six hours and Metronidazole at 10 mg/kg every twelve hours. This dual therapy aimed to combat potential intestinal, and bacterial translocation and infections while addressing gastrointestinal stability. Pain relief was managed through a multimodal approach, incorporating buprenorphine, metamizole sodium, hyoscine butylbreomide, and a constant rate infusion (CRI) of lidocaine at dose 1mg/kg/h, ensuring Lady’s comfort during her recovery.

Nause, vomiting, and regurgitation were challenging symptoms in this gastrointestinal upset condition. The combination of maropitant, pantoprazole, ondansetron, and metoclopramide facilitated a significant alleviation of these distressing symptoms, allowing for the resumption of feeding and subsequent recovery. Maropitant, administered at a dosage of 1 mg/kg every 24 hours, serves as a potent antiemetic, specifically targeting the neurokinin-1 (NK1) receptors in the central nervous system. Its use was instrumental in controlling nausea and vomiting episodes and also may act as mild pain control medication. In conjunction with maropitant, pantoprazole was prescribed at a dosage of 1 mg/kg every 24 hours. As a proton pump inhibitor, pantoprazole plays a crucial role in reducing gastric acid secretion, preventing the potential for gastric irritation and ulcers that may result from chronic vomiting. The synergistic effect of combining maropitant with pantoprazole not only addressed the challenges posed by nausea but also provided a protective mechanism for the gastrointestinal tract, promoting an environment for healing. Additionally, ondansetron was incorporated into Lady’s treatment regimen at a dosage of 0.3 mg/kg every 12 hours. Ondansetron’s mechanism of action, which involves blocking serotonin receptors in the central nervous system and the gastrointestinal tract, proved valuable in achieving comprehensive control over Lady’s nausea and vomiting episodes. Recognizing the importance of gastrointestinal motility in managing nausea, metoclopramide was also included in Lady’s therapy as CRI at a dosage of 2mg/kg for 24 hours. Administered to enhance peristalsis, metoclopramide not only functions as an effective antiemetic but also facilitates gastric emptying. This dual action was particularly beneficial in this case, as it mitigated the regurgitation and associated complications. Achieving coordinated motility ensured that Lady’s digestive system could efficiently process the food that would be introduced once her nausea was under control. Once adequate control of nausea and regurgitation was established, the placement of a nasoesophageal tube permitted the safe initiation of feeding and administration of additional probiotic therapy. This intervention was pivotal in delivering necessary nutrition while circumventing the challenges related to oral intake, which could have exacerbated Lady’s condition.

S-adenosyl-methionine (Transmetil ®) is known due to its hepatoprotective properties.  It’s crucial role in detoxification, metabolism, and the synthesis of various biochemicals essential for digestion, growth and potent antioxidants within hepatic tissues, can offer significant benefits in restoring liver function and mitigating cellular damage. At the moment of presence Lady’s liver enzymes were elevated (AST 549 U/I, ALP 1031 U/I). In this case dose of 10mg/kg every twelve hours was used due the hospitalization.  Colchicine is lipid- a soluble alkaloid, and to enhance its safe excretion and mitigate its adverse effects, the use of Intralipid emulsion of 20% has been included in the treatment.  Administered at a rate of 1.5 mL/kg over 15 minutes, followed by a continuous infusion of 0.25 mL/kg/min over two hours, Intralipid serves to expedite colchicine clearance. The emulsion encapsulates the lipophilic drug, facilitating its removal from the body system and subsequent elimination. Due to the hypoproteinemic and albuminemic state (ALB 28.5 g/L; TP 38.6 g/L) coupled with electrolyte imbalance (K 3.6- 3.44mmol/L; Cl 91.9mmol/L; Na 135mmol/L) the administration of amino acid solution has emerged as a vital solution. Amino acids are the building blocks of proteins and play an essential role in addressing the underlying hypoproteinemic and hypoalbuminemia state and recovery from malnutrition. The amino acid glutamine has been recognized for its role in maintaining the gut barrier and modulating electrolyte absorption in the intestines. A serum albumin level of 28.5 g/L indicates a clear departure from the normal range, which typically hovers between 30 to 40 g/L. The context of hypoproteinemia and albuminemia often underscores systemic issues such as malnutrition, liver dysfunction, or protein loss through renal or gastrointestinal pathways. The noted total protein concentration of 38.6 g/L appears low as typical total protein levels fall within the range of 60 to 80 g/L in a healthy individual. However, the focus remains on the significance of low albumin as it plays a crucial role in maintaining oncotic pressure and transporting various substances in the bloodstream. A deficit in albumin can lead to interstitial edema, impaired wound healing, and diminished immune response, exacerbating a patient’s overall clinical condition. In conjunction with hypoproteinemia, the electrolyte profile reveals imbalances: a potassium level fluctuating between 3.6 and starts dropping to 3.44 mmol/L, chloride at 91.9 mmol/L, and sodium at 135 mmol/L, which is a complication described in human clinical cases of colchicine intoxication. These values highlight a tendency to hyponatremia, which can lead to neurological disturbances, and hypokalemia, which can adversely affect cardiac function and muscle contraction.

One of the critical complications arising from HGE is anemia, often characterized by a marked decrease in red blood cell (RBC) count, hemoglobin (HGB) levels, and hematocrit (HCT). Platelet count (PLT) except as a consequence of colchicine intoxication could be indicative of starting DIC or a hypercoagulable state. Recent clinical assessments have indicated RBC levels ranging from 4.61 x 10^12/L to 3.69 x 10^12/L, HGB decreasing from 109 g/L to 89 g/L, HCT dropping from 28% to 23%, and PLT counts diminishing from 21 x 10^9/L to 18 x 10^9/L. The prevalence of anemia in HGE patients necessitates prompt and comprehensive management of potential complications, including the risk of a hypercoagulable state. In managing anemia associated with HGE, the administration of tranexamic acid at a dosage of 10 mg/kg every 12 hours has emerged as an effective therapeutic intervention. Tranexamic acid, an antifibrinolytic agent, functions by inhibiting fibrinolysis, thus promoting clot stability and reducing bleeding tendencies. In the context of HGE, where the loss of blood can lead to both acute anemia and a coagulopathy, tranexamic acid serves a dual purpose: it treats active bleeding while simultaneously preventing the progression to a hypercoagulable state that can occur due to a compensatory increase in coagulation factors. Supportive measures need to include close monitoring for signs of coagulopathy, which can arise due to microvascular changes associated with both the inflammatory response and anemia itself.  Because of that D- dimer was measured and was in normal ranges of 174ng/ml.

Fluid therapy was also critical, compensating for dehydration resulting from vomiting and diarrhea while restoring electrolyte balance; this was further supported with a per-axis supplement to correct hypokalemia and hypochloremia.

Other complications as pancreatitis were observed. The CPL measurement of 702 mcg/L indicates a severe elevation that signals significant pancreatic distress, which may correlate with the severity of pancreatitis and potential progression toward complications. Furthermore, systemic complications including acute respiratory distress syndrome (ARDS) and multi-organ failure can arise as the body attempts to respond to the inflammatory mediators released from the damaged pancreas.

Despite the initial treatment, Lady’s condition showed minimal improvement on the first days of hospitalization, characterized by persistent refusal to eat, regurgitation, and laboratory findings indicative of leukocytosis, anemia, thrombocytopenia, and hypoproteinemia. By the seventh day of hospitalization, Lady demonstrated remarkable improvement. She regained her appetite but still with the NE tube and exhibited heightened vitality and mobility, signifying a positive response to the comprehensive treatment strategy instituted. A careful transition to home care entailed a tailored prescription that included antibiotics, an anemia supplement, probiotics, and regular clinical check-ups.

Drugs affecting colchicine toxicity

 

Interactions with colchicine Representative drugs
CYP3A4 inhibitors (↑ toxicity) Almorexant, alpha, amiodarone, amprenavir, aprepitant, atazanavir, boceprevir, casopitant, ceritinib, chloramphenicol, cimetidine, ciprofloxacin, clarithromycin, clotrimazole, cobicistat, conivaptan, crizotinib, cyclosporine, dalfopristin, danazol, darunavir, dasatinib, deferasirox, delavirdine, diltiazem, dronedarone, erythromycin, fluconazole, fluoxetine, fluvoxamine, fosamprenavir, fosaprepitan, fusidic acid, grapefruit juice, idelalisib, imatinib, indinavir, interferon alpha, isoniazid, itraconazole, ketoconazole, lapatinib, lopinavir, lomitapide, miconazole, natural, nefazodone, nelfinavir, paroxetine, posaconazole, propoxyphene, quinupristin, ritonavir, saquinavir, simeprevir, telaprevir, telithromycin, tipranavir, troleandomycin, verapamil, voriconazole, etc
P-glycoprotein inhibitors (↑ toxicity) Atorvastatin, budesonide, clarithromycin, cyclosporine, diltiazem, erythromycin, grapefruit juice, hydrocortisone, itraconazole, ketoconazole, lovastatin, propafenone, quinidine, ranolazine, saquinavir, simvastatin, tacrolimus, verapamil, etc
CYP3A4 inducers (↓ toxicity) Aminoglutethimide, armodafinil, barbiturates, bexarotene, bosentan, carbamazepine, dabrafenib, dexamethasone, efavirenz, enzalutamide, eslicarbazepine, etravirine, fosamprenavir, fosphenytoin, griseofulvin, lumacaftor, modafinil, nafcillin, nevirapine, oxcarbazepine, phenytoin, primidone, rifabutin, rifampin, rifapentine, St. John’s wort, etc
P-glycoprotein inducers (↓ toxicity) Phenytoin, curcumin, carbamazepine, genistein, St. John’s wort extract, quercetin, rifabutin, etc

Expected Outcome

In the event of colchicine overdose, the prognosis is often considered dubious, primarily due to the drug’s potent mechanism and the body’s capacity to metabolize and excrete it. Following significant exposure, patients are at considerable risk for developing disseminated intravascular coagulation (DIC), characterized by widespread activation of the coagulation cascade leading to the formation of small blood clots throughout the body’s small vessels. This pathological process can severely impact organ function and culminate in multiple organ failure. Clinically, the anticipated symptoms would include gastrointestinal distress, cardiovascular instability, and hematological anomalies. The toxicological implications of colchicine are further exacerbated by its narrow therapeutic index and long half-life, which complicates both clinical monitoring and the treatment regimen.

Actual Outcome

In a divergence from the expected prognosis, after seven days of aggressive therapy, the patient demonstrated remarkable clinical recovery. Intensive supportive care measures, including intravenous fluids, symptomatic therapy, and close monitoring of organ function, culminated in the complete restoration of health. This outcome highlights not only the resilience of the body in the face of potentially lethal drug toxicity but also underscores the critical importance of timely intervention and appropriate medical management.

Conclusion

In conclusion, this case serves as an important reminder of the unpredictable nature of drug toxicity and the potential for recovery even in seemingly dire circumstances. While the expected outcomes of colchicine overdose typically carry a grim prognosis due to all possible complications and the risk of DIC, and multiple organ failure, the actual outcome observed here emphasizes the effectiveness of proactive therapeutic measures. Given the underreported clinical cases, it is difficult to create a protocol for the treatment of colchicine poisoning, so I hope this material will help in the future creation of one and help in better management of this rare intoxication condition.

WSAVA Alerts to Emerging ‘Canine Welfare Crisis’ Caused by the Popularity of Short-Nosed Breeds

Veterinarians around the world are warning about an emerging canine welfare crisis caused by the rapidly increasing number of short-nosed (brachycephalic) dogs. These dogs can have exaggerated anatomical features that can seriously affect their health and well-being. The most concerning of the health issues they face is Brachycephalic Obstructive Airway Syndrome (BOAS).

 

The Hereditary Disease Committee (HDC) of the World Small Animal Veterinary Association (WSAVA) has produced an educational video highlighting the problems that BOAS can cause in brachycephalic breeds, including French bulldogs, English bulldogs, and pugs. During the video, members of the WSAVA HDC and other experts explain how the appearance of short-nosed breeds has been affected by breeding for extreme and exaggerated anatomical conformation. While dogs which snore or pant are considered cute by some, the experts point out that these traits are not normal and that the dogs are, in fact, struggling to breathe. Many short-nosed dogs require surgery to survive and have a significantly shorter lifespan than other dogs.

Dr Jerold Bell

Speaking during the video, Dr Peter Sandøe, Director of the Centre for Companion Animal Welfare at the University of Copenhagen, says: “With French bulldogs now the most popular breed in many countries and with English bulldogs and pugs also very popular, the number of affected dogs is increasing dramatically. Selective breeding for an exaggerated short nose has created dogs whose health, in many cases, is compromised for the sake of perceived ‘cuteness’. It is simply unethical to breed dogs which struggle to breathe.”

 

The WSAVA Hereditary Disease Committee is calling on all stakeholders – breeders, owners, veterinarians, media, regulators, and others – to work together to improve the welfare of these breeds going forward, and change perceptions of what ‘healthy’ looks like in these dogs.

 

It urges them to work together on health-focused breeding initiatives to produce dogs with less exaggerated anatomical features so that BOAS and other related health issues are not passed on. The selective breeding which caused these problems in the first place, can return these breeds to better respiratory health by selecting for more moderate anatomical conformation and for normal breathing. Many kennel clubs have instituted Respiratory Function Grading (RFG) to screen prospective breeding dogs against BOAS. If RFG screening is not available, prospective breeding dogs should be able to go on a brisk three-minute walk without laboring to breathe. If they cannot do this, they should not be used for breeding.

 

The need for a united approach is reinforced by WSAVA HDC member Dr Monique Megens, who contributes to the video explaining that brachycephalic dogs are bred – legally and illegally – around the world and transported across borders so a global approach is the only way to make progress.

 

The 17-minute video, available in several languages, also features contributions from:

 

  • Dr Jerold Bell, Chair of the WSAVA HDC, Cummings School of Veterinary Medicine, Tufts University, USA
  • Dr Åke Hedhammar, WSAVA HDC member, Senior Professor in Internal Medicine at the University of Agricultural Sciences, Uppsala, Sweden
  • Dr Jane Ladlow, Clinical Lead of the BOAS Research Group, Cambridge University, UK

 

Dr Bell said: “Breeders did not purposefully select for dogs with impaired breathing but there is no doubt that breeding to create dogs with ever shorter muzzles has created serious health issues in these breeds.

“We hope our video will help educate breeders, owners, and all of those involved in or influencing the breeding and care of short-nosed dogs.  We also hope it will give them useful advice on the steps they can take to help as we work together to resolve a serious welfare issue. All dogs deserve to live healthy lives. We must not let them down.”

The video can be seen here: https://bit.ly/3HmL5fk

 

The WSAVA represents more than 200,000 veterinarians worldwide through its 115 member associations and works to enhance standards of clinical care for companion animals. Its core activities include the development of WSAVA Global Guidelines in key areas of veterinary practice, including pain management, nutrition and vaccination, together with lobbying on important issues affecting companion animal care worldwide.

 

The WSAVA Hereditary Disease Committee aims to facilitate clinician diagnoses, treatment and control of hereditary diseases and genetic predispositions in dogs and cats, thereby improving the health of patients now and in future generations.

Diagnosis of multiple myeloma in a Labrador Retriever

florinFlorin Cristian Delureanu

MRCVS, DVM

November 2021

 

History

A 12 years old intact male labrador retriever was presented to the practice in 05.03.2021 with a history of diarrhea and hyporexia. The diarrhea was present for few days and the appetite was decreased for about 2 weeks but there were moments when the patient was eating normally. The patient was up to date with the booster vaccination and was regulary using antyparasitic treatment.

 

Physical examination

At the moment of examination the patient was bright, alert, with normal temperature (38.7 °C), the palpable lymphnodes were normal in size, nothing abnormal detected in the oral cavity and thoracic ascultation unremarkable. A mass of approximate 5cm diameter with soft consistency, mobile, and without local reaction on the surrounding soft tissue was identified in the xiphoid area.

 

Investigations

Initially general blood tests including complete blood count, biochemistry, electrolytes and total T4 were performed as a routine screening in order to identify any abnormalities. The results from the haemoleucogram demonstrate mild microcytic hypochromic non-regenerative/ pre-regenrative anemia, neutropenia, monocytopenia and eosinopenia. On the biochemistry just hyperproteinaemia due to increased globulins was the single abnormality. Also the thyroid hormone was under the normal reference range (picture 1).

fig 1

Coroborating the blood results with the history and the clinical examination the following differential diagnostic list was discussed with the owner: occult chronic blood loss, iron deficiency, inflammatory/infectiouse cause, neoplastic, immune mediated disease, endocrine (anemia secondary to hypothyroidism), gammopathies.

Aditional history: the last time when the patient went to a veterinary practice was 5 months prior for the regular booster vaccination.

Because of no evident clinical symptoms the presumption of chronic blood loss due to diarrhoea or anemia secondary to hypothyroidism was suspected. After discussion with the owner the decision of repeating blood tests in 4 days was taken. The patient was discharged with oral probiotics and was put on gastro intestinal veterinary diet to treat the diarrhoea. At reevaluation blood was collected and was send to the reference laboratory for complete blood count and blood smear interpretation, SDMA, Coomb’s test and C-reactive protein and complete thyroid panel including total T4, freeT4, cTSH, thyroglobulin autoandibody

The SDMA was normal also the thyroid panel was normal and negative on thyroglobulin autoandibody. The C-reactive protein was mildly elevated and the Coomb’s test was negative. On haematology the anemia had the same characteristics but was normocytic the reticulocytes and platelets under the normal limit. There were no modifications on the leucogram compared with the one performed at the first presentation (picture 2).

fig 2

The blood film was evaluated and a mild microcytosis and no increased in polycromasia was noted. Marked rouleaux formation and occasional metarubricyte were present too and leucopenia was confirmed. Estimation of free platelets (3-8 platelets seen per HPF) suggested platelet numbers are mildly/moderately decreased with and very small platelet clumps seen was identified.

 

Based on the second blood tests (pancytopenia is observed but also marked rouleaux and occasional metarubricyte) and hyperglobulinaemia from the initial blood tests a suspicion of neoplastic disease like multiple myeloma or lymphoma less likely non-neoplastic disorders like monoclonal gammopatihes (Erlichiosis or Dirofilariasis) because the patient was regulary using antiparasitic medication and no history of travelling. In the same day results were reported to the owner and additional questions regarding the origin, travel status and lameness episodes were asked to the owner in order to find more informations. There was no history of travelling, the dog origin was United Kingdom and transitory episode of weakness were observed in the past months.

 

Further investigations

To investigate more the suspicion serum and urine protein electrophoresis, urinalysis including urine protein creatinine ratio, radiographs and bone marrow aspiration were recommended. Five days later the patient presented to the practice but the owner accepted initially just the non-invasive investigation and declined the x-rays and bone marrow aspiration. An additional in house haemoleucogram was performed at this stage to monitor the trend of the red and white blood cells (picture 3)

fig 4

 

 

 

 

 

 

 

The urinalysis revealed proteinuria 3+ and a pH of 8 with active sediment and no crystals or casts, the urine beign collected via urethral catheterisation. The urine protein creatinine ratio was marked elevated (picture 4).

 

fig 4-1

 

 

 

 

At serum protein electrophoresis hypoalbuminaemia was present with a mild increase in alpha 1 globulins and marked increase in gamma globulins migrating in a gamma region and a depletion of the globulins thereafter, consistent with a monoclonal band (picture 5)

fig 5

 

 

 

 

 

 

 

 

 

The urine protein electrophoresis showed that majority of the protein was presented in the alpha-beta region and this was interpreted as overflow proteinuria secondary to the marked gammopaty present at the serum protein electrophoresis. No bands consisting with Bence Jones protein were noted but this would be masked by the overflow proteinuria (picture 6).

fig 6

After these last results a highly suspicion of neoplastic disease was made. Radiography and bone marrow aspiration were recommended to confirm the disease. The owners were reluctant to put the dog under sedation because in the past he had general anesthesia and was not stable according to the previouse veterinarian. At this moment the patient was sent to a referral center to have the imagistic investigation.

 

In 09.04.2021 the patient arrived at the referral center for the last investigations. After clinical examination a firm mobile mass was noted in the caudal abdomen. Initially HLG, blood film evaluation, ionised calcium and 4Dx were performed followed by CT scan of the thorax and abdomen and fine needle aspiration of the liver, spleen and abdominal mass ultrasound guided. The ionised calcium was mild elevated (1.95 mmol/L), the 4Dx was negative. The haematology findings consist with normal white blood cell count with a slight improvement from the 5th March and a stable red blood cell count (HCT 31%) – with a mild non-regenerative anaemia. An initial review of the CT scan confirms the presence of a 4.5-5cm encapsulated mass in the caudal abdomen, with no obvious association with the intestinal wall. A small amount of free fluid is present between the liver lobes. After these investigations the patient was sent home with Fortekor as a treatment of proteinuria.

 

Seven days later the full CT report, aspirates results and blood smear interpretation were ready.

 

Cytology interpretation

 

A detailed haematology showed a mild, normocytic normochromic, poorly regenerative anaemia (HCT 36.9%, reticulocyte count 95.05×109/L). His white blood cell and platelet count were low-normal. There was no evidence to support haemolysis and leucocyte morphology was unremarkable.

Aspirates from the liver and spleen identify a population of extremely atypical plasma cells, supportive of multiple myeloma. Prominent extra medullary haematopoiesis is also noted within the spleen.

Aspirates from the caudal abdominal mass show adipocytes and a mixed inflammatory cell population, comprising of neutrophils ageing in situ and undergoing pyknosis. An atypical plasmacytoid population is identified but in low numbers, suggesting infiltration with myeloma.

 

CT findings from the report

 

Musculoskeletal:

There are multifocal osteolytic lesions throughout the entire included portion of the skeleton, including essentially all included vertebrae (thoracic, lumbar, sacral), multiple ribs, the sternebrae, the proximal humeri, the pelvis and the proximal femurs (picture 7).

 

Thorax:

No soft tissue attenuating pulmonary nodules are identified. There are multiple small (<5mm), mineral attenuating, geometrically shaped foci throughout the pulmonary parenchyma (predominately within the periphery), consistent with benign osteomata.

 

Abdomen:

An ovoid, well encapsulated mass is identified within the mesentery of the right caudal abdomen, which measures approximately 4.7cm x 4cm x 5.7cm (height x length x width) (picture 8). The mass is predominately fat attenuating, with a soft tissue attenuating rim and patchy regions of internal soft tissue attenuation (which ranges in appearance from ill-defined to linear).

 

A soft tissue attenuating (isoattenuating to the adjacent renal cortical tissue on pre-contrast), minimally contrast enhancing nodule, measuring approximately 1cm in largest diameter, is present in the right lateral renal cortex (picture 9).

 

The liver and spleen are diffusely mildly enlarged, with rounded margins, however they demonstrate normal attenuation and contrast enhancement. A mildly enlarged splenic lymph node is also present.

fig 7 fig 8 fig 9

 

 

 

Diagnosis: Multiple myeloma – advanced stage

 

Discussion

 

Multiple myeloma is a lymphoproliferative cancer arising from plasma cells and their precursors, characterised by clonal proliferation of plasma cells infiltrating the bone marrow and then affecting other organs such as the spleen. Diagnosis of MM usually follows the demonstration of bone marrow or

visceral organ plasmacytosis, the presence of osteolytic bone lesions and the presence of urine myeloma proteins. Renal disease is present in approximately one-quarter to one half of dogs with MM, and azotemia is observed in 30% to 40% of cats.

Bence Jones proteinuria was not evident in the pacient urine protein electrophoresis due to overflow proteinuria secondary to the marked gammopaty. Bence Jones proteinuria occurs in approximately 25% to 40% and hypercalcemia is reported in 15% to 50% of dogs with multiple myeloma. The clinical signs can vary from lethargy and weakness to inappetence, weight loss, lameness, polyuria/polydipsia, bleeding diathesis and central nervouse system deficits. The patient presented with a history of mild inappetence and isolated episodes of lameness.

Chemotherapy is effective at reducing malignant cell burden and to improve the quality of life of the patient. Variouse alkylating agents such as melphalan, cyclophosphamide, chlorambucil, lomustine can be used together with steroid therapy. The most common protocol is a combination between melphalan and prednisolone. This protocol is usually well tolerated by the vast majority of the dogs, the most clinically significant toxic events beign represented by myelosuppression and delayed thrombocytopenia.

 

After the last investigations performed at the referral center the patient started to deteriorate significantly this manifested by presence of a severe swelling over the left side of the face associated with pain and ptyalis. Two days later, a chemotherapeutic protocol including melphalan, cyclophosphamide orally with intravenous dexamethasone was started. Despite this, the dog developed neutropenia and pyrexia, raising concern for sepsis. As a result, a decision was made to euthanase him one day later.

 

 

 

 

 

 

 

 

 

 

 

BSAVA Congress 2021, one of the world’s largest small animal veterinary events goes live

BSAVA-Logo-with-Strap-Blue-500W

 

 

15 January 2021 – The full programme for the 2021 Virtual Congress of the British Small Animal Veterinary Association (BSAVA) is now live.
This year’s edition of one of the world’s largest event for the small animal veterinary sector will be held from Thursday 25 to Saturday 27 March. It is set to deliver everything people expect of BSAVA Congress – and more:
Excellent International speakers, more than 130 hours of CPD and an extensive range of practice resources to take away.

C21-Programme-Graphic

A new, more interactive formula

With more than 100 speakers and a new format that blends clinical, practical and interactive content across a massive number of topics, Congress is highly relevant for every member of the practice. Shorter sessions and the introduction of new two-speaker sessions on day-to-day topics will focus on the information vets need to know in primary care practice with regular opportunities for delegate engagement and questions.

“Following months of meticulous planning we are thrilled that the programme is now live,” said Professor Ian Ramsey, President of the BSAVA. “The sheer range and high quality of our speakers and content, together with our new, more dynamic format takes webinar learning to a new level.”

 

Who’s who of the veterinary world

The list of speakers is akin to an international ‘who’s who’ of the veterinary world. As a small taster of what’s in store, Holger Volk (Germany) will present on aspects of neurology on a shoestring, including a case-based panel discussion. Bianca Hettlich (Switzerland/Germany) will present a case-based interactive session to help general practitioners decide if a lameness case is of orthopaedic or neurological origin and will be busting some myths. The USA’s Ernie Ward will be speaking about recruitment and retention.

The speakers – including Mike Willard (USA), Jens Ruhnau (Denmark), Daniel Pang (Canada) and Milinda Lommer (USA) – will give short ‘live’ presentations, often in joint sessions, allowing ample time for discussion allowing a dynamic interaction.

The list of UK speakers includes Rebecca Geddes (kidney medicine and nursing), Nicki Reed (feline nursing), Sarah Heath (behavioural alopecia), Adrian Boswood (asymptomatic cardiac patients), Jane Ladlow (BOAS surgery), Penny Watson (liver biopsies, feline triaditis), Dick White (the surgical team); Tim Nuttall (atopic dermatitis), John Chitty on several rabbits, small furries and exotics topics, and many more.

C21-Programme-Graphic-v2

130 hours of CPD available on the platform for two months

Four simultaneous live streams will deliver 80+ live sessions covering 24 module topics, together with a library of 100 on-demand webinars and other resources for the practice to bring delegates more than 130 hours of CPD. Many modules have relevant presentations woven in to make them suitable for the whole practice team from clinical directors to practice nurses and managers. There will also be a dedicated exhibitor stream every day. BSAVA Congress headline sponsors include Idexx and Hill’s Pet Nutrition.

The live and on-demand content will be available to delegates on the platform for 60 days, and then via the BSAVA Library.

“Delegates will be able to develop their skills and knowledge on topics they see regularly in practice,” said Professor Ramsey. “To make things even easier we will be providing practical resources such as client handouts for delegates to take back to their clinics. This, coupled with many speakers sharing their own notes and practical resources means less note-taking and a quicker and easier way for delegates to share what they have learnt with their colleagues.”

 image003

Great value with rates starting at just £99 +VAT

On the social side the focus is on bringing people together on-line to share light-hearted entertainment and laughter. Delegates can throw some shapes with a virtual disco, exercise their bodies as well as their minds with yoga and unwind with some restorative meditation practices.

“This year’s BSAVA Congress is going to be the most innovative ever and deliver like never before,” said Professor Ramsey. There is plenty of relevant and engaging CPD for every practice professional, with all the convenience of a virtual event. If you haven’t already taken a look at the programme and registered, I urge you to do so now. With prices starting at just £99 (approx. €110) +VAT for BSAVA and FECAVA members*, it represents really great value.” The Congress will be held in English.

 

To register now visit https://www.bsavaevents.com/bsavacongress2021/en/page/home

*As FECAVA member, proof of membership of one of FECAVA’s member associations may be required. To check, please visit https://www.fecava.org/associations. Veterinarians who are members of WSAVA through their national organisation can claim a 10% discount on the BSAVA non-member rate.

For information on how to become a BSAVA member visit: https://www.bsava.com/Membership/Member-categories

“We are all together”- such a beautiful initiative and wonderful vets from 12 countries share their love, because sharing is carying

10334323_1650417485231859_7490271749546982451_nVeterinarians from 12 countries have shown their concern for the veterinary world in time of Pandemic and social isolation.

We would like to express our gratitude to all of them:

Romania: Dr Robert Popa, Dr Constantin Ifteme, Dr Florin Delureanu, Dr Raluca Zvorasteanu, Dr Lucian Fodor, Dr Diana Soare, Dr Giulia Nadasan, Dr Alexandra Curac, Dr Alexandru Vitalaru, Vet student Ilinca Zarinschi

Bulgaria: Dr Yovko Haralanov, Dr Spas Spasov. Dr Luba Gancheva, Dr Todor Kalinov, Dr Sofia Sinadinova, Dr Yavor Stoyanov

Serbia: Dr Andrija Dakovic, Dr Zoran Loncar, Dr Nikola Katic, Dr Goran Cvetkovic, Dr Ivana Jovandine

Slovenia: Dr Ana Nemec

Croatia: Dr Lea Kreszinger

North Macedonia: Dr Svetla Drakulovska

Turkey: Dr Murat Saroglu

Italy: Dr Luca Formaggini

UK: Dr Luca Ferasin

Belgium: Dr Ann Criel

Switzerland: Dr Katharina Brunner

Portugal: Dr Dr Goncalo Da Garca Periera

 

Here you can watch all of them here in our channel: https://www.youtube.com/channel/UCj3rBMaB1sD1hXHWIhcrkmw/videos