Natalia Kucharczyk

Anna Cisło-Pakuluk

Ośrodek Okulistyki Weterynaryjnej

Przychodnia Weterynaryjna Viva s.c.

Atypical uveitis in syberian husky

12 years old siberian husky female was referred for ophthalmic examination because of sudden blindness. Owner reported the that dog went to play in the garden and couldn’t come back. Dog had never been ill so far, also didn’t have any blood tests. Vaccination and deworming were according to schedule. Mother of the dog was euthanized because of complication of pemphigus.

During clinical examination performed by primary care veterinarian bilateral hyphema was found. Doctor, who made the referral recognized uveodermatologic syndrome (VKH Syndrome) and treatment was started. Primary care veterinarian administered: etamsylat (Cyclonamine 12,5%, amp., Bayer), cefalexine (Cefalexim 18%, ScanVet) - 1 ml/ 18 kg m.c.s.c/i.m., vitamin C (Vitaminum C 10%, Biowet Puławy) -100-500mg, dexamethasone (Rapidexon 2mg/ml, euroVet) - 0,5ml/10kg m.c.

Tobrex (Alcon) - 1 drop every 3 hours and dexapanthenol (Corneregel,Bausch&Lomb) - 1 drop 3 x daily were advised and the next day eye drops with dexamethasone( Dexamethason WZF 0,1%) were added - 1 drop 3 x daily.

Treatment improved sight, blindness resolved (as owner reported “partially”) and inflammation decreased. General condition of the dog was improved. Bitch was referred for ophthalmic examination.

Clinical examination revealed clotting disorders. Pale mucus membranes wet with petechiae. Normal lymph nodes , non-painful, movable. Normal auscultation findings, heart rate normal, lack of heart murmur. Many petechiaes within skin of abdomen were found.

Ophthalmic examination revealed : normal menace reflex, which means that neurological path responsible for moving back of the head and eyelids closure in reaction to an object moving fast towards the face, is normal. Normal palpebral reflex, which is reaction to touch and normal dazzle reflex which is reflex reaction(blinking, third eyelid protrusion or even head movement) to illuminate the eye with bright light. This reflex depends on functioning of retina and cranial nerve II and VII. Physiological reaction to objects arranged in examinations room confirmed that after pharmacological treatment vision was restored. Only bilateral straight and consensual pupillary light reflex were lazy (movie 1).

Schirmer tear test (SchirmerStrips, Eickemeyer ) revealed normal tear production and fluorescein staining(Fluorosan, Fatro) was negative and lacrimal drainage was normal.

Anterior aspect of the eye, palpebras and conjunctiva were examined with slit lamp KOWA SL-17. Conjunctiva in both eyes was slightly hyperemic with petechiae. Cornea was transparent with mild dystrophy with calcifications. There was aqueous flare in anterior chamber, which means that inflammatory cells are present. There was episcleral hypearemia and rubeosis iridis but without aqueous flare. There were many petechiaes on the surface of the iris (Fig. 1 and 2).

Figure 1

Figure 2

In ophthalmic examination with indirect ophthalmoscope Keeler Spectra Plus normal lens, vitreous and many subretinal hemorrhages were observed.

Because of many retinal hemorrhages hematological blood test were advised. There were erythropenia and values of hematocrit and hemoglobin was decreased. Horiba ABC device wasn’t able to count the amount of platelets. There was also increased the amount of granulocytes.

During clinical examination VHK Syndrome was declined. Patient was referred for further diagnostic procedures with suspicion of tick-borne disease or autoimmune hemolytic anemia.

Further examination performed on the same day confirmed clotdg disorders.

Further clinical examination performed in another Veterinary Clinic revealed pale conjunctiva with petechiae, wet, pale pink mucus membranes with petechiae and normal , non-painful and movable lymph nodes. Normal auscultation findings. Heart rate was 80 per minute. There were no murmurs .Many petechiaes within skin of abdomen were visible. Feces visible on thermometer during body temperature measurement, which was normal, were dark brown without evidence of blood.

Because of hematological changes additively blood smears were advised. There were many reacting lymphocytes, erythroblasts, spherocytes, hypochromic erythrocytes, reticulocytes, anulocytes and stomatocytes. Babesia canis was not found. Severe thrombocytopenia was diagnosed. Agglutination test was negative.

Tick-born disease-boreliosis, anpalasmosis, ehrlichiosis and dirofilariosis- Snap 4Dx blood test was performed, which confirmed anaplasmosis.

Ophthalmic treatment consist of installing into conjunctival sac eye drops with atropine sulfas(Atropinum sulfuricum 1% WZF)- 1 drop 3 x daily and dexamethasone(Dexamethason

WZF 0,1%)- 1 drop 3 x daily. There were no increasing in dose of drugs, because dose recommended by primary care veterinarian was enough to diminish symptoms of uveitis.

Doxycycline was started on dosis of 5mg/kg 2 x daily(Unidox Solutab 100 mg; Astellas) with protection of BioProtect- 1 capsule 1 x daily(VetExpert). Prednisolone was advised- 1mg/kg 1 x daily(Encorton 20 mg; Polfa Pabianice S.A.) with omeprazole-1 capsule 1 x daily(Omeprazol Teva) to diminish adverse effects of prednisolone on mucus membrane of the stomach.

During treatment control blood tests were being done. At the begging the total count of platelets increased, after few days decreased with another red blood parameters. Although there were no evident Babesia canis in smears imidocarb dipropionate were given as single dose-0,5 ml/10kg body weight (Imizol, Intervet) and blood transfusion was done. Hyphaema and subconjunctival hemorrhages resolved. Patient was stable for few months. Because of steroid hypothyroidism occurred. Count of platelets decreased again to 13000 and petechiaes within skin of abdomen appeared. The owner administered on her own pills against malaria without consultation( which she was taken on her own) because she suspected babesiosis. Few day after treatment general condition of the dog improved, platelets count rised to 300000. After another few days general condition of the dog started to worsen again. During control bitch was very weak with body temperature of 39 degree of Celsius. The owner reported lack of appetite and thirst. Blood test and ultrasound of abdomen were done. There was hepatic enlargement with many hypoechoic changes within liver and spleen. There were leucocytosis(34 000), normal platelets count 363G/L, high levels of liver enzymes: ALT =1026 U/L, AST= 177U/L, GLDH=93,7U/L, AP=2215U/L and increase of glucose level= 16,3 mmol/l and pancreatitis(DDGR lipase=389 u/l), calcium level decreased=2,06 mmol/l and decrease of serum iron=10,1umol/l. Two days later renal insufficiency and hydro-abdomen appeared. Animal was euthanized.

DISCUSSION

Anaplasmosis is a disease transmitted by ticks. It’s zoonosis which means that ticks can also infect human. Disease is caused by microorganism which belongs to Rickettsia. These are Anaplasma phagocytophilum (transmitted by tick Ixodes), which attacks granulocytes and Anaplasma platum (transmitted by tick Dermacentor) which affects platelets. First one is responsible for symptoms of lameness and painful joints; clinical signs are similar to boreliosis. Blood tests in A. phagocytophilum infection show lymphopenia, later lymphocytosis and thrombocytopenia in 80% of dogs. Sometimes in blood smear intracytoplasmic organisms are visible. In Europe most affected are people and animals living in the center of Europe or in the north. Anaplasma platum causes mainly cyclic thrombocytopenia (platelet count less than 20 000) and signs such as patechiaes , hemorrhages and pale mucus membrane. Infections caused by A. platum appear mainly in Greece, Spain, Portugal or Israel [Sainz et al. 2015].

In this case ophthalmic findings with the disease were obscured because of therapy with steroids. Most often signs of A. phagocytophilum infection are not specific- there is often pyremia, lethargy, lack of appetite and anorexia. Additively pale mucus membranes and signs from gastrointestinal tract such as vomits or diarrhea, lymph nodes enlargement , superficial bleedings appear. During RTG or USG splenomegaly is common finding. General weakness sometimes is because of autoimmune arthritis. Rarely collapse , cough, episcleral vessel congestion or uveitis appears. Since ophthalmic findings in reported case were so severe in comparison to general findings it could mistakenly lead to wrong diagnosis.

In anaplasmosis first sign in laboratory tests is thrombocytopenia , which is seen in routinely screen tests. In 60% of blood smears characteristic morules are visible in neutrophils. In dogs experimentaly infected with A. phagocytophilum morules appeared at 4th day of inoculation and were visible for 4-8 days. Test which definitely confirms diagnosis is PCR. More available is SNAP test 4Dx(Idexx), described earlier. In this case there was erhytropenia and values of hematocrit and hemoglobin was decreased. There was also increased the amount of granulocytes . Horiba ABC device wasn’t able to count the amount of platelets. There was erythropenia with mild regeneration. Quick SNAP test confirmed anaplasmosis. Improvement after treatment confirmed diagnosis.

Treatment of anaplasmosis consist of systemic doxycycline therapy for 2-3 weeks (up to 4 weeks) in dose of 5mg/kg 2 x daily or 10mg/kg 1 x daily [Gelatt, 2000, Maggs et al., 2009, Martin, 2010]. Further treatment depends on course of the disease an main signs. In some cases hospital with blood transfusion, fluid therapy and pyrexia and pain therapy is mandatory. In typical cases steroid are not necessary unless ther is no improvement after previous treatment or there are autoimmune signs- autoimmune anemia, trombocythopenia, uveitis, glomerulonephritis, vasculitis [Peiffer, 2009]. In such cases prednisone (or prednisolone) is recommended in dose of 0,5 to 2 mg/kg/day [Smith et al., 2005].

In this patient initial treatment was effective and caused improvement. Deterioration was caused by steroids, which were necessary. Despite of treatment with steroid with recommended dose multiple organ dysfunction appeared. It is suspected in this case that additive problems were involved in the course of disease.

In available publications [Cockwill et al., 2009, Internal medicine case studies, Case 16] there are described two siberian huskies suffering from anaplasmosis. In both cases clinical signs were reluctant to move, lethargy, lack of appetite, pyrexia. In one dog painless oedema around stifle join appeared without stiffness. In both cases thrombocytopenia occurred. Treatment with doxycycline in dose of 5mg/kg 2 x daily for 21 days in early diagnosis resolved the symptoms and patients completely recovered.

Ocular signs were not present in any described case. Since that it should be outline, that early diagnosis in our case and breed predilections could suggest VHK (Fig. 3)

Figure 3

In differential diagnosis attention should be paid on skin changes, which are common in uveodermatologic syndrome, like in Siberian husky showed on pictures (Fig. 4 and 5) treated also in our Veterinary Ophthalmic Center. Depigmentation of skin-mucosa junction, eyelids and coat in general could be present. These signs could appear before ophthalmic changes, with them or could be very mild so final diagnosis is based on histopathology from for example edges of the lips.

Figure 4

Figure 5

Both VKH syndrome and anaplasmosis could lead to death of the patient which is the reason why testing, which leads to right diagnosis and treatment, performed soon enough are crucial. In described case first diagnosis of VKH was motivated by breed predilection. But sings of petechiaes suggested clotting disorders which are not typical for VKH. Lack of skin changes also suggested different diagnosis, but in very rare cases of VKH skin lesions could not be present indeed, especially in the first phase of the disease. General blood tests and fast diagnostic tests confirmed one of tick -borne diseases. In described case despite of suitable

treatment and initial good response for it, multiple organ deficiency appeared, which obscured the disease.

BIBLIOGRAPHY

1. Gelatt K.: Essentials of Veterinary Ophthalmology. Lipincott, Williams & Wilkins, Philadelphia 2000.

2. Maggs D.J., Miller P.E., Ofri R.: Okulistyka weterynaryjna Slattera. Wyd. 1. polskie, red. Garncarz J., Elsevier Urban & Partner Sp. z o.o., 2009.

3. Martin C.L.: Ophthalmic diseases in veterinary medicine, Manson Publishing/The Veterinary Press, p. 221, 2010.

4. Peiffer R.L., Petersen Jones S.M.: Small Animal Ophthalmology: A Problem-Oriented Approach. 4 edycja, Saunders Elsevier, 2008.

5. Smith Jr F.W.K., Tilley L.: 5 minut konsultacji weterynaryjnej. Psy i koty. Elsevier Urban & Partner Sp. z o.o., 2008.

6. Ken R. Cockwill, Susan M. Taylor, Elisabeth C.R. Snead, Ryan Dickinson, Kevin Cosford, Sarah Malek, L. Robbin Lindsay, and Pedro Paulo Vissotto de PaivaDiniz: Granulocytic anaplasmosis in three dogs from Saskatoon, Saskatchewan, Can Vet J. 2009 Aug; 50(8): 835–840.

7. Ángel Sainz, Xavier Roura, Guadalupe Miró, Agustín Estrada-Peña, Barbara Kohn, Shimon Harrus and Laia Solano-Gallego: Guideline for veterinary practitioners on canine ehrlichiosis and anaplasmosis in Europe, Parasit Vectors. 2015; 8: 75.

8. Internal medicine case studies, Case 16: Anaplasm aphagocytophilum infection in a 2 year old neutered male Siberian Husky, http://www.ed.ac.uk/