A dog in pain

Antonio Meléndez-Lazo DVM PhD DipECVCP MRCVS

SIGNALMENT AND HISTORY

A 6-year-old, male neutered, German shepherd dog presented to the veterinarian with a history of reluctance to move, hyporexia, lethargy and exfoliative cutaneous lesions on the nose and ear tips. The dog was adopted 6 months ago, and previous clinical and travel history was unknown.

 

PHYSICAL EXAMINATION

On clinical examination, submandibular, popliteal and prescapular lymphadenomegaly was noted.  The dog showed severe pain during palpation of both carpi tarsi and knees.

 

INVESTIGATION

Haematology and biochemistry

Blood work was performed as part of routine diagnostic workup. Haematology revealed mild non-regenerative anemia and mild leukocytosis due to mature neutrophilia and monocytosis. Lymphopenia was also present.  Peripheral blood smear evaluation was unremarkable. Biochemistry showed mild increased in urea, and severe hyperproteinemia due to increased gamma globulins, while albumin concentration was decreased (Figure 1). No other abnormalities were found.

Figure 1. Electrophoretogram showing polyclonal gammopathy

Joint cytology

Fine-needle aspiration (FNA) cytology of different joints was performed, and they showed similar findings (Figure 2).

Figure 2. Representative micrograph of synovial fluid findings. FNA cytology (Wright-Giemsa stain, 50x objective).

What is your interpretation of the clinicopathological results?

The most common cause of mild non-regenerative anemia is inflammation. Other possible interpretation would be a pre-regenerative state (regeneration takes 3 to 5 days to occur in dogs after an episode of hemolysis or blood loss).

The leukogram is typical of exposure to corticosteroids (i.e. due to stress secondary to pain).

Hypoalbuminemia is most likely due to inflammation, as albumin is a negative acute phase protein (its production is decreased in inflammatory states). Increased gamma-globulins indicates severe antigenic stimulation due to inflammation, infection or neoplasia.

The presence of increased numbers of neutrophils in synovial fluid from different joins is diagnostic for polyarthritis.

 

Which are your differential diagnoses for the findings in the joints?

Polyarthritis can be degenerative, septic or immune-mediated in origin. Immune-mediated polyarthritis (IMPA) are classified in erosive and non-erosive, being the latter the most common. In the non-erosive polyarthritis group, several causes are identified: infectious diseases such as Ehrlichia spp., Leishmania infantum, Borrelia burgdorferi, Bartonella spp. and occult bacterial infections (discospondilits, endocarditis, pyometra, pyelonephritis); vaccinations and drugs such as trimetoprim-sulfonamides, cephalosporines and penicillins; immune-mediated syndromes such as systemic lupus erythematosus (SLE), polyarthritis / polymyositis syndrome, polyarthritis / meningitis syndrome and other breed specific syndromes; and idiopathic. Idiopathic IMPA are classified in 4 types: type I (no underlying disease), type II (associated with infections distant to the joint), type III (associated with GI disorders) and type IV (associated with occult neoplasia).


What further tests would you perform?

Diagnostic workout should be progressive, from the easiest and cheapest test to those more expensive and invasive if needed.

-          Fine needle aspiration (FNB) from the lymph nodes

-          Serologies/PCRs for infectious diseases present in the geographic area

-          Imagine diagnostic techniques

-          Skin biopsies if necessary

 

Additional tests

-          Cytology

Fine needle biopsy from submandibular and popliteal lymphnodes was performed (Figure 3). Cytological examination revealed reactive lymphoid hyperplasia characterized by a moderate increased in plasma cells. Frequently, small structures morphologically consistent with Leishmania amastigotes were found in the background and phagocytosed by macrophages.

-          Serological testing

Because travel history of the patient was unknown and coinfections are frequent, serologies against Leishmania infantum, Ehrlichia canis and Anaplasma spp. were done by enzyme-linked immunosorbent assay (ELISA), revealing high positivity of anti-leishmanial antibodies and being negative for the rest of infectious agents.

DIAGNOSIS: Leishmaniosis with likely secondary immune-mediated polyarthritis

 

STAGING, TREATMENT AND FOLLOW-UP

 

Clinical staging was done according to the guidelines established by the LeishVet group.

For that purpose, urine protein-to-creatinine ratio was determined, revealing proteinuria. Therefore, it was classified on stage III (moderate disease). This stage includes dogs with medium to high positive antibody levels, clinical signs such as cutaneous lesions and weight loss and signs originating from immune-complex deposition (such as polyarthritis in this case).

 

Treatment with alopurinol (10 mg/Kg twice a day) and meglumine antimoniate (75-100 mg/kg once a day for 4 weeks) was instituted.

 

At 1-month follow-up, clinical signs had notably improved, and articular pain was gone. Although antibody levels remained high, serum protein electrophoresis showed higher albumin-to-globulin ratio and proteinuria decreased.

 

Clinical improvement of polyarthritis after treatment for leishmaniosis demonstrated the relationship between both clinical entities.

 

SUMMARY

 

Canine leishmaniosis is a protozoal, life-threatening disease and worldwide distributed zoonosis transmitted by phlebotomine sand flies. The disease is endemic in over 70 countries with especially high prevalence in the Mediterranean basin and Brazil. With the upswing of global tourism and international trade and transport of dogs, CanL is becoming an emerging disease other in several countries. The diagnosis is in some cases complex due to the wide variety of clinical signs in infected dogs.

 

It has been hypothesized that Leishmania can cause arthritis by two mechanisms, one being the direct presence of the parasite within the joint, which can cause a granulomatous inflammatory reaction, and the second being a type III hypersensitivity reaction, with deposition of immune complexes within the joint.

 

References:

 

-          Solano-Gallego L, Miró G, Koutinas A, Cardoso L, Pennisi MG, Ferrer L, Bourdeau P, Oliva G, Baneth G, The LeishVet Group. LeishVet guidelines for the practical management of canine leishmaniosis. Parasit Vectors. 2011 May 20;4:86.

-          Sbrana, S., Marchetti, V., Mancianti, F., Guidi, G., & Bennett, D. (2014). Retrospective study of 14 cases of canine arthritis secondary to Leishmaniainfection. Journal of Small Animal Practice, 55(6), 309–313.