Steroid-Responsive Idiopathic Neutropenia

INTERNAL MEDICINE CASE STUDIES Case 5: Steroid responsive immune mediated neutropenia in 4 year old female neutered Italian Spinone A 4 year old female neutered Italian Spinone was referred to the R(D)SVS Internal Medicine Service with a 1 week history of lethargy and inappetance. Evaluation by the referring veterinarian revealed neutropenia. Clinical examination revealed that the dog was pyrexic (40.1°C). Haematology revealed that the neutropenia was still present (table 1). Serum biochemistry was unremarkable. Due to the profound neutropenia, treatment with potentiated amoxicillin and marbofloxacin was initiated. In order to evaluate the dog for an infective process, thoracic radiographs, abdominal ultrasonography and infectious disease PCR screens were performed which were unremarkable. Bone marrow aspiration was performed to evaluate maturation of the neutrophilic lineage. The bone marrow aspirate was consistent with myeloid hypoplasia and maturation arrest at the neutrophilic promyelocyte stage. Although this may be consistent with an early marrow response to increased consumption, the fact that no underlying septic focus was identified on clinical and diagnostic evaluations and the neutropenia was persistent made this unlikely. Immune-mediated destruction was considered most likely at this stage. As no underlying cause had been identified, an idiopathic possibly primary immune-mediated neutropenia was the presumptive diagnosis. Antibiotic cover was continued and oral prednisolone was administered. Fortyeight hours after starting immunosuppression (Day 4), the dog appeared bright, alert responsive and had a good appetite. Haematology revealed that the neutrophil count was within the reference range (table 1). Rectal temperature was within reference range. Twelve days after discharge, the dog was reported to be behaving normally aside from polydipsia and polyuria. Clinical examination was unremarkable and the dog was normothermic. Haematology revealed a normal neutrophil count, the monocytosis was less pronounced and lymphopenia had resolved (Table 1). Antibiotic cover was withdrawn after 5 days. Twenty-three days after discharge the owners only concern was polydipsia. Clinical examination was unremarkable. Haematology showed a mild neutrophilia and reduction in monocytosis (Table 1). The prednisolone dose was tapered by 25%. At day 37 the owner noted that the polydipsia had decreased. Routine haematology showed a reduction in the neutrophilia and that the other cell lines had normalised. The prednisolone dose was further tapered by 25%. The diagnosis was steroid-responsive idiopathic neutropenia in this case as no underlying cause could be found and a prompt response was seen to prednisolone1-3. It is suspected that immune-mediated destruction was the cause of the neutropenia. Immune-mediated neutropenia is well described in humans and anti-neutrophil antibody tests are recommended to reach a diagnosis. Although direct and indirect testing for anti-neutrophil page 1 of 3 antibodies have been described in dogs, these are not commercially available and were not available for this case4,5. It has been suggested that until these tests are available, the diagnosis of immune-mediated neutropenia be based on fulfilment of three of four criteria; 1) Exclusion of other known causes of neutropenia, 2) Presence of concurrent immunemediated disease, 3) Bone marrow cytology supportive of immune-mediated destruction of neutrophils and 4) Prompt response to corticosteroid administration. Although this case had no other concurrent immune-mediated disease, it did fulfil the other 3 criteria and, as a result on this basis could be classified as immune-mediated neutropenia. In dogs, immune-mediated attack has been reported the level of mature neutrophils, in which case the myeloid series may appear normal or increased on bone marrow examination. Alternatively, destruction of neutrophil precursors may occur and an absence of neutrophil precursors may be seen. This case demonstrated apparent maturation arrest at the level of neutrophilic promyelocyte, suggesting that immune-mediated attack was at the precursor stage. Consistent with previously reported cases of canine immune-mediated neutropenia, this case showed a rapid response to immunosuppressive medication. Spontaneous remission is reported in human cases and canine cases have been reported to have good prognoses. Parameter Day 0 Day 2 Day 4 Day 12 after discharge Day 37 After discharge Reference Range 0.39 Day 23 after discharge . 0.42 Packed Cell Volume Red Blood cells Haemoglobin Mean Cell Volume MCHC Total WBC Neutrophils 0.41 0.4 0.39 0.45 0.39-0.55l/l 6.29 6.29 6.14 6.1 6.35 6.5 13.6 65 12.9 66 12.8 66 13.7 65 14.8 65 5.5-8.5 x 1012/l 12-18g/l 60-77fl 13.5 66 32.4 4.8 0.24 33 6.3 0.06 32.5 14.6 4.23 33 20.2 11.7 33 24.75 21.3 34 18.3 16.2 Lymphocytes 2.01 2.83 0.29 4 0.65 0.75 Monocytes Eosinophils Basophils Platelets 2.44 0.1 0 277 3.4 0 0 250 9.9 0 0 221 4 0.3 0 231 2.4 0.4 0 482 1.35 0 0 374 32-36% 6-15 x109/l 3.6-12 x109/l 0.7-4.8 x109/l 0-1.5 x109/l 0-1 x109/l 0-0.2 x109/l 200-500 x109/l Table 1 : Haematology results page 2 of 3 References 1 Brown, C.D., Parnell, N.K., Schulman, R.L., Brown, C.G., Glickman, N.W., Glickman, L., 2006, Evaluation of clinicopathologic features, response to treatment, and risk factors associated with idiopathic neutropenia in dogs: 11 cases (1990-2002). J Am Vet Med Assoc 229, 87-91. 2 McManus, P.M., Litwin, C., Barber, L., 1999, Immune-mediated neutropenia in 2 dogs. J Vet Intern Med 13, 372-374. 3 Perkins, M.C., Canfield, P., Churcher, R.K., Malik, R., 2004, Immune-mediated neutropenia suspected in five dogs. Aust Vet J 82, 52-57. 4 Weiss, D.J., 2007a, Evaluation of antineutrophil IgG antibodies in persistently neutropenic dogs. J Vet Intern Med 21, 440-444. 5 Weiss, D.J., 2007b, An indirect flow cytometric test for detection of anti-neutrophil antibodies in dogs. Am J Vet Res 68, 464-467. The University of Edinburgh is a charitable body, registered in Scotland, with registration number SC005336. www.ed.ac.uk/vet/hfsa-int-med page 3 of 3