NODULAR PANNICULITIS AND BILATERAL UVEITIS IN A DOG: IS IT RELATED TO TOXOPLASMOSIS? Ekrem Çağatay ÇOLAKOĞLU 1, İrem ERGİN 2, Hasan Basri ŞENEL 3 1 Ankara University, Faculty of Veterinary Medicine, Department of Internal Medicine, 06110 Ankara, Turkey 2 Ankara University, Faculty of Veterinary Medicine, Department of Surgery, 06110 Ankara, Turkey 3 Diskapi Yildirim Beyazit Training and Research Hospital, Department of Pathology, 06110 Ankara, Turkey ABSTRACT Canine nodular panniculitis is defined as the inflammation of subcutaneous fat tissue with a wide variety of ethiologies. A 10 year old, mixed-breed dog referred to Small Animal Hospital with a history of bilateral vision loss and recurrent dermatologic problems. Both eyes had uveitis. The skin lesions were lumpy or crater-like in appearance, 5-10 mm in diameter and nodular. Swab samples taken from the lesions for routine microbiological culture were negative. Routine blood work revealed severe leukocytosis. However, ELISA result of blood samples revealed Toxoplasmosis. Nodular panniculitis with tachyzoites were diagnosed with excisional biopsy. Methylprednisolone and Clindamycine were received and healing of the all skin lesions occurred. Key words: Dog, Methylprednisolone, Nodule, Panniculitis, Skin INTRODUCTION Canine nodular panniculitis is defined as the inflammation of subcutaneous fat tissue with a wide variety of ethiologies including infection, trauma, foreign body, postinjection site inflammation, vasculitis, vitamin E deficiency, drug eruption, insect bite, pancreatic disease, lupus erythematous and neoplasia (Moreau et al., 1982; Scott and Anderson, 1988; Scott et al., 2001). However, in most cases, an underlying aetiology can not be found and most cases described as idiopathic sterile nodular panniculitis (German et al., 2003). Exact pathogenesis of the disease has not been still well understood (Scott et al., 2001). The skin lesions in dogs with panniculitis characterized by solitary or multiple nodular, lumpy and crater-like in appearance (Torres, 1999). It is also possible to be an association between skin lesions and systemic signs including pyrexia, lethargy, anorexia and uveitis (Torres, 1999). Few cases of histologically confirmed panniculitis regarding cutaneous toxoplasmosis have been reported (Hoffmann et al., 2012; Oliveira et al., 2014). The report presented here reflects the nodular panniculitis and bilateral uveitis in a dog with cutaneous toxoplasmosis. CASE HISTORY A 10-year old, 23 kg, neutered female mixed breed dog with a history of recurrent nodular wounds, anorexia and bilateral vision loss referred to Small Animal Hospital of Veterinary Faculty, Ankara University. The dog was not receiving any medication at the time of referral investigation. The dog had also routine vaccination against rabies, distemper, parainfluenza and herpes virus infection, parvoviral enteritis and leptospirosis. Physical examination revealed poor skin health status, normothermia (39.1 C o ), normal heart rate (161 bpm) and capillary refill time (<3s). Appearing the ulcerative lesions with suppurative inflammation (Figure 1) following the forming of lumpy masses (Figure 2) were more remarkable on the face of the dog. Skin lesions on the body were also crater-like in appearance and 5-10 mm in diameter (Figure 3a, Figure 3b). In opthalmoscopic examination, dog was totally blind. Both eyes had Volume VI, 2016, Number 5: VETERINARY MEDICINE, ANIMAL STUDIES 97
iridial hemorrhages, discolorations and myosis. Intraocular pressures were in normal limits in both eyes. Ultrasonographic exam revealed hyperechoic iris, cliary body and choroidea. Severe iridocyclitis (anterior uveitis) and moderate choroiditis (posterior uveitis) were also determined. A rapid Heartworm and Leishmania antigen test was negative. Routine blood work of the dog were shown in Table 1. Abdominal ultrasound, fecal examination, blood smear and sterile swab samples taken from the crater-like lesions for fungal and bacterial culture revealed any pathological changes. Toxoplasma Ab were defined by ELISA as OD:0.811 (Negative control Toxo-Ab: 0.055; Positive control Toxo- Ab: 1.094; OD>0.570 for positivity). Excisional biopsy samples taken from the effected lumpy skin fixed in 10% buffered formalin and processed for paraffin embedding. The sections were stained with hematoxylen and eosin (H&E). Histological findings in skin biopsies revealed panniculitis with vasculitis and pyogranulomatous inflammation including neutrophils, fragments of necrotic debris and multinucleated giant cells (Figure 4). Large numbers of tachyzoites were also identified in the cytoplasm of the cells (Figure 5). Following medications were initiated in the dog: Clindamycine (10 mg/kg, PO, BID for 2 weeks) and Methylprednisolone (1 mg/kg, IM, two injections with 3 week intervals). The clinical signs decreased within 2 weeks following the medication. Routine blood work in the 2nd week of therapy was shown in Table 2. Follow-up controls of the skin revealed recovery of the lesions (Figure 6, Figure 7, Figure 8). No recurrence was occurred. Lomefloxacine (BID for 7 days) and hyaluronic acid (TID for 10 days) eye drops were performed. Within a week, the dog started to have a vision with her left eye. Uveitis was successfully treated in both eyes but the right eye with high intraocular pressure (51 mmhg) was completely blind. Dorsolamide eye drop (BID) used in this eye for the control of intraocular pressure. DISCUSSION Cutaneous toxoplasmosis is a rare infection reported in human and Veterinary Medicine (Amir et al., 2008; Oliveira et al., 2014). Clinical cases in Veterinary Medicine have often reported in cats (Anfray et al., 2005; Park et al., 2007). However, few cases of histological confirmed cutaneous toxoplasmosis defined in dogs (Webb et al., 2005; Hoffmann et al., 2012). This rare case presented here reflects the cutaneous toxoplasmosis confirmed histologically in a dog. It is described the immunsuppression or concomitant secondary disease as a possible cause of cutaneous toxoplasmosis in dogs (Dubey et al., 2009). In the case presented here, no concomitant disease such as systemic lupus, demodicosis or leishmaniasis were defined. The dog was not receiving any immunsuppressive medication for any disease at the time of referral investigation. Although the dog had indoor/outdoor status, no reflection we defined in complete blood count for immunsuppression. Clinical lesions of cutaneous toxoplasmosis in dogs described as multiple raised ulcerated nodules with suppurative inflammation (Webb et al., 2005). The dog presented here had not only multiple stable cutaneous nodules but also cutaneous nodules with suppurative imflammation. In cases of cutaneous toxoplasmosis previously described, histopathology revealed necrotizing and pyogranulomatosus dermatitis and, panniculitis with vasculitis. It is also possible to see the tachyzoites in clusters within the cells or cytoplasm in biopsy sections taken from cutaneous lesions (Dubey et al., 2009; Webb et al., 2005). Smilar histological findings in this case were observed. In addition, smilar histological findings can also be observed in animals infected with N. Caninum (Poli et al., 1998). Because of this challange, making an exact histopathological differential diagnosis was not possible in the case. The major limitation to confirm the diagnosis was not to be used of PCR and electron microscopy in the case. Although Clindamycin has been successfully used in toxoplasmosis, clinical signs of occular Volume VI, 2016, Number 5: VETERINARY MEDICINE, ANIMAL STUDIES 98
toxoplasmosis have responded more slowly to treatment with Clindamycin (Greene et al., 1985). In the case presented here, uveitis started to regress slowly by administration of methylprednisolone. With the adding of Clindamycin to therapy, the regression became more rapidly. However, it would not be true to say that the regression is from Clindamycin. No significant occular changes were also observed in the follow-up controls of the right eye. Figure 1 Figure 2 Figure 3a Figure 3b Volume VI, 2016, Number 5: VETERINARY MEDICINE, ANIMAL STUDIES 99
Table 1. Routin Blood Work of the Case Results Ranges * Results Ranges * WBC 10 9 /l 43.6 6-17 RDW % 16.9 12-17.5 LYM 10 9 /l 2.8 0.9.5 PLT 10 9 /l 391 200-500 MONO 10 9 /l 3.0 0.3-2.5 Glucose mg/dl 102.7 65-118 NEUT 10 9 /l 27.4 3.5-12 Urea mg/dl 52.2 15-59.9 EOS 10 9 /l 10.4 0.1-19 Creatinin mg/dl 1.12 0.5-1.5 LYM % 6.5 12-30 T. Protein g/dl 5.12 5.4-7.1 MONO % 6.9 2-13 Albumin g/dl 2.0 3.1-4 NEUT % 62.8 35-70 T. Bilirubin mg/dl 0.15 0.1-0.3 EOS % 23.8 0.1-19 ALP IU/L 190 20-156 RBC 10 12 /l 5.82 5.5-8.5 ALT IU/L 21.8 21-102 HGB g/dl 11.9 12-18 AST IU/L 74.2 23-66 HCT % 32.5 37-55 CK IU/L 533.9 <200 MCV fl 55.8 60-72 GGT IU/L 1.0 6-28 MCH pg 20.5 19.5-25.5 Na mmol/l 132 140-154 MCHC g/dl 36.8 32-38.5 P mmol/l 3.8 3.8-5.6 RDWa fl 29.5 35-53 *Kaneko et al., 2008 Figure 4 Figure 5 Volume VI, 2016, Number 5: VETERINARY MEDICINE, ANIMAL STUDIES 100
Figure 6 Figure 7 Figure 8 Volume VI, 2016, Number 5: VETERINARY MEDICINE, ANIMAL STUDIES 101
Results Table 2. Routin Blood Work of the Dog Following Therapy Ranges * Results Ranges * WBC 10 9 /l 10.0 6-17 MCV fl 54.5 60-72 LYM 10 9 /l 1.2 0.9.5 MCH pg 21.1 19.5-25.5 MONO 10 9 /l 1.1 0.3-2.5 MCHC g/dl 38.6 32-38.5 NEUT 10 9 /l 3.3 3.5-12 RDWa fl 33.2 35-53 EOS 10 9 /l 4.4 0.1-19 RDW % 19.8 12-17.5 LYM % 11.9 12-30 PLT 10 9 /l 167 200-500 MONO % 11.4 2-13 T. Protein g/dl 6.7 5.4-7.1 NEUT % 33.6 35-70 Albumin g/dl 2.9 3.1-4 EOS % 43.1 0.1-19 ALP IU/L 270 20-156 RBC 10 12 /l 3.77 5.5-8.5 AST IU/L 31.4 23-66 HGB g/dl 7.9 12-18 CK IU/L 326 <200 HCT % 20.6 37-55 *Kaneko et al., 2008 REFERENCES 1. Amir G, Salant H, Resnick IB, Karplus R. 2008. Cutaneous toxoplasmosis after bone marrow transplantation with molecular confirmation. J Am Acad Dermatol, 59:781 784. 2. Anfray P, Bonetti C, Fabbrini F, Magnino S, Mancianti F, Abramo F. 2005. Feline cutaneous toxoplasmosis: a case report. Vet Dermatol, 16:131 136. 3. Dubey JP, Lindsay DS, Lappin MR. 2009. Toxoplasmosis and other intestinal coccidial infections in cats and dogs. Vet Clin North Am Small Anim Pract, 39:1009 1034. 4. German AJ, Foster AP, Holden D, Hotston Moore A, Day MJ, Hall EJ. Sterile nodular panniculitis and pansteatitis in three weimaraners. JSAP, 2003; 44, 449-455. 5. Greene CE, Cook JR JR, Mahaffey EA. 1985. Clindamycin for treatment of Toxoplasma polymyositis in a dog. J Am Vet Med Assoc, 187:631 634. 6. Hoffmann AR, Cadieu J, Kiupel M, Lim A, Bolin SR, Mansell J. 2012. Cutaneous toxoplasmosis in two dogs. JVDI, 24(3), 636 640. 7. Kaneko JJ, Harvey JW, Bruss ML. 2008. Clinical Biochemistry of Domestic Animals, 8th ed, Academic Press, 889-895. 8. Moreau PM, Fiske RA, Lees GE, Corrier DE. 1982. Disseminated necrotizing panniculitis and pancreatic nodular hyperplasia in a dog. J Am Vet Med Assoc, 180:422 425. 9. Oliveira TS, Turchetti AP, Barbosa FBS, Bicalho ALF, Alencar CAD, Paixão TA, Santos RL, 2014. Cutaneous toxoplasmosis in an immunosuppressed dog. Arq. Bras. Med. Vet. Zootec, 66(3), 797-800. 10. Park CH, Ikadai H, Yoshida E, Isomura H, Inukai H, Oyamada T. 2007. Cutaneous toxoplasmosis in a female Japanese cat. Vet Pathol, 44: 683 687. 11. Poli A, Mancianti F, Carli MA, Stroscio MC, Kramer L. 1998. Neospora caninum infection in a Bernese cattle dog from Italy. Vet Parasitol, 78:79 85. 12. Scott DW, Anderson WI. 1988. Panniculitis in dogs and cats: A retrospective analysis of 78 cases. J Am Anim Hosp Assoc, 24:551 559. Volume VI, 2016, Number 5: VETERINARY MEDICINE, ANIMAL STUDIES 102
13. Scott DW, Miller WH, Griffin DE. 2011. Muller and Kirk s Small Animal Dermatology, 6th ed, Philadelphia, Elsevier, 1156-1162. 14. Torres SMF. 1999. Sterile nodular dermatitis in dogs. Vet Clin North Am Small Anim Pract, 29:1311 1314. 15. Webb JA, Keller SL, Southorn EP, Armstrong J, Allen DG, Peregrine AS, Dubey JP. 2005. Cutaneous manifestations of disseminated toxoplasmosis in an immunosuppressed dog. J Am Anim Hosp Assoc, 41:198 202. Volume VI, 2016, Number 5: VETERINARY MEDICINE, ANIMAL STUDIES 103