ttp://www.bsava.com
CASE REPORT
Carbimazole-associated hypersensitivity vasculitis in a cat K. Bowlt, I. Cattin and J. Stewart Animal Health Trust, Lanwades Park, Newmarket, Suffolk CB8 7UU
Feline hyperthyroidism can be treated medically, surgically or with radioactive iodine. Carbimazole inhibits both triiodothyronine and thyroxine synthesis in the thyroid gland and reported side effects include mild eosinophilia, leucopenia and lymphocytosis, thrombocytopenia, elevated liver enzyme activities, gastrointestinal signs and skin abnormalities. This case report describes a cat with carbimazole-associated apparent hypersensitivity vasculitis causing digital and tail necrosis, with multiple renal infarcts. Withdrawal of carbimazole resulted in stable disease.
Journal of Small Animal Practice (2013) DOI: 10.1111/jsap.12154 Accepted: 3 September 2013
INTRODUCTION Feline hyperthyroidism affects as many as 1 in 300 middle-aged and older cats and can be treated medically, surgically or with radioactive iodine (Mooney et al. 1992, Frenais et al. 2009). Carbimazole is the prodrug of thiamazole (methimazole) and is commonly used to treat feline hyperthyroidism. It functions by inhibiting both triiodothyronine (T3) and thyroxine (T4) synthesis in the thyroid gland (Janson et al. 1983). Reported side effects include mild eosinophilia, leucopenia, lymphopenia, agranulocytosis, anaemia, thrombocytosis, leucocytosis, lymphocytosis, thrombocytopenia, elevated liver enzyme activities, gastrointestinal signs and skin abnormalities (Frenais et al. 2009). This case report describes an additional adverse effect of apparent hypersensitivity vasculitis causing digital and tail necrosis, with multiple renal infarcts in a cat receiving oral carbimazole.
CASE HISTORY A nine-year-old, 2·4-kg female neutered domestic longhair cat was presented to the primary veterinary surgeon by a rescue centre (day 1). With the exception of a chronic herpetic ulcer in the left eye and intermittent vomiting, which resolved after provision of a prescription diet (Hills i/d), there was no significant previous history. The cat received regular parasiticide medication [imidacloprid/moxidectin (Advocate; Bayer) spot on every 4 to 6 weeks]. Physical examination demonstrated a large right palpable goitre, emaciation and tachycardia (200 bpm). A dose of 15 mg carbimazole (Vidalta; MSD Animal Health) orally once daily was instituted for presumptive hyperthyroidism. No blood samples were taken because of the aggressive temperament of the cat. Journal of Small Animal Practice © 2013 British Small Animal Veterinary Association
On day 28, 150 g of weight had been gained, and a blood sample was taken. Abnormalities are listed in Table 1 and all remaining biochemical parameters (electrolytes, albumin, glucose, cholesterol, creatine kinase (CK), total protein) were all within their respective reference intervals. Haematology was not performed. On day 56, multifocal cutaneous crusts and an interscapular patch of acute moist pyodermatitis were reported. The cat tested negative for ectoparasites and received clavulanic acid potentiated amoxicillin (Noroclav; Norbrook) at an unknown dose orally twice daily for 14 days. Carbimazole was continued at the same dose. The cat was referred to the Animal Health Trust (AHT) to assess suitability for radioactive iodine (131I) therapy on day 70. Physical examination was generally unaltered compared with previous records (bodyweight: 2·9 kg, heart rate: 200 bpm, blood pressure: 143 mmHg, rectal temperature: 38·8 °C), but the multifocal crusts had reduced in severity. Systolic (Doppler) blood pressure was 143 mmHg. Full haematological, biochemical and T4 assessment were within their respective reference limits (Table 1). Urinalysis demonstrated slight proteinuria (++), but was otherwise unremarkable (specific gravity: 1·038) and urine culture was negative. Echocardiography was unremarkable. Abdominal ultrasound examination demonstrated enlargement of the medial iliac, gastric, hepatic and jejunal lymph nodes: these nodes maintained a normal shape and echogenicity. Kidneys were ultrasonographically normal. Cytological assessment of the medial iliac lymph node was consistent with a reactive lymphoid population. Scintigraphy was not performed as is not a routine procedure before radioiodine treatment at the AHT. 131I was ordered and the cat was discharged. On day 72, the cat re-presented to the referring veterinary surgeon for assessment of acute onset left hindlimb lameness. 1
K. Bowlt et al.
Examination demonstrated a cranial drawer of the left stifle. Radiography of the long bones were unremarkable. Cage rest was recommended. Examination 2 days (day 74) later revealed severe necrosis of all digits of the left hindlimb. A dose of 18·75 mg aspirin orally every third day, 20 µg/kg buprenorphine (Vetergesic; Alstoe) sublingually every 8 hours and 10 mg/kg metronidazole (Metronidazole, TEVA) orally twice daily were prescribed. On day 77, necrosis of the tail tip was reported and the carbimazole was discontinued, after which no further lesions were identified. Hills Y/D was prescribed. On day 83, the cat was re-presented to the AHT, where it was noted to be 4 of 10 lame on the left hindlimb, with rectal temperature of 38·5 °C, heart rate of more than 250 bpm, and respiratory rate of 36 bpm. Blood pressure was not assessed. The left digits II to IV were firm, cold and discoloured from the metatarsophalangeal joint distally (Fig 1a). No deep pain sensation could be elicited. Bilateral metatarsal pulses were palpable and were of good quality with no deficits. No heart murmurs were audible. No sensation was present in the distal half of the tail, which was cold, firm and discoloured (Fig 1b). All other extremities were normal. No other dermatological abnormalities were found; neurological and ophthalmological examinations were normal. Haematological and biochemical results are presented in Table 1 (results not presented were within reference intervals). Urinalysis was not performed. Prothrombin time, activated partial thromboplastin time and fibrin degradation products were within reference limits. Thromboelastography and T4 were not assessed. Echocardiography was unremarkable and the aorta was ultrasonographically normal along its entire length. Despite ultrasound of the kidneys on day 70 being unremarkable, repeat examination identified bilateral multiple, variably sized, hyperechoic, wedge-shaped renal infarcts, involving greater than 20% of the renal circumference (Fig 2a). Assessment of glomerular filtration was not performed. Routine mid femoral amputation and tail amputation was performed under general, local and epidural anaesthesia. Surgery was uneventful and the cat was discharged the following day with oral metronidazole (dose unaltered), a dose of 20 mg/kg clavulanic acid potentiated amoxicillin (Synulox; Pfizer) orally (a)
(b)
twice daily, aspirin (dose unaltered) and buprenorphine (dose unaltered). The limb and tail were fixed in 10% formalin and embedded in paraffin blocks. Sections of haired skin traversing grossly viable and non-viable tissue of the tail and distal hindlimb were taken and stained with haematoxylin and eosin (H&E). Infiltrating the viable aspect of haired skin were moderate numbers of lymphocytes, plasma cells and small numbers of neutrophils within the superficial and mid-dermis. There was abrupt necrosis of the epidermis, with loss of dermal adnexal structures and infiltration of large numbers of degenerate neutrophils within a fibrinoserous background. Moderate fibrosis replaced the pre-existing dermal structures. Intralesional capillaries were markedly congested and dilated. Neutrophils infiltrated the tunica media of small muscular arteries within the deep dermis, accompanied by fibrin, cellular and karyorrhectic necrotic debris. Vascular lumens were partially to fully occluded by mature fibrin thrombi with variable degrees of recanalisation evident (Fig 3). On day 91, repeat biochemical assessment (excluding T4) was within reference intervals. The wounds were healing uneventfully. Full abdominal ultrasound examination was comparable with the previous report, with no alteration in the renal changes. Both kidneys were assessed with both colour and spectral Doppler. No abnormalities were detected within the kidneys on colour Doppler evaluation. Resistive indices were obtained with spectral Doppler analysis of the renal arteries within both kidneys. The left kidney had mild elevation of the resistive index (RI=0·79), whereas the right kidney was normal (RI=0·68) (normal RI in cats
CASE REPORT
Carbimazole-associated hypersensitivity vasculitis in a cat K. Bowlt, I. Cattin and J. Stewart Animal Health Trust, Lanwades Park, Newmarket, Suffolk CB8 7UU
Feline hyperthyroidism can be treated medically, surgically or with radioactive iodine. Carbimazole inhibits both triiodothyronine and thyroxine synthesis in the thyroid gland and reported side effects include mild eosinophilia, leucopenia and lymphocytosis, thrombocytopenia, elevated liver enzyme activities, gastrointestinal signs and skin abnormalities. This case report describes a cat with carbimazole-associated apparent hypersensitivity vasculitis causing digital and tail necrosis, with multiple renal infarcts. Withdrawal of carbimazole resulted in stable disease.
Journal of Small Animal Practice (2013) DOI: 10.1111/jsap.12154 Accepted: 3 September 2013
INTRODUCTION Feline hyperthyroidism affects as many as 1 in 300 middle-aged and older cats and can be treated medically, surgically or with radioactive iodine (Mooney et al. 1992, Frenais et al. 2009). Carbimazole is the prodrug of thiamazole (methimazole) and is commonly used to treat feline hyperthyroidism. It functions by inhibiting both triiodothyronine (T3) and thyroxine (T4) synthesis in the thyroid gland (Janson et al. 1983). Reported side effects include mild eosinophilia, leucopenia, lymphopenia, agranulocytosis, anaemia, thrombocytosis, leucocytosis, lymphocytosis, thrombocytopenia, elevated liver enzyme activities, gastrointestinal signs and skin abnormalities (Frenais et al. 2009). This case report describes an additional adverse effect of apparent hypersensitivity vasculitis causing digital and tail necrosis, with multiple renal infarcts in a cat receiving oral carbimazole.
CASE HISTORY A nine-year-old, 2·4-kg female neutered domestic longhair cat was presented to the primary veterinary surgeon by a rescue centre (day 1). With the exception of a chronic herpetic ulcer in the left eye and intermittent vomiting, which resolved after provision of a prescription diet (Hills i/d), there was no significant previous history. The cat received regular parasiticide medication [imidacloprid/moxidectin (Advocate; Bayer) spot on every 4 to 6 weeks]. Physical examination demonstrated a large right palpable goitre, emaciation and tachycardia (200 bpm). A dose of 15 mg carbimazole (Vidalta; MSD Animal Health) orally once daily was instituted for presumptive hyperthyroidism. No blood samples were taken because of the aggressive temperament of the cat. Journal of Small Animal Practice © 2013 British Small Animal Veterinary Association
On day 28, 150 g of weight had been gained, and a blood sample was taken. Abnormalities are listed in Table 1 and all remaining biochemical parameters (electrolytes, albumin, glucose, cholesterol, creatine kinase (CK), total protein) were all within their respective reference intervals. Haematology was not performed. On day 56, multifocal cutaneous crusts and an interscapular patch of acute moist pyodermatitis were reported. The cat tested negative for ectoparasites and received clavulanic acid potentiated amoxicillin (Noroclav; Norbrook) at an unknown dose orally twice daily for 14 days. Carbimazole was continued at the same dose. The cat was referred to the Animal Health Trust (AHT) to assess suitability for radioactive iodine (131I) therapy on day 70. Physical examination was generally unaltered compared with previous records (bodyweight: 2·9 kg, heart rate: 200 bpm, blood pressure: 143 mmHg, rectal temperature: 38·8 °C), but the multifocal crusts had reduced in severity. Systolic (Doppler) blood pressure was 143 mmHg. Full haematological, biochemical and T4 assessment were within their respective reference limits (Table 1). Urinalysis demonstrated slight proteinuria (++), but was otherwise unremarkable (specific gravity: 1·038) and urine culture was negative. Echocardiography was unremarkable. Abdominal ultrasound examination demonstrated enlargement of the medial iliac, gastric, hepatic and jejunal lymph nodes: these nodes maintained a normal shape and echogenicity. Kidneys were ultrasonographically normal. Cytological assessment of the medial iliac lymph node was consistent with a reactive lymphoid population. Scintigraphy was not performed as is not a routine procedure before radioiodine treatment at the AHT. 131I was ordered and the cat was discharged. On day 72, the cat re-presented to the referring veterinary surgeon for assessment of acute onset left hindlimb lameness. 1
K. Bowlt et al.
Examination demonstrated a cranial drawer of the left stifle. Radiography of the long bones were unremarkable. Cage rest was recommended. Examination 2 days (day 74) later revealed severe necrosis of all digits of the left hindlimb. A dose of 18·75 mg aspirin orally every third day, 20 µg/kg buprenorphine (Vetergesic; Alstoe) sublingually every 8 hours and 10 mg/kg metronidazole (Metronidazole, TEVA) orally twice daily were prescribed. On day 77, necrosis of the tail tip was reported and the carbimazole was discontinued, after which no further lesions were identified. Hills Y/D was prescribed. On day 83, the cat was re-presented to the AHT, where it was noted to be 4 of 10 lame on the left hindlimb, with rectal temperature of 38·5 °C, heart rate of more than 250 bpm, and respiratory rate of 36 bpm. Blood pressure was not assessed. The left digits II to IV were firm, cold and discoloured from the metatarsophalangeal joint distally (Fig 1a). No deep pain sensation could be elicited. Bilateral metatarsal pulses were palpable and were of good quality with no deficits. No heart murmurs were audible. No sensation was present in the distal half of the tail, which was cold, firm and discoloured (Fig 1b). All other extremities were normal. No other dermatological abnormalities were found; neurological and ophthalmological examinations were normal. Haematological and biochemical results are presented in Table 1 (results not presented were within reference intervals). Urinalysis was not performed. Prothrombin time, activated partial thromboplastin time and fibrin degradation products were within reference limits. Thromboelastography and T4 were not assessed. Echocardiography was unremarkable and the aorta was ultrasonographically normal along its entire length. Despite ultrasound of the kidneys on day 70 being unremarkable, repeat examination identified bilateral multiple, variably sized, hyperechoic, wedge-shaped renal infarcts, involving greater than 20% of the renal circumference (Fig 2a). Assessment of glomerular filtration was not performed. Routine mid femoral amputation and tail amputation was performed under general, local and epidural anaesthesia. Surgery was uneventful and the cat was discharged the following day with oral metronidazole (dose unaltered), a dose of 20 mg/kg clavulanic acid potentiated amoxicillin (Synulox; Pfizer) orally (a)
(b)
twice daily, aspirin (dose unaltered) and buprenorphine (dose unaltered). The limb and tail were fixed in 10% formalin and embedded in paraffin blocks. Sections of haired skin traversing grossly viable and non-viable tissue of the tail and distal hindlimb were taken and stained with haematoxylin and eosin (H&E). Infiltrating the viable aspect of haired skin were moderate numbers of lymphocytes, plasma cells and small numbers of neutrophils within the superficial and mid-dermis. There was abrupt necrosis of the epidermis, with loss of dermal adnexal structures and infiltration of large numbers of degenerate neutrophils within a fibrinoserous background. Moderate fibrosis replaced the pre-existing dermal structures. Intralesional capillaries were markedly congested and dilated. Neutrophils infiltrated the tunica media of small muscular arteries within the deep dermis, accompanied by fibrin, cellular and karyorrhectic necrotic debris. Vascular lumens were partially to fully occluded by mature fibrin thrombi with variable degrees of recanalisation evident (Fig 3). On day 91, repeat biochemical assessment (excluding T4) was within reference intervals. The wounds were healing uneventfully. Full abdominal ultrasound examination was comparable with the previous report, with no alteration in the renal changes. Both kidneys were assessed with both colour and spectral Doppler. No abnormalities were detected within the kidneys on colour Doppler evaluation. Resistive indices were obtained with spectral Doppler analysis of the renal arteries within both kidneys. The left kidney had mild elevation of the resistive index (RI=0·79), whereas the right kidney was normal (RI=0·68) (normal RI in cats
