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A case report of locally invasive Aspergillus fumigatus infection in a patient on canakinumab

A case report of locally invasive Aspergillus fumigatus infection in a patient on canakinumab Downloaded from https://academic.oup.com/ehjcr/article-abstract/2/3/1/5090794 by Ed 'DeepDyve' Gillespie user on 16 October 2018 CASE REPORT European Heart Journal - Case Reports (2018) 2, 1–4 doi:10.1093/ehjcr/yty098 A case report of locally invasive Aspergillus fumigatus infection in a patient on canakinumab 1 2 3 Anchalia Chandrakumaran *, Manpreet Malik , Michael P. Stevens , and Antonio Abbate 1 2 Department of Internal Medicine, Virginia Commonwealth University Medical Center, Richmond, VA 23298, USA; Division of Hospital Medicine, Department of Internal Medicine, Virginia Commonwealth University Medical Center, Richmond, VA 23298, USA; Division of Infectious Diseases, Department of Internal Medicine, Virginia Commonwealth University Medical Center, Richmond, VA 23298, USA; and Division of Cardiology, Department of Internal Medicine, Virginia Commonwealth University Medical Center, Richmond, VA 23298, USA Received 31 May 2018; accepted 17 August 2018; online publish-ahead-of-print 4 September 2018 Background Canakinumab is a human monoclonal interleukin-1 antibody that has been studied in the Canakinumab Anti- Inflammatory Thrombosis Outcome Study (CANTOS) trial and shown to prevent recurrent cardiovascular events, while increasing the incidence of neutropenia and risk of severe infections. ................................................................................................................................................................................................... Case summary This is a case report of a locally invasive aspergillus infection in a patient with uncontrolled diabetes mellitus who was receiving canakinumab for 3.5 years as part of the CANTOS trial. He presented with headaches and left eye pain and was found to have a large left ethmoid sinus mass extending into the orbit on computed tomography scan of the head. Cultures from an endoscopic biopsy of left ethmoid sinus grew Aspergillus fumigatus. Canakinumab was discontinued, and he was discharged on voriconazole with improvement in his headaches and left eye pain. ................................................................................................................................................................................................... Discussion The anti-inflammatory properties of canakinumab could have blunted the patient’s immune response allowing the mycetoma to invade adjacent tissue. If canakinumab was approved for the secondary prevention of cardiovascular events then it is important to be cognizant of its potential to delay the presentation of any infection. Keywords Case report Aspergillus Canakinumab CANTOS• Myectoma Ethmoidectomy • • • • • Learning points Canakinumab may alter and delay the presentation of infection. It is very important to educate patients about alerting providers of any new symptoms and thoroughly screen for infections, including locally invasive fungal infection. . Canakinumab induced inhibition of inflammation could potentially Introduction . . preserve pancreatic beta cell function and decrease the progression Canakinumab is a human monoclonal IL-1b antibody and targets IL- . of atherosclerosis in coronary arteries of patients with Type 2 dia- 1b dependent inflammation. It is approved for the treatment of . betes mellitus (DMII) who are at significantly higher risk of developing cryopyrin-associated periodic syndromes in 2009 by both the Food . coronary artery disease. Interleukin-1b inhibition with canakinumab and Drug Administration and the European Medicines Agency. markedly reduces plasma levels of interleukin-6 and high-sensitivity * Corresponding author. Email: anchalia.ck@gmail.com. This case report was reviewed by Hafiz Naderi, Joshua Chai, Anastasia Vamvakidou, and Christian Fielder Camm. V The Author(s) 2018. Published by Oxford University Press on behalf of the European Society of Cardiology. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com Downloaded from https://academic.oup.com/ehjcr/article-abstract/2/3/1/5090794 by Ed 'DeepDyve' Gillespie user on 16 October 2018 2 A. Chandrakumaran et al. C-reactive protein (hsCRP). Canakinumab is being studied in the Canakinumab Anti-Inflammatory Thrombosis Outcome Study (CANTOS), a double-blinded randomized control trial, to determine whether the long-term inhibitory effects of canakinumab on inflam- mation decreases the rate of cardiovascular events in patients who are at an increased risk due to elevated levels of hsCRP. Here, we report a case of locally invasive aspergillus infection in a patient who was receiving canakinumab for 3.5 years as part of the CANTOS trial. Timeline Day 0 Presentation with left eye pain and headaches in a pa- tient who has been on canakinumab for 3.5 years. Computed tomography head revealed soft tissue density mass in the left ethmoid sinus with erosion of the medial orbital wall, left cribriform plate, and anterior cranial fossa. Patient was admitted for surgery. Day 1 Endoscopic left total ethmoidectomy with biopsy of left ethmoid and orbital mass was performed and preliminary pathology was significant for mycetoma. Figure 1 A computed tomography head upon presentation sig- Infectious disease was consulted. He was started on nificant for a soft tissue density mass in left ethmoid sinus with ero- intravenous imipenem (to cover potential sion and extension into the orbital space. Actinomyces and Nocardia) and liposomal ampho- tericin infusion. Canakinumab was discontinued. Day 2 Amphotericin dosing was increased. Ophthalmology evaluation did not reveal any optic nerve . normal neurological examination. Initial ophthalmologic examination compression. revealed decreased visual acuity on the left eye (20/70), pupils were Day 5 Developed acute kidney injury from the amphotericin. . equal round and reactive to light bilaterally with intact extraocular Fungal pathology was suggestive of mould. . muscle movement. His left eye had decreased temporal and superior Day 6 Aspergillis fumigatus was isolated on culture. Antibiotics nasal field deficits and his right eye had superior nasal field deficits. switched to voriconazole. Headache, swelling, and vi- . Left eye dilated eye examination was significant for a large cup to disc sion were improving. . ratio, attenuated vasculature with scattered micro-haemorrhages Day 9 Discharged home on voriconazole. Headaches and and a small intra-retinal haemorrhage supero-nasal to the optic disc. acute kidney injury improved. His left 2nd toe amputation site showed good healing. Laboratory evaluation was significant for haemoglobin A1C of 8.2% with recent values as high as 10.5%, white blood cell (WBC) count 4400/mL (nor- mal 3700–9700/mL) with 55.0% neutrophils and creatinine 1.26 mg/ dL (0.60–1.20 mg/dL). Erythrocyte sedimentation rate (ESR) was Case summary 38 mm/h (normal 0–15 mm/h), and C-reactive protein (CRP) level The patient is a 63-year-old man with a history of acute myocardial was 0.9 mg/dL (0.0–0.5 mg/dL). Computed tomography (CT) head infarction, coronary artery bypass surgery with stent implant prior to with contrast was notable for a soft tissue mass in left ethmoid sinus enrolment in the CANTOS trial, systolic heart failure with left ven- extending into orbit with erosion of anterior cranial fossa (Figure 1). tricular ejection fraction of 40%, implant of cardioverter defibrillator, . Nasal endoscopy revealed a mass in the left posterior ethmoid cell DMII (on home insulin glargine 32 units daily), chronic kidney disease . with material consistent with mycetoma and non-necrotic surround- Stage III (baseline creatinine 1.4 mg/dL), and a recent history of left . ing mucosa. Debridement with left ethmoidectomy was performed. 2nd toe amputation for a diabetic foot infection who had been on . Fungal culture from his left posterior ethmoid biopsy grew Aspergillus canakinumab 300 mg every 3 months as a CANTOS trial participant . fumigatus. There was no evidence of angioinvasion on pathology. No for 3.5 years. He does not have a history of recurrent sinusitis or . ophthalmologic involvement was present on serial eye exams. other systemic infections. His social history was relevant for frequent He was initially started on 1000 mg every 6 h of intravenous gardening. He presented with a 1 week history of headaches and imipenem–cilastatin and 800 mg daily of liposomal amphotericin but blurry vision. developed acute kidney injury while on amphotericin. Once culture On examination, he was afebrile and haemodynamically stable data became available, he was transitioned to oral 300 mg every 12 h with left ptosis and left periorbital tenderness, with an otherwise of voriconazole. Canakinumab treatment was discontinued. He was Downloaded from https://academic.oup.com/ehjcr/article-abstract/2/3/1/5090794 by Ed 'DeepDyve' Gillespie user on 16 October 2018 Aspergillus fumigatus infection in a patient on canakinumab 3 discharged after resolution of acute kidney injury and improvement in his symptoms with a plan to complete several months of therapy for possible mycetoma-associated osteomyelitis. He was discharged on an increased dose of glargine of 35 units daily and glipizide 5 mg daily for better glycemic control. He continued voriconazole and laboratory testing confirmed ad- equacy of his dosing regimen of 300 mg every 12 h (voriconazole trough level was 1.6 mg/mL). The patient continued to do well on out- patient voriconazole therapy for 3 months before developing right sided headaches. He reported no fevers or chills and laboratory evaluation did not show leucocytosis (WBC count was 3400/mL with 55.4% neutrophils). Haemoglobin A1C was 7.0%, ESR 37 mm/h, and CRP was 1.2 mg/dL. Repeat CT imaging of his head without con- trast revealed improved disease at the site of prior aspergillus infec- tion in the left ethmoid air cells but increasing density and debris in his maxillary sinuses bilaterally (Figure 2). He underwent endoscopic debridement of his maxillary sinuses and was found to have path- ology consistent with mycetoma from his right maxillary sinus with- out evidence of tissue invasion; his fungal cultures did not reveal any growth at 1 month. Voriconazole was subsequently discontinued. Repeat CT imaging of his head 6 months later showed interval reso- lution of the inflammatory changes involving the left ethmoid air cells and the medial aspect of the left orbit and no evidence of the recur- rent acute sinusitis. There was mild mucosal thickening of the residual Figure 2 Repeat computed tomography imaging 3 months after ethmoid cells and bilateral maxillary sinuses. Patient has been off of initial presentation showing improved infection in left ethmoid sinus the CANTOS study since the sinus infection and was asymptomatic air cells and left orbit but an increased mucosal disease in the maxil- in his 8 month post-discharge hospital follow-up. lary sinuses bilaterally with new high-density contents. Discussion . concluded that there was a small, non-significant increase in the inci- dence of infection in canakinumab users compared with those receiv- Patients develop invasive systemic or pulmonary aspergillosis, primar- ing placebo. However, the incidence of delayed fungal infections in ily from inhalation. Risk factors for developing this include prolonged patients who had been exposed to canakinumab therapy has not or severe neutropenia, poorly controlled diabetes mellitus or an im- been reported. munocompromised state. Gardening potentially exposed this pa- tient to A. fumigatus. The lack of classic signs and symptoms of infection, despite the increasing size of his presenting mass, is unusual Conclusions and potentially related to canakinumab therapy. We postulate that If canakinumab was approved for the secondary prevention of cardio- the anti-inflammatory properties of canakinumab were blunting this vascular events, it is likely to be prescribed to a large number of patient’s immune response thus allowing his mycetoma to invade ad- patients with diabetes. Therefore, it is crucial to be cognizant of how jacent tissue. Although no evidence of angioinvasion was determined . canakinumab therapy may alter and delay the presentation of infec- pathologically, his initial imaging was highly concerning for concomi- . tion in order to educate patients about alerting providers of any new tant osteomyelitis, and he received an extended course of voricon- . symptoms and thoroughly screen for infections, including locally inva- azole therapy. Infection is the most common adverse effect reported . sive fungal infection. with the use of canakinumab; however, there was no significant differ- ence in the incidence of opportunistic infections between the groups Consent: The author/s confirm that written consent for submission that received canakinumab and placebo. In a multicentre nationwide . and publication of this case report including image(s) and associated study from France involving both adults and children receiving canaki- . text has been obtained from the patient in line with COPE guidance. numab for various rheumatologic conditions, 13% of patients had . . Conflict of interest: none declared. mild respiratory infections, 9% had liver toxicity, and 4% had injection . 4 . site reactions. . . References The incidence of zygomycosis is higher in patients with DMII. . 1. Lachmann HJ, Kone-Paut I, Kuemmerle-Deschner JB, Leslie KS, Hachulla E, A French population based study examining the trends in the inci- . Quartier P, Gitton X, Widmer A, Patel N, Hawkins PN. Use of canakinumab in dence of zygomycosis between 1997 and 2006 reported a 9% per the cryopyrin-associated periodic syndrome. N Engl J Med 2009;360:2416–2425. 2. Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C, year increase in the incidence of zygomycosis in patients with DMII. Fonseca F, Nicolau J, Koenig W, Anker SD, Kastelein JJP, Cornel JH, Pais P, Pella Interestingly, a pooled analysis of the safety and tolerability of canaki- . D, Genest J, Cifkova R, Lorenzatti A, Forster T, Kobalava Z, Vida-Simiti L, Flather numab in DMII patients from three randomized double blind trials M, Shimokawa H, Ogawa H, Dellborg M, Rossi PRF, Troquay RPT, Libby P, Glynn Downloaded from https://academic.oup.com/ehjcr/article-abstract/2/3/1/5090794 by Ed 'DeepDyve' Gillespie user on 16 October 2018 4 A. Chandrakumaran et al. RJ. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl 5. Bitar D, Van Cauteren D, Lanternier F, Dannaoui E, Che D, Dromer F, Desenclos J Med 2017;377:1119–1131. J-C, Lortholary O. Increasing incidence of zygomycosis (mucormycosis), France, 3. Sugui JA, Kwon-Chung KJ, Juvvadi PR, Latge J-P, Steinbach WJ. Aspergillus fumigatus 1997–2006. Emerg Infect Dis 2009;15:1395–1401. and related species. Cold Spring Harb Perspect Med 2015;5:a019786. 6. Howard C, Noe A, Skerjanec A, Holzhauer B, Wernsing M, Ligueros-Saylan 4. Rossi-Semerano L, Fautrel B, Wendling D, Hachulla E, Galeotti C, Semerano L, . M, Thuren T. Safety and tolerability of canakinumab, an IL-1b inhibitor, Touitou I, Kone ´ -Paut I. Tolerance and efficacy of off-label anti-interleukin-1 treat- in type 2 diabetes mellitus patients: a pooled analysis of three ments in France: a nationwide survey. Orphanet J Rare Dis 2015;10:19. randomised double-blind studies. Cardiovasc Diabetol 2014;13:94. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Heart Journal - Case Reports Oxford University Press

A case report of locally invasive Aspergillus fumigatus infection in a patient on canakinumab

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Oxford University Press
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© The Author(s) 2018. Published by Oxford University Press on behalf of the European Society of Cardiology.
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Abstract

Downloaded from https://academic.oup.com/ehjcr/article-abstract/2/3/1/5090794 by Ed 'DeepDyve' Gillespie user on 16 October 2018 CASE REPORT European Heart Journal - Case Reports (2018) 2, 1–4 doi:10.1093/ehjcr/yty098 A case report of locally invasive Aspergillus fumigatus infection in a patient on canakinumab 1 2 3 Anchalia Chandrakumaran *, Manpreet Malik , Michael P. Stevens , and Antonio Abbate 1 2 Department of Internal Medicine, Virginia Commonwealth University Medical Center, Richmond, VA 23298, USA; Division of Hospital Medicine, Department of Internal Medicine, Virginia Commonwealth University Medical Center, Richmond, VA 23298, USA; Division of Infectious Diseases, Department of Internal Medicine, Virginia Commonwealth University Medical Center, Richmond, VA 23298, USA; and Division of Cardiology, Department of Internal Medicine, Virginia Commonwealth University Medical Center, Richmond, VA 23298, USA Received 31 May 2018; accepted 17 August 2018; online publish-ahead-of-print 4 September 2018 Background Canakinumab is a human monoclonal interleukin-1 antibody that has been studied in the Canakinumab Anti- Inflammatory Thrombosis Outcome Study (CANTOS) trial and shown to prevent recurrent cardiovascular events, while increasing the incidence of neutropenia and risk of severe infections. ................................................................................................................................................................................................... Case summary This is a case report of a locally invasive aspergillus infection in a patient with uncontrolled diabetes mellitus who was receiving canakinumab for 3.5 years as part of the CANTOS trial. He presented with headaches and left eye pain and was found to have a large left ethmoid sinus mass extending into the orbit on computed tomography scan of the head. Cultures from an endoscopic biopsy of left ethmoid sinus grew Aspergillus fumigatus. Canakinumab was discontinued, and he was discharged on voriconazole with improvement in his headaches and left eye pain. ................................................................................................................................................................................................... Discussion The anti-inflammatory properties of canakinumab could have blunted the patient’s immune response allowing the mycetoma to invade adjacent tissue. If canakinumab was approved for the secondary prevention of cardiovascular events then it is important to be cognizant of its potential to delay the presentation of any infection. Keywords Case report Aspergillus Canakinumab CANTOS• Myectoma Ethmoidectomy • • • • • Learning points Canakinumab may alter and delay the presentation of infection. It is very important to educate patients about alerting providers of any new symptoms and thoroughly screen for infections, including locally invasive fungal infection. . Canakinumab induced inhibition of inflammation could potentially Introduction . . preserve pancreatic beta cell function and decrease the progression Canakinumab is a human monoclonal IL-1b antibody and targets IL- . of atherosclerosis in coronary arteries of patients with Type 2 dia- 1b dependent inflammation. It is approved for the treatment of . betes mellitus (DMII) who are at significantly higher risk of developing cryopyrin-associated periodic syndromes in 2009 by both the Food . coronary artery disease. Interleukin-1b inhibition with canakinumab and Drug Administration and the European Medicines Agency. markedly reduces plasma levels of interleukin-6 and high-sensitivity * Corresponding author. Email: anchalia.ck@gmail.com. This case report was reviewed by Hafiz Naderi, Joshua Chai, Anastasia Vamvakidou, and Christian Fielder Camm. V The Author(s) 2018. Published by Oxford University Press on behalf of the European Society of Cardiology. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com Downloaded from https://academic.oup.com/ehjcr/article-abstract/2/3/1/5090794 by Ed 'DeepDyve' Gillespie user on 16 October 2018 2 A. Chandrakumaran et al. C-reactive protein (hsCRP). Canakinumab is being studied in the Canakinumab Anti-Inflammatory Thrombosis Outcome Study (CANTOS), a double-blinded randomized control trial, to determine whether the long-term inhibitory effects of canakinumab on inflam- mation decreases the rate of cardiovascular events in patients who are at an increased risk due to elevated levels of hsCRP. Here, we report a case of locally invasive aspergillus infection in a patient who was receiving canakinumab for 3.5 years as part of the CANTOS trial. Timeline Day 0 Presentation with left eye pain and headaches in a pa- tient who has been on canakinumab for 3.5 years. Computed tomography head revealed soft tissue density mass in the left ethmoid sinus with erosion of the medial orbital wall, left cribriform plate, and anterior cranial fossa. Patient was admitted for surgery. Day 1 Endoscopic left total ethmoidectomy with biopsy of left ethmoid and orbital mass was performed and preliminary pathology was significant for mycetoma. Figure 1 A computed tomography head upon presentation sig- Infectious disease was consulted. He was started on nificant for a soft tissue density mass in left ethmoid sinus with ero- intravenous imipenem (to cover potential sion and extension into the orbital space. Actinomyces and Nocardia) and liposomal ampho- tericin infusion. Canakinumab was discontinued. Day 2 Amphotericin dosing was increased. Ophthalmology evaluation did not reveal any optic nerve . normal neurological examination. Initial ophthalmologic examination compression. revealed decreased visual acuity on the left eye (20/70), pupils were Day 5 Developed acute kidney injury from the amphotericin. . equal round and reactive to light bilaterally with intact extraocular Fungal pathology was suggestive of mould. . muscle movement. His left eye had decreased temporal and superior Day 6 Aspergillis fumigatus was isolated on culture. Antibiotics nasal field deficits and his right eye had superior nasal field deficits. switched to voriconazole. Headache, swelling, and vi- . Left eye dilated eye examination was significant for a large cup to disc sion were improving. . ratio, attenuated vasculature with scattered micro-haemorrhages Day 9 Discharged home on voriconazole. Headaches and and a small intra-retinal haemorrhage supero-nasal to the optic disc. acute kidney injury improved. His left 2nd toe amputation site showed good healing. Laboratory evaluation was significant for haemoglobin A1C of 8.2% with recent values as high as 10.5%, white blood cell (WBC) count 4400/mL (nor- mal 3700–9700/mL) with 55.0% neutrophils and creatinine 1.26 mg/ dL (0.60–1.20 mg/dL). Erythrocyte sedimentation rate (ESR) was Case summary 38 mm/h (normal 0–15 mm/h), and C-reactive protein (CRP) level The patient is a 63-year-old man with a history of acute myocardial was 0.9 mg/dL (0.0–0.5 mg/dL). Computed tomography (CT) head infarction, coronary artery bypass surgery with stent implant prior to with contrast was notable for a soft tissue mass in left ethmoid sinus enrolment in the CANTOS trial, systolic heart failure with left ven- extending into orbit with erosion of anterior cranial fossa (Figure 1). tricular ejection fraction of 40%, implant of cardioverter defibrillator, . Nasal endoscopy revealed a mass in the left posterior ethmoid cell DMII (on home insulin glargine 32 units daily), chronic kidney disease . with material consistent with mycetoma and non-necrotic surround- Stage III (baseline creatinine 1.4 mg/dL), and a recent history of left . ing mucosa. Debridement with left ethmoidectomy was performed. 2nd toe amputation for a diabetic foot infection who had been on . Fungal culture from his left posterior ethmoid biopsy grew Aspergillus canakinumab 300 mg every 3 months as a CANTOS trial participant . fumigatus. There was no evidence of angioinvasion on pathology. No for 3.5 years. He does not have a history of recurrent sinusitis or . ophthalmologic involvement was present on serial eye exams. other systemic infections. His social history was relevant for frequent He was initially started on 1000 mg every 6 h of intravenous gardening. He presented with a 1 week history of headaches and imipenem–cilastatin and 800 mg daily of liposomal amphotericin but blurry vision. developed acute kidney injury while on amphotericin. Once culture On examination, he was afebrile and haemodynamically stable data became available, he was transitioned to oral 300 mg every 12 h with left ptosis and left periorbital tenderness, with an otherwise of voriconazole. Canakinumab treatment was discontinued. He was Downloaded from https://academic.oup.com/ehjcr/article-abstract/2/3/1/5090794 by Ed 'DeepDyve' Gillespie user on 16 October 2018 Aspergillus fumigatus infection in a patient on canakinumab 3 discharged after resolution of acute kidney injury and improvement in his symptoms with a plan to complete several months of therapy for possible mycetoma-associated osteomyelitis. He was discharged on an increased dose of glargine of 35 units daily and glipizide 5 mg daily for better glycemic control. He continued voriconazole and laboratory testing confirmed ad- equacy of his dosing regimen of 300 mg every 12 h (voriconazole trough level was 1.6 mg/mL). The patient continued to do well on out- patient voriconazole therapy for 3 months before developing right sided headaches. He reported no fevers or chills and laboratory evaluation did not show leucocytosis (WBC count was 3400/mL with 55.4% neutrophils). Haemoglobin A1C was 7.0%, ESR 37 mm/h, and CRP was 1.2 mg/dL. Repeat CT imaging of his head without con- trast revealed improved disease at the site of prior aspergillus infec- tion in the left ethmoid air cells but increasing density and debris in his maxillary sinuses bilaterally (Figure 2). He underwent endoscopic debridement of his maxillary sinuses and was found to have path- ology consistent with mycetoma from his right maxillary sinus with- out evidence of tissue invasion; his fungal cultures did not reveal any growth at 1 month. Voriconazole was subsequently discontinued. Repeat CT imaging of his head 6 months later showed interval reso- lution of the inflammatory changes involving the left ethmoid air cells and the medial aspect of the left orbit and no evidence of the recur- rent acute sinusitis. There was mild mucosal thickening of the residual Figure 2 Repeat computed tomography imaging 3 months after ethmoid cells and bilateral maxillary sinuses. Patient has been off of initial presentation showing improved infection in left ethmoid sinus the CANTOS study since the sinus infection and was asymptomatic air cells and left orbit but an increased mucosal disease in the maxil- in his 8 month post-discharge hospital follow-up. lary sinuses bilaterally with new high-density contents. Discussion . concluded that there was a small, non-significant increase in the inci- dence of infection in canakinumab users compared with those receiv- Patients develop invasive systemic or pulmonary aspergillosis, primar- ing placebo. However, the incidence of delayed fungal infections in ily from inhalation. Risk factors for developing this include prolonged patients who had been exposed to canakinumab therapy has not or severe neutropenia, poorly controlled diabetes mellitus or an im- been reported. munocompromised state. Gardening potentially exposed this pa- tient to A. fumigatus. The lack of classic signs and symptoms of infection, despite the increasing size of his presenting mass, is unusual Conclusions and potentially related to canakinumab therapy. We postulate that If canakinumab was approved for the secondary prevention of cardio- the anti-inflammatory properties of canakinumab were blunting this vascular events, it is likely to be prescribed to a large number of patient’s immune response thus allowing his mycetoma to invade ad- patients with diabetes. Therefore, it is crucial to be cognizant of how jacent tissue. Although no evidence of angioinvasion was determined . canakinumab therapy may alter and delay the presentation of infec- pathologically, his initial imaging was highly concerning for concomi- . tion in order to educate patients about alerting providers of any new tant osteomyelitis, and he received an extended course of voricon- . symptoms and thoroughly screen for infections, including locally inva- azole therapy. Infection is the most common adverse effect reported . sive fungal infection. with the use of canakinumab; however, there was no significant differ- ence in the incidence of opportunistic infections between the groups Consent: The author/s confirm that written consent for submission that received canakinumab and placebo. In a multicentre nationwide . and publication of this case report including image(s) and associated study from France involving both adults and children receiving canaki- . text has been obtained from the patient in line with COPE guidance. numab for various rheumatologic conditions, 13% of patients had . . Conflict of interest: none declared. mild respiratory infections, 9% had liver toxicity, and 4% had injection . 4 . site reactions. . . References The incidence of zygomycosis is higher in patients with DMII. . 1. Lachmann HJ, Kone-Paut I, Kuemmerle-Deschner JB, Leslie KS, Hachulla E, A French population based study examining the trends in the inci- . Quartier P, Gitton X, Widmer A, Patel N, Hawkins PN. Use of canakinumab in dence of zygomycosis between 1997 and 2006 reported a 9% per the cryopyrin-associated periodic syndrome. N Engl J Med 2009;360:2416–2425. 2. Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C, year increase in the incidence of zygomycosis in patients with DMII. Fonseca F, Nicolau J, Koenig W, Anker SD, Kastelein JJP, Cornel JH, Pais P, Pella Interestingly, a pooled analysis of the safety and tolerability of canaki- . D, Genest J, Cifkova R, Lorenzatti A, Forster T, Kobalava Z, Vida-Simiti L, Flather numab in DMII patients from three randomized double blind trials M, Shimokawa H, Ogawa H, Dellborg M, Rossi PRF, Troquay RPT, Libby P, Glynn Downloaded from https://academic.oup.com/ehjcr/article-abstract/2/3/1/5090794 by Ed 'DeepDyve' Gillespie user on 16 October 2018 4 A. Chandrakumaran et al. RJ. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl 5. Bitar D, Van Cauteren D, Lanternier F, Dannaoui E, Che D, Dromer F, Desenclos J Med 2017;377:1119–1131. J-C, Lortholary O. Increasing incidence of zygomycosis (mucormycosis), France, 3. Sugui JA, Kwon-Chung KJ, Juvvadi PR, Latge J-P, Steinbach WJ. Aspergillus fumigatus 1997–2006. Emerg Infect Dis 2009;15:1395–1401. and related species. Cold Spring Harb Perspect Med 2015;5:a019786. 6. Howard C, Noe A, Skerjanec A, Holzhauer B, Wernsing M, Ligueros-Saylan 4. Rossi-Semerano L, Fautrel B, Wendling D, Hachulla E, Galeotti C, Semerano L, . M, Thuren T. Safety and tolerability of canakinumab, an IL-1b inhibitor, Touitou I, Kone ´ -Paut I. Tolerance and efficacy of off-label anti-interleukin-1 treat- in type 2 diabetes mellitus patients: a pooled analysis of three ments in France: a nationwide survey. Orphanet J Rare Dis 2015;10:19. randomised double-blind studies. Cardiovasc Diabetol 2014;13:94.

Journal

European Heart Journal - Case Reports – Oxford University Press

Published: Sep 1, 2018

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