G Model BONSOI-3944; No. of Pages 2
ARTICLE IN PRESS Joint Bone Spine xxx (2013) xxx–xxx
Available online at www.sciencedirect.com
Letter to the Editor
Disseminated nocardiosis in a patient with rheumatoid arthritis treated with abatacept
a r t i c l e
i n f o
Keywords: Nocardiosis Abatacept Rheumatoid arthritis
Opportunistic infections as tuberculosis are well-known complications in rheumatoid arthritis (RA) especially with biologic agents [1]. Nocardiosis is a rare severe bacterial disease caused by Gram-positive bacillus [2]. Only few cases were reported in RA. We herein report an RA patient, who developed cerebral nocardiosis during abatacept therapy. A 59-year-old woman was followed for an erosive anticitrullinated protein antibody positive RA. She was for a long-time treated with steroids (10 mg/day) and had received numerous synthetic disease-modifying anti-rheumatic drugs (DMARDs) (methotrexate, ciclosporine, leflunomide and azathioprine) and also biologic agents (infliximab and etanercept). Her past medical history was significant for adult onset diabetes mellitus. In 2010, as the disease was still active (DAS28: 6.2), she was treated with abatacept (750 mg per 4 weeks) and methotrexate (20 mg/week). Two years after the initiation of abatacept, she was admitted in our hospital for dyspnea and fever caused by bilateral pneumonitis. No infectious agent was isolated despite bronchoscopy with microbacterial studies. Abatacept and methotrexate were discontinued and she was treated by empirical antibiotic treatments (ceftriaxone and spiramycine for 15 days) leading to an improvement of the symptoms. One month later, she was readmitted for left progressive hemiplegia with seizures. An MRI revealed an abscess in the frontal area associated with a mass effect (Fig. 1). Evacuation of abscess allowed the identification of Nocardia asteroides. The association trimethoprim-sulfamethoxazole (TMP-SMX) was started in association with meropenem intravenously for 6 weeks, followed by association with oral minocycline, leading to an improvement of neurological symptoms. Brain MRI showed a decrease of the lesion size (Fig. 1). The patient is currently treated with TMP-SMX and mynocycline since 18 months. Abatacept was not reintroduced and the patient was treated with corticosteroids (5 mg/day) without sign of neurological complications or RA activity. Nocardiosis is a severe infectious disease due to a Gram-positive bacillus that can affect lungs, brain and skin [2]. Pulmonary nocardiosis is the most common clinical presentation with unspecific symptoms. Abscess formation of the central nervous system is the most common extrapulmonary location [2]. There is no recommendation for treatment of Nocardia infections but TMP-SMX is the most commonly used with prolonged duration of treatment (6 to
Fig. 1. MRI evolution of the abscess between baseline and after 6 months of antibacterial agents. MRI follow-up demonstrated disappearance of the abscess.
12 months) [2]. Several cases of nocardiosis have been reported in RA. All cases had been treated with steroids, five received DMARDs, mainly methotrexate [3–9] and two were also treated with antiTNF␣ agents [4,6]. We report here the first case of Nocardia infection in an RA patient treated with abatacept. The responsibility of abatacept in the occurrence of this infection remains speculative. Our patient had multiple risk factors for infection, including diabetes mellitus, and concomitant treatment with methotrexate and corticosteroids. Corticosteroids were identified as a risk of Nocardia infection in organ transplants recipients [10]. The clinician must be aware of this infection, particularly in RA patients with a history of cumulative immunosuppressive agents because initial symptoms are nonspecific. In absence of identification of Nocardia leading to ineffective treatment, severe complications can occur. Disclosure of interest The authors declare that they have no conflicts of interest concerning this article. References [1] Ruderman EM. Overview of safety of non-biologic and biologic DMARDs. Rheumatology (Oxford) 2012;51:vi37–43.
1297-319X/$ – see front matter © 2013 Published by Elsevier Masson SAS on behalf of the Société Française de Rhumatologie. doi:10.1016/j.jbspin.2013.11.001
Please cite this article in press as: Tourte M, et al. Disseminated nocardiosis in a patient with rheumatoid arthritis treated with abatacept. Joint Bone Spine (2013), doi:10.1016/j.jbspin.2013.11.001
G Model BONSOI-3944; No. of Pages 2 2
ARTICLE IN PRESS Letter to the Editor / Joint Bone Spine xxx (2013) xxx–xxx
[2] Wilson JW. Nocardiosis: updates and clinical overview. Mayo Clin Proc 2012;87:403–7. [3] Cornelissen JJ, Bakker LJ, Van der Veen MJ, et al. Nocardia asteroides pneumonia complicating low dose methotrexate treatment of refractory rheumatoid arthritis. Ann Rheum Dis 1991;50:642–4. [4] Doraiswamy VA. Nocardia infection with adalimumab in rheumatoid arthritis. J Rheumatol 2008;35:542–3. [5] Fabre S, Gibert C, Lechiche C, et al. Primary cutaneous Nocardia otitidiscaviarum infection in a patient with rheumatoid arthritis treated with infliximab. J Rheumatol 2005;32:2432–3. [6] Wendling D, Murad M, Mathieu S, et al. Systemic nocardiosis in a case of rheumatoid arthritis treated with tumor necrosis factor blockers. J Rheumatol 2008;35:539–42. [7] Gruberg L, Thaler M, Rozenman J, et al. Nocardia asteroides infeccomplicating rheumatoid arthritis. J Rheumatol 1991;18: tion 459–61. [8] Yoshida K, Bandoh S, Fujita J, et al. Pyothorax caused by Nocardia otitidiscaviarum in a patient with rheumatoid vasculitis. Intern Med 2004;43: 615–9. [9] Narushima M, Suzuki H, Kasai T, et al. Pulmonary nocardiosis in a patient treated with corticosteroid therapy. Respirology 2002;7: 87–9. [10] Peleg AY, Husain S, Qureshi ZA, et al. Risk factors, clinical characteristics, and outcome of Nocardia infection in organ transplant recipients: a matched casecontrol study. Clin Infect Dis 2007;44:1307–14.
Maylis Tourte a Sébastien Ottaviani a Aurore Aubrun a Christophe Rioux b Elisabeth Palazzo a Philippe Dieudé a,∗ a Université Paris-Diderot, service de rhumatologie, hôpital Bichat, AP–HP, 46, rue Henri-Huchard, 75018 Paris, France b Université Paris-Diderot, service de maladies infectieuses, hôpital Bichat, AP–HP, 75018 Paris, France ∗ Corresponding
author. E-mail address: [email protected] (P. Dieudé) Accepted 7 November 2013 Available online xxx
Please cite this article in press as: Tourte M, et al. Disseminated nocardiosis in a patient with rheumatoid arthritis treated with abatacept. Joint Bone Spine (2013), doi:10.1016/j.jbspin.2013.11.001
ARTICLE IN PRESS Joint Bone Spine xxx (2013) xxx–xxx
Available online at www.sciencedirect.com
Letter to the Editor
Disseminated nocardiosis in a patient with rheumatoid arthritis treated with abatacept
a r t i c l e
i n f o
Keywords: Nocardiosis Abatacept Rheumatoid arthritis
Opportunistic infections as tuberculosis are well-known complications in rheumatoid arthritis (RA) especially with biologic agents [1]. Nocardiosis is a rare severe bacterial disease caused by Gram-positive bacillus [2]. Only few cases were reported in RA. We herein report an RA patient, who developed cerebral nocardiosis during abatacept therapy. A 59-year-old woman was followed for an erosive anticitrullinated protein antibody positive RA. She was for a long-time treated with steroids (10 mg/day) and had received numerous synthetic disease-modifying anti-rheumatic drugs (DMARDs) (methotrexate, ciclosporine, leflunomide and azathioprine) and also biologic agents (infliximab and etanercept). Her past medical history was significant for adult onset diabetes mellitus. In 2010, as the disease was still active (DAS28: 6.2), she was treated with abatacept (750 mg per 4 weeks) and methotrexate (20 mg/week). Two years after the initiation of abatacept, she was admitted in our hospital for dyspnea and fever caused by bilateral pneumonitis. No infectious agent was isolated despite bronchoscopy with microbacterial studies. Abatacept and methotrexate were discontinued and she was treated by empirical antibiotic treatments (ceftriaxone and spiramycine for 15 days) leading to an improvement of the symptoms. One month later, she was readmitted for left progressive hemiplegia with seizures. An MRI revealed an abscess in the frontal area associated with a mass effect (Fig. 1). Evacuation of abscess allowed the identification of Nocardia asteroides. The association trimethoprim-sulfamethoxazole (TMP-SMX) was started in association with meropenem intravenously for 6 weeks, followed by association with oral minocycline, leading to an improvement of neurological symptoms. Brain MRI showed a decrease of the lesion size (Fig. 1). The patient is currently treated with TMP-SMX and mynocycline since 18 months. Abatacept was not reintroduced and the patient was treated with corticosteroids (5 mg/day) without sign of neurological complications or RA activity. Nocardiosis is a severe infectious disease due to a Gram-positive bacillus that can affect lungs, brain and skin [2]. Pulmonary nocardiosis is the most common clinical presentation with unspecific symptoms. Abscess formation of the central nervous system is the most common extrapulmonary location [2]. There is no recommendation for treatment of Nocardia infections but TMP-SMX is the most commonly used with prolonged duration of treatment (6 to
Fig. 1. MRI evolution of the abscess between baseline and after 6 months of antibacterial agents. MRI follow-up demonstrated disappearance of the abscess.
12 months) [2]. Several cases of nocardiosis have been reported in RA. All cases had been treated with steroids, five received DMARDs, mainly methotrexate [3–9] and two were also treated with antiTNF␣ agents [4,6]. We report here the first case of Nocardia infection in an RA patient treated with abatacept. The responsibility of abatacept in the occurrence of this infection remains speculative. Our patient had multiple risk factors for infection, including diabetes mellitus, and concomitant treatment with methotrexate and corticosteroids. Corticosteroids were identified as a risk of Nocardia infection in organ transplants recipients [10]. The clinician must be aware of this infection, particularly in RA patients with a history of cumulative immunosuppressive agents because initial symptoms are nonspecific. In absence of identification of Nocardia leading to ineffective treatment, severe complications can occur. Disclosure of interest The authors declare that they have no conflicts of interest concerning this article. References [1] Ruderman EM. Overview of safety of non-biologic and biologic DMARDs. Rheumatology (Oxford) 2012;51:vi37–43.
1297-319X/$ – see front matter © 2013 Published by Elsevier Masson SAS on behalf of the Société Française de Rhumatologie. doi:10.1016/j.jbspin.2013.11.001
Please cite this article in press as: Tourte M, et al. Disseminated nocardiosis in a patient with rheumatoid arthritis treated with abatacept. Joint Bone Spine (2013), doi:10.1016/j.jbspin.2013.11.001
G Model BONSOI-3944; No. of Pages 2 2
ARTICLE IN PRESS Letter to the Editor / Joint Bone Spine xxx (2013) xxx–xxx
[2] Wilson JW. Nocardiosis: updates and clinical overview. Mayo Clin Proc 2012;87:403–7. [3] Cornelissen JJ, Bakker LJ, Van der Veen MJ, et al. Nocardia asteroides pneumonia complicating low dose methotrexate treatment of refractory rheumatoid arthritis. Ann Rheum Dis 1991;50:642–4. [4] Doraiswamy VA. Nocardia infection with adalimumab in rheumatoid arthritis. J Rheumatol 2008;35:542–3. [5] Fabre S, Gibert C, Lechiche C, et al. Primary cutaneous Nocardia otitidiscaviarum infection in a patient with rheumatoid arthritis treated with infliximab. J Rheumatol 2005;32:2432–3. [6] Wendling D, Murad M, Mathieu S, et al. Systemic nocardiosis in a case of rheumatoid arthritis treated with tumor necrosis factor blockers. J Rheumatol 2008;35:539–42. [7] Gruberg L, Thaler M, Rozenman J, et al. Nocardia asteroides infeccomplicating rheumatoid arthritis. J Rheumatol 1991;18: tion 459–61. [8] Yoshida K, Bandoh S, Fujita J, et al. Pyothorax caused by Nocardia otitidiscaviarum in a patient with rheumatoid vasculitis. Intern Med 2004;43: 615–9. [9] Narushima M, Suzuki H, Kasai T, et al. Pulmonary nocardiosis in a patient treated with corticosteroid therapy. Respirology 2002;7: 87–9. [10] Peleg AY, Husain S, Qureshi ZA, et al. Risk factors, clinical characteristics, and outcome of Nocardia infection in organ transplant recipients: a matched casecontrol study. Clin Infect Dis 2007;44:1307–14.
Maylis Tourte a Sébastien Ottaviani a Aurore Aubrun a Christophe Rioux b Elisabeth Palazzo a Philippe Dieudé a,∗ a Université Paris-Diderot, service de rhumatologie, hôpital Bichat, AP–HP, 46, rue Henri-Huchard, 75018 Paris, France b Université Paris-Diderot, service de maladies infectieuses, hôpital Bichat, AP–HP, 75018 Paris, France ∗ Corresponding
author. E-mail address: [email protected] (P. Dieudé) Accepted 7 November 2013 Available online xxx
Please cite this article in press as: Tourte M, et al. Disseminated nocardiosis in a patient with rheumatoid arthritis treated with abatacept. Joint Bone Spine (2013), doi:10.1016/j.jbspin.2013.11.001
