QJM Advance Access originally published online on March 10, 2008
QJM 2008 101(5):419-421; doi:10.1093/qjmed/hcn028
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Pulmonary actinomycosis in a patient with diffuse systemic sclerosis treated with infliximab
Department of Internal Medicine, Rouen University
Hospital, 76031 Rouen Cedex, France
Laboratory of Pneumology, Rouen University
Hospital, 76031 Rouen Cedex, France
email: isabelle.marie{at}chu-rouen.fr
Opportunistic infections have been frequently reported in patients with acquired immunodeficiency syndrome (AIDS) or other conditions with compromised host defenses, such as malignancy and transplantation. More recently, opportunistic infections have also been increasingly reported in patients with connective tissue diseases, including systemic lupus erythematosus, systemic sclerosis and polymyositis/dermatomyositis.1, 2 Many factors, especially immunosuppressive medications, have been mentioned to account for the elevated frequency of opportunistic infections in these patients.1, 2 We report a case of Actinomyces meyeri pneumonia in a patient with diffuse cutaneous systemic sclerosis (dcSSc), which occurred shortly after institution of anti-tumor necrosis factor 
(anti-TNF-) therapy.
A 44-year-old woman was diagnosed as having dcSSc in 1999. Systemic manifestations of dcSSc included: (i) Raynaud's phenomenon, pitting scars; (ii) esophageal involvement, with both absence of peristalsis in the lower two-thirds of the esophageal body and low pressure in the lower esophageal sphincter; (iii) mild bibasilar interstitial lung disease (ILD) on computed tomography (CT)-scan; and (iv) joint impairment, with erosive polyarthritis involving the hands, wrists, feet, ankles and knees. Autoantibody screening tests were positive for antinuclear antibodies (1:1200), anti-Scl 70 and anti-CCP antibodies. She received combined theray with diltiazem, omeprazole and prednisone (7 mg/day). As joint involvement continued to deteriorate gradually, subsequent treatments were started: prednisone (15 mg/day), methotrexate, azathioprine and leflunomide (cumulative doses of 120 mg, 27 000 mg and 7200 mg, respectively), which all proved ineffective. Indeed, 4 months after the disruption of leflunomide therapy, the patient was given anti-TNF-: infliximab (3 mg/kg) at weeks 0 and 2, in addition to prednisone (15 mg, daily; cumulative dose of 27 375 mg). Before initiation of infliximab, gastric aspiration products cultures for mycobacteria was performed, which proved negative. Moreover, lung CT-scan showed unchanged bibasilar mild ILD; both pulmonary function tests and echocardiography were within normal limits. One month after the second infliximab infusion, the patient presented with a 3-week history of fatigue, non-productive cough night sweats and progressive dyspnea. On admission, she was febrile (38.9°C), and her general condition was poor. Physical examination showed inspiratory fine crackles bilaterally. Laboratory findings were as follows: erythrocyte sedimentation rate 70 mm/h, C-reactive protein 164 mg/l, hemoglobin 12.8 g/dl, white blood cell count 19 x 109/l (lymphocytes 10.8%, CD4 cell count 0.63 x 109/l). Lung CT-scan showed bilateral nodular opacities, involving mainly subpleural areas (Figure 1). Blood cultures, bacterial (Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella), viral (cytomegalovirus, influenza viruses) and Toxoplasma gondii serologies were negative. Bronchoscopy was normal. Analysis of bronchoalveolar lavage (BAL) fluid was negative for Gram and Gomori-Grocott staining and fungal cultures. The patient was empirically treated with ceftriaxone (2 g daily), amikacin (15 mg/kg/day) and ofloxacin (200 mg/12 h) for 7 days. However, pulmonary clinical manifestations continued to deteriorate. Further microbiological studies (Ziehl-Neelsen stain) proved negative for acid-fast bacilli in sputum, gastric aspiration products and BAL fluid. BAL cultures yielded gram positive rods, subsequently identified as Actinomyces meyeri; the isolate was susceptible to: penicillin, amoxicillin, cefoxitin, imipenem and clindamycin. Other tests, including abdominal CT-scan, echocardiography and orthopanthomography, were normal. The patient received amoxicillin (3 g/day), which resulted in resolution of clinical and radiological pulmonary manifestations. Infliximab therapy was not reinstituted.
|
Infections are potential complications of anti-TNF-
therapy.3–7 In patients with rheumatoid arthritis being treated with anti-TNF- agents, Kroesen et al.5 have found an elevated incidence of severe infections (0.181 per anti-TNF- therapy vs. 0.008 in the 2 year preceding anti-TNF- therapy). Moreover, in a series of patients receiving anti-TNF- therapy, Wallis et al.7 found the incidence rate of opportunistic infections to be as high as 313/100 000 patients; tuberculosis was the most common infection. Opportunistic infections due to other pathogenic micro-organisms have also been observed in association with anti-TNF- therapy, e.g.: Pneumocystis jiroveci, Histoplasma, Aspergillus, Candida, Nocardia, Cryptococcus, non-tuberculous Mycobacteria, Listeria, Toxoplasma, Leishmania, Sporothrix and Zygomycetes.3–7 Our case report suggests that Actinomycetes infections should be added to the list of opportunistic infections associated with immunosuppression related to infliximab therapy. Actinomycosis has, in fact, been reported in patients with immunosuppressed conditions including AIDS, malignancy and transplantation; dental procedures and aspiration of oropharyngeal contents are recognized risk factors for pulmonary actinomycosis in these patients.8–10 In our patient, several factors favored Actinomyces meyeri pneumonia onset: (i) immunodeficiency secondary to steroids and infliximab. rapidly progressive Actinomyces meyeri pneumonia, in fact, occurred shortly after initiation of infliximab. Our data confirm previous reports demonstrating that 75% of opportunistic infections occurred within 90 days after anti-TNF- therapy institution;1, 3–5,7 in a series of patients with rheumatoid arthritis treated with infliximab (n = 850) and etanercept (n = 1412), Curtis et al.11 further mentioned recently a higher risk of bacterial infection onset during the first 6 months after anti-TNF- therapy institution [<6 months: IC 95%: (1.23–4.68) for infliximab vs. (0.75–3.47) for etanercept; >6 months: IC 95%: (0.55–2.24) for infliximab vs. (0.74–2.53) for etanercept]. Moreover, this pulmonary clinical presentation may have been due to the immunosuppressive effects of infliximab therapy; and (ii) SSc-related esophageal impairment may have resulted in repeated micro-aspirations of acid content into the lungs; these repeated micro-aspirations may have led to the onset of pulmonary actinomycosis. Finally, physicians, caring for patients with connective tissue diseases receiving anti-TNF- therapy, need to be aware of the whole spectrum of associated opportunistic infections; they should also maintain a high index of suspicion because of both atypical and systemic presentation of such complications.
References
1. Juarez M, Misischia R, Alarcon GS. Infections in systemic connective tissue disease: systemic lupus erythematosus, scleroderma, and polymyositis/dermatomyositis. Rheum Dis Clin North Am (2003) 29:163–84.[CrossRef][Web of Science][Medline]
2. Marie I, Hachulla E, Cherin P, Hellot MF, Herson S, Levesque H, et al. Opportunistic infection in polymyositis and dermatomyositis. Arthritis Rheum (2005) 53:155–65.[CrossRef][Web of Science][Medline]
3. Crum NF, Lederman ER, Wallace MR. Infections associated with tumor necrosis factor- antagonists. Medicine (Baltimore) (2005) 84:291–302.[CrossRef][Medline]
4. Flendrie M, Creemers MCW, Welsing PMJ, den Broeder AA, van Riel PLCM. Survival during treatment with tumour necrosis factor blocking agents in rheumatoid arthritis. Ann Rheum Dis (2003) 62(Suppl. II):ii30–3.
5. Kroesen S, Wildmer AF, Tyndall A, Hasler P. Serious bacterial infections in patients with rheumatoid arthritis under anti-TNF-alpha therapy. Rheumatology (Oxford) (2003) 42:617–21.[CrossRef][Medline]
6. Singh SM, Rau NV, Cohen LB, Harris H. Cutaneous nocardiosis complicating management of Crohn's disease with infliximab and prednisone. CMAJ (2004) 171:1063–4.
7. Wallis RS, Broder MS, Wong JY, Hanson ME, Beenhouwer DO. Granulomatous infectious diseases associated with tumour necrosis factor antagonists. Clin Infect Dis (2004) 38:1261–5.[CrossRef][Web of Science][Medline]
8. Cendan I, Klapholz A, Talawera W. Pulmonary actinomycosis: a cause of endobronchial disease in a patient with AIDS. Chest (1993) 103:1886–7.[CrossRef][Web of Science][Medline]
9. Charalabopoulos K, Charalabopoulos AK, Papalimneou V, Ioachim E, Constantopoulos SH. Lung, pleural and colon actinomycosis in an immunocompromised patient: a rare form of presentation. Chemotherapy (2003) 49:209–11.[CrossRef][Web of Science][Medline]
10. Yildiz O, Doganay M. Actinomycoses and Nocardia pulmonary infections. Curr Opin Pulm Med (2006) 12:228–34.[Medline]
11. Curtis JR, Xi J, Patkar N, Xie A, Saag KG, Martin C. Drug-specific and time-dependent risks of bacterial infection among patients with rheumatoid arthritis who were exposed to tumor necrosis factor antagonists. Arthritis Rheum (2008) 56:4226–7.[CrossRef][Web of Science]
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||