|Year : 2021 | Volume
| Issue : 3 | Page : 117-122
Disseminated nocardiosis coinfection with extrapulmonary tuberculosis in a patient with metastatic thymoma: A case report and literature review
Cho-Hao Lee, Ching-Liang Ho, Ren-Hua Ye
Division of Hematology and Oncology Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
|Date of Submission||20-Jan-2021|
|Date of Decision||21-Apr-2021|
|Date of Acceptance||22-Apr-2021|
|Date of Web Publication||01-Sep-2021|
Dr. Ren-Hua Ye
Division of Hematology and Oncology Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, No. 325, Sec. 2, Chenggong Rd., Neihu Dist., Taipei
Source of Support: None, Conflict of Interest: None
Patients with metastatic thymoma postintensive chemotherapy and radiotherapy are prone to opportunistic infectious diseases. Disseminated nocardiosis is a rare disease; however, its incidence has increased in recent years due to the growing population of immunocompromised hosts. We present the first report of Nocardia beijingensis infection with extrapulmonary tuberculosis coinfection causing muscular and brain abscesses in a patient with metastatic thymoma postintensive chemotherapy and radiotherapy. This case illustrates the possibility of coinfection with two pathogens and the difficulty in establishing a rapid diagnosis. Awareness of opportunistic infections and the early initiation of appropriate antibiotic therapy are important for the treatment of immunocompromised patients with infectious diseases.
Keywords: Nocardiosis, thymoma, tuberculosis
|How to cite this article:|
Lee CH, Ho CL, Ye RH. Disseminated nocardiosis coinfection with extrapulmonary tuberculosis in a patient with metastatic thymoma: A case report and literature review. J Cancer Res Pract 2021;8:117-22
|How to cite this URL:|
Lee CH, Ho CL, Ye RH. Disseminated nocardiosis coinfection with extrapulmonary tuberculosis in a patient with metastatic thymoma: A case report and literature review. J Cancer Res Pract [serial online] 2021 [cited 2021 Nov 28];8:117-22. Available from: https://www.ejcrp.org/text.asp?2021/8/3/117/324921
| Introduction|| |
Two-third of thymomas are encapsulated and benign, and most are the round epithelial or spindle cell type. Chemotherapy is considered the standard therapy for metastatic thymoma, followed by radiotherapy or thymectomy. However, intensive chemotherapy or radiotherapy may impair the patient's immunity, which makes them more vulnerable to opportunistic infections. Nocardia species belong to the aerobic actinomycetes group of bacteria, which are Gram-positive bacilli with mildly acid-fast features. These saprophytic bacteria are often found in soil and water. Inhalation (pulmonary nocardiosis-pneumonia, lung abscess, and cavitary lesions) or contact with the bacteria via a cut or skin abrasion (cutaneous nocardiosis-cellulitis and ulcers) may result in human infection with Nocardia. Nocardia species are capable of causing disseminated diseases that can readily enter the bloodstream and spread throughout the body, including the skin, lungs, central nervous system, and abdominal organs. Tan et al. reported that the major types of nocardial infection were cutaneous (56.6%), pulmonary (33.6%), and disseminated (7.1%) infections. In developing countries, more than 60% of cases of human nocardiosis occur in immunocompromised individuals, and more frequently in males than females. Nocardia farcinica or Nocardia asteroides have been shown to more frequently cause disseminated nocardial infection. Herein, we report a rare coinfection with disseminated nocardiosis and extrapulmonary tuberculosis in a patient with metastatic thymoma.
| Case Report|| |
A 52-year-old male presented with Masaoka stage IV malignant thymoma with metastases of the left lung, pleura, and neck lymph nodes [Figure 1]a. He received six courses of systemic chemotherapy with the ADOC regimen (doxorubicin, cisplatin, vincristine, and cyclophosphamide), followed by radiotherapy to targeted sites of the neck and mediastinal region with 33 fractions, with a total 6600 cGy, and he exhibited a partial treatment response [Figure 1]b. He had been well except for grade 3 radiotherapy-related mucositis and one episode of neutropenia (white blood cell: 2986 per microliter, absolute neutrophil count: 1346/<Symbol>μ</Symbol>L). Six weeks later, he experienced a progressive night cough and low-grade fever. He did not have any travel history or contact with drugs, insects, animals, or soil and water during the follow-up period. Chest computed tomography (CT) revealed a residual thymoma, bilateral multiple (newly developed) pulmonary nodules, and pleural effusion [Figure 1]c. Under the impression of thymoma progression, he was admitted to our hospital for salvage chemotherapy.
|Figure 1: (a) Computed tomography of the chest, before concurrent chemotherapy and radiotherapy. (b) Computed tomography of the chest, during concurrent chemotherapy and radiotherapy. (c) Computed tomography of the chest, after concurrent chemotherapy and radiotherapy|
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On admission, he was afebrile with an intermittent dry cough. However, no significant abnormalities were observed during a physical examination, except for the presence of rales in the right lung field. Pulmonary sputum and pleural effusion samples were collected for infectious pathogen screening, which revealed negative findings for Mycobacterium tuberculosis, fungi, and viral infections.
Three days later, he complained of a painful sensation at the left thigh, which was accompanied by a regional erythematous change. CT of the left leg demonstrated abscess formation [Figure 2]a. Abscess drainage was subsequently performed, and the pus was collected for pathogen identification, including aerobic and anaerobic bacteria, fungi, and Mycobacterium tuberculosis (TB) [Figure 2]b. A polymerase chain reaction and sputum culture reported positive findings of TB pathogen. Empiric antibiotics including piperacillin/tazobactam and fluconazole were administered; however, a tender and swollen cutaneous mass developed at the left shoulder region 7 days later [Figure 2]c. Soft tissue sonography also revealed a deep muscle abscess, and tubal drainage was repeatedly performed. Both abscess culture results yielded Nocardia beijingensis infection. In addition, he had a sudden onset of conscious disturbance and delirium. Magnetic resonance imaging (MRI) of the brain revealed a nodular lesion over the left thalamus, which was considered to be focal abscess formation [Figure 3]a. Disseminated N. beijingensis infection with muscular and brain abscesses was suspected, and antibiotics including intravenous trimethoprim/sulfamethoxazole (TMP/SM × 10 mg/kg/day) and imipenem were administered. He recovered after the muscle abscess had been drained, and his psychological condition improved after the antibiotic therapy. The brain lesion totally disappeared as revealed in subsequent MRI of the brain [Figure 3]b. Three weeks later, M. tuberculosis was cultured from the pus but not from sputum specimens, leading to the diagnosis of N. beijingensis infection with coinfection of extrapulmonary TB. Antituberculosis medication including rifampin, isoniazid, pyrazinamide, and ethambutol was prescribed, and he recovered well after completing 6 months of TMP-SMX and 9 months of anti-TB therapy.
|Figure 2: (a) Computed tomography of the lower legs, white arrow demonstrates abscess formation in the left thigh. (b) Tubal drainage of the left thigh abscess. (c) A tender and swollen cutaneous mass in the left shoulder region|
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|Figure 3: (a) T1-weighted magnetic resonance imaging of the brain showed a nodular lesion over the left thalamus, which was considered to be focal abscess formation. (b) T1-weighted magnetic resonance imaging of the brain demonstrated total resolution of the focal abscess after trimethoprim/sulfamethoxazole treatment|
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| Discussion|| |
Two-third of thymomas are encapsulated and benign, and most are round epithelial or spindle cell type., The standard therapy for metastatic thymoma is adjuvant chemotherapy and salvage radiotherapy or thymectomy.
Radiation therapy of the mediastinum causes a rapid decrease in circulating B- and T-lymphocytes. While the acute decrease in lymphocytes postprocedure is short lived, most patients show a modest chronic depression in both numbers and function of circulating lymphocytes., CD4 + lymphocyte recovery after dose-intense chemotherapy is constrained in adults both by a limited thymic regenerative capacity, as well as an increased susceptibility to apoptosis within the expanding peripheral CD4+ population., Radiation-induced T-cell deficiency in patients may be irreversible.
Infections which are thought to be due to defects in humoral immunity include XLA and CVID., Recurrent sinopulmonary infections are the most commonly reported, often resulting in bronchiectasis., Other infections including bone, joint, skin, and central nervous system infections have also been reported.,,
Nocardia infection is attributed to suppression of cell-mediated immunity. In Ekrami et al., study, the coincidence of pulmonary TB and nocardiosis was 1% for the entire study population and 6.25% among HIV-infected patients. In addition, Alnaum et al. reported that 3% of HIV-infected patients with suspected pulmonary TB had pulmonary nocardiosis. Severe disseminated nocardial infections are mostly caused by N. farcinica or N. asteroides; however N. beijingensis is a very rare Nocardia species. Furthermore, infections with opportunistic agents such as Nocardia have been associated with suppression of cell-mediated immunity.
According to a large cohort study, the incidence of TB is about 0.2 cases per 1000 new cancer diagnoses, and extrapulmonary TB cases account for 15% of all TB infections. Malignant thymomas have an overall incidence of only 0.15 per 100,000 person/years, and thus, disseminated N. beijingensis coinfection with extrapulmonary infection in a patient with metastatic thymoma is considered to be extremely rare.
To the best of our knowledge, there are no previous reports on extrapulmonary TB with nocardiosis coinfection. Our patient had received intensive chemotherapy and radiotherapy, and so he may have had a compromised immune status and acquired rare opportunistic infections. N. beijingensis infection is less severe and has a good response to antibiotic therapy. Its treatment includes intravenous carbapenem or TMP/SMX as the first-line therapy, which is maintained with oral TMP/SMX with a duration of 2 weeks to 1 year depending on clinical symptoms and signs., In our case, the clinical symptoms were improved after 1 month of antibiotic treatment. The patient completed 6 months of TMP-SMX and 9 months of anti-TB therapy without the recurrence of N. beijingensis infection.
We systematically searched PubMed and Embase for published cases of N. beijingensis infection, and only 15 case reports were found. Of these cases, 66.7% had underlying immunocompromised diseases or were taking immunosuppression medications. Most of the patients (73.3%) had clinical symptoms including cough, fever, or body weight loss, and others (20%) had cutaneous lesions. The major types of N. beijingensis infection were pulmonary nocardiosis (60.0%), cutaneous nocardiosis (20.0%), isolated local infection (13.3%), and disseminated subretinal and cerebral abscess (6.7%). N. beijingensis is less severe and has a good response to antibiotic therapy. Most patients received intravenous imipenem, meropenem, amikacin, or TMP/SMX as the first-line therapy and were maintained by oral TMP/SMX with a duration from 2 weeks to 1 years depending on the clinical symptoms and signs [Table 1]. In the present case, the clinical symptoms improved after 1 month of antibiotics treatment. He completed 6 months of TMP-SMX and 9 months of anti-TB therapy without recurrence of N. beijingensis infection. In conclusion, the present study is the first report on disseminated N. beijingensis infection with the coinfection of extrapulmonary TB in a patient with metastatic thymoma postintensive chemotherapy and radiotherapy. Disseminated nocardiosis is a rare disease; however, its incidence has increased in recent years due to the growing population of immunocompromised hosts. This case illustrates the possibility of coinfection with two pathogens and the difficulty in establishing a rapid diagnosis. Awareness of opportunistic infections and the early initiation of appropriate antibiotic therapy are important for the treatment of immunocompromised patients with infectious diseases.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Chalabreysse L, Roy P, Cordier JF, Loire R, Gamondes JP, Thivolet-Bejui F. Correlation of the WHO schema for the classification of thymic epithelial neoplasms with prognosis: A retrospective study of 90 tumors. Am J Surg Pathol 2002;26:1605-11.
Conville P, Witebsky F. Nocardia, Rhodococcus, Gordonia, Actinomadura, Streptomyces, and Other Aerobic Actinomycetes, p In Versalovic J, Carroll K, Funke G, Jorgensen J, Landry M, Warnock D (eds.), Manual of Clinical Microbiology, 10th
Edition. ASM Press, Washington, DC; 2011. p. 443-71. doi: 10.1128/9781555816728.ch27.
Ambrosioni J, Lew D, Garbino J. Nocardiosis: Updated clinical review and experience at a tertiary center. Infection 2010;38:89-97.
Shahapur PR, Peerapur BV, Shahapur RP, Honnutagi RM, Biradar MS. Lymphocutaneous nocardiosis caused by Nocardia
otitidiscaviarum: A case report and review of literature. J Nat Sci Biol Med 2014;5:197-201.
Saubolle MA, Sussland D. Nocardiosis: Review of clinical and laboratory experience. J Clin Microbiol 2003;41:4497-501.
Tan CK, Lai CC, Lin SH, Liao CH, Chou CH, Hsu HL, et al.
Clinical and microbiological characteristics of nocardiosis including those caused by emerging Nocardia
species in Taiwan, 1998-2008. Clin Microbiol Infect 2010;16:966-72.
Gray GF, Gutowski WT 3rd
. Thymoma. A clinicopathologic study of 54 cases. Am J Surg Pathol 1979;3:235-49.
Stratton JA, Byfield PE, Byfield JE, Small RC, Benfield J, Pilch Y. A comparison of the acute effects of radiation therapy, including or excluding the thymus, on the lymphocyte subpopulations of cancer patients. J Clin Invest 1975;56:88-97.
Tisch M, Heimlich F, Daniel V, Opelz G, Maier H. Cellular immune defect caused by postsurgical radiation therapy in patients with head and neck cancer. Otolaryngol Head Neck Surg 1998;119:412-7.
Hakim FT, Cepeda R, Kaimei S, Mackall CL, McAtee N, Zujewski J, et al.
Constraints on CD4 recovery postchemotherapy in adults: Thymic insufficiency and apoptotic decline of expanded peripheral CD4 cells. Blood 1997;90:3789-98.
Sfikakis PP, Gourgoulis GM, Moulopoulos LA, Kouvatseas G, Theofilopoulos AN, Dimopoulos MA. Age-related thymic activity in adults following chemotherapy-induced lymphopenia. Eur J Clin Invest 2005;35:380-7.
Gray WC, Chretien PB, Suter CM, Revie DR, Tomazic VT, Blanchard CL, et al.
Effects of radiation therapy on T-lymphocyte subpopulations in patients with head and neck cancer. Otolaryngol Head Neck Surg 1985;93:650-60.
Kelleher P, Misbah SA. What is Good's syndrome? Immunological abnormalities in patients with thymoma. J Clin Pathol 2003;56:12-6.
Leibovitz I, Zamir D, Polychuck I, Reitblat T, Gheorghiu D. Recurrent pneumonia post-thymectomy as a manifestation of Good syndrome. Eur J Intern Med 2003;14:60-2.
Kelesidis T, Yang O. Good's syndrome remains a mystery after 55 years: A systematic review of the scientific evidence. Clin Immunol 2010;135:347-63.
Cucchiara BL, Forman MS, McGarvey ML, Kasner SE, King D. Fatal subacute cytomegalovirus encephalitis associated with hypogammaglobulinemia and thymoma. Mayo Clin Proc 2003;78:223-7.
Ekrami A, Khosravi AD, Samarbaf Zadeh AR, Hashemzadeh M. Nocardia
co-infection in patients with pulmonary tuberculosis. Jundishapur J Microbiol 2014;7:e12495.
Alnaum HM, Elhassan MM, Mustafa FY, Hamid ME. Prevalence of Nocardia
species among HIV-positive patients with suspected tuberculosis. Trop Doct 2011;41:224-6.
Filice GA. Nocardiosis in persons with human immunodeficiency virus infection, transplant recipients, and large, geographically defined populations. J Lab Clin Med 2005;145:156-62.
Kmeid J, Kulkarni PA, Batista MV, El Chaer F, Prayag A, Ariza-Heredia EJ, et al.
Active Mycobacterium tuberculosis
infection at a comprehensive cancer center, 2006-2014. BMC Infect Dis 2019;19:934.
Falkson CB, Bezjak A, Darling G, Gregg R, Malthaner R, Maziak DE, et al.
The management of thymoma: A systematic review and practice guideline. J Thorac Oncol 2009;4:911-9.
Pintado V, Gómez-Mampaso E, Cobo J, Quereda C, Meseguer MA, Fortún J, et al.
Nocardial infection in patients infected with the human immunodeficiency virus. Clin Microbiol Infect 2003;9:716-20.
Wilson JW. Nocardiosis: Updates and clinical overview. Mayo Clin Proc 2012;87:403-7.
Kageyama A, Poonwan N, Yazawa K, Mikami Y, Nishimura K. Nocardia
beijingensis, is a pathogenic bacterium to humans: The first infectious cases in Thailand and Japan. Mycopathologia 2004;157:155-61.
Chu RW, Lung D, Wong SN. Pulmonary abscess caused by Nocardia
beijingensis: The second report of human infection. Pediatr Infect Dis J 2008;27:572-3.
Takayanagi K, Kimura Y, Kawakami K, Koyama K, Harada Y, Yamaryo T. A case of pulmonary nocardiosis with Nocardia
beijingensis. Kansenshogaku Zasshi 2008;82:43-6.
Ohmori S, Kobayashi M, Yaguchi T, Nakamura M. Primary cutaneous nocardiosis caused by Nocardia
beijingensis in an immunocompromised patient with chemotherapy for advanced prostate cancer. J Dermatol 2012;39:740-1.
Martinaud C, Verdonk C, Bousquet A, Macnab C, Vaylet F, Soler C, et al.
Isolation of Nocardia
beijingensis from a pulmonary abscess reveals human immunodeficiency virus infection. J Clin Microbiol 2011;49:2748-50.
Ogawa T, Kasahara K, Yonekawa S, Nakagawa C, Maeda K, Konishi M, et al. Nocardia
beijingensis pulmonary infection successfully treated with intravenous beta-lactam antibiotics and oral minocycline. J Infect Chemother 2011;17:706-9.
Derancourt C, Theodose R, Deschamps L, Liautaud B, Briand E, Derancourt S, et al.
Primary cutaneous nocardiosis caused by Nocardia
beijingensis. Br J Dermatol 2012;167:216-8.
Arunachalam M, Galeone M, Bassi A, Scarfi F, Mariottini A, Simonetti MT, et al. Nocardia
beijingensis outside of Asia. J Eur Acad Dermatol Venereol 2016;30:168-9.
Aragaki-Nakahodo A, Benzaquen S, Kirschner M. Coinfection by Nocardia
beijingensis and Nocardia
arthritidis in an immunocompromised patient diagnosed by endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA). Respir Med Case Rep 2014;12:22-3.
Crozier JA, Andhavarapu S, Brumble LM, Sher T. First report of Nocardia
beijingensis infection in an immunocompetent host in the United States. J Clin Microbiol 2014;52:2730-2.
Rigotti S, Marocco S, Angheben A, Screpis D, Piovan G, Zorzi C. The first case of Nocardia
beijingensis isolated infection to lumbar spine. J Neurosci Rural Pract 2015;6:462-3.
] [Full text]
Palavutitotai N, Chongtrakoo P, Ngamskulrungroj P, Chayakulkeeree M. Nocardia
beijingensis psoas abscess and subcutaneous phaeohyphomycosis caused by phaeoacremonium parasiticum in a renal transplant recipient: The first case report in Thailand. Southeast Asian J Trop Med Public Health 2015;46:1049-54.
Abdel-Rahman N, Izhakian S, Wasser WG, Fruchter O, Kramer MR. Endobronchial enigma: A clinically rare presentation of Nocardia
beijingensis in an immunocompetent patient. Case Rep Pulmonol 2015;2015:970548.
Richards AD, Stewart C, Karthik H, Lake SR. Bilateral subretinal abscesses: The first case of disseminated Nocardia
beijingensis in Australia. Clin Exp Ophthalmol 2015;43:843-5.
Sheikh-Taha M, Corman LC. Pulmonary Nocardia
beijingensis infection associated with the use of alemtuzumab in a patient with multiple sclerosis. Mult Scler 2017;23:872-4.
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