Adjunctive Effects of Oral Steroids Along with Anti-Tuberculosis Drugs in the Management of Cervical Lymph Node Tuberculosis

Adjunctive Effects of Oral Steroids Along with Anti-Tuberculosis Drugs in the Management of Cervical Lymph Node Tuberculosis

Babulal Bansiwal¹

Maneesha Jelia²

Ramesh Chand Meena²

Satyam Agarwal²

Shinu A²

Departments of ¹Respiratory Medicine and ²Anatomy

Government Medical College, Kota

Rajasthan 324010, India

Abstract

Background: Tuberculosis (TB) can infect both pulmonary and extra-pulmonary organs. In India pulmonary TB accounts for 80% of cases and extrapulmonary TB (EPTB) accounts for 20% cases. Cervical lymph nodes are the most location for EPTB.

Aims and Objectives: To study the efficacy of treatment with oral steroids along with anti-tuberculosis treatment in cervical lymph node tuberculosis.

Methods: A total of 60 patients were enrolled in the study all with EPTB and cervical lymphadenitis. These 60 study patients were randomised into two groups. Group-I consisted of 30 patients given anti-tuberculosis therapy along with prednisolone 1mg/kg body weight for 4 weeks followed by tapering at 0.5 mg/kg body weight over 4 weeks. Group-II was comprised of 30 patients given antituberculosis treatment plus placebo

Results: After completion of treatment 27 patients in Group 1 (90%) showed complete resolution and 3 patients (10%) had residual evidence of lymphadenitis with no change. In contrast, only 19 patients (63.3%) showed complete resolution in Group 2 and 11 patients (36.7%) had residual lymphadenitis present (10 had no change, 1 had increase in size).

Conclusion: We conclude that steroids given with antituberculosis treatment to patients with cervical lymphadenitis led to faster and earlier resolution of tuberculous lymphadenitis.

Introduction

Tuberculosis (TB) is an ancient disease that affects both pulmonary and extra-pulmonary organs. In India most TB cases are pulmonary (80%) but extrapulmonary TB (EPTB) accounts for a substantial proportion (20%) (1). Peripheral lymph node tuberculosis is observed in about 5% of all TB patients and 30-55% of extra-pulmonary TB cases (2). Cervical lymph nodes are the most common lymph nodes affected, classically termed as “scrofula”, although supraclavicular, axillary, inguinal nodes may also be involved (3-5). Lymphadenopathy may lead to complications by compression of adjacent structures, organs, and blood vessels or fistula formation (6-10). Multiple studies have shown better outcomes with addition of steroids to anti-tuberculosis treatment in extrapulmonary tuberculosis including pleural effusion, pericardial effusion, tubercular meningitis, and mediastinal lymphadenopathy (11,12). However, the safety and efficacy of this approach remains largely unproven except in cases of intrathoracic obstruction where it was found to relieve the pressure on the compressed bronchus (13).

Aims and Objectives

To study the efficacy of treatment with oral steroids along with anti-tuberculosis treatment in cervical lymph node tuberculosis.

Materials and Methods

Patients: Sixty patients with cervical lymph node tuberculosis seen from 1st October 2013 to 30^th September 2014 in the Department of Respiratory Medicine, Government Medical College, Kota, India participated in the study. All cases of cervical lymph node tuberculosis found to have cyto-pathological, histo-pathological, immunological and/or bacteriological evidence of TB and who had not received any anti- tuberculosis therapy in the past, were included in the study. Patients were excluded if they were pregnant or had a chronic disease such as diabetes mellitus, hypertension, peptic ulcer disease, alcoholism, or HIV-AIDS. Patients were also excluded if they had a detectable abscess.

Study Design: The study was an open label, randomized, prospective and placebo-controlled interventional study comparing the efficacy of the addition of two months treatment with oral corticosteroids along with Revised National Tuberculosis Control Programme (RNTCP) recommended anti-TB therapy.

Sixty patients were randomised into two groups by a computer-generated random table. All patients were given category I anti-tuberculosis therapy (ATT) consisting of INH 600 mg and rifampicin 450 mg daily for 6 months with pyrazinamide 1500 mg daily for the first 2 months. Group-I consisted of 30 patients given category I RNTCP-recommended therapy along with prednisolone 1mg/kg body weight for 4 weeks followed by tapering at 0.5mg/kg body weight for 4 weeks. Group-II was comprised of 30 patients given category I RNTCP-recommended therapy plus placebo.

All the study cases were monitored clinically by visits after 1, 2 and 6 months.

Statistical Analysis: Pearson’s x² test or Fisher’s exact test was used to evaluate correlations between categorical variables, as appropriate. Relationships among continuous variables was evaluated using Student’s t- test. All tests of significance are two-tailed, and p < 0.05 was considered to reflect significance.

Results

The patients were well matched between groups in age (27.5 + 12.9 years vs. 26.3 + 11.7 years, p=0.612) and sex (12M/18F vs. 11M/19F). The groups were well-matched in other clinical characteristics (Table 1).

Table 1. Clinical characteristics of patients at beginning of therapy.

In addition to the above, the patients were well-matched by the extent of both upper and lower lymphadenopathy (Group I, 25/30; Group 2, 28/30), absence of chest lesions (Group I, 1/30; Group 2, 2/30), and positive histopathology on needle aspiration (Group I, 27/30; Group 2, 26/30). Out of 26 patients of Group II, 4 (13.3%) patients were diagnosed by AFB smear of the needle aspirate as well as cytopathological examination, 2(6.7%) had only AFB smear positivity and 22 (86.7%) had only cytopathological confirmation. None had a positive sputum smear.

Most of the patients in Group-I had earlier lymph node resolution compared to Group-II (Table 2).

Table 2. Initial lymph node status and after varying durations of treatment.

This table shows the status of the lymph node initially and after varying duration of treatment. After completion of treatment 27 patients (90%) showed complete resolution and only 3 patients (10%) had no change in Group-I. In contrast, only 19 patients (63.3%) in Group-II showed complete resolution and 11 patients (36.7%) had residual lymph nodes (10 with no change, 1 with an increase in size). Most patients had a negative AFB smear from the needle aspirate after 6 months in both Group-I (27 patients) and group-II (26 patients).

Only 2 patients in Group-I (6.67%) had complications as compared to 09 (30.0%) in Group-II (p<0.001). The complications were in the form of abscess, sinus and/or new lymph node/s. All these patients needed surgical exploration during the course of treatment. Sequelae in form of residual lymph node was also higher in Group II patients (10 out of 30 patients) as compared to Group I (3 out of 30, p<0.001).

Overall, the incidence of side effects was greater in Group-II. This difference was mostly due to a higher occurrence of joints pain and skin rashes in Group-II than Group-I, (8 and 4 patients vs. 1 and 1 patients respectively).

Discussion

The present study was done to determine the role of steroids in the management of cervical lymph node tuberculosis. In contrast to 20 patients (66.67%) in the non-steroid group-II who had complete resolution after 6 months, 27 patients (90%) in the steroid group had complete resolution. Blaikely et al. (14) reported complete resolution in 82% of their non-steroid study patients which was similar to results of our study.

In the present clinical study, only 2 patients (6.66%) in the steroid group had complications as compared to 9 (30.0%) in the non-steroid group. The complications were in the form of abscess, sinus and/or new lymph node/s. In Group II, fresh lymph nodes appeared in 4, existing lymph node increased in 1, abscess formation occurred in 3 while 2 patients developed sinuses. Sequela in the form of residual lymph node was also higher in the non-steroid patients (10 out of 30, 33.33%) as compared to the steroid treated patients (3 out of 30 patients, 5%, p<0.001). Results were comparable to other studies (15).

We used a moderate dose of steroids for 2 months. The major concern against the use of steroids when given along with anti-TB treatment in tubercular lymphadenitis are adverse systemic effects. However, the overall incidence of side effects with anti-TB treatment were more in the non-steroid group in the form of joint pains and skin rashes, (8 and 4 patients v/s 1 and 1 patients respectively). Gastro-intestinal side effects i.e. nausea/vomiting and pain abdomen, were slightly higher in the steroid-treated patients.

Conclusion

We conclude that steroids when given along with anti-tubercular treatment led to faster and earlier resolution of tuberculous lymphadenitis. Complication and sequela in form of residual lymph node are also less in steroid group as compared to non-steroid group. It is unclear if long-term outcomes are affected. However, this data suggests that justification for routine use of corticosteroids could be made in tubercular cervical lymphadenitis.

References

1. Arora V, Jaiswal AK, Gupta S, Gupta MB, Jain V, Ghanchi F. Implementation of RNTCP in a private medical college: five years' experience. Indian J Tuberc. 2012 Jul;59(3):145-50. [PubMed].
2. Asghar RJ, Pratt RH, Kammerer JS, Navin TR. Tuberculosis in South Asians living in the United States, 1993-2004. Arch Intern Med. 2008 May 12;168(9):936-42. [CrossRef] [PubMed]
3. Lazarus AA, Thilagar B. Tuberculous lymphadenitis. Dis Mon. 2007 Jan;53(1):10-5. [CrossRef]  [PubMed]Thompson MM, Underwood MJ, Sayers RD, Dookeran KA, Bell PR. Peripheral tuberculous lymphadenopathy: a review of 67 cases. Br J Surg. 1992 Aug;79(8):763-4. [CrossRef] [PubMed]
4. Dandapat MC, Mishra BM, Dash SP, Kar PK. Peripheral lymph node tuberculosis: a review of 80 cases. Br J Surg. 1990 Aug;77(8):911-2. [CrossRef] [PubMed]
5. Singh B, Moodley M, Goga AD, Haffejee AA. Dysphagia secondary to tuberculous lymphadenitis. S Afr J Surg. 1996 Nov;34(4):197-9. [PubMed]
6. Gupta SP, Arora A, Bhargava DK. An unusual presentation of oesophageal tuberculosis. Tuber Lung Dis. 1992 Jun;73(3):174-6. [CrossRef] [PubMed]
7. Ohtake M, Saito H, Okuno M, Yamamoto S, Ohgimi T. Esophagomediastinal fistula as a complication of tuberculous mediastinal lymphadenitis. Intern Med. 1996 Dec;35(12):984-6. [CrossRef] [PubMed]
8. Wilson RS, White RJ. Lymph node tuberculosis presenting as chyluria. Thorax. 1976 Oct;31(5):617-20. [CrossRef] [PubMed]
9. Puri S, Khurana SB, Malhotra S. Tuberculous abdominal lymphadenopathy causing reversible renovascular hypertension. J Assoc Physicians India. 2000 May;48(5):530-2. [PubMed]
10. Mansour AA, Al-Rbeay TB. Adjunct therapy with corticosteroids or paracentesis for treatment of tuberculous pleural effusion. East Mediterr Health J. 2006 Sep;12(5):504-8. [PubMed]
11. Reuter H, Burgess LJ, Louw VJ, Doubell AF. The management of tuberculous pericardial effusion: experience in 233 consecutive patients. Cardiovasc J S Afr. 2007 Jan-Feb;18(1):20-5. [PubMed]
12. Nemir RL, Cardona J, Vaziri F, Toledo R. Prednisone as an adjunct in the chemotherapy of lymph node-bronchial tuberculosis in childhood: a double-blind study. II. Further term observation. Am Rev Respir Dis. 1967 Mar;95(3):402-10. [CrossRef] [PubMed]
13. Jha BC, Dass A, Nagarkar NM, Gupta R, Singhal S. Cervical tuberculous lymphadenopathy: changing clinical pattern and concepts in management. Postgrad Med J. 2001 Mar;77(905):185-7. [CrossRef] [PubMed]
14. Blaikley JF, Khalid S, Ormerod LP. Management of peripheral lymph node tuberculosis in routine practice: an unselected 10-year cohort. Int J Tuberc Lung Dis. 2011 Mar;15(3):375-8. [PubMed]
15.  Allen MB, Cooke NJ. Corticosteroids and tuberculosis. BMJ. 1991 Oct 12;303(6807):871-2. [CrossRef] [PubMed]

Cite as: Bansiwal B, Jelia M, Chand Meena RC, Agarwal S, A S. Adjunctive Effects of Oral Steroids Along with Anti-Tuberculosis Drugs in the Management of Cervical Lymph Node Tuberculosis. Southwest J Pulm Crit Care. 2021;22(1):16-20. doi: https://doi.org/10.13175/swjpcc067-20 PDF 

September 2019 Pulmonary Case of the Month: An HIV Patient with a Fever

William P. Diehl IV, DO

Nicholas Villalobos, MD

Department of Internal Medicine

University of New Mexico

Albuquerque, NM USA

History of Present Illness

A 33-year old transgender male to female presented from human immunodeficiency virus (HIV) clinic for two months of fevers, intermittent shortness of breath, cough with blood streaked sputum, headache, and nausea. The clinic provider was concerned when labs showed up trending HIV viral load (3.3 million copies) and an absolute CD4 count of 57.

Past Medical History, Social History and Family History

The patient had a history of stage-III HIV diagnosed in 2014 on bictegravir, emtricitabine, tenofovir (Biktarvy) and latent tuberculosis (TB) diagnosed 2017 on isoniazid and B6. She is from Nicaragua and arrived in Albuquerque, NM in 2017. Social history is pertinent for sex trafficking and methamphetamine use.

Physical Examination

Upon admission, the patient’s vital signs were notable for a temperature of 39.2 degrees Celsius, blood pressure of 114/71 mmHg, oxygen saturation of 95% on room air with a respiratory rate of 18 breaths per minute. Physical exam was notable for an absence of rash, palpable lymphadenopathy or cachexia.

Which of the following should be done? (Click on the correct answer to be directed to the second of six pages)

1. Blood cultures
2. Lumbar puncture
3. Sputum for AFB and tuberculosis
4. 1 & 3
5. All of the above

Cite as: Diehl WP IV, Villalobos N. September 2019 pulmonary case of the month: an HIV patient with a fever. Southwest J Pulm Crit Care. 2019;19(3):87-94. doi: https://doi.org/10.13175/swjpcc056-19 PDF 

February 2017 Pulmonary Case of the Month

Abdalla Fadda, MD

Phoenix VA and Banner University Medical Center Phoenix

Phoenix, AZ USA

History of Present Illness

A 45-year-old man presented with weight loss, copious amounts of light green sputum, low grade fever and chest discomfort on the right. He had moved to Arizona 8 months ago. Two months later he developed hemoptysis and had increased cough with copious phlegm. He denied any fever, chills, malaise or fatigue.

Past Medical History, Social History and Family History

He has a history of tuberculosis in 2010 treated with 4 drug therapy for a year. The tuberculosis was not drug resistant. He had been treated with a 6-month course of voriconazole about 2 years ago.

Physical Examination

He was afebrile and his vital signs were unremarkable. He had decreased breath sounds in his right lower chest.

Laboratory

His CBC, electrolytes and urinalysis were unremarkable.

Chest Radiography

His admission chest x-ray is shown in Figure 1.

Figure 1. Admission PA of chest.

In regards to the chest x-ray which of the following are true? (Click on the correct answer to proceed to the second of six pages)

1. There are cavities in the right lung
2. There is a large right pleural effusion
3. There is volume loss in the right lung
4. 1 and 3
5. All of the above

Cite as: Fadda A. February 2017 pulmonary case of the month. Southwest J Pulm Crit Care. 2017;14(2):45-53. doi: https://doi.org/10.13175/swjpcc005-17 PDF

December 2016 Pulmonary Case of the Month

Lewis J. Wesselius, MD

Department of Pulmonary Medicine

Mayo Clinic Arizona

Scottsdale, AZ

Pulmonary Case of the Month CME Information

Members of the Arizona, New Mexico, Colorado and California Thoracic Societies and the Mayo Clinic are able to receive 0.25 AMA PRA Category 1 Credits™ for each case they complete. Completion of an evaluation form is required to receive credit and a link is provided on the last panel of the activity. 

0.25 AMA PRA Category 1 Credit(s)™

Estimated time to complete this activity: 0.25 hours

Lead Author(s): Lewis J. Wesselius, MD.  All Faculty, CME Planning Committee Members, and the CME Office Reviewers have disclosed that they do not have any relevant financial relationships with commercial interests that would constitute a conflict of interest concerning this CME activity.

Learning Objectives:
As a result of this activity I will be better able to:

1. Correctly interpret and identify clinical practices supported by the highest quality available evidence.
2. Will be better able to establsh the optimal evaluation leading to a correct diagnosis for patients with pulmonary, critical care and sleep disorders.
3. Will improve the translation of the most current clinical information into the delivery of high quality care for patients.
4. Will integrate new treatment options in discussing available treatment alternatives for patients with pulmonary, critical care and sleep related disorders.

Learning Format: Case-based, interactive online course, including mandatory assessment questions (number of questions varies by case). Please also read the Technical Requirements.

CME Sponsor: University of Arizona College of Medicine at Banner University Medical Center Tucson

Current Approval Period: January 1, 2015-December 31, 2016

Financial Support Received: None

History of Present Illness

The patient is a 29-year-old man who presented to the emergency room with right-sided pleuritic chest pain, fever, cough, and progressive dyspnea over 2 weeks.

Past Medical History, Social History and Family History

He had no prior significant medical issues and had been well until 2 weeks ago. A native of India, he has been in the US for about 5 months and works at American Express. He is a nonsmoker. Family history is noncontributory.

Physical Examination

• Vitals signs: Temperature 38.0^◦ C, Blood Pressure 155/85 mm Hg, Heart Rate 140 beats/min, Respirations 24 breaths/min
• General: Appears to be in moderate pain and respiratory distress
• Lungs: Decreased breath sounds on the right
• Heart: regular rhythm with a tachycardia
• Abdomen: unremarkable
• Extremities: unremarkable
• Neurologic: unremarkable

Radiography

His initial chest x-ray is shown in Figure 1.

Figure 1. Initial chest radiograph.

Which of the following best describes the chest x-ray? (Click on the correct answer to proceed to the second of seven pages)

1. Elevated right hemidiaphragm
2. Large right pleural effusion
3. Right lower lobe and middle lobe consolidation
4. Right lung atelectasis
5. None of the above

Cite as: Wesselius LJ. December 2016 pulmonary case of the month. Southwest J Pulm Crit Care. 2016;13(6):268-75. doi: https://doi.org/10.13175/swjpcc122-16 PDF

32 Year Old Man with “Community-Acquired” Pneumonia

Jill K. Gersh, M.D., MPH¹, Michelle K. Haas MD^2,3,4

¹Department of Medicine, University of Colorado Denver, Aurora, CO; ²Denver Health Medical Center, Denver, CO; ³Denver Metro Tuberculosis Clinic, Denver, CO; ⁴Division of Infectious Diseases, Department of Medicine, University of Colorado Denver, Aurora, CO

Corresponding author: Jill Gersh, M.D., MPH Phone: 303-602-5052 Fax: 303-602-5055. Email: JILL.GERSH@UCDENVER.EDU

All authors declare they have no conflicts of interest to disclose.

Abstract

Background: Community-acquired pneumonia is a common reason for hospital admission; however underlying pathogens vary depending on host immunity and circulating pathogens in the community.

Case Summary: A 32 year old man from Malawi presented with community-acquired pneumonia. After failing outpatient management, he was admitted and found to have underlying HIV disease. His diagnostic work up was initially inconclusive for M. tuberculosis (TB) and thus his diagnostic evaluation and treatment focused on other etiologies. He was ultimately diagnosed with TB after an invasive procedure and had a rapid clinical response after initiating TB treatment.

Conclusion: Both failure to recognize that TB can present with a syndrome similar to bacterial pneumonia and over-reliance on diagnostic testing delayed the diagnosis of TB. Delays in diagnosis contributed to substantial morbidity and risked nosocomial transmission.  Despite declining incidence in the US, providers should remain cognizant of diagnostic limitations for TB disease and have a low threshold for empiric treatment.

Introduction

Community-acquired pneumonia (CAP) is a common reason for presentation to care. The epidemiology of CAP can vary depending on the patient’s community of origin and underlying co-morbidities (1). We present a case of a 32 year old man who presented with CAP in whom his diagnosis was delayed due to failure to fully consider these factors.  

Case

A 32 year old man from Malawi[1] presented to the emergency department (ED) with cough and dyspnea that failed to respond to a 5 day course of azithromycin. Chest radiography (CXR) was performed (Figure 1), demonstrating right middle lobe consolidation with ipsilateral hilar lymphadenopathy (LAD).

Figure 1. PA view of the chest demonstrating right middle lobe consolidation and ipsilateral hilar lymphadenopathy at the time of his first ED presentation and approximately 10 days into his illness.

He was diagnosed with CAP and discharged with a 7 day course of amoxicillin-clavulanate. His symptoms progressed with fevers, and weight loss.  He presented for the second time to the ED and repeat CXR showed worsening right-sided hilar LAD and right middle lobe consolidation (Figure 2).

Figure 2. PA view of the chest demonstrating worsening of right middle lobe consolidation and right sided hilar lymphadenopathy at the time of admission to the hospital and approximately 17 days into his illness.

A rapid HIV test was positive and his CD4 count was 60 cells/µL. He was admitted and started on ceftriaxone, azithromycin and trimethoprim-sulfamethoxazole daily. He was placed on respiratory isolation and three sputum samples for acid-fast bacilli (AFB) smear and culture were collected, all of which were AFB smear negative. He then underwent bronchoscopy and his bronchoalveolar lavage smear was negative for AFB. His tuberculin skin test (TST) was negative as was an interferon gamma release assay (IGRA). He was then removed from respiratory isolation.

He continued to worsen with daily fevers as high as 43ºC while antimicrobial coverage was broadened to vancomycin and cefepime. He eventually underwent mediastinoscopy and lymph node (LN) biopsy. The following day LN tissue was positive for AFB and probe identified Mycobacterium tuberculosis (TB). Twenty-nine days after his initial presentation and 15 days into his hospitalization he was started on anti-tuberculosis therapy with isoniazid, rifampin, pyrazinamide and ethambutol. His cough improved within 2 days, his fevers were gone by day 4 and he was discharged. All sputum cultures grew TB. Antiretroviral therapy was initiated five weeks into his TB treatment. He had an excellent clinical and radiographic response (Figure 3) and completed 9 months of TB treatment.

Figure 3. PA view of the chest after 9 months of treatment for M. tuberculosis. Noted here is resolution of right sided hilar lymphadenopathy and resolution of his right middle lobe consolidation with some residual scarring noted. Sputum culture converted at 2 months.

Diagnosis: Pulmonary tuberculosis.

Discussion

TB is the leading cause of death among HIV-infected individuals globally and the leading cause of morbidity in HIV-infected individuals (2). TB can present as an acute pneumonia with rapid progression of disease including sepsis and respiratory failure. Cough may not be a prominent feature and may be of less than two weeks duration. Additional signs and symptoms include fevers, night sweats, weight loss, hepatosplenomegaly, and lymphadenopathy. Individuals with CD4 counts < 100 cells/µL are more likely to present with disseminated disease and less likely to have cavitary disease. HIV-infected patients are also more likely to present with AFB smear negative disease even when severely ill (3). Chest radiograph findings vary from normal appearing films to hilar lymphadenopathy, diffuse infiltrates, and lobar consolidation.

TST and IGRAs are often negative and serve as poor screening tools for active disease. Up to 25% of individuals may have a negative TST or IGRA while having active disease, particularly HIV-infected individuals with advanced immunodeficiency (4). A negative result should never lower the clinical suspicion for active TB.

Delays in TB treatment are a major contributor to excess mortality in HIV-infected patients (2). The importance of early empiric treatment in HIV-infected individuals cannot be overstated. The World Health Organization (WHO) published guidelines in 2007 for the management of HIV-infected individuals suspected of having TB (5). While WHO guidelines are developed for low resource settings, these guidelines have relevance in the U.S. when managing patients with HIV who have lived or traveled to areas with a high burden of TB. 

The failure to recognize that his clinical syndrome of CAP included TB as the underlying pathogen led to delayed treatment, prolonged hospitalization and risked nosocomial transmission. One unintended consequence of the success of our TB control programs may be the growing lack of clinical experience with TB among our providers. More broadly, how much of what we do as U.S. healthcare providers is because we can, and instead of what we should? Imagine if he couldn't get a mediastinoscopy and biopsy. Is it possible that his treatment course would have been improved by a lack of these resources?  We would do well to learn from our colleagues practicing in resource limited settings where prescribing empiric TB treatment and assessing for a clinical response is standard of care. In this patient’s case, less really would have been more.

References

1. Nyamande K, Lalloo UG, John M. TB presenting as community-acquired pneumonia in a setting of high TB incidence and high HIV prevalence. Int J Tuberc Lung Dis. 2007;11(12):1308-13. [PubMed] 
2. Wong EB, Omar T, Setlhako GJ, et al. Causes of death on antiretroviral therapy: a post-mortem study from South Africa. PloS one. 2012;7(10):e47542. [CrossRef] [PubMed]
3. Elliott AM, Halwiindi B, Hayes RJ, Luo N, Tembo G, Machiels L, Bem C, Steenbergen G, Pobee JO, Nunn PP, et al. The impact of human immunodeficiency virus on presentation and diagnosis of tuberculosis in a cohort study in Zambia. J Trop Med Hyg. 1993;96(1):1-11. [PubMed] 
4. Cattamanchi A, Ssewenyana I, Davis JL, Huang L, Worodria W, den Boon S, Yoo S, Andama A, Hopewell PC, Cao H. Role of interferon-gamma release assays in the diagnosis of pulmonary tuberculosis in patients with advanced HIV infection. BMC Infect Dis. 2010;10:75. [CrossRef] [PubMed]
5. Improving the diagnosis and treatment of smear-negative pulmonary and extrapulmonary tuberculosis among adults and adolescents: recommendations for HIV-prevelent and resource constrained settings. Geneva: World Health Organization;2007.

Acknowledgements

The authors wish to thank Carolyn Welch, MD for her thoughtful review of this case report.

Reference as: Gersh JK, Haas MK. 32 year old man with "community-acquired' pneumonia. Southwest J Pulm Crit Care. 2013;7(6):355-9. doi: http://dx.doi.org/10.13175/swjpcc173-13 PDF

Cough and Pleural Disease in a Burmese Immigrant – A Masquerader

George M. Solomon, MD¹

Eric Schmidt, MD^1,2

Randall Reves, MD³

Carolyn Welsh, MD¹

Department of Medicine, Divisions of Pulmonary Sciences and Critical Care Medicine, University of Colorado Denver¹

Denver Health Medical Center²

Denver Metro Tuberculosis Control Program, Denver Public Health Department³

Corresponding Author:         George M. Solomon, MD

                                          Research Building 2

                                          9th Floor12700 E. 19th Ave

                                          Aurora, Colorado 80045

                                          Phone 303-398-1392

                                          George.solomon@ucdenver.edu

Financial Disclosures: No authors report any financial conflicts to disclose

Abstract

We present a case of a 58 year old Burmese male who presented to our center with progressive pulmonary and constitutional symptoms after treatment for pulmonary tuberculosis. Our investigation revealed peripheral and bronchogenic eosinophilia and clinical features consistent with progressive pulmonary paragonimiasis. After serological confirmation of the diagnosis, the patient had resolution of symptoms with praziaquantel therapy for the condition.  This case highlights the importance of considering this diagnosis when there is a possibility of undercooked shellfish exposure especially in immigrants from endemic areas for paragonimiasis where raw shellfish is more commonly ingested.

Case Presentation 

A 58 year old Burmese male was referred for evaluation of cough and pleural abnormalities on a chest radiograph.  The patient had arrived in Boston as a Burmese refugee the previous year.  Upon arrival in the United States, he was found to have a right middle lobe infiltrate, multiple cavitary nodules on chest CT, three negative sputum AFB smears and 10 mm induration on Mantoux tuberculin skin testing.  He was treated with rifampin, isoniazid, pyrazinamide, and ethambutol for 2 months with resolution of the cavitary nodules but developed an increasing right pleural opacity. Sputum cultures were negative for mycobacteria.

He moved to Denver, Colorado where an additional four months of isoniazid and rifampin were completed for presumed culture negative pulmonary tuberculosis. At the end of treatment he noted an increase in his persistent cough and fatigue associated with low grade fevers.  A repeat chest radiograph now revealed a small right-sided pleural effusion (Figure 1).

Figure 1. Chest radiograph demonstrating right-sided small pleural effusion

Assessment at the pulmonary clinic revealed persistent cough and a 6.8 kg weight loss.  Physical examination was pertinent for a temperature of 99.0 ºF, dullness to percussion and crackles in the right lung.  The patient reported occasional tobacco use and reported occasional raw seafood consumption in Burma.  He denied other medical history at this time except for untreated hypertension. 

Laboratory investigation was pertinent for a white blood cell count of 10,000 per µl with a differential of 22% eosinophils and normal platelet and hemoglobin levels. Anti-nuclear antibodies (ANA), anti-neutrophil cytoplasmic antibodies (ANCA), and rheumatoid factor levels as well as a comprehensive metabolic profile and coagulation labs were all normal. 

Computed tomography of the chest at the time of presentation to the pulmonary clinic compared to the one a year earlier in Boston are shown in Figure 2.

Figure 2. A. Computed Tomography image of the chest demonstrating right middle lobe opacification and pleural effusion at presentation to the pulmonary clinic. B. Computed Tomography image of the chest at time of initial treatment in Boston demonstrating right-sided cavitary disease and pleural process.

Fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) revealed 960 nucleated cells, 68% of which were eosinophils.  Routine cultures grew normal oral flora and were negative for actinomyces, fungi and mycobacteria.  Wet prep for oocysts and larvae was negative. 

Ultrasound revealed only a small loculated pleural effusion, precluding thoracentesis.

Because of suspicion for parasitic illness, a filarial antibody panel was also sent and was negative. Paragonimus antibody immunoblot assay was positive.

Case Follow-up

The patient was treated with praziquantel 25 mg/kg orally three times daily for 3 days with improvement in symptoms and radiographic abnormalities as show in Figure 3. 

Figure 3. Chest radiograph following treatment with praziquantel demonstrating resolution of resolving right-sided pleural effusion and right-sided infiltrates.

Discussion

Paragonimiasis results from infection by one of the more than fifty species of the genus paragonimus (most commonly P. westermanii).  There are approximately 2.5 million cases annually reported in endemic areas, mostly in Indo-China and sub-Saharan Africa.  In the western world, most cases are reported in immigrants from endemic regions where undercooked shellfish are culturally consumed.  Approximately 50-70% of infections are initially diagnosed as tuberculosis in the U.S. (1), as demonstrated in this case.  

The lifecycle of the organism begins with early ingestion and early disease characterized by cough, fever, and pleuritic chest pain resulting from a transdiaphragmatic spread of larvae into the pleural space from the abdomen.  Prominent features of this “early” disease are pneumothorax or pleural effusion and peripheral eosinophilia (2).  Additionally, transient pulmonary infiltrates may be observed. This presentation may help to explain the response of parenchymal abnormalities in response to the anti-tuberculosis treatments.  In fact, the “response” to treatment may have been a consequence of the natural history of early stage paragonimiasis. 

The failure of resolution of pleural disease in this case to anti-tuberculosis drugs should have alerted clinicians to consider alternative diagnoses.  The progressive pleural disease in this case while on anti-tuberculosis drugs highlights progression of paragonimiasis pulmonary disease.  “Late” stage lung disease results from mature fluke inhabitation in the lung parenchyma. During this phase, patients typically resolve their peripheral eosinophilia and fever but may have persistent dark brown hemoptysis.   Radiographic features in this stage are varied and include parenchymal mass-like lesions or chronic pleural lesions (2).

If paragonimiasis is suspected, diagnosis is most readily made by serological evaluation. Heretofore, microscopic evaluation of oocysts and larvae from sputum or BAL yielded a diagnosis in only 50-75% of cases (3).  Serological evaluations including immunoblot assays for P. Westermanii antibodies have a reported sensitivity of 96% and specificity of 99% (4) and ELISA-based assays have a reported sensitivity of 92% and specificity of 90% (5); thereby, these assays have therefore largely supplanted other microscopic evaluation given the superior diagnostic performance

Treatment regimens are nearly 100% effective in cure for pulmonary disease. Typical regimens include three days of praziquantel therapy at 25mg/kg given three times daily. It is additionally important to counsel patients and their families on avoidance of raw seafood as well as contact prophylaxis, as cross-contamination from soiled utensils can result in illness to others (6).  A recent case series of locally-acquired paragonimiasis from undercooked river shellfish in the U.S. acquired from undercooked shellfish in restaurants (7) further highlights the importance of considering this diagnosis especially if the history of potential exposure is substantiated, thus raising awareness of paragonimiasis infection as a potential public health hazard in food/beverage establishments. 

In summary, paragonimiasis is a relatively common infection in endemic areas of the world. Infection is often mistaken as tuberculosis in immigrants to the western world. However, knowledge of the clinicopathologic features of the disease should lead to appropriate consideration and treatment for at-risk patients. 

References

1. Kagawa FT. Pulmonary paragonimiasis. Seminars in Respiratory Infections 1997;12:149-158.
2. Mukae H, Taniguchi H, Matsumoto N, Iiboshi H, Ashitani J, Matsukura S, Nawa Y. Clinicoradiologic features of pleuropulmonary paragonimus westermani on Kyusyu Island, Japan. Chest 2001;120:514-520.
3. Khan R, Sharma OP. Bronchial lavage in tropical pneumonias. Curr Opin Pulm Med 2007;13:225-229.
4. Slemenda SB, Maddison SE, Jong EC, Moore DD. Diagnosis of paragonimiasis by immunoblot. Am J Trop Med Hyg 1988;39:469-471.
5. Imai J. Evaluation of elisa for the diagnosis of paragonimiasis westermani. Trans R Soc Trop Med Hyg 1987;81:3-6.
6. Johnson RJ, Jong EC, Dunning SB, Carberry WL, Minshew BH. Paragonimiasis: Diagnosis and the use of praziquantel in treatment. Reviews of infectious diseases 1985;7:200-206.
7. Human paragonimiasis after eating raw or undercooked crayfish --- Missouri, July 2006-September 2010. MMWR 2010;59:1573-1576.

Reference as: Solomon GM, Schmidt E, Reves R, Welsh C. Cough and pleural disease in a Burmese immigrant-a masquerader. Southwest J Pulm Crit Care 2012;4:205-10. (Click here for a PDF version of the manuscript)

June 2012 Pulmonary Case of the Month: What’s a Millet Seed Look Like?

Alexis Christie, MD

Robert Viggiano, MD

Lewis J. Wesselius, MD

Pulmonary Medicine

Mayo Clinic Arizona

Scottsdale, AZ

History of Present Illness

A 32 year old woman presents with a week long history of dyspnea, cough, fatigue, tiredness and pruritis. She has a past medical history (PMH) of Stage IIB, nodular sclerosing Hodgkin’s disease diagnosed in January, 2011. She underwent several cycles of chemotherapy and eventually an autologous stem cell transplant in January, 2012. Her current medications include:

• Acyclovir 800mg bid
• Ativan 0.5mg q4h/ prn
• Hydromorphone 8mg q4h/ prn
• Atarax 100mg q6h/ prn
• Compazine 10mg q6h/ prn

She had just finished a course of levofloxacin.

PMH, SH and FH

As above. She is a life-long nonsmoker and has no history of lung disease.

Physical Examination

Her physical examination was normal.

Chest X-ray

Her chest x-ray was interpreted as unchanged from previous examinations. 

Which of the following are indicated?

1. Thoracic CT scanning
2. PET scanning
3. Empiric treatment with broad spectrum antibiotics
4. All of the above

Reference as: Christie A, Viggiano R, Wesselius LJ. June 2012 pulmonary case of the month: what's a millet seed look like? Southwest J Pulm Crit Care 2012;4:182-8. (Click here for a PDF version of the case)