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Infectious Causes of Right Middle Lobe Syndrome Aatif Rashid, MD, Sowmya Nanjappa, MBBS, MD, and John N

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Infectious Causes of Right Middle Lobe Syndrome Aatif Rashid, MD, Sowmya Nanjappa, MBBS, MD, and John N Case Series Infectious Causes of Right Middle Lobe Syndrome Aatif Rashid, MD, Sowmya Nanjappa, MBBS, MD, and John N. Greene, MD Summary: Right middle lobe (RML) syndrome is defined as recurrent or chronic obstruction or infection of the middle lobe of the right lung. Nonobstructive causes of middle lobe syndrome include inflammatory processes and defects in the bronchial anatomy and collateral ventilation. We report on 2 case patients with RML syndrome, one due to infection with Mycobacterium avium complex followed by M asiaticum infection and the other due to allergic bronchopulmonary aspergillosis. A history of atopy, asthma, or chronic obstruc- tive pulmonary disease has been reported in up to one-half of those with RML. The diagnosis can be made by plain radiography, computed tomography, and bronchoscopy. Medical treatment consists of bronchodilators, mucolytics, and antimicrobials. Patients whose disease is unresponsive to treatment and those with obstruc- tive RML syndrome can be offered surgical treatment. Introduction monary disease due to MAC infection in immunocom- The term middle lobe syndrome (MLS) was first used petent individuals can be divided into a primary form, by Graham et al1 in 1948, and the disease is defined which occurs in healthy persons who do not smoke, as recurrent or chronic collapse or infection of the middle lobe of the right lung. MLS can present in per- sons of any age. The syndrome is divided into an ob- Table 1. — Obstructive and Nonobstructive Causes of structive type (demonstrable airway occlusion) and a Middle Lobe Syndrome nonobstructive type (patent right middle lobe [RML] Sign/Symptom Obstructive Non- bronchus). Obstructive MLS can be caused either by Cause obstructive endobronchial lesions or extrinsic compression of the Cause RML bronchus. Malignancy is the most common cause Aspirated foreign body (especially in X of the obstructive type followed by an infectious etiolo- children) gy (Tables 1 and 2).2-14 Benign tumors (eg, hamartomas) Benign tumor (eg, hamartoma) X and malignant tumors (eg, primary lung cancer, me- Broncholiths endobronchially eroding X tastasis) alike can cause obstructive MLS and account from adjacent, calcified lymph nodes for up to 25% of cases.2 The most common cause of ex- Cardiovascular anomaly X trinsic compression of the RML bronchus is peribron- Endoluminal granuloma associated X chial lymphadenopathy due to infection, sarcoidosis, with sarcoidosis and metastasis.3 Nonobstructive causes of MLS include Enlarged peribronchial lymph nodes X inflammatory processes and defects in the bronchial (infection, sarcoidosis, metastasis) 15,16 causing extrinsic compression of anatomy and collateral ventilation. right middle lobe bronchus We report on 2 cases of RML syndrome, one due Etiology not completely understood X to infection with Mycobacterium avium complex Inflammation of the middle lobe and X (MAC) followed by infection with M asiaticum and the lingual area other due to allergic bronchopulmonary aspergillo- Infectious etiology X sis (ABPA). MAC is the most common nontuberculous Mycobacteria (NTM) species to infect humans.6 Pul- Inspissated mucus associated with X cystic fibrosis or allergic bronchopul- monary aspergillosis From the Departments of Internal Hospital Medicine (SN) and Insufficient collateral ventilation X Infectious Diseases (JNG), H. Lee Moffitt Cancer Center & Research Institute (AF), and the University of South Florida Morsani Col- Malignant tumor (eg, primary lung X lege of Medicine (SN), Tampa, Florida. cancer, metastases) Address correspondence to John N. Greene, MD, Department of Primary ciliary dyskinesia X Infectious Diseases, Moffitt Cancer Center, 12902 Magnolia Drive, FOB-3 BMT PROG, Tampa, FL 33612. E-mail: [email protected] Situs inversus/other congenital X malformations Submitted March 1, 2016; accepted June 24, 2016. No significant relationships exist between the authors and the Traction diverticula of the esophagus X companies/organizations whose products or services may be Data from references 2 to 5, 7 to 10, and 13. referenced in this article. 60 Cancer Control January 2017, Vol. 24, No. 1 and a secondary form, which occurs new changes in the left lower lobe, in persons with underlying lung dis- Table 2. — Infectious Causes of posterior bronchiectasis, and distal Middle Lobe Syndrome ease (eg, chronic obstructive pulmo- nodularity when compared with the nary disease [COPD], latent tubercu- Actinobacteria results on CT obtained 4 years prior losis, bronchiectasis, cystic fibrosis). Aspergillus species (Fig 1). She was treated with azithro- In general, the primary form affects Blastomyces species mycin and trimethoprim/sulfa- elderly women who are otherwise Bordetella pertussis methoxazole and advised to undergo healthy nonsmokers, and it presents surgical removal of the RML. Chlamydophila psittaci with an interstitial/nodular pattern Six months later she underwent on chest radiography.6 M asiaticum is Echinococcal pulmonary hydatid disease RML resection due to progressive a slow-growing mycobacterium spe- Haemophilus influenza symptoms and severe bronchiec- cies first recognized in Australia by Histoplasma species tasis predominantly in the RML. Blacklock et al17 in the early 1980s. Moraxella catarrhalis Findings on histopathology showed They surmised that M asiaticum Mycobacterium avium intracellulare necrotizing granulomatous bron- was a potential pulmonary pathogen Mycobacterium fortuitum chiolitis. Results from acid-fast ba- among individuals with an underly- cilli tissue staining were positive Mycobacterium tuberculosis ing chronic respiratory problem such with areas of chronic bronchitis and as COPD.17 Staphylococcus aureus bronchiolitis. She was then treated Persons with chronic lung dis- Streptococcus pneumonia on azithromycin monotherapy for ease are at risk of Aspergillus coloni- Data from references 6, 8, and 11 to 14. approximately 5 years with inter- zation and infection.18 ABPA occurs mittent courses of trimethoprim/ as a result of hypersensitivity to colonizing Aspergillus sulfamethoxazole. species in the airways of persons with asthma, NTM Five years following resection of the RML, she infection, and cystic fibrosis.8 It affects 2% of those returned for evaluation with symptoms of hemopty- with asthma.19 MLS caused by ABPA has rarely been sis, persistent cough, and pleuritic chest pain. Find- documented.19 ings on CT demonstrated new areas of nodularity in the anterior medial lingular area with bronchial wall Case Reports thickening, tree-in-bud nodules in the right posterior Case 1 lung, and an increase in nodularity in the left medial A woman aged 55 years presented with a 10-year his- posterior lung (Fig 2). BAL cultures grew M asiaticum tory of chronic cough with no prior history of smoking. sensitive to amikacin, ciprofloxacin, azithromycin, Serial computed tomography (CT) of the chest was ob- ethambutol, moxifloxacin, rifabutin, and trime- tained prior to her referral to our center. Bronchoalve- thoprim/sulfamethoxazole. olar lavage (BAL) was performed and the culture grew She was treated with azithromycin and trime- M avium intracellulare (MAI). She was treated with oral thoprim/sulfamethoxazole for 6 months. Her symptoms azithromycin, ethambutol, and rifampin for 1.5 years. resolved, and she has remained without any unwanted After several years of taking antibiotics, she devel- change in weight or significant pulmonary complaints, oped hemoptysis. Repeat BAL was performed and the except for an occasional nonproductive cough, for culture grew methicillin-resistant Staphylococcus au- 3 years following the discontinuation of the antibiotics. reus, so she was treated with oral clindamycin and trimethoprim/ sulfamethoxazole for 2 weeks. Following treatment the patient felt better but still had intermit- tent cough and periodic right lat- eral chest pain. Following 1 month off antibiotics, BAL was again performed and the culture grew both MAI and methicillin-resistant S aureus. CT of the chest was obtained and revealed persistent RML bron- chiectasis and distal nodularity, with new nodules and bronchiectasis in Fig 1. — Computed tomography showing the right middle lobe with large amounts of clustered the superior segment of the right bronchiectasis, distal nodularity. Nodules and bronchiectasis in the superior segment of the right lower lobe. CT results also showed and left lower lobes are also present. January 2017, Vol. 24, No. 1 Cancer Control 61 Case 2 A white woman aged 48 years with a history of rheumatoid arthri- tis was receiving treatment with methotrexate, adalimumab, and sulfasalazine. She also had a history of asthma requiring therapy with a β-agonist inhaler and intermittent corticosteroids. Approximately 3 months prior to her presentation, she developed right upper quadrant abdominal pain. Imaging of her abdomen and Fig 2. — Computed tomography of the chest showing a large mass with a lobulated, scalloped border chest was obtained, the results of in the right middle lobe. which showed a large mass in her RML approximately 6 cm in diam- eter. Transthoracic needle biop- sy was performed that revealed chronic nongranulomatous inflam- mation with septate hyphae con- sistent with Aspergillus infection. No cultures were sent. Findings from acid-fast bacilli stains were negative. CT and positron emis- sion tomography were performed, and the results showed increasing uptake and a lesion thought to be postobstructive pneumonia (Fig 3). Repeat needle biopsy was per- formed and demonstrated septate
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