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A case of bronchiolitis obliterans organizing pneumonia in an HIV-infected Korean patient successfully treated with clarithromycin
© Jung et al. 2015
Received: 8 March 2015
Accepted: 14 July 2015
Published: 23 July 2015
Bronchiolitis obliterans organizing pneumonia (BOOP) is a type of diffuse interstitial lung disease characterized by the pathology of fibroblastic plugs in the lumens of the respiratory bronchioles, alveolar ducts, and alveoli. The occurrence of BOOP in human immunodeficiency virus (HIV)-infected patients has rarely been described, and there have been no clinical case reports in Korea.
A 24-year-old female who had been diagnosed with HIV ten years prior was admitted due to a 1-year history of cough and sputum production and a 3-day history of fever. She had poor adherence to anti-retroviral therapy (ART) due to gastrointestinal troubles. At the time of admission, her CD4 T-cell count was 5 cells/mm3. A high resolution computed tomography (CT) scan showed tiny centrilobular nodules with a tree-in-bud pattern in both lungs. Bacterial culture, Pneumocystis jirovecii polymerase chain reaction (PCR), Aspergillus galactomannan antigen (Ag) assay, and respiratory virus PCR were negative. Rapid chest x-ray improvement was seen after a 7-day treatment with anti-tuberculosis medication, ceftriaxone, and clarithromycin. Miliary tuberculosis seemed unlikely considering the rapid radiologic improvement and negative tuberculosis PCR results. Due to the unknown etiology, we performed video-assisted thoracoscopic surgery (VATS) to determine the cause of the diffuse lung infiltration. Pathologic findings were consistent with BOOP, while tissue acid-fast bacilli (AFB) stain and tuberculosis PCR results were negative. Tuberculosis medication and intravenous ceftriaxone were discontinued, while treatment with clarithromycin monotherapy was sustained. Five months after discharge, the patient was asymptomatic with a normal chest x-ray and as her adherence to ART improved, her CD4 T-cell count rose to 181 cells/mm3. Clarithromycin was discontinued at that time and the patient is currently receiving regular outpatient follow-up.
This case suggests that macrolides are a potential treatment option in HIV-infected patients with mild BOOP. In cases that are otherwise unexplained or unresponsive to treatment, BOOP should be taken into consideration and surgical biopsy performed to confirm a diagnosis of BOOP.
Bronchiolitis obliterans organizing pneumonia (BOOP) is a type of diffuse interstitial lung disease characterized by the pathology of fibroblastic plugs in the lumens of the respiratory bronchioles, alveolar ducts, and alveoli . Various lung diseases have been reported in patients infected with human immunodeficiency virus (HIV), but there are few reports of the occurrence of BOOP in HIV patients and prior to this study, there was no clinical case report in Korea . Here, we describe a unique case of BOOP in a HIV-infected patient diagnosed by surgical lung biopsy and successfully treated with clarithromycin.
BOOP is a diffuse interstitial lung disease that affects the small airways . The precise incidence and prevalence of BOOP is unknown, though a study performed in Italy confirmed 78 cases of biopsy-proven BOOP in a 7 year period in a single center . Clinical features of this disease include fever, mild dyspnea, and cough, similar to flu-like symptoms . The pathogenesis of BOOP is thought to be due to epithelial injury followed by formation of fibrinoid inflammatory cell clusters and consequently intra-alveolar fibrosis . The pathologic hallmark of BOOP is the presence of fibroblastic plugs in the lumens of the respiratory bronchioles, alveolar ducts, and alveoli. . Due to these characteristic pathologic findings, biopsy for diagnosis of BOOP is essential [4, 5]. Transbronchial lung biopsy may be performed, but video-assisted thoracoscopic lung biopsy is the preferred technique because it is more likely to provide an adequate amount of tissue [4, 5]. Because BOOP occurs as a result of an inflammatory response to lung injury, a good treatment response is seen with broad-spectrum anti-inflammatory agents, such as corticosteroids and immune-modulatory macrolides . A few case reports have described treatment of BOOP in non-HIV-infected patients with macrolide antibiotics, but there have been no studies of their use in HIV-positive patients . High dose oral glucocorticoid therapy of 0.75-1 mg/kg per day is suggested for initial treatment of patients with severe symptoms . There are no established guidelines regarding duration of treatment, though a total of 1 year is often recommended due to frequent relapses in cases in which therapy was discontinued earlier . Immune-modulatory macrolides treat mild diseases such as BOOP by inhibiting pro-inflammatory cytokine production [8, 9].
There is a reasonable chance that BOOP in a HIV-infected patient may be underdiagnosed, considering that areas of high HIV prevalence are usually resource-limited and lung biopsies are not readily performed in these places. Until now, concurrent BOOP and HIV infection has been reported in only 11 patients. Diagnoses were made via transbronchial or thoracoscopic biopsy, and a rapid treatment response was seen with the use of corticosteroids. However, in one case, fatal pulmonary aspergillosis occurred, and CMV retinitis and esophagitis occurred in two cases. These complications imply that prolonged use of corticosteroids in HIV-infected BOOP patients may result in fatal clinical outcomes secondary to their immunocompromised state . Both HIV and non-HIV infected patients respond well to glucocorticoid therapy; however, prolonged use of steroids in patients with concomitant HIV and BOOP can increase the risk of opportunistic infections . While there are many known side-effects associated with long-term use of corticosteroids, macrolides have been shown to be effective and relatively safe to use on a long-term basis . In previous case reports (Allen et al., Liote et al., Laguna Del Estal et al. and Santio et al.), HIV infected patients with BOOP presented with a low CD4 cell count or a low CD4/CD8 ratio, suggesting that severe immune deficiency may be needed for BOOP to develop in this scenario . When treating HIV-infected patients who have low immune status, physicians should consider a diagnosis of BOOP in patients unresponsive to treatment for more common conditions, such as Pneumocystis jirovecii pneumonia, or when the etiology is unknown .
The limitations of this case report are as follows. The patient’s CD4 T-cell count improved significantly (from 5 to 181 cells/mm3) from the time of diagnosis of BOOP until the end of macrolide treatment. This improvement in immune status may have provided protection from other opportunistic infections. Empirical treatment with ceftriaxone may have improved the clinical course, and there is also the chance that the BOOP resolved spontaneously. Our evaluation of the patient’s response to clarithromycin treatment may not have been accurate for the above reasons.
In summary, this case suggests that macrolides are a potential treatment option in HIV-infected patients with mild BOOP. In cases that are otherwise unexplained or unresponsive to treatment, BOOP should be taken into consideration and surgical biopsy performed to confirm a diagnosis of BOOP.
Written informed consent was obtained from the patient for publication of this case report. A copy of the written consent is available for review by the Editor of this journal.
This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (NRF-2013R1A1A2005412), a Chronic Infectious Disease Cohort grant (4800-4859-304-260) from the Korea Centers for Disease Control and Prevention, and the BioNano Health-Guard Research Center funded by the Ministry of Science, ICT, and Future Planning of Korea as a Global Frontier Project (Grant H-GUARD_2013M3A6B2078953).
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