Follicular bronchiolitis is a bronchiolar lesion characterized by the presence of hyperplastic lymphoid follicles with reactive germinal centers distributed along bronchovascular bundles. This disorder can be idiopathic or occur in association with systemic disorders such as connective tissue diseases or immunodeficiency syndromes. Relatively little is known regarding prognostic implications and treatment of this disorder. Herein, we report a case of successful treatment of this condition with a macrolide antibiotic.
A 45 year old ex-smoker who initially presented to her primary care physician with shortness of breath. She was treated at that time for a presumed chest infection, but had no clinical improvement. Subsequently, pulmonary function studies revealed a reduced diffusing capacity and oxygen desaturation with exercise. A CT scan demonstrated a mosaic attenuation pattern. Bronchoscopy was non-diagnostic with negative cultures. She experienced symptomatic improvement with prednisone treatment but her dyspnea and fatigue worsened again as the prednisone dose was tapered. She had no significant environmental or occupations exposures. She had no clinical or laboratory features to suggest an underlying systemic connective tissue disorder or immunodeficiency syndrome. Surgical lung biopsy revealed histopathologic features of follicular bronchiolitis. Clinically, she had done relatively well, but was experiencing the side effects of chronic corticosteroid therapy including weight gain and hyperglycemia. A trial of azithromycin was initiated along with further tapering of the prednisone dose. After 3 months of azithromycin therapy, she was noticing improvement in her respiratory symptoms. After one year of therapy, she had normalization of her oxygen saturation with exercise and slight improvement of the diffusing capacity.
Follicular bronchiolitis is an uncommonly form of bronchiolar lesions that can be idiopathic or occur in association with connective-tissue disorders –particularly rheumatoid arthritis, immunodeficiency syndromes including AIDS, pulmonary infections, or ill-defined hypersensitivity reactions. Patients usually present with progressive dyspnea and variable pulmonary function abnormalities have been reported, including obstructive, restrictive, and mixed patterns. The predominant finding on chest radiography is bilateral, small nodular, or reticulonodular infiltrates with intrathoracic adenopathy, though occasionally chest radiographs may look normal. The cardinal features of follicular bronchiolitis on HRCT consist of bilateral and diffusely distributed centrilobular nodules measuring 1 to 12 mm in diameter, variably associated with peribronchial nodules and patchy areas of ground-glass opacity. Treatment is generally directed to the underlying disease when such association is recognized. Those patients with no identifiable underlying cause have generally been treated with bronchodilators and corticosteroids. More recently, Hayakawa and colleagues reported on the therapeutic benefits of chronic erythromycin therapy in patients with follicular bronchiolitis associated with rheumatoid arthritis. Based on this preliminary data our patient was also treated with chronic macrolide therapy and had experienced improvement. Macrolide antibiotics possess non-bactericidal immunomodulatory properties that include inhibiting inflammatory cell chemotaxis, cytokine synthesis, adhesion molecule expression, and reactive oxygen species production.
Follicular bronchiolitis is a bronchiolar lesion that can be idiopathic or occur in association with systemic disorders. Relatively little is known about the treatment or prognostic implications of this disorder. Our case suggests that chronic macrolide therapy may be useful in the treatment of follicular bronchiolitis in the non-rheumatoid population.