Bronchiolitis obliterans as manifestation of pulmonary graft-versus-host-disease

Clinical History

40-year-old male patient presented with mild shortness of breath. He had a history of multiple myeloma and had received autologous stem cell transplant eight years before, and a second, allogeneic stem cell transplant from matched sibling donor ten months before.

Imaging Findings

Chest radiograph demonstrated mild hyperinflation with central bronchial wall thickening. Conventional non-contrast CT obtained at end expiration with 5 mm slices demonstrated mild mosaic attenuation, which was better demonstrated on the high-resolution end-expiration images with a 1.25 mm slice thickness. Mild bilateral bronchial wall thickening consistent with bronchiectasis can be appreciated on both studies. On end expiratory images, there was evidence of air trapping seen as geographic areas of decreased attenuation. There were no increased reticular markings or honeycombing to suggest underlying fibrosis. There were no focal consolidations or evidence of pulmonary oedema. Central airways were patent.

Discussion

Bronchiolitis obliterans (BO) is a late-phase pulmonary finding seen in up to 10% of bone marrow transplant patients, occurring as sequela of graft-versus-host disease (GHVD). Other less common pulmonary manifestations of GHVD include diffuse alveolar damage, organizing pneumonia, or lymphocytic interstitial pneumonitis. GHVD occurs more commonly in the setting of allogenic rather than autologous grafts. Pathologically, BO is characterised by obstructive granulation tissue in the lumen of bronchioles. Histologic features include bronchiolitis with a peribronchiolar neutrophilic and lymphocytic infiltrate [1]. In bone marrow transplant recipients, BO can arise from chronic rejection related to GVHD or drug toxicity. Other causes of bronchiolitis include previous viral or bacterial infection, medication treatment, collagen vascular disease, toxic inhalation exposure, and small vessel vasculitis [2].

Symptoms of BO are of variable severity and can include dyspnoea upon exertion, breathlessness, dry cough, or severe airflow obstruction [3]. BO is a diagnosis of exclusion. Other causes for obstructive lung disease including emphysema, chronic bronchitis, and asthma must be excluded first. Diagnosis is clinical as determined by FEV1 testing and can be confirmed with transbronchial biopsy.

Supportive plain radiographic findings include hyperinflation, vascular attenuation, and nodular opacities; however, chest radiograph is often normal or nonspecific. Standard CT is usually obtained at end-inspiration and may mask findings of BO. High-resolution end-expiratory images with 1-2 mm slice thickness will best demonstrate the geographic distribution of deceased attenuation due to localised air-trapping [4, 5]. Alveolar ventilation occurs from collateral air drift and relative obstruction of the alveoli connected to affected bronchioles. Oligaemia can be an associated finding, as sequela of reflexive local hypoxemic vasoconstriction. Additional supportive imaging features include subsegmental bronchial dilatation [6].

The primary treatment for BO in bone marrow transplant recipients is increased immunosuppression to counter the graft-versus-host response. Outcome is associated with the rate of onset. Patients with rapid onset BO and severe obstruction, typically have a poor outcome; in contrast, in patients with gradual onset BO, the outcome is improved, as the degree of obstruction may stabilise in about half of patients [7].

Teaching points:
1- Bronchiolitis obliterans is the most common pulmonary manifestation of graft-versus-host-disease.
2- CT imaging should include end-expiratory images when the diagnosis is suspected.
3- Bronchiolitis obliterans on end-expiratory HRCT is characterised by a mosaic attenuation pattern due to air trapped in the alveoli secondary to bronchiolar obstruction.
4- Differential diagnosis includes viral or other infectious bronchiolitis and drug toxicity.

Differential Diagnosis List

Final Diagnosis

Bronchiolitis obliterans from pulmonary graft-versus-host-disease

URL:	https://www.eurorad.org/case/9444
DOI:	10.1594/EURORAD/CASE.9444
ISSN:	1563-4086