Diffuse alveolar haemorrhage associated with subsequent development of ANCA positivity and emphysema in three young adults

Abstract

BackgroundDiffuse alveolar haemorrhage (DAH) is characterized by the diffuse accumulation of red blood cells within the alveoli, presence of ground glass opacities and/or consolidation on computed tomography (CT). Aside from identifiable non-immune causes, DAH is classically subdivided into idiopathic (idiopathic pulmonary haemosiderosis, IPH) and autoimmune DAH. Here we describe three cases presenting with recurrent pulmonary haemorrhage, initially classified as IPH, who, several years after first presentation, develop anti myeloperoxidase antibodies (MPO) positivity, emphysema on CT and, in one case, renal involvement.Case presentationPatient 1 was diagnosed with IPH aged 14. Her disease remained poorly controlled despite immunosuppression, although ANCA remained negative over the years. Nineteen years from initial presentation, she developed MPO-ANCA positive antibodies and mild renal impairment. She was treated with Rituximab with good response. From first presentation, the chest CT was consistently characterized by diffuse ground-glass opacities and interlobular septal thickening. Ten years later, cystic opacities consistent with emphysema, with a striking peribronchovascular distribution, developed. Patient 2 was diagnosed with IPH aged 32. He was treated with corticosteroids and methotrexate, with fluctuating response. At 11 years from initial presentation, MPO-ANCA positivity was identified, and emphysema with a peribronchovascular distribution was observed on CT, with subsequent significant increase in extent. Patient 3 was diagnosed with IPH at the age of seven, and had recurrent episodes of haemoptysis of varying degree of severity, treated with intermittent courses of corticosteroids until age 11, when he was intubated due to severe DAH. Eight years after the diagnosis emphysematous changes were noted on CT and MPO-ANCA positivity developed for the first time 11 years after initial diagnosis.ConclusionsWe believe these three cases highlight: 1) the possibility of development of ANCA positivity several years down the line from first DAH presentation 2) the possibility that DAH may lead to cystic/emphysematous changes with peribronchovascular distribution on CT. Moreover, the need for ongoing immunosuppressive treatment and the development of emphysema, emphasize a possible role played by autoimmune phenomena, even when DAH is initially diagnosed as “idiopathic”. Further studies are required to better understand the relationship between DAH, ANCA positivity and development of emphysema.

Assessment of Type I Interferon Signatures in Undifferentiated Inflammatory Diseases: A Japanese Multicenter Experience

“…IPH is a rare disorder characterized by diffuse alveolar hemorrhage. Although its etiology remains unknown, the involvement of immunological abnormalities has been suggested based on the presence of autoimmune antibodies [47][48][49] and the subsequent development of other autoimmune disorders, which have been observed in number of patients with IPH during follow-up [49][50][51][52]. Some investigators have suggested that circulating immune complexes deposited into the pulmonary capillaries were involved in the disease pathogenesis [47], which may provoke the upregulation of type IFN signaling.…”

Idiopathic Pulmonary Hemosiderosis Associated with Emphysematous Change in an Adult Who Underwent Lung Transplantation

“…Stainer et al reported that anti-neutrophil cytoplasmic antibody (ANCA) positivity and peribronchovascular emphysema developed with repeated hemoptysis in patients initially diagnosed with IPH. They speculated that proteolytic enzymes and free oxygen radicals released by vasculitis destroyed the alveolar walls and caused emphysema ( 16 ). However, in our case, although the involvement of noxious insults associated with hemorrhaging cannot be ruled out, the formation of emphysema is considered to involve bronchioles strictured by hemosiderosis potentially causing air trapping, which expands to more peripheral bronchioles and alveoli, thereby eventually leading to emphysematous change.…”

Comparative Analysis of Adult Patients With Idiopathic Pulmonary Hemosiderosis and Lane-Hamilton Syndrome: A Systematic Review of the Literature in the Period 1971-2022

“…The cytokines are expressed by the immunologic cells, such as eosinophils, basophils, and lymphocytes, when exposure to an unknown antigen occurs locally in the lung or through another route such as enterally. Moreover, an overall immune dysregulation in IPH could explain the susceptibility among these individuals to develop autoantibodies and other immune-mediated diseases [ 16 , 79 - 83 ]. We have proposed a new name, immune-mediated pulmonary hemosiderosis (ImPH), to focus on the immunologic causation of DAH [ 84 - 85 ].…”