Clinical diagnosis
Case 244
【Progress】
He received steroid pulse treatment, inducing improvement of pulmonary function.
【Discussion】
Radiologic findings of interstitial fibrosis are largely categorized into non-specific interstitial pneumonia (NSIP) and usual interstitial pneumonia (UIP). NSIP is characteristic of homogeneous and same-progressive stage on chest CT. Further, NSIP does contain reticular pattern but not honey-comb pattern. Meanwhile, UIP is characteristic of being inhomogeneous and mixed with various stages: minute nodules and/or thorns, reticular and honey-comb pattern. Further, bronchiectasis with traction due to fibrotic stress and sudden change from normal pulmonary parenchyma to advanced honey-comb pattern without intermediate stage are also specific to UIP (1-3). Radiologists should recognize the difference NSIP from UIP because prognosis of patients with UIP is poorer than those with NSIP.
The etiology of UIP is yet to be clarified. However, recent studies are promising to clarify the mechanism of forming UIP. There are two approaches for initiation of UIP: one is from myoblast/fibroblast and from alveolar cell 2 (AC2). In case of normal reparative process to micro-injury of pulmonary parenchyma, myofibroblast transforming from fibroblast and epithelial cell (type II alveolar cell, epithelial-mesenchymal transition, EMT), works for damaged parenchyma with forming fibrosis and extracellular matrix. After finishing roles, myofibroblast causes apoptosis, naturally disappears. In case of UIP, myofibroblast does not cause apoptosis and continues to form fibrin, inducing fibrosis. Then, one approach for developing medicine is to list up mediators (cytokine) to stimulate or survive fibroblasts and to form fibrosis by myofibroblasts (4,5). Another approach is to preserve AC2. The origin of UIP is reported to be unknown micro-injury causing apoptosis of AC2 which secretes surfactant to preserve alveolar space (6). When surfactant decreases, alveolar spaces collapse or enlarge forming fibrosis and honey-comb pattern. Idiopathic pulmonary fibrosis is deficit of inflammatory cells on histologic specimen. The sudden change of normal parenchyma to honey-comb pattern meets to loss of surfactant due to AC2 apoptosis. The substance to cause AC2 apoptosis is investigated for developing medicine.
In our case, he suffered from rheumatoid arthritis and chest CT showed UIP with honey-comb pattern. As treatment, steroid pulse therapy was effective to improve pulmonary function. The histologic pattern of pulmonary fibrosis with auto-immune disease includes not only fibrotic foci which is appeared on idiopathic pulmonary fibrosis but also infiltration of lymphocytes, plasma cells and formation of germ center. It is not clear whether immune cells foster apoptosis of AC2 or inhibit apoptosis of myofibroblasts.
There are three unclarified mysteries; why AC2 cell apoptosis occur; why myofibroblasts does not cause apoptosis: why honey-comb pattern first occurs in pulmonary marginal area.
【Summary】
We presented a seventy nine year-old male with rheumatoid arthritis. CT showed UIP pattern with honey-comb prominent in the pulmonary lower marginal area plus ground glass and/or consolidation. Pulse steroid therapy was effective to improve pulmonary function. It is borne in mind that there are two theories of causing UIP; continuous working of myofibroblasts without apoptosis by themselves: abrupt apoptosis of alveolar cell 2. Further, UIP is characteristic of triads; honey-comb pattern; abrupt change from honey-comb pattern to normal pulmonary parenchyma: traction bronchiectasis. On histology specimen, idiopathic pulmonary fibrosis is characteristic of fibrous foci without immune response, while autoimmune interstitial lung disease including rheumatoid arthritis is characteristic of fibrous foci plus infiltration of lymphocytes and plasma cells forming germ cells. As treatment, anti-mediator (anti-fibrosis) is the first choice for idiopathic pulmonary fibrosis while steroid is still the treatment of choice for autoimmune-related pulmonary fibrosis.
【References】
1.Christina MM, et al. What Every Radiologist Should Know about Idiopathic Interstitial Pneumonias. Radiographics 2007;27:595-615
2.Lynch DA, et al. Idiopathic interstitial pneumonias: CT features.Radiology. 2005 Jul;236(1):10-21.
3.Palmucci S, et al. Clinical and radiological features of idiopathic interstitial pneumonias (IIPs): a pictorial review. Insights Imaging. 2014 ;5(3):347-64.
4.Kim HC, et al. Histologic features suggesting connective tissue disease in idiopathic pulmonary fibrosis. Sci Rep 2020;10:21137
5.Roschmann RA, et al. Pulmonary fibrosis in rheumatoid arthritis: a review of clinical features and therapy. Semin Arthritis Rheum. 1987 ;16:174-185.
6.Liu J et al. Type 2 Alveolar Epithelial Cells Differentiated from Human Umbilical Cord Mesenchymal Stem Cells Alleviate Mouse Pulmonary Fibrosis Through β-Catenin-Regulated Cell Apoptosis. Stem Cells Dev 2021 Jul 1;30(13):660-670
2021.9.21