Clinical diagnosis
Case 128
【Progress】She was given anti-fungus treatment and antibiotics, improving respiratory condition. She was scheduled to enter the care center because of difficulty of care at home.
【Discussion】
3-β-D-glucan is produced by fungus and a constitute of fungus wall. Serum 3-β-D-glucan becomes to be available for screening of invasive fungus infection such as invasive Candida, invasive Aspergillosis and pneumocystis jirovecii pneumonia (PCP) (1, 2). Especially, the value of 3-β-D-glucan rises markedly in PCP rather than invasive Candida and Aspergillosis. The cutoff value of 3-β-D-glucan for the diagnosis of PCP was 31.1 pg/mL, with 0.610 of positive predictive value and 0.980 of negative predictive value (1). In our case, the 3-β-D-glucan value was 43.6 pg/dL, implying the possibility of falling in PCP infection.
Typical findings of Chest CT are ground glass opacity and pneumatocele in both upper and lower lobes associated with sparing peripheral zone of less than 40 % (3-6). When prophylactic treatment including aerosol inhalation is given, pneumatocele occurs in the upper lobe with a risk of pneumothorax. Cavity formation is possibly followed by (3-6). The typical findings of laboratory test are associated with the decrease of lymphocytes count (7). In our case who received immunosuppressive drugs, CT showed bilateral ground glass opacity with cavity formation in the left apical area, and lymphocytes count was 750 to 811/mm3, relatively less.
The mechanism of ground glass opacity and pneumatocele is reported to result from lymphohistiocytic interstitial pneumonia based on the histopathology using a rat (7). In short, lymphocytes and macrophages infiltrate to perivascular area of the alveolar septum and alveoli itself. Thereafter, the lymphohistiocytic interstitial pneumonia results in the alveolar septal thickening with lymphocytes infiltration and extensive leukocytes alveolar infiltration (7, 8). Further, foamy eosinophilic exudates containing fungus, pneumocystis jiroveci, are observed at the same area (7, 8). Pneumatocele is probably formed by the foamy eosinophilic exudates or occlusion of respiratory bronchiole by lymphocytes infiltration.
Meanwhile, PCP is usually accompanied with hypoxemia and severe ground glass opacity in the whole lung. This phenomenon is reported to be due to intensive neutrophils infiltration after continuous and long-term infiltration of lymphocytes and macrophages which play a main role to combat fungus (8). Namely, the long-term usage of corticosteroids induces the decrease of lymphocyte counts and its function. Macrophages secretes Interleukin 8 to recruit neutrophils probably because of the less aids from lymphocytes. Neutrophils have a double-edged sword. One sword is that neutrophils combat and kill invading pathogens followed by its own apoptosis and phagocytosis by macrophages. Another sword is that neutrophils over-activation using toxic agents including protease and reactive oxygen agents (which are weapons originally for bacteria and virus) cause damages to capillary endothelial cells and alveolar cells (8, 9), leading to acute respiratory distress syndrome. Fortunately, our patient could escape from ARDS thanks to cordial treatment.
【Summary】
We present a seventy-year-old female suffering from dyspnea. She had been given steroid for a relatively long term due to rheumatoid arthritis. Laboratory test revealed high values of β-D glucagon 43.6 pg/mL. Pulmonary CT showed not only reticular to honey comb pattern in the basal area, indicating rheumatoid pneumonitis but also ground glass opacity and cavity formation. These two findings met the criteria of pneumocystis pneumonia (PCP). It is borne in mind that 3-β-D-glucan is a constitute of fungus wall and plays a role of screening for invasive fungus infection. The characteristic findings of chest CT are ground glass opacity and pneumatocele, indicative of lympho-histiocyte interstitial pneumonia. It is the etiologic mechanism of PCP that the long term infiltration of lymphocytes and macrophages to alveolar wall and alveolar itself, followed by extensive leukocytes infiltration to alveolar itself. Leukocytes have double-sword edges. It is a negative edge that neutrophils over-activation using toxic agents including protease and reactive oxygen agents (which are weapons originally for bacteria and virus) cause damages to capillary endothelial cells and alveolar cells, leading to acute respiratory distress syndrome.
【References】
1.Tasaka S, et al. Serum indicators for the diagnosis of pneumocystis pneumonia. Chest: 2007;131:1173-1180.
2.Onishi A, et al. Diagnostic accuracy of serum 1,3-β-D-glucan for pneumocystis jiroveci pneumonia, invasive candidiasis, and invasive aspergillosis: systematic review and meta-analysis. J Clin Microbiol.2012;50:7-15
3.Müller NL, et al. Imaging of pulmonary infections. Lippincott Williams & Wilkins. (2007) ISBN:078177232X.
4.Ghosh AK. Mayo Clinic Internal Medicine Review, Eighth Edition. Informa HealthCare. (2008) ISBN:142008478X.
5.Maffessanti M, et al. Diffuse lung diseases, clinical features, pathology, HRCT. Springer Verlag. (2006) ISBN:8847004292.
6.Kanne JP, et al. Pneumocystis jiroveci Pneumonia: High-Resolution CT Findings in Patients With and Without HIV Infection, American Journal of Roentgenology. 2012;198: W555-W561
7.Kim HS, et al. Histopathology of Pneumocystis carinii pneumonia in immunocompetent laboratory rats. Exp Ther Med. 2014 Aug; 8(2): 442–446.
8.Pechous RD, et al. With Friends Like These: The Complex Role of Neutrophils in the Progression of Severe Pneumonia. Front Cell Infect Microbiol. 2017; 7: 160.
9.Thomas Jr CF, et al. Pneumocystis Pneumonia. N Engl J Med 2004; 350: 2487-98.
2018.11.7