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CASE REPORT
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Diffuse Alveolar Hemorrhage in a Patient with Acute Poststreptococcal Glomerulonephritis Caused by Impetigo Masahiro Yoshida 1, Hideaki Yamakawa 1, Masami Yabe 1, Takeo Ishikawa 1, Masamichi Takagi 1, Kei Matsumoto 2, Akihiko Hamaguchi 2, Makoto Ogura 2 and Kazuyoshi Kuwano 3
Abstract We herein report a case of pulmonary renal syndrome with nephritis in a 17-year-old boy with diffuse alveolar hemorrhage (DAH) associated with acute poststreptococcal glomerulonephritis (APSGN). The patient exhibited hemoptysis two weeks after developing impetigo, and DAH was diagnosed on bronchoscopy. Respiratory failure progressed, and high-dose methylprednisolone therapy was administered; the respiratory failure regressed immediately after the onset of therapy. Streptococcus pyogenes was detected in an impetigo culture, and, together with the results of the renal biopsy, a diagnosis of APSGN was made. This case demonstrates the effects of high-dose methylprednisolone therapy in improving respiratory failure. Key words: diffuse alveolar hemorrhage, pulmonary renal syndrome, impetigo, acute poststreptococcal glomerulonephritis, Streptococcus pyogenes (Intern Med 54: 961-964, 2015) (DOI: 10.2169/internalmedicine.54.3838)
Introduction
Case Report
Pulmonary renal syndrome (PRS) is a group of disorders in which diffuse alveolar hemorrhage (DAH) and glomerulonephritis progress rapidly and concomitantly. Often, the patient already exhibits respiratory failure at the onset of pulmonary renal syndrome, a condition that may be lifethreatening. In general, autoimmune diseases, such as antineutrophil cytoplasmic autoantibody-related vasculitis and Goodpasture syndrome, may be associated with DAH. However, it is rare to encounter DAH in a case of acute poststreptococcal glomerulonephritis (APSGN). We herein report a case of concomitant DAH and APSGN in which the patient’s respiratory failure was treated effectively with highcapacity steroids.
The patient was a 17-year-old male high-school student who was healthy by nature. He had injured the lateral malleolus of his right foot during club activities approximately two weeks before hospitalization, although he received no treatment. He noticed dyspnea while coughing and exhibited hemoptysis of approximately 30 mL two days prior to hospitalization. Anasarca developed the next day, and the patient underwent a checkup at our hospital because his dyspnea worsened. On a physical examination, he showed impetigo (Fig. 1), type 1 respiratory failure, hypertension, proteinuria, hematuria and impetigo on the right lateral malleolus at the time of consultation. The initial blood test findings were as follows: white blood cell count, 11,500/μL (neutrophils: 67.5%, lymphocytes: 18.6%, eosinophils: 3.5%); hemoglobin, 12.5 g/dL; platelet count, 286,000/L; serum creatinine, 1.25 mg/dL; blood urea nitrogen, 22 mg/dL. A uri-
１
Department of Internal Medicine, Division of Respiratory Medicine, Jikei University School of Medicine, Kashiwa Hospital, Japan, ２Department of Internal Medicine, Division of Nephrology and Hypertension, Jikei University School of Medicine, Kashiwa Hospital, Japan and ３Department of Internal Medicine, Division of Respiratory Medicine, Jikei University School of Medicine, Japan Received for publication August 10, 2014; Accepted for publication October 19, 2014 Correspondence to Dr. Masahiro Yoshida, [email protected]
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Intern Med 54: 961-964, 2015
DOI: 10.2169/internalmedicine.54.3838
Figure 1. Right foot lateral malleolus exhibiting impetigo.
A
B
Figure 2. (A) Chest X-ray on admission shows ground-glass opacity in the bilateral lungs. (B) Chest computed tomography demonstrates diffuse ground-glass opacity, interlobular septal thickening, centrilobular nodules and bilateral pleural effusion.
nalysis showed 3+ albuminuria and 2+ hematuria, and the urinary sediment contained numerous red blood cells in addition to many granular and hyaline casts. A 24-hour urine
collection revealed 2.8 g of protein. Chest X-rays showed ground-glass opacity in the total lung field (Fig. 2A), and chest computed tomography demonstrated diffuse ground-
962
Intern Med 54: 961-964, 2015
DOI: 10.2169/internalmedicine.54.3838
glass opacity, interlobular septal thickening, centrilobular nodules and bilateral pleural effusion (Fig. 2B). Based on the patient’s clinical course and imaging findings, we sus-
Figure 3. Bronchoalveolar lavage shows hemoid deposits. The rate of harvest for bronchoalveolar lavage was 55.3%. A
pected DAH and performed urgent bronchoscopy. The bronchoalveolar lavage fluid was bloody (Fig. 3), consistent with a diagnosis of DAH. Due to edematous exacerbation and the progression of respiratory failure, the patient was placed in the intensive care unit. A percutaneous renal biopsy was performed on the second hospitalization day, and methylprednisolone (mPSL; 1,000 mg/day) was administered intravenously for three days. Additional blood test findings were as follows: C3, 12 mg/dL; CH50, 18 U/mL (both of which were low); C4, 20 mg/dL (normal); anti-streptolysin-O, 396 U/mL; and anti-streptokinase, 1 : 2,560. Therefore, hemolytic streptococcus infection was suspected. All other autoantibodies, including antinuclear antibodies, anti-DNA antibodies, antiglomerular basement membrane antibodies and antineutrophil cytoplasmic autoantibodies, were negative. Streptococcus pyogenes was detected on an impetigo culture. The results of a renal biopsy were as follows: light microscopy showed swelling of most glomeruli, with diffuse and global neutrophilic infiltration and swollen and increased endothelial cells in the glomerular capillary tube (Fig. 4A). No extracapillary proliferative changes or glomerulus sclerosis were observed. Immunohistochemical staining showed diffuse granular deposition in the mesanB
C
Figure 4. (A) A renal biopsy specimen under light microscopy exhibits swollen glomeruli, extensive neutrophilic infiltration and swollen and increased endothelial cells in the glomerular capillary tube (Hematoxylin and Eosin staining, 200× magnification). (B) Immunohistochemical staining shows C3 complement deposition in the mesangium. (C3 staining, 200× magnification). (C) Electron microscopy reveals the presence of “hump-like” formations in the glomerular capillary tube. 963
Intern Med 54: 961-964, 2015
DOI: 10.2169/internalmedicine.54.3838
gium. C3 was positive in the composed material (Fig. 4B), and we detected a few “hump-like” formations on electron microscopy (Fig. 4C). Based on the results of bronchoscopy and the renal biopsy, we established a diagnosis of DAH accompanying APSGN. The serum creatinine level was elevated at 1.8 mg/dL on the fourth day of hospitalization but recovered gradually, reaching the normal range on the seventh hospital day. We gradually decreased the dose of mPSL due to an improvement in the respiratory failure and discontinued the drug on the 14th day of hospitalization. The patient did not require respirator management or transfusion, and his overall status recovered during hospitalization, allowing him to be discharged on the 19th hospital day.
Discussion
is common in patients infected with hemolytic streptococcus and becomes positive at a high rate in the acute phase of infection (5). The use of immune-staining in NAPLr in lung tissues and positive findings in lung tissue collected via bronchoscopy may explain the onset of DAH observed in patients with APSGN. We wish to emphasize the relationship between APSGN and DAH, as assessed on bronchoscopy, renal biopsies and culture examinations. In the present case, mPSL pulse therapy improved the patient’s respiratory failure, proteinuria and renal dysfunction. The authors state that they have no Conflict of Interest (COI).
References
It is well known that APSGN is a type of glomerulonephritis that occurs after hemolytic streptococcus infection; however, DAH very rarely develops in cases of APSGN. Only three patients have been reported to date, and high-capacity steroid therapy appears to be effective (1-3). Fukuda et al. reported the findings of a nephritic autopsy of a patient with DAH (4) and noted the possibility of alveolar hemorrhage caused by immune complex deposition on the capillary basement membrane and bronchial alveolar epithelium in Goodpasture syndrome. The immune complexes produced in patients with APSGN yield an air vesicle capillary basal membrane that exhibits inflammation. In the present case, we considered that the alveolar hemorrhage was induced by inflammation associated with the antigen-antibody reaction in Goodpasture syndrome. In cases of APSGN, the presence of a nephritis-associated plasmin receptor (NAPLr)
1. Sung HY, Lim CH, Shin MJ, et al. A case of post-streptococcal glomerulonephritis with diffuse alveolar hemorrhage. J Korean Med Sci 22: 1074-1078, 2007. 2. Gilboa N, McIntire S, Hopp L, et al. Acute noncrescentic poststreptococcal glomerulonephritis presenting with pulmonary hemorrhage. Pediatr Nephrol 7: 147-150, 1993. 3. Chugh KS, Gupta VK, Singhal PC, et al. Case report: poststreptococcal crescentic glomerulonephritis and pulmonary hemorrhage simulating Goodpasture’s syndrome. Ann Allergy 47: 104-106, 1981. 4. Fukuda Y, Yamanaka N, Ishizaki M, et al. Immune complexmediated glomerulonephritis and interstitial pneumonia simulating Goodpasture’s syndrome. Acta Pathol Jpn 32: 361-370, 1982. 5. Oda T, Yoshizawa N, Yamakami K, et al. The role of nephritisassociated plasmin receptor (NAPlr) in glomerulonephritis associated with streptococcal infection. J Biomed Biotechnol 2012: 417675, 2012.
Ⓒ 2015 The Japanese Society of Internal Medicine http://www.naika.or.jp/imonline/index.html
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CASE REPORT
□
Diffuse Alveolar Hemorrhage in a Patient with Acute Poststreptococcal Glomerulonephritis Caused by Impetigo Masahiro Yoshida 1, Hideaki Yamakawa 1, Masami Yabe 1, Takeo Ishikawa 1, Masamichi Takagi 1, Kei Matsumoto 2, Akihiko Hamaguchi 2, Makoto Ogura 2 and Kazuyoshi Kuwano 3
Abstract We herein report a case of pulmonary renal syndrome with nephritis in a 17-year-old boy with diffuse alveolar hemorrhage (DAH) associated with acute poststreptococcal glomerulonephritis (APSGN). The patient exhibited hemoptysis two weeks after developing impetigo, and DAH was diagnosed on bronchoscopy. Respiratory failure progressed, and high-dose methylprednisolone therapy was administered; the respiratory failure regressed immediately after the onset of therapy. Streptococcus pyogenes was detected in an impetigo culture, and, together with the results of the renal biopsy, a diagnosis of APSGN was made. This case demonstrates the effects of high-dose methylprednisolone therapy in improving respiratory failure. Key words: diffuse alveolar hemorrhage, pulmonary renal syndrome, impetigo, acute poststreptococcal glomerulonephritis, Streptococcus pyogenes (Intern Med 54: 961-964, 2015) (DOI: 10.2169/internalmedicine.54.3838)
Introduction
Case Report
Pulmonary renal syndrome (PRS) is a group of disorders in which diffuse alveolar hemorrhage (DAH) and glomerulonephritis progress rapidly and concomitantly. Often, the patient already exhibits respiratory failure at the onset of pulmonary renal syndrome, a condition that may be lifethreatening. In general, autoimmune diseases, such as antineutrophil cytoplasmic autoantibody-related vasculitis and Goodpasture syndrome, may be associated with DAH. However, it is rare to encounter DAH in a case of acute poststreptococcal glomerulonephritis (APSGN). We herein report a case of concomitant DAH and APSGN in which the patient’s respiratory failure was treated effectively with highcapacity steroids.
The patient was a 17-year-old male high-school student who was healthy by nature. He had injured the lateral malleolus of his right foot during club activities approximately two weeks before hospitalization, although he received no treatment. He noticed dyspnea while coughing and exhibited hemoptysis of approximately 30 mL two days prior to hospitalization. Anasarca developed the next day, and the patient underwent a checkup at our hospital because his dyspnea worsened. On a physical examination, he showed impetigo (Fig. 1), type 1 respiratory failure, hypertension, proteinuria, hematuria and impetigo on the right lateral malleolus at the time of consultation. The initial blood test findings were as follows: white blood cell count, 11,500/μL (neutrophils: 67.5%, lymphocytes: 18.6%, eosinophils: 3.5%); hemoglobin, 12.5 g/dL; platelet count, 286,000/L; serum creatinine, 1.25 mg/dL; blood urea nitrogen, 22 mg/dL. A uri-
１
Department of Internal Medicine, Division of Respiratory Medicine, Jikei University School of Medicine, Kashiwa Hospital, Japan, ２Department of Internal Medicine, Division of Nephrology and Hypertension, Jikei University School of Medicine, Kashiwa Hospital, Japan and ３Department of Internal Medicine, Division of Respiratory Medicine, Jikei University School of Medicine, Japan Received for publication August 10, 2014; Accepted for publication October 19, 2014 Correspondence to Dr. Masahiro Yoshida, [email protected]
961
Intern Med 54: 961-964, 2015
DOI: 10.2169/internalmedicine.54.3838
Figure 1. Right foot lateral malleolus exhibiting impetigo.
A
B
Figure 2. (A) Chest X-ray on admission shows ground-glass opacity in the bilateral lungs. (B) Chest computed tomography demonstrates diffuse ground-glass opacity, interlobular septal thickening, centrilobular nodules and bilateral pleural effusion.
nalysis showed 3+ albuminuria and 2+ hematuria, and the urinary sediment contained numerous red blood cells in addition to many granular and hyaline casts. A 24-hour urine
collection revealed 2.8 g of protein. Chest X-rays showed ground-glass opacity in the total lung field (Fig. 2A), and chest computed tomography demonstrated diffuse ground-
962
Intern Med 54: 961-964, 2015
DOI: 10.2169/internalmedicine.54.3838
glass opacity, interlobular septal thickening, centrilobular nodules and bilateral pleural effusion (Fig. 2B). Based on the patient’s clinical course and imaging findings, we sus-
Figure 3. Bronchoalveolar lavage shows hemoid deposits. The rate of harvest for bronchoalveolar lavage was 55.3%. A
pected DAH and performed urgent bronchoscopy. The bronchoalveolar lavage fluid was bloody (Fig. 3), consistent with a diagnosis of DAH. Due to edematous exacerbation and the progression of respiratory failure, the patient was placed in the intensive care unit. A percutaneous renal biopsy was performed on the second hospitalization day, and methylprednisolone (mPSL; 1,000 mg/day) was administered intravenously for three days. Additional blood test findings were as follows: C3, 12 mg/dL; CH50, 18 U/mL (both of which were low); C4, 20 mg/dL (normal); anti-streptolysin-O, 396 U/mL; and anti-streptokinase, 1 : 2,560. Therefore, hemolytic streptococcus infection was suspected. All other autoantibodies, including antinuclear antibodies, anti-DNA antibodies, antiglomerular basement membrane antibodies and antineutrophil cytoplasmic autoantibodies, were negative. Streptococcus pyogenes was detected on an impetigo culture. The results of a renal biopsy were as follows: light microscopy showed swelling of most glomeruli, with diffuse and global neutrophilic infiltration and swollen and increased endothelial cells in the glomerular capillary tube (Fig. 4A). No extracapillary proliferative changes or glomerulus sclerosis were observed. Immunohistochemical staining showed diffuse granular deposition in the mesanB
C
Figure 4. (A) A renal biopsy specimen under light microscopy exhibits swollen glomeruli, extensive neutrophilic infiltration and swollen and increased endothelial cells in the glomerular capillary tube (Hematoxylin and Eosin staining, 200× magnification). (B) Immunohistochemical staining shows C3 complement deposition in the mesangium. (C3 staining, 200× magnification). (C) Electron microscopy reveals the presence of “hump-like” formations in the glomerular capillary tube. 963
Intern Med 54: 961-964, 2015
DOI: 10.2169/internalmedicine.54.3838
gium. C3 was positive in the composed material (Fig. 4B), and we detected a few “hump-like” formations on electron microscopy (Fig. 4C). Based on the results of bronchoscopy and the renal biopsy, we established a diagnosis of DAH accompanying APSGN. The serum creatinine level was elevated at 1.8 mg/dL on the fourth day of hospitalization but recovered gradually, reaching the normal range on the seventh hospital day. We gradually decreased the dose of mPSL due to an improvement in the respiratory failure and discontinued the drug on the 14th day of hospitalization. The patient did not require respirator management or transfusion, and his overall status recovered during hospitalization, allowing him to be discharged on the 19th hospital day.
Discussion
is common in patients infected with hemolytic streptococcus and becomes positive at a high rate in the acute phase of infection (5). The use of immune-staining in NAPLr in lung tissues and positive findings in lung tissue collected via bronchoscopy may explain the onset of DAH observed in patients with APSGN. We wish to emphasize the relationship between APSGN and DAH, as assessed on bronchoscopy, renal biopsies and culture examinations. In the present case, mPSL pulse therapy improved the patient’s respiratory failure, proteinuria and renal dysfunction. The authors state that they have no Conflict of Interest (COI).
References
It is well known that APSGN is a type of glomerulonephritis that occurs after hemolytic streptococcus infection; however, DAH very rarely develops in cases of APSGN. Only three patients have been reported to date, and high-capacity steroid therapy appears to be effective (1-3). Fukuda et al. reported the findings of a nephritic autopsy of a patient with DAH (4) and noted the possibility of alveolar hemorrhage caused by immune complex deposition on the capillary basement membrane and bronchial alveolar epithelium in Goodpasture syndrome. The immune complexes produced in patients with APSGN yield an air vesicle capillary basal membrane that exhibits inflammation. In the present case, we considered that the alveolar hemorrhage was induced by inflammation associated with the antigen-antibody reaction in Goodpasture syndrome. In cases of APSGN, the presence of a nephritis-associated plasmin receptor (NAPLr)
1. Sung HY, Lim CH, Shin MJ, et al. A case of post-streptococcal glomerulonephritis with diffuse alveolar hemorrhage. J Korean Med Sci 22: 1074-1078, 2007. 2. Gilboa N, McIntire S, Hopp L, et al. Acute noncrescentic poststreptococcal glomerulonephritis presenting with pulmonary hemorrhage. Pediatr Nephrol 7: 147-150, 1993. 3. Chugh KS, Gupta VK, Singhal PC, et al. Case report: poststreptococcal crescentic glomerulonephritis and pulmonary hemorrhage simulating Goodpasture’s syndrome. Ann Allergy 47: 104-106, 1981. 4. Fukuda Y, Yamanaka N, Ishizaki M, et al. Immune complexmediated glomerulonephritis and interstitial pneumonia simulating Goodpasture’s syndrome. Acta Pathol Jpn 32: 361-370, 1982. 5. Oda T, Yoshizawa N, Yamakami K, et al. The role of nephritisassociated plasmin receptor (NAPlr) in glomerulonephritis associated with streptococcal infection. J Biomed Biotechnol 2012: 417675, 2012.
Ⓒ 2015 The Japanese Society of Internal Medicine http://www.naika.or.jp/imonline/index.html
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