http://informahealthcare.com/mor ISSN 1439-7595 (print), 1439-7609 (online) Mod Rheumatol, 2014; Early Online: 1–3 © 2014 Japan College of Rheumatology DOI: 10.3109/14397595.2014.954742
CASE REPORT
Gastrointestinal involvement at the onset of granulomatosis with polyangiitis: A case report Ayaka Yoshikawa, Shuzo Yoshida, Tohru Takeuchi, Yohei Fujiki, Shigeki Makino, and Toshiaki Hanafusa
Mod Rheumatol Downloaded from informahealthcare.com by Queen's University on 03/06/15 For personal use only.
Department of Internal Medicine (I), Osaka Medical College, Takatsuki City, Osaka, Japan Abstract
Keywords
A 30-year-old man had developed fever, bloody stools, and oral aphtha. Proteinase 3-antineutrophil cytoplasmic antibody level was 31 EU. Lower intestinal endoscopy revealed edematous mucosa with hemorrhage in the transverse colon. Biopsies of oral aphtha showed necrotizing angiitis with granuloma. Based on these findings, he was diagnosed with granulomatosis with polyangiitis (GPA). Digestive symptoms were remitted by treatment with prednisolone and azathioprine. GPA with digestive symptoms as the initial development is rare.
Granulomatosis with polyangiitis, Oral intestinal symptoms, Azathioprine, PR3-ANCA, Primary manifestation
Introduction Granulomatosis with polyangiitis (GPA) is a systemic angiitis syndrome presenting with antineutrophil cytoplasmic autoantibody (ANCA). It is characterized by the following findings: 1) necrotizing granulomatous inflammation mainly in the nose, ears, eyes, upper airway, and lung; 2) focal segmental necrotizing glomerular nephritis; and 3) systemic necrotizing angiitis of the middle and small muscular arteries [1]. Necrotizing granulomatous lesions are observed in the upper airway, lung, and blood vessels throughout the body. Gastrointestinal involvement is rare in ANCA-associated vasculitis, particularly GPA, but it is a serious complication. We report a rare case of GPA in a patient presenting with gastrointestinal involvement as the initial symptom and review two similar cases reported in the literature.
Case presentation A 30-year-old man developed fever, bloody stools, and painful oral aphtha in mid-September 2009. The symptoms aggravated, and pharyngeal pain and a skin ulcer in the subumbilical region developed. He was treated with ceftriaxone, doripenem, and meropenem by a home-visiting doctor, but the response was unfavorable; he was admitted to our hospital in October 2009. Anemia was noted in the palpebral conjunctiva. The abdomen was flat and soft with tenderness, and bowel sounds were normal. Several painful aphtha of 1 cm were present in the oral cavity. A skin ulcer of 2 cm was present in the subumbilical region. Laboratory findings showed that urinalysis was normal, white blood cell counts were 12,710/μl (neutrophils: 77.0%), C-reactive protein was 15.9 mg/dl, and creatinine was 0.85 mg/dl (Table 1). Serological tests showed a proteinase 3(PR3)-ANCA level of 31 EU (standard: ⬍ 10 EU). No abnormalities were observed in chest X-ray and computed tomographic (CT) images. However,
Correspondence to: Ayaka Yoshikawa, Department of Internal Medicine (I), Osaka Medical College, 2-7 Daigakumachi, Takatsuki City, Osaka 569-8686, Japan. Tel: ⫹ 81-72-683-1221. Fax: ⫹ 81-72-684-6531. E-mail: [email protected]
History Received 13 August 2013 Accepted 12 August 2014 Published online 15 September 2014
paranasal and abdominal CT imaging showed mass lesions in the paranasal sinus and thickening of the transverse colon wall (Figure 1a). Lower intestinal endoscopy revealed reddened edematous mucosa with continuous bleeding on the oral side of the right transverse colon, but not other intestinal parts such as the ileum and rectum (Figure 1b). Superficial inflammatory cell infiltration and edema were noted in the lamina propria mucosae of this region on biopsy (Figure 2c). Oral aphtha biopsy showed necrotizing granulomatous inflammation with the infiltration of plasma cells, lymphocytes, and histiocytes (Figure 2a). Perivascular infiltration of lymphocytes and neutrophils was noted in the skin ulcer biopsy specimen (Figure 2b). No eosinophil infiltration, multinucleated giant cells, or fibrinoid degeneration was noted in the histology of either biopsy specimen. Based on the above findings, GPA was diagnosed following the protopathic systemic vasculitis classification algorithm [2]. On the 5th day in hospital, 65 mg/day of prednisolone (PSL) and 50 mg/ day of azathioprine (AZP) were initiated. The bloody stools, oral ulcers, and the subumbilical skin ulcer disappeared with the reduction in C-reactive protein (CRP) and PR3-ANCA levels. CT imaging on the 12th day in hospital showed improvement in wall thickening of the transverse colon and the granulomatous lesions in the right paranasal cavity (Figure 1c). Lower intestinal endoscopy performed on the 15th day in hospital showed improvement in the edematous mucosa and ulcer (Figure 1d). No serious complications occurred thereafter. The symptoms of the patient were well controlled with 5 mg/day of PSL and 75 mg/day of AZP.
Discussion Gastrointestinal involvement of ANCA-associated vasculitis is rare with a reported incidence of 7% [3], but severe gastrointestinal hemorrhage and acute celiopathy may occasionally occur. Twenty cases of gastrointestinal involvement that complicates GPA have been reported previously [4–21]. The incidence of gastrointestinal involvement is high in middle-aged men, and the small intestine and colon are frequently involved. Lower intestinal endoscopy shows the multiple shallow ulcers with or without perforation [4]. Digestive manifestations develop simultaneously with or after
2
A. Yoshikawa et al.
Mod Rheumatol, 2014; Early Online: 1–3
Table 1. Laboratory values.
Mod Rheumatol Downloaded from informahealthcare.com by Queen's University on 03/06/15 For personal use only.
WBC Neut Mono Eos Baso Lymph Hb PLT TP Alb AST ALT LDH ALP γ-GTP BUN Cr CRP Erythrocyte sedimentation rate
12,710/μl 77.0% 9.0% 0.0% 0.0% 12.0% 12.0 g/dl 48.2 ⫻ 104/μl 5.8 g/dl 2.3 g/dl 21 U/l 28 U/l 188 U/l 746 U/l 136 U/l 9 mg/dl 0.85 mg/dl 15.9 mg/dl 83 mm/hr
PT–INR APTT Fibrinogen FDP AT-III IgG IgA IgM C3 Antinuclear antibody Rheumatoid factor MPO-ANCA PR3-ANCA Endotoxin β–D glucan CMV antigenemia QFT Various culture tests (blood, sputum, and urine cultures)
1.24 34.8 sec 593 mg/dl 3.8 μg/ml 89% 1,492 mg/dl 313 mg/dl 74 mg/dl 145 mg/dl (⫺ ) ⬍ 3 IU/ml ⬍ 10 EU 31 EU ⬍ 1.82 pg/ml ⬍ 3.58 pg/ml Negative Negative Negative
WBC white blood cell, Neut neutrophils, Mono monocytes, Eos eosinophils, Baso basophils, Lymph lymphocytes, Hb hemoglobin, PLT platelets, TP total protein, Alb albumin, AST aspartate aminotransferase, ALT alanine aminotransferase, LDH lactate dehydrogenase, ALP alkaline phosphatase, g-GTP gamma guanosine triphosphate, BUN blood urea nitrogen, Cr creatinine, CRP C-reactive protein, PT–INR prothrombin time and international normalized ratio, APTT activated partial thromboplastin, FDP fibrinogen degradation products, AT-III antithrombin III, IgG immunoglobulin G, IgA immunoglobulin A, IgM immunoglobulin M, MPO-ANCA myeloperoxidase-antineutrophil cytoplasmic antibody, PR3-ANCA proteinase 3-antineutrophil cytoplasmic antibody, CMV antigenemia cytomegalovirus antigenemia, QFT quantiFERON
renal and pulmonary manifestations in active GPA disease [3]. Only 3 cases of GPA manifesting digestive symptoms as the initial development have been reported, which includes our patient [5,6] (Table 2). In all 3 cases, gastrointestinal lesions were present in the colon with bloody stools. Severe complications, such as renal dysfunction and pulmonary alveolar hemorrhage, rapidly developed within 3 weeks after the appearance of digestive symptoms in the other two reported cases. The algorithm to classify systemic vasculitis was recently proposed by Watts et al. [2]. Using this algorithm, it may be difficult to classify GPA in the cases that lack renal and pulmonary involvements. Behcet’s disease and inflammatory bowel diseases, such as ulcerative colitis and Crohn’s disease, are ruled out from the
Figure 1. Abdominal CT and lower intestinal endoscopy before and after the treatment. Wall thickening of the transverse colon was noted on abdominal CT (a), which improved after treatment (c). Lower intestinal endoscopy revealed reddened edematous mucosa with hemorrhage in the right transverse colon (b). Inflammation was improved, edema disappeared, and cicatrization was observed after treatment (d).
differential diagnosis. Behcet’s disease is characterized by single ulcer or a few deep ulcers with discrete margins at the site opposite to mesenteric attachment in the small intestine and colon, especially
Figure 2. Biopsy of oral aphtha (a), skin ulcer (b), and right transverse colon (c). Necrotizing granulomatous inflammation with infiltrating plasma cells, lymphocytes, and histiocytes was noted in the oral aphtha biopsy specimen (a). Perivascular infiltration of lymphocytes and neutrophils (arrow) was observed in the skin ulcer biopsy specimen (b). Superficial inflammatory cell infiltration and edema were noted in the lamina propria mucosae of the right transverse colon biopsy specimen (c).
Gastrointestinal involvement in GPA 3
DOI 10.3109/14397595.2014.954742
Table 2. Details of the present and two reviewed cases of GPA with digestive symptoms at onset.
Time from onset to initiation of treatment Treatment
About 2 weeks
Morchón-Simón and Martín-Escudero [5] 43 Male Colon Bloody stool Renal disorder, finger ulcer, splenic infarction, pulmonary lesion About 4 weeks
PSL, AZP
PSL, CY
Prognosis
Survived
Survived (dialysis)
Age (years) Sex Intestinal region Digestive symptom Complications
Our case 30 Male Colon Bloody stool Skin ulcer, oral aphtha
Qian et al. [6] 79 Female Colon Bloody stool Pulmonary alveolar hemorrhage, renal disorder About 2 weeks m-PSL pulse, PSL, CY, Plasmapheresis Survived
Mod Rheumatol Downloaded from informahealthcare.com by Queen's University on 03/06/15 For personal use only.
AZP azathioprine, CY cyclophosphamide, GPA granulomatosis with polyangiitis, PSL prednisolone, m-PSL methylprednisolone
the ileum [22]. Ulcerative colitis shows continuous involvement of the colon above the rectum [23]. Crohn’s disease is characterized by involvement of the colon or terminal ileum with patchy distribution and “cobblestone”-like appearance [24]. Our case lacked the above characteristic symptoms of Behcet’s disease and inflammatory bowel diseases, showed inflammatory granuloma in the biopsy of oral ulcer, and was diagnosed as GPA. Gastrointestinal involvement in GPA is treated with immunosuppressive therapies such as steroid pulse treatment and cyclophosphamide therapy [3,5,6]. Some patients with severe disease require additional surgical treatment. It is difficult to diagnose the gastrointestinal involvement of GPA because it is a rare disease and the manifestations are not specific for GPA. Although the biopsy specimens of the transverse colon in this case showed leukocytoclastic vasculitis without granulomatous lesions, the gastrointestinal involvement is suggested to be due to GPA in early-onset disease, which may have led to remission by treatment with PSL and AZP. GPA developing with digestive symptoms at the initial onset is rare, but it can rapidly progress with complications of pulmonary and renal disorders. Examination of the entire body and early intervention with immunosuppressive drugs may be important in treating such cases of GPA before serious illness occurs. We presented this case at the 55th annual meeting of Japanese College of Rheumatology 2011.
Conflict of interest None.
References 1. Wegener F. Über eine eigenartige rhinogene Granulomatose mit besonderer Beteiligung des Arteriensystems und der Nieren. Beitr Path Anat Pathol. 1939;102:36–68. 2. Watts R, Lane S, Hanslik T, Hauser T, Hellmich B, Koldingsnes W, et al. Development and validation of a consensus methodology for the classification of the ANCA-associated vasculitides and polyarteritis nodosa for epidemiological studies. Ann Rheum Dis. 2007;66(2): 222–7. 3. Pagnoux C, Mahr A, Cohen P, Guillevin L. Presentation and outcome of gastrointestinal involvement in systemic necrotizing vasculitides: analysis of 62 patients with polyarteritis nodosa, microscopic polyangiitis, Wegener granulomatosis, Churg-Strauss syndrome, or rheumatoid arthritis-associated vasculitis. Medicine (Baltimore). 2005;84(2):115–28. 4. Deniz K, Ozşeker HS, Balas S, Akpýnar E, Sökmensüer C. Intestinal involvement in Wegener’s granulomatosis. J Gastrointestin Liver Dis. 2007;16(3):329–31.
5. Morchón-Simón D, Martín-Escudero JC. Hemorrhagic colitis as the onset of Wegener’s granulomatosis. Int J Colorectal Dis. 2011;26(2):259–60. 6. Qian Q, Cornell L, Chandan V, Hartman R, Caples S. Hemorrhagic colitis as a presenting feature of Wegener granulomatosis. J Gastrointestin Liver Dis. 2010;19(4):445–7. 7. McNabb WR, Lennox MS, Wedzicha JA. Small intestinal perforation in Wegener’s granulomatosis. Posagrad Med J 1982;58(676):123–5. 8. Haworth SJ, Pusey CD. Severe intestinal involvement in Wegener’s granulomatosis. Gut. 1984;25(11):1296–300. 9. Geraghty J, Mackay IR, Smith DC. Intestinal perforation in Wegener’s granulomatosis. Gut 1986;27(4):450–1. 10. Tokuda M, Kurata N, Daikuhara H, Akisawa M, Onishi I, Asano T, et al. Small intestinal perforation in Wegener’s granulomatosis. J Rheumatol. 1989;16(4):547–9. 11. Pinkney JH, Clarke G, Fairclough PD. Gastrointestinal involvement in Wegener’s granulomatosis. Gastrointest Endosc. 1991;37(3):411–2. 12. Wilson RH, Kerr PP, McLoughlin J, Gormley M. Symptomatic colitis as the initial presentation of Wegener’s granulomatosis. Br J Clin Pract. 1993;47(6):315–8. 13. Schneider A, Menzel J, Gaubitz M, Keller R, Lugering N, Domschke W. Colitis as the initial presentation of Wegener’s granulomatosis. J Intern Med. 1997;242(6):513–7. 14. Corne P, Grosleron S, Cayrol B, Reynoud D, Yeche S, Capron F, Dubois A. Wegener’s disease, a rare cause of granulomatous colitis. Gastroenterol Clin Biol. 1997;21(2):163–4. 15. Storesund B, Gran JT, Koldingsnes W. Severe intestinal involvement in Wegener’s granulomatosis report of two cases and reiew of the literature. Br J Rheumatol. 1998;37(4):387–90. 16. Srinivasan U, Coughlan RJ. Small intestinal perforation complicating Wegener’s granulomatosis. Rheumatology (Oxford). 1999;38(3): 289–90. 17. Steele C, Bohra S, Broe P, Murray FE. Acute upper gastrointestinal haemorrhage and colitis: an nunusual presentation of Wegener’s granulomatosis. Eur J Gastroenterol Hepatol. 2001;13(8):993–5. 18. Chow FY, Hooke D, Kerr PG. Severe intestinal involvement in Wegener’s granulomatosis. J Gastroenterol Hepatol 2003;18(6): 749–50. 19. Veinot JP, Logan CA, Thomas MJ. Wegener’s granulomatosis arteritis causing small bowel infarction. Pathology 2003;35(3):268–9. 20. Akca T, Colak T, Cadlykulekci M, Ocal K, Aydyn S. Intestinal perforation in Wegener’s granulomatosis: a case report. Ulus Travma Derg 2005;11(4):348–51. 21. David MS, Juan ME. Hemorragic colitis as the onset of Wegener’s granulomatosis. Int J Colorectal Dis. 2011;26(2):259–60. 22. Lee CR, Kim WH, Cho YS, Kim MH, Kim JH, Park IS, Bang D. Colonoscopic findings in intestinal Behcet’s disease. Inflamm Bowel Dis. 2001;7(3):243–9. 23. Di Sabatino A, Biancheri P, Rovedatti L, Macdonald TT, Corazza GR. Recent advances in understanding ulcerative colitis. Intern Emerg Med. 2012;7(2):103–11. 24. Hisabe T, Hirai F, Matsui T, Watanabe M. Evaluation of diagnostic criteria for Crohn’s disease in Janan. J Gastroemterol 2013.
CASE REPORT
Gastrointestinal involvement at the onset of granulomatosis with polyangiitis: A case report Ayaka Yoshikawa, Shuzo Yoshida, Tohru Takeuchi, Yohei Fujiki, Shigeki Makino, and Toshiaki Hanafusa
Mod Rheumatol Downloaded from informahealthcare.com by Queen's University on 03/06/15 For personal use only.
Department of Internal Medicine (I), Osaka Medical College, Takatsuki City, Osaka, Japan Abstract
Keywords
A 30-year-old man had developed fever, bloody stools, and oral aphtha. Proteinase 3-antineutrophil cytoplasmic antibody level was 31 EU. Lower intestinal endoscopy revealed edematous mucosa with hemorrhage in the transverse colon. Biopsies of oral aphtha showed necrotizing angiitis with granuloma. Based on these findings, he was diagnosed with granulomatosis with polyangiitis (GPA). Digestive symptoms were remitted by treatment with prednisolone and azathioprine. GPA with digestive symptoms as the initial development is rare.
Granulomatosis with polyangiitis, Oral intestinal symptoms, Azathioprine, PR3-ANCA, Primary manifestation
Introduction Granulomatosis with polyangiitis (GPA) is a systemic angiitis syndrome presenting with antineutrophil cytoplasmic autoantibody (ANCA). It is characterized by the following findings: 1) necrotizing granulomatous inflammation mainly in the nose, ears, eyes, upper airway, and lung; 2) focal segmental necrotizing glomerular nephritis; and 3) systemic necrotizing angiitis of the middle and small muscular arteries [1]. Necrotizing granulomatous lesions are observed in the upper airway, lung, and blood vessels throughout the body. Gastrointestinal involvement is rare in ANCA-associated vasculitis, particularly GPA, but it is a serious complication. We report a rare case of GPA in a patient presenting with gastrointestinal involvement as the initial symptom and review two similar cases reported in the literature.
Case presentation A 30-year-old man developed fever, bloody stools, and painful oral aphtha in mid-September 2009. The symptoms aggravated, and pharyngeal pain and a skin ulcer in the subumbilical region developed. He was treated with ceftriaxone, doripenem, and meropenem by a home-visiting doctor, but the response was unfavorable; he was admitted to our hospital in October 2009. Anemia was noted in the palpebral conjunctiva. The abdomen was flat and soft with tenderness, and bowel sounds were normal. Several painful aphtha of 1 cm were present in the oral cavity. A skin ulcer of 2 cm was present in the subumbilical region. Laboratory findings showed that urinalysis was normal, white blood cell counts were 12,710/μl (neutrophils: 77.0%), C-reactive protein was 15.9 mg/dl, and creatinine was 0.85 mg/dl (Table 1). Serological tests showed a proteinase 3(PR3)-ANCA level of 31 EU (standard: ⬍ 10 EU). No abnormalities were observed in chest X-ray and computed tomographic (CT) images. However,
Correspondence to: Ayaka Yoshikawa, Department of Internal Medicine (I), Osaka Medical College, 2-7 Daigakumachi, Takatsuki City, Osaka 569-8686, Japan. Tel: ⫹ 81-72-683-1221. Fax: ⫹ 81-72-684-6531. E-mail: [email protected]
History Received 13 August 2013 Accepted 12 August 2014 Published online 15 September 2014
paranasal and abdominal CT imaging showed mass lesions in the paranasal sinus and thickening of the transverse colon wall (Figure 1a). Lower intestinal endoscopy revealed reddened edematous mucosa with continuous bleeding on the oral side of the right transverse colon, but not other intestinal parts such as the ileum and rectum (Figure 1b). Superficial inflammatory cell infiltration and edema were noted in the lamina propria mucosae of this region on biopsy (Figure 2c). Oral aphtha biopsy showed necrotizing granulomatous inflammation with the infiltration of plasma cells, lymphocytes, and histiocytes (Figure 2a). Perivascular infiltration of lymphocytes and neutrophils was noted in the skin ulcer biopsy specimen (Figure 2b). No eosinophil infiltration, multinucleated giant cells, or fibrinoid degeneration was noted in the histology of either biopsy specimen. Based on the above findings, GPA was diagnosed following the protopathic systemic vasculitis classification algorithm [2]. On the 5th day in hospital, 65 mg/day of prednisolone (PSL) and 50 mg/ day of azathioprine (AZP) were initiated. The bloody stools, oral ulcers, and the subumbilical skin ulcer disappeared with the reduction in C-reactive protein (CRP) and PR3-ANCA levels. CT imaging on the 12th day in hospital showed improvement in wall thickening of the transverse colon and the granulomatous lesions in the right paranasal cavity (Figure 1c). Lower intestinal endoscopy performed on the 15th day in hospital showed improvement in the edematous mucosa and ulcer (Figure 1d). No serious complications occurred thereafter. The symptoms of the patient were well controlled with 5 mg/day of PSL and 75 mg/day of AZP.
Discussion Gastrointestinal involvement of ANCA-associated vasculitis is rare with a reported incidence of 7% [3], but severe gastrointestinal hemorrhage and acute celiopathy may occasionally occur. Twenty cases of gastrointestinal involvement that complicates GPA have been reported previously [4–21]. The incidence of gastrointestinal involvement is high in middle-aged men, and the small intestine and colon are frequently involved. Lower intestinal endoscopy shows the multiple shallow ulcers with or without perforation [4]. Digestive manifestations develop simultaneously with or after
2
A. Yoshikawa et al.
Mod Rheumatol, 2014; Early Online: 1–3
Table 1. Laboratory values.
Mod Rheumatol Downloaded from informahealthcare.com by Queen's University on 03/06/15 For personal use only.
WBC Neut Mono Eos Baso Lymph Hb PLT TP Alb AST ALT LDH ALP γ-GTP BUN Cr CRP Erythrocyte sedimentation rate
12,710/μl 77.0% 9.0% 0.0% 0.0% 12.0% 12.0 g/dl 48.2 ⫻ 104/μl 5.8 g/dl 2.3 g/dl 21 U/l 28 U/l 188 U/l 746 U/l 136 U/l 9 mg/dl 0.85 mg/dl 15.9 mg/dl 83 mm/hr
PT–INR APTT Fibrinogen FDP AT-III IgG IgA IgM C3 Antinuclear antibody Rheumatoid factor MPO-ANCA PR3-ANCA Endotoxin β–D glucan CMV antigenemia QFT Various culture tests (blood, sputum, and urine cultures)
1.24 34.8 sec 593 mg/dl 3.8 μg/ml 89% 1,492 mg/dl 313 mg/dl 74 mg/dl 145 mg/dl (⫺ ) ⬍ 3 IU/ml ⬍ 10 EU 31 EU ⬍ 1.82 pg/ml ⬍ 3.58 pg/ml Negative Negative Negative
WBC white blood cell, Neut neutrophils, Mono monocytes, Eos eosinophils, Baso basophils, Lymph lymphocytes, Hb hemoglobin, PLT platelets, TP total protein, Alb albumin, AST aspartate aminotransferase, ALT alanine aminotransferase, LDH lactate dehydrogenase, ALP alkaline phosphatase, g-GTP gamma guanosine triphosphate, BUN blood urea nitrogen, Cr creatinine, CRP C-reactive protein, PT–INR prothrombin time and international normalized ratio, APTT activated partial thromboplastin, FDP fibrinogen degradation products, AT-III antithrombin III, IgG immunoglobulin G, IgA immunoglobulin A, IgM immunoglobulin M, MPO-ANCA myeloperoxidase-antineutrophil cytoplasmic antibody, PR3-ANCA proteinase 3-antineutrophil cytoplasmic antibody, CMV antigenemia cytomegalovirus antigenemia, QFT quantiFERON
renal and pulmonary manifestations in active GPA disease [3]. Only 3 cases of GPA manifesting digestive symptoms as the initial development have been reported, which includes our patient [5,6] (Table 2). In all 3 cases, gastrointestinal lesions were present in the colon with bloody stools. Severe complications, such as renal dysfunction and pulmonary alveolar hemorrhage, rapidly developed within 3 weeks after the appearance of digestive symptoms in the other two reported cases. The algorithm to classify systemic vasculitis was recently proposed by Watts et al. [2]. Using this algorithm, it may be difficult to classify GPA in the cases that lack renal and pulmonary involvements. Behcet’s disease and inflammatory bowel diseases, such as ulcerative colitis and Crohn’s disease, are ruled out from the
Figure 1. Abdominal CT and lower intestinal endoscopy before and after the treatment. Wall thickening of the transverse colon was noted on abdominal CT (a), which improved after treatment (c). Lower intestinal endoscopy revealed reddened edematous mucosa with hemorrhage in the right transverse colon (b). Inflammation was improved, edema disappeared, and cicatrization was observed after treatment (d).
differential diagnosis. Behcet’s disease is characterized by single ulcer or a few deep ulcers with discrete margins at the site opposite to mesenteric attachment in the small intestine and colon, especially
Figure 2. Biopsy of oral aphtha (a), skin ulcer (b), and right transverse colon (c). Necrotizing granulomatous inflammation with infiltrating plasma cells, lymphocytes, and histiocytes was noted in the oral aphtha biopsy specimen (a). Perivascular infiltration of lymphocytes and neutrophils (arrow) was observed in the skin ulcer biopsy specimen (b). Superficial inflammatory cell infiltration and edema were noted in the lamina propria mucosae of the right transverse colon biopsy specimen (c).
Gastrointestinal involvement in GPA 3
DOI 10.3109/14397595.2014.954742
Table 2. Details of the present and two reviewed cases of GPA with digestive symptoms at onset.
Time from onset to initiation of treatment Treatment
About 2 weeks
Morchón-Simón and Martín-Escudero [5] 43 Male Colon Bloody stool Renal disorder, finger ulcer, splenic infarction, pulmonary lesion About 4 weeks
PSL, AZP
PSL, CY
Prognosis
Survived
Survived (dialysis)
Age (years) Sex Intestinal region Digestive symptom Complications
Our case 30 Male Colon Bloody stool Skin ulcer, oral aphtha
Qian et al. [6] 79 Female Colon Bloody stool Pulmonary alveolar hemorrhage, renal disorder About 2 weeks m-PSL pulse, PSL, CY, Plasmapheresis Survived
Mod Rheumatol Downloaded from informahealthcare.com by Queen's University on 03/06/15 For personal use only.
AZP azathioprine, CY cyclophosphamide, GPA granulomatosis with polyangiitis, PSL prednisolone, m-PSL methylprednisolone
the ileum [22]. Ulcerative colitis shows continuous involvement of the colon above the rectum [23]. Crohn’s disease is characterized by involvement of the colon or terminal ileum with patchy distribution and “cobblestone”-like appearance [24]. Our case lacked the above characteristic symptoms of Behcet’s disease and inflammatory bowel diseases, showed inflammatory granuloma in the biopsy of oral ulcer, and was diagnosed as GPA. Gastrointestinal involvement in GPA is treated with immunosuppressive therapies such as steroid pulse treatment and cyclophosphamide therapy [3,5,6]. Some patients with severe disease require additional surgical treatment. It is difficult to diagnose the gastrointestinal involvement of GPA because it is a rare disease and the manifestations are not specific for GPA. Although the biopsy specimens of the transverse colon in this case showed leukocytoclastic vasculitis without granulomatous lesions, the gastrointestinal involvement is suggested to be due to GPA in early-onset disease, which may have led to remission by treatment with PSL and AZP. GPA developing with digestive symptoms at the initial onset is rare, but it can rapidly progress with complications of pulmonary and renal disorders. Examination of the entire body and early intervention with immunosuppressive drugs may be important in treating such cases of GPA before serious illness occurs. We presented this case at the 55th annual meeting of Japanese College of Rheumatology 2011.
Conflict of interest None.
References 1. Wegener F. Über eine eigenartige rhinogene Granulomatose mit besonderer Beteiligung des Arteriensystems und der Nieren. Beitr Path Anat Pathol. 1939;102:36–68. 2. Watts R, Lane S, Hanslik T, Hauser T, Hellmich B, Koldingsnes W, et al. Development and validation of a consensus methodology for the classification of the ANCA-associated vasculitides and polyarteritis nodosa for epidemiological studies. Ann Rheum Dis. 2007;66(2): 222–7. 3. Pagnoux C, Mahr A, Cohen P, Guillevin L. Presentation and outcome of gastrointestinal involvement in systemic necrotizing vasculitides: analysis of 62 patients with polyarteritis nodosa, microscopic polyangiitis, Wegener granulomatosis, Churg-Strauss syndrome, or rheumatoid arthritis-associated vasculitis. Medicine (Baltimore). 2005;84(2):115–28. 4. Deniz K, Ozşeker HS, Balas S, Akpýnar E, Sökmensüer C. Intestinal involvement in Wegener’s granulomatosis. J Gastrointestin Liver Dis. 2007;16(3):329–31.
5. Morchón-Simón D, Martín-Escudero JC. Hemorrhagic colitis as the onset of Wegener’s granulomatosis. Int J Colorectal Dis. 2011;26(2):259–60. 6. Qian Q, Cornell L, Chandan V, Hartman R, Caples S. Hemorrhagic colitis as a presenting feature of Wegener granulomatosis. J Gastrointestin Liver Dis. 2010;19(4):445–7. 7. McNabb WR, Lennox MS, Wedzicha JA. Small intestinal perforation in Wegener’s granulomatosis. Posagrad Med J 1982;58(676):123–5. 8. Haworth SJ, Pusey CD. Severe intestinal involvement in Wegener’s granulomatosis. Gut. 1984;25(11):1296–300. 9. Geraghty J, Mackay IR, Smith DC. Intestinal perforation in Wegener’s granulomatosis. Gut 1986;27(4):450–1. 10. Tokuda M, Kurata N, Daikuhara H, Akisawa M, Onishi I, Asano T, et al. Small intestinal perforation in Wegener’s granulomatosis. J Rheumatol. 1989;16(4):547–9. 11. Pinkney JH, Clarke G, Fairclough PD. Gastrointestinal involvement in Wegener’s granulomatosis. Gastrointest Endosc. 1991;37(3):411–2. 12. Wilson RH, Kerr PP, McLoughlin J, Gormley M. Symptomatic colitis as the initial presentation of Wegener’s granulomatosis. Br J Clin Pract. 1993;47(6):315–8. 13. Schneider A, Menzel J, Gaubitz M, Keller R, Lugering N, Domschke W. Colitis as the initial presentation of Wegener’s granulomatosis. J Intern Med. 1997;242(6):513–7. 14. Corne P, Grosleron S, Cayrol B, Reynoud D, Yeche S, Capron F, Dubois A. Wegener’s disease, a rare cause of granulomatous colitis. Gastroenterol Clin Biol. 1997;21(2):163–4. 15. Storesund B, Gran JT, Koldingsnes W. Severe intestinal involvement in Wegener’s granulomatosis report of two cases and reiew of the literature. Br J Rheumatol. 1998;37(4):387–90. 16. Srinivasan U, Coughlan RJ. Small intestinal perforation complicating Wegener’s granulomatosis. Rheumatology (Oxford). 1999;38(3): 289–90. 17. Steele C, Bohra S, Broe P, Murray FE. Acute upper gastrointestinal haemorrhage and colitis: an nunusual presentation of Wegener’s granulomatosis. Eur J Gastroenterol Hepatol. 2001;13(8):993–5. 18. Chow FY, Hooke D, Kerr PG. Severe intestinal involvement in Wegener’s granulomatosis. J Gastroenterol Hepatol 2003;18(6): 749–50. 19. Veinot JP, Logan CA, Thomas MJ. Wegener’s granulomatosis arteritis causing small bowel infarction. Pathology 2003;35(3):268–9. 20. Akca T, Colak T, Cadlykulekci M, Ocal K, Aydyn S. Intestinal perforation in Wegener’s granulomatosis: a case report. Ulus Travma Derg 2005;11(4):348–51. 21. David MS, Juan ME. Hemorragic colitis as the onset of Wegener’s granulomatosis. Int J Colorectal Dis. 2011;26(2):259–60. 22. Lee CR, Kim WH, Cho YS, Kim MH, Kim JH, Park IS, Bang D. Colonoscopic findings in intestinal Behcet’s disease. Inflamm Bowel Dis. 2001;7(3):243–9. 23. Di Sabatino A, Biancheri P, Rovedatti L, Macdonald TT, Corazza GR. Recent advances in understanding ulcerative colitis. Intern Emerg Med. 2012;7(2):103–11. 24. Hisabe T, Hirai F, Matsui T, Watanabe M. Evaluation of diagnostic criteria for Crohn’s disease in Janan. J Gastroemterol 2013.
