International Journal of Rheumatic Diseases 2013; 16: 606–608
CORRESPONDENCE
Spontaneous splenic rupture complicating granulomatosis with polyangiitis (Wegener’s granulomatosis)
Dear Editor, Granulomatosis with polyangiitis (GPA; Wegener’s granulomatosis) is a systemic vasculitis that primarily affects the upper respiratory tract, lungs and kidneys of most patients and only occasionally involves the spleen. The pathologic splenic changes associated with GPA include necrotizing granulomatous inflammation, vasculitis, fibrinoid change of blood vessels and infarction.1 Although extremely rare, with only three published cases to date,2–4 spontaneous splenic rupture may occur as a complication in GPA. Here, we report a fourth case of spontaneous splenic rupture, which occurred during treatment for GPA with corticosteroids. A 47-year-old woman presented in September 2010 with a 4-month history of fever and refractory sinusitis. She had paranasal sinus pain with purulent and bloody nasal discharge and swelling of the face. She also reported having right anterior uveitis requiring treatment with corticosteroid eye drops. Examination of her respiratory and abdominal systems was unremarkable. Laboratory tests showed a leukocyte count of 8380/lL, hemoglobin 11.1 g/dL, hematocrit 36.8%, platelet count 23.9 9 104/lL, and serum C-reactive protein (CRP) 4.37 mg/dL (normal < 0.30). Liver function tests showed aspartate aminotransferase level of 15 IU/L, alanine aminotransferase 12 IU/L, alkaline phosphatase 271 IU/L, and total bilirubin 0.3 mg/dL. Renal function tests were normal. A serological test was positive for proteinase 3 – antineutrophil cytoplasmic antibodies (PR3-ANCA) with a titer of 37 IU/L (normal < 10). Antinuclear antibody was negative. Urine examinations were normal. Computed tomography (CT) scan showed extensive mucosal thickening in the bilateral maxillary sinuses. Plain X-ray and high-resolution CT scan of the chest showed no pulmonary disease. On the basis of the findings of antibiotic-resistant sinusitis, uveitis and PR3-ANCA positivity, she was suspected as having a limited form of GPA. She was started on prednisolone (30 mg/day) and low-dose weekly oral methotrexate (8 mg/week)
and within a few days her fever disappeared and sinusitis and inflammatory laboratory data were improved. Neither anticoagulants nor antiplatelet agents were given to the patient to prevent steroid-induced thrombosis. When tapering the steroid dose to 17.5 mg/day in December 2010, the patient complained of pain in the left upper quadrant and fever. Serum CRP was elevated at 12.31 mg/dL, leukocyte count was 12 930/lL, and the PR3-ANCA level was 12 IU/L. Contrast-enhanced CT scan showed a well-defined hypodense area within the spleen, with some enhanced small patches within the larger hypodense area (Fig. 1a). The provisional diagnosis was splenic infarction. Cardiac ultrasonography to detect vegetations was normal. Pulmonary and abdominal CT scan and upper and lower intestinal endoscopy showed no features of malignant disease with potential to cause thromboembolic events. Abdominal pain and inflammatory laboratory abnormalities improved comparatively quickly with prophylactic antibiotic treatment. In February 2011, while taking prednisolone 12.5 mg/day, the patient presented with intractable abdominal pain and fever. Laboratory findings were CRP 21.36 mg/dL and leukocyte count 15 260/lL. Contrast-enhanced CT scan revealed splenic rupture (Fig. 1b) and she underwent emergency laparoscopic splenectomy. Pathological findings showed massive necrosis at the rupture site (Fig. 2a), with a palisaded granuloma in the vicinity of the necrotic area (Fig. 2b). The patient’s postoperative course was uneventful and she was subsequently discharged feeling quite well. A search of the PubMed database identified only three documented cases of spontaneous splenic rupture in GPA.2–4 In all three cases rupture was the first presenting sign of GPA. The present case is unique in that splenic rupture developed after the diagnosis of GPA and during treatment with corticosteroids. Histological findings revealed extensive splenic necrosis and a palisaded granuloma, which alongside the appearance on CT scan,
© 2013 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd
Correspondence
(a)
(a)
(b)
(b)
Figure 2 Splenic findings on (a) gross pathology and (b) histology. Site of rupture (arrows) is apparent in large yellow necrotic areas (a). Microscopic findings of a palisaded granuloma present in the vicinity of necrosis (hematoxylin and eosin staining, 9200) (b).
Figure 1 Enhanced computed tomography (CT) scan of the abdomen (a) before and (b) after splenic rupture. Welldefined areas of low attenuation and the peripheral rim of normally enhanced tissue in the spleen (a). Effusion in the dorsal part of the spleen (arrow), consistent with splenic rupture (b).
supported a diagnosis of splenic infarction in GPA.5 Thus, splenic infarction caused extensive necrosis, which in turn probably led to the rupture in our case. This mechanism of splenic rupture in our case may differ from that in the three previous cases:2–4 one had central arteritis and segmental necrosis in the resected spleen,2 while the other two had neutrophilic infiltration at the rupture site without signs of vasculitis or infarction.3,4 There was extensive necrosis without any histological evidence of vasculitis in our case, and it should also be noted that there were no findings suggestive of embolic disease such as cardiac vegetation. Therefore, it may be reasonable to consider that the mechanism of splenic infarction leading to rupture in the present case was localized occlusion of distal parts of the splenic artery or its branches, presumably due to microscopic peripheral vasculitis.
International Journal of Rheumatic Diseases 2013; 16: 606–608
Without pursuing the pathological diagnosis and performing a comprehensive evaluation, we initially considered the patient had a limited form of GPA. A nasal biopsy should have been attempted, even though the result is often negative. Patients with GPA may develop abdominal manifestations other than glomerulonephritis. For instance, hydronephrosis due to peri-iliac arterial inflammation or spontaneous perirenal hematoma has been reported as a complication of GPA.6,7 If abdominal manifestations or vasculitis had been evaluated and identified before the initiation of treatment, or even after splenic infarction was suspected, more aggressive therapy, including cyclophosphamide along with a higher dose of corticosteroids should have been used in the present case. Some cases of splenic infarction in GPA have been reported,8–10 although splenic rupture is uncommon. Splenic infarction can be asymptomatic in some cases, unlike in the present case. Unless there are signs of imminent rupture of the spleen or bleeding, a conservative approach with aggressive immunosuppressive treatments appears to be justified.8,9 It is also important to note that severe splenic bleeding caused by GPA-related vasculitis has been reported in some patients receiving antithrombotic treatment.11 The clinical lesson to be learnt from our case is that comprehensive evaluation at the time of diagnosis and early recognition of the presentation of abdominal lesions, including those in the spleen, can contribute to appropriate and timely management of this potentially fatal complication.
607
Correspondence
Akiko NAGASU,1 Yumi SASAE,1 Hiroyasu HIRANO,1 Hirotake NISHIMURA,2 Yuko AOYAMA,3 Atsushi URAKAMI3 and Yoshitaka MORITA1 Rheumatology, 2Pathology, and 3Digestive Surgery, Kawasaki Medical School, Kurashiki, Okayama, Japan, 1
Correspondence: Yoshitaka Morita, email: [email protected]
REFERENCES 1 Gal AA, Masor JJ (1996) Splenic involvement in Wegener’s granulomatosis. Arch Pathol Lab Med 120, 974–7. 2 Hawley PH, Copland G, Zetler P (1996) Spontaneous splenic rupture in c-ANCA positive vasculitis. Aust N Z J Med 26, 431–2. 3 McCain M, Quinet R, Davis W et al. (2002) Splenic rupture as the presenting manifestation of vasculitis. Semin Arthritis Rheum 31, 311–6. 4 Franssen CF, Ter Maaten JC, Hoorntje SJ (1993) Spontaneous splenic rupture in Wegener’s vasculitis. Ann Rheum Dis 52, 314.
608
5 Fonner BT, Nemcek AA Jr, Boschman C (1995) CT appearance of splenic infarction in Wegener’s granulomatosis. AJR Am J Roentgenol 164, 353–4. 6 Ishii T, Katada Y, Saeki Y (2011) Spontaneous perirenal hematoma due to Wegener’s granulomatosis after initiation of immunosuppressant. Mod Rheumatol 21, 203–6. 7 Umemoto A, Ikeuchi H, Hiromura K et al. (2012) Hydronephrosis caused by a relapse of granulomatosis with polyangiitis (Wegener’s). Mod Rheumatol 22, 616–20. 8 Papaioannides D, Nikas SN, Fotinou M, Akritidis NK (2002) Asymptomatic splenic infarction in Wegener’s granulomatosis. Ann Rheum Dis 61, 185–6. 9 Roy DK, George A, Chattopadhyay C, Grennan DM (1999) Splenic infarction in a patient with Wegener’s granulomatosis. Rheumatology 38, 1162–3. 10 Rentsch J, McColl G (2000) Splenic infarction in Wegener’s granulomatosis. J Rheumatol 27, 1554–5. 11 Papo T, Huong DL, Piette JC et al. (1999) Spleen haemorrhagic infarction and hazards of anticoagulation in Wegener’s granulomatosis. Ann Rheum Dis 58, 654–5.
International Journal of Rheumatic Diseases 2013; 16: 606–608
Copyright of International Journal of Rheumatic Diseases is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
CORRESPONDENCE
Spontaneous splenic rupture complicating granulomatosis with polyangiitis (Wegener’s granulomatosis)
Dear Editor, Granulomatosis with polyangiitis (GPA; Wegener’s granulomatosis) is a systemic vasculitis that primarily affects the upper respiratory tract, lungs and kidneys of most patients and only occasionally involves the spleen. The pathologic splenic changes associated with GPA include necrotizing granulomatous inflammation, vasculitis, fibrinoid change of blood vessels and infarction.1 Although extremely rare, with only three published cases to date,2–4 spontaneous splenic rupture may occur as a complication in GPA. Here, we report a fourth case of spontaneous splenic rupture, which occurred during treatment for GPA with corticosteroids. A 47-year-old woman presented in September 2010 with a 4-month history of fever and refractory sinusitis. She had paranasal sinus pain with purulent and bloody nasal discharge and swelling of the face. She also reported having right anterior uveitis requiring treatment with corticosteroid eye drops. Examination of her respiratory and abdominal systems was unremarkable. Laboratory tests showed a leukocyte count of 8380/lL, hemoglobin 11.1 g/dL, hematocrit 36.8%, platelet count 23.9 9 104/lL, and serum C-reactive protein (CRP) 4.37 mg/dL (normal < 0.30). Liver function tests showed aspartate aminotransferase level of 15 IU/L, alanine aminotransferase 12 IU/L, alkaline phosphatase 271 IU/L, and total bilirubin 0.3 mg/dL. Renal function tests were normal. A serological test was positive for proteinase 3 – antineutrophil cytoplasmic antibodies (PR3-ANCA) with a titer of 37 IU/L (normal < 10). Antinuclear antibody was negative. Urine examinations were normal. Computed tomography (CT) scan showed extensive mucosal thickening in the bilateral maxillary sinuses. Plain X-ray and high-resolution CT scan of the chest showed no pulmonary disease. On the basis of the findings of antibiotic-resistant sinusitis, uveitis and PR3-ANCA positivity, she was suspected as having a limited form of GPA. She was started on prednisolone (30 mg/day) and low-dose weekly oral methotrexate (8 mg/week)
and within a few days her fever disappeared and sinusitis and inflammatory laboratory data were improved. Neither anticoagulants nor antiplatelet agents were given to the patient to prevent steroid-induced thrombosis. When tapering the steroid dose to 17.5 mg/day in December 2010, the patient complained of pain in the left upper quadrant and fever. Serum CRP was elevated at 12.31 mg/dL, leukocyte count was 12 930/lL, and the PR3-ANCA level was 12 IU/L. Contrast-enhanced CT scan showed a well-defined hypodense area within the spleen, with some enhanced small patches within the larger hypodense area (Fig. 1a). The provisional diagnosis was splenic infarction. Cardiac ultrasonography to detect vegetations was normal. Pulmonary and abdominal CT scan and upper and lower intestinal endoscopy showed no features of malignant disease with potential to cause thromboembolic events. Abdominal pain and inflammatory laboratory abnormalities improved comparatively quickly with prophylactic antibiotic treatment. In February 2011, while taking prednisolone 12.5 mg/day, the patient presented with intractable abdominal pain and fever. Laboratory findings were CRP 21.36 mg/dL and leukocyte count 15 260/lL. Contrast-enhanced CT scan revealed splenic rupture (Fig. 1b) and she underwent emergency laparoscopic splenectomy. Pathological findings showed massive necrosis at the rupture site (Fig. 2a), with a palisaded granuloma in the vicinity of the necrotic area (Fig. 2b). The patient’s postoperative course was uneventful and she was subsequently discharged feeling quite well. A search of the PubMed database identified only three documented cases of spontaneous splenic rupture in GPA.2–4 In all three cases rupture was the first presenting sign of GPA. The present case is unique in that splenic rupture developed after the diagnosis of GPA and during treatment with corticosteroids. Histological findings revealed extensive splenic necrosis and a palisaded granuloma, which alongside the appearance on CT scan,
© 2013 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd
Correspondence
(a)
(a)
(b)
(b)
Figure 2 Splenic findings on (a) gross pathology and (b) histology. Site of rupture (arrows) is apparent in large yellow necrotic areas (a). Microscopic findings of a palisaded granuloma present in the vicinity of necrosis (hematoxylin and eosin staining, 9200) (b).
Figure 1 Enhanced computed tomography (CT) scan of the abdomen (a) before and (b) after splenic rupture. Welldefined areas of low attenuation and the peripheral rim of normally enhanced tissue in the spleen (a). Effusion in the dorsal part of the spleen (arrow), consistent with splenic rupture (b).
supported a diagnosis of splenic infarction in GPA.5 Thus, splenic infarction caused extensive necrosis, which in turn probably led to the rupture in our case. This mechanism of splenic rupture in our case may differ from that in the three previous cases:2–4 one had central arteritis and segmental necrosis in the resected spleen,2 while the other two had neutrophilic infiltration at the rupture site without signs of vasculitis or infarction.3,4 There was extensive necrosis without any histological evidence of vasculitis in our case, and it should also be noted that there were no findings suggestive of embolic disease such as cardiac vegetation. Therefore, it may be reasonable to consider that the mechanism of splenic infarction leading to rupture in the present case was localized occlusion of distal parts of the splenic artery or its branches, presumably due to microscopic peripheral vasculitis.
International Journal of Rheumatic Diseases 2013; 16: 606–608
Without pursuing the pathological diagnosis and performing a comprehensive evaluation, we initially considered the patient had a limited form of GPA. A nasal biopsy should have been attempted, even though the result is often negative. Patients with GPA may develop abdominal manifestations other than glomerulonephritis. For instance, hydronephrosis due to peri-iliac arterial inflammation or spontaneous perirenal hematoma has been reported as a complication of GPA.6,7 If abdominal manifestations or vasculitis had been evaluated and identified before the initiation of treatment, or even after splenic infarction was suspected, more aggressive therapy, including cyclophosphamide along with a higher dose of corticosteroids should have been used in the present case. Some cases of splenic infarction in GPA have been reported,8–10 although splenic rupture is uncommon. Splenic infarction can be asymptomatic in some cases, unlike in the present case. Unless there are signs of imminent rupture of the spleen or bleeding, a conservative approach with aggressive immunosuppressive treatments appears to be justified.8,9 It is also important to note that severe splenic bleeding caused by GPA-related vasculitis has been reported in some patients receiving antithrombotic treatment.11 The clinical lesson to be learnt from our case is that comprehensive evaluation at the time of diagnosis and early recognition of the presentation of abdominal lesions, including those in the spleen, can contribute to appropriate and timely management of this potentially fatal complication.
607
Correspondence
Akiko NAGASU,1 Yumi SASAE,1 Hiroyasu HIRANO,1 Hirotake NISHIMURA,2 Yuko AOYAMA,3 Atsushi URAKAMI3 and Yoshitaka MORITA1 Rheumatology, 2Pathology, and 3Digestive Surgery, Kawasaki Medical School, Kurashiki, Okayama, Japan, 1
Correspondence: Yoshitaka Morita, email: [email protected]
REFERENCES 1 Gal AA, Masor JJ (1996) Splenic involvement in Wegener’s granulomatosis. Arch Pathol Lab Med 120, 974–7. 2 Hawley PH, Copland G, Zetler P (1996) Spontaneous splenic rupture in c-ANCA positive vasculitis. Aust N Z J Med 26, 431–2. 3 McCain M, Quinet R, Davis W et al. (2002) Splenic rupture as the presenting manifestation of vasculitis. Semin Arthritis Rheum 31, 311–6. 4 Franssen CF, Ter Maaten JC, Hoorntje SJ (1993) Spontaneous splenic rupture in Wegener’s vasculitis. Ann Rheum Dis 52, 314.
608
5 Fonner BT, Nemcek AA Jr, Boschman C (1995) CT appearance of splenic infarction in Wegener’s granulomatosis. AJR Am J Roentgenol 164, 353–4. 6 Ishii T, Katada Y, Saeki Y (2011) Spontaneous perirenal hematoma due to Wegener’s granulomatosis after initiation of immunosuppressant. Mod Rheumatol 21, 203–6. 7 Umemoto A, Ikeuchi H, Hiromura K et al. (2012) Hydronephrosis caused by a relapse of granulomatosis with polyangiitis (Wegener’s). Mod Rheumatol 22, 616–20. 8 Papaioannides D, Nikas SN, Fotinou M, Akritidis NK (2002) Asymptomatic splenic infarction in Wegener’s granulomatosis. Ann Rheum Dis 61, 185–6. 9 Roy DK, George A, Chattopadhyay C, Grennan DM (1999) Splenic infarction in a patient with Wegener’s granulomatosis. Rheumatology 38, 1162–3. 10 Rentsch J, McColl G (2000) Splenic infarction in Wegener’s granulomatosis. J Rheumatol 27, 1554–5. 11 Papo T, Huong DL, Piette JC et al. (1999) Spleen haemorrhagic infarction and hazards of anticoagulation in Wegener’s granulomatosis. Ann Rheum Dis 58, 654–5.
International Journal of Rheumatic Diseases 2013; 16: 606–608
Copyright of International Journal of Rheumatic Diseases is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
