21 August 2024 - Case of the Month #541
All cases are archived on our website. To view them sorted by case number, diagnosis or category, visit our main Case of the Month page. To subscribe or unsubscribe to Case of the Month or our other email lists, click here.
Thanks to Dr. Patrick Maher, Dr. Juhi Mahadik and Dr. Naziheh Assarzadegan, University of Florida, Gainesville, Florida, USA for contributing this case and discussion and to Dr. Aaron Huber, University of Rochester Medical Center, Rochester, New York, USA for reviewing the discussion.
Case of the Month #541
Clinical history:
A 51 year old man presented with a stomach perforation.
Microscopic images:
What is your diagnosis?
Diagnosis: Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome)
Test question (answer at the end):
Which antibody is most commonly associated with eosinophilic granulomatosis with polyangiitis?
Discussion:
Eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as Churg-Strauss Syndrome, is typically a multisystemic autoimmune disorder that is characterized by multiple clinical features (StatPearls: Eosinophilic Granulomatosis With Polyangiitis (Churg-Strauss Syndrome) [Accessed 11 July 2024]). The hallmark clinical features are respiratory symptoms (specifically asthma), mono or polyneuropathy, peripheral blood eosinophilia and eosinophilic tissue infiltration. Additionally, MPO-ANCA (P-ANCA) is the antibody most commonly seen in this disease. In the gastrointestinal tract, eosinophilic infiltration can lead to nonspecific symptoms like nausea, vomiting and diarrhea. It can also cause more severe symptoms like obstruction secondary to submucosal nodular masses, mesenteric vasculitis and ischemia, as well as perforation secondary to the ischemia and vasculitis (Clin Rheumatol 2007;26:216).
Eosinophilic granulomatosis with polyangiitis affects between 11 million and 14 million adults worldwide. The median age of onset is 40 years but it has been seen as young as 4 and as old as 74. There is no gender difference in incidence. EGPA is rare in children but there is a higher prevalence of cardiomyopathy in this group. The pathogenesis of EGPA appears to involve two major pathways: the eosinophil mediated pathway and the ANCA mediated endothelial induced injury pathway. The eosinophil mediated pathway mainly results in end organ damage like myocarditis, serosal effusions and mesenteric vasculitis. The ANCA mediated pathway is more often associated with MPO-ANCA (P-ANCA). This pathway mainly results in vasculitis and the clinical sequelae associated with vasculitis like crescentic glomerulonephritis, alveolar hemorrhage and coronary arteritis (Clin Rheumatol 2007;26:216).
The histologic hallmarks of EGPA are extravascular granulomas, small and medium sized vasculitis and eosinophilic infiltrates. Microscopically, different organs will have different histologic features. Gastrointestinal involvement can occur in up to 50% of EGPA cases. Accurate diagnosis is difficult on endoscopic biopsies due to absence of small to medium sized vessels with hallmark findings within the mucosa. In fact, the condition may be misdiagnosed as an eosinophilic gastroenteritis on biopsy specimens, which can also present with similar symptoms such as abdominal pain and diarrhea. A high index of suspicion and exclusion of other potential etiologies including parasitic infections, drugs, inflammatory bowel disease and hypereosinophilic syndrome is necessary. Although mucosal ulcers are a common manifestation of EGPA in the gastrointestinal tract, perforations have rarely been reported in the small bowel, stomach and colon. Definitive diagnosis largely relies on clinical criteria, as diagnostic resection specimens are seldom available for evaluation (Front Immunol 2014;5:549, Cardiovasc Pathol 2020;47:107193, Case Rep Gastroenterol 2014;8:329, World J Gastrointest Pharmacol Ther 2016;7:513).
Test question answer:
C. MPO-Anti neutrophil cytoplasmic antibody (P-ANCA) is the most common antibody associated with eosinophilic granulomatosis with polyangiitis.
All cases are archived on our website. To view them sorted by case number, diagnosis or category, visit our main Case of the Month page. To subscribe or unsubscribe to Case of the Month or our other email lists, click here.
Thanks to Dr. Patrick Maher, Dr. Juhi Mahadik and Dr. Naziheh Assarzadegan, University of Florida, Gainesville, Florida, USA for contributing this case and discussion and to Dr. Aaron Huber, University of Rochester Medical Center, Rochester, New York, USA for reviewing the discussion.
Website news:
(1) The Q1 report for our Worldwide Directory of Pathologists is at pathologyoutlines.com/directoryreport2024q1.html. It provides information not available elsewhere, including pathologist totals by U.S. state and Canadian province, subspecialty totals, the largest pathology institutions and the most popular pathologist profiles. Make sure your profile is current by visiting pathologyoutlines.com/directory.
(2) Our July Curing Cancer Network newsletter discusses our recent work on cancer precursors. Read the full newsletter at conta.cc/4bHlcTj and subscribe to these newsletters at pathologyoutlines.com/subscribe.html.
(3) Our textbook content is written directly for us by pathologists, and we take the copyright of our text and images extremely seriously. Please visit our copyright page at pathologyoutlines.com/copyrightinfo.html to see what's allowed or email us at Comments@PathologyOutlines.com with any questions.
Visit and follow our Blog to see recent updates to the website.
(1) The Q1 report for our Worldwide Directory of Pathologists is at pathologyoutlines.com/directoryreport2024q1.html. It provides information not available elsewhere, including pathologist totals by U.S. state and Canadian province, subspecialty totals, the largest pathology institutions and the most popular pathologist profiles. Make sure your profile is current by visiting pathologyoutlines.com/directory.
(2) Our July Curing Cancer Network newsletter discusses our recent work on cancer precursors. Read the full newsletter at conta.cc/4bHlcTj and subscribe to these newsletters at pathologyoutlines.com/subscribe.html.
(3) Our textbook content is written directly for us by pathologists, and we take the copyright of our text and images extremely seriously. Please visit our copyright page at pathologyoutlines.com/copyrightinfo.html to see what's allowed or email us at Comments@PathologyOutlines.com with any questions.
Visit and follow our Blog to see recent updates to the website.
Case of the Month #541
Clinical history:
A 51 year old man presented with a stomach perforation.
Microscopic images:
What is your diagnosis?
Click here for diagnosis, test question and discussion:
Diagnosis: Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome)
Test question (answer at the end):
Which antibody is most commonly associated with eosinophilic granulomatosis with polyangiitis?
- Antimitochondrial antibody (AMA)
- Antinuclear antibody (ANA)
- MPO-Anti neutrophil cytoplasmic antibody (P-ANCA)
- PR3-Anti neutrophil cytoplasmic antibody (C-ANCA)
Discussion:
Eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as Churg-Strauss Syndrome, is typically a multisystemic autoimmune disorder that is characterized by multiple clinical features (StatPearls: Eosinophilic Granulomatosis With Polyangiitis (Churg-Strauss Syndrome) [Accessed 11 July 2024]). The hallmark clinical features are respiratory symptoms (specifically asthma), mono or polyneuropathy, peripheral blood eosinophilia and eosinophilic tissue infiltration. Additionally, MPO-ANCA (P-ANCA) is the antibody most commonly seen in this disease. In the gastrointestinal tract, eosinophilic infiltration can lead to nonspecific symptoms like nausea, vomiting and diarrhea. It can also cause more severe symptoms like obstruction secondary to submucosal nodular masses, mesenteric vasculitis and ischemia, as well as perforation secondary to the ischemia and vasculitis (Clin Rheumatol 2007;26:216).
Eosinophilic granulomatosis with polyangiitis affects between 11 million and 14 million adults worldwide. The median age of onset is 40 years but it has been seen as young as 4 and as old as 74. There is no gender difference in incidence. EGPA is rare in children but there is a higher prevalence of cardiomyopathy in this group. The pathogenesis of EGPA appears to involve two major pathways: the eosinophil mediated pathway and the ANCA mediated endothelial induced injury pathway. The eosinophil mediated pathway mainly results in end organ damage like myocarditis, serosal effusions and mesenteric vasculitis. The ANCA mediated pathway is more often associated with MPO-ANCA (P-ANCA). This pathway mainly results in vasculitis and the clinical sequelae associated with vasculitis like crescentic glomerulonephritis, alveolar hemorrhage and coronary arteritis (Clin Rheumatol 2007;26:216).
The histologic hallmarks of EGPA are extravascular granulomas, small and medium sized vasculitis and eosinophilic infiltrates. Microscopically, different organs will have different histologic features. Gastrointestinal involvement can occur in up to 50% of EGPA cases. Accurate diagnosis is difficult on endoscopic biopsies due to absence of small to medium sized vessels with hallmark findings within the mucosa. In fact, the condition may be misdiagnosed as an eosinophilic gastroenteritis on biopsy specimens, which can also present with similar symptoms such as abdominal pain and diarrhea. A high index of suspicion and exclusion of other potential etiologies including parasitic infections, drugs, inflammatory bowel disease and hypereosinophilic syndrome is necessary. Although mucosal ulcers are a common manifestation of EGPA in the gastrointestinal tract, perforations have rarely been reported in the small bowel, stomach and colon. Definitive diagnosis largely relies on clinical criteria, as diagnostic resection specimens are seldom available for evaluation (Front Immunol 2014;5:549, Cardiovasc Pathol 2020;47:107193, Case Rep Gastroenterol 2014;8:329, World J Gastrointest Pharmacol Ther 2016;7:513).
Test question answer:
C. MPO-Anti neutrophil cytoplasmic antibody (P-ANCA) is the most common antibody associated with eosinophilic granulomatosis with polyangiitis.
