ORIGINAL ARTICLE

Coexistent Pulmonary Granulomatosis With Polyangiitis (Wegener Granulomatosis) and Crohn Disease Laszlo T. Vaszar, MD,* Nicole M. Orzechowski, DO,w Ulrich Specks, MD,z Steven R. Ytterberg, MD,y Edward V. Loftus, Jr, MD,8 Eugene J. Mark, MD,z and Henry D. Tazelaar, MD#

Abstract: Crohn disease (CD) may be associated with various extraintestinal manifestations, including, rarely, respiratory tract involvement. When necrobiotic pulmonary nodules are present, the differential diagnosis includes granulomatosis with polyangiitis (Wegener granulomatosis) (GPA). The respiratory tract manifestations of CD and GPA may mimic each other, complicating the diagnosis and suggesting the possible coexistence of these 2 conditions. The aim of this study was to describe the clinical, radiographic, and pathologic features of patients in whom CD and GPA coexist. We reviewed the teaching files of the authors and searched the Mayo Clinic medical records for coexistent inflammatory bowel diseases and antineutrophilic cytoplasmic antibodies (ANCA)-associated vasculitides. We reviewed in detail 97 patient charts and excluded cases of ulcerative colitis and those in whom only one of the diagnoses was present. Pulmonary and gastrointestinal biopsies were reviewed when available. We also searched the medical literature for previously published cases. We found 6 cases of coexistent CD and pulmonary GPA and 4 cases with extrapulmonary GPA; 3 cases (all with extrapulmonary GPA) have been published previously. The diagnosis of CD preceded that of GPA in 11 cases. Proteinase 3-ANCA was positive in 6 cases, negative in 2, and not reported in 5 cases. Myeloperoxidase-ANCA was negative in 6 cases and unavailable in the remainder of patients. Pathology revealed features diagnostic of GPA in all cases with necrotizing granulomatous inflammation and segmental vasculitis. Pulmonary findings in patients with CD or the presence of granulomatous colitis in patients with GPA should prompt the inclusion in the differential diagnosis of a possible coexistence of CD and GPA.

Key Words: Crohn disease, inflammatory bowel disease, granuloma, pulmonary granulomatosis with polyangiitis (Wegener), review (Am J Surg Pathol 2014;38:354–359)

A

lthough inflammatory bowel diseases (IBD) may be associated with a variety of extraintestinal manifestations,1,2 the respiratory tract is less often affected compared with other organs. When present, pulmonary manifestations are more commonly seen in ulcerative colitis (UC) than in Crohn disease (CD).3–6 The nonspecific clinical presentations and protean chest imaging abnormalities lead to extensive differential diagnoses in these settings, including infections and drug reactions, in addition to the direct manifestations of the underlying IBD. Granulomatosis with polyangiitis (Wegener granulomatosis) (GPA) is a rare necrotizing granulomatous vasculitis with preferential sino-pulmonary and renal manifestations.7 However, involvement of other organ systems including multiple gastrointestinal manifestations have been reported.8,9 Antineutrophilic cytoplasmic antibodies (ANCA) are common in both IBD and GPA and show a distinctive distribution, in that cytoplasmic staining ANCA (C-ANCA) reacting with proteinase 3 (PR3) predominates in GPA and may be present in CD, whereas perinuclear ANCA (P-ANCA) reacting with a

TABLE 1. Diagnostic Criteria for CD

From the *Division of Thoracic Medicine; #Department of Laboratory Medicine and Pathology, Mayo Clinic, Scottsdale, AZ; wSection of Rheumatology, Dartmouth-Hitchcock Medical Center, Lebanon, NH; Divisions of zThoracic Medicine; yRheumatology; 8Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN; and zDepartment of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA. Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Correspondence: Laszlo T. Vaszar, MD, Division of Thoracic Medicine, Mayo Clinic, 13400 E Shea Blvd, Scottsdale, AZ 85259 (e-mail: [email protected]). Copyright r 2014 by Lippincott Williams & Wilkins

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At least 2 of the following criteria were present over at least 2 mo: Clinical history of abdominal pain, weight loss, malaise, diarrhea, and/or rectal bleeding Endoscopic findings of mucosal cobblestoning, linear ulcerations, skip areas, or perianal disease Radiologic findings of stricture, fistula, mucosal cobblestoning, or ulceration Macroscopic appearance of bowel wall induration, mesenteric lymphadenopathy, and “creeping fat” at laparotomy Pathologic findings of transmural inflammation and/or epithelioid granulomas Reprinted from Gastroenterology, Loftus, E.V., Jr., M.D. Silverstein, W.J. Sandborn, et al., Crohn’s disease in Olmsted County, Minnesota, 1940-1993: incidence, prevalence, and survival.114(6):1161-8, Copyright 1998, with permission from Elsevier.

Am J Surg Pathol



Volume 38, Number 3, March 2014

r

Dx Sex Age

Extent

2014 Lippincott Williams & Wilkins

F

6

Jejunal

Inflammatory

F

F

9

10

29

35

23

F

F

18

NA

Ileocolonic

NA

Penetrating

NA

Penetrating

Colectomy; resections of rectum and small bowel segments (twice)

Right-sided hemicolectomy NA

Emergent hemicolectomy due to perforation after stricture dilation Ileocecectomy

None

Control

Inactive

47

52

16

20

Control

Active

54

37

29

Control

Control

Control

Dx Response Age

Nose

Lungs, nose, trachea, kidneys, peripheral nerves Lungs, nose, hearing loss, eye (scleritis)

Lungs

Lungs

Nose, lungs

Lungs

Affected Organ(s)

Ssz, gcc, aza

NA

Mesalamine

Mesalamine, ssz, pred

Inactive

NA

Inactive

Control

Nose

Renal

Skin, Bell palsy, nose 31 Nose, middle ear, corneal ulcers, kidney

78

36

33

Inactive 34 Nose, trachea Mesalamine, 6-mp, cs-A, pred, mtx, infliximab Pred, Control,