Figure 1. (A) and lateral (B) views from a chest radiograph demonstrates subtle narrowing of the upper to mid trachea.  A sagittal reconstruction from a contrast-enhanced CT (C) demonstrates circumferential tracheal wall thickening with surrounding fat stranding suggesting tracheal inflammation. (Click here to view Figure 1 in a separate, enlarged window)

Figure 2. Initial contrast-enhanced CT with axial reconstructions through the trachea (A) show tracheitis with involvement of the posterior membrane.  On this CT the right bronchus intermedius (B) appears normal. On a 5-year follow-up contrast-enhanced CT, the tracheal inflammation has resolved (C) and there is new thickening and inflammation of the bronchus intermedius (D, arrow). Findings are consistent with a waxing and waning inflammatory process impacting the large airways, in this case granulomatosis with polyangiitis. (Click here to view Figure 2 in a separate, enlarged window)

Figure 3. Soft tissue neck CT with coronal reconstructions through the maxillary sinuses (A) and trachea (B) demonstrates significant mucosal thickening of the sinuses and also acute inflammatory changes along the trachea. (Click here to view Figure 3 in a separate, enlarged window)

A 79-year-old man presented to our institution for evaluation of intermittent fevers, profound nasal pain with congestion, cough, sore throat, voice changes, fatigue, generalized weakness, and loose stools which had been progressively affecting the patient for the last 6 months.  The patient has a past medical history of ulcerative colitis, hypothyroidism, atrial fibrillation, and hypertension. Just preceding the onset of symptoms, the patient had gone on a month-long trip through Africa and Asia. His symptoms were presumed infectious in the outpatient setting and had responded somewhat to an extended course of ciprofloxacin and metronidazole.

The patient had an outpatient head and neck CT that demonstrated significant mucosal thickening of the maxillary sinuses (Figure 4A). An outside hospital CT of the abdomen/pelvis was unremarkable aside from sigmoid diverticulosis. The patient’s significant nasal pain and congestion along with the fevers was suggestive of granulomatosis with polyangiitis (GPA). The differential also included hematologic malignancy and malaria (with travel history) which were ruled out with bone marrow biopsy and blood smears, respectively. Laboratory testing at this point was notable for leukocytosis of 12.6 and C-reactive protein elevated at 10. Rheumatologic testing was positive for ANA and proteinase-3 ANCA. Imaging findings of paranasal sinus mucosal thickening and tracheobronchial thickening (Figure 1, 2A) without sparing of the posterior membrane also supported GPA. Nasal endoscopy revealed mucosal inflammation and thickening. Biopsy was deemed unnecessary in this case. With the clinical history in addition to congruent laboratory, imaging, and endoscopic findings, the patient was diagnosed with GPA and started on oral prednisone for treatment.

This case demonstrates that, although many organ systems can be involved in GPA, not all need to be involved to make the diagnosis. Paranasal sinus thickening (Figure 3) is a common, non-specific finding on CT head that only found significance in this case when combined with the clinical history. The pattern of tracheitis seen was more specific. Involvement of the posterior membrane (see image 1C, 2A) can be seen in GPA, sarcoidosis, or amyloidosis, but importantly not with relapsing polychondritis. Waxing and waning through time is classic for GPA and illustrated in Figure 2. Pulmonary nodules, often with cavitation, are frequently described with GPA but not seen in this case. Renal involvement was lacking in this case, although there are not typically renal findings on imaging and the diagnosis of renal involvement is usually made with biopsy and lab findings.

Granulomatosis with polyangiitis (GPA) is an ANCA (antineutrophil cytoplasmic antibody) associated small to medium blood vessel vasculitis that can affect the tracheobronchial tree. The multisystem imaging and clinical disease manifestations of GPA are the consequence of underlying necrotizing granulomatous inflammation. Most patients with GPA are seropositive for proteinase 3-ANCA (PR3) rather than myeloperoxidase-ANCA (MPO), however ANCA immunoassays have been shown to be negative in 5-15% of patients with GPA (1,2). GPA is a rare disease with an estimated prevalence of 3 cases per 100,000 individuals in the United States, most commonly occurring in white people (90% of cases) and often in the sixth and seventh decade of life (3).

Although pulmonary involvement is common, affecting approximately two thirds of patients with GPA, tracheobronchial involvement is not a frequent disease manifestation (1,2). However, a striking majority (>70%) of patients who exhibit tracheobronchial involvement, particularly related to subglottic inflammation, are women (2,4). The large airway mucosal inflammation that these patients endure can be seen as smooth or nodular circumferential mucosal or submucosal thickening on CT (1,5). The most common tracheobronchial manifestation of GPA, subglottic stenosis, is the debilitating culmination of prolonged uncontrolled tracheal inflammation (6). Acute large airway manifestations of GPA can be similarly devastating as in the case of a 43yo woman with biopsy proven GPA (negative CRP and PR3-ANCA) found to have acute mainstem bronchus occlusion resulting in severe atelectasis (7).

The histopathologic changes of GPA include the following characteristic features: vasculitis with fibrinoid necrosis and occasionally intramural granulomatous inflammation of small to medium blood vessels as well as a pattern of “geographical” necrosis with giant cells, palisading histiocytes, neutrophilic microabscesses, and polymorphic granuloma (2,8). Given the often protracted disease course of tracheobronchial GPA and limited patient seropositivity, the presence of multisystem disease manifestations including concomitant pulmonary nodules, cavitary masses, renal disease, and/or sinonasal disease is integral to ascertaining the correct diagnosis (6).  Ultimately, histopathologic evidence remains the gold standard for diagnosis and first line treatment involves glucocorticoids with immunomodulatory adjuncts such as methotrexate and rituximab (2,8).

Gabriel Swenson MD, Steven Herber MD, Clinton Jokerst MD

Department of Radiology

Mayo Clinic Arizona, Scottsdale, AZ USA

References

1. Jalaber C, Puéchal X, Saab I, Canniff E, Terrier B, Mouthon L, Cabanne E, Mghaieth S, Revel MP, Chassagnon G. Differentiating tracheobronchial involvement in granulomatosis with polyangiitis and relapsing polychondritis on chest CT: a cohort study. Arthritis Res Ther. 2022 Oct 28;24(1):241. [CrossRef]  [PubMed]
2. Thompson GE, Specks U. Update on the Management of Respiratory Manifestations of the Antineutrophil Cytoplasmic Antibodies-Associated Vasculitides. Clin Chest Med. 2019 Sep;40(3):573-582. [CrossRef] [PubMed]
3. Carnevale C, Arancibia-Tagle D, Sarría-Echegaray P, Til-Pérez G, Tomás-Barberán M. Head and Neck Manifestations of Granulomatosis with Polyangiitis: A Retrospective analysis of 19 Patients and Review of the Literature. Int Arch Otorhinolaryngol. 2019 Apr;23(2):165-171. [CrossRef] [PubMed]
4. Quinn KA, Gelbard A, Sibley C, et al. Subglottic stenosis and endobronchial disease in granulomatosis with polyangiitis. Rheumatology (Oxford). 2019 Dec 1;58(12):2203-2211. [CrossRef] [PubMed]
5. Mayberry JP, Primack SL, Müller NL. Thoracic manifestations of systemic autoimmune diseases: radiographic and high-resolution CT findings. Radiographics. 2000 Nov-Dec;20(6):1623-35. [CrossRef] [PubMed]
6. Pakalniskis MG, Berg AD, Policeni BA, Gentry LR, Sato Y, Moritani T, Smoker WR. The Many Faces of Granulomatosis With Polyangiitis: A Review of the Head and Neck Imaging Manifestations. AJR Am J Roentgenol. 2015 Dec;205(6):W619-29. [CrossRef] [PubMed]
7. Kuwata R, Shirota Y, Ishii T. Severe Acute Atelectasis Caused by Complete Obstruction of Left Main Stem Bronchus Associated with Granulomatosis with Polyangiitis. J Rheumatol. 2020 Aug 1;47(8):1293-1294. [CrossRef] [PubMed]
8. Masiak A, Zdrojewski Z, Pęksa R, Smoleńska Ż, Czuszyńska Z, Siemińska A, Kowalska B, Stankiewicz C, Rutkowski B, Bułło-Piontecka B. The usefulness of histopathological examinations of non-renal biopsies in the diagnosis of granulomatosis with polyangiitis. Reumatologia. 2017;55(5):230-236. [CrossRef] [PubMed] 

Cite as: Swenson G, Herber S, Jokerst C. September 2024 Medical Image of the Month: A Curious Case of Nasal Congestion. Southwest J Pulm Crit Care Sleep. 2024;29(3):26-29. doi: https://doi.org/10.13175/swjpccs040-24 PDF