Wegener's granulomatosis presenting as a parapharyngeal mass.
Wegener's Granulomatosis (WG), also known as Granulomatosis with Polyangitis (GPA), is an autoimmune vasculitis characterized primarily by inflammatory necrotizing granulomatous lesions within the upper and lower respiratory tract and kidneys. (1) Head and neck manifestations of this disease are the presenting symptom in 80-95% of cases and may include sinonasal, otologic, pharyngeal, and laryngeal pathologies. (2)
Sinonasal involvement may range from non-specific symptoms such as nasal obstruction, discharge, and crusting to more classic WG symptomology such as septal perforation and saddle nose deformity. Otologic manifestations are also common, as otitis media with effusion is described frequently within the literature. (2) Although WG most often manifests in the head and neck as one of the aforementioned entities, a growing body of literature reveals a new subset of disease presentation.
Otolaryngological literature has increasingly recognized WG as a worthy diagnostic consideration for patients presenting with atypical lesions of the head and neck with secondary cranial neuropathies. (1-5) Moreover, such lesions are notoriously difficult to diagnose, with only 15-25% of all biopsies described as meeting the pathologic criteria of WG. (1) This can create a prolonged diagnostic interval and favors an interdisciplinary approach to ensure proper management. Here we discuss one such case of Wegener's Granulomatosis, emphasizing the difficulties faced in diagnosis, the need for a thorough history and physical exam, and the value of the interdisciplinary medical team.
A 24-year-old Caucasian male with no past medical history presented to clinic with a two-month history of odynophagia, dysphagia, and weight loss. He had previously been evaluated by otolaryngologists at three separate outside facilities. The first presentation resulted in outpatient management with oral antibiotics. The second presentation resulted in a right tonsillectomy with placement of bilateral pressure equalization tubes at an outside hospital. The third visit led to an inpatient admission with administration of intravenous antibiotics and steroids for a suspected parapharyngeal abscess. Despite three very different treatment strategies, his odynophagia worsened to the point of dehydration and culminated in a 30-pound weight loss. At this time, he also developed bilateral conjunctivitis, dysuria, and persistent polyarthritis involving his knees, elbows, and ankles.
On physical exam, he had bilateral conjunctival injection with right anisocoria. There were no other focal findings in the remainder of his head and neck examination. This included a very thorough oropharyngeal, sinonasal, and subglottic examination performed with flexible fiber-optic laryngoscopy. Laboratory values were as follows: white blood cells of 7,400/[micro]L, hemoglobin of 10.9 g/ dL, hematocrit of 32.1%, platelet count of 476,000/[micro]L, sodium of 132mEq/L, and albumin of 2.6g/dL. Blood cultures showed no growth. A CT scan of the neck with contrast revealed a right parapharyngeal soft tissue infiltrate concerning for infection or neoplasm, but no discrete abscess was evident (Figure 1). The patient was then admitted to the Otolaryngology service and started on broad-spectrum antibiotics. At this point, due to his constellation of symptoms and broad differential diagnosis, a multidisciplinary team was assembled initially involving internal medicine, infectious disease, oncology, and ophthalmology.
On hospital day three, the patient was taken to the operating room for a right neck exploration. Reactive adipose tissue and several reactive lymph nodes at the level of the skull base were removed and sent for pathologic and microbiologic analysis. An MRI of the orbit, face, and neck demonstrated a right jugular vein thrombophlebitis consistent with Lemierre's Syndrome (Figure 2).
During the workup for the patient's dysuria, urinalysis revealed microscopic hematuria without evidence of infection. In addition, his serum creatinine increased from 0.7-3.28 mg/dL despite adequate hydration and appropriate medication dosing regimens. A subsequent renal ultrasound was inconclusive, but could not exclude intraparenchymal disease. Rheumatology and nephrology consults were then placed for workup of potential WG, yielding the following result: negative antinuclear antibodies (ANA), negative anti-mitochondrial antibody, anti-streptolysin O titer within normal limits, C3 complement within normal limits, decreased C4 complement, elevated IgE, positive rheumatoid factor, positive cytoplasmic anti-neutrophil cytosplasmic antibody (c-ANCA), and positive anti-proteinase 3 antibodies (anti-PR3).
Surgical pathology of the neck exploration returned as acute lymphadenitis with eosinophilia, eosinophilic myositis, and no evidence of malignancy in any sample. For definitive diagnosis of WG, the patient underwent a renal biopsy on hospital day eight, ultimately revealing focal necrotizing glomerulonephritis (non immune-complex mediated). With a firm diagnosis of WG, the multi-disciplinary treatment team started the patient on daily oral prednisone and twice daily Azathioprine. The patient made immediate improvements in his health status, both subjectively and objectively. He was discharged on hospital day twelve and continues to receive outpatient care with otolaryngology, nephrology, and rheumatology services.
Two elements paramount to the successful diagnosis and management of an atypical lesion of the head and neck are the development of a broad differential diagnosis and the utilization of a multidisciplinary approach. A growing body of literature supports the notion that we overemphasize the classical clinical triad of upper respiratory tract, lungs, and kidney when diagnosing WG. (3) While this triad is pathognomonic of WG, it is not an absolute criterion and is based solely on broad clinical findings. This is especially important to keep in mind, as head and neck involvement is encountered as the first symptom of disease in up to 80-95% of cases. (1)
As suggested by Gottschlich et al., the diagnosis of WG should be made microscopically, based on findings suggestive of vasculitis and granulomatous inflammation. (1) This fact is true even in the setting of a negative biopsy result, as biopsies of regions within the head and neck have historically had a low sensitivity. 1 6-8 Jennings et al., for example, demonstrated a specificity of 100% but a sensitivity of only 53% when comparing results of intranasal biopsies of patients with WG. (6) Gottschlich et al. also discussed how biopsies of the head and neck frequently demonstrate only nonspecific or inconclusive histopathological changes, such as acute or chronic inflammation. (1) For an absolute diagnosis of WG, one must demonstrate necrosis, granulomatous inflammation, and vasculitis. (7) However, this triad is only seen in 50-65% of biopsies of the head of neck. (8) As a result, one must take the entire clinical picture into context when suspecting WG in the head and neck. In this case Lemierre's Syndrome is believed to be the result of polynangitis affecting the internal jugular vein, thereby causing the pathognomonic finding of acute thrombophlebitis within.
Similarly, testing for the standard laboratory markers can also come with mixed value. The most helpful markers for diagnosing WG are by far anti-nuclear antibody (ANA), cytoplasmic antineutrophil cytoplasmic antibody (c-ANCA), and anti-proteinase 3 antibodies (anti-PR3). Gottschlich et al. notes that while c-ANCA and anti-PR3 antibodies are positive in 95% of patients demonstrating the generalized phase of WG, only 50% of patients will be positive during the localized phase. (1)
The patient discussed in the above case presentation was one whose laboratory results and history were suggestive of Wegener's Granulomatosis, though certain elements of his clinical picture were inconsistent with the classic presentation of this disease. Specifically, he did not display nasal manifestations such as epistaxis or saddle nose deformity, and he had no tracheopulmonary symptoms or signs such as subglottic stenosis, hemoptysis and/or pulmonary nodules on X-Ray. This patient was part of a subset defined by an ever-growing body of literature, one that includes parapharyngeal and retropharyngeal manifestations with subsequent cranial neuropathies and/or superior cervical chain compression. (1-5)
Though head and neck manifestations are often the chief complaint of patients presenting with WG, the classic triad of sinonasal, pulmonary, and renal pathology is not always evident at initial presentation and will not always develop during the course of disease. As demonstrated by this case, WG should be included within the differential diagnosis of atypical head and neck lesions refractory to multiple treatment regimens. Moreover, the assembly of an interdisciplinary medical team leads to an expeditious diagnosis, optimized inpatient management, and coordinated outpatient care.
(1.) Gottschlich S, Ambrosch P, Kramkowski D, et al. Head and neck manifestations of Wegener's granulomatosis. Rhinology 2006; 44:227-33.
(2.) Finley JC Jr, Bloom DC, Thiringer JK. Wegener granulomatosis presenting as an infiltrative retropharyngeal mass with syncope and hypoglossal paresis. Arch Otolaryngol Head Neck Surg 2004; 130:361-5.
(3.) Soderstrom A, Revaz S, Dudler, J. Cranial neuropathies in granulomatosis with polyangiitis (Wegner's): a case-based review. Clin Rheumatol. 2013 Dec 19. [Epub ahead of print].
(4.) Erickson VR, Hwang PH. Wegener's granulomatosis: current trends in diagnosis and management. Curr Opin Otolaryngol Head Neck Surg 2007; 15:170-76.
(5.) Nagashima T, Maguchi S, Terayama Y, et al. P-ANCA-positive Wegener's granulomatosis presenting with hypertrophic pachymeningitis and multiple cranial neuropathies: case report and review of literature. Neuropathology 2000; 1:23-30.
(6.) Jennings CR, Jones NS, Dugar J, Powell RJ, Lowe J. Wegener's granulomatosis: a review of diagnosis and treatment in 53 subjects. Rhinology 1998; 36:188-91.
(7.) Devaney K, Ferlito A, Hunter B, Devaney S, Rinaldo A. Wegener's granulomatosis of the head and neck. Ann Otol Rhinol Laryngol 1998; 107:439-45.
(8.) Devaney K, Travis W, Hoffman G, Leavitt R, Lebovics R, Fauci A. Interpretation of head and neck biopsies in Wegener's granulomatosis. Am J Surg Pathol 1990; 14:555-64.
Mr. Nelson, Dr. Hildrew and Mr. Guittard and are affiliated with the Department of Otolaryngology/ Head and Neck Surgery at Tulane University School of Medicine in New Orleans, LA. Mr. Deblieux and Dr. Brickman are affiliated with the Department of Otolaryngology/ Head and Neck Surgery at Louisiana State University School of Medicine in New Orleans, LA.
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|Author:||Nelson, Ryan E.; Hildrew, Douglas M.; Deblieux, Tyler; Guittard, Jesse A.; Brickman, Todd M.|
|Publication:||The Journal of the Louisiana State Medical Society|
|Article Type:||Clinical report|
|Date:||Mar 1, 2016|
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