Nasal Manifestations of Systemic Diseases

CHAPTER 43 Nasal Manifestations of Systemic Diseases



Rose Stavinoha, Thomas V. McCaffrey



Key Points



• The classic triad of Wegener’s granulomatosis involves the following organ systems: the upper respiratory tract, lungs, and kidneys.

• The cytoplasmic antineutrophil cytoplasmic autoantibody (c-ANCA) test is highly sensitive for Wegener’s granulomatosis but a negative result does not exclude the diagnosis of the disease.

• The main agents used to induce remission of Wegener’s granulomatosis are cyclophosphamide, methotrexate, and/or glucocorticoids.

• Approximately 40% of patients with sarcoidosis have granulomatous changes in extrapulmonary organs. The involvement of the nose and paranasal sinuses by sarcoidosis is relatively infrequent, and most reports are anecdotal, so the true incidence of nasal involvement is not known with certainty.

• Angiotensin-converting enzyme elevations occur in 83% of patients with active sarcoidosis.

• The most common nasal manifestation of AIDS is chronic rhinitis. Patients present with drying, crusting, nasal congestion, partial obstruction, and pain or discomfort.

• Clinical manifestations of nasal T-cell lymphoma usually start with nasal obstruction followed by purulent rhinorrhea and serosanguineous discharge. As symptoms progress, usually unilateral mucosal ulceration with extension into the palate, maxillary sinus, and upper lip help distinguish lymphoma from Wegener’s granulomatosis, which is associated with diffuse nasal mucosal ulceration.

• Cicatricial pemphigoid is more likely to affect the mucosa whereas bullous pemphigoid is confined to skin. Nasal findings occur in 25% to 50% of affected patients. The usual site of involvement is the anterior nasal region, which is found to have painful, ulcerative crusting.

• Primary ciliary dyskinesia is characterized by chronic respiratory tract disease beginning in childhood and leading to a constellation of symptoms, including chronic rhinitis, sinusitis, bronchiectasis, chronic cough, otitis media, and sterility.

• Cystic fibrosis is the most common fatal inherited disease among whites. It affects 1 in 2000 live births. The disease is characterized as an exocrinopathy with clinical features of chronic lung disease, chronic sinusitis, and pancreatic insufficiency.

The nasal airway and paranasal sinuses can be affected by systemic diseases in both specific and nonspecific ways. In some cases, the nasal findings in a systemic disease may be the first indication of disease. The understanding of the various ways in which systemic disease can manifest in the nose is important for both otolaryngologists and the medical specialists who often work with them to treat these diseases.


Systemic diseases affecting the nasal airway can produce pathologic changes in three general ways. First, the general pathophysiology of the disease may affect the tissues of the nose, as in recurrent or severe epistaxis secondary to a coagulopathy. Second, the unique mucosal histology of the nose may make an otherwise minor pathologic process more severe and apparent, as seen in hereditary hemorrhagic telangiectasia. In this particular disease, telangiectasia causes few symptoms in the skin, but in the superficial, easily traumatized vessels of the nasal mucosa, severe epistaxis may occur (see Chapter 45). Third, a systemic disease may affect the tissues of the nose as part of a symptom complex, as seen in Wegener’s granulomatosis.



Granulomatous Disease


Several granulomatous diseases have a predilection to involve tissue in the airways. They include Wegener’s granulomatosis (WG), Churg-Strauss syndrome, and sarcoidosis. These diseases are often characterized by local inflammatory response in the airways, particularly in the upper nasal passages. WG is perhaps the most common granulomatous disease to affect the upper airway and the nasal airway in particular. Sarcoidosis and Churg-Strauss syndrome, although much less frequently found to involve the nasal airway, also have characteristic findings that may permit earlier diagnosis.



Wegener’s Granulomatosis


Wegener’s granulomatosis involving the nose is now being recognized at an earlier stage. Friedrich Wegener first clearly defined WG in 1939 as a systemic disease characterized by necrotizing granulomas with vasculitis of the upper and lower respiratory tract, systemic vasculitis, and focal necrotizing or proliferative glomerulonephritis.1 The classic triad of WG involves the following organ systems: the upper respiratory tract, lungs, and kidneys. Formerly, WG was often confused with several other entities causing midline granulomas or midface destruction, including lymphomas, carcinomas, and infectious processes. WG can now be easily separated with more precise nasal biopsies, histopathologic examination, and the cytoplasmic antineutrophilic cytoplasmic antibody (c-ANCA) test.


The prevalence of WG is estimated to be 3 cases per 100,000, and the mean age at diagnosis is 55 years.2 Men and women are similarly affected, and more than 90% of all patients with WG are white according to later studies. The remaining 1% to 4% of patients are African-Americans, Hispanics, and Asians.3


Rhinologic symptoms of patients with WG may include nasal congestion, rhinorrhea, and anosmia. These symptoms may progress to rhinitis, sinusitis, septal perforation, and/or nasal airway stenosis. Nasal endoscopy typically reveals mucosal cobblestoning, edema, and crusting.4


Clinical features of WG can be divided into three categories. Patients with type 1 WG present with a limited form of the disease characterized by upper airway symptoms and few systemic findings. They typically present with several weeks of symptoms that are similar to those of an upper respiratory tract infection but are unresponsive to antibiotics. There is often associated nasal pain with serosanguineous rhinorrhea and crusting.


Patients with type 2 disease are sicker and present with systemic features although not as severe as those with type 3 disease. Their initial presentation is similar to that of patients with type 1 WG. There is a characteristic prolonged upper respiratory tract infection with a continued nasal discharge that progresses to nasal pain, tenderness, serosanguineous discharge, ulceration, and crusting. Pulmonary involvement is often present and is associated with a cough, hemoptysis, and cavitary lesions on chest radiography.


Type 3 WG is a widely disseminated form of the systemic disease, commonly consisting of upper and lower airway involvement, cutaneous lesions, and progressive renal involvement. Systemic features are more profound and, as with type 1 and type 2 disease, nasal ulcerations and symptoms are present.



Diagnosis


The clinical diagnosis of WG is suggested by the history and characteristic nasal findings. Laboratory values that are often abnormal in WG include the erythrocyte sedimentation rate (ESR) and hemoglobin, serum creatinine, and serum cytoplasmic antineutrophil cytoplasmic autoantibody (c-ANCA) levels. These serologic findings in conjunction with nasal biopsy can provide a definitive diagnosis of WG.


Immunofluorescence is a study that distinguishes antiproteinase-3 (anti-PR3) ANCAs from antimyeloperoxidase antibodies according to the pattern of staining; The cytoplasmic pattern is seen with ANCAs for anti-PR3, and the perinuclear pattern with ANCAs for antimyeloperoxidase.5 The characteristic pattern of coarse granular staining of c-ANCAs is caused by antibodies against proteinase-3 and neutral serine protease present in the azurophilic granules of neutrophils. The c-ANCA test is highly sensitive for WG, but a negative result does not exclude the diagnosis of WG. The specificity of c-ANCA testing for WG has been confirmed in large studies and may in some cases preclude biopsy.6–8 The c-ANCA titer may be used to monitor disease activity because a rise in the titer may be predictive of a relapse of disease, although this concept remains controversial. However, it is clinically appropriate to interpret an increase in c-ANCA titer as an indicator to closely monitor the patient for signs of relapse.


Nasal biopsy, which may be performed with use of local anesthesia and/or intravenous sedation, provides supportive evidence for the diagnosis. All visible nasal crusts must be removed, followed by liberal removal of tissue from the septum, nasal floor, and turbinates in order to provide ample tissue for stains and culture.8 Culture is necessary to rule out granulomatous infectious agents such as fungi and mycobacteria.


Because of the nonspecific nature of many of the symptoms of WG, diagnosis and treatment may be delayed even by specialists.



Pathology


The histopathologic features of WG include vasculitis of medium and small vessels with intramural eccentric necrotizing granulomatous lesions. Typically, arteries, arterioles, capillaries, venules, and veins are involved. Large vessels are rarely affected. There may also be microabscesses that enlarge and coalesce into larger necrotic areas.



Treatment


Patients with WG often have multiorgan involvement and are best treated by a team of physicians including an otolaryngologist and internists or specialists with knowledge of the disease. Treatment algorithms are often based on disease severity and the organ system affected.9 Patients are typically treated with immunosuppression in order to induce remission, and then dosages are adjusted to maintain the state of remission. The main agents used to induce remission are cyclophosphamide, methotrexate, and/or glucocorticoids.


Cyclophosphamide is an alkylating agent that impairs DNA replication and transcription. The current standard regimen for treatment of WG with cyclophosphamide is oral administration of 2 mg/kg per day with a maximum dose of 200 mg/day. It is typically continued for 6 months to 1 year and then the dosage is tapered gradually after the disappearance of symptoms.


Methotrexate is an alternative to cyclophosphamide in patients with limited forms of WG, such as type 1 disease. It acts as an antimetabolite and inhibits dihydrofolate reductase in order to impair folate metabolism. The standard dose begins at 0.25 mg/kg/week, which can be increased to 25 mg/week. This is typically continued for 1 year; it may be continued indefinitely, the dosage may be tapered, or the drug may be stopped abruptly.


Glucocorticoids are given concurrently whether cyclophosphamide or methotrexate is used. The recommended starting dose is prednisone 0.5 to 1.0 mg/kg/day up to a maximum of 80 mg/day.9 Dosage tapering may begin after 1 month with the goal to discontinue the agent completely within 6 to 9 months.


After the symptoms are stabilized, the patient with WG may be effectively maintained on a regimen of trimethoprim-sulfamethoxazole.10 Although the mechanism of action of this drug is not known with certainty, it has been shown to prevent relapses, and it has minimal side effects.


New therapeutic agents have been shown to be promising in resistant cases. Rituximab, a chimeric monoclonal antibody, has been reported to be effective in treating resistant WG.11


Surgical reconstruction may be used to restore function once the disease is in remission. It includes correction of saddle nose deformity and septal perforation repair. Functional endoscopic sinus surgery may benefit selected patients with chronic nasal crusting. Saline irrigations with or without antibiotics are essential to management, although nasal débridement may be helpful with mucosa-sparing techniques and frequent postoperative care to minimize scar formation.



Sarcoidosis


Sarcoidosis is a chronic systemic granulomatous disease capable of involving almost any organ in the body. It frequently involves the lymphatic system, lungs, liver, spleen, and bones. Although involvement of the epithelium of the upper respiratory tract is comparatively uncommon, nasal symptoms may be the first manifestation of this disease.


The etiology of sarcoidosis is unknown, but etiologic claims have been made for various infective agents, chemicals (including beryllium and zirconium), pine pollen, and peanut dust.12 It has also been associated with cell-mediated and humoral immune abnormalities.


Sarcoidosis has a worldwide distribution, but the incidence is higher in northern Europe, southern United States, and Australia. Women are slightly more often affected than men, and the disease is 10 to 20 times more prevalent in blacks than whites.


The clinical course in most cases is benign, with spontaneous resolution within 2 years, although 10% of cases may progress to pulmonary fibrosis. The lung is the primary organ affected by sarcoidosis. Ninety percent of patients have evidence of thoracic involvement, either enlarged intrathoracic lymph nodes or pulmonary parenchymal infiltrates. Approximately 40% of patients with sarcoidosis have granulomatous changes in extrapulmonary organs.


The involvement of the nose and paranasal sinuses by sarcoidosis is relatively infrequent and most reports are anecdotal, so the true incidence of nasal involvement is not known with certainty. The observed incidence of histologically confirmed nasal involvement in large populations of patients with sarcoidosis has ranged between 1% and 6%.13,14 The most common symptom of nasal involvement is nasal obstruction, but epistaxis, dyspnea, nasal pain, epiphora, and anosmia may also occur.


Nasal sarcoidosis commonly affects the mucosa of the septum and inferior turbinate. The nasal mucosa is usually dry and friable with crusting.15 Submucosal nodules with a characteristic yellow color may be noted. These nodules are the macroscopic presentation of intramucosal granulomas, which can be identified in mucosal biopsy specimens. In more advanced disease, irregular polypoid mucosa is seen, which is friable and bleeds readily.

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  2. Nasal Reconstruction
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  4. Malignant Tumors of the Larynx

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Jun 5, 2016 | Posted by in OTOLARYNGOLOGY | Comments Off on Nasal Manifestations of Systemic Diseases

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