Granulomatous Diseases of the Head and Neck



  • What is a granuloma?

    1. A granuloma is created by a chronic immunologic process resulting clinically in localized nodular inflammation.

  • Histology

    1. The inflammatory response is mediated by monocytes and macrophages. Macrophages can give rise to epithelioid cells, which can secrete extracellular enzymes. Multinucleated giant cells are often found in granulomas and are thought to arise from the fusion of macrophages.

    2. These cells are surrounded by lymphocytes and eosinophils.

    3. A granuloma is complete with a fibroblastic proliferation occurring around the cells.

  • What is the differential diagnosis of a granuloma in the head and neck?

    1. There is a significant range of symptoms caused by granulomatous diseases, not limited to the head and neck. A full history and physical examination should be performed for all patients with a granulomatous biopsy. Refer to Table 12-1.

Table 12-1Differential Diagnosis: Granulomatous Diseases of the Head and Neck

Differential Diagnosis




Granulomatosis With Polyangiitis (GPA, Renamed From Wegener Granulomatosis)

  • Small and medium-vessel vasculitis.

  • Belongs to a larger group of necrotizing vasculopathy syndromes, all of which involve an autoimmune attack by abnormal circulating anti-neutrophil cytoplasmic antibodies (ANCA).

  • Thought to be a T-cell mediated hypersensitivity reaction.

  • Initially named after Friedrich Wegener, a German pathologist whose Nazi past was uncovered, leading to the eponym being abandoned and renamed in 2011.


  • Cause unknown.

  • 10 to 20 cases per million per year.

  • 5-year survival is over 80% with adequate treatment.

  • Commonly occurs in whites, in third to fifth decades.


  • Extremely variable.

  • Classic triad: airway necrotizing granulomas, systemic vasculitis, and focal glomerulonephritis.

  • Most common presenting symptom is rhinitis.

  • Renal: rapidly progressive glomerulonephritis (75%).

  • Sinonasal: nasal congestion, crusting, rhinitis, epistaxis, septal perforation, and possible saddle nose deformity.

  • Otologic: conductive hearing loss from Eustachian tube dysfunction, middle ear effusion, possible sensorineural hearing loss.

  • Oral cavity: gingival hypertrophy, gingivitis, tooth decay, nonspecific ulcerations.

  • Ocular: pseudotumors, conjunctivitis, scleritis, episcleritis, uveitis, nasolacrimal obstruction.

  • Larynx: subglottic stenosis.

  • Pulmonary: cavitary lesions, nodules, infiltrates, pulmonary hemorrhage.


  • Characteristic patchy necrosis surrounded by giant cells, causing necrotizing granuloma formation in nonspecific inflammatory background

  • Macrophages, inflammatory cells, and giant cells

  • True vasculitis, demonstrating granulomatous inflammation of vessel wall in arteries and veins


  • cANCA (cytoplasmic anti-neutrophil cytoplasmic antibodies) that react with proteinase (PR3) are associated with GPA but are not definitely sensitive or specific.

  • Elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP).

  • Anemia, urine sediment (RBC casts or > 5 RBCs/high power field (HPF)).

  • Imaging: CXR, consider CT sinus as clinically indicated.

  • Must have tissue biopsy demonstrating necrotizing granulomatous inflammation.


  • Induce remission with cyclophosphamide or rituximab in addition to high-dose corticosteroids.

  • Maintenance with less toxic immunosuppressant therapy, such as methotrexate, azathioprine, leflunomide, or mycophenolate mofetil.

  • Role of trimethoprim/sulfamethoxazole

    1. May help prevent relapse, especially in disease limited to the upper airway

    2. Pneumocystis jiroveci pneumonia (PJP) prophylaxis.

Churg-Strauss (Eosinophilic Granulomatosis with Polyangiitis [EGPA])

  • Allergic, granulomatous, small and medium-vessel vasculitis

  • Necrotizing vasculopathy syndrome, in same group as GPA


  • Extremely variable.

  • Classic triad: asthma, systemic vasculitis, eosinophilia.

  • Occurs in patients with history of airway allergic hypersensitivity, with asthma developing 3 to 9 years prior to onset of other signs and symptoms.

  • 70% have nasal involvement (allergic rhinitis, polyps, obstruction, rhinorrhea, crusting).

  • Usually manifests in following three stages:

    1. Allergic stage: Prodromal, allergic rhinitis and asthma, polyps, nasal obstruction

    2. Eosinophilic stage (aka Loeffler syndrome): Hypereosinophilia causes damage to respiratory and GI tracts; may experience weight loss, night sweats, asthma, cough, abdominal pain, GI bleeding

    3. Vasculitic stage: Inflammation of vessels causes decreased perfusion of tissues and organs; may be severe and life threatening. May develop thrombi, peritonitis or perforation, or heart disease


  • Fibrinoid, epithelioid, and eosinophilic extravascular granulomas with necrosis


  • Associated with pANCA (perinuclear anti-neutrophil cytoplasmic antibodies) that bind myeloperoxidase (MPO), positive in 50%

  • Elevated eosinophils and granulomas in affected tissues

  • American College of Rheumatology Criteria (1990); require 4/6

    1. Asthma

    2. Eosinophils more than 10% of complete blood count with differential

    3. Mononeuritis multiplex or polyneuropathy

    4. Nonfixed pulmonary infiltrates

    5. Paranasal sinus abnormalities (rhinitis, sinusitis, polyps)

    6. Histological evidence of extravascular eosinophils


  • High-dose corticosteroids and immunosuppressive agents such as azathioprine or cyclophosphamide are the mainstays of treatment.

Relapsing Polychondritis

  • Rare disorder characterized by episodic recurrent inflammation and deterioration of cartilage and tissues containing glycosaminoglycans; eventually replaced by granulation and fibrosis


  • Often presents in fifth or sixth decades, and no gender predilection


  • Recurrent episodes of sudden, painful chondritis that resolve within 7 days.

  • Nasal chondritis 15%.

  • Auricular chondritis 50% and “lobule sparing.”

  • Nonerosive polyarthritis 50%.

  • Respiratory tract chondritis 15%.

  • Ocular inflammation 15%.

  • Sequelae can include saddle nose deformity, auricular deformity, collapse of laryngotracheal cartilage framework and airway compromise, visual disturbance.

  • Often presents with other autoimmune disorders.


  • Inflammatory cells infiltrate perichondrium with tissue destruction.

  • Gross appearance is nonspecific thickening of cartilages.


  • Elevated inflammatory markers (ESR or CRP) during disease activity

  • Testing for autoantibodies to type II collagen, found only in cartilage

  • McAdam criteria (6) classically used for clinical diagnosis

    1. Recurrent chondritis of both auricles

    2. Chondritis of nasal cartilages

    3. Laryngotracheal chondritis

    4. Nonerosive seronegative polyarthritis

    5. Ocular inflammation

    6. Cochleovestibular damage

  • Diagnostic if

    1. 3+ of 6 McAdam criteria alone

    2. 1+ criteria and histopathological confirmation with biopsy

    3. Chondritis in two or more separate anatomical locations with response to steroids and/or dapsone


  • Immunosuppressive agents, primarily corticosteroids.

  • Colchicine, dapsone, nonsteroidal anti-inflammatory drugs (NSAIDs).

  • Upper airway collapse may require tracheostomy.


  • Caused by deposition of antibodies and immune complexes, Type 3 hypersensitivity reaction


  • Typically occurs in young, female patients; more common in ethnic and minority groups, blacks, Hispanics, and Asians

  • Associated with human leukocyte antigen (HLA) DR2 and DR3


  • Three subtypes.

  • Discoid lupus erythematosus (DLE): Least aggressive type, only affecting superficial tissues. Oral or cutaneous erythematous plaque lesions, alopecia. May develop scarring.

  • Subacute cutaneous lupus (SCL): Papulosquamous lesions that do not scar; mild systemic involvement.

  • Systemic lupus erythematosus (SLE): The most severe form of lupus. Typically present with malar butterfly rash. Hoarseness and pain may result from laryngotracheal perichondritis and true vocal fold thickening. May have nasal crusting, dryness, or septal perforation.


  • DLE: Clinical diagnosis alone (serology negative).

  • SCL: Clinical diagnosis, inconsistent results from anti-nuclear antibodies (ANA), SS-A, and SS-B.

  • SLE: Nonspecific tests are typically positive and used to establish initial diagnosis (ANA, SS-A, SS-B). Specific markers include anti-double-stranded DNA (ds-DNA) and Sm Antigen (SmAg).

    1. ACR diagnostic criteria require 4/11 for SLE (acronym is “SOAP BRAIN MD”); Serositis, Oral ulcers, Arthritis, Pulmonary fibrosis, Blood dyscrasias, Raynaud/renal, ANA, Immunologic (anti-Sm or anti-dsDNA), Neuropsychiatric, Malar rash, Discoid rash


  • Typically consists of NSAIDs and corticosteroids.

  • Other options include azathioprine, cyclophosphamide, and antimalarial agents such as hydroxychloroquine.

Behcet Disease


  • Recurrent aphthous ulcers on the oral mucosa and genitalia.

  • Uveitis and ocular inflammation also present.

  • May experience neurologic disease, brain stem or spinal cord involvement.

  • Progressive sensorineural hearing loss.

  • Vasculitis; affects vessels of all sizes, even as large as pulmonary artery.

  • Venous thromboembolic events, arthritis, and renal and cardiac involvement are all possible.


  • Recurrent oral ulcers (three or more episodes per year) and two of genital ulcers, uveitis, skin lesions (erythema nodosum), or positive pathergy test (pustular response to skin trauma)


  • Interferon alpha-2a is effective in long-term treatment of severe uveitis.

  • Steroid cream for topical treatment.

  • Colchicine or Dapsone.

  • Eye drops.




  • Idiopathic, systemic noncaseating granulomatous disease of unknown origin; commonly affects lungs, hilar lymph nodes, and upper respiratory tract

  • Most cases clear without treatment


  • Predominates in females, third to fifth decades.

  • 10 to 20 times more common in black patients in North America.


  • Often presents with hilar adenopathy on chest radiography or cervical adenopathy.

  • 90% of patients have pulmonary involvement (hilar adenopathy, cough, dyspnea).

  • Laryngeal sarcoid: Presents as supraglottic submucosal mass, usually in epiglottis, and possible vocal cord paralysis.

  • Sinonasal sarcoid: May present with crusting, “cobblestone” mucosa, epistaxis, synechiae, stenosis, or cartilage destruction.

  • Salivary gland involvement: Can range from asymptomatic parotid mass to “Heerfordt syndrome” or uveoparotid fever, an extrapulmonary manifestation of sarcoid consisting of uveitis, parotitis, fever, facial palsy, and sensorineural hearing loss.

  • Cutaneous findings include erythema nodosum, Darier-Roussy (subcutaneous) nodules, and “lupus pernio.”

  • Lupus pernio: Chronic, red or purple indurated cutaneous plaques on nose, cheeks, ears, and hands that is pathognomonic for sarcoidosis.

  • Lofgren syndrome: Acute form of sarcoidosis characterized by polyarthralgias, erythema nodosum, bilateral hilar LAD.

  • Cardiac arrhythmia, neuropathy, sensorineural hearing loss, renal and hepatic involvement may also be present.


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Apr 30, 2020 | Posted by in OTOLARYNGOLOGY | Comments Off on Granulomatous Diseases of the Head and Neck

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