Systemic Diseases With Sinonasal Manifestations

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Systemic Diseases With Sinonasal Manifestations

Rhinology
Author Credentials 

Carrie Flanagan, MD
Assistant Professor
Department of Otolaryngology
Emory University
Medical Office Tower, 9th Floor
550 Peachtree St NE
Atlanta, GA 30308
Carrie.elizabeth.flanagan@emory.edu

Module Summary

There are a myriad of very diverse systemic diseases that can adversely affect the nose and sinuses. These include infectious conditions, autoimmune disorders, immunodeficiencies, and genetic diseases. These conditions can result in recalcitrant rhinosinusitis, rhinologic masses, and destructive sinonasal lesions. Performing a thorough history and physical examination is imperative, although there is significant overlap in the presentation of many of these disease processes. Being familiar and knowledgeable of the multitude of systemic diseases and infectious processes that can have sinonasal manifestations will aid in directing an appropriate focused work-up. Because multiple organ systems are often affected, the otolaryngologist is usually part of a multidisciplinary team of medical subspecialists caring for these patients. Medical management is the cornerstone of treatment, although surgical intervention can play a beneficial role.

Module Learning Objectives 
  1. Recognize when systemic disease may be contributing to chronic rhinosinusitis.
  2. Develop a differential diagnosis for necrotizing sinonasal lesions, granulomatous sinonasal disease, and refractory chronic sinusitis.
  3. Explain the main risk factors that are associated with refractory chronic rhinosinusitis.
  4. Cite the appropriate diagnostic evaluation for those patients with chronic rhinosinusitis caused by systemic disease.
  5. Differentiate between the various granulomatous and infectious diseases based on physical examination, laboratory, imaging and pathologic findings.
  6. Discuss other organ systems that are involved in patients with systemic diseases that involve the sinonasal cavity.
  7. Explain the underlying mechanism responsible for chronic rhinosinusitis caused by cystic fibrosis.
  8. Describe the role of the otolaryngologist with respect to management of patients with systemic disease affecting the nose and paranasal sinuses.
  9. Recognize when surgical intervention is appropriate for those patients with sinusitis or nasal deformity secondary to a systemic disease.

Anatomy

Learning Objectives 
  1. Describe sinonasal anatomy, including the structure of the septum and paranasal sinuses.
  2. Understand the anatomy and function of the sinonasal mucosa, including the epithelium, mucus and cilia structure and function.
References 
  1. Standring, S. Gray’s Anatomy. 41st ed. London:Elsevier Limited; 2016:556-570.
  2. Johnson, JT, Rosen, CA. Bailey’s Head & Neck Surgery Otolaryngology. 5th ed. Baltimore: Lippincott Williams & Wilkins; 2014:359-69.
  3. Gudis, DA, Cohen, NA. Cilia Dysfunction. Otolaryngol Clin N Am. 2010 Jun;43(3):461-72, vii.

Pathogenesis

Learning Objectives 
  1. Describe the underlying pathogenesis of the various granulomatous diseases that affect the sinonasal cavity and how they differ from each other
    1. Inflammatory
      1. Wegener’s Granulomatosis (Granulomatosis with Polyangiitis)
      2. Churg-Strauss (Eosinophilic Granulomatosis with Polyangiitis)
      3. Sarcoidosis
    2. Infectious
      1. Tuberculosis
      2. Leprosy
      3. Syphilis
      4. Rhinoscleroma
      5. Leishmaniasis
      6. Others
  2. State how other disease processes can affect the sinonasal cavity
    1. Inflammatory
      1. Relapsing Polychondritis
      2. Systemic Lupus Erythematosus
      3. Others
    2. Genetic diseases
      1. Cystic Fibrosis
      2. Primary Ciliary Dyskinesia
    3. Immunodeficiencies
      1. AIDS
      2. Immunoglobulin deficiencies
    4. Hematologic
      1. Hereditary Hemorrhagic Telangiectasia
References 
  1. Tami, TA, Granulomatous Diseases and Chronic Rhinosinusitis. Otolaryngol Clin N Am. 2005 Dec;38(6):1267-78, x.
  2. Prokopakis, E., et al. Nasal Manifestations of Systemic Disease. B-ENT. 2013;9:171-84.
  3. Laudien, M. Orphan Diseases of the Nose and Paranasal Sinuses: Pathogenesis Clinic Therapy. GMS Curr Top Otorhinolaryngol Head Neck Surg. 2015;Dec 22;14:Doc04. 
  4. Montone, KT. Differential Diagnosis of Necrotizing Sinonasal Lesions. Arch Pathol Lab Med. 2015;139:1508-1514.
  5. Sardana, K, Goel, K. Nasal Septal Ulceration. Clin Derm. 2014;32:817-26.
  6. Greco, A, Rizzo, MI, De Virgilio, A, et al. Churg-Strauss Syndrome. Autoimmunity Reviews. 2015;14:341-8.
  7. Badhey, AK, Kadakia, S, Carrau, RL. Sarcoidosis of the Head and Neck. Head and Neck Pathol. 2015;9:260-8.
  8. Gubbels, SP, Barkhuizen, A, Hwang, PH. Head and Neck Manifestations of Wegener’s Granulomatosis. Otolaryngol Clin N Am. 2003;36:685-705.
  9. Stevens, WW, et al. Immunodeficiency in Chronic Sinusitis: Recognition and Treatment. Am J Rhinol Allergy. 2015;29:115-8.
  10. Chaaban, MR, Kejner, A, Rowe, SM, et al. Cystic Fibrosis Chronic Rhinosinusitis: A Comprehensive Review. Am J Rhinol Allergy. 2013;27:387-95.
  11. Knowles, MR, et al. Primary Ciliary Dyskinesia. Clin Chest Med. 2016;37:449-61.

Basic Science

Learning Objectives 
  1. Know the common microbiologic and histologic findings in granulomatous and infectious disease processes that affect the nose and sinuses.
  2. Describe the difference between p-ANCA and c-ANCA.
  3. Recognize the differences between a Th1 and Th2 immune response.
  4. Demonstrate an understanding of the genetic mechanism that ultimately results in the clinical manifestations of cystic fibrosis.
References 
  1. Prokopakis, E, Nikolaou, V, Vardouniotis, A, et al. Nasal Manifestations of systemic Diseases. B-ENT. 2013;9:171-84.
  2. Montone, KT. Differential Diagnosis of Necrotizing Sinonasal Lesions. Arch Pathol Lab Med. 2015;139:1508-1514.
  3. Chen, M, Kallenberg, CGM. New Advances in the Pathogenesis of ANCA-Associated Vasculitides. Clinical and Experimental Rheumatology. 2009;27(Suppl. 52):S108-114.
  4. Chaaban, MR, Kejner, A, Rowe, SM, et al. Cystic Fibrosis Chronic Rhinosinusitis: A Comprehensive Review. Am J Rhinol Allergy. 2013;27:387-95.

Incidence

Learning Objectives 
  1. Know the regions of endemic infectious agents that affect the nose/sinuses.
  2. Know the incidence of granulomatous disorders that are associated with sinonasal disease.
  3. Know the incidence of the most common immunodeficiencies.
  4. Know the incidence of cystic fibrosis and primary ciliary dyskinesia.
References 
  1. Laudien, M. Orphan Diseases of the Nose and Paranasal Sinuses: Pathogenesis Clinic Therapy. GMS Curr Top Otorhinolaryngol Head Neck Surg. 2015; Dec 22;14:Doc04. 
  2. Chaaban, MR, Kejner, A, Rowe, SM, et al. Cystic Fibrosis Chronic Rhinosinusitis: A Comprehensive Review. Am J Rhinol Allergy. 2013;27:387-95.
  3. Schwitzguébel, AJP, Jandus, P, Lacroix, JS, et al. Immunoglobulin Deficiency in Patients with Chronic Rhinosinusitis: Systematic Review of the Literature and Meta-analysis. J Allergy Clin Immunol. 2015 Dec;136(6):1523-1531.

Genetics

Learning Objectives 
  1. Know the inheritance pattern and discuss the primary genetic abnormality of cystic fibrosis and how that translates to changes on the cellular level.
  2. Know the most common inheritance pattern of primary ciliary dyskinesia and the role of genetic defects in this disease process.
  3. Know the inheritance pattern of hereditary hemorrhagic telangiectasia.
References 
  1. Chaaban, MR, Kejner, A, Rowe, SM, et al. Cystic Fibrosis Chronic Rhinosinusitis: A Comprehensive Review. Am J Rhinol Allergy. 2013;27:387-95.
  2. Knowles, MR, et al. Primary Ciliary Dyskinesia. Clin Chest Med. 2016;37:449-61.
  3. Johnson, JT, Rosen, CA. Bailey’s Head & Neck Surgery Otolaryngology. 5th ed. Baltimore: Lippincott Williams & Wilkins; 2014:359-69.

Patient Evaluation

Learning Objectives 
  1. Identify those patients with sinonasal disease who should be evaluated for a systemic disease as the source.
  2. Develop a differential diagnosis for patients with recalcitrant/refractory chronic rhinosinusitis, granulomatous sinonasal disease, and necrotizing sinonasal disease.
  3. Describe the extrasinus manifestations of the systemic diseases that can affect the nose and paranasal sinuses.
  4. Recite classic diagnostic findings or diagnostic criteria for various disease processes including:
    1. Churg-Strauss
    2. Wegener’s granulomatosis
    3. Sarcoidosis
    4. Cystic Fibrosis
    5. Combined Variable Immunodeficiency
    6. Hereditary Hemorrhagic Telangiectasias
  5. Know appropriate serologic and ancillary studies to obtain for patients with granulomatous diseases or vasculitides affecting the sinonasal cavity and be able to differentiate various granulomatous diseases based on serologic evaluation and extrasinus manifestations.
  6. Recognize that diagnosis of systemic disease is primarily based on clinical history and physical examination findings, with serology and imaging aiding in confirmation of disease
    1. Understand the role of tissue biopsy in the diagnosis of a systemic disease affecting the nose/sinuses
    2. Discuss sensitivity and specificity of various serologic tests
  7. Know when to consider an immunodeficiency as an etiology and the appropriate work-up for a patient suspected to have an immunodeficiency.
  8. Name common presenting symptoms and the diagnostic studies necessary to diagnose cystic fibrosis in a patient with chronic rhinosinusitis.
  9. Understand the role of the otolaryngologist in the context of a multidisciplinary team when caring for these patients.
References 
  1. Prokopakis, E, Nikolaou, V, Vardouniotis, A, et al. Nasal Manifestations of systemic Diseases. B-ENT. 2013;9:171-84.
  2. Tami, TA. Granulomatous Diseases and Chronic Rhinosinusitis. Otolaryngol Clin N Am. 2005;1267-78.
  3. Wojciechowska, J, et al. Granulomatosis with Polyangiitis in Otolaryngologist Practice: A Review of Current Knowledge. Clin Experimental Otorhinolaryngology. 2016;9(1):8-13.
  4. Groh, M, et al. Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss) (EPGA) Consensus Task Force Recommendations for Evaluation and Management. Eur J Internal Medicine. 2015;26:545-53.
  5. Heinle, R, Chang, C. Diagnostic Criteria for Sarcoidosis. Autoimmun Rev. 2014;13:383-87.
  6. Wessendorf, TE, et al. Diagnosis of Sarcoidosis. Clinic Rev Allerg Immunol. 2015;49:54-62.
  7. Chaaban, MR, et al. Cystic Fibrosis Chronic Rhinosinusitis: A Comprehensive Review. Am J Rhinol Allergy. 2013;27:387-95.
  8. Chopra, R. Relapsing Polychondritis. Rheum Dis Clin N Am. 2013;39:263-76.
  9. Knowles, MR, et al. Primary Ciliary Dyskinesia. Clin Chest Med. 2016;37:449-61.
  10. Ocampo, CJ, Peters, AJ. Antibody Deficiency in Chronic Rhinosinusitis: Epidemiology and Burden of Illness. Am J Rhinol Allergy. 2013;27:34-8.
  11. Patel ZM, Lin FY eds. ENT Board Prep High Yield Review for the Otolaryngology Inservice and Board Exams. Springer, New York, NY. 2013.

Imaging

Learning Objectives 
  1. Recognize the importance of sinus CT scan in the evaluation of sinonasal disease and be able to identify each paranasal sinus on imaging.
  2. Understand appropriate indications for obtaining CT imaging in patients with chronic rhinosinusitis.
References 
  1. Johnson, JT, Rosen, CA. Bailey’s Head & Neck Surgery Otolaryngology. 5th ed. Baltimore:Lippincott Williams & Wilkins; 2014:359-69.
  2. Rosenfeld, RM, Piccirillo, JF. Chandrasekhar, SS, et al. Clinical Practice Guideline (Update): Adult Sinusitis. Otolaryngol Head Neck Surg. 2015;152(2 Suppl):S1-S39.

Pathology

Learning Objectives 
  1. Be able to histologically identify and define a granuloma.
  2. Differentiate various disease processes based on histopathological or microbiological examination.
References 
  1. Montone, KT. Differential Diagnosis of Necrotizing Sinonasal Lesions. Arch Pathol Lab Med. 2015;139:1508-1514.
  2. Wenig, BM. Atlas of Head and Neck Pathology. 3rd ed. Philadelphia;Elsevier; 2016:4-80.

Treatment

Learning Objectives 
  1. Recognize the role of the otolaryngologist in the treatment of patients with systemic disease as part of a multidisciplinary team.
    1. Describe appropriate local treatments of the nasal and sinus cavities
    2. Be familiar with the role of systemic therapies
    3. Recognize the importance of identifying and treating extrasinus manifestations.
    4. Know the appropriate indications for sinus surgery, septal perforation repair and nasal reconstruction in this patient population.
  2. Describe the importance of aggressive management of sinus disease in cystic fibrosis and the role of surgery.
References 
  1. Erickson, VR, Hwang, PH. Wegener’s Granulomatosis: Current Trends in Diagnosis and Management. Curr Opin Otolaryngol Head Neck Surg. 2007;15:170-6.
  2. Groh, M, Pagnoux, C, Baldini, C, et al. Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss) (EPGA) Consensus Task Force Recommendations for Evaluation and Management. Eur J Internal Medicine. 2015;26:545-53.
  3. Tami, TA. Sinonasal Sarcoidosis: Diagnosis and Management. Seminars in Resp Crit Care Med. 2002;22:549-54.
  4. Gubbels, SP, Barkhuizen, A, Hwang, PH. Head and Neck Manifestations of Wegener’s Granulomatosis. Otolaryngol Clin N Am. 2003;36:685-705.
  5. Chaaban, MR, et al. Cystic Fibrosis Chronic Rhinosinusitis: A Comprehensive Review. Am J Rhinol Allergy. 2013;27:387-95.
  6. Crosby, DL, Adappa, ND. What is the Optimal Management of Chronic Rhinosinusitis in Cystic Fibrosis. Curr Opin Otolaryngol Head Neck Surg. 2014;22:42-6.
  7. Chopra, R. Relapsing Polychondritis. Rheum Dis Clin N Am. 2013;39:263-76.
  8. Knowles, MR, et al. Primary Ciliary Dyskinesia. Clin Chest Med. 2016;37:449-61.

Medical Therapies

Learning Objectives 
  1. Describe appropriate systemic treatment options for various disease processes:
    1. Inflammatory disease
    2. Infectious disease
    3. Genetic disease
    4. Immunodeficiency
  2. Explain local nasal care and local medical therapies that should be initiated by the otolaryngologist.
References 
  1. Wojciechowska, J, Krajewski, W, Krajewski, P, et al. Granulomatosis with Polyangiitis in Otolaryngologist Practice: A Review of Current Knowledge. Clin Exp Otorhinolaryngol, 2016;9(1):8-13.
  2. Illing, EA, Woodworth, BA. Management of the Upper Airway in Cystic Fibrosis. Curr Opin Pulm Med. 2014 Nov;20(6):623-31.
  3. Ocampo, CJ, Peters, AJ. Antibody Deficiency in Chronic Rhinosinusitis: Epidemiology and Burden of Illness. Am J Rhinol Allergy. 2013;27:34-8.

Pharmacology

Learning Objectives 
  1. Be familiar with the different systemic medications that are used in the treatment of patients with systemic disease:
    1. Inflammatory disease
    2. Infectious disease
    3. Genetic disease
    4. Immunodeficiency
References 
  1. Groh, M, Pagnoux, C, Baldini, C, et al. Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss) (EPGA) Consensus Task Force Recommendations for Evaluation and Management. Eur J Internal Medicine. 2015; 26:545-53.
  2. Chopra, R. Relapsing Polychondritis. Rheum Dis Clin N Am. 2013;39:263-76.
  3. Ocampo, CJ, Peters, AJ. Antibody Deficiency in Chronic Rhinosinusitis: Epidemiology and Burden of Illness. Am J Rhinol Allergy. 2013;27:34-8.

Surgical Therapies

Learning Objectives 
  1. Recognize the role and limitations of surgical intervention in patients with systemic disease causing sinonasal manifestations.
  2. Know appropriate indications for surgical intervention in patients with recalcitrant chronic rhinosinusitis with systemic disease.
  3. Discuss endoscopic medial maxillectomy and its importance in patients with cystic fibrosis.
References 
  1. Prokopakis, E, Nikolaou, V, Vardouniotis, A, et al. Nasal Manifestations of systemic Diseases. B-ENT. 2013;9:171-84.
  2. Chaaban, MR, et al. Cystic Fibrosis Chronic Rhinosinusitis: A Comprehensive Review. Am J Rhinol Allergy. 2013;27:387-95.

Case Studies

  • 36 y.o. African American female presents for a 6-month history of worsening nasal congestion. In the last month, she has had some purulent discharge and crusting. She has been diagnosed with “asthma” brought on by exercise a couple of years ago. She has had a persistent dry cough for a few years also. She has some fatigue, but attributed this to having 2 young children at home. She denies weight loss, fevers, or night sweats. Anterior rhinoscopy reveals a mildly deviated septum and enlarged inferior turbinates bilaterally with some crusting anteriorly. Nasal endoscopy is notable for erythematous mucosa with bilateral small synechiae between the inferior turbinate and the nasal septum. There is no septal perforation. There are some slightly raised nodules along the anterior septum.
    • Provide a differential diagnosis
    • What labs should be ordered?
    • What ancillary studies should be ordered?

    The diagnosis is sarcoidosis.

    • What are recommended treatment options for this patient? What other subspecialists should be involved in this patient’s care?
    • What other subspecialists should be involved in this patient’s care?
  • 27 y.o. male presents with a 5-year history of rhinorrhea and progressive nasal obstruction. The rhinorrhea began as clear, but has been purulent for several months. The patient is otherwise healthy and has no other complaints. He just moved to the United States from the Middle East. Nasal endoscopy is notable for granulation tissue and crusting in both nasal cavities. There are firm nodules in the nasal vestibule.
    • Provide a differential diagnosis

    Biopsy was performed of the vestibular nodules. Histology revealed plasma cells, lymphocytes, Russell bodies and Mikulicz cells.

    • What is your diagnosis?
    • What is the pathogenic organism?
  • 24 y.o. male presents to your clinic for evaluation of recurrent sinusitis. He has had multiple sinus infections since he was a teenager, but has managed to delay any surgical intervention. He complains of nasal obstruction, purulent rhinorrhea and anosmia. He has had one episode of pneumonia as a teenager. He denies typical allergy symptoms. He occasionally has some gastrointestinal distress, but otherwise has no other complaints. Nasal endoscopy is notable for nasal polyposis with purulence in the middle meatus. There are no other masses or lesions. There is no septal ulceration. CT sinus w/o contrast reveals pansinusitis with absent right frontal sinus and hypoplasia of the left frontal and bilateral maxillary sinuses.
    • Provide a differential diagnosis

    The patient undergoes functional endoscopic sinus surgery once and is under your care for the next several years. His sinus disease improved briefly after surgery, but recurred shortly thereafter. He has required several additional courses of antibiotics for recurrent sinus infections. He also, during this time, developed another pneumonia.

    • What is the most likely diagnosis?
    • What sort of additional testing would you consider?

    The patient is diagnosed with Cystic Fibrosis by a pulmonologist.

    • What testing is used to diagnose Cystic Fibrosis?
    • Would you offer this patient additional surgery?

Complications

Learning Objectives 
  1. Describe the typical progression of the various systemic disease processes and how they affect the nose and sinuses.
  2. Know the potential complications of endoscopic sinus surgery.
  3. Know the complications of medical therapy, particularly systemic corticosteroids.
References 
  1. Greco, A, et al. Churg-Strauss Syndrome. Autoimmunity Reviews. 2015;14:341-8.
  2. Humphreys, IM, Hwang, PH. Avoiding Complications in Endoscopic Sinus Surgery. Otolaryngol Clin N Am. 2015;48:871-881.
  3. Svider, PF, et al. Pitfalls in Sinus Surgery – An Overview of Complications. Otolaryngol Clin N Am. 2015;48:725-737.
  4. Poetker, DM, Reh, DD. A Comprehensive Review of the Adverse Effects of Systemic Corticosteroids. Otolaryngol Clin N Am. 2010;43:753-68.

Review

Review Questions 
  1. Name the microbiological organism and the appropriate microbiological test for the following sinonasal infections: Tuberculosis, rhinoscleroma, leprosy, syphilis, and leishmaniasis.
  2. Provide a differential diagnosis of necrotizing sinonasal lesions.
  3. What are the three main granulomatous diseases and how do they differ clinically and serologically?
  4. Provide a differential diagnosis for recalcitrant chronic rhinosinusitis.
  5. What are the common extrasinus manifestations of the primary granulomatous, autoimmune, and vasculitic diseases? Hereditary hemorrhagic telangiectasia?
  6. What would be included in your work-up of a patient with granulomatous or necrotizing lesions of the nasal cavity?
  7. What is the mechanism responsible for cystic fibrosis, both on a genetic and a protein level?
  8. What is primary ciliary dyskinesia?
  9. Describe local therapies that an otolaryngologist can provide for patients with systemic disease resulting in sinonasal disease
  10. What are indications for surgical intervention for patients with recalcitrant chronic sinusitis secondary to a systemic disease process?
  11. When is the optimal time to perform any surgical intervention for defects secondary to granulomatous or vasculitic disease?
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