Sinusitis and Immunodeficiency

By: Andrew Pugliese, MD

Doctor: You know that check you gave me last week? Well it came back.

Patient: That’s okay, so did my sinusitis!

A patient goes to their Doctor

According to a 2012 National Health Survey: 1. 12% or 1 in 8 adults were reported of being

diagnosed with rhinosinusitis since 2011.2. Making this one of the most common chronic

conditions seen in the United States today.3. It is seen more frequently than hay fever (7%),

bronchitis (4%), COPD (4%).

Blackwell DL, Lucan JW, Clarke TC. Summary health statistics for US adults national health interview survey, 2012. Vital Health Stat. 2014; 10: 1-171.

The Burden of Sinusitis

4. About 20 Million cases of bacterial sinus infections are seen annually. 5. One of the most common encountered

conditions seen by clinicians annually.

Blackwell DL, Lucan JW, Clarke TC. Summary health statistics for US adults national health interview survey, 2012. Vital Health Stat. 2014; 10: 1-171.

The Burden of Sinusitis, Cont.

Both acute sinusitis and chronic sinusitis account for more primary ambulatory care visits with antibiotic prescriptions than any other diagnosis or diagnoses.

Otolaryngology– Head and Neck Surgery 2015, Vol. 152(2S) S1–S39 © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0194599815572097 http://otojournal.org Clinical Practice Guideline (Update): Adult SinusitisRichard M. Rosenfeld, MD, MPH1, Jay F. Piccirillo, MD2, Sujana S. Chandrasekhar, MD3, Itzhak Brook, MD, MSc4, Kaparaboyna Ashok Kumar, MD, FRCS5, Maggie Kramper, RN, FNP6, Richard R. Orlandi, MD7, James N. Palmer, MD8, Zara M. Patel, MD9, Anju Peters, MD10, Sandra A. Walsh11, and Maureen D. Corrigan12

Antibiotics and Sinusitis

Acute Sinusitis has significant economic implications.1. Healthcare expenditures exceed 3 billion

annually.2. Average cost per patient per year is around

eleven hundred dollars annually.3. Indirect cost related to acute sinusitis as far as

decreased productivity and days lost is significant.

Wu JH, Howard DH, McGowan JE, et al. Patterns of health care resource utilization after macrolide treatment failure: results from a large, population-based cohort with acute sinusitis, acute bronchitis, and community-acquired pneumonia. Clin Ther. 2004;26:2153-2162.

Economic Impact of Acute Sinusitis

Over 18 million office visits for chronic sinusitis occurred in 2001.

Patients with chronic sinusitis see their primary care twice as often than those without the disorder.

Anand VK. Epidemiology and economic impact of rhinosinusitis. Ann Oto Rhinol Laryngol. 2004;193:3-5. Ray NF, Baraniuk JN, Thamer M, et al. Healthcare expenditures for sinusitis in 1996: contributions of asthma, rhinitis, and other airway disorders. J Allergy Clin Immun. 1999;103:408-414.

Socio-economic Implications of Chronic Sinusitis

In 2007, approximately 8.3 billion dollars was spent annually on chronic sinusitis.

Primarily due to prescription drugs and office based care.

Bhattacharyya N. Incremental health care utilization and expenditures for chronic rhinosinusitis in the United States. Ann Oto Rhinol Laryngol. 2011;120:423-427.

Socio-economic Implications of Chronic Sinusitis, Cont.

Nearly a quarter million sinus surgeries are performed annually.

Average cost: $7,700 per patient. Average annual per-patient spending $2,450

in the year prior to surgery, which decreases $895 in the year after surgery.

A significant proportion of CRS patients require ongoing treatment of their sinus disease for years.

Bhattacharyya N, Orlandi RR, Grebner J, et al. Cost burden of chronic rhinosinusitis: a claims-based study. Otolaryngol Head Neck Surg. 2011;144:440-445.

Socioeconomics Implications of Sinusitis Surgery

Patients with chronic sinusitis are absent from work an average of 6.5% of the time.

An average of 36% reduction in on-the-job effectiveness.

An average of 38% of lost productivity.

Stankiewicz J, Tami T, Truitt T, et al. Impact of chronic rhinosinusitis on work productivity through one-year follow-up after balloon dilation of the ethmoid infundibulum. Int Forum Allergy Rhinol. 2011;1:38-45.

Indirect Cost of Chronic Sinusitis

Patients with medically refractory sinusitis miss approximately 18 days of work annually.

The overall annual productivity cost for refractory sinusitis is approximately $10,000 per patient per year.

Rudmik L, Smith TL, Schlosser RJ, et al. Productivity costs in patients with refractory chronic rhinosinusitis. Laryngoscope. 2014;124:2007-2012.

Indirect Cost of Refractory Chronic Sinusitis

Patients with chronic sinusitis score significantly higher on measures of bodily pain and social functioning than those with angina, back pain, congestive heart failure, and COPD.

Gliklich RE, Metson R. The health impact of chronic sinusitis in patients seeking otolaryngologic care. Otolaryngol Head Neck Surg. 1995;113:104-109.

Quality of Life with Chronic Sinusitis

Treatment of chronic sinusitis can improve health state utility values and substantially reduce fatigue and bodily pain.

Soler ZM, Wittenberg E, Schlosser RJ, et al. Health state utility values in patients undergoing endoscopic sinus surgery. Laryngoscope. 2011;121:2672-2678.

Quality of Life with Chronic Sinusitis, Cont.

AnatomyPhysiology

Complex Disease

Anatomy

Any process causing damage to sinus mucosa

Most common culprits:• Allergies• Reflux• Fungus• Immuno-deficiencies

Physiology

Creates inflammation within the sinus cavities

Loss of mucosal integrity Potential for secondary bacterial infections

Allergies

Silent: only symptom may be sinusitis More than the “Purple Pill”

◦ Esophageal stricture◦ Hiatal hernia◦ Failed Nissan◦ Achalasia

Reflux

Allergic Fungal Sinusitis◦ Eosinophilic Mucin◦ Fungal elements◦ Nasal discharge

Peanut butter, rubber cement, axle grease, and wallpaper paste

Invasive Disease◦ Immuno-deficient patients◦ Immuno-competent patients

Fungus Involvement

Biofilm formation Recalcitrant 40% of patients with refractory CRS

Fungal Associated Bacterial Infections

Biofilm

The “Slug”

DNA Analysis

Several immunodeficiency states have been documented in patients with chronic sinusitis.

Common immuno-deficiencies identified include: IgA and IgG abnormalities and IgG functional response to polysaccharide vaccines.

Chee L, Graham SM, Carothers DG, et al. Immune dysfunction in refractory sinusitis in a tertiary care setting. Laryngoscope. 2001;111:233-235.

Immunodeficiency and Sinusitis

28 year old female with recurrent chronic sinusitis.

Long standing history of respiratory tract infections since her teen years.

Diagnosed with bacterial pneumonia twice in the past 5 years.

Case Study #1

Case Study #1

Case Study #1

A French national survey found that 36% of the patients with CVID had chronic sinusitis.

Another study revealed that patients with chronic sinusitis that were refractory to medical and surgical therapy: 10% had CVID and 6% had IgA deficiency.

11% of patients that fail medical therapy and are undergoing sinus surgery have specific antibody deficiency.

Chee L, Graham SM, Carothers DG, et al. Immune dysfunction in refractory sinusitis in a tertiary care setting. Laryngoscope. 2001;111:233-235.Oksenhendler E, Gérard L, Fieschi C, et al. Infections in 252 patients with common variable immunodeficiency. Clin InfectDis. 2008;46:1547-1554.Carr TF, Koterba AP, Chandra R, et al. Characterization of specific antibody deficiency in adults with medically refractory chronic rhinosinusitis. Am J Rhinol Allergy. 2011;25:241-244.

Gammaglobulin Deficiencies and Chronic Sinusitis

30-68% of patients with HIV are affected by chronic sinusitis due to T-Cell number and function.

Zurlo JJ, Feuerstein IM, Lebovics R, et al. Sinusitis in HIV-1 infection. Am J Med. 1992;93:157-162.

T-Cell deficiency and Chronic Sinusitis

40 year old female diagnosed with HIV 10 years ago and was not on anti-retroviral therapy.

Long standing history of recurrent sinusitis. Recently started on HAART. Sinus symptoms have improved.

Case Study #2

IgG subclasses should not be checked routinely in immunodeficiency evaluation as the connection of IgG subclass deficiency to recurrent or CRS is controversial, and the clinical significance of abnormal IgG subclasses in patients with recurrent infections is unclear.

Clinical Practice Guideline (Update): Adult Sinusitis Executive SummaryRichard M. Rosenfeld, MD, MPH1, Jay F. Piccirillo, MD2, Sujana S. Chandrasekhar, MD3, Itzhak Brook, MD, MSc4, Kaparaboyna Ashok Kumar, MD, FRCS5, Maggie Kramper, RN, FNP6, Richard R. Orlandi, MD7, James N. Palmer, MD8, Zara M. Patel, MD9, Anju Peters, MD10, Sandra A. Walsh11, and Maureen D. Corrigan12 Otolaryngology– Head and Neck Surgery 2015, Vol. 152(4) 598–609 © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0194599815574247 http://otojournal.org

IgG Subclass Controversy

Clinical correlation must be considered when diagnosing CVID.

Clinical Correlation: To Treat or Not to Treat

66 year old female who meets all criteria for CVID.

No history of recurrent sinusitis or respiratory tract infections.

Question, Treat or not to treat?

Case Study #3

Case Study #3

Case Study #3

Answer: No!!

Monitor every 6 months.

Cont. Case Study #3

Antibiotic Utilization

45 year old male diagnosed with CVID 6 years ago.

Prior to CVID diagnosis patient received antibiotic therapy for recurrent sinusitis 8 times a year.

Since starting IVIg therapy 6 years ago he has only taken antibiotics twice for sinus infections.

Case Study #4

1. Sinusitis is one of the most common chronic conditions in the United States requiring antibiotic therapy.

2. Direct and indirect cost are substantial.3. Conservative estimates are that at least

10% of patients with chronic sinusitis have a variation of gammaglobulin deficiency. (Probably Higher)

Conclusion

4. Approximately 40% of patients with T-cell dysfunction have sinus issues.

5. In the era of antibiotic stewardship it is important to minimize antibiotic resistance by decreasing the use of antibiotics. Treating underlining immuno-deficiencies improves antibiotic utilization.

Conclusion Cont.

Thank you!!