CASE REPORT

Chronic Rhinosinusitis and Irritable Bowel Syndrome: A Case Report Mikhail Kogan, MD; Carlos Cuellar Castillo, MS; Melissa S. Barber, MS

Abstract Introduction: Chronic rhinosinusitis (CRS) and irritable bowel syndrome (IBS) can be comorbidities that are difficult to treat. In this patient, an evidenceinformed treatment pathway guided by laboratory biomarkers was used to address both conditions. Case Presentation: A 69-y-old female patient presented with a 50-y history of sinusitis that was worse in the winter, postnasal drip, frequent sore throats, gastrointestinal complaints, headaches, and yeast

Mikhail Kogan, MD, is medical director at George Washington University, G. W. Center for Integrative Medicine, in Washington, DC. Carlos Cuellar Castillo, MS, is a graduate of the physiology master of science program and complementary and alternative medicine at Georgetown University, in Washington, DC. Melissa S. Barber, MS, is at Helfgott Research Institute, National University of Natural Medicine, in Portland, Oregon. Corresponding author: Mikhail Kogan, MD E-mail address: [email protected]

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hronic rhinosinusitis (CRS) and irritable bowel syndrome (IBS) are common in the United States and microbiome alterations are associated with both conditions.1–4 CRS affects approximately 1 in 8 adults in the United States and is often associated with seasonal exacerbations.5 IBS affects approximately 1 in 10 adults in North America and can be associated with pancreatic insufficiency and food sensitivities—two conditions often untreated in primary care.6,7,8 The 2014 “American College of Gastroenterology Monograph on the Management of Irritable Bowel Syndrome and Chronic Idiopathic Constipation” discussed the prevalence and treatments of IBS and the absence of reliable laboratory biomarkers.9 This case demonstrated the use of laboratory biomarkers for pancreatic insufficiency and food sensitivities for treatment of both 44

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infections. Two sinus surgeries (in years 2000 and 2002) and multiple courses of antibiotics had not resolved her sinus symptoms. In addition to CRS and IBS, this patient was noted to have intestinal overgrowth of Candida albicans, multiple food sensitivities, and leaky gut syndrome. Conclusion: Antifungal medication and dietary changes in the course of 8 mo resulted in the resolution of her CRS and IBS.

CRS and IBS. A timeline of the patient’s medical history and course of care is described in Table 1. Patient Information A 69-year-old female patient with a 50-year history of gastrointestinal (GI) and sinus symptoms (worse in the winter) was self-referred to the George Washington Center for Integrative Medicine in February 2011. Ten years earlier, in 2000 and 2002, she had sinus surgery that did not relieve her symptoms. She also experienced frequent fatigue, disturbed sleep, headaches, sore throats, runny nose, and chronic cough, and she had a history of recurrent vaginal and intestinal symptoms consistent with overgrowth of Candida albicans several times per year. Her diet consisted of freshly prepared foods with some sensitivity to cheese and yogurt (which she avoided). Despite osteoarthritis in both knees, she walked 3.5 miles (5.6 km) daily and regularly played tennis. The patient was retired, lived at home with her dog, and had 2 adult children; she reported no known toxic exposures at home. She had previously been diagnosed with ovarian cancer with surgery in 2007 and chemotherapy in 2008, which exacerbated her CRS and IBS symptoms. Patient medications at her initial visit included azithromycin for CRS and vitamin D3 supplementation. She had begun taking a selfprescribed dietary supplement—broccoli seed extract (OncoPLEX ES from Xymogen, Orlando, FL, USA).

Kogan—Chronic Rhinosinusitis and IBS

Table 1. Timeline of Patient’s Medical History and Course of Care Relevant Medical History 50-y history of CRS and multiple GI symptoms consistent with IBS. Previous treatments included antibiotics and 2 unsuccessful sinus surgeries (in years 2000 and 2002). Other health problems included food sensitivities, chronic vaginal and intestinal yeast overgrowth, osteoarthritis, and ovarian cancer (surgery in 2007 and chemotherapy in 2008). Patient Visits

Chief Complaints

− Sinusitis/postnasal drip Visit 1: − Multiple GI 02/2011 symptoms − Osteoarthritis

− Sinusitis/postnasal drip Visit 2: − Multiple GI 03/2011 symptoms − Osteoarthritis − Improving sinusitis/postnasal Visit 3: drip 04/2011 − Improving GI symptoms − Osteoarthritis

− Resolving sinusitis Visit 4: − Resolving GI 07/2011 symptoms − Osteoarthritis

Visit 5: 09/2011 2-y Followup: 03/2013

− CRS and GI symptoms resolved − Osteoarthritis − Sinus and IBS symptoms flare with increased sugar in diet − Osteoarthritis

Laboratory Biomarkers CDSA 2.0: − C albicans: 2+ − Low pancreatic elastase and β-glucuronidase IgG FAA: − Multiple food sensitivities



Diagnostic Significance

− CRS − IBS − Intestinal overgrowth of C albicans − Multiple food sensitivities − Leaky gut syndrome (increased intestinal permeability) − Chronic yeast infection



CDSA 2.0 − C albicans: 0 − Normal pancreatic elastase and β-glucuronidase levels IgG FAA: − Few food sensitivities —



Recommendations and Interventions − Continue azithromycin, vitamin D3, OncoPLEX ES − Begin fish oil, Zyflamend, BCQ, Mushroom Mix, raw garlic, nasal lavage − Stop OncoPLEX ES, Zyflamend, BCQ, Mushroom Mix, raw garlic − Continue fish oil, nasal lavage, azithromycin, vitamin D3 − Begin nystatin; GI Revive; probiotics; yeast-free, antiinflammatory diet − Stop azithromycin − Continue nystatin; GI Revive; probiotics; yeast-free, antiinflammatory diet; fish oil; nasal lavage; vitamin D3 − Begin Zyflamend

− Resolved CRS, overgrowth of C albicans, − Stop nystatin, GI revive, leaky gut Zyflamend syndrome, − Continue probiotics; yeast-free, yeast infection anti-inflammatory diet; fish oil; − Few food nasal lavage; vitamin D3 sensitivities − Resolving IBS —

Continue probiotics; yeast-free, anti-inflammatory diet; fish oil; nasal lavage; vitamin D3

CRS and GI symptoms under Resume (continue) yeast-free, good control with anti-inflammatory diet attention to diet

Abbreviations: CRS, chronic rhinosinusitis; GI, gastrointestinal; IBS, irritable bowel syndrome; CDSA, comprehensive digestive stool analysis; IgG, immunoglobulin G; FAA, F-actin antibody.

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Figure 1. IgG Food Antibody Assessment, February 2011 and July 2011 High

Reactivity

Moderate Low

02/22/2011 07/04/2011

Very Low None Detected 0

20

40 60 Number of Reactive Foods

80

100

Abbreviation: IgG, immunoglobulin G. Clinical Findings Her physical exam was remarkable for boggy turbinates and postnasal drip. Diagnostic Assessment Comprehensive Digestive Stool Analysis (CDSA) 2.0 (Genova Diagnostics, Asheville, NC, USA) revealed potentially pathogenic levels of C albicans and low levels of pancreatic elastase 1 and β-glucuronidase, supporting a diagnosis of dysbiosis (Appendix 1). An IgG Food Antibody Assessment (Genova Diagnostics) revealed moderate to high reactivity to several different foods, indicative of multiple immunoglobulin G (IgG) food sensitivities. Her symptoms were suggestive of leaky gut syndrome (Figure 1; Appendix 1). Her vitamin D level was 28.4 ng/mL (low). She was diagnosed with CRS, IBS, overgrowth of C albicans, multiple food sensitivities, and leaky gut syndrome. Therapeutic Interventions and Follow-up This patient had 5 visits in 8 months and received therapeutic interventions—antifungal medication, nutritional, and dietary supplements—guided by laboratory testing (Table 1 and Table 2). At the third visit (April 2011), the patient was much improved and grains, fruit, and dairy were gradually reintroduced. In June 2011, a repeat stool test showed resolution of C albicans overgrowth and improved pancreatic elastase 1 levels (increase from 121 mg/g to 273 mg/g) and β-glucuronidase levels (increase from 367 U/g to 1475 U/g) (Appendix 1) and the nystatin was discontinued in July 2011. Repeat IgG F-actin antibody 46

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(FAA) results (Figure 1) revealed a nearly 4-fold decrease in the number of highly reactive foods and a 30-fold increase in nonreactive foods—suggestive of normalized intestinal permeability. At her fourth and fifth visits, the patient continued to improve and noted resolution of her CRS and IBS symptoms as well as an increase in energy. In September of 2011, she was instructed to continue with the yeast-free, anti-inflammatory diet, nasal lavage, probiotics, fish oil, and vitamin D3 (Table 1). The patient was seen in March 2013 after noting relapse of some of her CRS and IBS symptoms, which she attributed to increased sugar consumption and dietary indiscretions. She was counseled to continue on the yeastfree, anti-inflammatory diet as much as possible—to which she adhered. Patient Perspective I am a very active person and enjoy playing tennis and gardening. My symptoms prior to coming to George Washington (GW) Center for Integrative Medicine prevented me from participating in the leisure activities that I enjoy. The quality of my sleep and my overall quality of life were not good. After coming to the GW Center for Integrative Medicine all of my symptoms improved and I experienced a drastic improvement in my quality of life. I did not follow an “Elimination Diet” per se, but rather was instructed to follow a diet with foods to avoid based on my testing. I experienced a relapse of my sinus symptoms when I deviated too much from the diet, but am now able to control the symptoms by adjusting my diet accordingly. Kogan—Chronic Rhinosinusitis and IBS

Table 2. Prescribed Interventions in Course of Care Intervention

Information

Rationale

Antifungal Medication Nystatin

1 million units, PO, BID, ×4 mo

CRS, IBS, chronic yeast infections

Dietary Supplements Fish oil supplement

1 teaspoon (4.93 mL) Improve gut function and (Liquid 3:1, EPA:DHA – Genestra) (liquid), PO, QD reduce inflammation

Rosmarinus officinalis, Curcuma longa, Zingiber officinale, 2 capsules, PO, QD, Ocimum sanctum, Camellia sasanqua, Polygonum ×1 mo californicum, Coptis chinensis, Berberis vulgaris, Origanum vulgare, Scutellaria baicalensis (Zyflamend – New Chapter)

CRS, pain

Boswellia serrata, Bromelain, C longa, quercetin 1–3 capsules, PO, (BCQ – Vital Nutrients) BID, ×1 mo

IBS, pain

Mushroom Mix

IBS, leaky gut syndrome

2 capsules, PO, BID, (My Community – Host Defense) ×1 mo

L-Glutamine, N-acetyl glucosamine, citrus pectin, 7.5 g in water, PO, Glycyrrhiza glabra, Aloe barbadensis, Ulmus pumila, QD, ×4 mo mucin, Althea officinalis, Matricaria chamomilla, Abelmoschus esculentus, Uncaria tomentosa, methylsulfonylmethane, quercetin, prune powder, zinc (GI-Revive – Designs for Health)

IBS, leaky gut syndrome

Probiotic: Saccharomyces boulardii lyo 1 capsule, PO, BID, (FloraMyces – Designs for Health) ×6 mo Probiotic: Lactobacillus acidophilus (CUL-60 and CUL1 capsule, PO, BID, 21), Bifidobacterium bifidum (CUL-20), Bifidobacterium ×6 mo animalis subsp. lactis (CUL-34), FOS (HMF Forte – Genestra) Probiotic: Lactobacillus reuteri, Lactobacillus acidophilus, 1 capsule, PO, BID, Lactobacillus casei, Lactobacillus paracasei, Lactobacillus ×2 mo salivarius, Lactobacillus brevis, Lactobacillus plantarum, Streptococcus tigurinus, Bifidobacterium bifidum, Bifidobacterium longum, Bifidobacterium bifidum (Therabiotic Complete – Klaire Labs)

IBS, leaky gut syndrome

Lifestyle Nasal lavage (Neti Pot)

BID

CRS

Yeast-free, anti-inflammatory diet (See Appendix 2)

Avoid sugar 2–4 wk; grains, fruit, dairy gradually reintroduced

IBS, CRS

Abbreviations: PO, by mouth; BID, twice per day; CRS, chronic rhinosinusitis; IBS, irritable bowel syndrome; EPA, eicosapentaenoic acid; DHA, docosahexaenoic acid; QD, every day; FOS, fructooligosaccharides.

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Discussion and Limitations CRS- and IBS-related symptoms are commonly reported complaints by patients.5,6 A recent case-controlled study of 133 subjects found a statistically significant association between CRS and IBS (odds ratio [OR] = 17.8; 95% confidence interval [CI] = 4.9 to 64.2; P < .001).2 When CRS has been present for 50 years, it is difficult to treat— particularly in a patient with a history of unsuccessful sinus surgeries and antibiotic use. Smith et al10 estimated direct and indirect costs for CRS in the United States at more than $20 billion in 2014. In addition to sinus surgery and antibiotics, the medical management of CRS commonly includes steroids and nasal lavage with saline.11 More than 1 in 5 antibiotic prescriptions are for treating acute and chronic rhinosinusitis.12 Antibiotics often provide little benefit, contribute to the occurrence of adverse events, alter the microbiome, and contribute to antibiotic resistance.13,14 Dietary supplements and nutritional recommendations have some evidence in treating CRS15—long-chain polyunsaturated fatty acids (LCPUFAs) may be helpful to patients with CRS that are refractory to treatment with antibiotics.16,17 Such LCPUFAs include docosahexaenoic acid (DHA) and arachidonic acid (ARA), found in fish oil or DHA/ARA-enriched foods. IBS is both prevalent and costly with the annual cost burden of IBS estimated at more than $20 billion.6 IBS may be associated with exocrine pancreatic insufficiency and overgrowth of C albicans.7,18 Although Candida is part of a normal gut microbiome, increased levels may be associated with inflammation of the GI tract.18 Food sensitivities associated with food-specific IgG antibodies and IBS have been shown to have a response to elimination diets.19 Dietary changes, such as a low FODMAP diet or an IBS-specific diet, have also been shown to reduce IBS symptoms and food sensitivities and to improve nutritional status.20,21 A multistrain probiotic has been shown to improve the symptom severity of IBS and quality of life scores after 8 weeks in patients with IBS.19 A single case using an individualized approach with multiple interventions may have limited applicability to a broader population of patients. This patient’s IBS was diagnosed based on the patient’s self-reported symptoms without using the Rome criteria or a validated IBS quality of life scale. However, this case demonstrates that specific laboratory biomarkers can guide individualized treatment. In this case, addressing biomarker imbalance associated with pancreatic insufficiency and food sensitivities may have led to the resolution of CRS and IBS in this patient. Conclusion This case reports presents a cost-effective, successful treatment of a patient with chronic CRS and IBS using laboratory biomarkers to guide treatment that included dietary recommendations, antifungal medication, and nutritional supplements. Structured stool and IgG testing reduced the overall cost of diagnosis and guided 48

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management of this patient. The testing linked laboratory biomarker abnormalities with therapeutic interventions and outcomes, strengthening the association of specific laboratory biomarkers abnormalities and the diagnosis of IBS and CRS. This case offers testable hypotheses for future research to evaluate the effect of structured stool testing and IgG antibody testing to guide therapeutic interventions and improve patient outcomes. Acknowledgements

This case report was prepared according to the CARE guidelines. Genova Diagnostics provided an unrestricted medical writing grant to assist with the preparation of this manuscript.

Author Disclosure Statement

Written consent was obtained from the patient for publication of this case report. A copy of the written consent is available for review.

References

1. Lam K, Schleimer R, Kern RC. The etiology and pathogenesis of chronic rhinosinusitis: A review of current hypotheses. Curr Allergy Asthma Rep. 2015;15(7):41. 2. Darweesh M. PWE-240  Relationship between irritable bowel syndrome and chronic rhinosinusitis: A case control study. Gut. 2015;64(Suppl 1):A317.2-A318. 3. Salonen A, De Vos WM, Palva A. Gastrointestinal microbiota in irritable bowel syndrome: Present state and perspectives. Microbiology. 2010;156(11):3205-3215. 4. Carroll IM, Ringel-Kulka T, Siddle JP, Ringel Y. Alterations in composition and diversity of the intestinal microbiota in patients with diarrheapredominant irritable bowel syndrome. Neurogastroenterol Motil. 2012;24(6):521-530. 5. Blackwell DL, Lucas JW, Clarke TC. Summary health statistics for U.S. adults: National health interview survey, 2012. Vital Health Stat 10. February 2014;260:1-161. 6. Brandt LJ, Chey WD, Foxx-Orenstein AE, et al. An evidence-based position statement on the management of irritable bowel syndrome. Am J Gastroenterol. 2009;104(Suppl 1):S1-S35. 7. Leeds JS, Hopper AD, Sidhu R, et al. Some patients with irritable bowel syndrome may have exocrine pancreatic insufficiency. Clin Gastroenterol Hepatol. 2010;8(5):433-438. 8. Yang C, Li Y. The therapeutic effects of eliminating allergic foods according to food-specific IgG antibodies in irritable bowel syndrome. Zhonghua nei ke za zhi. 2007;46(8):641-643. 9. Ford AC, Moayyedi P, Lacy BE, et al. American College of Gastroenterology Monograph on the management of irritable bowel syndrome and chronic idiopathic constipation. Am J Gastroenterol. 2014;109(S1):S2-S26. 10. Smith KA, Orlandi RR, Rudmik L. Cost of adult chronic rhinosinusitis: A systematic review. Laryngoscope. 2015;125(7):1547-1556. 11. Hamilos DL. Chronic rhinosinusitis: Epidemiology and medical management. J Allergy Clin Immunol. 2011;128(4):693-707. 12. Anon JB, Jacobs MR, Poole MD, et al. Antimicrobial treatment guidelines for acute bacterial rhinosinusitis. Otolaryngol Head Neck Surg. 2004;130(Suppl 1):1-45. 13. Small CB, Bachert C, Lund VJ, Moscatello A, Nayak AS, Berger WE. Judicious antibiotic use and intranasal corticosteroids in acute rhinosinusitis. Am J Med. 2007;120(4):289-294. 14. Piromchai P, Thanaviratananich S, Laopaiboon M. Cochrane Database of Systematic Reviews. Chichester, UK: John Wiley & Sons, Ltd; 1996. 15. Taw MB, Nguyen CT, Wang MB. Complementary and integrative treatments: Rhinosinusitis. Otolaryngol Clin North Am. 2013;46(3):345-366. 16. Birch EE, Khoury JC, Berseth CL, et al. The impact of early nutrition on incidence of allergic manifestations and common respiratory illnesses in children. J Pediatr. 2010;156(6):902-906. 17. Linday LA, Dolitsky JN, Shindledecker RD. Nutritional supplements as adjunctive therapy for children with chronic/recurrent sinusitis: Pilot research. Int J Pediatr Otorhinolaryngol. 2004;68(6):785-793. 18. Kumamoto CA. Inflammation and gastrointestinal Candida colonization. Curr Opin Microbiol. 2011;14(4):386-391. 19. Williams E, Stimpson J, Wang D, et al. Clinical trial: Multistrain probiotic preparation significantly reduces symptoms of irritable bowel syndrome in a double-blind placebo-controlled study. Aliment Pharmacol Ther. 2008;29:97-103. 20. Bohn L, Storsrud S, Liljebo T, et al. Diet low in FODMAPs reduces symptoms of irritable bowel syndrome as well as traditional dietary advice: A randomized controlled trial. Gastroenterology. 2015;149(6):1399-1407. 21. Yoon SR, Lee JH, Lee JH, et al. Low-FODMAP formula improves diarrhea and nutritional status in hospitalized patients receiving enteral nutrition: A randomized, multicenter, double-blind clinical trial. Nutr J. 2015;14(1):116.

Kogan—Chronic Rhinosinusitis and IBS

Appendix 1. CDSA 2.0 Results Prior to Treatment in February of 2011 and During Treatment in July of 2011 Analyte Pancreatic elastase 1 Putrefactive SCFAs

Eosinophil protein X Calprotectin

Analyte

Analyte Beneficial SCFASs (total) n-butyrate pH β-glucuronidase Secondary Bile Acids LCA DCA LCA/DCA ratio

Digestion/Absorption 02/25/2011 121 3.0 Gut Immunology 02/25/2011

Chronic Rhinosinusitis and Irritable Bowel Syndrome: A Case Report.

Chronic rhinosinusitis (CRS) and irritable bowel syndrome (IBS) can be comorbidities that are difficult to treat. In this patient, an evidence-informe...
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