Treatment of Chronic Atopy and Irritable Bowel Syndrome in a 7-year-old: A Case Report

Abstract

Irritable bowel syndrome and atopic conditions can co-occur in children and appear to be associated with alterations in the gut microbiota and immune function. A 7-y-old girl was frequently sent home from school due to symptoms related to her long-standing urticaria and gastrointestinal complaints. She was evaluated by pediatric gastroenterologists and allergists; however, she did not respond to treatment. The successful approach to this patient’s treatment included dietary modifications and probiotics guided by clinical insight gleaned from often-overlooked diagnostic biomarkers.

Irritable bowel syndrome (IBS) and atopic conditions, when present in children, can affect school performance, social function, and quality of life, which, in turn, can impart a time and cost burden on parents.^1,2 IBS and atopy may be interrelated through alterations in the gut microbiota and immune function.^3,8 Therapeutic options include medications, cognitive behavioral therapy, hypnotherapy, probiotics, and dietary and lifestyle modifications.^9-12 Although no single effective intervention has emerged from clinical trials, select laboratory testing may guide treatment of conditions underlying IBS symptomology.⁹ In this case, a 7-year-old girl presents with a long-standing history of atopy and gastrointestinal complaints. The identification of abnormal specialty diagnostic biomarkers guided treatment.

Case Presentation

This 7-year-old female of European and Lebanese descent was first seen in December 2013 (Figure 1). Her chief complaints were intermittent, diffuse urticaria and gastrointestinal symptoms. She was frequently sent home from school—sometimes weekly. The patient’s parents had taken her to multiple specialists—pediatricians, gastroenterologists, and allergists. At 4 years of age, she was seen by a pediatric gastroenterologist at Boston Children’s Hospital and had a normal endoscopic evaluation. She was, however, started on a proton pump inhibitor (omeprazole). She had no reduction of symptoms while on the medication. Repeat allergy testing by multiple allergy specialists was also normal.

Her medical history was significant for urticaria, atopic dermatitis, exercise-induced asthma, and aphthous stomatitis that began in early childhood. She experienced nausea and severe gastrointestinal pain daily with frequent excess gas, diarrhea, and constipation. She had a family history of gastrointestinal complaints and autoimmune diseases.

The patient was on multiple medications before her first appointment with an internist with expertise in functional medicine. These included a proton pump inhibitor, diphenhydramine (prn), albuterol inhaler for exercise-induced asthma, and montelukast for seasonal allergies.

Timeline.

Diagnostic Assessment

A nutritional evaluation assessed amino acids via a first-morning void urine sample (NutrEval FMV Amino Acids, Genova Diagnostics, Asheville, NC). Immunoglobulin E (IgE) and immunoglobulin G (IgG) food antibody assessments (Genova Diagnostics) and a comprehensive fecal biomarker evaluation (GI Effects Comprehensive Stool Profile, Genova Diagnostics) were ordered at the initial visit in December 2013 to assess the patient’s immune and gastrointestinal function that may have contributed to her symptoms.

Abnormal biomarkers are highlighted in Tables 1 and 2 revealing multiple abnormalities associated with inflammation, poor assimilation of nutrients, and a gastrointestinal microbe imbalance. It was determined this patient might benefit from changes in her diet and dietary supplementation. This patient was diagnosed with urticaria and irritable bowel syndrome-mixed subtype (IBS-M) at her second visit.

Table 1.

NutrEval FMV Amino Acids

Biomarker Abnormalities	Concentration (mmol/mol creatinine)	Reference Range
Gastrointestinal Imbalance Markers
Dihydroxyphenylpropionic Acid	14.9	≤7.0
3-Hydroxyphenylacetic Acid	10.5	≤9.2
Arabinose	210	≤132
Tartaric Acid	56	≤20
Cellular & Mitochondrial Metabolites
Lactic Acid	20.5	3.7 to 14.6
Pyruvic Acid	61	12 to 39
α-Ketoglutaric Acid	83	12 to 55
Malic Acid	3.3	≤2.7
Neurotransmitter Metabolites
5-OH-Indole Acetic Acid	48.1	6.4 to 24.3
Kynurenic Acid	9.6	≤9.2
Quinolinic Acid	15.2	≤11.6
Vitamin Markers
α-Ketoadipic Acid	2.5	≤2.1
α-Ketoisovaleric Acid	1.46	≤0.85
α-Ketoisocaproic Acid	1.23	≤0.91
α-Keto-β-Methylvaleric Acid	2.8	≤2.3
Glutaric Acid	1.02	≤0.92
Methylmalonic Acid	2.7	≤2.2
Xanthurenic Acid	1.5	≤1.07
3-Hydroxypropionic Acid	26	6 to 23
3-Hydroxyisovaleric Acid	47	≤38
Toxin & Detoxification Markers
α-Ketophenylacetic Acid	0.52	≤0.50
α-Hydroxyisobutyric Acid	12.7	≤8.7
Orotic Acid	1.74	0.38 to 0.91

Abbreviations: IgG, immunoglobulin G;

IgE, immunoglobulin E; FAA, food antibody assessment;

GI, gastrointestinal; SCFAs, short-chain fatty acids;

LCFA, long-chain fatty acid.

Table 2.

IgG and IgE FAA and GI Effects (12/2013)

Diagnostic Test	Date	Biomarker Abnormalities	Diagnostic Significance	Diagnoses	Interventions
IgE FAA	12/23/2013	High total IgE levels (211, RR: ≤87.0 IU/mL)	Unclear	No food, mold, or inhalant allergies
IgG FAA	12/23/2013	Normal	Normal testing	No food sensitivities
GI Effects	01/23/2014	Low levels of beneficial bacteria High putrefactive SCFAs High LCFA and total fat levels	Maldigestion & malabsorption Impaired nutrient production Impaired immune function	Gut microflora disturbances	Gluten-free diet Dairy-free diet Avoid acidic foods Increase green leafy vegetable intake Probiotics Vitamin D3 Multivitamin
		Low acetate	Altered gut microbiota
		High lactoferrin	Inflammation

Abbreviations: IgG, immunoglobulin G; IgE, immunoglobulin E; FAA, food antibody assessment; GI, gastrointestinal; SCFAs, short-chain fatty acids; LCFA, long-chain fatty acid.

Therapeutic Interventions

The patient was recommended to follow a gluten-free and dairy-free diet and avoid other potentially aggravating foods at her first visit in December of 2013.

In February 2014, the patient reported that she continued to experience urticaria and had been sent home from school on several occasions. Repeat allergy testing was unremarkable. At home, the patient adhered to a gluten-free and dairy-free diet. Based on the results from the diagnostic evaluations (Tables 1 and 2), the patient was recommended liquid Vitamin D₃ 4000 IU QD, a multivitamin BID, and Aloe vera. The patient was also recommended a probiotic powder (VSL No. 3) 225 billion CFU, PO, QD, containing the following: Streptococcus thermophiles; Bifidobacterium breve and B lactis; and Lactobacillus acidophilus, L plantarum, L paracasei, and L helveticus. The patient and her family received physician counseling on the importance of nutrition and lifestyle. She was encouraged to increase vegetable consumption, including green leafy vegetables. The proton pump inhibitor (omeprazole) and rescue inhaler (albuterol) were discontinued. The patient declined the recommended Aloe vera.

Follow-up and Outcomes

In April 2014, the girl reported dramatic improvements with no episodes of hives or abdominal pain. The mother adjusted dosing of the probiotic (between 100 and 225 billion CFU) and vitamin D₃ (2000-4000 IU) with the improvement in symptoms. The patient continued to follow a gluten and dairy-free diet at home. She experienced symptoms only when not adherent to her treatment recommendations.

Continued improvement was noted at her June 2014 visit and 1 year later, in June 2015. She continues to take the probiotic, vitamin D₃, and multivitamin. Follow-up testing was attempted, but the patient had vasovagal syncope episodes. The mother believed the rare urticaria and gastrointestinal symptoms to be associated with consuming high-sugar foods.

Discussion

Laboratory testing revealed that the patient had low levels of beneficial bacteria. Increasing evidence demonstrates a relationship between an altered gut microbiota, immune function, inflammation, and the development of atopic disease.^3-5,8,13 This complex interplay should be considered when treating allergic conditions and IBS, one of the most common gastrointestinal disorders.⁶

This patient’s improvement in her atopic and IBS symptoms coincided with reducing gluten and dairy from her diet and adding a probiotic, vitamin D₃, and a multivitamin. Low-FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) diets and low LFSD (low fermentable substrate diet) have been shown to be helpful in alleviating IBS-related symptoms.^14,15 Randomized controlled trials have shown an association of Lactobacillus rhamnosus, L brevis, and a probiotic mixture containing Bifidobacterium infantis, B breve, and B longum with a reduction or resolution of pain, decreased pain frequency, and improved quality of life in children with IBS.^10,16-19 The growing importance of the gut microbiota in a variety of conditions raises questions regarding the role of probiotics in treatment.²⁰ It is possible the dietary changes and the probiotic supported the improvements in this patient’s symptoms.

Despite previous assessments from other providers including gastroenterologists and allergists, no effective treatment had been identified. Evaluation of this patient’s complex and recurrent symptoms and the identification of laboratory biomarker abnormalities supported this patient’s diagnosis of urticaria and IBS-M.

Some limitations noted in this case report include not testing for calprotectin and C-reactive protein (CRP) levels (higher calprotectin and CRP levels occur in patients with inflammatory bowel disease as opposed to IBS).^21,22 Testing for interleukin 10 and interleukin 12 and transforming growth factor-β may have also informed understanding of the inflammatory profile of the patient and supported diagnosis.^7,23 Children with IBS have a 4 times higher risk of having celiac disease than children without IBS, which may have explained her symptomology; however, she tested negative for celiac disease.²⁴ Nonceliac gluten sensitivity may have also been a possible diagnosis, but because symptom resolution seemed to better correlate with limiting sugar intake as opposed to gluten, it is unlikely.²⁵ The multifaceted interventions make it difficult to draw conclusions about the effectiveness of any one component.

Vlieger et al²⁶ tracked that the prevalence of complementary and alternative medicine (CAM) use was nearly at 40% of children visiting pediatric gasteroenterology clinics in 9 hospitals. Predictors of CAM use were a perceived low effect of or adverse effects from conventional therapy, school absenteeism, and children aged ≤11 years.²⁶ Clinicians and researchers have acknowledged that IBS and atopic conditions are complex, inflammatory processes with heterogeneous etiologies, and that they difficult to treat.^8,9,11

Conclusion

This case suggests a role for laboratory biomarker assessment in the treatment of chronic atopy and IBS-M. In children, this may be important in preventing social disability. This patient was able to control her symptoms and able to regularly attend school with dietary modifications.

Learning Points

• Laboratory biomarker testing can help guide successful treatment of chronic atopy and IBS.

• Chronic atopy and IBS may be comorbidities and should be considered when patients are diagnosed with one of these conditions.

• Dietary interventions can play a role in modifying chronic atopy and IBS.

Patient Perspective

“For many years we had been trying to help our daughter who had hives and stomach aches. Each doctor looked through his or her individual lens, and it seemed to go nowhere and was quite frustrating. Dr Kathy seemed to look at the whole picture beginning with the gut. Through her, we have made major strides in understanding and controlling our daughter’s medical conditions.”

Biographies

Kathleen O’Neil-Smith, MD, FAARM, is owner and chief medical officer at Treat Wellness in Newton, Massachusetts.

Melissa S. Barber, MSc, is a research associate at Integrative Medicine Institute in Portland, Oregon.