Intractable Anaphylaxis and Eczema in a 21-month-old Child

TREATING CLINICIAN: Joe Mather, MD, MPH&TM

Patient Info:

• John Michael, 21 months, male
• Intractable and regular episodes of anaphylaxis, not responsive to antihistamines, topical and systemic steroids, and extremely restricted diet
• Severe eczema
• History of multiple severe respiratory infections (Parainfluenza, RSV)

Phone Call Prior to First Visit

History

• John Michael’s (JM) mother described an unending series of frustrating visits with multiple physicians who had been unable to diagnose or help. Immediately after eating he regularly experienced suffering with hives, redness around mouth, swollen eyes, itching, diarrhea.
  • “My son, John Michael, has severe eczema that will not clear up ever. He is limited to eating about five foods right now. Our allergist just keeps increasing the antihistamine dosage and adding more creams and steroids. All of which do not help and seem to add to his problem. I suspect mast cell activation and/or oral allergy syndrome.”
• “Just before this began, John Michael had his lip and tongue-tie clipped. He had a hospital stay for croup. And we moved into a new house.”
  • Before seeing JM, I expressed my concern that he was likely being exposed to mold or heavy metals. I recommend Dr. Nathan’s book Toxic, and suggested that the family obtain an ERMI and hire a mold inspector.
• Mother’s goal for treatment: “For John Michael to be able to eat regular foods (fruits and veggies) without me having to sit next to him with Benadryl or an EpiPen.”

Medications

• “We have weaned off of all medications and prescription creams unless there is an emergency anaphylactic reaction. Too many side effects—- rashes, burning, hives, itching, diarrhea, headaches.”
  

Visit 1 (Day 1) – History and Exam:

Initial Impression:

• JM was quite miserable.
• He was being fed a GF and DF diet and reacting to nearly everything: “Eggs, peanuts, dairy, soy, most fresh fruits, and some vegetables.” He was only sleeping 8-10 hours of fitful sleep with frequent nighttime awakenings. He was also quite sensitive to his environment: “He does break out in hives when bathing or the two times in a pool.”
• The family is using well water.

Previous Testing:

• Home ERMI (Environmental Relative Moldiness Index) was done – quite high at 9.5.
• “My husband is currently ripping out the insulation under our house which was hiding the mold underneath our flooring, and the mold remediation guy is coming tomorrow.”
  • Mold is hard to find, and tests can be misleading. Air traps can only catch airborne spores, which have weight and fall to the floor. Often air traps give a negative report because the mold is under the floor, behind a cabinet, or in the wall cavity.

Family History:

• Lupus, RA, vasculitis, Sjögrens

Medical History:

• Premature birth and NICU stay
• RSV
• Croup

Visit 2 (a few days later) – Testing and Initial Recommendations

Testing:

• Tests ordered
  • Comprehensive Drinking Water analysis from Doctor’s Data
  • Mycotoxin Urine Test from RealTime Laboratories
  • Urinary Heavy Metals from Doctor’s Data
• Rationale
  • JM’s troubles began after a move to a new home. This history points to environmental toxin exposure.

Recommendations:

• Diet:
  • Add one vegetable to JM’s diet
• GI:
  • Lacto/Bifido Blend – ¼ cap daily
  • Saccharomyces Boulardii – ¼ capsule daily
• Environment:
  • Continue home remediation. Make sure that mold is completely eliminated from your house.

Visit 3 – 1 Week Later

Subjective Assessment:

• “John Michael has had a great week. Skin is clearest it’s been in a long time. He ate a couple bites of refried beans and rice. He slept last night. “

Recommendations:

• Continue to slowly add vegetables, legumes, and fruit to JM’s diet

Visit 4 - 4 Weeks Later

Subjective Assessment:

• “So many people have commented on how good he looks! Doing so much better!!!”
• Diet: “unbelievable, huge change!”
  • Eating: organic chicken breast, miracle noodles (shirataki), sweet potatoes, brown rice cereal, GF fig bar, rice cakes
    • Recently added pork, cauliflower, broccoli, squash, sweet peas, bananas, golden delicious apples, blueberries, and pears without reaction
    • Still reacting to white potatoes
• Environment:
  • AC system cleaned, changing out floors
  • Some mildew by one of the doors
  • “2nd dust test came back clean.”
• Review of Symptoms:
  • No more runny stools
  • Food reactions diminishing
  • Skin clearing up
    

Lab Interpretation:

• RealTime Lab Mycotoxin Testing
  • Aflatoxin: 1.24
  • Glio: 0.34 – (0.3 was the old cut-off for positivity on this test. Some clinicians consider any amount of 0.3 positive)
• Doctor’s Data Heavy Metals
  • Elevated levels of arsenic, lead, and mercury

Recommendations:

• “I’m going to want J.M. to start on three binders: chlorella, bentonite clay, and charcoal. We will use very small doses, so powder or liquid forms are preferred. Please buy the below binders so that we can start them shortly. You may also want to buy a specialty set of measuring spoons that gives you 1/32 tsp and 1/16 tsp so that we can accurately get small doses.”
  • Start with 1/32 of bentonite clay. If he does well with this, then increase to 1/16 tsp.
  • After a week, if he tolerates the clay without issues, then repeat the same process with the charcoal.
  • After a week, if he tolerates the charcoal without issues, then repeat the same process with the chlorella.

Visit 5 - 6 Weeks Later

Subjective Assessment:

• “Skin looks great, every now and then a small breakout, but so much better, looks completely normal most days. He has added quite a bit of vegetables, still having trouble with most fruits which are causing rashes.”
  • Diarrhea has resolved, having normal stools.
  • She suspects that J.M is gaining weight. He is sleeping well.
• Environment:
  • Remediation ongoing: Mold on outside underneath the house in the subfloor. Some areas of the floor were pulled up, an ERMI test of those specific areas was performed.  It was negative.
• Binders:
  • Tolerating without reaction 1/16 tsp Bentonite Clay, 1/32 tsp activated charcoal. Chlorella pending.

Doctor’s Data Comprehensive Drinking Water Analysis

• Elevated arsenic and lead in home’s well water

Recommendations:

• Increase each of the binders from 1/32 tsp to 1/16 as we discussed.
• To help him excrete heavy metals – start with 1/8 tsp modified citrus pectin mixed in water or juice daily, then slowly increase up to 1/2 tsp twice daily as tolerated. Make sure that he is drinking plenty of water to help him detoxify!
• Plan to follow up after he’s been on all three binders for 2-3 weeks.

Visit 6 - 10 Weeks Later

Subjective Assessment:

• Broke out in a rash on his legs
• Diet:
  • “Eating non-stop, appetite is ridiculous. Still GF/DF.”
  • Tried dairy 2 weeks ago – diarrhea and a rash.
• Meds:
  • No Zyrtec x 2 days, decreased hydroxyzine to 2.5
• Binders:
  • Bumped charcoal, bentonite clay to 1/4 tsp and chlorella to 1/8 tsp

Impression:

• Due to JM’s rapid improvement, Mom began giving him slightly more binders than he was able to tolerate. Most mycotoxin binders do not actually “bind,” but adsorb to toxins. This means that the toxins can break away from the binder. In practice, increasing doses of binders means that more toxin will be bound and excreted in the stool but at the cost of some extra toxin being mobilized in the system. This is why dose adjustments should go slowly and it is critical to have patients monitor for side effects when increasing doses of binders. I advise never pushing through these symptoms and instead to lower the dose of binders to the dose that doesn’t cause issues.

Recommendations:

• Please decrease all binders to 1/8 tsp (chlorella, clay, charcoal).
• Keep the modified citrus pectin powder at 1/2 tsp daily.
• Send an update in 1-2 days after he has been on the lower dose of binders.
• Following this, I will have you slowly add Nystatin and a nasal spray.
  • I use a nystatin suspension initially so that we can titrate the dose easily. He was started on Nystatin to address the high likelihood of candida. This occurs at a high rate with mold toxicity. Using nystatin prior to introducing antifungals like itraconazole reduces the incidence of die-off.
  • I also tend to start addressing nasal colonization early with silver hydrosol spray, which is very well tolerated.

Visit 7 - 14 Weeks Later

Subjective Assessment:

• JM is doing well. “Trucking along – he hasn’t had Zyrtec in a couple of weeks. Nystatin now up to 1/2 BID. Mild skin dryness being managed with moisturizing. He seems to be doing fine with the added nystatin and nasal spray. He has had a few breakouts, but he continues to eat his teenage siblings’ leftovers from the garage (french fries and pizza crust are his favorite finds!)”

Follow-Up Doctor’s Data Urinary Heavy Metals:

• “Slow improvement in overall heavy metal levels, with the arsenic dropping from 100 to 74, but still with high levels arsenic, cesium, lead, and thallium.”

Recommendations:

• Increase modified citrus pectin to ½ tsp twice daily.
• Add soil-based probiotic – Start with 1/4 capsule daily, then slowly increase to 1 capsule daily as tolerated.
• Repeat RTL Urinary Mycotoxin Test.

Clinician’s Comments:

• JM has done great. As his new full head of hair shows, he is growing nicely and back on track to develop into a healthy young man. He has been free of anaphylaxis, has greatly expanded his diet, sleeps well, no longer suffers with eczema, and has been able to take less medication.
• Completely detoxifying from mold is a long-term process, but the clinical change when a sensitive individual is removed from toxic mold is often remarkable. JM’s progress began as soon as the mold in his home was addressed. This underscores how essential it is for patients to take remediation and mold exposure seriously.
• Those of my patients who are unable or unwilling to remediate their environment can be made somewhat better (10-15% improvement) with a lot of effort (intense focus on diet and lifestyle, limbic retraining, binders, MCAS support, and antifungals) but they fail to get their health back in a meaningful way such as we see here.
• Now that JM is tolerating binders and the basic anti-infective treatments of nystatin and silver, the next step will either be widening his daily binders, moving to specific antifungals such as itraconazole or amphotericin B, or both. We are waiting on a repeat mycotoxin test to help guide this decision.
• Regarding expanding binders, most of my patients do best when they are able to include either cholestyramine or colesevelam, and either of these medications will likely be added to his program to be taken with the other binders.
• Saccharomyces boulardii is a binder for gliotoxin, zearalenone, and aflatoxin. As you will learn later in this newsletter, probiotics function as mycotoxin binders. I suspect that the early and gentle use of a lacto/bifido and saccharomyces probiotic helped reduce the toxin burden on his gut and helped him begin to tolerate a large number of foods that previously caused anaphylaxis.

The Role of Modified Citrus Pectin as an Effective Chelator of Lead in Children Hospitalized with Toxic Lead Levels

PMID 18616067

Study Purpose

• Lead toxicity is an ongoing concern worldwide, and children, the most vulnerable to the long-lasting effects of lead exposure, are in urgent need of a safe and effective heavy metal chelating agent to overcome the heavy metals and lead exposure challenges they face day-to-day.

Intervention

• Hospitalized children with a blood serum level greater than 20 microg/dL, as measured by graphite furnace atomic absorption spectrometry (GFAAS), who had not received any form of chelating and/or detoxification medication for 3 months prior were given 15 g of modified citrus pectin (MCP) (PectaSol) in 3 divided doses a day. Blood serum and 24-hour urine excretion collection GFAAS analysis were performed on day 0, day 14, day 21, and day 28.

Main Results

• This study showed a dramatic decrease in blood serum levels of lead (P = .0016; 161% average change) and a dramatic increase in 24-hour urine collection (P = .0007; 132% average change).

Authors Conclusion

• The need for a gentle, safe, heavy metal-chelating agent, especially for children with high environmental chronic exposure, is great. The dramatic results and no observed adverse effects in this pilot study along with previous reports of the safe and effective use of MCP in adults indicate that MCP could be such an agent. Further studies to confirm its benefits are justified.

Clinical Takeaways

• The dose of MCP used in this study was equivalent to 1 scoop of PectaSol-C three times daily for 3 months. In my practice, treating adults with 1 scoop twice daily for 45 – 90 days has been effective at lowering serum lead levels.

The Effect of Modified Citrus Pectin on Urinary Excretion of Toxic Elements

PMID-16835878

Study Purpose

• This study was undertaken to evaluate the effect of modified citrus pectin (MCP) on the urinary excretion of toxic elements in healthy individuals.

Intervention

• Subjects ingested 15 g of MCP (PectaSol, EcoNugenics Inc., Santa Rosa, California 95407) each day for 5 days and 20 g on day 6. Twenty-four hour urine samples were collected on day 1 and day 6 for comparison with baseline. The urine samples were analyzed for toxic and essential elements.

Main Results

• In the first 24 h of MCP administration, the urinary excretion of arsenic increased significantly (130%, p < 0.05). On day 6, urinary excretion was increased significantly for cadmium (150%, p < 0.05). In addition, lead showed a dramatic increase in excretion (560%, p < 0.08).

Authors Conclusion

• This pilot trial provides the first evidence that oral administration of MCP increases significantly the urinary excretion of toxic metals in subjects with a ‘normal’ body load of metals. It is suggested that systemic chelation of toxic metals by MCP may in part be attributable to the presence of rhamnogalacturonan II, which has been shown previously to chelate metals.

Interesting Notes

• MCP has the ability to selectively bind problematic heavy metals:
  • Urinary excretion of lead increased by 230%, mercury increased by 150%, cadmium 150%, and arsenic 130%.
  • At the same time, no significant changes in the excretion of calcium, magnesium, zinc, selenium, or iron were seen.
• Patients with mycotoxicity often cannot tolerate even small doses of MCP. I suspect that this fiber also binds mycotoxins.

Binding Rather Than Metabolism May Explain the Interaction of Two Food-Grade Lactobacillus Strains with Zearalenone and Its Derivative a-Zearalenol

PMID – 12089040

Study Purpose

• The interaction between two Fusarium mycotoxins, zearalenone (ZEN), and its derivative alpha-zearalenol, with two food-grade strains of Lactobacillus was investigated.
• Zearalenone is an estrogenic mycotoxin produced by the mold Fusarium. It can be detected clinically using either the RealTime or Great Plains Urinary Mycotoxin tests.

Rational

• The co-occurrence of ZEN and trichothecenes in contaminated corn has been correlated with the incidence of human esophageal cancer in China (8).

Intervention

• The mycotoxins were incubated with either Lactobacillus rhamnosus strain GG or L. rhamnosus strain LC705.

Main Results

• Both heat-treated and acid-treated bacteria were capable of removing the toxins, indicating that binding, not metabolism, is the mechanism by which the toxins are removed from the media. Binding was a rapid reaction: approximately 55% of the toxins were bound instantly after mixing with the bacteria.
• “The ability of both Lactobacillus strains to remove ZEN and ¯α-ZOL similarly to aflatoxin B1 and trichothecenes led us to believe that these bacteria have many binding sites for different toxins.”
• “We have found that specific strains of bacteria of both food and intestinal origin, and with a good safety record in the human diet, effectively bind aflatoxin (3) and trichothecenes (2) in vitro.
  • It is likely that probiotics bind a larger variety of mycotoxin and other toxic exposures. This may be an overlooked but critical mechanism of action that results in their effectiveness in a wide range of clinical conditions.

Authors Conclusion

• “Treatment of the bacteria by heat and acid significantly enhanced the ability of the bacteria to remove both ZEN and ¯α-ZOL from liquid media.”
• “The peptidoglycan structure of the cell wall is usually quite thick in these organisms (9), but its thickness may be reduced and/or its pore size may be increased via heat and acid treatments. This perturbation of the bacterial cell wall may allow both ZEN and ¯α-ZOL to bind to the cell wall and plasma membrane constituents that are not available when the bacterial cell is intact.”
• “Cell wall polysaccharide and peptidoglycan are the two main elements responsible for the binding of mutagens to Streptococcus and Lactobacillus. “
  • Probiotics do not need to be live to bind. Polysaccharide components in the bacterial cell wall seem to be the primary binding site.
    • In the paper, the authors further speculate that lysed probiotic strains release intracellular components that also bind to toxins.

• This study clearly shows that both rhamnosus GG and L. rhamnosus LC705 significantly reduce the levels of ZEN and its main derivative ¯α-ZOL) in liquid media. Both L. rhamnosus GG and L. rhamnosus LC705 are probiotic strains and are currently used by the food industry in different dairy products. These strains can bind aflatoxin B1 in the chicken duodenum (5) and influence the absorption of aflatoxins in humans (6). Similar studies are planned for ZEN and ¯α-ZOL to investigate whether the binding ability is functional under physiological conditions and if such binding will reduce the absorption of these toxins from the intestine and hence reduce the estrogenic effects of these toxins. These studies, together with the ability of these strains to bind aflatoxins and trichothecenes, offer a potential approach to reduce the intestinal absorption of mycotoxins from the human diet and animal feeds.

Clinical Takeaways

• • This study helps us to understand the role that probiotics hold in binding mycotoxins. There is a large base of literature supporting their effectiveness.
  • Based on the growing I have been introducing all three strains.

Rapid-Fire Research: Ultra-Concise Summaries of Noteworthy Studies

Ability of dairy strains of lactic acid bacteria to bind a common food carcinogen, aflatoxin B1

PMID: 9651049

“Aflatoxins are a group of a growing list of fungal secondary metabolites which are recognized as being of economic and health importance. They are produced by two toxic strains of Aspergillus, namely A. flavus and A. parasiticus. They are potent hepatocarcinogens in several species of animals (Eaton and Callagher, 1994), and epidemiological studies have implicated them as acute toxicants as well as hepatocarcinogens in man (IARC, 1993).”

“Our results clearly indicate the strain differences in removal of AFB1. The most efficient removal was achieved using LBGG and LC705, while the poorest removal was achieved by E. coli. All the other Gram-positive bacteria were more efficient than E. coli. This finding suggests that the bacterial ability to remove AFB1 is dependent on bacterial cell wall structure. This hypothesis is supported further by the removal differences between pre cultured and heat killed bacteria. The differences between precultured and freeze-dried bacteria may also reflect that preculturing may induce changes in the cell wall components which enhance the ability of the bacteria to remove more AFB1. Further Gram-positive and negative strains are being tested to determine the extent of this observed ability.”

Clinical Takeaway

Not every probiotic strain binds toxins, and different strains have different affinity for particular toxins.

Melatonin Mini Round-Up

After a few years of recommending 1.5-3 mg of melatonin taken before bed for patients with insomnia I began to doubt its efficacy. I wondered if any benefit was a placebo effect. Given that melatonin was an exogenous hormone I wondered if I was potentially suppressing the pituitary gland’s ability to produce melatonin while not getting clinical benefit. The following mini-research review has convinced me of melatonin’s role in helping support sleep. What I found was meta-analyses supporting its use in primary, secondary, and delayed sleep phase disorders in both adults and children.

Exogenous melatonin as a treatment for secondary sleep disorders: A systematic review and meta-analysis

PMID – 29908879

• Melatonin is a physiological indoleamine involved in circadian rhythm regulation and it is currently used for secondary sleep disorders supported by empirical evidence. A small amount of evidence and some controversial results have been obtained in some randomized controlled trials (RCT). The objective of this meta-analysis is to determine the efficacy of exogenous melatonin versus placebo in managing secondary sleep disorders. Literature retrieval of eligible RCT was performed in 5 databases (PubMed, Embase, Cochrane Library, ClinicalTrials.gov, and Web of Science). In total, 7 studies of 205 patients were included. Pooled data demonstrate that exogenous melatonin lowers sleep onset latency and increases total sleep time, whereas it has little if any effect on sleep efficiency. Although the efficacy of melatonin still requires further confirmation, this meta-analysis clearly supports the use of melatonin as management for patients with secondary sleep disorders.

Evidence for the efficacy of melatonin in the treatment of primary adult sleep disorders

PMID – 28648359

• Melatonin is a physiological hormone involved in sleep timing and is currently used exogenously in the treatment of primary and secondary sleep disorders with empirical evidence of efficacy, but very little evidence from randomized, controlled studies. The aim of this meta-analysis was to assess the evidence base for the therapeutic effects of exogenous melatonin in treating primary sleep disorders. An electronic literature review search of MEDLINE (1950-present) Embase (1980- present), PsycINFO (1987- present), and Scopus (1990- present), along with a hand-searching of key journals was performed in July 2013 and then again in May 2015. This identified all studies that compared the effect of exogenous melatonin and placebo in patients with primary insomnia, delayed sleep phase syndrome, non 24-h sleep-wake syndrome in people who are blind, and rapid eye movement-behavior disorder. Meta-analyses were performed to determine the magnitude of effect in studies of melatonin in improving sleep. A total of 5030 studies were identified; of these citations, 12 were included for review based on the inclusion criteria of being: double or single-blind, randomized, and controlled. Results from the meta-analyses showed the most convincing evidence for exogenous melatonin use was in reducing sleep onset latency in primary insomnia (p = 0.002), delayed sleep phase syndrome (p < 0.0001), and regulating the sleep-wake patterns in blind patients compared with placebo. These findings highlight the potential importance of melatonin in treating certain first-degree sleep disorders. The development of large-scale, randomized, controlled trials is recommended to provide further evidence for therapeutic use of melatonin in a variety of sleep difficulties.

The use of exogenous melatonin in delayed sleep phase disorder: A meta-analysis

PMID – 21120122

• Measurements and Results: A meta-analysis of data of randomized controlled trials involving individuals with delayed sleep phase disorder that were published in English, compared melatonin with placebo, and reported 1 or more of the following: endogenous melatonin onset, clock hour of sleep onset, wake-up time, sleep-onset latency, and total sleep time. The 5 trials including 91 adults and 4 trials including 226 children showed that melatonin treatment advanced mean endogenous melatonin onset by 1.18 hours (95% confidence interval [CI]: 0.89-1.48 h) and clock hour of sleep onset by 0.67 hours (95% CI: 0.45-0.89 h). Melatonin decreased sleep-onset latency by 23.27 minutes (95% CI: 4.83 -41.72 min). The wake-up time and total sleep time did not change significantly.
• Dosing – For the purpose of this meta-analysis, the dose was not taken into account.
  • In 7 of the studies, a 5-mg dose of melatonin was administered. One study in adults compared the efficacy of 0.3 mg of melatonin with the efficacy of 3 mg of melatonin and with placebo (with no difference in effectiveness seen). One study in children differentiated the dose according to body weight: children weighing less than 40 kg received 3 mg, those weighing 40 kg or more received 6 mg.
• Conclusions: Melatonin is effective in advancing sleep-wake rhythm and endogenous melatonin rhythm in delayed sleep phase disorder.

Practitioner Question

Listener asks:

“I have a question regarding HAbx resistance. Let’s say a patient progresses moderately with the core HAbx protocol, instead of doing another 2 month round + biofilm disruptors and artemisinin, would you consider a different selection of HAbx with the addition of artemisinin? I am not aware of any long-term data on HAbx so I’m wondering if we are potentially running into the issue of antimicrobial resistance with up to 4 months of therapy. Thoughts?”

Great question!

There is no question in my mind that bacteria can develop resistance to herbal antimicrobials. Here is a 2015 paper that delves into what is known on this issue: Emergence of Herbal Antimicrobial Drug Resistance in Clinical Bacterial Isolates. Check out the table on page 4 reviewing which natural treatments are now ineffective against a variety of microbes.

We have to balance the risk of herbal antimicrobial resistance with clinical benefit to the patient.

Here are a few thoughts:

• The chance of you causing resistance is quite low with a 4-month course of treatment.
• I generally limit HAbx to 4 months at a time, as I observe that most patients who benefit from Habx don’t continue to benefit from further treatment after the 4-month mark.
• If you are using the HGHY HAbx protocol then you are rotating different antimicrobials from the first month (1a, 1b) to the second (2a, 2b) which reduces the likelihood of resistance than using a single agent for a longer course of time.

Overall, we at the Austin Center for Functional Medicine, have made a slight shift in recent months and are prioritizing supportive therapies (probiotics, immunoglobulins, GI repair nutrients) before HAbx in many cases and still seeing excellent outcomes. This is not to say that we aren’t using HAbx, but being a touch more conservative with their use. My sense is that emphasizing these supportive pieces earlier has my patients doing better while being able to use less aggressive HAbx programs.