Online publication only

As this issue covers the role of inflammation in several disease aspects, the authors thought it fitting to apply this topic to seasonal allergic rhinitis, otherwise known as "allergies" or "hay fever." Seasonal allergic rhinitis, or for that matter, perennial allergic rhinitis (defined as allergic rhinitis lasting 9 or more months of the year), is an inflammatory condition marked by inappropriate immune responses to benign environmental substances. Of all cases of allergies, the perennial variety occurs in 40% of all those affected. The allergens in these cases are typically those with no or little seasonal variation, such as cockroaches, dust mites, indoor molds, and animal dander (fur, feathers, skin, urine). Consider the numbers surrounding this inflammatory condition:

· Based on the results of skin test allergies only, 40 to 50 million Americans are affected with allergies, making it the 6th leading cause of chronic disease in the US,¹ or 20% of the entire US population.²
· Of those affected by allergy in general, close to 36 million people have seasonal allergic rhinitis,³ leading to 16.7 million visits to health care providers each year.⁴
· The approximate overall cost of allergic rhinitis in the US in the year 1996 alone was 6 billion dollars.⁵

Conventional medical options for this condition are diverse and include blockage of histamine receptors (antihistamines) and stabilization of cells that release this compound (mast cell stabilizers), steroid therapy (nasal and sometimes systemic steroid preparations), and immunotherapy. Immunotherapy is a particularly interesting approach; it consists of a preventive and anti-inflammatory approach to allergies by injecting gradually increasing amounts of the allergic substance into the person, in hopes that the minute increases of allergens will lead to a less sensitive immune system. While this sounds like homeopathy, it is not but does follow a similar line of thinking in that small substances of offending substances, when introduced into the body, will stimulate it into overcoming symptoms.

While all of these approaches have their merits and downsides, they are not necessarily applicable or entirely curative for all people suffering from allergic disease. More importantly, those suffering from one allergic condition are highly likely to be affected by others such as asthma and eczema. These three conditions, allergies, asthma, and eczema, are referred to as atopic disease; and the literature is extensive regarding prevention and alteration of the immune response in these conditions. Giving due attention to all of these approaches is best served by addressing them in a larger compendium; the following are highlights of some of the more popular approaches to allergy prevention and control. (Please see the May 2004 issue of Townsend Letter for a look at inflammation and asthma).

Prior to treating allergies, the differentiation between true allergic responses and sensitivity must be established. Allergy is defined as an acquired, abnormal immune response to a substance (the allergen) that does not normally cause a reaction, resulting in a broad range of immune (inflammatory) responses. Sensitivity is defined merely as "susceptibility to a substance." More specifically, this means that a substance (most typically benign as well) may lead to physiologic perturbations in any number of ways. These include, but are not limited to, migraines, apthous ulcers (canker sores), bedwetting, and itching. It is important to make this distinction because both diagnosis and treatment may be completely different in this case.

Antigenic Load and Food Allergy
While the causes of allergic rhinitis are often obvious (that is, allergies occur for most people during specific seasonal time periods associated with plant pollens, and so on), uncovering what makes the immune system respond in this way is key. One prevailing theory is that of antigenic load, whereupon it is hypothesized that an excessive amount of antigenic stimulus overwhelms the immune system, leading to inflammatory responses. For instance, exposure to small amounts of allergens may not typically amount to symptoms, until simultaneous exposure to a number of antigens leads to "spillover" of symptoms. It is thought that in this manner, the immune system can deal adequately with substances that it perceives as allergens when exposed in limited quantities; however, when continually bombarded by allergens, or presented with several different allergens, the immune system is overwhelmed, and as such, symptoms appear. Likewise, repeated chronic immune response to allergens can overwhelm the immune system when we are tired, stressed, or in otherwise less than optimal health. And, it may be possible that sensitivities may contribute to the "load" mentioned here as well. While much of this is speculative theory, it makes great clinical sense when confronting allergy symptoms.

One of the most direct ways to lighten the antigenic load is by identifying and removing food allergens. A subject unto itself, food allergies and sensitivities play a key role in resolving many physical symptoms in people, including allergic responses. When we look at foods as a culprit, this makes complete sense, as they comprise the largest pool of antigenic challenges to the immune system.⁶ (Please see the Townsend Letter on food allergies). Additionally, food groups are very consistent in the majority of people, as diets rarely vary from 10 different food types on a weekly basis. Continuous exposure to sensitivities or allergies in this fashion is an understatement. Food sensitivities and allergies themselves set up the immune system for even more reactivity toward other substances.

Allergic/inflammatory processes become active in the gut; transportation of food proteins across the intestinal wall becomes altered resulting in increased permeability and motility of the intestine.⁷ Coupled with other conditions such as intestinal infections/flora imbalance, and decreased secretory IgA, this may lead to further intestinal compromise and increased antigen-immune interaction. Thus we may hypothesize that not only will increasing the antigenic load in the form of food allergy/sensitivity increase the food allergy problem, it will also overburden the immune system, possibly leading to overreaction against airborne or other seasonal allergens.

Milk is an interesting food to look at while on the subject of food allergy. Commonly thought of as an allergen (especially incorrect in those with lactose-intolerance) because of its ability to increase mucus secretion, its status as such was evaluated in one interesting study. Investigators looked at people's sensations and symptoms immediately after drinking milk and a placebo beverage.⁸ The study went like this: 169 subjects, 70 of whom believed that milk leads to increased mucus production, were enrolled in a randomized, double-blind trial of a "flavored" cows' milk drink and a similar-appearing and -tasting soy milk drink. In a pretest of 185 people, the researchers claim that the two drinks were indistinguishable. A survey was administered to each subject in both groups asking them to rate 14 milk-mucus indicator variables; only 3 of the 14 variables were elevated in both groups. They were: "coating/lining over the mouth, throat or tongue," "need to swallow a lot," and "saliva thicker, harder to swallow than before." Investigators concluded, in their oft-quoted study, that milk does not increase mucus, and the sensation of increased mucus production can be duplicated after consuming a soy drink as well, thereby negating the claim that milk leads to increased mucus production.

What is most interesting about (and the biggest flaw in) this study is that researchers looked only at immediate reactions to mucus production, and not at longer-term outcomes (hours to even a day later). Clinically, many people with allergies are averse to milk, as are people like athletes, singers, and speakers, or for that matter anyone whose performance may be affected by excess mucus production. Another study looking at mucus production hours after milk consumption is in order here.

Preventive Measures
Preventing the allergic response is, of course, our first line against this condition. Preventive approaches can take place as early as gestation and throughout infancy. While prevention always makes the most sense, there are other treatment strategies for adults with allergies as well.

Hygiene
A discussion about inflammation, especially allergic, is not complete without mention of the Hygiene Hypothesis. The central tenet of this hypothesis states that increases in hygiene have led to an immune system left unchallenged. The widespread use of antibacterial cleaners and the intense methods in which children are prevented from encountering "germs" may have led to an increase in atopic disease. The hypothesis was created after patterns of risk factors for allergic disease in Europe; apparently hygienic practices have removed a protective influence against allergic disease by reducing the number of infectious challenges early in life.⁹ That is, as young children are exposed to and become infected by various agents, the immune system is kept "busy" combating these infections. Now that modern medicine and intense hygiene (food that falls on the floor is never eaten, hands are washed several times a day, and great alarm occurs if dirt, rocks, or other "unclean" items go into a child's mouth) have removed much of the infections that previous generations suffered, the modern immune system now reacts against typically benign environmental substances, such as animal dander and pollens.

This theory poses an interesting question, especially when considering the upcoming discussion of probiotics. Can allowing young children to exist in a less-sanitary environment prevent some allergic disease? This is of course, a charged discussion, especially with the prevailing media endorsement of household cleaning agents as well as media exposés of the many germs found in dishcloths and on restaurant tables. The majority of such "germs" found in these frightening stories are commensal organisms that exist practically everywhere, including in and on our bodies.

Probiotics
The current progressive increase in frequency of atopic disease (asthma, allergies, and eczema) appears throughout the modern Western world. Probiotics, or cultures of beneficial, commensal bacteria that typically dwell in the gut, have been researched as potential primary inhibitors of the atopic process.

There are many recent investigations of the effects of supplementation with probiotics on the prevention and treatment of allergic disease, with promising results. Despite its wide acceptance as the best source of nutrition for the infant and its role in optimizing infant health, breast-feeding as a protection against allergic disease remains elusive today with both pro and con studies.¹⁰ However, studies investigating the effects of probiotics both in the ante- and postnatal periods have also produced fascinating results in this area; however, they mainly focus on eczema.

In a study of 62 mother-infant pairs, administration of probiotics to the mother both during pregnancy and in lactation increased the immunoprotective properties of the breast milk as assessed by the amount of transforming growth factor beta2 (TGF-beta2) in the milk.¹¹ Infants whose mothers took probiotics had a significantly reduced risk of atopic eczema development in their first 2 years of life, compared with the infants whose mothers were not supplemented. The risk for eczema development was 15% in the mother-supplemented babies and 47% in the non-supplemented-mother infants. It was revealed further that maternal atopy was a clear risk factor for eczema in the infant, and those most likely to benefit from maternal probiotic supplementation were those who had an elevated umbilical cord blood concentration of immunoglobulin E (IgE), a primary mediator of allergy.

Administration of probiotics during pregnancy and breast-feeding appears to offer a safe (no side effects were reported in any of the probiotic studies) and effective tool for protection against atopic disease early in life. More needs to be learned about the preventive role of probiotics in seasonal allergic rhinitis, or a tendency toward its development.

Adjunctive Treatments
Urtica Dioica
A popularly prescribed allergy treatment is Urtica dioica, or stinging nettle. Nettle has long been the subject of much herbal lore regarding allergy treatment. Nettles have been subjected to surprisingly little scientific scrutiny in relation to their anti-allergy affect. While some amount is known about this plant in this regard, it does provide interesting insight into its allergy-preventive effects. Nettle is known to contain histamine, serotonin, and acetylcholine in the stinging portions of the leaves.^12,13 While using a plant containing the very substances that standard allergy medication works against (antihistamines), it seems strange to use this botanical medicine for allergy treatment. However, histamine has been used to treat several different types of allergic conditions, including seasonal allergic rhinitis.¹⁴ Surprisingly, it had been demonstrated that high serum levels of histamine do not accompany some allergic responses; rather, low amounts of plasma histamine have been associated with more severe reactions to inhalation of known allergens.¹⁵

One double-blind, placebo-controlled study tested the efficacy of nettle in allergic rhinitis.¹⁶ A total of 69 patients completed the study, with 59% rating nettle as effective in treating symptoms compared with 37% of the placebo group finding relief as well. Other descriptive actions relating to older herbal texts describe nettle as "astringent to the mucous membranes" and a "histamine stabilizer."

Ammi Visnaga (Khellin)
This herb has many applications in preventing symptoms of allergic disease; it is available as a commercially produced bronchial inhaler, nasal inhaler, and opthalmic solution. While relatively far removed from its natural state, khellin is altered and its commercial preparations are referred to as sodium cromoglycate. This medicine is useful for treating asthma, allergic rhinitis, and allergic conjunctivitis as a preventive medicine. Khellin is known to stabilize mast cells (the main producers of histamine in allergic reactions), thereby blocking the release of inflammatory and allergic mediators. When applied in the above-mentioned forms, it is used frequently to disallow mast cell degranulation in the allergic cascade. Used in this manner, both early- and late-phase allergic reactions are avoided, and development of inflammatory processes are quelled as well.

The commercial form, sodium cromoglycate, is poorly absorbed on a systemic basis (thereby necessitating direct application to mucous membranes) rather than oral administration. It is well tolerated with very few side effects, the most often-reported being headaches.¹⁷ There are no associated drug or herb interactions, and its efficacy is comparable to prescription antihistamines and intranasal corticosteroids. It is most effective with prophylactic use.

Acupuncture
Acupuncture can be a useful adjunctive therapy for treating allergies. While the authors do not practice acupuncture clinically, both have observed rather impressive results in patients using acupuncture as part of their treatment of seasonal allergic rhinitis. While a discussion of acupuncture and allergies are beyond the scope of this article, it is recommended that those suffering from allergic symptoms seek acupuncture as part of their treatment plan. One interesting study looked at the effects of real versus sham acupuncture on cytokine levels in patients with allergic rhinitis.¹⁸ Cytokine levels were markedly lower after the real acupuncture treatment, whereas they remained elevated and unchanged following the sham acupuncture treatment. This is one of many fascinating studies that endorses the use of acupuncture for treatment of many conditions, allergies being yet another.

Prevention and treatment of the inflammatory cascade in seasonal allergic rhinitis is an extremely large topic; this article only briefly addressed a few methods and theories. Natural medicine encompasses an enormous array of treatment methodologies for addressing not only allergic disease but inflammation as well. As practitioners of natural medicine, we must also incorporate the wisdom of these additional therapies and lifestyle approaches:

· nutrition: Vitamins and minerals (vitamin C, B6, magnesium), and fatty acid modification using essential fatty acids;
· bedroom hygiene: removing carpeting and drapery, frequent changing of sheets (avoidance of dust mite allergens);
· saline nasal rinse: saline is a weak mast cell stabilizer as well;
· washing hair and face before retiring at night (removes accumulated pollens and other allergens encountered during the day);
· homeopathic remedies;
· other botanical medicines: Euphrasia officinalis, Achillea millefolium, Cochlearia armorica, Hydrastis canadensis, and others;
· energetic-based allergen removal, including Nambudripad allergy elimination technique (NAET) and related forms.

Notes
1. American Academy of Allergy, Asthma and Immunology (AAAAI). The Allergy Report: Science Based Findings on the Diagnosis & Treatment of Allergic Disorders. 1996–2001.
2. American Academy of Allergy, Asthma and Immunology. Task Force on Allergic Disorders. Executive summary report. 1998.
3. Natahn RA, Meltzer EO, Selner JC, Storms W. Prevalence of allergic rhinitis in the United States. J Allergy Clin Immunol. 1997;99:S808–S814.
4. US Centers for Disease Control and Prevention. National Center for Health Statistics. Vital and Health Statistics. 1999;10(13).
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 Immunol. 1999;103(3 Pt 1):408–514.
6. Buckley RH, Metcalfe D. Food allergy. JAMA. 1982. Nov 26;248(20):2627–2631.
7. Ahmed T, Fuchs GJ. Gastrointestinal allergy to food: a review. J Diarrhoeal Dis Res. 1997 Dec;15(4):211–223.
8. Pinnock CB, Arney WK. The milk-mucus belief: sensory analysis comparing cow's milk and a soy placebo. Appetite. 1993 Feb;20(1):61–70.
9. Matricardi PM, Bouygue GR, Tripodi S. Inner-city asthma and the hygiene hypothesis. Ann Allergy Asthma Immunol. 2002 Dec;89(6 Suppl 1):69–74.
10. Wills-Karp M, Brandt D, Morrow AL. Understanding the origin of asthma and its relationship to breastfeeding. Adv Exp Med Biol. 2004;554:171–191.
11. Rautava S, Kalliomaki M, Isolauri E. Probiotics during pregnancy and breast-feeding might confer immunomodulatory protection against atopic disease in the infant. J Allergy Clin Immunol. 2002 Jan;109(1):119–121.
12. Collier HOJ, Chester GB. Identification of 5-hydroxytryptamine in the sting of the nettle. British J Pharmacol. 1956;11:18689.
13. Saxena PR, Pant MC, Kishor K, Bhargava KP. Identification of pharmacologically active substances in the Indian stinging nettle, Urtica parviflora (Roxb.). Can J Phys Pharmacol. 1965;40:869–876.
14. Horton BT. The clinical use of histamine. Postgrad Med. 1951;9:1–11.
15. Zimmerman I, Ulmer WT. Effect of intravenous histamine, allergen (Ascaris suum extract) and compound 48/80 and inhaled allergen aerosol on bronchoconstriction and histamine release. Respiration. 1981;42:30–42.
16. Mittman P. Randomized, double blind study of freeze dried urtica dioica in the treatment of allergic rhinitis. Planta Med. 1990;56:44–47.
17. Meltzer EO; NasalCrom Study Group. Efficacy and patient satisfaction with cromolyn sodium nasal solution in the treatment of seasonal allergic rhinitis: a placebo-controlled study. Clin Ther. 2002 Jun;24(6):942–952.
18. Petti FB, Liguori A, Ippoliti F. Study on cytokines IL-2, IL-6, IL-10 in patients of chronic allergic rhinitis treated with acupuncture. J Tradit Chin Med. 2002 Jun;22(2):104–111.