In my last entry, I talked about 3 reasons why sublingual immunotherapy (SLIT) has been slow in gaining acceptance: "turf wars" between ENT's and allergists, the "tomato effect" in medicine, and the commitment and work it would take an allergist to change his/her practice from SCIT to SLIT.  

But wait...there's more.

In pondering this issue and discussing it with my colleagues, an obvious answer exists--the proverbial "elephant in the room" that nobody discusses:  

Allergy society leadership.

Let's face it--many of our society leaders are academic allergists.  Their viewpoint--philosophically AND financially--is far different than the allergist "in the trenches"  coping on a daily basis with  competition for patients between ENT's, family physicians, chiropracters, etc...

Although I love to read the Annals, and the JACI, and delve into the esoterics of various allergy issues (I didn't know that prostatic kallikrein was a major dog allergen until now), I was trained as an engineer.  I do what works.  Practicality and positive results are what count--for my patients and for myself.  I've utilized SLIT in my practice since Feb, 1981.  And despite "competition" from local allergists using SCIT, I've more than managed to survive.  This "real world" experiment answers the question "can an allergist convert from SCIT to SLIT and still be successful?"  It's been done.  At least once!  

Later, Dude

In my last entry, I've written about the extensive history of SLIT--going back over one century...many, many years prior to the European literature,which largely began in the 1980s...Invariably, in any discussion about SLIT the one key question that arises is...

Why has recognition of this technique as a safe and efficacious treatment for allergic disease taken so long?  

To my knowledge, there has never been a medical article that addresses that question...and it seems to be a perfect blog topic...so here goes...

Lack of American acceptance of SLIT as a viable treatment modality is probably because of several factors:

1.  The "turf wars" between ENT's and Allergists:  Face it.  The majority of early proponents of SLIT were not allergists.  They were ENT  physicians (Hansel, Pfeiffer), or non-ENT non-allergists (Dickey--a urologist by training).  Medical history has a tendency to repeat itself...when Edward Jenner discovered vaccination for smallpox, his discovery was unrewarded by the medical establishment, largely because of bias against him--he was a rural general physician and his 1798 paper was rejected and never published by the medical establishment.  Similarly, why would a board-certified allergist look kindly on a technique condoned--and discovered--as effective by his non-board certified colleagues??

2.  The profound implications of SLIT--it's potential to revolutionize the office practice of allergic disease:  Let's face it.  As allergists, we can rapidly incorporate a new medication into our practice with minimal problems...but incorporation of SLIT into an office practice would take far more work, and (according to conventional wisdom), considerable financial  risk.  Technicians would have to be trained, and a doctor would have to be educated and confident of his success in using it...in the face of non-insurance coverage.  The American allergist, before he/she dives into a SLIT-based practice, simply wants iron-clad, irrefutable, American-based evidence that SLIT is safe and effective.  Anything less is simply unacceptable...Money can be made with SCIT, and with SLIT...well, insurance coverage just isn't there...yet...so "let's wait and see", right?

3.The "tomato effect".  Allergists were trained during fellowship to believe that SLIT didn't work, because...everyone knew it didn't work. This is an example of "The Tomato Effect", written about by Goodwin, JS & Goodwin JM, JAMA 251:  2387-2390, 1984.  Briefly put, the tomato effect is defined whereby a potentially efficacious medical therapy is discounted because "it doesn't make sense".  The conventional wisdom--common knowledge--is that "it just doesn't work".  In 1560, the tomato was becoming a staple of the European diet, having been brought back from Peru.  As the Goodwins put it, 

“Of interest is that while this exotic fruit from South America was revolutionizing European eating habits, at the same time it was ignored/actively shunned in America.  

"The reason tomatoes were not accepted until relatively recently in North America is simple:  they were poisonous.  Everyone knew they were poisonous, at least everyone in North America. “Not until 1820, when Robert Gibbon Johnson ate a tomato on the steps of the courthouse in Salem, New Jersey, and survived, did the people of America begin, grudgingly, we suspect, to consume tomatoes..."

4.  If SLIT is accepted, we have a technique safe enough that potentially even non-allergists will do it and create increased competition for the allergist.  This gets into my "hidden agenda" blog post from earlier.  To the trained allergist using SCIT, there is only one solution to the dilemma of having a form of immunotherapy that is simply "too safe"...and that is to "spin" SLIT to make it as dangerous as possible...this benefits the allergist--since it keeps the treatment "in his camp".  No one but the board-certified allergist would dare to do it (pretty much like injection immunotherapy presently).  Presentations and studies by American allergists will therefore be overly cautious and negative in their portrayal of the benefits of SLIT...

In short, the American allergist (unlike their European counterpart), comes with psychological "baggage" of years past regarding inherent bias against SLIT (a technique largely proposed by non-allergists), and a fear about maintaining financial security when adopting this technique and giving up SCIT.  Instead of objectively looking at European studies and aggressively pursuing SLIT, we employ a strong "denial of reality"--a defensive, fearful posture--we think "if we just don't think about SLIT, it'll go away"...And we employ tired, worn arguments (i.e., "it's not FDA approved, we don't have American studies...") that don't even make rational sense (after all those of us who use SLIT use FDA approved extracts in an off-label useage--something perfectly legal).  

It's hard to be creative and innovative when you're fearful, and that's just the place where the American Allergist is...now, more than any other time in our history, the American Allergist needs to be resourceful, creative, and innovative.  Not fearful.  Our attitude with SLIT is but one example of something that needs to be changed...and soon.  

Later, Dude

I was on the phone recently with a colleague whom I admire...we were discussing an allergy case at his request when he said..."You know, it does my heart good to see you've gotten over your anger issues and renamed your blog  "The Renaissance Allergist"...

Inwardly, I beamed...maybe getting in touch with my Inner Child was finally doing me some good...it was amazing...maybe, just maybe, all that hard work I had done in resolving my previously unresolved suppressed anger at my father for not taking me to a Chicago Bears game in 1955 was finally coming to fruition...

And I was in a truly mellow mood when I picked up the latest issue of  Current Allergy and Asthma Reports, Volume 8, Number 4, 2008.  In it, the lead article was entitled "Recent Advances in Immunotherapy of Allergic Rhinitis", by Lee & Mo.  Not surprisingly, their first topic of discussion was Sublingual Immunotherapy (SLIT).  They had this to say in their first sentence of their first paragraph:

SLIT was first introduced in the 1980s in Europe."

Say whaaat?  

Screw my Inner Child.  I'm mad.  

Hey, wait just ONE minute....it may be becoming fashionable to quote the newer European literature on SLIT, but it's important not to ignore the "pioneers" when it comes to this technique. How long has SLIT been around?  20 years?  30 years?  40 years?

How about 109 years...

In 1900 a New York physician H.H. Curtis relieved his patients' hayfever by placing pollen antigen drops in their mouths.  Yes, 1900.  Not 2000.  Written up in "The immunizing cure of Hay Fever"  Medical News, New York 1900; 77:16-19.  In 1905 German doctors used oral immunotherapy to desensitize infants allergic to cow's milk (Finkelsteim, H. Kulmilch als Ursache von Ernahrungsstorungen bei Sauglingen Mmonatsschr Kinderheilk.  1905; 4:65-72.)  Actually allergy injection immunotherapy (SCIT) was first used 11 years AFTER oral immunotherapy by English physicians John Freeman and Leonard Noon.  

In the 30s and 40s, doctors used oral immunotherapy, mostly reporting favorable results.  Black desensitized 150 patients to pollen using oral drops--40% of them got satisfactory symptom relief. (Black, J.  The oral administration of ragweed pollen.  Journal of Allergy and Clinical Immunology.  1939. 10:156.)  Leo Conway began using oral antigen drops to control seasonal allergies by 1934.  (Conway, L.  Pollen allergy.  South Med Surg. 1943; 4.).  Gutterdam in 1933 reported on 85 patients receiving oral antigen drops, finding good symptom relief in 75-85% of patients.  (Gutterdam, E.  Oral administration of pollen extracts.  Southwest Medicine.  1933:17:199.)  They took 3-15 drops of pollen extract twice each day.  In 1937 Hollister & Stier reported good results in 78% of hay fever patients and in those allergic to animal dander and foods.  (Stier, R. Hollister, G.  Desensitization by oral administration of pollen extracts.  Northwest Medicine.  1937; 36:166).  

Were there others?  Of course.  Schofield, Walker, Stuart, Farnham, Keston, Waters, Hopkins to name a few.  I have written a previous entry on Oscar Schloss   who had successfully desensitized a child with anaphylaxis from eggs with serial dilutions of oral egg drops administered orally....in 1912.  

But for my money, the three real pioneers in the field were:  French Hansel, Larry Dickey, and David Morris...

I have been extremely privileged in my life to have known all three.  

French Hansel can be called the modern "father of sublingual immunotherapy".  Hansel experimented with sublingual drops for dust mites while he was a Mayo Clinic Fellow in the 1920s and published his results in 1936.  (Hansel, F.  Allergy of the nose and paranasal sinuses.  CV Mosby.  1936).  He was the first physician to observe that actually placing antigen drops specifically under the tongue prompted faster, more effective desensitization than in any other part of the mouth. He had this to say:

It is not unreasonable to assume that this highly absorptive sublingual area has definite immunologic function.  Through this route practically all the injectables, many of which are not well tolerated, can be introduced without apparent injury to or reaction in the local tissues"  ((Hansel, F.  Clinical Allergy.  CV Mosby.  1953)

He later described in greater detail sublingual treatment in "Sublingual testing and therapy. Trans Soc. Opthalmol Otolaryngol Allergy, 11: 93, 1970. During my early training, I was fortunate to have lunch with Dr. Hansel, and to discuss his experience with SLIT in particular.  How fortunate!  Guy Pfeiffer, MD, a student of Hansels, developed sublingual drops for foods.  Like Hansel, he was an ENT physician, who presented his five years of experience with SLIT at a 1963 ENT conference.  

Lawrence Dickey, a Colorado surgeon and urologist by training, started offering shot immunotherapy to his urology patients who had allergies, and after hearing Pfeiffer, he stopped treating his patients with shots and started treating them with SLIT.  Dickey wrote about the use of SLIT in Trans Soc Ophthalmol Otolaryngol Allergy 5:37, 1964, in an article entitled "Sublingual therapy in Allergy", and he also wrote in JAMA in 1971, with an article entitled "Sublingual Antigens", JAMA 217: 214, 1971.  Once again, I had the enormous priviledge of knowing Dr. Dickey; he was exceedingly gracious and generous in sharing his knowledge in this area.  At a 1964 ASOOAS conference, Dickey had this to say about SLIT:  

'sublingual therapy is more acceptable to our patients sand more convenient for our office personnel.  There have been fewer drop-outs from sublingual therapy than we had with injection treatment".  

Finally, my own colleague, to whom I owe such a personal debt of gratitude, wrote truly groundbreaking articles on SLIT.  David Morris, MD was at the ASOOAS conference in 1966.  He heard Pfeiffer and Dickey presenting at the conference.  And he became interested in SLIT and subsequently published in the Annals of Allergy in 1969 on SLIT for foods and in 1970 on SLIT for molds.  His 1970 paper on SLIT for molds broke new ground--he was the first to report success using SLIT specifically for treating respiratory diseases caused by mold allergy.  

 I wish to thank Dr. Morris for his historical lectures on SLIT, which are the foundation for this lecture (diatribe??)  But this raises a bigger question...if SLIT has been around for over 100 years, why haven't we heard more about it until now, and why do we promulgate the misplaced notion that "the Europeans discovered it?"  What does this imply about our specialty? 

My next post will address that intriguing question.  Until then, I'm back to my anger management program....  Again.  

Later, Dude

In my last entry, I promised to write about one clinical pattern (mold and Candida cross-sensitization) but that all changed when I recently received the following e-mail from a savvy Physician's Assistant who is a friend of mine.  Here's the key excerpt:  

"...13 year old with 5+ years of vomiting 10 to 12 times daily on and off.  Had seen gastro multiple times with no answers.   Saw me and I suggested wheat free, dairy free diet and ran a RAST IgE food panel on him.  He came back positive to eggs at 3+, dairy 2+, wheat at 2+ and soy at 1+.    Took him off of all of these and his symptoms resolved almost completely...He did see GI after this again and was told he may have eosinophilic esophagitis based on endoscopy and some "general inflammation".    Also sent him to allergy and they said he didn't really have true food allergies despite positive RAST and a clear improvement off of the offending atents.  They in fact suggested he go BACK on his foods and that his underlying issue may in fact be eosinophilic esophagitis.  

Are the allergists here in question total morons...?  My understanding is that studies have been done show that an elemental or elimination diet can resolve some cases of Eosinophilic esophagitis and patient symptoms.  Isn't this a clear allergic issue?   I also suggested to my patient's mother to ask about SLIT to the allergist just to see what would occur and the note returned to me clearly states "patient's mother asked about SLIT which we discouraged considering because it hasn't been shown to work". 

   This letter pretty much sums up the frustration many primary care doctors have in dealing with allergists...in this case, there is a failure by the allergist in question in two separate areas:

1. A failure in focusing on  a disease and disregarding potentially  causative triggers of the disease.  

2. A failure in recognizing that a fluctuating load of "low grade" allergens can cause a "critical mass" effect of an acute allergic reaction...i.e., a failure in "pattern recognition".  

Let's discuss the first of these two failures:  

I have previously written on Jerome Groopman's excellent book, "How Doctor's Think" In the book there is an interesting story told by an ER doctor...a elderly man presented with a broken ankle.  The ER physician focused on fixing the ankle...and the man presented later to the ER...having fallen again.  It turned out the reason he had fallen--and broken his ankle--was because he was weak and anemic.  And it turns out he was anemic because...he had colon cancer.  So the ER doctor focused on the illness, to the exclusion of inciting triggers for the illness.  With disastrous results.  In a similar manner, the physician's assistant is really asking in his email:  "do we really do a "complete" service to our patient by focusing on whether or not he has an illness (i.e., eosinophilic gastroenteritis--or eosinophilic esophagitis) if we ignore possible causative triggers--in this case the dietary management that put the child in remission?  

The second failure in the above case is the failure of pattern recognition:  we can often have patients present with intermittent severe allergic-type reactions.  More often than not, there are only two possibilities for these intermittent severe reactions:  i.e., a HIGHLY allergenic item (usually hidden to the patient) that he/she intermittent has exposure to, or (and this is far more common), an accumulation of MILDLY alllergenic products reaching a "critical mass" in unfortunate circumstances.  I have seen this scenario played out multiple times in diseases such as "idiopathic anaphylaxis".  

It's important to understand that low grade food sensitivities can be responsible for intermittent severe attacks of GI upset.  The child's symptoms were "off and on", and resemble the clinical entity Cyclic Vomiting Syndrome.  There is medical literature to support the idea that Cyclic Vomiting Syndrome can be a manifestation of allergic gastroenteritis, which in turn can be triggered by food allergy.  Tokodi et al presented the case of Cyclic vomiting syndrome in a child which resolved on elimination of milk from the diet.   Further, Lucarelli et al, writing in the Eur J Pediatrics  had this to say:  

Cyclic vomiting syndrome (CVS) is characterized by repeated unpredictable, explosive and unexplained bouts of vomiting. The episodes have a rapid onset, persist over a number of hours or days, and are separated by symptom-free intervals. Despite the recent interest in this disorder, its aetiology, pathogenesis and even its target organ remain unknown. The purpose of this study is to investigate the role played by food allergy in CVS. The report concerns eight children (five male, three female), mean age 8 years (3-13 years), suffering from CVS for 2 years at least. The diagnosis of CVS was based on characteristic history, normal physical examination and negative laboratory, radiographic, neurological and endoscopic studies. Despite the absence of clinical signs typical of food allergy, skin prick tests were positive in six of the eight patients (75%). Specific IgE were present in 4/8 (50%) of the patients. Skin tests and specific IgE were positive for cow's milk proteins, egg white and soya. IgE levels were higher than the mean + 2SD in 5/8 (63%) of the patients. A double blind placebo controlled food challenge (DBPCFC) was carried out on seven of the eight patients who displayed clinical improvement after an elimination diet for cow's milk (and other foodstuffs indicated by positive skin tests). The DBPCFC was positive in all seven children. Clinical follow-up revealed a state of well-being over the 6 months of observation. CONCLUSION: It appears reasonable to suggest that food allergy plays a role in cyclic vomiting syndrome.

I have seen the pattern of intermittent GI upset (particularly in children) from mild food sensitivities in many children.  More often than not, the mother or father will bring their child in to me because they are having a few episodes a month of severe gastrointestinal distress.  Very often, there is a low grade reaction to one or more foods responsible for the episode.  Remember:  it takes 3 1/2 days for food to completely transit the GI tract, so a "load effect" can take place.  Case in point:

A minister sees me in the office.  He has ice cream as his "special treat" every Friday night.  Last month it was his birthday--on a Saturday--so he had his ice cream Friday AND Saturday--and he suffered a horrible attack of GI distress and upper respiratory congestion on Sunday morning!

This is graphically illustrated in the following slide:

In this slide, the fluctuating size bars represent the fluctuating levels of food allergens present in the patient's system, which in turn are shown by the different colored boxes.  The threshold for reaction, shown as a dotted line, can be lowered by stress (viral infection, emotional trauma, etc). 

In another part of his email, the physician's assistant related that "the allergist said that those RAST levels were not positive enough to be a problem".  Nothing could be farther from the truth.  Like the statement by the allergist that "SLIT doesn't work".  Enough now.  I'm going to take my high BP pill and sign off. 

Later, Dude

The other day I was driving down the road, and turned on the radio...flipping the channels, I realized it took me less than 1-2 seconds to instantly recognize whether a radio station I was listening to was playing "classical music", or "country western music", or "hard rock".  Of course, we all can do this--simply because we've had enough "experience" with music over the years to recognize different characteristic music "patterns" very quickly.  In fact, if we instantly recognize "classical music", we may not know the specific piece we're listening to...the uniqueness of each piece only comes with thorough listening.  In short, we can recognize broad patterns quickly in music, but realize that each piece is unique, and the longer we listen to it, the more likely we'll be able to identify its uniqueness (i.e., the composer).  

And so it is with the field of Allergy.

And although each patient is unique, they often present with a "pattern" we've seen before, which helps immensely in their diagnosis and management.   

Unfortunately, my own experience is that most allergists like to discuss specific isolated allergens (dust mite, mold, etc.) or specific disease states (allergic rhinitis, asthma), but pattern recognition in the diagnostic history  (i.e., characteristic relationships between multiple allergens over time in an individual) is sorely lacking.  And pattern recognition is critical to helping the allergist in deciding upon the appropriate diagnostic tests to run.  Indeed, if one is good at pattern recognition in taking the allergy history, then the subsequent allergy tests become almost an anticlimax.  

There's one hidden advantage for the allergist in knowing allergy patterns.  It makes the practice of allergy fun.  Why?  Nothing gives me more pleasure than to "put the pieces together" in a difficult diagnostic puzzle, and to virtually "know the answer" to a patient's problems before beginning testing.

So I've decided to start off the New Year with a series on pattern recognition in allergy.  In my next entry I'll be discussing mold allergy, with cross-sensitization to Candida and food yeast--a pattern I've frequently seen in patients.  

Later, Dude