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

It's happening already, and a major crisis is present:  A powerful American institution, whose leaders lack vision, has largely pursued a "business as usual economic  model".  They suffer increasing competition from their more visionary overseas counterparts,who are more  aggressively promoting alternative (hybrid) technology. Demand by U.S. consumers for the overseas products increases, perceived by the consumer as more safe, and efficient.  In addition, workers in the industry, who have generous benefits through their contracts, are reluctant for change.  In short, the American institution is in increasing danger as being perceived by consumers as "out of touch".  They don't want a "business as usual" business model.  They want--and indeed demand--innovation.  

Think I'm talking about the Big 3 Automotive industry?  Wrong.  Think again.

I'm talking about the "Allergy Industry." 

Bailout:  An ugly word for ugly times.  Yet, that's what Detroit Automakers want (and think they need).  And the American public doesn't like it.  One bit.  Thomas Friedman, in the New York Times, wrote a devastating commentary on this issue in "How to Fix a Flat"  In it he states the frustration of The Common Man on this matter:

How could these companies be so bad for so long?  Clearly the combination of a very un-innovative business culture, visionless management, and overly generous labor contracts explains a lot of it....We have to subsidize Detroit so that it will innovate?  What business were you people in other than innovation?" 

 

And what's with the flood of big truck commercials?  Personally, as I watch commercials for American vehicles, I ask--does everyone in the world really NEED a big honkin' truck that has 4 wheel drive and can climb 50 degrees up the side of a mountain while hauling the Titanic behind it with a steel chain?  Does my vehicle really need to survive a chain-suspended drop from a helicopter? Maybe a simple fuel-efficient Honda would do just fine.  Know what?--it does for me. I don't need a vehicle that can survive being tossed out of the lake by the Loch Ness Monster.  I need a vehicle to get me to work and back home again as efficiently and safely as possible. And I suspect most people do too.  

Which gets me to the Allergist and the Allergy Profession...

Sublingual immunotherapy (SLIT) has now proven a convenient, efficient way to deliver disease-modifying treatment to the allergy population.  At the recent ACAAI conference, there was no longer any questionas to whether SLIT is effective.  (And that's a first). Meanwhile our overseas European counterparts don't just talk about SLIT, they continue to use  SLIT effectively and produce prodigious research.  I've never really heard of SLIT described as a "hybrid" technology. but if we continue to use our "automotive industry analogy",  that's exactly what it is--a blending of a conventional form of treatment (antigen extracts initially designed for injection) and combining it with a new delivery system (sublingually).  And, like most automotive hybrid technology now-in-days, it will continue to evolve and become more and more efficient.  SLIT as it now exists, will give way eventually to "second generation" vaccines designed exclusively for the sublingual mucosa.  Case in point:  Razafindratsita et al in the JACI (vol 120, pp 278-285), in an article entitled "Improvement of sublingual immunotherapy efficacy with a mucoadhesive allergen formulation", concluded that 

Mucoadhesive formulations offer the opportunity to improve dramatically sublingual immunotherapy in human beings, most particularly by simplifying immunization schemes. 

I've stressed throughout this blog how the individual allergist needs to develop his/her sense of curiosityin order to be a superior allergy clinician.  On an individual basis, working allergists, like their unionized labor counterparts in the automotive industry,  have "generous benefits" in terms of reimbursement for allergy injection immunotherapy (SCIT).  They worry about losing these benefits if they start utilizing SLIT.  As one allergist said, "I make a good living with SCIT--why should I change?"  Since insurance contracts largely don't cover SLIT, the average allergist doesn't  want to "risk" changing over to SLIT, even though the literature shows it to be more economicaly efficient, convenient, and safe.  Insurance companies won't pay for it if it isn't a "usual and customary" procedure, and allergists don't want to do SLIT if they lose their lucrative insurance contracts.  A "Catch-22" of the first order...

However, the problem is compounded by our "institutional leaders".  Our institutional leaders in allergy need not only curiosity, but the capacity for creative innovation.  While our overseas counterparts were developing "hybrid technology", we continued to have our own "allergy factory" geared towards injection immunotherapy exclusively, effectively ignoring the obvious public interest in alternative forms of immunotherapy that have potential for increased convenience and safety.  As an organization, we should be falling all over ourselves in aggressively investigating SLIT.  Instead, our institutions have a defensive posture.  The glass is either half full or half empty.  And they see it as half empty.  Plenty of old, tired arguments abound regarding SLIT:  "the European literature doesn't apply to our American (polysensitized) patients", or "homeopathic doses are used", or "there is no consistenet recognized effective dose for SLIT", or "It's not FDA approved for use" (a blatant lie--it's off-label use of an FDA approved extract--perfectly legal) My response to all this nonsense by the allergy community?

So What?  Let's get a life.  Dickering with tired, old arguments is  getting us nowhere--fast.  Let's be thinking creatively.  Let's be innovative.  Let's pursue new "technology" aggressively--in a positive fashion.  In short:

Let's get to work. Let's get a vision.  

Because if we continue dickering amongst ourselves on technicalities, other groups will bypass us, and we'll simply be left with a less efficient, less convenient outmoded technology, utilized by a dwindling "customer base".  And then the real crisis begins...

Is the Allergy Industry headed to a bailout?  It's already there--we're not financially bankrupt, but we have a more serious bankruptcy issue--with creative innovation.  Someone needs to rescue us from ourselves. I'm afraid we have run out of new ideas, creativity, and innovation.  We're scared. Not innovative. In short, we're intellectually bankrupt--and that, my friends, is where the bailout is needed.  

Later, Dude

One of the great theological writers of our time was C.S. Lewis,--a true "Thinking Man's Theologian".  One of his greatest works was "The ScrewTape Letters", and it was largely because of this work (and others) that he eventually made the cover of Time Magazine.  The Screwtape Letters" is a Christian Satire, first published in book form in 1942. The story takes the form of a series of letters from a senior demon, Screwtape, to his nephew, a junior tempter named Wormwood, so as to advise him on methods of securing the damnation of an earthly man, known only as "the Patient.  It's a truly great work...and as I was reading it again, I couldn't help but think...

                   What if there was a Screwtape Letter...                               for Allergists?   

Well, read on...

                                                                                     My dear Wormwood,

I have been informed of a most dire circumstance in your patient--namely, that he wants to become an Allergist.  This is very worrisome, and bears extreme concern and attention--for Allergists have the capacity to help many people (30% of humankind, so I'm told), and offer relief from suffering in the human condition--something that obviously we want to perpetuate whenever possible and The Enemy weeps to see.  However, we must make the best of the situation, and there is no need to despair, provided you work hard on certain things. At best, we can render him a frustrated, ineffectual healer who misses the true Potential of what Allergy care and treatment is, and lives out his life in a dull, monotonous manner, helping as few people as possible.  How do we do this?  It's not hard:  

First, if you notice, infectious disease specialists never have forgotten that they have to deal with bacteria, viruses, all the time.  Their starting point is the organisms that affect humans.  They seem to have the nasty habit of dealing with all organ systems affected by viral and bacterial particles.  The Allergist has exactly the same relationship with the environment--except with allergens instead of bacteria.  Therefore, it is extremely important that you do everything possible to help your patient forget that allergens are the focus of his work, and that they can effect multiple organ systems, just like viruses and bacteria.  There is fortunately, much you can do in helping him along this pathway of amnesia.  For one thing, make him think of himself as a one-organ doctor.  "Asthma, not allergens", should be the mantra whispered in his ear whenever you get the chance.  Get him enamored with the various colored inhalers that humans so like to use.  Make him lose site of his focus.  Remember--loving asthma (as if "love" is a word that we even approve of down here!) is not enough--we prefer to have him passionately obsessed (there it is!  a much more favorable word!) with it.   This will help immensely in limiting his potential to help all people who suffer from allergy.  Because It's true that all mucous membranes (and the skin!) can have allergic manifestations--but don't let your budding allergist realize that!  And remember--one of our great Allies in this effort are the many medical societies now-in-days that seem to focus on asthma, to the exclusion of the "bigger picture".  Remember, we want him to see Allergy as Asthma, and Asthma as Allergy. Period.   It's that simple!  

Secondly, stifle his sense of curiosity whenever possible. The most dangerous characteristic an allergist can have is curiosity.  You can do this in several ways.  By all means, encourage him wherever possible to view lab tests and prick tests as Gods themselves.  He should "stop thinking and start pricking" whenver he sees a new patient. Believe me, this works!  If a patient has a curious story that doesn't "fit" with a few negative tests, encourage him to--and I repeat myself--stop thinking.  Another good phrase to whisper in his ear when he can't come up with an easy answer to a human's problems is, "you do not have IgE mediated allergy".  That will make him superficially satisfied, and the human can continue to suffer!  Get him solely--completely--interested in IgE mediated issues.  The discovery of IgE was the best thing--and the worst thing--to happen in allergy.  Let's concentrate on the "worst" part whenver possible.  It will pay rich dividends for us!  

Thirdly, whenver possible, your future Allergist should not be encouraged to use immunotherapy for his patients.  For it's the only disease-modifying therapy at his disposal, and it carries the grave risk of helping patients to the greatest degree.  How do we keep the allergist from dealing with allergens, and using immunotherapy?  It's not really that hard--especially with the number and amount of symptom relieving medications at his disposal.  Help him get disoriented--to think he is helping the most when he merely controls an allergic process symptomatically.  Human Allergists love the word control.  They talk about controlling asthma.  Controlling allergic disease, etc. etc. etc.  Get him to love the word control. But better yet--get him to be (and here's one of my favorfite words used once again!) obsessed with it.  Avoid the word "cause" wherever possible.  You will have magnificently and completely failed if he becomes a curious allergist trying to find a cause for his patients illness! He should not be thinking of "causes" for his patients ills--just control.  The irony is that when he is thinking he is "controlling" asthma with his fancy inhalers and monitoring peak flow charts, all the while the "allergic march" they talk about continues!  The irony is he really isn't "controlllng" anything at all!  

But now I have to mention one more item...of gravest consequence and concern.  There is currently a movement in Europe espousing a newer form of immunotherapy.  As I mentioned earlier, your young allergist should not even be thinking about immunotherapy.  But I'm afraid it's to no avail in this case...he'll hear about sublingual immmunotherapy (SLIT) no matter what--and be thinking about it.  A dangerous development, to be sure.  But I'm confident we can make the most of it, if we're careful.  First, remember what I told you earlier about curiosity--you must stifle it in this regard.  Keep him happy with his old ways.  Bring up the emotions of fear and uncertainty and confusion to nullify any temporary excitement he might have for this new business of treatment.  Above all, make him think in a defensive manner when it comes to change in his field.  Again, our great Allies in this area will be his professional societies, so encourage him to dutifully follow their dictums, rather than thinking for himself.  Rather than embracing newer forms of immunotherapy it, he should be fighting them!  Remember, it's dangerous for the Allergist to think about allergens.  He could help somebody.  

I'm confident if you follow my advice above, you'll get the desired result, and we'll have one more unhappy, frustrated allergist brought into the fold!  

Your affectionate uncle, 

ScrewTape