Go ahead.  Try it out.  Make my day.  Try to find case histories on SLIT in medical journals.  Sorry, pal, but you won't find any.  None at all.  Zip.  Well, somebody has to start producing case reports on Sublingual Immunotherapy (SLIT) use, right?  Alright, it's a dirty job, but somebody has to do it, and so, since I've had 27 years of experience with SLIT, here goes....

You already know where I stand on the importance of case reports; in my prior entry on The Iatrogenic Atrophy of the Case Report, I gave a Case Report on...you guessed it...the Case Report--since The Annals of Allergy Announced they were no longer going to accept unsolicited case reports in their journal. So here's another unsolicited case report, which I'm publishing online, to outline the versatility of  SLIT in treating a complex case of allergic disease...

Case Report 

Patient X was referred to me by a local allergist on January 4, 2007.  This 20-something patient was referred by her allergist to me, principally to help deal with a loss of food tolerance and progressive food sensitivities.

Background history: 

Patient X had a history of eczema transiently as a young child, and had a lifelong history of asthma beginning in childhood.  Throughout childhood she had recurrent sinusitis.  She was treated symptomatically with antihistamines, and steroid inhaler medications, and overall was doing acceptably well in her teenage years.  As a college student, she was under much stress, working 15 hours part-time and taking 15-18 hours of college credit per semester.  Things were going well until...

The fall of 2005 she suffered from a serious aggravation of upper and lower respiratory tract allergies in Sept & October, followed by bronchitis in October and November.  In December 2005 she developed her first migraine headache, and migraines have been bothersome since then. Interestingly, they were helped partially with benadryl useage...

Not only were migraines bothersome, but in the fall of 2005 she began to notice nausea, satiety, and general stomach distress with eating.  She reduced her food intake and lost about 40 pounds.  Her stomach distress was significant enough to keep her from concentrating on her academic studies. In December of 2006  she had formal gastrointestinal  evaluation;  esophageal biopsies  demonstrated short segment  Barrett's,  and mid-esophageal biopsies demonstrated 25 eos per HPF, borderline for eosinophilic esophagitis.  Her gastric emptying study demonstrated a mild delay to solid phase gastric emptying. 

Past medical history:  Remarkable for multiple concussions playing basketball, with heavy NSAID use; infection while traveling overseas requiring doxycycline useage for 2 months, June-July 2006. 

Prior Allergy Testing & Treatment 

Her referring allergist had enclosed records from still ANOTHER allergist (!!), who had previously done prick testing for inhalants, revealing strongly positive ++++ pricks to ash, aspergillus, curvularia, fusarium, pullularia, rhizopus, stemphylium, mucor, and +++ prick tests to dust mite, alternaria, botrytis, ragweed. 

Prick testing to foods revealed ++++ pricks to corn, +++ to carrot, soybean.   

RAST testing had revealed IgE class I to corn, banana, almond, potato, and soy.  Additional RAST testing had revealed IgG class IV to casein, corn, soy, and IgG III to wheat. Gliadin antibody to wheat was negative. 

She had peripheral eosinophilia at 8%.   

She did not receive immunotherapy. She initially tried to eliminate wheat and corn from her diet, and noted a reduction in migraine headaches for about one month, only to return with a vengance after that.  

Status on Presentation 

Patient's X's major goal was "to help my health so I can complete college."  She had lost 40 pounds, and was afraid to eat.  She had dropped out of school because of her multiple illnesses.  She had chronic migraine headaches, and continual stomach distress.  She was afraid her asthma would again act up in the fall and cause even more problems, but on a day-to-day basis she struggled with frequent migraine headaches and stomach upsets.    

Medications on arrival:  Allegra 180 mg/d, Topamax 50 mg BID, Prevacid 30 mg/d, Advair 500/50 1-2 x per day, depending on season, albuteral prn, midrin prn, skelaxin 800 prn.   

Current diet:  avoiding wheat, corn, corn, milk, beef, soy, bananas, carrots, rye, pork, MSG.  Craving peanut butter.   

Physical Exam:  remarkable for nasal turbinate congestion, coated tongue, cold hands with poor capillary filling.  Lungs clear at time of presentation.  No hepatosplenomegaly or localized abdominal tenderness.

Our Initial Test Results:   

IDT Testing: immediate test results

dust:             9mm       dil #4

Ragweed:    15 mm      dil #5 

Grass:          11 mm      dil #5 

Alternaria:  11 mm      dil #5 

Fall pollen   10 mm      dil #5

Candida       11 mm      dil #1

Mold mix      10 mm      dil #3

Rast Tests: inhalants

Kentucky/June grasses:               IgE Class III

Alternaria mold:                         IgE Class III

Ragweed:                                   IgE Class III

Rast Tests: selected foods in diet currently eating

Egg:                                            IgE Class II

Pea                                             IgE Negative          IgG Class II

Peanut                                        IgE Class I

Almond                                       IgE Class II             IgG Class III

Tomato                                       IgE Class II             IgG Class III

Potato                                        IgE Class I              IgG Class II

Chicken                                      IgE Negative

Candida                                      IgE Negative         IgG Class III

Oral Challenge Testing:

Peanut challenge--immediate severe migraine (eating daily)

Egg challenge--immediate exhaustion (eating frequently)

Potato challenge--immediate sinus pain and pressure

Milk challenge--stomach distress

Candida challenge--exhaustion 

Assessment & Discussion:

On the "surface", this patient suffers from multiple problems:

1.  Bronchial Asthma
2. Seasonal Allergic Rhinitis
3. Recurrent sinusitis & Bronchitis
4. Chronic gastrointestinal distress, nausea, anorexia
5. Migraine Headaches
6. GERD with Barrett's esophagus
7. Eosinophilic Esophagitis (borderline)
8. Gastrointestinal hypomotility
9. Multiple food sensitivities
10. Multiple inhalant sensitivities
11. Oral allergy syndrome from fresh carrots, bananas
    

However, it's necessary to use a chronological, "flow-chart" approach to really appreciate what the hell is going on.  Believe it or not, getting an "integrated" view of this case isn't really that hard if you go back to some of the principles I outlined in my prior entry Diagnostic Synthesis in Multiple Food Sensitivities.  Basically, here's how I saw it on the first day I saw her: 

She has had a lifelong history of multiple allergic sensitivities, beginning in childhood with  manifestations of eczema and asthma.  These were not treated with disease-modifying immunotherapy, but "patched up" with inhalers, antihistamines, etc.  Her high-stress college-environment made her susceptible to a flareup in her allergic condition and a further "allergic march to other organ systems.  In fact, it turns out she  had an allergic march through her life--not just the usual respiratory "allergic march", but a VERTICAL allergic march involving her GI tract and Neurological systems (migraine) when she hit the fall allergy season and had an overload of ragweed and alternaria exposure. 

She had enhanced permeability brought about by high NSAID useage and Candida overgrowth.  (Prior concusions and high NSAID use followed by 2 months of doxycycline immediately before the onset of her symptoms).  Enhanced intestinal permeability subsequently caused aspread of food sensitivities during the fall mold season; Candida growth was further aggravated by the additional antibiotics she took in the later part of the fall for bronchitis.  Since enhanced intestinal permeability was her real problem, it didn't surprise me to hear she was only temporarily better on a wheat and corn free diet.  It didn't surprise me she had a migraine triggered by peanut on her first visit, since this cross-reacts with soy protein, already a formerly diagnosed food allergen.  (The beauty of food challenges is you can actually see what "target organ" is affected by a particular food.  For example, peanut triggered a migraine, but milk triggered intense stomach upset.)

Treatment Plan 

This involved 3 major areas:

1.  Improve intestinal integrity:

     ---Probiotics, oral cromolyn sodium, and short-course  fluconazole

2.  Reduce inhalant and food sensitivities with immunotherapy:

      ---SLIT immunotherapy to inhalants & foods (including all molds), titrated off RAST & IDT tests

3.   Offer patient food choices in a structured manner, since she was afraid to eat anything when first seen:

      ---Rotary Diversified Elimination Diet avoiding initially wheat, peanut, soy, carrot, banana, melon, egg, almond, pork, milk, corn, tomatos, MSG but allowing other foods on rotation

4.  Prevent a recurrence of a "crash" in the fall of 2007, like she had in the fall of 2006, by using highpotency preseasonal Ragweed treatment. 

Clinical Course:

We had first seen this patient on Jan 4; by Feb 5 (one month later) she her migraines were in complete remission and she was feeling well enough to return to school and complete her course requirements.  On her March 5 visit she related she had 1 migraine (stress from midterms).  She found improved food tolerance on SLIT, and at that point was able to reintroduce milk and beef back into her diet on rotation.  By May 2007 she was able to taper off of gastrocrom, and able to handle most foods, but still had problems with wheat and soy.  Her eosinophilia of 8% had improved by July to 2%.  She took high-potency preseasonal Ragweed treatment for 6 weeks before the ragweed season.  When she was last seen by me in November, she related she had an excellent fall allergy season, especially in light of camping out 3 weekends in August!  She was delighted she did not have her bronchitis episodes in the late fall like she had last year.  Food tolerance continued to improve, migraines were in remission, she was gaining weight, and only used gastrocrom when eating out at restaurants but still took SLIT for inhalants and foods faithfully.  She was off of Advair ("I don't need it") and her FEV1 was 4.546, 116% of predicted. 

Important Points:

There are actually several points to be made with this Case Report:

1.  Bad things can happen to a patient with multiple allergies who receives no disease-modifying immunotherapy approach, especially if their allergic "load" continues to build in a hidden fashion.    

2.  The "allergic march" can include not only the classic upper/lower respiratory tracts and skin, but also the development of neurological symptoms, including migraine headaches, and (arguably) eosinophilic esophagitis.

3.  The concept of a "critical allergic mass" is important in this case--the patient began to decompensate during the fall ragweed/alternaria mold season, when the additional load of inhalant allergens on previously existing occult food/Candida sensitivities put her in an "overload."

4.  Enhanced intestinal permeability needs to be addressed to stop the spreading of food sensitivities.

5.  SLIT can be safely used, even in patients who are polysensitized.

6.  Eosinophilic esophagitis is one more manifestation of a broadening allergic picture in this patient, rather than a totally distinct issue to be dealt with separately.  Interestingly, I have had one more patient (a doctor's son) treated with SLIT for eosinophilic esophagitis, who had a repeat biopsy confirming complete remission (the current patient has not had a repeat biopsy). 

7.  High-potency preseasonal ragweed SLIT helped the patient enjoy a healthy fall allergy season, with no recurrence of previous chronic bronchitis or other serious respiratory illness.

Her referring allergist was initially skeptical of SLIT useage, indicating in his first letter to me that "I would be somewhat hesitant to use SLIT, taking into account her current gastrointestinal complaints."  His most recent letter to me is as follows:

"I am very impressed with your management of patient X.  You and your staff have done a very nice job in managing a patient who is difficult to manage with the standard allergy management.  Keep up the good work.  

 It is gratifying to have tools to help complex patients such as this.  SLIT is one of them.  

Later, Dude   

Certain things in life you just can't get seem to get enough of--money, chocolate, a Chicago Bears win, and...nice letters from blog readers. An  Italian Allergist recently wrote me in response to my prior blog entries, Why we DON'T need more allergists, and The Allergist:  Odd Man Out.   Here's what he says: 

"I am an Italian allergist and I have read with much interest your reply to the title "we need more allergists" from the ACAAI.   I agree with nearly all your points about the shortcomings of today's allergists, but I think that you are wrong in one point:  the idea that the answer is SLIT.  As you know, SLIT in Europe and particularly in Italy is widely studied, prescribed, and used.  But the problem is that some companies producing SLIT are offering this treatment to general practitioners and family paediatricians, hoping to increase in this way the number of prescriptions.  In Europe in the next years SLIT will be available in the public pharmacies, just like anti-histamines, etc.  In my opinion, and in the opinion of nearly all Italian allergists, we do have to go back to immunological control and immunotherapy, as you correctly state, but in order to differentiate our profession from other specialists the answer is turning to subcutaneous immunotherapy, especially now the new biotechnological products, such as recombinant immunotherapies, are really around the corner.  Congratulations for your site and happy new year!"

Awesome letter.  On several points.  First and foremost, he likes my site, so this means of course he's truly an intelligent and discerning individual.  But beyond that he raises an interesting question--is SLIT truly "the answer" for the allergy profession, when it will be available for seemingly everyone to use--patient, family physician, pediatrician, ENT physician? 

On one hand, we can treat a larger proportion of our patients safely with SLIT, but is this meaningless if we get no referrals because everyone else is doing it?   In a sense, the author poses a large and critical question--The Allergist and immunotherapy:  Quo Vadis?  The author above apparently feels that injection immunotherapy (SCIT) is "the answer", since he states "in order to differentiate our profession from other specialists the answer is turning to subcutaneous immunotherapy, especially now the new biotechnological products, such as recombinant immunotherapies, are really around the corner."  I take exception to this view, for several reasons:

1.  On a practical basis, when SLIT is available over-the-counter, many people will logically use this first, before going to an allergist. If they get relief, they'll stop there.  If they don't get relief, or have side-effects from SLIT, then they'll see an allergist.  Are these "tough cases" the ones we want to put on SCIT, after they've had side-effects from SLIT or not responded?  If they had side-effects from SLIT, they will likely have side-effects from SCIT--probably more severe.  If they didn't get relief with SLIT for (as an example) grass pollen, then they might be unstable and polysensitized, for example, to grass AND mold--again, not an ideal SCIT population to treat. 

2.  It's hard to "market" SCIT to a patient population and emphasize they should see an allergist for it, when there is SLIT available over-the-counter, as the author mentions, in the very near future.  SLIT is just too damn  convenient.  I talked about this in an earlier blog entry when I likened SCIT to "painting" and SLIT to "photography".  We still use both in our society, but one technique is used alot more--because of its ease, convenience, and cost-effectiveness.  (See entry One picture is worth a thousand words:  immunotherapy, painting, and the birth of photography) 

3.  SLIT is more versatile than SCIT.  And it's versatility, like Rodney Dangerfield, just "doesn't get respect".  SCIT just doesn't work for molds, and SLIT does.  SCIT just doesn't work for late-phase reactions, and SLIT does.  SCIT hasn't been shown to work for foods, but there's emerging evidence that SLIT works for foods.  Multiple protocols should be developed for SLIT--and we use these in our office. 

4.  Granted, recombinant immunotherapy is attractive and sexy, but it's way farther back than SLIT for approval--at least in our country. 

The author is truly correct in that--technically speaking-- "SLIT is not the answer".  I'll tell you what is:  Doing SLIT better than everyone else.  And I mean everyone. 

I've used SLIT for 27 years, with multiple protocols--high dose European-style and IDT low dose for late-phase mold allergy.  As times change, I  have increasingly seen patients on SLIT from other practitioners who have failed treatment--and we have to offer them more than SCIT to help them. The "next-generation" allergist better be ready for these patients!   Example 1:  A patient on low-dose SLIT from a practitioner treating her for mold allergy, when her real problem was a moldy home and inadequate SLIT dosing. SCIT wouldn't have helped this patient at all.   IAQ improvement in her home, and higher dose SLIT for molds did.  Example 2:  A patient not getting relief on SLIT from another pracitioner because of an undetected food yeast allergy in a patient who was mold sensitive.   Again, SCIT wouldn't have helped this patient. And SLIT did. 

Finally, It's always risky to differentiate our profession from another by just a technique--and that's all SCIT and SLIT are---techniques.  Tools.  It's not the hammer and nail that make the carpenter, it's the other way around...We not only need to be the best at delivering immunotherapy, but we need to be the best diagnosticians around--for all allergic diseases, not just asthma.  This (I guarantee you) will make patients come knocking at your door.  See my entry "How we can fix it" for more. 

The Allergist, immunotherapy:  Quo Vadis?  The answer to this question will determine the direction of our specialty and its survival in the future. 

Later, Dude 

As a blogger, I love it when readers write in...it means somewhere out there people are actually READING this stuff...my last entry talked about the potential for a "Hidden Agenda" propagated by the major allergy societies for SLIT..."packaging" it so that the traditional allergist is the sole purveyor of treatment, by "pumping up" it's side effect potential so that other physicians won't be as tempted to use it.  A reader wrote to me after this entry,

I have been thinking about an interesting medical legal point.
Traditional allergists live in fear of lawsuits from anaphylaxis. It is a problem of their own making.If SLIT is accepted and recognized as very safe, then a physician using a much less safe method does not have a defensible position.A reasonable patient would choose a safe method of treatment which is effective. So part of the SLIT anaphylaxis campaign is to protect against reasonable lawsuits from SCIT anaphylaxis where the physician
did not choose a prudent treatment method, ie SLIT.Even if there really are a handful of adverse reaction from SLIT, the relative risk is several orders of magnitude higher for SCIT.

You're right, pal.  This is one more reason to inflate the side effects of SLIT.  So look for more emphasis on SLIT side-effects in the future.  We can't have a treatment that's TOO safe, right?  It would make injection immunotherapy (SCIT) look bad.  And we don't want that now, do we? 

Later, Dude

I'm a father of 3 teenagers; and I've learned that sometimes underneath the apparently innocent straight-forward question, "Dad, can I borrow the car?" there's a hidden agenda.  I love my teenagers dearly, and usually (if there is) a hidden agenda, it's relatively innocuous. 

But sometimes I've been glad I've asked myself if there's been a hidden agenda.  Because occasionally there was a hidden agenda.

And I was glad I asked the question. 

And it is in this spirit that I have comments and concerns about how our major allergy societies will view sublingual immunotherapy (SLIT).  Like my teenagers, I dearly love my allergy societies that I belong to.  But like my beloved teenagers, I think it's healthy to ask if there is sometimes a "Hidden Agenda" at work.  I realize that there is always a fine line between being paranoid and being prudent.  But for argument's sake, let's let the ultimate "loose cannon" of allergy--the Angry Allergist--fire off a shot or two, and "weigh in" on this topic.  

We all know that our major allergy socities have SLIT on their agendas--ostensibly to study, debate, and ultimately comment on the usefulness of SLIT to treat our allergy patient population. 

But what if there's another agenda--a Hidden Agenda that is either consciously or subconsciously on our collective minds?   

Why would the Hidden Agenda make sense?  How could it involuntarily arise?  In my opinion, the Allergy Profession  is going through its Second Great Crisis.  What was the first crisis?  The development and subsequent wide availability of effective non-sedating antihistamines and effective asthma controller medications that non-allergists could prescribe.    Non-allergists could suddenly treat asthma and allergic rhinitis cases without referral to the allergist for injection immunotherapy.  I remember being interviewed on television about one of our professional allergy societies stating they were against loratadine being OTC.  Why?  To protect "our" patient population, it seemed to me.  And it really made no sense that benadryl could be OTC but not loratadine. ..unless a Hidden Agenda is invoked, that is...

Now we have a second Great Crisis in the Allergy Profession:  The potential availability of a form of immunotherapy that is safe enough to be done by non-allergists.  Grazax is available in Europe.  SLIT will be available soon here.  And the ENT community has shown a great deal of interest in it. In fact, alot of family physicians have shown an interest in incorporating it into their practices.  But not allergists.  They still have injection immunotherapy, and it's their Exclusive Domain.  Could this have something to do with why we don't have a rush for more American-based SLIT studies?  Where are they?  If we understand the Hidden Agenda, the answer becomes obvious--as long as we have no American-based SLIT studies, insurance companies will exclusively cover injection immunotherapy as "the only game in town"...and the allergist is safe with his patient population.  A recent ACAAI poll of allergists on their biweekly newsletter gave a telling statistic--over half of all allergists surveyed were fearful that SLIT would result in a loss of income to their practices.   Could this be one reason  the American Allergist isn't rushing to prove SLIT works?  Just a thought...

Here's another puzzling phenomenon that could be explained with a Hidden Agenda--an emphasis in major American allergy position papers on anaphylaxis risk of SLIT and its potential for problems, even though many studies have shown its safety.  As long as SLIT is seen as something with potential serious complications, we have "packaged it" for being done by allergy specialists exclusively.  Generally, SLIT is so safe that non-allergists can make use of it, but if there is a Hidden Agenda, then we should be prepared for an emphasis on how scarey SLIT is, and how it is "best" left exclusively for the Allergist to do...Just a thought... 

So I wonder whether there's a potential hidden agenda that we have to watch for:  "packaging" SLIT as a technique to be used exclusively by allergists for their patients--to "capture" our patient population.  As I implied before, maybe there's a Hidden Agenda, and maybe there's not.  Also As I said before, the line between paranoia and prudence is a fine one.  But as a father of 3 teenagers, it has paid off to watch for hidden agendas.  And we allergists should do the same.

Later, Dude