I love movies...any movie.  But the movies I love the most are from what I call "The Golden Age of Movies"...You see, way back before the digital "light and sound shows" of today, there were...Actors.   When Bogie walked into Rick's Cafe with his white tux and cigarette, he didn't need any sissy digitized backdrop to jazz things up or to compensate for any lack of acting on his part.  The movie and the power behind the movie was:  himself. Pure and simple. No Pixar.  No computers. 

And it was magic.

And a long time ago, I contend we had a similar Golden Age:  Of Allergy.  Am I just being maudlin?  Think about it.  There was a time when allergists diagnostically didn't have serum IgE levels or other immunological parameters to measure and follow; to "fall back on" when seeing a patient.  They only had their 4 senses, and a skin test.  They would listen to their patient, observe, and draw their own conclusions, not preconceived by the "tyranny" of IgE (i.e, "it's not IgE mediated, so who cares?").  If a patient ached after eating a food, they recorded it.  If a patient had vaginitis symptoms after an exposure, they recorded it.  If a patient had headaches after  ingesting a food, they recorded it.  It was in this spirit of observation that Albert Rowe's textbook on food allergy was born.  Likewise Arthur F. Coca's textbook "Familial Nonreaginic Food Allergy".  And Rinkel, Randolph, and Zeller's work "Food Allergy".  The list goes on and on.  These are seminal examples of the Clinician At Work.  And just like we can learn alot about how to make great movies NOW, when we watch the Old Masters at work in classic flicks, so we as modern allergists can take a cue from the Old Masters when it comes to broadening our horizons in the present day allergy field.  As I've said before in prior entries, the discovery of IgE was the best thing--and the worst thing--for the field of allergy....for when we got IgE... we ceased being curious...

  In the Golden Age, the allergist also didn't have effective "asthma controller" medications for their patient population.  Perhaps this made immunotherapy much more attractive than it is today--it was, so to speak, "the only show in town".  We certainly had a number allergists actively trying to optimize immunotherapy treatment  at that time--Herbert Rinkel, French Hansel, and others were very active in this area....Our mantra at the time was not "Asthma Controller Medication" because we didn't have effective controller medication at the time--immunotherapy was the only performer on stage....

Now, am I suggesting that the "old days" of allergy were better than what the modern allergist has to offer?  No, of course not.  But I am suggesting that we can learn from early clinicians, who were unencumbered by the "knowledge" we now have about immunological mechanisms, and take away a valuable lesson:  focus on the patient and their reactions to the environment, even if it is non-IgE mediated.  ... Which brings me to the topic of my next miniseries, "The Late Show", which will begin shortly... 

"The Late Show" stars "The delayed skin test reaction", which, like Rodney Dangerfield, "just gets no respect" by the allergy community at large.  Yet, this is not a new phenomenon:   it was first described by Walker & Adkinson in 1917.  They described "hot, very red, slightly elevated reactions..resembling a mild infection, but sterile...(which) disappear over the next two days..."  And over the next 90 years, have we made any progress in this area?  Take a look at what a standard allergy textbook says about the matter...

"Late phase reactions are often not recorded because their exact significance is unknown..."

       --Allergy, Principles & Practice, 5th Edition

         Elliott Middleton, Ed
 

Here is an official statement by the ACAAI concerning delayed skin test reactions:

Delayed reactions can occur several hours after skin testing, sometimes causing swollen, reddened bumps at the spot where the testing was done. The delayed reaction usually disappears 24 to 48 hours later, but should be reported to the physician. However, when there has been no immediate reaction, delayed reactions do not signify the presence of allergy. (my emphasis)

As clinicians, we should follow the skin text to extinction.  Not become bored with it after ten minutes of observation.  Where is our sense of curiosity?  What an incredible cop-out to say it "doesn't signify the presence of allergy".    Well, what DOES it signify, Gaylord?  "Shouldn't we be listening to the patient, recording their delayed skin test reactions, and trying to make sense of this mystery without preconceived notions--in short, trying to emulate the Old Masters  in "The Golden Age" of allergy?  As the late Keith Eaton MD explained, in writing about the delayed skin test, he concluded:

"there must be a strong presumption that such reproducible and marked bodily reactions are not going to be without biological significance, which is probably associated with a disease state..."

"But you're not talking about an immediate skin test reaction", I can almost hear you say, "so it isn't a concern".  Well, you know how I feel about lack of interest? To quote another figure from the Golden Age of Movies,

Frankly, My Dear, I don't give a damn..." 

As I've mentioned before in a prior journal entry, one of the hallmarks of a superior allergist is simply being curious about what we can't easily explain.  And our sense of curiosity is unfortunately as empty as a cannister of albuterol in the hands of a status asthmaticus patient...but no more...for grab your popcorn, because we're going to "The Late Show"--and confront the mystery behind the delayed allergy reaction. Stay tuned...I promise this show is a good one...and in the meantime, as one of my favorite actors was fond of saying, "Here's looking at you, kid..."

Over the years I've been perplexed by the "deep" questions in life...questions like "Why does evil exist?", or "Why do men have nipples?".  Questions such as these have caused me many sleepless nights.  Sometimes, I've found answers to these tough questions, such as "How Many Allertists does it take to change a light bulb?"--see my journal entry of the same name for the answer to this profound question.  Sometimes, however, I need help.  And such was the case when recently the the most profound, perplexing question of my life entered my head:

Why did the Allergist cross the road? 

I needed help on this one.  And I needed it bad.   I was fortunate to catch Jim   in the hallway, and query him on this.  Jim is a savvy doc and I knew he'd have the answer.  His answers/comments were so profound that I am copying the transcript verbatim, for the benefit of my blog readers.  Herewith is our conversation: 

Me:  "Hi Jim"

Jim:  "Hi George"

Me:  "Jim, I've been thinking, and I need--"

Jim:  "Whoa there.  You've been thinking again?  You know that's a high-risk lifestyle behavior for you...  Ever think of cutting back?  Gradually tapering down?  I think I could order you a patch to help.  I know it'll be tough to quit, but would you give it a try?

Me:  "Cut the crap, Jim.  This is serious.  I need help.  I'm going crazy with a question I can't answer.

Jim:  "You're already crazy.  But no matter.  What's the question?

Me:  "Why did the Allergist cross the road? 

Jim:  "Why did the Allergist cross the road?

Me:  That's what I said.  I'm not looking for an echo chamber, I'm looking for an intelligent response.  Think you're up to it, or will I be disappointed again?

Jim:  That's an easy question to answer.  Because he didn't.

Me:  He didn't what?

Jim:  He didn't cross the road.  He never has.

Me:  Your're kidding.

Jim:  No, I'm not kidding. Crosslink-my-IgE-and-hope-to-die-not-kidding.

Me:  He didn't cross the road--this is for real?

Jim:  Right.  Like I said.  Never crossed.

Me:  Didn't cross at all.

Jim:  Nope.

Me:   Jim, this isn't one of your sick jokes, is it? 

Jim:  My jokes aren't sick--they maintain a very healthy proactive lifestyle--unlike your thought processes...But to answer your question, no, this isn't one of my jokes.

Me:  You're sure?

Jim:  I'm sure.

Me:  So the Allergist never crossed the road, then?

Jim:  You're a quick learner.

Me:  But what about the chicken data?  You know, that chickens cross the road to get to the other side?

Jim:  Yeah, yeah, yeah.  We all know about the animal studies, and in fact four recent meta-analyses on randomized double-blind placebo-controlled crossover trials in chickens concluded that road crossing is safe and effective--in animals.  But unfortunately there are no human studies, and you know what that means...

Me:  Oh no, that doesn't mean what I think it means, does it?

Jim:  You bet your basophils it does.  Road crossing is an unapproved technique; the FDA hasn't approved it for human use yet. 

Me:  An unapproved technique?  That's like having smallpox!  No allergist will ever attempt to cross the road if it's labeled an unapproved technique...

Jim:  That's right.  And most importantly, no insurance company will reimburse the allergist to cross the road either.

Me:  You mean all the allergists are standing on the side of the road, and have never even tried to cross?  So they're going nowhere? They're just standing on the side of the road?

Jim:  George, when did allergists ever get enthusiastic about going anywhere with a new technique?  Simply put:  Chickens cross the road, allergists are sheep...But cheer up, George, there are anecdotal reports of some ENT's crossing the road successfully to get to the other side. 

Me:  But what about the American Chicken Agricultural Association Industry and the American Animal Agricultural Association Industry? What's their position on this issue?

Jim:  You mean the ACAAI and the AAAAI? 

Me:  Yeah, what do they say?

Jim:  Well, the ACAAI and the AAAAI and their corporate sponsors from Big Farma have formed committees to look into road crossing although I would add that to my knowledge, no one on these committees has actually had clinical road crossing experience. 

Me:  But road crossing is safe, and it's effective to get to the other side!

Jim:  Well, we may know that, but the ACAAI and the AAAAI have adopted a "slow walk" policy to assess safety and efficacy of this "unproven technique"... They say many questions remain unanswered: exactly how fast should we walk?  Do we look both ways or one way before crossing?  Do we hold hands when we walk across the road?  Many questions remain. 

Me: That sounds like chicken sh** to me. 

Jim:  Relax--cut the profanity, ok?  No need to get so hot and bothered about this...You know, you're getting to be like that head-case whose got that blog...the Angered-Allergist, or something like that out there. 

Me:  ...

Jim:  Face it:  that's the way life is sometimes....eventually, the Allergist will cross the road, and get to the other side. 

Me:  Yeah, well I just hope it's in my lifetime...

Jim:  And by the way, remember what I said about cutting back on your thinking?  I've changed my mind on that one.  You should just quit.  Cold turkey. 

Our miniseries is coming to an end...I always hated the end of a good miniseries.  You get so comfortable with all the characters in the first few episodes, and then--poof!  End of show.  But, like "Roots", this is a miniseries with a message...and in this case the message is that we--as allergists--need to take responsibility for all allergic disease, and not pay "lip service" to allergic vaginitis (or other illnesses involving other target organs), and still call ourselves "allergists".  In that sense, my "example" of allergic vaginitis as something ignored is part of a much wider picture of other diseases that allergists have de-emphasized in our quest to become the Super-Asthma-Doctor.  What should we do?  Here's a specific suggestion:

Get involved with your local gynecologists, and seek referral of women with chronic recurrent vaginitis with current atopic histories, for starters.  Over the years I've worked with several savvy gynecologists on mutual cases--cases that would have never improved without the concurrent treatment of a gynecologist and an allergist (myself). Take a good allergy history, treat with SLIT, and watch the vaginal symptomatology improve.   In my experience, when you have a highly atopic patient with recurrent vaginitis issues, you are dealing with an allergic vaginitis issue until proven otherwise.  This would be a safe--and potentially very rewarding place--to start. 

In this miniseries I believe the primary actor--the allergist--has "set out" for most of the performance. We haven't seen hide nor hair of him/her...I have a dream of the allergist returning in a sequel to this original miniseries--as a major player--and not a two-bit actor.   Let's enter the miniseries now, and say "Play it again, Sam..."

Yeah, I know.  Some of you may have written in and suggested that I am too sarcastic; my cynicism about our profession is too great; that my satire on the allergy profession is too biting, that I am too bitter.  But hey, you could think of me like that ice-cold shower you take on the morning after a long night out--painful, hard-to-take, but in a way refreshing, and it gets the job done.  Nevertheless, there may be some merit in what you say, so...well, I hear ya, Ralph.  So I'm turning over a new leaf.  No more Mr. Bad Guy.  So here goes:  I would request that all of you allergists take a moment from your busy lives and please--pretty please, if you will--clear your desks (and minds) of your asthma inhalers, asthma patient education booklets, asthma medication samples, asthma peak flow meters and color charts, asthma guideline protocols, asthma posters, asthma questionnaires, asthma textbooks, asthma journals, asthma-tips-for patients brochures, asthma controller meds, asthma semi-controller meds, asthma ultra-controller meds, and begin to think about a topic too rarely discussed amongst colleagues and friends in our own little bronchospastic let's-control-asthma world--a topic so radical it's almost beyond bearing: 

allergy.

yes, allergy.  allergy  on another mucosal surface.  

Oops.  Sorry.  ...And I promised to turn over a new leaf...but hey...I've got liftoff, so I feel great...

  But honestly, In our eagerness to examine the respiratory tract, how many of us really take an allergy history with an emphasis on vaginal pathology?  I have.  For 26 years.  And I have to say it's been an eye-opening 26 years. You see, basically, the vaginal mucosa responds to same 3 things that the respiratory tract mucosa does:  allergens, irritants, and infections.  And these 3 items are not mutually exclusive, and may co-exist together.  Keeping this concept in mind has helped me in achieving perspective in observing  allergic vaginitis in my allergy patients.   The following observations have come from listening to patients, testing them, and following their treatment.

1.  True atopic sensitivity to Candida antigen exists. Allergic vaginitis may exist by itself, in clinical "isolation"  (like the child who "just" has rhinitis) but many times in my experience it is associated with coexisting respiratory tract disease.  Suspect allergic vaginitis with Candida sensitivity  when a woman has positive immediate (not delayed) reactivity to Candida antigen on prick or intradermal testing, and when she has a history of vaginal pruritis with repeated negative gynecological exams.  Often a woman will complain to her gynecologist of intense itching or burning but be subsequently told she that has "just a few yeast cells" (or none at all) on exam, and told she "shouldn't worry."  She then may use an OTC antifungal vaginal cream with some relief. If she has a seasonal component to any traditional allergic illness, she may note that the vaginal symptoms flare the same time as her respiratory tract flares. 

2.  The vaginal lining may be reactive to food antigens.   Typically, food yeast, dairy and wheat are frequent offenders in the allergic vaginitis patient, but just like with other target organs in the body, virtually any food may play a potential aggravating role.  And, just like the respiratory mucosa, if an allergic response goes on for a long enough time, subsequent infection can ensue.  For example, I have a nurse I've treated who could eat citrus in limited quantities--a small amt would give leukorrhea, and 3 successive days would result in a documented yeast vaginitis episode on multiple separate occasions. Remember that small amounts of food antigen can be present in semen (see Part I of this series for the reference on the case of a woman sensitive to walnuts who had anaphylaxis on one occasion after having sex with her husband who had ingested walnuts prior to intercourse).  Thus, the vaginal mucosa is getting exposure to small amounts of food antigens in a woman having intercourse with her partner.  If a female allergic patient has a severe food reaction (like to peanuts) it is critical that her sexual partner avoid eating this food prior to intercourse! 

3.  Seasonal allergic vaginitis exists:   Many women who have a seasonal flareup of their respiratory condition in the spring/summer may have a flare-up of yeast vaginitis as well at the same time.     

4.  There is an allergic "triad" of Candida-mold-food yeast hypersentivity:  Just like there is the "hyperlipidemia-hypertension-cardiac disease" triad, we have a triad of "mold-Candida-yeast" triad for our profession.  For example, Airola et al last year described "clustered sensitivity" in a patient with documented reactions between multiple molds and baker's yeast.  Savolainen et all in Allergy in 1988 pointed out "atopic patients primarily sensitized by C. albicans and S. cerevisiae may develop allergic symptoms by exposure to other environmental yeasts due to cross-reacting IgE antibodies" .  Clinically, when you encounter a patient with documented sensitivity in one of these three areas (i.e., mold, yeast, Candida), --be sure to check out the other two.    In my experience, you will be richly rewarded diagnosticaly if you do this.  There is an intimate relationship between mold exposure and allergic vaginitis:  For example, patient X, a biology teacher, is one of my patients.  After being outdoors and digging in the dirt collecting mushroom samples with her studies, she returned back to the classroom with her students.  She was astonished to find that  within minutes after the mushroom exposure she had intense vaginal pruritis and burning.  This was accompanied by mild (and more tolerable) nasal congestion symptoms. I have one other patient with an identical story.   

5.  Vaginal symptoms with protected intercourse may be related to latex condom sensitivity:  warn your latex sensitive female patients about latex condom useage in their partners!   

6.  Antihistamines may be helpful for allergic vaginitis:  Just as for allergic rhinitis, I have occasionally found that routine systemic antihistamine medications may be helpful for allergic rhinitis.  I have also have used custom-compounded cromolyn sodium in coca butter intravaginally applied to be helpful on rare occasions.  There is a case report by Dhaliwal et al on allergic vaginitis due to ragweed, in which no success was obtained with antihistamines for controlling symptoms, and for which prednisone was provided for the ragweed season, with complete control of symptoms. 

7.  SLIT immunotherapy for offending allergens can greatly help the woman with allergic vaginitis and reduce the incidence of yeast vaginitis: Over the years, I have employed treatment for allergic vaginitis in the same protocol as I use for treating allergic rhinitis or asthma:  Identify the precipitating allergens, irritant, and infectious factors, and treat appropriately, with emphasis on SLIT for allergenic sensitivity issues.  This has been a rewarding experience for my patients, as well as myself, since treatment of allergic vaginitis can symptomatically help the patient, as well as reduce the incidence and severity of recurrent yeast infections...

So what's with the horse with the blinders, you ask?  Judging from the title, you were expecting vaginas--not horses, right?  Well, the whole point of my last two entries is that the typical allergist is so hung up on the respiratory tract, he/she cannot look either left or right--just straight ahead, plodding down the 'ol dusty respiratory tract:  from the tip of the nose down to the last terminal bronchiole.  And in the process of "putting on the blinders", he/she morphs into an "asthma doctor"--and becomes less of an allergist than he/she was meant to be.  And frankly the horse is to be given more credit than allergists--at least the horse had the blinders put on him by someone else.  In our case, we put the blinders on ourselves.  As an "asthma doctor" we offer less services than a pulmonologist (no bronchoscopy, no respiratory tract skills for handling the severely ill asthmatic) and we offer less services as a "compleate" allergist.  In truth, by trying to be both things, we really become neither. 

Succinctly put:  if we want to be better allergists, then we better "take off the blinders" and look around at all the mucosal membranes in the body.  In my last journal entry, I promised that "I'll give one more simple example of an area we have shamelessly ignored, to the detriment of our practices and our patients..."  And so begins The Vagina Monologues

By the way, this really is a mini-series, so set your DVR's for the next 3 installments:

• Part I--The Vagina as an immunologically reactive organ
• Part II-Clinical relevance in everyday practice
• Part III Suggestions for the future

Part I--The Vagina as an immunologically reactive organ

As I mentioned in my earlier comments, curiosity is essential in being a better allergist.  And why should we be curious about an organ that is so far removed from the respiratory tract?  In truth, there are some compelling reasons:

• The human vaginal basal lamina contains macrophages, lymphocytes, eosinophils, plasma cells, and mast cells
• IgE antibodies specific to C. albicans, seminal fluid components, pollen and spermicides have been identified in vaginal fluids of women with recurrent vaginitis
• Prostaglandin E2 can be found in the vagina
• Vaginal smears containing eosinophils have been observed
• IgE induced histamine release is a potent inducer of prostaglandin E2 from macrophages, which in turn suppresses the cell-mediated immune response necessary to keep Candida albicans in check
• At least eight publications from 1920 to 1995 describe allergic vulvovaginitis due to pollens
• In 1978 Haddad (Perspect Allergy 1:2-3, 1978)reported the case of a woman allergic to walnuts who developed anaphylaxis on one occasion after intercourse with her husband, who had ingested walnuts prior to coitus.  Seminal fluid revealed the presence of walnut protein. 
• In 1988 Witkin identified Candida albicans specific IgE in vaginal washes 
• There are in the literature at least five case reports and five open studies, including 177 patients suffering from recurrent vaginal candidiasis who had been prescribed Candida albicans allergen immunotherapy.  These women had positive immediate skin tests to yeast and showed improvement ranging from 65% to 80% on immunotherapy
  

In truth, allergic vaginitis is a well-defined clinically significant entity; there was a superb review article on this by Moraes, et. all in our own Annals of Allergy in October 2000. 

Now, I ask you, are there any follow-up articles, excited comments amongst allergists, letters to the editors, or frequent articles or talks at allergy meetings on this subject?  Nope.  None.  Zippo.  Dead end.  No curiosity.  No interest.  Void.  Null set.  All I hear is the sound of .....loud snoring...You see, we've got those blinders on, and we're too busy plodding down the 'ol respiratory tract road...Our heads are as empty as a 2 year old cannister of albuteral in the hands of a status asthmaticus patient...As Moraes and the other authors point out:

..."resulting symptomatic candidal vaginitis would be a secondary consequence to a primary allergic vaginitis"  (my emphasis)

And of course I don't have to tell you how big a problem recurrent yeast vaginitis is for women.  Like the fact that upwards of 70% of the general female population can have a yeast infection yearly.  But we don't care about that do we? 

In effect, allergic vaginitis is an "orphan illness" which nobody wants to "adopt".  Certainly not the gynecologist--and rightfully so, since they are not allergists and are not familiar with the allergic nuances of mucosal membranes, or with immunotherapy.  However, we as allergists have a bigger responsibility to deal with this illness, and I am confident if we work together with gynecologists we can much more effectively help our mutual patients with this difficult problem...

The vagina--an immunologically reactive mucosal surface.  Think about it...think about the potential to help others...pull the inhaler out of your mouth and get involved with treating this issue...Talk to your local gynecologist...Talk to your patients...Think about it...and be curious...after all, enquiring minds want to know.