Ever get side-tracked, lost your focus, and then shook your head and wondered what WERE you ever doing?  Well, before I got unexpectedly side-tracked by the recent editorial in the Annals of Allergy,  my intent was to use my prior journal entry, The Allergist and The Preschool, as a perfect lead-in to my next topic, "The Total Load" concept.  "The Total Load" concept is, in my opinion, the single most important principle that an allergist can use on a day-to-day basis when dealing with complex allergic cases. Why was the "Preschool" topic so appropriate to the Total Load concept?  I hope it's obvious.  In my parable, the allergist was only "playing" with the blue blocks, neglecting all the others.  Here's a picture of the total allergy load, taken from one of my lectures.  Now, if you can't guess correctly which "block" the typical allergist likes to "play with", I'll degranulate my own mast cells:

You're right, Herman.  It's the green block. (I thought I'd be sneaky on you and switch colors--from blue to green--but you still figured it out, right?)

Allergists LOVE that green block.  They study every single atom of it...meetings continually FOCUS on the green block. They  focus, study, analyze, scrutinize, ponder, meditate on, think about, concentrate on, ruminate about, and deliberate on it.  But there's one big problem here: 

It's not the only block in the stack.  

Allergists rarely look at the "other boxes" when they try to understand their difficult patients.  We're so addicted to looking ONLY at the green box, we ought to enter rehab.  Now, before you get all agitated, I really don't believe I need to  drop another "black box" warning on you--please rest assured you already "believe in" this concept.  You maybe just don't realize it.  Take a well-respected article on Exercise-induced anaphylaxis to celery.   The authors found that a patient could exercise ALONE without problems, eat celery ALONE without problems, but the COMBINATION of exercise AND celery ingestion caused anaphylaxis.  You remember this concept, right?  It's been reported in other journal articles too...and this is one simple example of The Total Load in action. But there are (trust me) alot more interesting (in my opinion) and varied manifestations of the Total Load phenomenon that you'll see in your everyday practice, if you just look for them.  Just "be curious" (my mantra) and "seek and you shall find".  But before I  go into  specific examples in my next  journal entries, there are two important over-arching principles that help you to "suspect" when you're dealing with a "Total Load" phenomenon in any given patient.

Principle One:  A patient with a fluctuating Total Allergy Load of several items often reports that he/she can SOMETIMES react to an item but not ALL the time. Their reactivity varies depending on their load; It depends on whether their total "block stack" exceeds their allergic threshold.  Depends on the number/size of the blocks they are "playing with".   These patients could drive you nuts if you don't understand what's behind their complaints.  You know the type.  They say that "sometimes I eat this/that food and it bothers me, and sometimes it doesn't", "sometimes I mow the lawn and it bothers me, and sometimes it doesn't"...Sometimes, sometimes, sometimes, sometimes,etc. etc. etc. Often they will go along in this "sometimes I react and sometimes I don't" state for a long time, getting progressively more reactive, until a sudden massive, emergency-room type reaction brings them into my office, and very often you can piece-together the total allergy overload they've had at that point.  An Illustration of the "sometimes I react and sometimes I don't" phenomenon is shown graphically below, where the hypothetical patient reacts to the tourquise item sometimes, and sometimes it is below their "threshold":

Principle Two:  A patient with a  fluctuating Total Allergy Load of several items will RARELY improve if just ONE item is treated.  I see this all the time (and I bet you do too!).  You know this type too.  They have chronic sinus/nasal congestion...you find they are dust mite sensitive and they take a nasal spray and don't get any help.  They quit.  They see the chiropracter.  Stop eating dairy.  Not alot of help either.  They then get on SLIT for inhalants, foods, and moderate their dairy intake and they do great!  The "parable" I use to help explain this to patients is "the person with 3 slivers in their foot."  They find one sliver, remove it.  No help.  So they put the sliver back in their food (it obviously didn't help to have it taken out, right?) and they search for another sliver.  They find it, remove it, --and no help.  So they put it back in too...and on and on it goes...until all the slivers are removed. 

In short, when you see a patient with fluctuating reactions to a variety of exposures/foods and who has tried a number of INDIVIDUAL therapies to help (but to no avail), think about the Total Allergy Load.  

This topic is too good to have just one entry.  Expect a sequel! 

Later, Dude.   

I love Case Reports.  And I love the Annals of Allergy.  Conclusion?  I love to read Case Reports in the Annals.  What don't I love?  Any change in the status of Case Reports that might threaten to diminish their importance.  The Editorial in this month's issue of the Annals, entitled "Annals Evolution--The Next Phase" states that "The Annals will no longer accept unsolicited case reports" Instead there will be a new "Letters" feature to replace this. OOOHHHH BOY.  So what's the Angry Allergist to  do?

Well, like the song says, "I gotta be me", so I'm offering a Case Report...on...you guessed it...The Case Report.   Why am I publishing this case report here and not in the Annals?  If you don't know the answer, you haven't been paying attention:  like I mentioned earlier, the Annals is no longer accepting unsolicited case reports...so here goes: 

Iatrogenic Atrophy of the Case Report:  A Case Report and Review of the Literature

Introduction 

Case reports are undoubtedly helpful in the progression and advance of medical knowledge.  They have been a time-honored medical communication for many years.  We describe a case of iatrogenic atrophy of the Case Report, relegated to "Letters to the Editor" status, from its former status with more formal article format in this prestigious major allergy journal.

Case Report:

C.R. presented to the Annals of Allergy with a longstanding history of good health.  A vigorous contributor to medical knowledge and academic medical advancement, C.R. was unexpectedly downgraded to "Letters to the Editor" status in The Annals of Allergy, from its former status amongst its peer articles in the Annals.  C.R.'s past history had been excellent--it had regularly visited the Annals for years, and frequently praised for its work.  However, In an article entitled "Annals Evolution--The Next Phase", it was unexpectedly stated that "The Annals Editorial Office will no longer accept unsolicited case reports".   Iatrogenic atrophy of The Case Report is expected to soon follow. 

Literature Review:

Vandenbroucke, in an article entitled "The Importance of Case Reports as Compared to Evidence-Based Medicine and Molecular Explanation" asks the rhetorical question, "Does the case report still have a place in modern medical science?"  He then states "The answer is an emphatic yes."  Clinical case reports form the basis for detecting new ideas--new disease entities, new etiological clues, new side effects, and new treatments.  In an article entitled "In Defense of Case Reports and Case Series" he writes that "Case reports and series have a high sensitivity for detecting novelty and therefore remain one of the cornerstones of medical progress..For example, Morris, in an article entitled "The Importance of Case Reports", relates the Case Report appearing in the summer of 1981 in The American Journal of Dermatopathology.  Gottlieb, et. al. wrote a very small, unassuming case report entitled "A preliminary communication on extensively disseminated Kaposi's sarcoma in young homosexual men".  In the article, the authors raised an interesting question--something characteristic of any good case report: 

"This sudden, very high incidence of the condition in male homosexuals suggests an epidemic and raises the possibility of an infectious cause." 

Arguably, this was one of the first (if not THE first) article describing what we would now call AIDS.  

In addition to giving us a forum for new ideas which would suggest new medical hypotheses and stimulate further medical research, the Case Report forms a time-honored tradition in medical education--the Clinical Pathological conferences where difficult or rare cases are discussed/described for the benefit of all.  They are necessary for medical education.  They are an excellent means of describing important adverse drug effects, and even offer a way for neophyte, young authors to find their way into the medical literature.   

 But enough with the generalizations.  Why are case reports particularly crucial in the allergy literature?  Easy.  Because in our own specialty, we are often dealing with highly sensitive individuals with multiple unique sensitivities.  No two people are exactly alike.  Yet we are deluged with randomized, controlled studies investigating ONE variable in otherwise homogeneous patient populations--let's say grass pollen allergy--and see how a particular SINGLE modality (antihistamine, SLIT, etc.) helps.  The typical allergy patient (if there is such a thing) is usually "messy"--they have multiple sensitivities involving multiple target organs.  An ideal situation for case reports--and not so ideal for randomized trials.  And an ideal situation for keeping the Case Report in a prominent position--and not in the backwaters of "Letters To The Editor" at the tail end of the Annals. 

I think it's about time to take a break from all of the flow-charts and diagrams I've been showing you over the last 2 weeks, and relate a parable--one that has to do with why I'm writing about Diagnostic Synthesis in the first place...but before I do so, I've got to (are you ready?) do another black box warning to weed out the faint-hearted..."oh nooooooooooooooo" you say.  But take heart.  This isn't just "any" black box warning, this is actually a BLUE box warning...and if you read the parable below, you'll understand why I changed colors on you...

The  Allergist & the Preschool:  A Parable

Once upon a time there was an allergist.  He was busy in his practice, treating asthma.  Truth be told, he was basically an asthma doctor.  But he was bored.  After all, you can only give out so many inhalers and monitor so many breathing tests before it gets a bit monotonous.  He looked around for other opportunities.  Surely it wasn't with his patients--a lot of them had stomach issues, fatigue, cognitive dysfunction, migraines, etc. but he really wasn't properly trained to DEAL with any of that.  Only wheezes, and sneezes, if you please.  So he sat in his office, and handed out the latest inhaler du jour while the time on the wall clock slowly crawled by.  So he was DELIGHTED one day when his wife (who ran a preschool) unexpectedly called--it turns out she had come down with a bad respiratory infection from one of the kids and she offered him the "job" of taking care of her preschoolers for one day.   He excitedly cancelled all of his patients for the next day, and went to the preschool. Boredom relieved! 

As he looked around at the wide-eyed faces of the young children, he asked them what they would like to do.  "Let's play with blocks!"  said one child.  "Yes!  I LOVE to play with blocks!" said another.  "Could you help us build something pretty?" asked another.  So the allergist got out all of the wood blocks from a box near the door.  They were all different colors.  Some were red, some were green, some were white, and some were....blue.  

Blue was his favorite color.  Always was.  Always will be.  I mean he really loved the color.  And the blue blocks?  He loved them too--every last sliver of them.   Was hypnotized by them.  Down to all 8 corners and all 6 faces of every blue block.  He knew he just wanted the kids to play with the blue blocks.  And only the blue blocks.  They were the prettiest.  They were the BEST.  And he know he would like to play with just the blue blocks too.  He was determined to learn everything about the blue blocks he could.  How they stacked on one another, how they fit together.  How he could use them to build interesting things.  And how the children would be so impressed with the  all-blue structures he'd create. 

There was only one small problem: 

There weren't enough blue blocks to go around. 

And there was one "not-so-small" problem:

The kids wanted to play with ALL the blocks; not just the blue ones.

As he handed out the blue blocks, he began hearing the protests.  "Why can't we play with ALL the blocks?" one child said.  "With more blocks we can build bigger and more beautiful things!" 

"Because I want you to play ONLY with the blue blocks" he said,  "What's the matter--don't you like blue blocks?" 

When children complained they also wanted to play with the red or the green or the orange blocks, he told them "that's not what we're playing with here".  (He almost allowed one child to use purple blocks--close enough to blue to be fairly attractive--but at the last moment said no.  He didn't want to set a precedent.)  And so they began playing.  The children were understandably disappointed when they couldn't build much.  After all, the blue blocks were merely ONE PART of the play set.  And there weren't that many blue blocks.    

The allergist was unperturbed.  "We will continue playing  with the blue blocks for now", he said.  "if you have any questions on how to build things with the blue blocks I'd be happy to help out." 

Meanwhile, while the children played, he spent his time minutely studying every last woodgrain pattern in each and every blue block they had, and explaining to each child the different grain patterns in each blue block.  The children weren't that interested in all the minutiae of the blue block composition--they were just frustrated they couldn't use all of the other brightly colored blocks.  The only one having some enjoyment in this was...the allergist.  But after a while even HE had to admit (to himself only) that he really couldn't build THAT much with just blue blocks.  In fact, he became...bored...just like at his office practice. 

...The next day the Allergist's wife returned to the preschool... She asked her children how they liked her husband, the "substitute teacher" allergist. 

"He was boring" said one child. 

"He didn't listen to us" said another child. 

"He didn't help us build anything pretty" said still another child, "It was really sad.  I think he could have really built pretty things if he was just CURIOUS about how all the blocks would fit together".    

"I don't understand all those big words you're using", said another child, "but I can tell you what I know-- he was just a blockhead". 

...And so he was.

Later, dude. 
 

Shhhhh...we're quietly discussing a taboo subject, so I want to keep this quiet.  Over the last several journal entries, I've focused on how "simple" allergy patients become "complex" allergy patients with multiple food sensitivities involving multiple target organ involvement.  This is an important subject, because we see these patients not infrequently in our allergy practices.  And what I'm going to say next will probably put you at risk for a dangerous elevation of your blood pressure, or even a seizure, so be forewarned--I've inserted another notorious black box warning for your protection, so read further at your own risk:

We get scant guidance from our professional societies on how to approach these patients.  Our professional societies prefer our immunology complex but our clinical patients simple.  We want to keep our focus on one target organ (the respiratory tract) and one set of triggers (inhalant allergens--preferably pollens).  In short, allergists arguably have some of the narrowest minds in medicine when it comes to thinking of their patients.  Narrow is not good.  Narrow is bad.  Narrow is very bad.  Check out this quote by Konrad Lorenz

Every man gets a narrower and narrower field of knowledge in which he must be an expert in order to compete with other people. The specialist knows more and more about less and less and finally knows everything about nothing.

But allergists aren't the only ones who succumb to the "tyranny of narrowness".  For the allergic patient, narrowed diets are equally bad.  And many allergy patients have them.  The combination of narrowed diets in patients with increased intestinal permeability is a disastrous combination.  Why?  Because narrowed diets promote repetition of foods--often items with high native allergic potential.  As an old engineer, I like to think in terms of system analysis, and formulas.  Here's a formula for you.  A formula that has helped me figure out hundreds of difficult cases over three decades of practice.  You won't see this formula repeated in any allergy society meetings.  I sure haven't.  But it's a killer when it comes to application:

allergic predisposition+ increased intestinal permeability+repetitious/narrowed diets= development of multiple food sensitivities

Check out this flow chart for a more in-depth analysis:

As you might expect, the permutations on this formula are endless.  Just take one item from the left hand box (narrowed diet) and one item from the right hand box (representing causes of increased intestinal permeability), and ...voila!  instant food sensitivities!  Let me present a few cases to you to illustrate what I've seen over the years:

Patient X presents to me with a history of getting sick from "everything she eats".  She had an interesting history--initially had seasonal respiratory allergies, followed by the development of recalcitrant diarrhea.  She finally had a small intestinal biopsy confirming celiac disease.  So she went on a gluten-free diet.  Diarrhea transiently subsided, only to return with a vengeance, AND with the development of worsening respiratory allergies, accompanied by urticaria.  The problem?  Intestinal permeability was enhanced by gluten enteropathy, she stopped gluten--and substituted corn for every snack food and main meal she was eating.  Guess what?  She was highly sensitive to corn.  And I knew this even before I did the RAST test and challenge test to confirm it...

Patient Y presents to me with the development of progressively feeling sick from everything he is eating...He had a history of relatively minor allergies earlier in life, "but he outgrew them" (his quote).  In midlife he went through a period of severe personal stress : New job, divorce, etc. etc.  Limited time to eat, so he began to eat repetitiously the typical "fast food" meals I call "The McDiet".  This was accompanied by liberal alcohol intake, causing increased intestinal permeability.  I knew before testing him that he was sensitive to milk, wheat, yeast, and probably potatoes.

Patient Z had a history of colic as an infant, and trouble tolerating all formulas.  She probably had a dairy allergy at birth, which "went underground" for a number of years.  It resurfaced in hidden form her elementary school years, when she had multiple recurrent respiratory infections, requiring multiple antibiotics.  The cause was missed.  As a teen she took 2 years of tetracycline for acne.  And then?  She presents to me with bloating, gas from multiple foods she eats, cravings for sweets, and fatigue, cognitive dysfunction, and worries about completing her college studies because she feels so bad.   Guess what?  She's got intestinal permeability enhancement from repetitiously eating a primary food allergen all her life (dairy) accompanied by intestinal dysbiosis from recurrent antibiotics later in life.  And her current diet?  The typical college students monotonously repetitive "fast foods" diet.  Not too hard to figure out. 

Clinical pearls:

1.  In the patient with developing multiple food sensitivities, look for causes of intestinal permeability.  It pays off.

2.  In the patient with developing multiple food sensitivities, look for repetitive eating patterns.  Foods with high native allergy potential (eggs, milk, soy, yeast, wheat, corn) would be immediately suspect if eaten repetitiously.

Hope this helps.

Later, dude.   

Have you ever noticed that we humans have a tendency to "solve" a problem--and the solution only gives birth to an even bigger problem?  Examples abound.  For instance, the development of the A-Bomb helped to end WWII...and then nuclear proliferation ensued.  Or, to take another case, we've developed a superior mode of 20th century transportation (i.e., the automobile), only to give birth to massive pollution problems.  And then...we developed antibiotics to end the scourge of infectious diseases, and...?

In my last journal entry, I mentioned that injury and the allergic patient are two things that just DON"T go together well.  Another item that can spell DISASTER for the allergic patient is recurrent antibiotics.  In this series on diagnostic synthesis, I've been discussing a taboo subject--how does a "simple" allergic patient (only one allergy+ one target organ--something which all allergists covet) end-up being a mess, with multiple complex food sensitivities?  One way this happens is through multiple antibiotic useage.  See the diagram below:

                        Let's start in the upper right corner and move clockwise.  Primary allergies such as a simple dairy allergy in early childhood, can lead to recurrent infections (such as otitis media) which in turn leads to multiple antibiotic useage.  Sadly, probiotics are often NOT given concurrently with the antibiotic administration.  Eventually, intestinal dysbiosis (imbalanced bacterial flora, usually with a predominance of commensal Candida species) ensues.  The end result?   Increased intestinal permeability, and subsequent risk for easy sensitization to any food the patient is eating alot of, especially foods with high native allergenic potential, such as wheat, soy, corn, etc.

Another common presentation on this theme is the patient with inhalant sensitivities to molds, unfortunately undiagnosed.  They have recurrent sinusitis as a result, take multiple courses of antibiotics, and present to the office with progressive food intolerances covering a wide-range of items.  Often, they feel sick with everything they eat. 

Now look at the left side of the diagram, starting with "Non-allergic infections".  Sometimes patients have NO prior history of typical allergically-related infections, but have an underlying susceptibility to allergic disease nonetheless.  They have an unfortunate non-allergic medical issue requiring repeated rounds of antibiotics, and wind up with intestinal dysbiosis and the development of multiple food sensitivities.  An example of this is the patient I saw in my office, who was in good health until having severe abdominal pain.  She was diagnosed as having a severely infected gallbladder with sepsis, and was hospitalized and on heavy doses of antibiotics, both during and after hospitalization.  Food reactions rapidly ensued for the first time in her life.

What about the dotted line you see between "non-allergic infections" and "primary" allergies, you ask?  Well, newer research has suggested that recurrent antibiotics in childhood put children at definite risk for developing an increase risk of asthmatic disease.  According to a recent article, Giving antibiotics to a child less than one for a non-respiratory tract infection greatly increases the risk of developing subsequent asthma.  Disruption of the gut flora in early childhood may accelerate/promote the development of "primary" asthma, and possibly subsequent allergy.  This is simply a reworking of the hygiene hypothesis to include the need for healthy gut flora--the so-called "extended hygiene hypothesis".  

Clinical Pearls from all this? 

1.  In the patient presenting with multiple food sensitivities, be sure to check their antibiotic use history.

2. In previously diagnosed allergic patients, try to minimize antibiotics whenever possible, and be sure to give concomitant probiotics when utilizing antibiotics for infections. 

What factor is most responsible for the intestinal permeability increase from disrupted gut flora?  Usually Candida.  But that's a discussion for another time, and another place.  Right now, I'm tired.  How about you?

Later, Dude