No one likes Dictators or Tyrants.  Especially in this country...the Land of the Free and the Home of the Brave, right?.  But do you know that one of the smallest tyrants in the world is also the most powerful?  Yep, it weighs in at barely 200,000 Daltons....

It's IgE.  

 

    Webster's dictionary defines a Tyrant as "an absolute ruler" who "uses power to oppress it's subjects".  And it's my contention that most allergists fall under IgE's overly oppressive power to define who--and who not--to treat as allergy patients.   Next month I'm going to launch into some allergy aphorisms of mine, and it is from these thoughts about IgE that one of my favorite aphorisms was born:   "IgE is a cruel taskmaster".   And the following case illustrates this perfectly...

...It was a hot August day in 2007, and I was sitting in my office, trying to mind my own business.  The pleasant quiet of the day was abruptly diminished when I heard a "plop".  I looked up.  My nurse dropped a "new patient" chart on my desk.  

Back to work. I put my journal down.  The fact that my investigation into reading about Toll-like receptor heterodimer variants that protect from childhood asthma...well, it just would have to wait.  So would Adenosine induction of airway hyperresponsiveness through activation of A3 receptors on mast cells.  It was difficult to do, but I tore myself away from the JACI.  Self-discipine, pure and simple.  I had to see the patient.  And the JACI would have to wait.  Again.  

I walked into the room.  A pleasant, middle-aged man sat in a chair, next to his wife.  

"You've got to help me." he said.  "It's been a living nightmare for 3 years.  I get swollen lips, eyes, and tongue, and sometimes I break out in hives all over my body.  And nobody can help me. Nobody.   I heard about you."  

He had been worked up at a large midwestern university.  I liked that, because the workups are usually thorough, and it leaves me to look into the mundane.  And he had been worked up well...Zebra-hunting didn't turn up a thing.  Hereditary or acquired C1 esterase inhibitor deficiency had been ruled out, based on normal C4, C1Q,, C1 esterase inhibitor (both functional and nonfunctional), and he had a normal tryptase, and no eosinophilia on CBC.  An IgE level was entirely normal.  Thyroid studies were normal and anti-thyroid antibodies were negative.  Allergy evaluation included negative skin prick testing to a wide panel of seasonal and perennial allergens as well as common foods.  

"I'm on a bunch of medications, but they don't really help", he said.   He had been on zyrtec, Zantac, prilosec, and Prednisone.  The latter was for short bursts, and only transiently helped.  

"Any other symptoms?" I asked.  "yes, I've got some GERD and some bad post nasal drainage" he replied.  "I think dust makes my drainage worse", he said.  "I sometimes have so much sinus drainage I can hardly sleep because of my coughing".  "Flonase, nasonex, Astelin--I've tried them all, and they don't touch it" he said.  

Another one of my axioms (aphorisms)  popped into my mind--that is, the patient with upper respiratory drainage from presumed  aeroallergens who also suffers from GERD has a food sensitivity until proven otherwise.  It's been my experience that in diagnostic conundrums, two distinct possibilities often emerge:  the patient either has a "Zebra" (i.e., a rare disease), or he has a horse painted with black-and-white stripes (i.e., a common disease with rare manifestations).  The latter possibility took shape with my patient...so in view of the above, we talked some more. ..Specifically, we talked about his diet...

"You know," he said, "I had something really strange happen in Colorado a couple months ago.  I went into a coffee shop, ate an organic bran muffin, and then seemed to immediately swell up and have hives.  Last night, while driving to La Crosse to see you, I ate at a local restaurant here.  I had the same experience".  

"What did you eat?" I asked.   

"Well, I had a sirloin, baked potato, salad, and bread from the bread basket", he said.  (Italics mine).  

"How do you do with beer?" I asked.  "Well, my sinuses get worse with it so I don't drink it any more" he said.  

 

Test results:

ID tests:  dust mite:       9 mm dil 1

 

                 alternaria:    10 mm dil 1

                 aspergillus:   9 mm dil 1

                penicillium     9 mm dil 1

all other test results negative

RAST tests:

IgE:  milk, wheat, oat, corn, beef, baker's yeast, gluten:  all negative.  0.00 IU/ml IgE

IgE:  milk, wheat, oat, corn, beef, baker's yeast, gluten:  all negative

 

Discussion:  

My working diagnosis was that this patient suffered from a combination of non-IgE mediated food sensitivities, coupled with minor prick test-negative but mild ID-positive inhalant sensitivity to dust and mold.  The combination of these contributed to his three major presenting symptoms:  urticaria/angioedema, chronic PND, and GERD.  

 

Treatment: 

We placed this patient on the following program: 

 

1.  Rotary Diversified Elimination diet, avoiding major food suspects (wheat, dairy, corn, sugars, yeast, beef)

2.  SLIT for dust and mold

3.  Temporary continuation of his medications as previously prescribed

4.  Trial of Gastrocrom for restaurant meals only

 

Clinical Course

Within 48 hours of beginning the diet, his daily urticarial lesions and facial swelling began to subside.  His stomach began to feel better, and he went off his prilosec.  He reduced his zantac by 50%.  He used Gastrocrom when eating out, since this seemed to block reactions when eating at Red Lobster.  I last saw him 2 weeks ago.  His congestion was alot better on SLIT, and dust wasn't bothering him like before.  He was afraid to stop his Zyrtec and Zantac, but...

  

  So there I was in my office last September, 2007, feet up on the desk and reading the latest JACI issue about some obscure immunological aberration of questionable practicality . when a "new patient" chart was dropped on my desk.. the nurse pointed me toward examination room 6  I reluctantly put the JACI issue down...I hadn't known that Yin-Yang 1 regulates effector cytokine gene expression and Th2 immune responses , but I somehow felt better for it, so dropped the issue, and in I walked...and there I found a pleasant 20 year old dark-haired young girl from Minnesota, who had an interesting story to tell...

"I want help with my stomach", she said; "it's upset 24 hours a day, and I have pain after eating." 

When I asked her about a past allergy history, I realized I had indeed opened up a Pandora's Box...

She had been diagnosed as having allergic rhinitis in childhood, and I reviewed the medical records she brought with her; indeed, they revealed she had been on prior injection immuntherapy for dust mite and grass , from 1996 through 2000.  Since that time, she had been doing well, without any significant respiratory problems, until a year and a half before she saw me, when...

...she went on an extended mission trip to Peru.  While there, she was working under extremely poor conditions with presumably heavy dust exposure.  Four months into her trip, upon consuming a meal containing cayenne pepper, her hands became red, burned, itched, and she developed urticarial lesions on her arms.  Two weeks later, while eating in a Peruvian restaurant, 20 minutes later she developed dizziness, throat closure, and generalized urticaria for which she took Benadry.  There were no peppers in this second meal, which admittedly contained nothing unusual for the patient, but nevertheless this reaction was worse than the first one.  One month later, in February of 2006, while still traveling in Peru, she ate a fairly regular meal containing potatoes, vegetables, chicken, and no spices at all.  Within 20 minutes,  her ears began to burn and itch, and her throat began to close. Her stomach cramped, and she began to have nausea and vomiting and collapsed.  She was taken to a local emergency room, where she received emergency treatment, and was advised to see a local Peruvian allergist.  Records from this visit were unavailable for review, but he apparently tested her and told her that she had "probably reached a threshold of tolerance on heavy dust mite exporsure in Peru".

She returned home from Peru in March of 2006, and ate mainly ad lib, with no severe reactions; she felt most of her problems were behind her...However, in June of 2006, she had a cappucino while on a family trip, and within 5-10 minutes, she felt severe stomach pain, and had nausea and vomiting, accompanied by urticaria.  In the spring of 2007, several months before seeing me in the fall, she had an episode of eating pecan pie from Perkins, and developed severe stomaches and diarrhea...

"...and since that point in time my stomach has been continually upset", she told me...Although she had minor spring and fall rhinitis issues, these were not a concern.   Understandably, her stomach issues were her major concern, and severely impacted her quality of life...

...Two months before seeing me, her local clinic had done a medical workup, including normal CBC, sed rate, stool for O&P, abdominal/pelvic CT,   peripheral smear for malaria--all of which were normal.  A GI consult was pending...Allergy prick testing was done and had showed strong sensitivity to cat, dust mite, and horse dander, and moderately strong reaction to trees, grasses and weeds.  Prick testing to a battery of foods was negative.  

What next??

Her physical exam was generally unremarkable, except for mild nasal turbinate congestion.  She had no dermagraphism, and abdominal exam showed no h/s megaly or point tenederness.  Remainder of exam was not noteworthy.

IDT testing

Dust mite:    10 mm        dil #7

Ragweed:    13mm         dil #3

Grasses       13mm        dil #3

Tree mix      13mm        dil #3

Cat                 8 mm        dil #5

Alternaria      6 mm       dil #2

Candida       8 mm         dil #2    blistered at 48 hours

RAST testing IgE

dermatophygoides farine   Class IV      8.22 IU/ml

Cow's milk                              Class I        .07  IU/ml

 All others negative:  wheat, corn, beef, potato, baker's yeast, apple, chicken, bell pepper

RAST testing IgG

Cow's milk                             Class III       22.48 ug/ml

Wheat                                     Class II         9.68 ug/ml

Discussion:
Certainly, the squalid, filthy living conditions she encountered on her missionary trip to Peru gave her large concentrations of dust mite exposure.  But "not all dust mites are dust mites"--and certainly not in Peru...Croce and colleagues in J Investig Allergol Clin Immunol 5:286-8, 2000 pointed out that the mite Blomia tropicalis was the organism most frequently detected in 59% of peruvian house dust samples, with dermatophagoides pteronyssinus second place at 15.9%.   Chortoglyphys arcuatus and Tyrophagus putrescentia were also found, and these four mites, taken together, accounted for more than 90% of the mites detected.  No specimen of Dermatophagoides farinae was detected.   What's the cross reactivity between D. farinae (which we did with RAST) and Blomia tropicalis? Again, this was studied this year by Croce and colleagues and published in P R Health Sci J 27: 163-70, 2008.   They found that although (as expected) cross-reactivity between homologous allergens from Dermatophagoides spp. is high, it is low to moderate to Blomia tropicalis.  It would certainly be possible that her severe reactions in Peru might be accounted for by the difference in mite populations between Peru and the U.S. 

Another factor to consider in her severe reactions in Peru would be whether she had a variation in "pancake syndrome" or oral mite anaphylaxis, as pointed out in the article by Hannaway and Miller in the Annals of Allergy in  Allergy Asthma Immunol 4: 397-8, 2008.    Storage mites in grains grow under humid conditions, and as pointed out by Croce, Lima Peru is a city of tropical climate located along the Pacific coast, and the relative air humidity is 80-90% in the districts they studied...Certainly, who knows how many mites she was eating in some meals the locals prepared for her?...Was she gradually ingesting more and more mites?...

Finally, what about the patients current commplaints--her continual GI tract pain and nausea?  Could the presumed heavy dust-mite associated anaphylaxis inflammed the patients GI tract, and made it more reactive to foods (i.e., milk, wheat?) and Candida?  An intriguing paper by Magnusson J in J Allergy Clin Immunol 112:45-50, 2003 indirectly addresses this question, when they studied the GI tract in individuals with seasonal birch pollen allergy.  Although the pre-season intestinal biopsies were normal,  nearly half of the post-seasonal biopsies showed intestinal inflammation...the authors stated that "birch pollen exposure triggered a local inflammation with an increase in duodenal eosinophils and IgE carrying mast cells in patients...there is an interplay between immunologically active cells in the airways and gut..." could the same thing have happened to this patient, with oral mite anaphylaxis aggravated a food sensitivity? 

Why the IgG RAST in my workup?  Although IgG RAST is controversial, there is a study by Dixon published in Otolaryngol Head Neck Surg 123:48-54, 2000, on 114 consecutive patients suggesting help in diagnosing the "hardest of the hard"--the delayed food reaction...and I thought it might be of help here, given the patients history of chronic daily gastrointestinal distress.... 

Finally, this is where SLIT shines...the other allergist she had seen just before her arrival in our clinic was "not interested" in giving her SCIT again, especially with her predominantly GI complaints and her prior severe reactions to dust mite.  But with the safety profile of SLIT, we can begin right away, and treat her comprehensively for all factors contributing to her total "allergy load"...and for those who have read my prior entries, I am a BIG believer in the total allergy load!!

 
Diagnosis:
1.  Dust mite anaphylaxis, with possible pancake syndrome and preferential sensitivity to Blomia tropicalis over dermatopagoides spp.
2.  Coexisting low-grade food sensitivities contributing to GI upset
3.  Abnormal delayed reaction to Candida antigen
4.  Irritable bowel syndrome with  inflammation aggravated by dust mite and food sensitivities
5.  Seasonal pollen sensitivites aggravating seasonal congestion in spring and fall, and heightening susceptibility to GI flares at those times

Treatment:
1.  SLIT to offending inhalants:  dust mite, grass, ragweed, tree
2.  Reduction in dairy, wheat in diet
3.  Short course of oral cromolyn sodium
4.  Short course of low-dose diflucan, 100 mg twice weekly x 1 month to reduce intestinal carriage of Candida

Clinical Course
On this treatment program, the patients gastrointestinal symptoms gradually subsided and within 3 months her stomach was improved, she had had no urticaria or anaphylaxis requiring emergency room visits, and she felt better..  By her last visit May 22, 208, she had had an excellent interval report, with no gastrointestinal distress, urticaria, or seasonal problems.  Spring season was going well, with no congestion.  She remained on SLIT, and was eating her dairy and wheat products carefully.  Life is good. 

Later, Dude
 

In my last entry, I mentioned I had read an article in the June issue of the JACI "The Allergy Archives--Pioneers and Milestones" entitled "Food Allergens:  Landmarks along a historic trail" by Sheldon Cohen, MD".  It's a good article,  and I recommend  reading it.  But, while reading it I kept coming to an image:  the image of a man vainly searching in the dark, looking at the ground, in a parking lot.  He would look under one parking light, and then the next.  When a stranger came up and approached him and asked what he was doing, he said "I'm looking for my car keys...I dropped them".  The stranger asked why he was only looking under the lights.  "Because that's where I can see the best", he said. 

We all like to "look under the lights" when we are searching for something valuable.  But sometimes remembering that valuable things aren't just what can be seen easily under the lights is worthwhile too. 

As I had said last time, there were two great men highlighted in the article by Cohen.  One was Walter Vaughan, and the other was Oscar  M . Schloss, M.D.   As I've said before, to get your picture published in the JACI you generally (1) have to be dead and (2) have made a VERY valuable contribution to the allergy field.  I talked about Vaughan in my last entry, so let's talk about Schloss...

Cohen points out in his article that Schloss held the positions of professor and chairman in the Departments of Pediatrics at Cornell Medical College and at Harvard.  As noted by Cohen: 

"In 1912, the controlled, in depth study of Oscar Schloss established the practicability of scratch tests for clinical hypersensitivity". 

Pretty impressive.  But did Schloss do anything else equally impressive?  In the interim since my last blog, I was curious enough about Vaughan's works to order a rare first edition of his work, "Strange Malady, the Story of Allergy", published 67 years ago, in 1941.  In a moment of rare inspiration, I checked the index to find whether his contemporary, Dr. Schloss, was mentioned. 

                                           Indeed, he was....

Here's what Warren Vaughan says about Dr. Schloss (missing from the JACI article):

A child was brought to Dr. Oscar Schloss, a New York pediatrist.  There was a most unusual story of idiosyncrasy.  The lad had had diarrhea when ten days old and was treated with barley water and raw egg white.  This relieved the complaint and caused no unpleasant symptoms.  He received no more egg until he was fourteen months old.  Almost immediately after eating part of a soft-boiled egg he cried out, clawed at his mouth, and his tongue and mouth swelled until they were many times normal size.  Hives soon appeared around the mouth...When the boy was two years old his mother noticed that if he were to play with empty eggshells he would break out with hives on his hands and arms.  Schloss suggested that the boy's experience might be due to this new condition, recently receiving so much attention, called allergy....He injected the boys blood into a guinea pig.  Later he injected egg white.  The animal had typical shock...

 ...He mixed the white of a raw egg with water and diluted it so many times that you would scarcely have thought there was any egg left.  He fed this to the boy with a medicine dropper.  Nothing happened.  He kept on giving this curious medicine every day, increasing the number of drops each time and gradually increasing the strength of the solution...He finally increased the tolerance to such an extent that the lad could eat eggs in moderation with no consequent discomfort....Here again was something well worth telling to the world  Schloss published his report in 1912.

...Two methods of desensitization were now available--hypodermic and oral.  We use both today..." 
    

So, in 4 years, we'll be celebrating the 100th anniversary of successfully documented sublingual food desensitization.  Schloss published his findings, entitled "A Case of Allergy to Common Foods", in Am J Dis Child 3:341, 1912. 
Sounds like a landmark to me.  And hidden away in a forgotten allergy textbook by Warren Vaughan for decades..But was Schloss the first one?  According to Lisa Lundy, in her superb review paper entitled  "Historical background of food allergy", she writes that

A physician in England, Dr. Alfred Schofield, wrote in 1908 about successfully treating a boy who suffered from angioedema and asthma because of an allergy to eggs.  (Schofield, Alfred:  A Case of Egg Poisoning, Lancet, p. 716, 1908).  This egg desensitization was confirmed by Drs. Keston, Walters, and Hopkins (Keston, B, Walters, I, Gardner, J:  Oral Desensitization to common foods.  J Allergy 6:431, 1935). 

.So SLIT for foods was documented by multiple doctors  at the turn of the 20th century, nearly 100 years ago. But Schloss deserves a major credit nonetheless.   Can we learn something from the classical literature?  You bet.  Schloss used a serial dilution technique for successful desensitization in a patient highly allergic to eggs...Seems to me that's important....We can also learn that we all have a bit of arrogance in "modern allergy" in "copping an attitude" that everything worth knowing in the field has been published within the last 10 years (or mentioned in the latest CME exercise we did...)   

...Open-mindedness and an obsessive sense of curiosity is  a hallmark of the Renaissance Allergist.  As Renaissance Allergists, we're interested in looking not just "under the lights" of our accepted (and preconceived) notions that SLIT for foods is a "new" idea and "new" treatment, never tried before. We look everywhere...whether it's under a light or not.  An interest in classical allergy literature pays many dividends for the Renaissance Allergist.  Here's one more.    

Later, Dude. 

As I sat in my office, perusing the latest June issue of the Journal of Allergy and Clinical Immunology, I was intrigued by the article by Sheldon G. Cohen, in "The Allergy Archives--Pioneers and Milestones" discusing "Food Allergens:  Landmarks along a historic trail.  As noted in the article, Dr. Warren T. Vaughan was the author of Practice of Allergy, 1939, and editor of the Journal of Laboratory and Clinical Medicine.  In his article, Dr. Cohen notes:

"In 1930, Vaughan, in collaboration with Frances Wilson, an academic botanist, initiated studies of shared characters of plant-derived foods as the first stage in the development of a classification intended to serve as a rational and workable basis for selecting test allergens representative of members of a group.  ...Of special interest is a 75-year-retrospective review of Vaughan's contribution, noting that with few exceptions his compilation was valid and met the test of time"  

 As a Renaissance Allergist, I have an interest in classical (medical) literature, and an overwhelming sense of curiosity--basically, what else did Vaughan write--and what might it tell us in addition to Cohen's article? 

Here's some things not pointed out in the article by Cohen:  

First, Vaughan wrote on a wide range of topics he felt were related to the allergy field:  check these out:

1.  Vaughan, WT.  Allergic Migraine.  JAMA 88:1383, 1927.

2.  Vaughan WT.  Role of specific and nonspecific factors in allergy and allergic equilibrium.  J Lab & Clin Med 13:633, 1928.  

3.  Vaughan WT.  Allergic factor in mucous colitis.  South M J 21:894, 1928.

4.  Vaughan WT.  Atypical and borderline allergic manifestations as important factors in general medicine.  South Med & Surg 95:15, 1933.  

5.  Vaughan WT.  Food allergy as a common problem.  J Lab & Clin Med 19:53, 1933.

6.  Vaughan WT.  Food idiosyncrasy as a factor of importance in gastroenterology and in allergy.  Rev Gastroenterol 5:1, 1938.  

7.  Vaughan WT.  Palindromic rheumatism among allergic persons.  J Allergy 14:256, 1943.

Secondly, we know Vaughan was a brilliant physician.  ( For anybody to get their picture in the JACI, you've got to be brilliant).  Even his son was a brilliant doctor--John Heath Vaughan, was an internationally recognized authority on allergy and autoimmune diseases and a former member of the University of Rochester School of Medicine and Dentistry, who recently passed away at the age of 85 on Nov 11, 2007.  So why was  a brilliant physician like Vaughan writing about palindromic rheumatism and it's relation to allergy?  What does his "classical" writing tell us?  Are you curious? I was. 

In his article, Vaughan described 27 cases with recurrent or chronic joint symptoms among a large group of allergic patients, in whom the arthritic symptoms were attributed to food sensitivity.  He called this syndrome "palindromic rheumatism", a term used by Hench and Rosenberg 2 years earlier to imply recurring joint disease without articular residue.  Vaughan would note that about half of his patients seemed to have abnormal joint changes at the time of exam.  His original discription of this group of patients is repeated here for its remarkable accuracy:

"The second consideration was a small group of allergic persons with intermittent attacks resembling subacute rheumatoid arthritis in whom we have demonstrated specific food incitants.   The evolution of the attacks resembled those of intermittent hydroarthrosis, but multiple small joints were involved; often just one hand or foot was affected.  Sometimes the reaction occurred in more than one extremity, and at times one or two large joints became inflammed either simultaneously or independelty.  The local picture was of swelling, redness, paind, and tenderness.  The attacks would last from several days to a week, rarely longer.  In some, the joints were objectively normal between attacks.  In others, there were low grade arthritic changes..."

Now--be honest--how many allergists take rheumatic histories on our patients?  I do.  For example, I can remember the patient with a strong dust sensitivity who suffered an acute attack of palindromic rheumatism after sweeping out her basement.  In truth, being curious and delving into the older "classical" allergic literature---which was devoid of the built-in constraints of IgE-mediation, may offer us new insights.  Remember what I wrote last month about the mast cells and the synovium?  

Warren T. Vaughan was a Renaissance Allergist.  A brilliant clinician.  And he believed that palindromic rheumatism could be triggered by food incitants.  Renaissance Allergists in today's world need to follow-up on his meticulous & compelling observations. ...

Later, Dude.  

 

 

 

 

 

In my last post I mentioned that I took a 3 month "blog sabbatical" to try to redefine what I felt we needed in the allergy field, and express it as succinctly as possible--in a positive manner.  I considered many ideas, but in the end, only one concept--one word-- made the final cut:  

                          Renaissance

The word "renaissance" is of French derivation--for rebirth.  What characterized the Renaissance?--a "rediscovery" of classical literature/art, curiosity and objectivity, and an emphasis on individualism (among other things.)  The true "Renaissance Man" embodies these ideals in a multi-talented fashion.   In my (humble?) opinion, the allergy field needs more "Renaissance Allergists", and alot less "asthma docs".  We made a fundamental mistake as allergists when we anatomically delimited our field--because the field is basically not one to anatomically demarcate.  In that respect, it's alot like our "brother specialty"--infectious disease.  Imagine if the IDSA  (Infectious Diseases Society of America) changed their name, for example, to emphasize "bronchitis", and became the Infectious Diseases Society of America and Bronchitis?  What if you went to infectious disease meetings, and all they talked about was the respiratory infections they cared about?  How interesting would that be?  We've done that with our own societies--tagged "asthma" along with the official titles, as if to say that's "who we are". Asthma docs. 

And that's what the Renaissance Allergist is not.   What is he?  Easy.  He's a multi-talented physician first, an allergist second, and an asthmalogist (a distant) third.  He/she is interested in all immunological aberrations (both non IgE and IgE mediated) over all mucosal surfaces, as well as the skin and joints.  And come to speak of it, he's even interested in the human synovium, and how his allergic patients might respond there.  Remember--mast cells have long been known to be present in the human synovium, and mast cell numbers also increase 1-10 fold with diverse disorders, including juvenile and adult rheumatoid arthritis.  (See "Mast Cells and arthritis"  by Malone & Metcalfe, Ann Allergy 61:  27-30, 1988 if you're interested).  Yes, a spirit of curiosity, individualism, and love of classical literature are characteristics of the Renaissance--and of the Renaissance Allergist. 

Which brings me to the latest Allergy Archives, and Warren T. Vaughn.  But that's for another time, and another post.

Later, Dude