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

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