A voice for reform in the field of allergy...You're entering the no-spin zone of the Renaissance Allergist...Straight talk by an allergist seeking reform in his profession and a renaissance in the field of allergy...
As allergists, we must not only be expert in our requisite field of technical immunological knowledge, but also in applying it in the context of the patient whom we carefully observe and listen to. It is the fusion of expert technical knowledge and expert practical observational and listeniing skills that makes us expert allergy clinicians. It's been my experience that certain signs seen in day-to-day allergy practice haven't been given enough emphasis, or reported in the literature. It was in this spirit that (In my last post), I had discussed what I had termed "Eaton's Sign"--the curious phenomenon of "recall" activity at prior skin test sites when an allergy patient subsequently is re-exposed to his/her allergen. But wait! There's more! In a sense, Eaton's sign is part of a bigger picture--the allergic "target organ" phenomenon. Here's the story:
When an allergy patient is exposed to an allergen (either by inhaling it or ingesting it), he/she may be principally/preferentially affected at a sight of prior trauma. The site of prior trauma may be accidental (an injury or infection) or deliberate (a prior surgery). Here are some examples:
Case 1: A patient comes to see me. He was aware that previously he would ingest milk and have problems with immediate sinus congestion and posterior nasal drainage. Then he had a car accident and suffered serious whiplash. Now when he ingests milk, he develops not only sinus congestion and drainage, but his neck aches terribly...
Case 2: A patient comes to see me with episodic urticaria and pruritis. When she ingests the wrong food or breathes an allergen, the first site that reacts is a small area on her abdomen....on exam, this is the exact site of a surgical scar where she had a laparoscopy years earlier.
Case 3: A patient comes to see me. He states that he is seeing me for knee pain. He has been scoped three times previously, and only old, degenerative knee disease is seen. Nothing new. His orthopedist is mystified that the patient has more kinee pain in the fall season, precisely when he has more sinus and mucous drainage.
Case 4: A patient comes to see me, with a history of a prior scabies episode adequately treated. But she continues to suffer from periodic episodes of intense pruritis at former sites of infection. When her corn allergy is diagnosed and treated, the residual pruritis resolves.
As might be expected, the permutations on this principle are endless. Among others, sites of prior herpes zoster are particularly vulnerable to subsequent allergic reactions. In short, sites of prior trauma--whether accidental, surgical, or infectious--are all fertile areas for subsequent allergic reactions. Presumably, cytokine release during allergy reactions preferentially "targets" these vulnerable areas that have preexisting prior trauma, damage, and residual inflammation.
In short, as good allergy clinicians, we must keep our "eye on the target" at all times.
Clinical medicine--including the specialty of allergy-- is about sight, touch, smell, and hearing--not just about the latest medical article we've read in the Annals of Allergy or JACI. One thing we've tended to underemphasize in our profession is late-phase skin test reactions--something we can see and touch hours after the test has been applied--if we just look for them. But there is another item that I've never seen described or documented in the lilterature--and that is the curious phenomenon of intradermal skin test "recall" days or even months after intradermal skin testing was done. Under certain occasions, it seems as if the site where a skin test was formerly applied retains a "memory" for furher reaction when a similar antigen is encountered in our environment many days later.
What do I mean? For example, I've seen patients receive intradermal skin tests for molds, and end up with strong delayed rections to them. Upon getting a subsequent airborne mold exposure many days later, (for example, mowing the lawn), the patient may note pruritis and swelling at the site of his former tests. If you ask patients about this phenomenon, they will frequently volunteer that it does indeed occur. Interestingly, I had a chance to examine this phenomenon first-hand in my office one day, in a patient who I had previously tested for mold allergy. She had had strong delayed reactions to mold when I initially tested her. . When she saw me, she had just had a major symptomatic mold exposure the day before. On her arm, there were faint areas of erythematous swelling and puriritis where I had previously tested her to mold on an earlier occasion.
I'd like to call this phenomenon "Eaton's Sign", named in memory of the late Dr. Keith Eaton, M.D.
I remember meeting Dr. Eaton in Manchester, England, when he excitedly came up to me and asked if I thought that heavy mold exposure could trigger depression in susceptible individuals. He was one of the earliest members of the BSACI (British Society for Allergy and Clinical Immunology), and a student of Professor Jack Pepys. He was a prolific writer, publishing some 80 papers, and specifically wrote about the delayed reaction to molds on intradermal testing, and described it thoroughly in his publications. He felt the delayed mold reaction, although obscure in cause, was "not without biological significance". In retrospect, his interest in mold was probably stimulated by his wife Susan's serious illness from mold, and a serious case of "dry rot" in his house! He was a consumate clinician and researcher, who tragically passed away with pancreatic cancer. Dr. David J Freed has this to say about him in his memorium:
As a doctor he was loved by his patients—they too could not get a word in edgeways, but did not seem to want to either because Keith intrigued and entertained them as well as giving sound medical advice. When lecturing at formal medical gatherings he used an impish sense of humour to illustrate points that might otherwise have been difficult for doctors to comprehend, as, for example, his famous comment on the cause of atopic eczema. To judge by the prescribing behaviour of doctors, he dryly noted, it must be caused by betamethasone deficiency! He was also multitalented, and few of us saw all sides of the man. Whatever he turned his attention to he became absorbed in and became good at, whether it was painting, sculpting, or restoring vintage cars (during his general practice years he could often be seen, on dry days, driving his open-top Alvis or Gilbern around the practice to visit patients, fully kitted out in goggles, beret, and huge motorman’s gloves...So what do we know about Eaton's sign? A few intriguing points I've found:
Throughout our lives, allergists listen to tales...and in the end, we become a storytellers, full of fascinating clinical viginettes from our experiences in caring for allergy patients. A recently article, entitled "The tale of the Allergists life: A series of interesting case reports" by Ray Slavin, M.D. in Allergy Asthma Proc. 2008 Jul-Aug;29(4):417-20, emphasizes this fact. A few quotes from the article are worth noting:
"The practicing allergist has the unique opportunity to see an extraordinary variety of fascinating patients. Identifying the precise cause of the patient's complaints makes for a satisfying intellectual endeavor...To get to the heart of the matter, rather than simply starting a new drug or increasing the dose of the present medications, makes for an intensely gratifying intellectual experience and one that also benefits the patient. What a great way to make a living!"It is ironic that one of my most interesting tales comes from an elderly man I met, who was actually a professional storyteller (and flute-player). It was a pleasant day in March of this year, when I turned the doorknob and entered the exam room.
"I want help with my neuropathy", he said. "I've been to the University of XX and after a detailed workup, they diagnosed idiopatic neuropathy. I began gabapentin in 2005. I continued with my symptoms and saw another neurologist for a second opinion, and after a further series of tests, I was given Lyrica to counteract the pain in my feet and legs in 2006. However, Dr. X is questioning the diagnosis of peripheral neuropathy, because I have tingling in my face, neck and back as well as my feet and legs, and he prefers to call it an immune or inflammatory neuropathy."
"I began weekly infusions of one gram of methylprednisolone in April of last year (2007), and these were changed to every other week in June of this year (2008). I immediately noticed benefits--dramatic lessening of need to take Gabapentin for pain, I had better balance, and a return of skin sensitivity where I was previously numb."
"Tell me about your current symptoms", I said.
He looked at me sadly, then began:
"I have a real struggle with my balance for the last couple of years, but the big thing is that I have terrible numbness and tingling in the legs and feet, below the knees. There is tingling, and some pain however, in all areas above the knees, including the face, neck, back, hands, and arms. The feet and lower leg pain and numbness is present most of the time, but can be reduced by the steroid infusions, which reduce the need for pain meds consideratly. I take the infusions on Monday and initially get good relief, but by Thursday, the pain and tingling in the lower legs recurs with a terrible vegance."
"Tell me about your alcohol ingestion", I said.
He looked at me.
"I'll be honest with you. I had considerable alcohol consumption from about 1966 to 1975, then a period of no consumption lasting until about 1983. Then I again had heavy consumption lasting until about 1995, then again a period of no consumption for 4 years.Then I began to drink heavily again, and haven't had a drink since Feb of 2004. I attend AA meetings now."
"Any respiratory problems?" I asked.
"I've got some nasal drainage and cough in the fall, but that's a minor issue" he said.
"How about your diet and your intestinal function?" I asked.
"Well, I am bothered by alot of intestinal bloating and gas" he admitted. "I've also found that some foods aggravate my pain--yogurt, peanut butter, nuts, citrus all intensive the symptoms in my feet and legs so I avoid them. "
I looked at the personal questionnaire he had typed out before the visit. He had a litany of problems in addition to his presenting one: glaucoma, rosacea, gout, sleep apnea, venous stasis dermatitis, tinnitus, hypertension, and a prior history of nasal polyposis.
When I examined him, he needed a cane for walking, and although his Romberg was intact, he had a very unsteady heel-to-toe walk, for which he needed assistance. He had decreased knee reflexes bilaterally, but at the time of exam, sensory exam was intact to light touch on both legs. Pedal edema was noted bilaterally. Mild pharyngeal posterior nasal drainage was seen.
Corn, peanut, soy, yeast, gluten--Negative
Gliadin IgA 9.45 (nl <5)
Gliadin IgG 6.98 (nl <7)
Tissue Transglutaminase IgA 2.31 (nl <20)
milk: increased pain, tingling in feet, swelling sensation in feet, imbalance & unsteady; flu-like sensation throughout body; increased pain in forehead & cheeks; increased impairment on heel-to-toe walking (on exam)
corn: increased impairment on heel-to-toe walking (on exam), slight numbness in feet
gluten: incresed impairment on heel-to-toe walking (on exam), weakness on walking
yeast: heavy sensation in legs "felt like wooden blocks"., slightly unsteady heel-to-toe walk
Candida: pain increasing from feet up to legs, heavy sensation in legs,
Antigen Immediate rxn Delayed rxn
dust 8mm dil 2 +
alternaria 9 mm dil 1 ++
Cladosporium 9 mm dil 1 ++
Candida 8 mm dil 2 +++
Histamine control 10 mm dil 2
Pollens (tree/grass/weed) 6 mm dil 2
1. Neuropathic pain, multifactorial, related to former alcohol abuse,--variant nature of pain related to celiac disease, food sensitivities, and Candida related illness.
2. Abnormal celiac antibodies, with evidence of gluten sensitivity clinically on challenge
3. Abnormal IgG antibodies to dairy & egg, with evidence of dairy sensitivity clinically on challenge
4. Abnormally strong ID delayed reaction to Candida, with evidence of Candida and food yeast sensitivity on challenge
5. Impaired gut integrity, with increased intestinal permeability likely, as a result of chronic alcohol use, and celiac disease, and enhanced carriage of Candida in gut secondary to chronic antibiotic use for rosacea
6. Chronic Tinnitus probably aggravated by allergy
7. Mild mold sensitivity causing seasonal fall congestion.
8. Sleep apnea
12. Chronic tinnitus
13. Venous stasis dermatitis
14. Penicillin allergy
15. s/p nasal polyposis
Here is my "discussion" that I shared with my patient in writing:
"I mentioned to Mr. X that I felt it would be possible that low grade food sensitivities have been worsened following a probable increase in intestinal permeability that could have occured as a result of chronic alcohol ingestion historically. His use of antibiotics chronically since 1999 for Rosacea could have caused Candida overgrowth and further impairment in intestinal integrity and heightened intestinal permeability or "leaky gut". The combination of alcohol ingestion and increasing Candida growth could have, in summary, caused a leaky gut with more food reactions developing. Clinically, he is already aware that certain foods bother him and seem to increase neuropathic pain. This would include yogurt, raspberries, peanut butter, nuts, and citrus. The fact that he has a very atypical neuropathic pain problem, with no concurrent muscle wasting, and the fact that his symptoms include intestinal issues, and areas of involvement outside of his lower legs per se would suggest that food sensitivities and yeast issues are aggravating his condition..."
1. SLIT for offending foods
2. Rotary-diversified elimination diet, both gluten and dairy free, and also eliminating eggs, yeast, citrus, corn, tomatos, nuts.
3. Nystatin antifungal medication, probiotics
4. Continuation of medications, except for doxycycline
5. Continuation of vitamin supplements already on
When I saw the patient back in the clinic, he was no longer using a cane. His heel-to-toe walk was unimpaired, and could be done without assistance. He handed me a written summary of his progress:
"My strength and stamina have increased dramatically since going on the diet 3 months ago... I have rapidly lost 40 pounds to date, and have eliminated the taking of protonix and gabapentin. I have reduced the steroid infusions to once every three weeks. Neuropathic pain still remains if I don't take Lycra, but greatly reduced. It appears that an element of neuropathy is reversing as I seem to have more control over the awareness of the need for urination and defecation and sexual responsiveness is improved. So, can celiac disease or/or food sensitivities cause or contribute to peripheral neuropathy? His neurologist currently thinks so, based on this patient's response and his improvements. I would refer you to an excellent review of the Subject by Grossman, published a few months ago in April 2008, entitled "Neurological complications of celiac disease: what is the evidence?" In Pract Neurol.
As Grossman points out in his article, ,
"This literature has become quite controversial, with disputes over the definition of coeliac disease and gluten sensitivity, whether neurological complications are caused by coeliac disease or are epiphenomena, and whether the proposed complications respond to a gluten-free diet."However, although the literature may be controversial, my patient really doesn't see any controversy to be concerned about on a personal level. He's getting better, and that's what matters to him. And the purpose of this tale?--simply to arouse our curiosity as allergists, and to "think outside the box" with our patients. And it all gets back to listening to tales...and becoming storytellers ourselves. But with one important difference. We try to end each story on a happy note... for the benefit of our patients.
I love aphorisms...and those of you with keen clinical eyesight will now see that I have a list of personal allergy aphorisms listed in the rightside menu bar of my Blog....Aphorisms give us memorable insights into the minds of others, and ideas to mull over....and it was in that spirit that I provide them...Maybe my love for aphorisms is because I was academically raised on them...while I was at the University of Iowa one of my attending physicians was the late Dr. William Bean.
Dr. Bean interned on the Osler service at Johns Hopkins, and he was named Sir William Osler Professor of Medicine at the University of Iowa. One of my most treasured medical posessions is a signed textbook I received from him, entitled "Sir William Osler: Aphorisms from his bedside teachings and writings". These aphorisms were collected by Dr. Bean's father (Robert Bennett Bean), who was a medical student under Osler, and my attending physician William Bean edited and published them. After 30 years, I still have the textbook. Through Dr. Bean, I felt I had a direct connection to the life of Osler--Dr. Bean stated "my memory does not go back to the time when Osler was not a household word...almost even a household god..." Dr. Bean remembered how personally devastated his family was at Osler's son's death. And the book of Osler's aphorisms I got from Dr. Bean? You can only imagine how they influenced my own thinking as an embryonic physician entering the grand specialty of medicine....
...But what about allergy? Do we have our "own" aphorisms, written and recorded by the giants of allergy? In truth, hardly any. Why? Perhaps it's because allergy is seen nowindays as a technical/immunological field...after all, how many aphorisms can you write about dust mite exposure modifying the effect of functional Il10 polymorphisms on allergy and asthma exacerbations? In this time and age, the patient may be seen more as a complex roadmap of cytokine interactions rather than a living, breathing organism. ...I am again reminded of one of Osler's aphorisms:
"The greatest art is the concealment of art, and I may say that we of the medical profession excel in this respect..."
There was, however, one article on the subject I found: "Aphorisms and Facetiae of Bela Schick, written by I.J. Wolf M.D. and published in Clinical Pediatrics, pp 495-497, 1968, subsequently made into a book. . Some great aphorisms abound:
"It is too bad we cannot cut the patient in Half to compare two regimens of therapy..."
"You can always make a theory. In making theories, always keep a window open so that you can throw one out if necessary. Twenty theories can be made in five minutes"
"There was no diagnosis--that's what makes the case interesting" (in responding to someone who remarked that a case was interesting)
"The human body is like a bakery with a thousand windows...We are looking into only one window of the bakery when we are investigating only one particular aspect of a disease..."
Now think about this one: Allergy as a profession is nearly 100 years old. We have only one article and one textbook of aphorisms about only one allergist. Aphorisms breathe "art" into the "science" of clinical medicine. They help us to remember what's really important in our life as clinicians. They are an endangered species. We must preserve them.
Chronic angioedema and urticaria: The Strange case of the water management employee...and the Tyranny of IgE
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....
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
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.
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 CourseWithin 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...
I've said it before, but I'll say it again. The most valuable diagnostic ally in the allergists armamentarium isn't a skin test or a blood test...it's a good clinical history coupled with a healthy sense of curiosity. When this patient told me about the curious incident involving eating a whole bran muffin, and noting an immediate reaction, I began to think along the lines of a non-IgE mediated food sensitivity. If we eat a food, it is in our system (assuming a normal GI transit time) of about 3 and 1/2 to four days. So if this patient is having wheat products daily, he always has a constant "load" of wheat in his system--which fluctuates from day to day. Walter Vaughn wrote in his textbook that he had a patient who could eat wheat twice weekly, but not daily--otherwise she would have symptoms. His prior allergists had shut out the possibility of extrinsic factors triggering a reaction--since his total IgE was normal. No IgE? No reaction, right? Wrong. ...