Alpha-gal (Meat) Allergy

Alpha-gal allergies are a reaction to Galactose-alpha-1,3-galactose, whereby the body is overloaded with immunoglobulin E antibodies on contact with the carbohydrate. Alpha-gal is found in all mammals apart from primates (including humans). Bites from the lone star tick, which transfer this carbohydrate to the victim, have been implicated in the development of this delayed allergic response which is triggered by the consumption of mammalian meat products.[1] Despite myths to the contrary, an alpha-gal allergy does not require the afflicted to become a vegetarian, as poultry and fish do not trigger a reaction.

The allergy most often occurs in the central and southern United States, which corresponds to the distribution of the lone star tick.[3] In the Southern United States, where the tick is most prevalent, allergy rates are 32% higher than elsewhere.[4] However, as doctors are not required to report the number of patients suffering the alpha-gal allergies, the true number of affected individuals is unknown.


The allergy was first formally identified as originating from tick bites in a 2007 paper by Sheryl van Nunen. Prior to the paper’s publication, Thomas Platts-Mills and Scott Commins, were attempting to discover why some patients were reacting negatively to the carbohydrate in the cancer drug Cetuximab.[6][7] They had previously hypothesized that a fungal infection or parasite could lead to the allergy.[6][8] It wasn’t until Platts-Mills was bitten by a tick and developed alpha-gal allergies, that his team also came to the conclusion that there was a link between tick bites and the allergy.[8]

Alpha-gal allergies are very similar to Pork-Cat Syndrome and hence misidentification can occur.[9]


Alpha-gal allergies develop after a person has been bitten by the Lone Star Tick in the United States, the European Castor Bean Tick, and the Paralysis Tick in Australia.[6][7] Alpha-gal is not naturally present in apes (including humans), but is in all other mammals. If a tick feeds on another mammal, the alpha-gal will remain in its alimentary tract.[2] The tick will then inject the alpha-gal into a person’s skin, which in turn will cause the immune system to release a flood of immunoglobulin E antibodies (a.k.a. IgE) to fight off the foreign carbohydrate.[2][6] Researchers still do not know which specific component of tick saliva causes the reaction.[10]

A 2012 preliminary study found unexpectedly high rates of alpha-gal allergies in the Western and North Central parts of the United States, which suggests that the allergy may be spread by unknown tick species.[4] Examples of alpha-gal allergies were even present in Hawaii, where none of the ticks identified with the allergies live.[10] Human factors were suggested but no specific examples were provided.[4]


A typical allergic reaction to alpha gal has a delayed onset, occurring 4–8 hours after the consumption of mammalian meat products, instead of the typical rapid onset with most food allergies. After the delayed onset, the allergic response is typical of most food allergies, and especially an IgE mediated allergy, including severe whole-body itching, hives, angioedema, gastrointestinal upset, and possible anaphylaxis.[11] These symptoms are caused by too many IgE antibodies attacking the allergen, in this case the alpha-gal.[6] In 70% of cases the reaction is accompanied by respiratory distress and as such is particularly harmful to those with asthma.[12]

Alpha-gal allergies are the first food allergies to come with the possibility of delayed anaphylaxis.[12][13] It is also the first food-related allergy to be associated with a carbohydrate, rather than a protein.[13][14]

Treatment and medical issues

Blood tests for IgE response indicating alpha gal allergy have not been approved by the U.S. Food and Drug Administration (FDA), and must usually be purchased by private individuals, but are available and are in use.

Alpha-gal is present in cancer drugs, as well as the IV fluid replacements Gelofusine and Haemaccel.

There has been at least one instance of a man with an alpha-gal allergy going into anaphylaxis after receiving a heart-valve.[6] Some researchers have suggested that the alpha-gal which is prevalent in pig’s tissue, and used for xenografts, may contribute to organ rejection.

Unlike most food allergies, the alpha-gal allergy will recede with time, as long as the person is not bitten by another tick. The recovery period can take anywhere from eight months to five years.

A new type of cancer treatment called HyperAcute immunotherapies, which utilizes humans’ usual immunity to alpha-gal is being tested by NewLink Genetics Corporation.[16] The treatment uses modified alpha-gal cells to provoke a strong reaction in the immune system, but targeted towards cancer, rather than attacking the alpha-gal cells themselves.[17] As of November 2013, the treatment was in a Phase 3 Trial with the FDA.[16]




Celiac Syndrome

The Controversy of Celiac Disease (Gluten Sensitivity)

The problem here is that we define a complex autoimmune disease spectrum by a traditional and end-stage histologic finding. Better tools are on the way… There is a spectrum of gluten intolerant disorders. I vote that she has gluten intolerance which is also called celiac syndrome. Treatment is a gluten free diet. Only the top 30% of gluten intolerant people meet the criteria of celiac disease with positive blood work and biopsy. The other 70% are not able to be diagnosed by current criteria but definitely have gluten intolerance or celiac syndrome.

A number of people without celiac disease may feel better on a restrictive diet, but I suspect for a lot of them it’s because their diet is now healthier. I have seen a lot of this and found out that it’s the lack of processed and junk foods rather than the lack of gluten that works for them. Just something to think about.


Fungal Issues and Gluten Sensitivity

Fungal Allergies and Sinus Issues


yeast_top_01_large-300x74Yeast, Candida, Thrush, Monilia, Mold, and Fungus are all terms that we routinely use interchangeably and incorrectly. This is often confusing to both physicians and patients. Mycology is the “study of” fungi and we really have very little of it in medical school. There are really separate pathologic conditions we must differentiate in order to understand the condition. Unfortunately, there is no rule that you cannot have a combination of things affecting you.

Fungal Sinusitis

Fungal sinusitis is really nebulous term that implies there are fungi creating problems within the paranasal sinuses. By definition there really must be some objective findings on a CAT scan of the sinuses. If indeed there are fungal organisms in the sinuses, these can cause inflammation via a number of mechanisms. First, by the fact that they are sitting there in close contact with our sinonasal mucosa, it is more likely that we develop sensitivities or allergies to them. No matter if there are allergies to the fungi or not, removing them from the sinonasal passages is paramount.

Allergic Fungal Sinusitis

When there are fungal organisms inappropriately occupying the sinuses they will often elicit an allergic response. The CT is often impressive for multiple fungal organisms and the allergy tests seem to correlate. Dr. Bradley Marple and colleagues at Dallas Southwestern really described this condition called Allergic Fungal Sinusitis. The treat ment is meticulous surgical debridement and subsequent allergic desensitization.

Eosinophilic (non allergic) Fungal Sinusitis

Mayo clinic physicians have discovered a non allergic (but immune mediated) inflammatory response to molds which causes sinusitis as well. They have termed this Eosinophilic Fungal Sinusitis. It is primarily Cell Mediated (not IgE Mediated) and seems to be related to a specific mold Alternaria. Again, removing any and all molds and then controlling the immune response is the treatment. They actually propose rinsing the sinonasal passages with antifungal agents.

Invasive Fungal Sinusitis

Invasive fungal disease really is largely limited to immunocompromised patients. We often see these as urgent life threatening conditions on the oncology ward. We immediately try to remove all of the offending fungi, however the survival of the patient is really more dependent on the patient mustering some type of an immunologic response. Whether or not the patient has allergies, it rarely makes sense to desensitize an immunocompromised patient.
Candidiasis and Mold Allergies

Fungi can also cause patients problems even if there sinuses are not loaded with organisms. In these patients, the CAT scan is less impressive and surgery is not in the treatment regimen.

Mold Allergies

Allergy to molds is a common ailment and can really keep patients miserable on a year round basis. Molds are often airborne20and unfortunately can cause symptoms on a year congestion, and fatigue. They can readily be diagnosed by either skin or blood testing for IgE against each type of mold. Again, removing the fungi and then desensitizing the patient is the treatment.


Candidiasis is really a diagnosis of exclusion, and a questionable one at that. Dr. William Crooks defined the condition as an overgrowth of yeast primarily within our digestive tract that leads to a chronic inflammatory state. It too is treated with elimination of the molds as much as possible, and then setting up conditions to avoid recurrent yeast overgrowth. These treatment options really seem to help a lot of patients, I am just not sure we understand the pathophysiology of what is really going on. In treating these patients we often try dietary manipulation that would preclude fungal overgrowth. This is often a low carbohydrate or gluten free type of diet. I suspect this may be the major reason these people feel better.

Gluten Sensitivity

Gluten intolerance (Celiac Disease) is probably an under recognized entity.  There is certainly a large portion of the population that has some sensitivity to gluten and feels much better avoiding it.  Whether or not they meet the criteria for Celiac seems academic.


For whatever reason, many patients seem to get clinical benefit from antifungals, probiotics, and or dietary changes. This makes sense, in that lessening exposure to substances patients are sensitive to, would make them feel better. Likewise, desensitizing them with immunotherapy, also seems to be helpful.






What is new in post op tonsillectomy?

Recovering From Throat Surgery

Unknown-4Recovering from throat surgery such as tonsillectomy, uvuloplasty, and or base of tongue surgery can be excruciating. There is no pain therapy that is out of bounds. I give 12 mg Decadron intra operatively and generously inject Exparel into the operated on area.

Topically Gelclair can be very helpful. It forms a barrier (similar to but also superior to Carafate). Magic mouth rinse with topical anethestics or Numbing throat sprays (Chloraseptic) can be temporarily helpful.

confezioniI personally use 10 mg of ocycontin po q 12, Lortab Elixir, Motrin Elixir and Amoxacillin or Zithromax Elixir. A Medrol Dose pack can be utilziled. Toradol can also be helpful, although bleeding risk must be considered.

Higher dose steroids (Prednisone) and or more powerful sustained release narcotics such as Oxycontin or Dilaudid can be considered.

Post on recent Angioedema Case

201312howarth-fig-1This is a case of angioedema, a significant swelling of tissues deep to the skin and mucous membranes. Angioedema differs from conditions such as urticaria where there is swelling of the skin. Angioedema most commonly affects the tongue and face. It can also affect abdominal organs.

Angioedema without urticaria can be induced by NSAIDs, or it can be part of a histamine-driven allergic reaction, or be driven by accumulation of bradykinin.1 The patient had not taken any NSAIDs and there was no response to treatments directed towards a histamine-driven allergic process. Reasonable explanations of this presentation of angioedema without urticaria include:13

  • ACE inhibitor angioedema, which occurs in ACE inhibitor users at a prevalence greater than 1:1000. Most cases are much milder than this one.
  • Hereditary angioedema is a condition with a prevalence of about 1:10 000 or less.2 There is a deficiency in C1 esterase inhibitor, or C1 esterase inhibitor is present but not functional, allowing accumulation of active C1 esterase. This in turn leads to, among other things, a periodic accumulation of bradykinin in tissues that results in angioedema.
  • Acquired C1 esterase inhibitor deficiency is an autoimmune condition in which there is autoimmune inactivation of C1 esterase inhibitor.4 This renders the C1 esterase inhibitor ineffective and excess C1 esterase activity can develop. This can result in accumulation of bradykinin in tissues. This condition is very rare with less than 150 described cases.
  • Hereditary angioedema without C1 esterase inhibitor deficiency appears to be due to abnormalities in clotting factor XII and occurs with a prevalence of less than 1:100 000 people.5 The majority of cases are female.

The absence of a family history made either type of hereditary angioedema very unlikely. Further this would be an extraordinarily delayed onset for either type of hereditary angioedema.

The patient was investigated for C1 esterase inhibitor deficiency. Functional C1 esterase inhibitor level was 105% (reference range 70–130%). This ruled out hereditary angioedema and acquired C1 inhibitor deficiency. With respect to hereditary angioedema without C1 esterase inhibitor, over 90% of patients with this very rare condition have a positive family history and most cases are female.

From the above we can conclude the diagnosis is ACE inhibitor angioedema. Neither of the treating doctors recognised the condition as ACE inhibitor angioedema at time of presentation and they treated it as an allergic reaction.


ACE inhibitor angioedema has long been a known adverse drug reaction occurring with the whole group of ACE inhibitors. It has been estimated by various means to occur in 0.1–0.42% of patients on an ACE inhibitor.68 It occurs most commonly in the first year of treatment with an ACE inhibitor but can occur after years of use.9,10 Patients may have multiple episodes of ACE inhibitor angioedema before the condition is recognised, and patients with initially mild episodes may progress to having severe life-threatening episodes.9,10

The condition is usually not correctly diagnosed on initial presentation and even in fatal cases the condition often appears to have been unrecognised.11,12 The incidence is likely to be underestimated, which is concerning because of the potential for the condition to be lethal.

The typical case involves swelling of the tongue, but the lips, pharynx, larynx and submandibular tissues can also be involved.9,12 In severe cases failure to secure an airway has led to death by asphyxia.11,12 There have been a number of reported cases where the condition has manifested only as angioedema of the gut. Such cases are usually initially diagnosed with primary abdominal complaints, such as irritable bowel or ischaemic colitis.13,14 Such patients are at risk of undergoing laparotomy.15

There are a number of risk factors for development of ACE inhibitor angioedema. African American patients have repeatedly been shown to be at approximately four times the risk of other patients.6,8,16 Smoking also increases the risk of developing this condition.16 A history of an ACE inhibitor-induced cough is associated with a 9-fold increase in the risk of angioedema.16 Thus it is important to take patients with an ACE inhibitor-induced cough off this group of drugs.

The lack of response to adrenaline, antihistamines and steroids in this case is typical and is due to the condition being related to accumulation of bradykinin and not histamine. With ACE inhibition the breakdown of bradykinin is partly dependent on dipeptidyl peptidase 4 (DPP4). Levels of DPP4 may be reduced in patients who have ACE inhibitor angioedema.1719 The incidence of angioedema with the combination of an ACE inhibitor and a DPP4 inhibitor seems to be 4–5 times higher than the risk with an ACE inhibitor alone.19

A concern for the future is that DPP4 inhibitors are rapidly entering the market for the treatment of type 2 diabetes. These drugs help control type 2 diabetes by inhibiting the breakdown of incretins. As ACE inhibition is usually seen as first-line therapy for hypertension in patients with type 2 diabetes, the incidence of angioedema, a potentially lethal condition, may become more common now that DPP4 inhibitors are regularly being used. If, as in this case, patients can develop angioedema after many years of stable ACE inhibitor use then adding a DPP4 inhibitor may become the destabilising trigger for an episode of angioedema.

Treatment options

In the long term, after an episode of ACE inhibitor angioedema, the patient must not take this class of drug again. Frequently, the patient will be switched to an angiotensin II receptor blocker (ARB). These drugs can also induce angioedema though at a much lower rate than ACE inhibitors. Further, ARBs do not seem to induce severe episodes.20

The acute management of this condition is not clear-cut. The use of antihistamines, steroids and adrenaline is often quoted although there does not seem to be any evidence for efficacy with this line of treatment and certainly in this case there was no apparent benefit. There is often an automatic response among clinicians to give an antihistamine for any condition that could be an immediate hypersensitivity reaction. In a case such as this there is a risk with the use of a sedating antihistamine as the airway may be about to become compromised and a sedating drug may lead to respiratory decompensation.

There are case reports of ACE inhibitor angioedema being successfully treated with fresh frozen plasma.2123 These reports have appeared for over a decade now. There is a recent study of seven patients given fresh frozen plasma for this condition, all of whom had failed to respond to antihistamines, steroid and adrenaline.24 All seven rapidly improved after fresh frozen plasma. Thus, faced with a patient exhibiting severe ACE inhibitor angioedema, a trial of a couple of units of fresh frozen plasma would seem very reasonable to hopefully shorten the attack or to reduce the need for what could be a very difficult intubation.

There are also reports of the successful use of the bradykinin receptor antagonist icatibant,25 a short peptide that has a structure related to bradykinin. It can be administered by subcutaneous injection and is used by patients with hereditary angioedema, often by self-administration. It is not available in rural hospitals and it costs about $3000 per dose.26 By comparison, fresh frozen plasma is available in most rural hospitals and is relatively cheap at $300 a bag.27 Fresh frozen plasma, however, has the disadvantage of having to be thawed, and the minor risk of being a blood product.

Clearly, cases of the severity of this one require urgent airway management and may require emergency cricothyroidotomy.

Oral Allergy Syndrome

69x75_antihistamines_decongestants_allergy_relief_ref_guideOral Allergy Syndrome, also known as pollen-food syndrome is caused by cross-reactive allergens found in both pollen and raw fruits, vegetables, and some tree nuts. Those with oral allergy syndrome typically have issues with the inhalants: birch, ragweed, and grass.  The cross reactors are as follows:

Birch Pollen: Apple, almond, carrot, celery, cherry, hazelnut, kiwi, peach, pear, plum.

Grass Pollen: celery, melons, oranges, peaches, tomato.

Ragweed Pollen: Bananna, cucumber, melons, sunflower seeds, Zucchini.

Mango and Cashew/Pistachio Cross Reactivity

220px-Apple_mango_and_cross_section_edit1Should a patient with proven allergy to cashew and pistachio always be told to avoid mango or should a separate evaluation for mango allergy be carried out on a case by case basis? Thank you for your advice and help.

As you know, the evergreen tree family includes mango, pistachio, cashew, and poison ivy.

The exact incidence of mango allergy is unknown. However, there have been series of patients with food allergy where the incidence of reactions to mango has been compared with that to other foods. For example, in a series of 132 children, ages 3 to 19 years, there was one case of mango allergy compared to cow’s milk in which there were 11 cases (1).

In another study carried out over nine years, in 580 patients with food allergy, mango was responsible for 6% of the foods to which patients reacted. This study was conducted in France (2).

Thus, although the exact incidence of reactions to mango remains unestablished, it is obvious that compared to other foods, reactions to mango occur less frequently.

Mango contains a number of different allergens which are found in many other foods besides pistachio and cashew. For example, there is a fruit profilin in mango which is also found in pear, peach, and apple. There is a panallergen found in celery, carrot, apple, peanut, paprika, anise, fennel, coriander, and cumin that demonstrates cross-reactivity with mango. Mango has also demonstrated cross-reactivity to foods in the “latex-fruit cross-reactivity syndrome.” A chitinase-like protein cross-reacting with latex has been found in mango as well as avocado, chestnut, banana, kiwi, tomato, passion fruit, and papaya.

Thus, the allergen profile of mango is complicated, and cross-reactivity spanning many other foods has been shown in vitro. Based upon the biological family containing mango, pistachio and cashew nut, one would expect there to be cross-reactivity between mango and these two nuts. However, such cross-reactivity probably occurs less frequently than predicted by the biological taxonomy of these foods (3).

Cross-reactivity has, as you know, been shown to exist between cashew and pistachio nut. However, this cross-reactivity did not extend to mango pulp, although it was present in mango seed (4).

Thus, based upon in vitro studies, there has been surprisingly little cross-reactivity demonstrated between mango pulp and pistachio and cashew. On the other hand, pistachio and cashew, as you know, demonstrate a great deal of cross-reactivity based on in vitro studies.

A similar profile is seen when one looks at case reports of patients reacting to mango. There are a number of case reports of allergic reactions to mango. In some of these, patients have also shown clinical reactivity to pistachio or cashew (5, 6). However, there clearly have been patients who have reacted to mango and yet tolerate pistachio and cashew nut without difficulty (7).

Taking all of these data and reports into consideration, one can draw the following conclusions:

1. The exact incidence of mango allergy is unknown, but clearly reactions to this fruit occur far less frequently than more common culprits.

2. There is an unexpectedly sparsely demonstrated in vitro cross-reactivity between mango and cashew, and pistachio. However, there is strong cross-reactivity between cashew and pistachio.

3. Clinical cross-reactivity varies. Some patients who react to mango have demonstrable cross-reactivity to pistachio or cashew, and others do not.

Thus, when faced with giving advice to a patient who has mango allergy, unfortunately there is no axiomatic approach. The only true test of allergy to a food, especially when we do not have negative and positive predictive value for in vitro tests, is an oral challenge. This clearly applies to potential cross-reactivity to pistachio and cashew in a patient with mango allergy.

One can gather information regarding potential allergy by skin test and serum-specific IgE determinations, but definitive information is not available.

Black Hairy Tongue

Basically a bacterial

The name black hairy tongue may sound scary, but the condition is harmless. Black hairy tongue is caused by bacteria or fungi in the mouth, which make the tongue appear black and hairy. It’s easily remedied by good old-fashioned oral hygiene.

What Causes Black Hairy Tongue?
A black hairy tongue is caused by too much bacteria or yeast growth in the mouth. The bacteria build up on tiny rounded projections called papillae. These lie along the surface of the tongue. Instead of shedding as they normally do, the papillae start to grow and lengthen, creating hair-like projections. They can grow to 15 times their normal length.

Normally, the papillae are pinkish-white. But as they grow, pigments from food, drinks, and possibly the bacteria or yeast themselves get caught in the papillae, dyeing the tongue a color. Most often that color is black, hence the name. But the tongue can also turn brown, yellow, green, or a variety of other colors.

Certain lifestyle habits and conditions can make people more likely to develop black hairy tongue. They include:
poor oral hygiene
smoking tobacco
drinking a lot of coffee or tea
using antibiotics (which may disrupt the normal balance of bacteria in the mouth)
being dehydrated
taking medications that contain the chemical bismuth (such as Pepto-Bismol for upset stomach)
not producing enough saliva
regularly using mouthwash that contains peroxide, witch hazel, or menthol
getting radiation therapy to the head and neck
Black hairy tongue is more common in men, people who use intravenous drugs, and those who are HIV-positive.

What Are the Symptoms of Black Hairy Tongue?
Other than the appearance of the tongue, most people with black hairy tongue don’t have any symptoms or feel any discomfort. The exception is when there is too much growth of the yeast Candida albicans, which can cause a burning sensation on the tongue. This burning sensation is called glossopyrosis.

Some people complain of a tickling feeling in the back of the roof of the mouth, a metallic taste in their mouth, or nausea. In more severe cases, the condition may lead to a gagging feeling. Sometimes, food getting caught inside the extra-long papillae can cause bad breath.

How Is Black Hairy Tongue Treated?
Practicing good oral hygiene is the best way to treat black hairy tongue. Gently brush your teeth twice a day with a soft toothbrush. Also, brush your tongue. You can use a tongue scraper to make sure you’re thoroughly cleaning the area. Drink plenty of water throughout the day to help keep your mouth clean.

Other tips include:

If you smoke, quit.
Add more roughage to your diet. Soft foods won’t clean off the tongue effectively.
Call your doctor or dentist if the problem doesn’t get better on its own. Your doctor may prescribe antibiotics or an antifungal drug to get rid of the bacteria or yeast. Topical medications, such as tretinoin (Retin-A), are also sometimes prescribed. As a last resort, if the problem doesn’t improve, the papillae can be surgically clipped off with a laser or electrosurgery.

Grass Antigen Pill

FDA Approves Grastek, Merck’s Grass Allergy Pill; Joins Oralair In New Round Of Immunotherapies


The FDA’s approval of Merck’s Grastek ushers in a new era of grass allergy immunotherapy, as it’s the second medication to be approved for grass allergies this month. Merck

Spring is here, and it’s bringing seasonal allergies along with it. So it’s no surprise that a new round of allergy medications are getting approved by the Food and Drug Administration (FDA) — though they probably should have looked to an earlier release — the most recent of which is Merck’s Grastek, a sublingual — going under the tongue — pill for treating grass allergies.

Grastek is the second sublingual oral immunotherapy (SLIT) to be approved this month and the first of three that Merck plans to market, MedPage Today reported. Once placed under the tongue, it dissolves and super small doses of timothy grass extract are released into the body with the purpose of weaning a person’s allergies out of severity. Although it’s only made with the extract of timothy grass pollen, it’s cross reactive, and therefore can help treat other grass allergies as well, including sweet vernal, orchard, perennial rye, Kentucky blue, and red top.

Sebaceous Adenoma

230px-Sebaceous_adenoma_-_low_magSebaceous adenoma is a cutaneous condition characterized by a slow-growing tumour usually presenting as a pink, flesh-coloured, or yellow papule or nodule.

Sebaceous adenomas, in isolation, are not significant; however, they may be associated with Muir-Torre syndrome, a genetic condition that predisposes individuals to cancer.[3] Thus, identification of a sebaceous adenoma may be a life saver.

It is associated with tuberous sclerosis complex. The term adenoma sebaceum is a misnomer.