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.


Trichilemmoma (also known as “tricholemmoma”) is a benign cutaneous neoplasm that shows differentiation toward cells of the outer root sheath.230px-SkinTumors-P6190341 The lesion is often seen in the face and neck region. Multifocal occurrence is associated with Cowden syndrome, in which hamartomatous intestinal polyposis is seen in conjunction with multiple tricholemmoma lesions.

Rhinoplasty Photography

The art and technology of photography can be overwhelming to the facial plastic surgeon. Photographic documentation of patients undergoing rhinoplasty is essential for patient consultation, perioperative planning, and postsurgical evaluation. Possession of a basic understanding of photographic principles, technique, equipment, as well as consideration regarding consistency of patient positioning is essential for producing the best photographic results. This article reviews the basic principles of photography and discusses their application to facial plastic surgery practice, and rhinoplasty in particular.

Post on Hiccups

What are hiccups?

Hiccups  occur when a spasm contracts the diaphragm, a large sheet of muscle that separates the chest cavity from the abdominal cavity. This spasm causes an intake of breath that is suddenly stopped by the closure of the vocal cords (glottis). This closure causes the characteristic “hiccup” sound.

What causes hiccups?

A very full stomach can cause bouts of hiccups that go away on their own. A full stomach can be caused by:

Eating too much food too quickly.
Drinking too much alcohol.
Swallowing too much air.
A sudden change in stomach temperature, such as drinking a hot beverage and then a cold beverage.
Emotional stress or excitement.
How long do hiccups last?

Hiccups usually stop within a few minutes to a few hours.

Hiccups that last longer than 48 hours are called persistent hiccups. Hiccups that last longer than a month are called intractable hiccups. While very rare, intractable hiccups can cause exhaustion, lack of sleep, and weight loss. Both persistent and intractable hiccups may be a sign of a more serious health problem and must be checked by a doctor.

There are many known causes of persistent or intractable hiccups, including:

Central nervous system problems, such as cancer, infections, stroke, or injury.
Problems with the chemical processes that take place in the body (metabolic problems), such as decreased kidney function or hyperventilation.
Irritation of the nerves in the head, neck, and chest (vagus or phrenic nerve).
Anesthesia or surgery.
Mental health problems.
How are hiccups treated?

Most bouts of hiccups go away on their own within a few minutes to a few hours and do not require any treatment.

Many home remedies are used to treat hiccups. Most of them involve increasing the level of carbon dioxide in the blood, which usually stops hiccups. Some of these remedies include:

Holding your breath and counting slowly to 10.
Breathing repeatedly into a paper bag for a limited period of time.
Quickly drinking a glass of cold water.
Eating a teaspoon of sugar or honey.
The treatment for persistent or intractable hiccups depends on the underlying cause of the hiccups and may range from medicine to acupuncture or hypnosis. Sometimes several treatments may be tried before persistent or intractable hiccups are controlled. If you have hiccups that last a few days or longer, your doctor may conduct tests to rule out a more serious problem.

Who is affected by hiccups?

Hiccups affect males more often than females. Hiccups occur in practically every human being, including babies and older adults.


Post on Helicobactor

Recently, pts. have become aware of the prevalance of H. pylori as a cause of ulcers and questioning why I don’t emperically tx. for it, rather than an initial trial of PPI’s. My response is that although H. pylori is present in >80% of ulcers, is has only been implicated as causative in ~20%. Plus, the potential risk of SE’s from triple therapy.

Blood test is easy. Unfortunately it detects antibodies, not infection. May remain positive for years even after eradication of infection. Detecting IgM vs. IgG is not always reliable.

Urea breath test and stool antigen test detect infection. As does biopsy for either rapid urease test or histology with special stains. Biopsy is most invasive, most expensive, and most accurate.