Acute vs. Chronic Urticaria: What You Need to Know

Urticaria can be both painful and unsightly.

Urticaria can be a debilitating condition. Patients suffer with a sometimes diffuse rash along with pruritus that can drive a person crazy. Dermatology offices are often the first referral destination for urticarial patients, but the complex issues surrounding these patients extend beneath the skin. The latest research brings insight to the underlying cause of urticarial lesions.

Getting to the bottom of acute urticaria usually involves basic medical detective work. A good history will usually lead you to the diagnosis. The most common culprits are foods (especially in children), medications and even infections. The patient usually identifies the source with a recounting of occurrences over the several hours or even days prior to the onset of the hives.

Among medications, common triggers include antibiotics like Penicillins, Cephalosporins and Sulfa-based drugs as well as over-the-counter NSAIDS or antipyretics like Advil, Alleve and aspirin. With that in mind, I check carefully in the patient’s history for meds first. Patients sometimes don’t realize that a simple antibiotic or OTC medication can cause a reaction so it’s important to ask specific questions. An infection can trigger an urticarial outbreak in highly allergic patients since they have an excess of histamine and infection facilitates the release of that histamine from skin mast cells. The treatment for acute urticaria is often simple: antihistamines for a week and avoidance of the allergic trigger.

Chronic urticaria is another story. These patients have hives that never seem to go away no matter which combination of antihistamines you throw at them. For many years, doctors tended to blame stress and psychological problems for the condition but the latest research points to an autoimmune disorder as the culprit. The mechanism of disease appears to be based in the production of autoantibody to the patient’s own IgE molecules. Just this year, the FDA approved the use of Xolair — the monoclonal antibody injection that was previously approved only for allergic asthma — for chronic urticaria. The new indication for Xolair is an exciting breakthrough for chronic urticaria as long-time sufferers may be symptom-free with just a few injections… and the results last for months!

In summary, urticaria has been a vexing condition that requires some patience on the part of both the sufferer and the physician. With good diagnostic evaluation along with advances in treatment options, the future may be looking much brighter.

Dr. Dean Mitchell

Drug Allergy: The Most Dangerous Reactions You Can’t Miss! Part 2

In Part 1 of this series I discussed the immediate hypersensitivity reactions that occur from a few minutes to a couple of hours after a patient takes a medication. Today, I am covering drug reactions that can occur up to two weeks after a medication is given. These reactions are tricky and dangerous for the clinician. A patient you may have seen for a sore throat and a cough two weeks ago now calls you up and tells you he has sores in his mouth and his eyes are red. What should you do? If it’s a Friday afternoon, don’t tell him you will  see him first thing Monday morning — it might be too late!

The drug reaction I’m describing is well known as the Stevens-Johnson Syndrome. Stevens and Johnson described this reaction back in 1922 in two children who developed extensive skin necrosis, fever, conjunctivitis and stomatitis. The syndrome that bears their name is a potentially life-threatening disease with a sudden onset of erythema and bulbous lesions on the skin; there is epidermal detachment involving less than 10% of the skin, which is accompanied by involvement of two mucosal areas. This syndrome is usually mentioned in the same breath as Toxic Epidermal Necrolysis, which has the same presentation, except here there is 10-30% skin involvement. I have seen just two cases of this in my career — when I was a resident in Internal Medicine. It was very frightening; the patients looked like burn victims. I was also horrified to hear that the son of a medical colleague developed this after a course of antibiotics and has been struggling to recover since.

Most cases of Stevens-Johnson syndrome are linked to specific medications: anticonvulsants such as phenytoin, antibiotics such as sulfonamides and tetracyclines, and widely used non-steroidal anti-inflammatory drugs. Why are some individuals more prone to this syndrome? The answer is probably genetic predisposition — individuals with the HLA types B*1502, B*5701, B*5801, Bw44 and DQB1*0601. Of course, as clinicians we will never know in advance that a patient has these HLA types. However, I would be very cautious in a patient that has told you they seem to get reactions to many different medications. These are not hypochondriacs, there is sufficient medical literature to document individuals with multiple drug reactions. It is only recently that we’ve begun understanding the connection to a person’s genetic-immune make-up.

So, if you get the call or see a patient in the office who is developing a severe desquamating rash along with red eyes and sores in their mouth send them immediately to the hospital. In fact, it’s important that it be a tertiary care hospital that can place this patient in an ICU isolation room. An infection on top of this reaction can be lethal for the patient that is now immune compromised—similar to a burn victim.

I would also suggest that the patient see a good dermatologist and an immunologist who is familiar with drug reactions. The recent medical literature supports using IV gamma globulin to ameliorate the intensity of the disease, and it also helps boost the patient’s immune system.

Today, in our busy practices, most doctors prescribe lots of medications and see just the occasional adverse reactions. It’s important to have your antenna on high alert if you hear a story like the one we just described.

– Dr. Dean Mitchell

Antibiotics and Asthma: A Surprising Relationship

The longer I practice medicine, the more amazed I am at the reversal of long held medical dogmas. Since the common use of antibiotics began around World War II, the medical profession has seen the effectiveness of antibiotics as evidence that science can prevail over infections. However, we didn’t foresee the downside of that success — the current rise of antibiotic resistance by common bacterial organisms. A similar arena of surprise in the medical field has taken place in the realm of allergy and asthma. We have observed an alarming rise in allergic diseases in Western countries over the past few decades. There are different hypotheses as to the cause of this allergy epidemic, but an article in the May issue of Annals of Allergy Asthma and Immunology seems to shed new light on one potential root of the problem: antibiotics.

Consider this common scenario: A six-month-old infant with a high fever and extreme irritability is brought to the pediatrician. The doctor examines her and sees a red tympanic membrane with fluid. The mother is desperate to relieve her child’s pain and suffering. The pediatrician wants to help and doesn’t want to miss a possible bacterial infection, despite the likelihood that the infection is viral. More often than not, the parent leaves with an antibiotic prescription. In medical practice, we are constantly faced with balancing risks and benefits, as well as attempting to perfect the art of doing good while upholding the oath to “do no harm.”  As we all know, this is a delicate balance. In order to maintain it, we have to keep ourselves constantly informed. The article cited above provides new and valuable information about the risks inherent in the above scenario. Here is the basic rundown …

Drs. Ong and Umetsu conducted a study on infants receiving antibiotics in the first year of life. The result: the antibiotic-receiving infants had double the incidence of asthma before three years of age. In addition, there appeared to be a dose-dependent relationship: the more antibiotic given, the more likely the child would develop asthma. Clearly, antibiotic usage in early infancy comes with risks. The explanation for the results lies in the alteration of the child’s microbiome. Antibiotic-induced biome alteration poses a concern for the development of atopy.

Where does this leave us in terms of treating infants with infections? As is so often the case, the key to the answer is patient/parent education. While effective for bacterial infections, antibiotics have no place in treating a child with viral infections — or allergic asthma. Doctors and parents need to be on the same page realizing that the best therapy for these young patients in the absence of definitive diagnosis of bacterial infection is close observation and supportive care. So many viral illnesses are self-limiting; a few days of rest and fluids go a long way. Powerful, broad-spectrum antibiotics are definitely not the answer to viral infection or allergic disease. Sometimes the parents just need an answer. While the febrile patient is clearly suffering from more than allergic disease, allergic inflammation sets up the ideal environment for infectious proliferation. The best thing you can do is definitively identify allergic children when they are not suffering from an acute infection.

Proper management of allergic disease, including avoidance where possible, appropriate medication use, and immunotherapy when indicated, can keep them well. A patient’s medical history is tremendously important in making the diagnosis of allergy, but a definitive IgE test is an equally important piece of the puzzle. If he or she has allergies or has asthma, if a parents smokes in the home, or if a pet lives in the house, allergies should be considered as the cause of the child’s problems. NIH guidelines indicate that all persistent asthmatics should be tested for allergic triggers and offered immunotherapy if indicated.

A new era in medicine is being ushered in, and the finding that antibiotic use in infancy increases the risk of asthma may be only the tip of the iceberg. Modern doctors must choose our treatments with care.

– Dr. Dean Mitchell

Anaphylaxis, The True Allergic Emergency – What You Need to Know

Anaphylaxis, which comes from the Greek term “reverse protection,” is the most

There are many possible signs of anaphylaxis…

dangerous type of allergic reaction. It is described as a type 1 Hypersensitivity reaction that involves release of IgE triggered, most often, by a food, medication or insect sting. Anaphylaxis is a frightening reaction where a patient, who moments before appeared fine and healthy, almost within seconds can be wheezing, hypotensive, and covered with hives.

The foods most commonly associated with anaphylaxis in children are peanuts and tree nuts; in their adult counterparts it’s usually shellfish. The confusing part for patients and clinicians is that a food allergy can develop after eating a particular food on many occasions. However, once that threshold has been crossed, even a minute amount of that food can cause an explosive reaction. If a food is the suspected cause of anaphylaxis, but the specific food unclear, it’s wise to evaluate the patient through several steps.

Initially, I would recommend a panel of food allergy blood tests. ImmunoCap is a common one used by most labs to evaluate IgE reactions to specific foods. The results range from zero to six, with a score of at least two indicating a positive reaction. If there is a positive reaction to peanut, the allergy should be further explored by ordering a UKnow Peanut test which analyzes the proteins Ara h1,2&3, as well as Ara h8. My article in Consultant for Pediatricians, “Pinpointing the Proteins in Peanut Allergy,” explains why these proteins are important to predict the severity of peanut allergy. If, for some reason, the blood test is negative, I would recommend referral to an allergist for skin testing and/or oral challenge in case there is a hidden allergen that requires more extensive testing.

Any medication can cause an anaphylactic reaction however the common culprits are antibiotics and non-steroidal anti-inflammatory drugs. Many antibiotics are mold-based, which may be part of the reason for their allergenicity. In the past, beta-lactam antibiotics such as penicillin and related cephalosporins were the most likely offenders but today we also see anaphylaxis to the widely used category of quinolone antibiotics. To complicate matters, it is not unusual for a patient to have multiple antibiotic sensitivities; there is a genetic component to this reaction. While Pre Pen can be used to diagnose penicillin allergy (talk to your AllerVision representative for more information), there is no such test for most antibiotics, and a drug challenge may be required for conclusive diagnosis.

Non-steroidal medications, such as Advil, Motrin and Alleve, work by blocking the cyclo-oxygenase pathway and trigger release of leukotrienes which are potent mediators of anaphylaxis. In my experience, patients allergic to NSAIDS are usually unaware of the source of reaction until they suffer several episodes of anaphylaxis. Be on high alert for NSAID hypersensitivity when evaluating a patient for anaphylaxis or urticaria. Unfortunately, a drug challenge is the only conclusive test NSAID hypersensitivity.

The clinical diagnosis of anaphylaxis can be complicated. The World Allergy Organization recently came out with new criteria. Essentially, it includes exposure to a possible or known allergen and the finding of two or more clinical signs: urticarial, bronchospasm, gastrointestinal distress and cardiovascular collapse. In case of cardiovascular collapse, no additional signs are needed — call 911 and immediately transport the patient to the hospital.

While anaphylaxis is fairly rare with allergy injections, and exceedingly rare with allergy skin testing, it is important that you and your staff be prepared just in case. When a patient is in your office, the question of whether or not to treat a potential reaction is simplified, and doesn’t include an extensive review of the clinical findings nor consideration about number of signs. If you place an allergenic substance on the patient’s skin, or inject them with a substance you know they are allergic to, and they have a reaction anywhere other than the local site of exposure, TREAT THEM! Common signs to look out for are itching of hands and feet, or clearing of throat that wasn’t happening when the patient came in to the office. If you apply antigen to one area of the body, and the patient has symptoms somewhere else, you have to assume that the reaction has gone systemic and you should treat accordingly.

The initial treatment of anaphylaxis is unambiguous: epinephrine intramuscularly into the lateral thigh. Don’t play around with Benedryl! Don’t give a cortisone shot! Anaphylaxis progresses immediately, and neither antihistamine nor steroid drugs act on the spot to reverse the severe pathophysiological reaction. Deaths resulting from anaphylaxis happen when epinephrine is not administered in under 3o minutes from the onset of symptoms. If you are giving allergy injections in your office, you MUST have the patient wait 20 minutes in the office to make sure they don’t have an immediate allergic reaction. If they develop ANY sign or symptom within that time, administer epinephrine. The EpiPen is convenient for an office because it contains the 0.3 ml of epinephrine with the needle size for an intramuscular injection. It also comes as the EpiPen Jr. for children or infants less than 66 lbs. Once epinephrine has been given, the patient must be monitored for several hours to make sure there isn’t a biphasic reaction; this usually takes place in a hospital.

Anaphylaxis can be the most frightening of clinical reactions. The good news is with quick recognition and prompt treatment with epinephrine, you can be a real hero!

– Dr. Dean Mitchell