How to Deal with Springtime Allergies

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Jeff Stokes, M.D., an associate professor of medicine with Creighton University School of Medicine and allergist/immunologist with Creighton Medical Associates.

Rising temperatures have lengthened the spring allergy season, because plants are pollinating longer. In addition, an increase in carbon dioxide in the atmosphere is most likely resulting in more pollen being emitted.

10-30% of adults and up to 40% of all children suffer from hay fever (allergic rhinitis). Those with a family history and young adults are most at risk. Allergies generally begin in childhood, peak in young adulthood and disappear as we get older.

In the Midwest this year, tree pollens have been the most likely culprit in March-April. Grass pollens will take over in May and June.

While it is impossible to avoid outdoor allergens, you can help minimize your exposure by:

- keeping windows closed
- using an air conditioner
- avoiding the outdoors in early morning when pollen counts are highest
- wearing an allergy face mask when outside

While there are effective over-the-counter antihistamines to treat hay fever, symptoms can frequently “break through”.

It’s time to schedule an appointment with an allergist/immunologist when you are:

- having trouble sleeping
- encountering negative side-effects from medication
- just feeling plain miserable
- allergies are affecting your lifestyle

The end goal is the feel your best with the least amount of drugs possible.

For some, immunotherapy or allergy shots is the most effective long-term treatment. The goal of shots is to increase your tolerance to allergens so that, ultimately, you have few or no symptoms within three-five years. It also may prevent asthma in children.



References:
Spring Allergies: Are They Getting Worse?

Identifying New Genetic Defects in Common Variable Immunodeficiency (CVID)

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Common variable immunodeficiency (CVID) covers a variety of different primary antibody deficiencies (PIDD) with specific clinical manifestations and immunological phenotypes. The first genetic defect correlating with CVID was discovered in 2002. Since then, there has been a steadily increasing number of yearly publications on CVID (Pubmed graph, http://www.medscape.com/viewarticle/733149_10).



Typical pattern of immunoglobulin levels (IgG, IgA, IgM) in humoral immunodeficiency. Click here to enlarge the table.

New gene defects associated with a CVID phenotype have been described in BAFF-receptor (BAFF-R), CD81, and CD20 in single consanguineous families.

New genetic defects in CVID:

- BAFF-receptor Deficiency

BAFF-receptor (BAFF-R), TACI, and BCMA are members of the TNF-R family, which regulate the survival and homeostasis of B cells. All three receptors bind a TNF-like ligand, termed BAFF or BLyS. TACI and BCMA also bind the BAFF-related ligand APRIL.

So far, only mutations in the TACI and in the BAFF-R gene have been associated with CVID.

BAFF-R and BCR are the most important survival receptors of B cells. Nevertheless, the lack of BAFF-R function can be compensated to some extent by the plasticity of the immune system, thus allowing protective immune responses in spite of BAFF-R deficiency.

- CD20 Deficiency

CD20 is a multimeric protein complex expressed on the cell surface of B cells. CD20 is involved in the regulation of Ca2+ transport across the cell membrane.

- CD81 Deficiency

CD19 forms a complex together with CD21, CD81, and CD225. The complex lowers the B-cell receptor-signaling threshold by amplifying the BCR signal in response to antigens.

TLR signaling defects in CVID

TLR signaling defects also play a role in the etiology of CVID. TLR7/8 function is even more impaired in CVID patients than TLR9 function.

CD21-low B Cells and calcium signaling in CVID

The CD21-low B-cell subpopulation in CVID is somewhat better understood now but still leaving their origin obscure. Complement receptor 2 (CR2/CD21) is part of the B-cell coreceptor and expressed by mature B cells and follicular dendritic cells. CD21 is a receptor for C3d-opsonized immune complexes and enhances antigen-specific B-cell responses. Viruses, such as HIV and EBV, use the complement receptors (CR2) to the enter the cell. Genetic CD21 deficiency is associated with hypogammaglobulinemia (JACI, 2011).

T cells in CVID

Further immunophenotypic analysis of T and B cells in large CVID patient cohorts revealed subgroups with signs of severely disturbed cellular immunity.

Several trials described the reduction of regulatory T cells in a subgroup of CVID patients. There is an association between low numbers of regulatory T cells and an autoimmune manifestation, granulomatous disease and splenomegaly.

References:
Common Variable Immunodeficiency at the End of a Prospering Decade: Towards Novel Gene Defects and Beyond. Curr Opin Allergy Clin Immunol. 2010;10(6):526-533, Medscape, 2011.

28% of patients with history of anaphylaxis don't even have a prescription for epinephrine

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An e-mail survey was conducted in Canada. Anaphylaxis was defined as the most severe sudden-onset allergic reaction ever experienced by the participants. The survey focused on survivors of anaphylaxis in the community.

Of the 1885 participants (survivors of anaphylaxis), only 27% were epinephrine users.

Epinephrine users were more likely to:

- report respiratory or shock symptoms

- report peanut, fish, or insect sting triggers

- be asthmatic

- have taken or been given asthma medication on the day of the episode

Epinephrine nonusers reported not injecting epinephrine for various reasons:

- use of an H(1)-antihistamine (38%)

- no prescription for epinephrine (28%)

- mild anaphylaxis episode (13%)

References:
Anaphylaxis in the community: Learning from the survivors. Simons FE, Clark S, Camargo CA Jr. J Allergy Clin Immunol. 2009 Jun 18.

Image source: Bee, Wikipedia, GNU Free Documentation License.

Allergy testing could pinpoint what makes you feel ill (video)

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From the news report:

"Every asthmatic should be tested. A common form of skin testing, sometimes called the prick-puncture test, is conducted by making a series of small pricks on the back to expose the patient to trace amounts of allergens, such as pollen, mold and dust mites.

Corbett likens it to “taking a toothpick and just poking on your back a little bit,” then waiting about 15 minutes to see if the skin reacts."

References:
Allergy testing could pinpoint what ails you

What causes chronic urticaria in children? (etiology study)

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This study examined some of the possible etiologies of chronic urticaria (CU) in children by focusing on causative factors such as:

- functional autoantibody to FcεRIα (via autologous serum skin test (ASST))

- IgE

- thyroid autoimmunity

- urticarial vasculitis

- parasitic infestation

- food allergy

Children 4–15 yr of age with chronic urticaria (CU) were investigated with:

- complete blood count

- erythrocyte sedimentation rate (ESR)

- antinuclear antibody (ANA)

- CH50

- free-T4 (FT4), thyroid stimulating hormone (TSH), anti-thyroglobulin and anti-microsomal antibody

- autologous serum skin test (ASST)

- skin prick tests (SPT) for foods

- food challenges

- stool examination for parasites

Patients with physical urticaria were excluded.

Eosinophilia and elevated ESR were found in 23% and 13%, respectively. High ANA titers were found in 2%.

None of these patients had clinical features of urticarial vasculitis, abnormal CH50 level, abnormal TSH and FT4. Anti-thyroglobulin and anti-microsomal antibodies were not detected.

Positive autologous serum skin test (ASST) was found in 38% (autoimmune urticaria). ASST is currently being replaced by anti-FceR1 autoantibodies.

Parasites were found in 5% - without clinical correlation.

Skin prick tests (SPT) to foods was positive in 35%. Food avoidance was beneficial to the subgroup of patients with positive history of food allergy only.

This is my suggested laboratory workup for selected patients with chronic urticaria:


Diagnosis of Chronic Urticaria (click to enlarge the image).



Anti-FceR1 autoantibodies in chronic autoimmune urticaria: IgG against FceRI (receptor for IgE) (click to enlarge the image).

References:
Identification of the etiologies of chronic urticaria in children: A prospective study of 94 patients. Pediatric Allergy and Immunology, 2009.

Image source: Urticaria, Wikipedia, public domain.

C1 esterase inhibitor dose of 20 U/kg provides rapid, effective, and safe treatment for HAE attacks

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Hereditary angioedema (HAE) is a rare disorder characterized by a quantitative or functional deficiency of C1 esterase inhibitor (C1-INH), resulting in periodic attacks of acute edema at various body locations.


C1 protein, showing subunits C1r, C1s, and the C1q tails. Image source: Wikipedia.


New therapies for hereditary angioedema (HAE) (click to enlarge the image).

Acute facial and abdominal attacks were each treated with C1-INH concentrate using a single intravenous dose of 20 U/kg body weight in this study.

663 abdominal attacks were treated in 50 patients and 43 facial attacks in 16 patients.

The time to onset of relief was 20 minutes for abdominal attacks and 28 minutes for facial attacks. The time for complete resolution was 11 hours.

No human immunodeficiency virus, hepatitis virus, or parvovirus B19 infections arose during the study.

The C1-INH concentrate dose of 20 U/kg provides rapid, effective, and safe treatment for successive HAE attacks at abdominal and facial locations.

References:

Prospective study of C1 esterase inhibitor in the treatment of successive acute abdominal and facial hereditary angioedema attacks. Wasserman RL, Levy RJ, Bewtra AK, Hurewitz D, Craig TJ, Kiessling PC, Keinecke HO, Bernstein JA. Ann Allergy Asthma Immunol. 2011 Jan;106(1):62-8. Epub 2010 Nov 20.

Optimal efficacy of C1INH therapy in HAE is achieved at doses ≥50 U/kg, target level ≥0.7 U/ml (70% of normal) http://goo.gl/HJM4X

Comments from Twitter:

@MatthewBowdish (Matthew Bowdish MD): rapid = 20 min

Birch Pollen-rich Honey May Help Patients with Birch Pollen Allergy

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This study from Finland assessed the effects of the preseasonal use of birch pollen honey (BPH; birch pollen added to honey) or regular honey (RH) on symptoms and medication during birch pollen season.

44 patients with birch pollen-related allergic rhinitis consumed either BPH or regular honey (RH) daily from November to March.

17 patients on their usual allergy medication served as the control group.

From April to May, patients recorded daily rhinoconjunctival and other symptoms, and their use of medication.

The results were encouraging - during birch pollen season, patients who took birch pollen honey (BPH) reported:

- 60% lower total symptom score
- twice as many asymptomatic days
- 70% fewer days with severe symptoms
- they used 50% less antihistamines

Patients who preseasonally used BPH had better control of their symptoms than did those on conventional medication only. The results should be regarded as preliminary, but they indicate that BPH could serve as a complementary therapy for birch pollen allergy.

This study is interesting mainly because previous trials have failed to show benefit of local honey as treatment of allergic rhinitis.

References:

Birch Pollen Honey for Birch Pollen Allergy - A Randomized Controlled Pilot Study. Saarinen K, Jantunen J, Haahtela T. Int Arch Allergy Immunol. 2010 Dec 23;155(2):160-166.

Does honey relieve allergy symptoms?

Can Eating Local Honey Cure Allergies? No, in most cases. NYTimes, 2011.

Image source: A jar of honey with honey dipper, Wikipedia, public domain.

Comments from Twitter:

@DrSilge (Robert Silge, MD): interesting. Hard to get the bees to care about anemophilous plants though.

@DrVes: correct, bees are not interested in those - there is no ragweed pollen-honey as far as I know...

Painless Allergy Test - Allergist Guides Patients Through a Virtual Visit

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Painless Allergy Test - Allergist Guides Patients Through a Virtual Visit. Dr. Bassett: Discover the testing procedure we use at my office to painlessly diagnose your allergies. Take a behind-the-scenes tour of how we work to cure your allergies and help you live a better life. I also share informational tips on how to minimize your suffering.

BCG vaccination protects against tuberculosis - number needed to treat (NNT) is 11

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A report from a 2007 outbreak of tuberculosis among toddlers in Ireland found that 24% of the exposed children had received BCG immunization, and none of those vaccinated developed active infection.

Based on absolute risk reduction, the number needed to treat (NNT) to prevent one case of active TB disease in their population is 11.3.

The results suggest effectiveness of BCG against all forms of TB in children rather than just the well known reduction in meningitis and invasive forms.

References:
BCG Vaccination Protects Toddlers Against Pulmonary Tuberculosis. Medscape.
Arch Dis Child 2009;94:392-393.

Xpert MTB/RIF is a rapid diagnostic test for tuberculosis with high sensitivity (90%) and specificity (99%). Lancet, 2011.

Image source: PPD, CDC, public domain.

Minimal remission of atopic dermatitis (eczema) as children grow

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Trends in the prevalence of eczema in the course of childhood and adolescence are not clear although often a remission during childhood is assumed.

Information regarding eczema was collected at ages 1, 2, 4, 10 and 18 years from the 1989 Isle of Wight birth cohort (n=1456). Skin prick testing was performed at 4, 10 and 18 years of age.

The prevalence of eczema from birth to 18 years of age remained relatively constant (12-14%) with minimal remission.

Up to 10 years of age, gender did not influence prevalence. From 10 to 18 years, eczema became more prevalent among girls (16% for girls vs. 8% for boys).

There was only a minimal reduction in the prevalence of eczema during childhood and adolescence. During adolescence, more girls develop eczema and more boys outgrow it.

References:
Trends in eczema in the first 18 years of life: results from the Isle of Wight 1989 birth cohort study. Ziyab AH, Raza A, Karmaus W, Tongue N, Zhang H, Matthews S, Arshad SH, Roberts G. Clin Exp Allergy. 2010 Dec;40(12):1776-84. doi: 10.1111/j.1365-2222.2010.03633.x.

Image source: Skin layers. Wikipedia, public domain.

Atopic dermatitis (eczema)-related tweets from 2011 AAAAI meeting

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Here are some of the atopic dermatitis-related tweets from the 2011 annual AAAAI meeting. They were labeled #AAAAI and based on real time updates by Sakina Bajowala, M.D @allergistmommy and Robert Silge, MD @utahallergy. The text was edited, modified, and added to by me.

Staph. aureus colonization

More than 75% of patients with atopic dermatitis have Staph. aureus colonization. It is significantly more likely to be MRSA than the colonization in the general population. 80% of atopic dermatitis patients are colonized with Staph. aureus, 16% with MRSA.

Bleach baths and Bactroban ointment significantly decrease symptom scores and body surface area affected by atopic dermatitis.

Dosing in bleach baths for eczema: half cup of bleach to a tub full of water. Alternatively, 2 tablespoons in a spray bottle for shower.

Intranasal mupirocin ointment and oral antibiotics may also help reduce Staph load and ensuing inflammation in eczema.

Omalizumab

Omalizumab (Xolair) is approved for IgE levels below 700 u/ml. It is difficult to get approval in allergic skin disease, where IgE is often very high, sometimes in the thousands.

Omalizumab is being studied in atopic dermatits, but early data suggests may be more useful in acute control.

Vitamin D

Vitamin D for atopic dermatitis: may increase production of antimicrobial peptides. However, the dose that is needed is unclear.

Foods, pets, mites and cockroaches can impact eczema control in children.

Atopic Dermatitis Treatment - Illustrated (click here for full size image).

Skin prick tests not useful in predicting allergenicity of apples

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Oral allergy syndrome (OAS) symptoms to apple are frequent.

The researchers aimed to identify low allergenic apple cultivars and to validate the prick-to-prick skin prick test (SPT) as a suitable screening method.

68 apple cultivars were tested by SPTs in 33 Dutch adults with OAS, before and during 2 birch pollen seasons.

3 apple cultivars yielding the largest number of negative SPTs (Elise, Santana and Pink Lady(®)) and one reference cultivar (Golden Delicious) were subsequently tested by single-blind oral food challenges (SBFC).

In fresh apples, OAS symptoms of Elise were lower than those of Santana, Pink Lady and Golden Delicious. Scores of Santana were significantly lower than those of Golden Delicious. Scores of fresh apples did not differ significantly from stored apples, except in Golden Delicious (spring < fall).

The SPTs did not predict the severity of OAS.

The researchers concluded that SPTs are not useful to assess the allergenicity of apple cultivars. By using oral food challenges (SBFC), Elise and Santana were identified as low allergenic apple cultivars in patient with OAS.


Cross-reactivity in Pollen-Food Allergy Syndrome (PFAS) or Oral Allergy Syndrome (OAS) (click to enlarge the image).

References:
Identification of low allergenic apple cultivars using skin prick tests and oral food challenges.
Vlieg-Boerstra BJ, Van De Weg WE, Van Der Heide S, Kerkhof M, Arens P, Heijerman-Peppelman G, Dubois AE. Allergy. 2010 Nov 8. doi: 10.1111/j.1398-9995.2010.02499.x.

Image source: Apple, Wikipedia, public domain.

Allergy to car seat

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Contact dermatitis induced by a leather car seat

This is a case report of a female patient showing a delayed allergic reaction to epoxy resin. The allergic contact dermatitis occurred after sitting in her new car equipped with artificial leather seats.

Inhaled allergens

In a 2002 study, dust mite allergen (Der 1) densities in some automobiles were sufficiently high to be risk factors for sensitization and allergic reactions. Most automobile seats had levels of dog and cat allergen that were well above the threshold levels considered to be risk factors for both sensitization and symptoms, regardless of the presence of a pet in the home.

References:
Allergy to car seat. Hautarzt. 2010 Oct 17. [Epub ahead of print]
Relationship among house-dust mites, Der 1, Fel d 1, and Can f 1 on clothing and automobile seats with respect to densities in houses. Ann Allergy Asthma Immunol. 2002 Apr;88(4):410-5.

Image source: OpenClipArt.org, public domain.

Intravenous immune globulin (IVIG) in autoimmune and inflammatory disorders: how does it work?

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Intravenous immune globulin (IVIG) is an important treatment modality in patients with humoral or B-cell immune deficiency as replacement therapy. Soon after its introduction in the early 1980s for the treatment of patients with immune deficiency, IVIG was used in the treatment of children with idiopathic thrombocytopenia purpura (ITP).

A lot more IVIG is used for the treatment of autoimmune and inflammatory disorders than as replacement therapy in patients with immune deficiency.

A number of mechanisms for the immune modulation and anti-inflammatory actions of IVIG have been described:

- Fc receptor blockade
- inhibition of complement deposition
- enhancement of regulatory T cells (T regs)
- inhibition or neutralization of cytokines and growth factors
- accelerated clearance of autoantibodies
- modulation of adhesion molecules and cell receptors
- activation of regulatory macrophages through the FcγRIIb receptor


An antibody has Fab (fragment, antigen-binding) and Fc (fragment, crystalizable) regions. Fc receptors bind to the Fc region. Image source: Wikipedia, public domain.


Fc receptor interaction with an antibody-coated microbial pathogen. Image source: Wikipedia, public domain.

IVIG affects many different pathways to modulate the immune and inflammatory response.

References:
The IgG molecule as a biological immune response modifier: Mechanisms of action of intravenous immune serum globulin in autoimmune and inflammatory disorders. Ballow M. J Allergy Clin Immunol. 2010 Dec 23.

Image source: OpenClipArt.org, public domain.

Chronic urticaria-related tweets from 2011 AAAAI meeting

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Here are some of the chronic urticaria-related tweets from the 2011 annual AAAAI meeting. They were labeled #AAAAI and based on real time updates by Sakina Bajowala, M.D @allergistmommy and Robert Silge, MD @utahallergy. The text was edited, modified, and added to by me.

Diagnostic tests for chronic urticaria

The practice parameter reinforces that there is no role for food or inhalant testing for chronic urticaria, unless there is contact urticaria.

There is little value in ordering ANA for chronic urticaria without clinical suspicion of systemic autoimmunity.

Thyroid antibodies are a marker for autoimmune urticaria (IgG to IgE receptor). This does not imply that thyroid hormone replacement will treat the hives.

Antihistamines

The 1st line therapy for chronic urticaria is nonsedating antihistamines. High doses may be needed (up to 4 times the normal dose).

If your urticaria patients complains of sedation, consider fexofenadine (Allegra), now available OTC. Fexofenadine is non-sedating even at high doses. Cetirizine (Zyrtec) is sedating at 2x or 4x normal dose.

Current 2nd generation antihistamines (even at high dose) do not appear to cause Q-T prolongation.

Histamine 4 receptor has a profound effect on itch. Need to develop new drugs for ocular and other pruritic conditions

Montelukast (Singulair)

Montelukast has varied results in treating chronic urticaria. Montelukast offers only minor benefit as an adjunct in therapy of urticaria. But it is very safe.

Comment from @Stolib: the interesting thing is that montelukast offers only minor benefit as an adjunct in the treatment of almost anything.

Immunosuppressants

Cyclosporine significantly decreases both urticaria wheals and itching, but requires monitoring and dose reduction for side effects. Approximately 80% of chronic urticaria patients on cyclosporine responded, but side effects are common, and may limit therapy.

Hydroxychloroquine is shown to be useful as well, but it takes 3 months to reach effect.

Many other options exist, including tacrolimus and omalizumab (Xolair).

When allergists are asked for CIU: "Do you find __(medication) can be useful?", the answer is "Yes, sometimes." There are lots of options out there, but no overwhelming data for benefit.

Skin biopsy

In skin biopsy, ask pathologist to comment on neutrophils vs. mononuclear cells. Dapsone works well for neutrophilic urticaria. Consider biopsy with more than 50% neutrophilic infiltrate to be neutrophilic predominant urticaria. Dapsone and/or colchicine can be more useful in neutrophilic urticaria.

New practice parameter for urticaria is coming soon.

Related:

Evidence for Methotrexate as a Useful Treatment for Steroid-dependent Chronic Urticaria http://goo.gl/tnFFd

Image source: Urticaria, Wikipedia, public domain.