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Immunotherapy for mosquito allergy


Is there any experience in the administration of allergen IT for Inge mediated reactions to mosquito bites? I saw one reference in the European literature from 2004 but none since.


I have attached some of the questions in the archives of Ask The Expert related to mosquito allergy. In general, the quality of the materials for testing and treatment are not standardized nor consistent making the efficacy for immunotherapy unpredictable. In general, local allergic reactions to mosquito bites are more common in children (‘skeeter syndrome’) and usually spontaneously improve with repeated bites or age or both (1,2). Large local reactions to insects in general are generally not treated with immunotherapy but, at least with the venoms, there is improvement in the size of local reactions with therapy (3). Venom immunotherapy is standardized and more effective than whole body extracts used for mosquito therapy. Mosquito allergy immunotherapy is described in the literature; but without consistent testing and treatment reagents, the efficacy is suspect at best.

There have been efforts to improve the reagents, but these are not commercially available (5).

In summary, there is some information that local reactions and possibly the systemic features of ‘skeeter syndrome’ may improve with immunotherapy. However, the limitations as described above make the effort likely futile. Generally, in my experience judicious use of insect repellants, such as DEET, coupled with local treatment of bites with high potency topical corticosteroids is the best course of action.

1. Pérez-Vanzzini, Rafael, et al. "Hypersensitivity to mosquito bite manifested as Skeeter syndrome." Revista Alergia México 62.1 (2015): 83-87.
2. Peng, Zhikang, et al. "Evidence for natural desensitization to mosquito salivary allergens: mosquito saliva specific Inge and IgG levels in children." Annals of Allergy, Asthma & Immunology 93.6 (2004): 553-556.
3. Golden, David BK, et al. "Venom immunotherapy reduces large local reactions to insect stings." Journal of Allergy and Clinical Immunology 123.6 (2009): 1371-1375.
4. Ariano, R., and R. C. Panzani. "Efficacy and safety of specific immunotherapy to mosquito bites." European annals of allergy and clinical immunology 36.4 (2004): 131-138.
5. Simons, F. Estelle R., and Zhikang Peng. "Mosquito allergy: recombinant mosquito salivary antigens for new diagnostic tests." International archives of allergy and immunology 124.1-3 (2001): 403-405.

I hope this information is of help to you and your practice.

All my best.
Dennis K. Ledford, MD, FAAAAI

9/24/2013: Mosquito allergy
Question: We have a patient with a history of large local reactions to Mosquito bites. He was skin tested in 2011 which was negative. He returned to the office in September of 2013 after possibly being bit by mosquitoes on multiple occasions. Each time he complains of swelling at the site, nausea, headache, light sensitivity and dizziness. Benadryl does relieve these symptoms after a couple of hours. The doctor is aware that there is the ability to desensitize patients with mosquito extract but would it still be indicated with negative skin testing?

Answer: First, I recommend an excellent review article on mosquito allergy which you should read prior to proceeding with treatment. The review should be readily available to you (Crisp HC, Johnson KS. Mosquito allergy. Ann Allergy Asthma Immunol 2013 Feb;110(2):65-9. doi: 10.1016/j.anai.2012.07.023).

There are several points in this review that are salient to your inquiry, and I will mention them briefly. But you will find a very helpful, more detailed discussion of the issues brought up by your inquiry in this excellent article.

First of all, the skin test material that we have for mosquito is not highly sensitive, and false-negative tests clearly occur in a significant number of individuals who have had documented allergic reactions to mosquito bites. There are a number of reasons for this, all of which are discussed in this review.

Secondly, there is an in vitro test for specific Inge (Immunocap) to mosquito which you should consider obtaining. On occasion, this can be positive in the face of a negative skin test.

Thirdly, according to this article and to the best of my knowledge, there is no treatment extract for mosquito allergy approved by the FDA in this country. Although mosquito extracts are available from several suppliers, to my knowledge, and based upon the information in this article, none of these have been approved for use for therapy in the United States. However, desensitization to mosquito has been shown to be effective in the published literature, and these reports are discussed in the review cited above.

Finally, I would be reluctant to consider a test performed in 2011 as definitive at this time, so I would suggest performing another skin test as well as ordering the in vitro test noted above.

Thank you again for your inquiry and we hope this response is helpful to you.

Phil Lieberman, M.D.

Question: I had the following questions regarding patients who have had very large local reactions (and possibly systemic cutaneous reactions) to mosquito:

1) Are there any commercially available skin testing materials for mosquito?
2) Is there data on immunotherapy for mosquito allergy?
3) If available, who makes these extracts?
4) Are RAST tests useful in diagnosis?
5) Is true anaphylaxis from mosquito frequent enough to warrant epi pens for kids with lesser reactions?

I suggest that you read a recent review about mosquito allergy by Dr. Estelle Simons of the Univ. of Manitoba, one of the leading investigators in this field. She points out that there are commercial mosquito extracts available. However, they have generally lacked sufficient sensitivity and specificity for clinical reactivity to be greatly helpful. Greer Labs markets a mosquito extract for diagnostic purposes only. The ALK labs, Hollister-Stier labs (as possibly others) also market mosquito extracts for testing. There have been reports of successful immunotherapy with mosquito extracts, generally homemade.

The large majority of allergic reactions to mosquito bites are local, with occasional systemic reactions reported. I know of one case report of 2 patients with anaphylactic reactions attributed to a mosquito bite approached subsequently with mosquito extract immunotherapy with reported reduced reactivity to mosquito bites (Ann Allergy Asthma Immunol 1995;74:39-44). You may wish to contact Dr. Renata Engler, FAAAAI, of the Walter Reed Medical Center in Washington DC who was the senior author in that report. She can tell you what extract they used for immunotherapy. However, I think that the likelihood of anaphylactic reactions to mosquito bites in allergic reactions must be extremely low (see enclosed abstract of the review article by Dr. Engler). Therefore, I would think that carrying an Epi-Pen by someone who previously experienced a lesser reaction would not be necessary. Better to use adequate prevention with DEET-containing repellents (see enclosed my review for the JACI of a report about comparative efficacy of various insect repellents which appeared in the New Eng J. of Medicine in 2002).

Allerg Immunol (Paris). 2004 Apr;36(4):131-8. Related Articles, Links
Efficacy and safety of specific immunotherapy to mosquito bites.
Ariano R, Panzani RC.
U.O. di Medicina Generale, Modulo di Allergologia ed Immunologia Clinica, A.S.L. n. 1 Imperiese, Ospedale "S. Charles" Bordighera, Italy.
Background: Adverse effects of mosquito bites are often very unpleasant and need a treatment.
Objective: To evaluate the efficacy of specific immunotherapy (S.I.T) with an extract of the whole body of the mosquito Aedes communis.
Method: Twenty patients having strong local immediate and delayed reactions within many cases also an allergic rhinitis were selected. A similar control group was included. In all these patients' skin tests, RASTs and nasal provocation tests were carried out with an extract of Aedes communis and a battery of the commonest allergens in our area including two insects: Blatella germanica (german cockroach) and Gasterophilus intestinalis (horse fly). The specific immunotherapy was carried out by the conventional subcutaneous route.
Results: After 18 months of S.I.T all the patients reported the disappearance of local reactions and symptoms of allergic rhinitis, which was correlated with a statistically improvement of symptom and drug consumption scores and a decrease of allergenic reactivity by the nasal provocation test.
Conclusions: S.I.T with an extract of Aedes communis produced after 18 months of treatment a significant improvement of allergic symptoms, a decrease of symptom and drug consumption scores and of allergen specific nasal reactivity. S.I.T in mosquito bite allergy appears to be effective and safe in the treatment of both cutaneous and respiratory symptoms.

Int Arch Allergy Immunol. 2004 Feb;133(2):198-209. Epub 2004 Feb 11.
Mosquito allergy: immune mechanisms and recombinant salivary allergens.
Peng Z, Simons FE.
Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Canada.
Reactions to mosquito bites are immunological in nature, with the involvement of Inge-, IgG- and T lymphocyte-mediated hypersensitivities. Acquired desensitization to mosquito saliva may occur during childhood and adolescence or during long-term exposure to mosquito bites. Due to the lack of salivary preparations, allergic reactions to mosquito bites are underdiagnosed and undertreated. Recombinant mosquito saliva allergens with biological activity are being developed. These recombinant allergens will significantly improve diagnosis of mosquito allergy and eventually will also improve specific immunotherapy for mosquito bite sensitivity.

Ann Allergy Asthma Immunol. 1996 Nov;77(5):371-6. Related Articles, Links
Comparison of proteins, Inge, and IgG binding antigens, and skin reactivity in commercial and laboratory-made mosquito extracts.
Peng Z, Simons FE.
Department of Pediatrics and Child Health, University of Manitoba, Canada.
Background: Commercial extracts are available for the diagnosis and treatment of mosquito allergy, but their antigen content has never been analyzed.
Objective: We wanted to analyze commercially available mosquito extracts and to compare these extracts with different laboratory preparations.
Methods: Seven commercially available mosquito whole body extracts from six companies and four laboratory mosquito preparations including saliva extract were studied. Epicutaneous tests and measurement of protein concentration were performed. Protein components were identified by sodium sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and silver stain. Inge and IgG binding antigens were analyzed by SDS-PAGE and immunoblotting with sera from mosquito-allergic subjects.
Results: The seven commercial materials produced wheals and papules ranging from 0 to 36 mm2. Their protein concentrations varied from 0.1 to 4.9 mg/mL. There were significant differences in their protein and antigen components. Some extracts contained multiple highly immunoreactive proteins and Inge- and IgG-binding antigens that are not present in mosquito saliva, but few actual salivary antigens. In the four laboratory preparations, rank ordered from whole body, head and thorax, salivary gland to saliva extracts, the amount of salivary antigens significantly increased, while non-salivary proteins and antigens significantly decreased.
Conclusions: Commercial mosquito extracts should be standardized. Purer mosquito extracts should be used in diagnosis and immunotherapy of mosquito allergy

Curr Opin Allergy Clin Immunol. 2001 Aug;1(4):349-52.
Mosquito bite pathogenesis in necrotic skin reactors.
Engler RJ.
Allergy-Immunology Department, Walter Reed Army Medical Center, Washington, DC 20307-5001, USA.
Mosquito bite exposure results in a variety of reactions and secondary complications. Clinical hypersensitivity manifests primarily as local reactions with anaphylaxis being a very rare event. Risk factors for more severe local reactions include immunodeficiency, young children and visitors to an area with new exposure to indigenous mosquitoes. Necrotic skin reactions to mosquito bites have been associated with a newly recognized hemophagocytic syndrome in predominantly oriental populations. Diagnostic and therapeutic agents in the clinical management of mosquito hypersensitivity remain limited, but recent discovery of 3 recombinant proteins (rAed a 1, rAed a 2, rAed a 3) shared by several mosquito species promise to be more specific skin test antigens for the future.

BZ review
Fradin and Day - Comparative efficacy of repellents against mosquito bites
N Eng J Med 2002;347:13-18
Information concerning mosquito repellents is particularly important in the care of individuals with large local reactions to mosquito bites. Multiple chemical, botanical and "alternative" mosquito repellent products are aggressively marketed to consumers. In this study involving experimental exposures to mosquitoes, the DEET-based repellents provided complete protection for the longest duration of time with such duration dependent on the concentration of DEET contained. Most other preparations tested, including a skin moisturizer advertised to have repellent properties (Skin So Soft) protected for an average of less than 20 minutes. Of note, the Environmental Protection Agency has promulgated guidelines for the safe use of DEET-based repellents on its website (