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Q:

2/7/2020
I have a young Asian gentleman who recovered late last year from Kikuchi disease, cervical adenitis (non lymphoma, benign condition - neg hematologic evaluation) with systemic symptoms. The mechanism and pathogenesis of Kikuchi disease is unknown, the clinical presentation, course, and histologic changes suggest an immune response of T cells and histiocytes to an infectious agent. He did well on a course of steroids last year and I received documentation from his rheumatologist that he has no active autoimmune disease and has no concerns about him receiving AIT. He was previously on IT in past few years with excellent results and he is pushing to resume his IT. The condition is extremely rare and there is no data to address any theoretical concerns with regard to starting AIT. Any thoughts or suggestions either way?

A:

I do not recommend allergen immunotherapy unless you have other justifications for the immunotherapy, e.g. allergic rhinitis. If a patient with Kikuchi disease benefitted from allergen immunotherapy then I would utilize. There are concerns about allergen immunotherapy with other immunologic diseases but none of these concerns have been validated.

In summary, if your patient has indication for allergen immunotherapy, I would not modify his treatment based upon the diagnosis of Kikuchi disease.

I have attached two prior Ask the Expert questions about allergen immunotherapy and other inflammatory or autoimmune disease. Although neither question addresses Kikuchi disease, some of the same issues arise with vaccination in general and allergen immunotherapy in particular.

1/26/2018: Immunotherapy and Guillain-Barre syndrome
I am seeing an 8 1/2 year old girl with environmental allergies who is interested in immunotherapy. She had a history of Guillain-Barre syndrome at age 3. She has not had any additional issues and was discharged from Neurology at age 4. She has had her IPV and MMR without any issues. Is having a history of Guillain-Barre a contraindication to starting immunotherapy?

Vaccinations, particularly to influenza, have been associated with Guillian Barre (1,2,3) although other vaccines have not been associated (4). Allergy immunotherapy is a type of vaccination which stimulates a Th1 response and suppresses a Th2 response. There is a theoretical concern but the experience of over a 100 years of allergen immunotherapy is very reassuring. There options for allergy care other than immunotherapy but there are great advantages of allergen immunotherapy. The decision would require documentation of some form of shared decision making but I do not think a history of Guillian Barre would make allergen immunotherapy contraindicated. Guillian Barre may be an autoimmune disorder triggered by vaccination or infection. The immunotherapy practice guidelines include the following statement, which I believe applies to this question.

"Although concern about the safety of allergen immunotherapy in patients with autoimmune disorders has been raised in the past, there is no substantive evidence that such treatment is harmful in patients with these diseases. Therefore the benefits and risks of allergen immunotherapy in patients with HIV infection, other immunodeficiencies, or autoimmune disorders must be assessed on an individual basis."

1.Veitia, Jesyree, et al. "Guillian-Barre Syndrome (GBS) in Children after Influenza Vaccination, An analysis of the Vaccine Adverse Event Reporting System (VAERS) Database, 1991–2015 (S30. 003)." (2017): S30-003.
2.Ghaderi, Sara, et al. "Risk of Guillain-Barré syndrome after exposure to pandemic influenza A (H1N1) pdm09 vaccination or infection: a Norwegian population-based cohort study." European journal of epidemiology 31.1 (2016): 67-72.
3. Vellozzi, Claudia, Shahed Iqbal, and Karen Broder. "Guillain-Barre syndrome, influenza, and influenza vaccination: the epidemiologic evidence." Clinical infectious diseases 58.8 (2014): 1149-1155.
4. Gee, Julianne, et al. "Risk of Guillain-Barré Syndrome following quadrivalent human papillomavirus vaccine in the Vaccine Safety Datalink." Vaccine 35.43 (2017): 5756-5758.

7/21/2017: Allergen immunotherapy and myasthenia gravis
Are allergy shots contraindicated in some one that is being treated for myasthenia gravis?
The simple answer is no as autoimmune disease of various forms is a potential concern but not a contraindication for allergen immunotherapy.

The practice parameters summarize the literature on this subjects and a quote from pages S17-18 is provided below (J Allergy Clin Immunol 2011;127:S1-S55).

Immunotherapy in patients with immunodeficiency and autoimmune disorders
Summary Statement 21: Immunotherapy can be considered in patients with immunodeficiency and autoimmune disorders.
C
There are no controlled studies about the effectiveness or risks associated with immunotherapy in patients with immunodeficiency or autoimmune disorders. Concern about the increased risk of immunotherapy in such patients is largely hypothetical. A review article suggested guidelines for treatment of HIVpositive patients who meet the criteria for allergen immunotherapy. Immunotherapy was recommended for pollen and mite allergy in patients who have early to middle HIV disease, which is defined as a peripheral CD4 count of 400 or more cells/mL with no history of opportunistic infections or other AIDS-associated pathology and no evidence of plasma HIV viremia.200 Close monitoring is recommended monthly for the first 3 months and then quarterly.

Cases of allergen immunotherapy in patients with HIV controlled with highly active antiretroviral therapy are reported. 201,202 In 1 case report, allergen immunotherapy appeared to induce a transient T-cell proliferation and modest increase in RNA viral load, which resolved with highly active antiretroviral therapy.201 In another patient a 3.5-year course of immunotherapy for tree pollen–induced allergic rhinitis was successful in reducing the reported visual analog scale for subjective symptoms and medication use by almost 90%.202 During therapy, his CD4 cell count remained greater than 350 cells/mL, and his HIV RNA level remained less than 50 copies/mL. His symptoms remained well controlled 3 years after discontinuation of immunotherapy.

Although concern about the safety of allergen immunotherapy in patients with autoimmune disorders has been raised in the past, there is no substantive evidence that such treatment is harmful in patients with these diseases. Therefore the benefits and risks of allergen immunotherapy in patients with HIV infection, other immunodeficiencies, or autoimmune disorders must be assessed on an individual basis.

In my experience, autoimmune diseases with more predictable courses and for which there is effective therapies are less a concern to me than other autoimmune conditions/diseases when considering immunotherapy. Thus, I would be comfortable with providing allergen immunotherapy in a patient with myasthenia gravis if the clinical indications were present and a discussion was documented with the patient. However, I am less comfortable with multiple sclerosis as the attacks seem less predictable and maybe less treatable. There is no contraindication with any autoimmune disease.

In summary, autoimmune disease in general and myasthenia gravis in particular are not a contraindication for allergen immunotherapy.

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

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

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