Q:

I have a 5 year-old girl with significantly exaggerated responses to mosquito bites. She has significant swelling that will last for days, but no signs of urticaria or any acute reaction. Despite its rarity we checked for IgE to mosquito with an Immunocap, unsurprisingly this was negative. But incidentally she is noted to have a mildly elevated ESR and a mild lymphopenia with no mention of atypical lymphocytes. I know some leukemias can cause reactions to mosquitoes, given her mild hematologic abnormalities how much of a concern is that, or should I simply recheck the CBC in a few months?

A:

Thank you for your recent inquiry.

It is true that large local reactions to insect bites, especially mosquitoes, have been associated with lymphoreticular neoplasms. The literature has a number of references to this association. For your convenience, I have copied below the abstracts from a few of these.

The decision as to whether or not to pursue a workup for malignancy in a pediatric patient with large local reactions to mosquito bites is probably best approached by a pediatric hematologist. From reading some of the literature regarding this relationship, I am afraid that I could not come up with a definitive suggestion for you as to how to approach this patient, and I believe this would best be answered, as noted, by consulting a pediatric hematologist. If I pursued it further, that is the route I would take at this time.

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

Insect Bite–like Reaction in Patients With Hematologic Malignant Neoplasms
Aviv Barzilai, MD, MSc; Dorit Shpiro, MD; Iris Goldberg, PhD; Yasmin Yacob-Hirsch, MSc; Carlos Diaz-Cascajo, MD;Dina Meytes, MD; Regina Schiby, MD; Ninette Amariglio, PhD; Henri Trau, MD
Arch Dermatol. 1999;135:1503-1507.
Abstract
Background Exaggerated reaction to insect bites, mainly to mosquitoes, is infrequently described in patients with chroniclymphocytic leukemia. Skin lesions usually appear months to years after the diagnosis of leukemia and are unrelated to laboratory findings, disease course, or therapy.Observations We describe 8 patients with various hematologic disorders (chronic lymphocytic leukemia, acute lymphoblastic leukemia, acute monocytic leukemia, mantle-cell lymphoma, large-cell lymphoma, and myelofibrosis) who developed insect bite–like reaction. Although the clinical picture and the histological characteristics of the lesions were typical for insect bites, none of the patients actually had a history, course, or response to treatment suggestive of arthropod assaults. In 2 patients, the eruption preceded the diagnosis of the malignant neoplasm. The rash persisted for months to years and was resistant to therapies other than systemic corticosteroids. The 3 patients with chronic lymphocytic leukemia seemed to have a worse prognosis than expected for their disease. In 1, the polymerase chain reaction detected leukemic cells in the infiltrate.
Conclusions Insect bite–like reaction is an infrequent, disturbing, and difficult-to-treat nonspecific phenomenon in patients with hematologic malignant neoplasms. Since it may precede the hematologic disorder, oriented evaluation is warranted.We speculate that immunodeficiency plays a role in its pathogenesis; however, the exact pathogenesis and its prognostic implications await further studies.

J Am Acad Dermatol. 2001 Oct;45(4):569-78.
Hypersensitivity to mosquito bites as the primary clinical manifestation of a juvenile type of Epstein-Barr virus-associated natural killer cell leukemia/lymphoma.
Tokura Y, Ishihara S, Tagawa S, Seo N, Ohshima K, Takigawa M.
Source
Department of Dermatology, Hamamatsu University School of Medicine, Japan.
Abstract
Hypersensitivity to mosquito bites or mosquito allergy is a mysterious disorder that has been reported mainly in Japanese patients (at least 58 patients) in the first two decades of life. The skin lesion at bite sites is typically a bulla that develops into necrosis. Patients simultaneously exhibit a high temperature and general malaise and subsequently may experience lymphadenopathy and hepatosplenomegaly. Recent studies have revealed that this mosquito hypersensitivity is associated with chronic Epstein-Barr virus infection and natural killer cell leukemia/lymphoma. The natural killer cell, infected with monoclonal (or oligoclonal) Epstein-Barr virus, seems to be involved in the pathogenesis of the hypersensitivity. Half of the patients reported died of hemophagocytic syndrome (or malignant histiocytosis), granular lymphocyte proliferative disorder, or lymphomas. We propose that this disease, defined as the triad of hypersensitivity to mosquito bites, chronic Epstein-Barr virus infection, and natural killer cell leukemia/lymphoma, is a clinical entity mostly seen in Asians.

Intern Med. 2005 Oct;44(10):1097-9.
Hypersensitivity to mosquito bites as a potential sign of mantle cell lymphoma.
Kunitomi A, Konaka Y, Yagita M.
Source
Division of Hematology and Rheumatology, Department of Medicine, The Tazuke Kofukai Medical Research Institute, Osaka.
Abstract
Hypersensitivity to mosquito bites (HMB) is known to be an allergic reaction and also a skin symptom in some cases of natural killer cell leukemia/lymphoma associated with Epstein-Barr virus (EBV) infection. We describe a patient who had suffered from HMB for 5 years, and subsequently developed mantle cell lymphoma (MCL), which resembled chronic lymphocytic leukemia in the early phase. EBV monoclonality was not detected in lymph nodes by Southern blotting. Serum levels of interleukin-4 and IgE were increased, but they decreased and HMB disappeared when MCL was predominant. We consider that HMB may be a potential sign of MCL.

Sincerely,
Phil Lieberman, M.D.

AAAAI - American Academy of Allergy Asthma & Immunology