Epstein-Barr virus-associated lymphoproliferative diseases Mosquito bite allergies afflict individuals who have any one of various types of
Epstein–Barr virus-associated lymphoproliferative diseases (EBV+ LPD). About 33% of patients with
chronic active EBV infection are afflicted by mosquito bite allergies. Other Epstein-Barr virus-associated lymphoproliferative disease reported to predispose individuals to mosquito bite allergies include Epstein-Barr virus-positive
Hodgkin disease,
hydroa vacciniforme,
hemophagocytic lymphohistiocytosis,
aggressive NK-cell leukemia (also termed aggressive NK-cell leukemia/lymphoma), In addition to the signs and symptoms of their specific Epstein-Barr virus-associated lymphoproliferative disease (see
Epstein-Barr virus-associated lymphoproliferative diseases), these individuals are subject to severe local as well as systemic reactions to mosquito bites. The eruptions may be accompanied by fever,
arthralgia or other systemic symptoms. The disorder predominantly affects adults, frequently takes a protracted course, and has a high rate of spontaneous remission but is often recurrent with relapses occurring even long after remissions. One study found a relapse rate of 56% during an observation period of up to 19 months. Relapses are more frequent in adults than in children. While these lesions usually resolve without sequelae, they may result in skin atrophy and hyperpigmentation.
chronic lymphocytic leukemia,
Hodgkin lymphoma,
nasopharyngeal cancer, and
renal cell carcinoma. Episodes of the disorder are sometimes triggered by: drugs (e.g. antimicrobial agents, biologics, antihypertensive agents,
diuretics, thyroid hormones,
analgesics,
cytostatic agents, and
anesthetics);
vaccines; skin contact with chemicals (e.g.
p-phenylenediamine,
thiomersal, and
cladribine); viral, bacterial, fungal, and parasitic infections; and insect bites. Mosquitoes trigger mosquito bite allergies in individuals with eosinophilic cellulitis. They are also thought to trigger mosquito bite allergies that are followed by and therefore trigger the development of eosinophilic cellulitis in individuals with no prior evidence of the disease. It is also possible, however, that these individuals have an undiagnosed, latent form of the disease. The acute eruptions, which may be singular or multiple, occur at the bite site and may spread locally or to more distant skin sites. The classification of all these eosinophilic cellulitis reactions, whether triggered by a mosquito bite, triggered by some other agent, or apparently untriggered, is argued; it has been proposed that eosinophilic cellulites is not a distinct clinical entity but rather a set of skin reactions in various diagnosed or yet-to be diagnosed disorders that involve hypereosinophilia, dysfunctional eosinophils, and/or pathological reactions to foreign antigens which predispose individuals to developing these reactions. Eosinophilic cellulitis-associated mosquito bite allergies appear to be non-specific
type IV hypersensitivity reactions in which
T helper cells release
cytokines such as IL5 to attract, activate, promote the degranulation, and prolong the survival of eosinophils. These eosinophils discharge
eosinophilic cationic,
major basic, and other proteins which injure cells and tissues and thereby may contribute to the severity of the skin lesions. The lesions typically are scattered red nodules or diffuse areas consisting of eosinophil infiltrates and flame-like figures composed of eosinophil deposits and
collagen bundles. Over time, these lesions become
granulomatous and scarred. Patients with the disorder may have numerous scars due to previous bouts of mosquito bite allergies. The diagnosis, which can be challenging to distinguish from other skin disorders, is based on a history of mosquito bites and previous or concurrent predisposing diseases, the course taken by the skin lesions, and the pathology of these lesions. Blood eosinophil levels are elevated in about half of these cases. The disorder has generally been either untreated or treated with short- or longer-term oral
glucocorticoids,
topical glucocorticoids, and/or injections of glucocorticoids into the skin lesions, depending on lesion severity. Oral antihistamines are used to alleviate associated itchiness.
Anti-inflammatory drugs and
immunomodulatory agents such as
dapsone,
hydroxychloroquine,
cyclosporine,
interferon alfa,
tacrolimus,
TNF inhibitors, various antifungal agents, and numerous other agents have been used to treat the disorder in
case reports but their value in treating the disorder as well as mosquito bite allergies is unclear. If a causative disorder triggering or predisposing to the development of eosinophilic cellulitis is identified, the best treatment option is to treat this disorder. Patients with eosinophilic cellulitis should be followed to determine if their disorder progresses into a more serious disease such as the
hypereosinophilic syndrome,
eosinophilic fasciitis, or the
eosinophilic granulomatosis with polyangiitis.
Chronic lymphocytic leukemia Several case reports have found that individuals with chronic lymphocytic leukemia are predisposed to develop severe skin reactions to mosquito and other insect bites. However, there are reports that chronic lymphocytic leukemia patients can develop similarly severe skin reactions in the absence of an insect bite history. The pathology of the insect bite sites in these cases resembles the findings in lesions of eosinophilic cellulitis in individuals with mosquito bite allergies but the mechanism behind these reactions is unknown. There are too few reports to establish treatment recommendations for mosquito bite allergy I chronic lymphocytic leukemia beyond those generally used to treat other types of mosquito bite allergies.
Mantle cell lymphoma In rare cases,
mantle cell lymphoma, a subtype of
B-cell lymphomas, has been reported in association with mosquito bite allergies. In several of these cases, the mosquito bite allergies occurred before the diagnosis of mantle cell lymphoma, suggesting that mosquito bite allergies can be a manifestation of early development, and therefore a harbinger of mantle cell lymphoma. While most of these cases have not been associated with EBV infection, some cases of mosquito bite allergies in Asia have been reported to occur in EBV-positive MBL. Due to the rarity of these cases, the difference between EBV-negative and EBV-positive mantle cell lymphoma, as well as the best treatments for mosquito bite allergies in these two forms of mantle cell lymphoma, has not been determined. ==References==