Hypersensitivity to mosquito bites and insect bite-like reaction T14.0

In 1965, RI Weed (Weed RI 1965) first reported a hypersensitive reaction to an insect bite in a patient with CLL who developed induration, edema, erythema, and blisters with severe itching at the site of the insect bite.

Insect bites induce toxic, allergic and hyperergic reactions that usually subside spontaneously. In rare cases, however, insect stings can cause severe hypersensitive reactions accompanied by fever and systemic symptoms. In such cases, hematologic diseases may also be associated with the Epstein-Barr virus (EBV). Associations with EBV infections and lymphoproliferative disorders of natural killer (NK) cells are frequently observed, particularly in connection with the occurrence of systemic reactions (Tatsuno K et al. 2016). Hyperergic insect sting reactions are also observed in Wells syndrome (Melski JW 1990).

In contrast to hyperergic insect stings is the occurrence of "insect sting-like reactions" (Barzilai A et al. 1999). These are evenly distributed between exposed and non-exposed areas (Kim JE et al. 2018). There are no seasonal fluctuations in the occurrence of the lesions (Bairey O et al. 2012). Such reactions have also been termed "eosinophilic eruptions in hematoproliferative disorders" (Byrd JA et al. 2001). Bullous eruptions with similar clinical and histological features to bullous pemphigoid have also been described (clarification by direct and indirect immunofluorescence tests!).

The following hematologic diseases have been described in association with insect bite-like reactions:

• chronic lymphocytic leukemia
• acute lymphocytic leukemia
• acute monocytic leukemia
• mantle cell lymphoma
• large cell lymphoma
• myelofibrosis
• Angioimmunoblastic T-cell lymphoma (Murao K et al. 2019)
• Severeinsect bite hypersensitivity, EBV-induced (Severe mosquito bite allergy - SMBA). This is a cutaneous form of chronic active EBV infection (CAEBV) that predominantly affects adolescents and children from East Asian countries. It is often associated with EBV-associated haemophagocytic lymphohistiocytosis (EBV-HLH).

The pathogenesis of the insect bite-like reactions is unclear. The skin lesions were considered to be a non-specific cutaneous reaction to certain stimuli in patients with hematologic diseases and not a specific reaction of leukemic cells. However, in situ hybridization analyses show that neoplastic cells (e.g. in CLL) are present in the insect bite-like skin lesions, suggesting that these are specific skin lesions and not non-specific skin reactions (Mitteldorf C et al. 2012).

In fact, insect bites, drugs, chemoimmunotherapy and pyogenic infections can trigger non-specific eosinophilic eruptions in patients with CLL (Bairey O et al. 2012). The altered immune response in patients with hematologic diseases can increase the secretion of interleukin 4 (IL-4) and IL-5, which stimulates eosinophilic skin infiltration. The development of these reactive skin lesions is not usually related to the course or activity of CLL (Bairey O et al. 2012).

A special etiopathogenetic position is occupied by"Severe insect bite hypersensitivity, EBV-induced (SMBA), which overlaps with hydroa vacciniforme-like LPD (HV-LPD).

Oral glucocorticoids, intravenous immunoglobulin, and dapsone have been shown to be effective in controlling the lesions. Resumption of chemotherapy may also help improve skin lesions in some patients (Kim JE et al 2018).

The lesions may heal under postinflammatory hyperpigmentation. A recurrent course, however, is more the rule. In versch. In various collectives, courses lasting > 5 years have been reported.

1. Bairey O et al. (2012) Insect-bite-like reaction in patients with chronic lymphocytic leukemia: a study from the Israeli chronic lymphocytic leukemia study group. Eur J Haematol 89:491-496.
2. Barzilai A et al. (1999) Insect bite-like reaction in patients with hematologic malignant neoplasms. Arch Dermatol 135:1503-1507.
3. Byrd JA et al (2001) Eosinophilic dermatosis of myeloproliferative disease: characterization of a unique eruption in patients with hematologic disorders. Arch Dermatol 137:1378-1380.
4. Kim JE et al (2018) Insect Bite-Like Reaction with Bullous Lesions Mimicking Bullous Pemphigoid in a Patient with Chronic Lymphocytic Leukemia. Ann Dermatol 30:468-472.
5. Mangana Jet al (2017) Angioimmunoblastic T-Cell Lymphoma Mimicking Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS Syndrome). Case Rep Dermatol 9:74-79.
6. Melski JW (1990) Wells' syndrome, insect bites, and eosinophils. Dermatol Clin 8: 287-293.
7. Mitteldorf C et al. (2012) Insect bite-like reactions in a patient with B-cell chronic lymphocytic leukaemia: fluorescence in situ hybridization analysis revealed neoplastic B cells within the skin infiltrate. Br J Dermatol 167:944-946.
8. Murao K et al (2019) A case of an insect bite-like reaction in a patient with angioimmunoblastic T-cell lymphoma. Eur J Dermatol 29:425-426.
9. Tatsuno K et al. (2016) Clinical categories of exaggerated skin reactions to mosquito bites and their pathophysiology. JDS 82: 145-152
10. Ulmer A et al (2007) Dapsone in the management of "insect bite-like reaction" in a patient with chronic lymphocytic leukaemia. Br J Dermatol 156:172-174.
11. Yamamoto T et al. (2016) Epstein-Barr virus reactivation is induced, but abortive, in cutaneous lesions of systemic hydroa vacciniforme and hypersensitivity to mosquito bites. J Dermatol Sci 82
12. Weed RI (1965) Exaggerated delayed hypersensitivity to mosquito bites in chronic lymphocytic leukemia. Blood 26:257-268.