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 resolve without spontaneous recovery. However, in rare cases, insect bites can cause more severe reactions, sometimes accompanied by fever and systemic symptoms. In such cases, underlying hematologic disorders, eosinophil granulocyte abnormalities, and/or an association with Epstein-Barr virus (EBV) may be present. Associations with EBV infection and lymphoproliferative disorder of natural killer (NK) cells are frequently observed, particularly in the setting 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 bites is the occurrence of "insect sting-like reactions"(Barzilai A et al 1999). These are evenly distributed among exposed as well as non-exposed areas (Kim JE et al. 2018). Seasonal variations in the occurrence of the lesions are absent (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 studies).

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

chronic lymphocytic leukemia

acute lymphoblastic leukemia

acute monocytic leukemia

Mantle cell lymphoma

large cell lymphoma

Myelofibrosis

Angioimmunoblastic T-cell lymphoma (Murao K et al 2019).

The following clinical and histological parameters have been defined (Byrd JA et al 2001):

1. Itchy papules, nodules and/or vesiculobullous (pemphigoid-like) eruptions unresponsive to conservative treatment;
2. Histopathologically confirmed eosinophilic, lymphohistiocytic infiltration of the skin at the surface and at depth;
3. exclusion of other causes of tissue eosinophilia; and
4. a pre-existing diagnosis of haematological malignancy.

The pathogenesis of the insect sting-like reactions is unclear. The skin lesions were considered to be a nonspecific cutaneous reaction to certain stimuli in patients with hematologic diseases and not a specific reaction of leukemic cells. However, in situ hybridization analyses demonstrate that neoplastic cells (e.g., in CLL) were observed in the insect-like skin lesions, suggesting that they may be specific skin lesions rather than nonspecific skin reactions (Mitteldorf C et al. 2012).

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

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.