Cases reported "Insect Bites and Stings"

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1/6. An adult patient with hypersensitivity to mosquito bites developing mantle cell lymphoma.

    hypersensitivity to mosquito bites (HMB) has been known to occur exclusively in the first 2 decades of life and is frequently associated with Epstein-Barr virus (EBV) infection and lymphoproliferative diseases. We report here the first adult patient with HMB, a 61-year-old Japanese man who developed mantle cell lymphoma. EBV was detected in the lymph node by polymerase chain reaction and by in situ hybridization. serum levels of interleukin (IL)-4, IL-6, and IL-10 were markedly increased, and the T-helper cell (Th)1/Th2 balance determined by intracellular cytokine levels was polarized to Th2. These findings suggest that the Th1/Th2 imbalance could partly be involved in the pathogenesis of HMB.
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2/6. hypersensitivity to mosquito bites is not an allergic disease, but an Epstein-Barr virus-associated lymphoproliferative disease.

    Recently, we showed that 5 cases of hypersensitivity to mosquito bites (HMB) concealed the clonal lymphoproliferation of Epstein-Barr viral (EBV) dna-positive natural killer (NK) cells. Although the symptoms of HMB have been supposed to derive from Arthus phenomenon, it has become apparent that this unique disorder has the potential to develop into so-called malignant histiocytosis (MH) or related disorders. Accordingly, the criteria for MH have been changed, and a newer diagnostic name, hemophagocytic syndrome, has been described as being associated with viral infection or leukemia/lymphoma. We previously reported that biopsy specimens taken from skin lesions demonstrated infiltration of lymphocytes bearing the phenotype of NK cells. In this study, we found that skin lesions exhibited infiltration of atypical lymphocytes around the small vessels, resembling angiocentric lymphoma, and that these infiltrating cells were positive for EBER-1 by in situ hybridization. These findings support the concept that HMB is the most important manifestation of a certain type of lymphoproliferative disease that presents with an intense local skin reaction and high fever following mosquito bites, and whose essence is the lymphoproliferation of EBV dna-positive NK cells.
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3/6. vidarabine therapy for severe chronic active Epstein-Barr virus infection.

    PURPOSE: Severe chronic active Epstein-Barr virus infection (SCAEBV) is an intractable disease with a poor prognosis, and a definitive treatment has not been established. We administered vidarabine to patients with natural killer (NK) cell-type SCAEBV and evaluated clinical and virologic effects. patients AND methods: Four patients with SCAEBV were enrolled in this study. These patients had various symptoms, including fever, chronic hepatitis, hepatosplenomegaly, and hypersensitivity to mosquito bites. All patients had increased numbers of NK cells in their peripheral blood, and most of these were infected with EBV. Viral load was measured by in situ hybridization and quantitative polymerase chain reaction (PCR). RESULTS: The patients all responded to the therapy, and their symptoms improved. After the therapy, the number of NK cells in their peripheral blood decreased. In two patients who were closely monitored, the viral load measured by in situ hybridization and quantitative PCR decreased in parallel with the symptomatic improvement. After discontinuing this drug, the patient's symptoms returned and the Epstein-Barr virus load increased again. CONCLUSION: These results indicate that vidarabine therapy is a therapeutic choice to control SCAEBV, although its effect may be transient.
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4/6. A case of exaggerated mosquito-bite hypersensitivity with Epstein-Barr virus-positive inflammatory cells in the bite lesion.

    We describe a unique patient with mosquito-bite hypersensitivity who had extremely high titres of Epstein-Barr virus antibodies. For many years he developed intractable ulcers on the sites of mosquito-bite. Epstein-Barr virus infection was detected in almost all inflammatory cells in the ulcers and in the peripheral blood lymphocytes by using in situ hybridization to Epstein-Barr virus-encoded small ribonucleic acids and by polymerase chain reaction to Epstein-Barr virus dna. The inflammatory cells in the ulcers were positive for T-cell marker. Our results suggest that the Epstein-Barr virus infection in T cells may participate in the pathogenesis of exaggerated mosquito hypersensitivity and in delayed healing of ulcers on the sites of mosquito-bite.
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5/6. Atypical hypersensitivity to mosquito bites without natural killer cell proliferative disease in an adult patient.

    hypersensitivity to mosquito bites (HMB) is a rare disorder that occurs in the first 2 decades of life and is considered to be associated with chronic Epstein-Barr virus (EBV) infection and natural killer (NK) cell leukemia/lymphoma. EBV-encoded small nuclear rna (EBER)-positive NK cells infiltrate the skin lesion at the site of the mosquito bite. In this report, we present the case of an adult patient with mantle cell lymphoma complicated by atypical HMB. The anti-EBV antibody titer of the patient indicated reactivation of chronic infection with this virus, and EBV dna in the peripheral blood mononuclear cells was detected after chemotherapy by quantitative polymerase chain reaction analysis. However, an in situ hybridization analysis did not detect EBER-positive cells in the skin lesion at the bite site or in the lymph node. Peripheral NK cell lymphocytosis and EBV-associated lymphoproliferative disease did not develop. These findings suggest that some patients with chronic EBV infection may develop HMB without NK cell proliferative disease.
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6/6. Natural killer cell-derived large granular lymphocyte lymphoma of lung developed in a patient with hypersensitivity to mosquito bites and reactivated Epstein-Barr virus infection.

    A 17-year-old female developed natural killer (NK) cell-derived large granular lymphocyte (LGL) lymphoma of the lung. She had a past history of hypersensitivity to mosquito bites (HMB). After an eight-year chronic, active Epstein-Barr virus (EBV) infection, she developed multiple lung lesions and pleural effusion. In the effusion, 60% of the cells were LGL. They were CD2 , 3-, 16 , 56 , 57 , 45RO /RA weak, and possessed strong NK activity. No rearrangement of T-cell-receptor genes was detected. From all these results, a diagnosis of NK-LGL lymphoma of the lung was made. EB virus dna was detected in cells infiltrating the pleural effusion. The clonality of the LGLs was determined by Southern blot hybridization with the terminal repeat sequence of EB virus as a probe, and by chromosomal abnormalities. The patient died from respiratory failure. Necropsy of the lung revealed diffuse lymphoma composed of polymorphic cells with typical angiocentric lesions. Reportedly, lymphomas of NK lineage show predominantly extranodal involvement, and primary lung lesions are rare. In the pleural effusion of the present case, abnormally high levels of soluble Fas ligand, interleukin-10 and interferon gamma were detected. This hypercytokinemia, reflecting the microenvironment of lymphoma cells, may play a role in the progression of the lymphoma and organ injury in the lung.
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