| Disease type |
Criteria for diagnosis |
Exclusion criteria |
EBV+ cells |
References |
| Chronic active EBV disease (CAEBV) |
1) EBV-related illness with ≥ 3 months duration
2) Disease manifestations may include fever, hepatitis, adenopathies, hepatosplenomegaly, pancytopenia, uveitis, pneumonitis, hydroa vacciniforme-like skin eruptions and hypersensitivity to mosquito bites.
3) EBV detected by Southern blot hybridization or EBER-positive cells in affected tissues or peripheral blood; ≥102.5 copies/μg of EBV DNA in peripheral blood mononuclear cells; titers of anti-EBV IgG antibodies: anti-VCA ≥ 5120 or anti-EA >640. |
1) Other immunological abnormalities or infections that might explain the observed condition.
2) Congenital immunodeficiency including X-linked lymphoproliferative disorders. |
T-cells
or
NK-cells |
[129,137,138,141] |
| Hemophagocytic lymphohistiocytosis
(HLH) |
1) Fever and splenomegaly
2) Cytopenias affecting two or three lineages, hypertriglyceridemia, and/or hypofibrinogenemia.
3) Hemophagocytosis in the BM, spleen and/or LN. |
1) Hemophagocytic syndrome in accelerated phase of CAEBV.
2) Congenital immunodeficiency including familial HLH. |
T-cells
or
NK-cells |
[129,142] |
| Severe mosquito bite allergy (SMBA) |
Hypersensitivity to mosquito bites, characterized by high fever after mosquito bites, ulcers, necrosis, and scarring. |
Patients with systemic symptoms in addition to the cutaneous lesions are categorized as CAEBV. |
NK-cells |
[129,145,146] |
| Hydroa vacciniforme (HV) |
Recurrent vesiculo-papules with central umbilication and crust formation, usually occurring on the sun-exposed areas. |
T-cells (usually gamma / delta) |
[129,149,150] |
BM: Bone Marrow; CAEBV: Chronic Active EBV Disease; EA: Early Antigen; EBV: Epstein Barr Virus; HLH: EBV-Associated Hemophagocytic Lymphohistiocytosis; HV:
Hydroa Vacciniforme; LN: Lymph Nodes; NK: Natural Killer; SMBA: Severe Mosquito Bite Allergy; VCA: Viral Capsid Antigen
‘Severe mosquito bites allergy’ and ‘hydroa vacciniforme’ are used as clinical categories, while the terms ‘hypersensitivity to mosquito bites’ and ‘hydroa vacciniforme-like
eruptions’ were used to designate disease manifestations |
