[1] Typically, the disorder presents with fever, decreased numbers of circulating white blood cells and/or platelets, enlarged liver and/or spleen, clinical evidence of hepatitis, and/or central nervous system disturbances[23] such as irritability, decreased levels of consciousness, seizures, meningitis (i.e. neck stiffness, photophobia, and headache), impaired cranial nerve function, hemiplegia, ataxia (i.e. poor coordination of complex muscle movements), and reduced muscle tone.
Following inductive therapy, allogenic hematopoietic stem cell transplantation preceded by a reduced intensity conditioning regimen has been employed selectively, particularly in cases with primary HLH, with early results reporting some success.
[12] Novel approaches to HLH particularly in cases of refractory or recurrent disease include the use of antithymocyte globulin, the DEP regimen (i.e. liposomal doxorubicin, etoposide, methylprednisolone), an anti-interferon gamma monoclonal antibody,[24] and, particularly in patients with EBV+-HLH, rituximab.
Characteristic findings that are also diagnostic criteria for the disorder are: 1) symptoms similar to those in infectious mononucleosis but persist for >3 months; 2) high blood levels of EBV DNA (i.e. >25 viral copies per mg of total DNA); 3) histologic evidence of organ disease; 4) presence of EBV RNA (e.g. an EBER) in an affected organ or tissue; and 5) occurrence of these findings in individuals who do not have a known immunodeficiency, malignancy, or autoimmune disorder.
Other symptoms of CAEBV include persistent or intermittent fever, enlargement of lymph nodes, spleen, and/or liver, severe mosquito bite allergy, rashes, herpes virus-like skin blistering, diarrhea, and uveitis.
In EBV+ T and NK cell-associated disease, the tissues affected by CAEBV usually exhibit an histology that is not suggestive of a malignancy: lymph nodes have areas of hyperplasia, focal necrosis, and small granulomas; spleen shows atrophy of white pulp with congested red pulp; liver contains infiltrations of small lymphocytes around portal vasculature and sinuses; and lung and heart have findings typical of interstitial pneumonitis and viral myocarditis, respectively.
In CAEV, the best studied or the predispositions to the disorder, SMBA is characterized by the development of skin redness, swelling, ulcers, necrosis and/or scarring at the site of a mosquito bite.
[28] Affected individuals have increased blood levels of immunoglobulin E (which plays an essential role in the development of type I hypersensitivity reactions of the skin and other tissues) and EBV+ NK cells.
[1] While the disorder's etiology is unclear, it is thought that the mosquito salivary gland allergenic proteins trigger reactivation of EBV in latently infected NK cells.
[30] Hydroa vacciniforme is a rare photodermatitis reaction in which sunlight causes itchy skin papules and vesicles that develop crusts and eventually become scarred tissue.
Furthermore, the disease in children or adults may progress to cause severe, extensive, and disfiguring skin lesions unrelated to sunlight exposure, facial edema, and systemic manifestations such as fever, weight loss, and enlargements of lymph nodes, liver, and/or spleen.
For malignant cases of the disease, Immunotherapeutic drugs prednisone, interferon-α, chloroquine, and thalidomide) have given temporary remissions and improvements; standard chemotherapy and radiotherapy regimens used to treat lymphoma and leukemia have produced only transient benefits while often causing unacceptable toxicities.
It is thought that the reduce efficacy of immune surveillance associated with these predisposing conditions or treatments maintain EBV in a dormant state systemically but not where EBV+ B cells are prevalent, i.e. in afflicted mucous membranes and skin.
[32] iBL commonly presents with fever, other constitutional symptoms, and tumors in the gastrointestinal tract, bone marrow, liver, lung, and central nervous system.
[41] The presentation of EBV+ HL is similar to that of EBV-HL, e.g. fever, night sweats, weight loss in the setting of swollen lymph nodes, and/or evidence of tumor invasion of other tissues.
These cases, termed Epstein–Barr virus-positive (EBV+) diffuse large B cell lymphoma, not otherwise specified (EBV+ DLBCL), occur predominantly in East Asia and Mexico and less commonly in Europe and the USA.
[16] The infiltrations typically do not spread beyond these initial sites and there is no evidence of lymph node, spleen, or other tissue involvement: FA-DLBCL appears to be a non-malignant proliferation of EBV+ large B cells.
When these lesions occupy the heart (e.g. on myxommas or prosthetic valves) or vasculature (e.g. on thrombus-laden vascular grafts) the disease may present as a life-threatening cardiovascular symptoms, particularly strokes.
Affected individuals are usually middle aged and present with obvious tumors, hemoptysis, ulcerating skin nodules, obstructions in the upper airways, and/or obstructions/bleeding in the lower gastrointestinal tract, particularly the colon.
For cancer grade I and II localized diseases, the recommended treatment is radiation directed at the tumor lesions plus a chemotherapy regimen such as DeVIC (dexamethasone, etoposide, ifosfamide, and carboplatin).
This lymphoma commonly occurs in men (median age ~60 years) who present with advanced stage III or IV disease (~70% of cases) characterized by T cell infiltrations that cause prevalent lymph node swelling often accompanied by evidence of bone marrow, liver, spleen, and/or skin involvement.
Recommended treatments for advanced stage PTCL, NOS (regardless of EBV status) include intensive chemotherapy regimens, e.g. CHOP, as induction therapy possibly followed by autologous hematopoietic stem cell transplantation.
The disease presents with generalized swelling of lymph nodes, enlarged liver and spleen, skin lesions (rash, or, less commonly, nodules, plaques, purpura, and urticarial), bone marrow involvement, and B symptoms of fever, weight loss, and night sweats.
Small studies have found that patients with refractory or relapsed AITL have positive responses to pralatrexate, romidepsin, belinostat, brentuximab vedotin, lenalidomide, alisertib, and mogamulizumab.
Individuals commonly (~73% of cases) present with advanced stage III or IV disease characterized by lymphadenopathy involving neck, armpit, and/or groin areas (~86%); enlarged liver (~25%) and/or spleen (25%); and malignant cell infiltrations in the bone marrow (~25%) or, rarely, tonsils, salivary glands, and/or hard palate.
Laboratory abnormalities include a positive Coombs test with or without accompanying autoimmune hemolytic anemia (~50%) and elevated blood levels of lactic acid dehydrogenase (45%) and gamma globulins (19%).
While complete remission rates are substantially lower than 90% and treated patients have inevitably relapsed, these regiments are recommended front-line treatments for symptomatic advanced stage follicular lymphoma.
[1] A study conducted in China found that all or almost all patients presented with B symptoms (weight loss, fever, night sweats) and an enlarged liver and/or spleen but not lymph nodes.
It includes only aggressive lymphomas while excluding all indolent forms of LPD except for the inclusion of EBV-positive mucocutaneous ulcer The EBV+ positivity of cells involved in these PTLD are similar to those occurring in immune-competent individuals.
The latter two EBV latency proteins are thought to promote the development and progression these PTLD by activating the NFkB pathway in and thereby stimulating the proliferation and survival of the infected host cells.