Mosquito bite allergies, also termed hypersensitivity to mosquito bites, are excessive reactions of varying severity to mosquito bites. They are allergic hypersensitivity reactions caused by the non-toxic allergenic proteins contained in the saliva injected by a female mosquito (male mosquitos do not take blood-meals) at the time it takes its blood meal, and are not caused by any toxin or pathogen. By general agreement, mosquito bite allergies do not include the ordinary wheal and flare responses to these bites although these reactions are also allergic in nature. [1] Ordinary mosquito bite allergies are nonetheless detailed here because they are the best understood reactions to mosquito bites and provide a basis for describing what is understood about them.
Mosquito bite allergies are informally classified as 1) the skeeter syndrome, i.e., severe local skin reactions sometimes associated with low-grade fever; 2) systemic reactions that range from high-grade fever, lymphadenopathy, abdominal pain, and/or diarrhea to, very rarely, life-threatening symptoms of anaphylaxis; and 3) severe and often systemic reactions occurring in individuals that have an Epstein-Barr virus-associated lymphoproliferative disease, Epstein-Barr virus-negative lymphoid malignancy, [2] or another predisposing condition such as eosinophilic cellulitis or chronic lymphocytic leukemia. [3] The term papular urticaria [4] is commonly used for a reaction to mosquito bites that is dominated by widely spread hives. Here, papular urticaria is regarded as a symptom of mosquito bite allergy manifested in individuals with one of the other mosquito bite allergies but particularly in those associated with eosinophilic cellulitis.
Mosquitos belong to the biological order of Diptera (which includes all two-winged insects), suborder Nematocera, family Culicidea. [5] There are >3,500 different mosquito species with the Aedes and Culex genera being common in North America. It is assumed that any species of mosquito that causes an ordinary mosquito bite reaction in humans is capable of causing mosquito bite allergies. [6] In addition to mosquitoes, the Diptera order includes numerous other types of biting insects such as midges (e.g. sand flies) and gnats. Bites by the latter insects [1] or possibly some other insects [7] may cause reactions that are mechanistically and clinically similar to those seen with mosquito bites. [1]
Mosquito bite allergies occur more often where insect bites are frequent. Consequently, cases (as well as various other allergic disorders) are more prevalent in tropical climates, underdeveloped areas, areas dominated by poverty, poor hygiene, and/or unawareness of these diseases, and urban areas plagued by social inequality, juvenile delinquency, and violence. That is, not only climate but also cultural and socioeconomic conditions play critical roles in facilitating the development and prevalence of diverse allergic disease including mosquito bite allergies. [7]
The typical reaction to mosquito bites involves the development of an itchy wheal that may contain a central red dot and is surrounded by splotchy redness. This "immediate reaction" occurs at some time during the first 20 minutes following the bite. Within hours of the bite, a "delayed reaction", in which the wheal evolves into a papule develops and then dissipates over the next few days or weeks. [1] However, there is a wide variability in the type of reaction which individuals mount in response to these bites. The initial mosquito bites in previously unexposed individuals does not cause a skin reaction but does initiate the development of antibodies and/or lymphocytes that are directed against the allergens in mosquito's saliva. These individuals thereby become sensitized and reactive to subsequent mosquito bites. After repetitive mosquito bites, individuals may become less sensitive or completely insensitive to the bites in the natural process of allergen desensitization. Individuals therefore progress through 5 stages in which the type of reaction to a mosquito bite depends on the number of their previous bite exposures and levels of acquired sensitization and desensitization to these bites. The 5 stages an individual may undergo in reacting to repetitive mosquito bites are: [6]
In a study of 41 Canadian adults experimentally exposed to mosquito bites, 11 individuals exhibited no reaction, 23 individuals exhibited immediate followed by delayed reactions, 6 individuals exhibited only immediate reactions, and 1 individual exhibited only a delayed reaction. [3] Overall, 70-90% of individuals experience an immediate reaction and 55-65% experience a delayed reaction to mosquito bites. [6]
Individuals also vary in the severity of their reactions to mosquito bites. Most individuals show a "small reaction" in which a 2–10 mm (0.1-0.4 inches) diameter wheal evolves into a similarly sized papule that dissipates over several days. [6] About 2.5% of individuals (based on self reports) [6] show a "large reaction" in which the wheal is much larger than 10 mm (it may exceed 3 cm, i.e. 1.2 inches) in diameter and evolves into an extensive lesion that has black and blue discolorations due to subcutaneous bleeding, blistering, and/or necrosis. The latter reactions, which appear to be caused by the development of an inflammatory Arthus reaction at the site, may be very painful. [1]
Mosquito saliva contains >30 potentially allergenic proteins. More than 11 of these have been identified in the saliva of the Aedes egypti mosquito. Four such proteins, termed Aed a 1 (an apyrase), Aed 2 (Female-specific protein, D7), Aed 3 (an as yet undefined protein), and Aed a 4 (an α-glucosidase) have been purified as recombinant proteins. Each of these recombinants causes immediate and delayed skin reactions when injected into volunteers with a history of mosquito bite reactivity. As exemplified by the Aed proteins, the proteins in the saliva of any biting mosquito are thought to cause individuals who have not been previously bitten to: a) make IgE and IgG antibodies that bind the proteins inducing their formation and b) develop T cells (a type of lymphocyte) that react against parts of the inducing proteins that are displayed on the surface of cells at the bite site (see Antigen presentation). In subsequent mosquito bites, IgE and IgG appear involved in the development of both immediate and delayed skin reactions while T cells appear involved in development of the delayed skin reactions. [8] The acquired IgE binds mosquito saliva proteins and then triggers skin tissue cells such as mast cells to release at least two mediators of allergic reactions, histamine and leukotriene C4. These mediators contribute to the development of the wheal, itch, and other components of the immediate reaction. This part of the immediate reaction is a classical type I hypersensitivity reaction. The acquired IgG binds mosquito saliva proteins to form an immune complex-triggered type III hypersensitivity reaction that recruits blood leukocytes, including T cells, into the bite area; this response it thought to be required for developing the early stage of the delayed reaction. T cells present in or recruited to the mosquito bite area appear responsible for mediating the full delayed reaction. The full delayed reaction is a type IV hypersensitivity reaction. [6]
The diagnosis of ordinary mosquito reactions is made on the basis of the history and clinical features of mosquito bites. [6]
Reducing mosquito breeding areas (e.g. eliminating standing water pools, stocking ponds with fish that consume mosquito larva) and the use of other mosquito control methods such as insecticides, mosquito traps, protective clothing, bed nets, and repellants (e.g. DEET or permethrin) are effective, highly recommended means for reducing mosquito bites. [6] Daily doses of a non-sedating second-generation anti-histamines (e.g. cetirizine or levocetirizine) can effectively reduce the immediate and delayed reactions to mosquito bites. [8] The use of recombinant mosquito saliva proteins to desensitize individuals against developing reactions to mosquito bites has yielded variable results and requires further study. [6]
Treatment of ordinary small or large mosquito bite reactions is limited to the use of non-sedative H1 antihistamines, e.g. cetirizine [6] or a drug with combined activity in inhibiting histamine and platelet-activating factor, e.g. rupatadine. [9] Randomized, double-blinded, placebo-controlled studies are needed to determine if antileukotriene drugs or topical steroids have beneficial effects in reducing the symptoms of these bites. [6]
The Skeeter syndrome is by definition a mosquito bite allergy that consists of a large mosquito bite reaction that may be accompanied by a brief or longer-term (i.e. days to weeks) low-grade fever. [8] and, on rare occasions, vomiting. [10] The bite site shows an intense, large reaction often resembling a cellulitis infection that persists for days to weeks. [5] The syndrome usually afflicts healthy children, immune-deficient persons, and individuals who are new to an area inhabited by mosquito species to which they have not been exposed. [6]
Mechanistically, the Skeeter syndrome appears to be a particularly intense variant of the ordinary mosquito bite reaction. It involves sequential Type I, III, and IV hypersensitivity reactions [6] that are mediated by the IgE, IgG, and T cells that are directed against mosquito salivary proteins. [1]
Children afflicted with the syndrome remain healthy although subject to recurrent severe reactions to mosquito bites. The development of desensitization that follows repetitive mosquito bites and reduces the intensity or completely blocks reactions to mosquito bites may take longer to develop and/or be less effective in those with Skeeter syndrome compared to those with ordinary mosquito bite reactions. [11]
The diagnosis of Skeeter syndrome is based mainly on the appropriate history of severe skin responses to mosquito bites that may be associated with fever. The diagnosis can be supported by the detection, using for example an ELISA assay), IgE directed against mosquito saliva proteins in the afflicted individuals serum. [8] Direct mosquito bite testing is perhaps the best method for diagnosing mosquito bite allergy but difficulty in determining which mosquito species to use for the test, the possibility of transmitting a mosquito-borne disease, and the risk of triggering a very severe response make this test impractical for routine use. [6]
The preventive measures listed for ordinary mosquito bite reactions are important for avoiding Skeeter syndrome reactions. In addition to second generation, non-sedative H1 antihistamines, antipyretics and nonsteroidal anti-inflammatory drugs are typically used to treat patients with acute attacks of the syndrome. [6]
Individuals with systemic mosquito bite allergies respond to mosquito bites with intense local skin reactions (e.g. blisters, ulcers, necrosis, scarring) and concurrent or subsequent systemic symptoms (high-grade fever and/or malaise; less commonly, muscle cramps, bloody diarrhea, bloody urine, proteinuria, and/or wheezing; [3] or very rarely, symptoms of overt anaphylaxis such as hives, angioedema (i.e. skin swelling in non-mosquito bite areas), shortness of breath, rapid heart rate, and low blood-pressure). [8] There are very rare reports of death due to anaphylaxis following mosquito bites. [6] Individual with an increased risk of developing severe mosquito bite reactions include those experiencing a particularly large number of mosquito bites, those with no previous exposure to the species of mosquito causing the bites, and those with a not fully developed immune system such as infants and young children. [8] Individuals with certain Epstein-Barr virus-associated lymphoproliferative, [12] non-Epstein-Barr virus malignant lymphoid, [2] or other predisposing disease [3] also have an increased rate of systemic mosquito bite reactions but are considered in a separate category .
Systemic mosquito bite reactions appear to be primarily Type I hypersensitivity reactions that are critically mediated by IgE directed against mosquito salivary gland proteins. [8]
The methods used to diagnose systemic mosquito bite allergies are similar to those used to diagnose the Skeeter syndrome, including typical case history and, in particular, ELISA tests to detect specific IgE directed against mosquito salivary proteins. [8]
The methods used to avoid mosquito bites (see Prevention in section on Ordinary mosquito bite reactions) are of particularly importance for preventing systemic mosquito bite allergies, given their severity. These include avoiding mosquito-infested areas, the use of repellants such as DEET or permethrin, and mosquito bite desensitization procedures once they have been shown to be safe and effective for this severest form of mosquito allergy. [8]
Systemic mosquito bite reactions are serious and on rare occasions may be life-threatening. [6] Individuals at risk for developing anaphylactic symptoms in response to mosquito bites should carry an Epinephrine autoinjector for immediate use following a mosquito bite. These individuals as well as those without self-injecting epinephrine who develop symptoms of anaphylaxis following a mosquito bite should be treated as medical emergencies requiring anaphylaxis management. [8] Individuals with less severe symptoms of systemic mosquito bite reactions require monitoring and treatments tailored to their symptoms. These treatments may include systemic corticosteroids, second generation H1 anti-histamines, and anti-pyretics similar to those used to treat the Skeeter syndrome. [6]
Mosquito bite allergies afflict individuals who have any one of various types of Epstein–Barr virus-associated lymphoproliferative diseases (EBV+ LPD). [13] About 33% of patients with chronic active EBV infection are afflicted by mosquito bite allergies. Other Epstein-Barr virus-associated lymphoproliferative disease reported to predispose individuals to mosquito bite allergies include Epstein-Barr virus-positive Hodgkin disease, [14] hydroa vacciniforme, [15] hemophagocytic lymphohistiocytosis, [16] aggressive NK-cell leukemia (also termed aggressive NK-cell leukemia/lymphoma), [14] and extranodal NK/T-cell lymphoma, nasal type. [13] Mosquito bite allergies in individuals with chronic active Epstein-Barr virus infection is the best studied of those that occur in Epstein-Barr virus-associated lymphoproliferative disease; much of what is known in this area is based on these individuals. [13]
Cases of mosquito bite allergies associated with Epstein-Barr virus-associated lymphoproliferative disease have been reported most often in Japan, Taiwan, Korea, and the native populations of Mexico, Central America, and South America. [14] This reaction occurs primarily in younger individuals (0–18 years old; mean age 6.7 years) who have evidence of one of the predisposing Epstein-Barr virus-associated lymphoproliferative disease. [3] Rarely, however, it occurs in individuals who exhibit no signs or symptoms of a predisposing disorder but later develop chronic active Epstein-Barr virus infection. [3] [17] In addition to the signs and symptoms of their specific Epstein-Barr virus-associated lymphoproliferative disease (see Epstein-Barr virus-associated lymphoproliferative diseases), these individuals are subject to severe local as well as systemic reactions to mosquito bites. [3] The bite sites are infiltrated with T helper cells, CD8+ T cells, and CD16+ NK cells. In this mixture of infiltrates, most of the cells exhibiting EBV positivity are T helper cells. [13] The systemic reactions include: fever and malaise; [12] enlarged lymph nodes, liver, and/or spleen; liver dysfunction; hematuria; and proteinuria. [1] The individuals exhibit greatly increased numbers off circulating NK cells, increased levels of T helper cells. and increased levels of IgE. [13] Some of the circulating NK cells are clearly infected with EBV. The mosquito bitten tissues show perivascular infiltrations containing T and NK cells; a large percentage of these NK cells are EBV positive. [14] Cases associated with chronic active Epstein-Barr virus infection commonly progress to a more serious Epstein-Barr virus-associated lymphoproliferative disease such as marginal zone B-cell lymphoma or a Hodgkin lymphoma-like B cell lymphoma. [14]
The allergenic proteins in the mosquito's salivary are thought to trigger the reactivation of EBV in the NK cells that are latently infected with the virus. Upon reactivation, the virus expresses certain of its gene products, particularly that of its LMP1 oncogene, [13] as well as induces its infected cells to release certain of their gene products, particularly interferon gamma and interleukin 10, [3] which cause the cells it infects to lyse and release EBV to infect other cells or, alternatively, to become immortalized, proliferate, and, possibly, become malignant. [13]
The diagnosis of mosquito bite allergies in Epstein-Barr virus-associated lymphoproliferative disease depends on finding evidence of the lymphoproliferative disease, a compatible clinical presentation, and detection of EBV in the NK and T cells (e.g. T helper cells) in blood and/or mosquito bitten tissues. The presence of high levels of EBV+ circulating NK cells strongly supports the diagnosis. However, an exceptionally high density of EBV+ in the skin lesions and/or blood raises the possibility that the individual has a NK-cell lymphoma/leukemia. [6] Lympoid cells at the bite site may also express the EBV1 viral gene, BZLF1; this gene promotes the lyses of its infected cell host and when detected in bite sites is a marker of a poor prognosis. [13]
The best treatment for mosquito bite allergy in individuals with an Epstein-Barr virus-associated lymphoproliferative disease varies. Mild and clearly uncomplicated cases with, for example, indolent CAEV, are treated conservatively focusing on obtaining relief of symptoms such as skin irritation, fever, and malaise. [17] Cases with evidence of significant complications of CAEFV such as the development of hemophagocytosis, NK/T cell lymphoma, or aggressive NK cell lymphoma generally require chemotherapeutic regimens directed at these complications. Individuals with EBV+ systemic mosquito bite allergy and clear evidence of concurrent aggressive chronic active Epstein-Barr virus infection have been treated with relative success by the 3 step regimen used to treat the latter. [2] Rare cases of systemic mosquito bite allergy have been reported to occur in individuals who have no apparent predisposing disease but later develop chronic active Epstein-Barr virus infection. [14] [17] Such cases require careful evaluation and follow-up for development of a predisposing disorder. [17]
Eosinophilic cellulitis, also known as Wells syndrome, is a rare skin disease usually occurring on the extremities and/or trunk that is characterized by episodic acute urticarial eruptions or erysipelas-like rashes which proceed to develop over the ensuing ~6 weeks into granuloma-like or morphea-like lesions. The initial lesions may be papules, plaques, vesicles, or blisters and give a burning or itchy sensation. [18] The eruptions may be accompanied by fever, arthralgia or other systemic symptoms. [19] The disorder predominantly affects adults, frequently takes a protracted course, and has a high rate of spontaneous remission but is often recurrent with relapses occurring even long after remissions. One study found a relapse rate of 56% during an observation period of up to 19 months. Relapses are more frequent in adults than in children. While these lesions usually resolve without sequelae, they may result in skin atrophy and hyperpigmentation. [18] Individuals afflicted with eosinophilic cellulitis may have a history of other diseases including various eosinophlic skin diseases, abnormally high levels of circulating blood eosinophils, the hypereosinophilic syndrome, the Churg-Strauss syndrome, ulcerative colitis, arthralgias, myalgias, facial nerve paralysis, photosensitivity, [18] polycythemia vera, chronic myeloid leukemia, [20] chronic lymphocytic leukemia, Hodgkin lymphoma, nasopharyngeal cancer, and renal cell carcinoma. [18] Episodes of the disorder are sometimes triggered by: drugs (e.g. antimicrobial agents, biologics, antihypertensive agents, diuretics, thyroid hormones, analgesics, cytostatic agents, and anesthetics); vaccines; skin contact with chemicals (e.g. p-phenylenediamine, thiomersal, [18] and cladribine); viral, bacterial, fungal, and parasitic infections; and insect bites. [18]
Mosquitoes trigger mosquito bite allergies in individuals with eosinophilic cellulitis, They are also thought to trigger mosquito bite allergies that are followed by and therefore trigger the development of eosinophilic cellulitis in individuals with no prior evidence of the disease. It is also possible, however, that these individuals have an undiagnosed, latent form of the disease. The acute eruptions, which may be singular or multiple, occur at the bite site and may spread locally or to more distant skin sites. The classification of all these eosinophilic cellulitis reactions, whether triggered by a mosquito bite, triggered by some other agent, or apparently untriggered, is argued; [3] it has been proposed that eosinophilic cellulites is not a distinct clinical entity but rather a set of skin reactions in various diagnosed or yet-to be diagnosed disorders that involve hypereosinophilia, dysfunctional eosinophils, and/or pathological reactions to foreign antigens which predispose individuals to developing these reactions. [19] Eosinophilic cellulitis-associated mosquito bite allergies appear to be non-specific type IV hypersensitivity reactions in which T helper cells release cytokines such as IL5 to attract, activate, promote the degranulation, and prolong the survival of eosinophils. These eosinophils discharge eosinophilic cationic, major basic, and other proteins which injure cells and tissues and thereby may contribute to the severity of the skin lesions. [18] The lesions typically are scattered red nodules or diffuse areas consisting of eosinophil infiltrates and flame-like figures composed of eosinophil deposits and collagen bundles. Over time, these lesions become granulomatous and scarred. Patients with the disorder may have numerous scars due to previous bouts of mosquito bite allergies. [18]
The diagnosis, which may be difficult to distinguish from other skin disorders, is based on history of mosquito bites and previous or concurrent predisposing diseases, the course taken by the skin lesions, and the pathology of these lesions. Blood eosinophil levels are elevated in about half of these cases. [19] The disorder has generally been either untreated or treated with short- or longer-term oral glucocorticoids, topical glucorocoricoids, and/or injections of glucocorticoids into the skin lesions, depending or lesion severity. Oral antihistamines are used to alleviate associated itchiness. Anti-inflammatory drugs and immunomodulatory agents such as dapsone, hydroxychloroquine, cyclosporine, interferon alfa, tacrolimus, TNF inhibitors, various antifungal agents, and numerous other agents [18] have been used to treat the disorder in case reports but their value in treating the disorder as well as mosquito bite allergies is unclear. [18] If a causative disorder triggering or predisposing to the development of eosinophilic cellulites is identified, the best treatment option is to treat this disorder. [18] Patients with eosinophilic cellulitis should be followed to determine if their disorder progresses into a more serious disease such as the hypereosinophilic syndrome, eosinophilic fasciitis, or the Churg-Strauss syndrome. [20]
Several case reports have found individuals with chronic lymphocytic leukemia are predisposed to develop severe skin reactions to mosquito and other insect bites. However, there are reports that chronic lymphocytic leukemia patients can develop similarly severe skin reactions in the absence of an insect bite history. The pathology of the insect bite sites in these cases resembles the findings in lesions of eosinophilic cellulitis in individuals with mosquito bite allergies but the mechanism behind these reactions is unknown. [3] There are too few reports to establish treatment recommendations for mosquito bite allergy I chronic lymphocytic leukemia beyond those generally used to treat other types of mosquito bite allergies. [3] [13]
In rare cases, mantle cell lymphoma, a subtype of B-cell lymphomas, has been reported in association with mosquito bite allergies. In several of these cases, the mosquito bite allergies occurred prior to the diagnosis of mantle cell lymphoma, suggesting that mosquito bite allergies can be a manifestation of early developing, and therefore a harbinger of mantle cell lymphoma. While most of these cases have not been associated with EBV infection, some cases of mosquito bite allergies in Asia have been reported to occur in EBV-positive MBL. Because of the rarity of these cases, the difference between EBV-negative and EBV-positive mantle cell lymphoma as well as the best treatments for mosquito bite allergies in these two forms of mantle cell lymphoma have not been determined. [3] [13]
The Epstein–Barr virus (EBV), formally called Human gammaherpesvirus 4, is one of the nine known human herpesvirus types in the herpes family, and is one of the most common viruses in humans. EBV is a double-stranded DNA virus.
Post-transplant lymphoproliferative disorder (PTLD) is the name given to a B cell proliferation due to therapeutic immunosuppression after organ transplantation. These patients may develop infectious mononucleosis-like lesions or polyclonal polymorphic B-cell hyperplasia. Some of these B cells may undergo mutations which will render them malignant, giving rise to a lymphoma.
Tumors of the hematopoietic and lymphoid tissues or tumours of the haematopoietic and lymphoid tissues are tumors that affect the blood, bone marrow, lymph, and lymphatic system. Because these tissues are all intimately connected through both the circulatory system and the immune system, a disease affecting one will often affect the others as well, making aplasia, myeloproliferation and lymphoproliferation closely related and often overlapping problems. While uncommon in solid tumors, chromosomal translocations are a common cause of these diseases. This commonly leads to a different approach in diagnosis and treatment of hematological malignancies. Hematological malignancies are malignant neoplasms ("cancer"), and they are generally treated by specialists in hematology and/or oncology. In some centers "hematology/oncology" is a single subspecialty of internal medicine while in others they are considered separate divisions. Not all hematological disorders are malignant ("cancerous"); these other blood conditions may also be managed by a hematologist.
Lymphoproliferative disorders (LPDs) refer to a specific class of diagnoses, comprising a group of several conditions, in which lymphocytes are produced in excessive quantities. These disorders primarily present in patients who have a compromised immune system. Due to this factor, there are instances of these conditions being equated with "immunoproliferative disorders"; although, in terms of nomenclature, lymphoproliferative disorders are a subclass of immunoproliferative disorders—along with hypergammaglobulinemia and paraproteinemias.
T-cell lymphoma is a rare form of cancerous lymphoma affecting T-cells. Lymphoma arises mainly from the uncontrolled proliferation of T-cells and can become cancerous.
Intravascular lymphomas (IVL) are rare cancers in which malignant lymphocytes proliferate and accumulate within blood vessels. Almost all other types of lymphoma involve the proliferation and accumulation of malignant lymphocytes in lymph nodes, other parts of the lymphatic system, and various non-lymphatic organs but not in blood vessels.
Aggressive NK-cell leukemia is a disease with an aggressive, systemic proliferation of natural killer cells and a rapidly declining clinical course.
Angioimmunoblastic T-cell lymphoma is a mature T-cell lymphoma of blood or lymph vessel immunoblasts characterized by a polymorphous lymph node infiltrate showing a marked increase in follicular dendritic cells (FDCs) and high endothelial venules (HEVs) and systemic involvement.
X-linked lymphoproliferative disease is a lymphoproliferative disorder, usually caused by SH2DIA gene mutations in males. XLP-positive individuals experience immune system deficiencies that render them unable to effectively respond to the Epstein-Barr virus (EBV), a common virus in humans that typically induces mild symptoms or infectious mononucleosis (IM) in patients. There are two currently known variations of the disorder, known as XLP1 and XLP2. XLP1 is estimated to occur in approximately one in every million males, while XLP2 is rarer, estimated to occur in one of every five million males. Due to therapies such as chemotherapy and stem cell transplants, the survival rate of XLP1 has increased dramatically since its discovery in the 1970s.
Skeeter syndrome is a localized severe allergic reaction to mosquito bites, consisting of inflammation, peeling skin, hives, ulceration and sometimes fever. It is caused by allergenic polypeptides in mosquito saliva, and therefore is not contagious. It is one of several forms, being one of the most severe, of allergic responses to mosquito bites, termed mosquito bite allergies.
Acute generalized exanthematous pustulosis (AGEP) is a rare skin reaction that in 90% of cases is related to medication.
There are several forms of Epstein–Barr virus (EBV) infection. These include asymptomatic infections, the primary infection, infectious mononucleosis, and the progression of asymptomatic or primary infections to: 1) any one of various Epstein–Barr virus-associated lymphoproliferative diseases such as chronic active EBV infection, EBV+ hemophagocytic lymphohistiocytosis, Burkitt's lymphoma, and Epstein–Barr virus positive diffuse large B-cell lymphoma, not otherwise specified); 2) non-lymphoid cancers such as Epstein–Barr virus associated gastric cancer, soft tissue sarcomas, leiomyosarcoma, and nasopharyngeal cancers; and 3) Epstein–Barr virus-associated non-lymphoproliferative diseases such as some cases of the immune disorders of multiple sclerosis and systemic lupus erythematosis and the childhood disorders of Alice in Wonderland Syndrome and acute cerebellar ataxia.
Hydroa vacciniforme (HV) is a very rare, chronic photodermatitis-type skin condition with usual onset in childhood. It was first described in 1862 by Pierre-Antoine-Ernest Bazin. It is sometimes called "Bazin's hydroa vacciniforme". A study published in Scotland in 2000 reviewed the cases of 17 patients and estimated a prevalence of 0.34 cases per 100,000 population. In this study they reported an average age of onset of 7.9 years. Frequently the rash first appeared in the spring or summer months and involved sun-exposed skin. The rash starts as a vesicular eruption, later becoming umbilicated, and results in vacciniform scarring. It is most frequently found on the nose, cheeks, ears, dorsum of the hand, and arms.
Extranodal NK/T-cell lymphoma, nasal type (ENKTCL-NT) is a rare type of lymphoma that commonly involves midline areas of the nasal cavity, oral cavity, and/or pharynx At these sites, the disease often takes the form of massive, necrotic, and extremely disfiguring lesions. However, ENKTCL-NT can also involve the eye, larynx, lung, gastrointestinal tract, skin, and various other tissues. ENKTCL-NT mainly affects adults; it is relatively common in Asia and to lesser extents Mexico, Central America, and South America but is rare in Europe and North America. In Korea, ENKTCL-NT often involves the skin and is reported to be the most common form of cutaneous lymphoma after mycosis fungoides.
Plasmablastic lymphoma (PBL) is a type of large B-cell lymphoma recognized by the World Health Organization (WHO) in 2017 as belonging to a subgroup of lymphomas termed lymphoid neoplasms with plasmablastic differentiation. The other lymphoid neoplasms within this subgroup are: plasmablastic plasma cell lymphoma ; primary effusion lymphoma that is Kaposi's sarcoma-associated herpesvirus positive or Kaposi's sarcoma-associated Herpesvirus negative; anaplastic lymphoma kinase-positive large B-cell lymphoma; and human herpesvirus 8-positive diffuse large B-cell lymphoma, not otherwise specified. All of these lymphomas are malignancies of plasmablasts, i.e. B-cells that have differentiated into plasmablasts but because of their malignant nature: fail to differentiate further into mature plasma cells; proliferate excessively; and accumulate in and injure various tissues and organs.
Chronic active EBV infection or in its expanded form, chronic active Epstein–Barr virus infection is a very rare and often fatal complication of Epstein–Barr virus (EBV) infection that most often occurs in children or adolescents of Asian or South American lineage, although cases in Hispanics, Europeans and Africans have been reported. It is classified as one of the Epstein-Barr virus-associated lymphoproliferative diseases.
Epstein–Barr virus–associated lymphoproliferative diseases are a group of disorders in which one or more types of lymphoid cells, i.e. B cells, T cells, NK cells, and histiocytic-dendritic cells, are infected with the Epstein–Barr virus (EBV). This causes the infected cells to divide excessively, and is associated with the development of various non-cancerous, pre-cancerous, and cancerous lymphoproliferative disorders (LPDs). These LPDs include the well-known disorder occurring during the initial infection with the EBV, infectious mononucleosis, and the large number of subsequent disorders that may occur thereafter. The virus is usually involved in the development and/or progression of these LPDs although in some cases it may be an "innocent" bystander, i.e. present in, but not contributing to, the disease.
Natural killer cell enteropathy, also termed NK cell enteropathy (NKCE), and a closely related disorder, lymphomatoid gastropathy (LG), are non-malignant diseases in which one type of lymphocyte, the natural killer cell, proliferates excessively in the gastrointestinal tract. This proliferation causes red, sore-like spots, raised lesions, erosions, and ulcers in the mucosal layer surrounding the GI tract lumen. Both disorders cause either no or only vague symptoms of GI tract disturbances such as nausea, vomiting, and bleeding.
Diffuse large B-cell lymphoma associated with chronic inflammation (DLBCL-CI) is a subtype of the Diffuse large B-cell lymphomas and a rare form of the Epstein–Barr virus-associated lymphoproliferative diseases, i.e. conditions in which lymphocytes infected with the Epstein-Barr virus (EBV) proliferate excessively in one or more tissues. EBV infects ~95% of the world's population to cause no symptoms, minor non-specific symptoms, or infectious mononucleosis. The virus then enters a latency phase in which the infected individual becomes a lifetime asymptomatic carrier of the virus. Some weeks, months, years, or decades thereafter, a very small fraction of these carriers, particularly those with an immunodeficiency, develop any one of various EBV-associated benign or malignant diseases.
Fibrin-associated diffuse large B-cell lymphoma (FA-DLBCL) is an extremely rare form of the diffuse large B-cell lymphomas (DLBCL). DLBCL are lymphomas in which a particular type of lymphocyte, the B-cell, proliferates excessively, invades multiple tissues, and often causes life-threatening tissue damage. DLBCL have various forms as exemplified by one of its subtypes, diffuse large B-cell lymphoma associated with chronic inflammation (DLBCL-CI). DLBCL-CI is an aggressive malignancy that develops in sites of chronic inflammation that are walled off from the immune system. In this protected environment, the B-cells proliferate excessively, acquire malignant gene changes, form tumor masses, and often spread outside of the protected environment. In 2016, the World Health Organization provisionally classified FA-DLBCL as a DLBCL-CI. Similar to DLBCL-CI, FA-DLBCL involves the proliferation of EBV-infected large B-cells in restricted anatomical spaces that afford protection from an individual's immune system. However, FA-DLBCL differs from DLBCL-CI in many other ways, including, most importantly, its comparatively benign nature. Some researchers have suggested that this disease should be regarded as a non-malignant or pre-malignant lymphoproliferative disorder rather than a malignant DLBCL-CI.