Complications
Develops in nearly all adults (less common in children) 5 to 10 days after starting treatment with ampicillin, amoxicillin, or other beta-lactam antibiotics.[45] It has also been associated with azithromycin. A recent review suggests that the incidence is not as high as previously thought.[76]
Even though it is associated with penicillins, this rash does not represent a true penicillin allergy.
Rash is typically maculopapular and pruritic.
Resolves in a few days after discontinuing antibiotic.
Occurs in 0.1% to 0.5% of cases, because of massive infiltration with lymphocytes. Mortality rates are up to 30%.[77]
The majority of patients are male with an average age of 22 years. The average time between onset of symptoms and rupture is 14 days (range up to 8 weeks).[78]
Spleen may dramatically enlarge and become vulnerable to spontaneous rupture, or rupture from minor trauma, such as coughing, vomiting, defecating, or simply turning in bed. However, a preceding history of trauma has been reported in only 14% of patients.[78]
The most common presenting symptom is abdominal pain, reported in 88% of patients.[78]
Although splenectomy is often performed in the majority of patients, careful serial observation or spleen-sparing interventions may be considered.[79] Observation and supportive care may suffice occasionally in haemodynamically stable patients.
Splenic infarction has also been reported.[80]
Encephalitis occurs overall in 1% of adolescent and adult IM cases, usually during the first 2 weeks of infection.[34]
In an aetiological study of encephalitis in children, up to 6% of cases had strong evidence of current EBV infection.[8]
Other possible complications include aseptic meningitis, Guillain-Barre syndrome, cranial nerve palsies, transverse myelitis, sub-acute sclerosing panencephalitis, acute cerebellar ataxia, and psychosis.[9][81]
Very rarely, patients develop chronic active disease, which carries a poor prognosis with high mortality. Diagnosis should be considered in patients with persistent symptoms of IM for >3 months.[33]
Characterised by EBV-positive T- or natural killer (NK)-cell proliferations and includes systemic and cutaneous forms, but symptoms can overlap. The systemic form presents with fever, lymphadenopathy, and splenomegaly following primary EBV infection, and the initial phase resembles an IM-like illness. The cutaneous form includes severe mosquito bite allergy and hydroa vacciniforme-like lymphoproliferative disorders.[82]
In some patients chronic active EBV infection follows a chronic, relapsing clinical course with a risk of progression to systemic EBV-positive T- or NK-cell lymphoma, while others experience a fulminant form of the disease accompanied by haemophagocytic lymphohistiocytosis.[82]
Most often occurs in children and adolescents without a history of immunodeficiency or autoimmunity. Adult onset is associated with a worse prognosis. Most frequent in East Asia and Central and South America, but rare in Western and African populations.[82]
Death usually is a result of lymphoma, haemophagocytic syndrome, or fulminant hepatitis.[83]
Studies suggest an association between EBV and autoimmune diseases, such as multiple sclerosis, Sjogren syndrome, rheumatoid arthritis, systemic lupus erythematosus (SLE), and other systemic autoimmune diseases. The mechanism by which EBV influences the risk remains unknown. [84][85][86][87][88]
A higher seroprevalence of EBV antibodies in SLE patients has been reported compared with controls.[89]
EBV is estimated to cause approximately 1% of all cancers. EBV is implicated in the development of haematolymphoid malignancies derived from B-, T-, and natural killer (NK)-cells, including Burkitt's lymphoma, gastric carcinoma, classic Hodgkin's lymphoma, extra-nodal NK-/T-cell lymphoma, nasal type, and immunodeficiency-associated lymphoproliferative disorders. The aetiology of EBV-associated cancers likely results from a complex intersection of clinical, genetic, and dietary factors.[90]
Recent advances in rapid cloning and sequencing of cancer-derived EBV genomes have revealed that various EBV strains are differentially distributed throughout the world, and that the behaviour of cancer-derived EBV strains is different from that of the prototype EBV strain of non-cancerous origin. The sequencing results have raised the hypothesis that certain EBV-associated diseases are caused by specific EBV strains.[91]
There is evidence of a distinct fatigue syndrome 6 months after diagnosis,[92] which in one study affected 9% to 22% of patients, compared with 0% to 6% following an ordinary upper respiratory infection.[93]
A prospective study of patients with EBV-IM found that patients required nearly 2 months to achieve pre-illness functional status.[35]
Female sex and pre-morbid mood disorder are risk markers for post-IM fatigue.
Chronic fatigue should be present for at least 6 months for a diagnosis of chronic fatigue syndrome; post-IM fatigue may be of shorter duration.
The association between IM and subsequent depression is unclear. While some studies indicated that IM can be followed by depression, large-scale studies were lacking. In the largest study to date, a prospective cohort study of over 12,000 children and adolescents, IM was associated with a 40% increased risk for a diagnosis of depression one year or later after infection.[94]
Interstitial nephritis, myositis-associated acute kidney injury, haemolytic uraemic syndrome, and jaundice-associated nephropathy have all been reported in patients with acute symptomatic IM. While rare, the outcome is potentially fatal and renal-replacement therapy may be required.[97]
Non-neoplastic EBV infection (typically seen in children) may present as EBV-associated HLH, a syndrome of severe, life-threatening hyperinflammation. It is most common in patients of Asian descent.
Presents acutely in patients without prior history of immunodeficiency or EBV infection. For patients who have genetic diseases that predispose them to the development of HLH, EBV infection is a life-threatening problem. Presence of hyperbilirubinaemia and hyperferritinaemia at diagnosis is poor prognostic sign. It may be self-limiting in some cases.[98]
Use of this content is subject to our disclaimer