When Are Steroids Indicated In The Setting Of Known Acute Epstein-Barr Virus Infections?
Masako
Shimamura,
MD
Rebecca W.
Widener,
MD
Infectious mononucleosis, caused by Epstein-Barr virus, is generally characterized by a triad of pharyngitis, fatigue, and cervical lymphadenopathy. Fever and splenomegaly are also common in presentation. These are symptoms primarily manifested by the host response rather than direct viral infection. The severity and duration of symptoms are variable and most commonly resolve by 2 to 3 months postinfection. However, some such as lymphadenopathy and fatigue may persist. Treatment is generally supportive and con- sists of rest (although strict bed rest is not necessary), over-the-counter symptomatic relief for fever and throat pain, and avoidance of contact sports until the patient is asymptomatic and, if splenomegaly is present, you are no longer able to palpate the spleen.
The use of steroids for treatment of infectious mononucleosis has long been contro- versial. As early as the 1960s, several studies have sought to provide the answer to this question. A Cochrane review most recently evaluated 7 randomized-controlled trials comparing the effectiveness of corticosteroid regimens to that of placebo. Two of these trials showed no difference between steroid treatment and placebo in regards to the time to resolution of clinical symptoms; one of which specifically evaluated the use of a combined treatment regimen consisting of acyclovir and prednisolone.1 Two trials showed initial short-term improvement in sore throat with corticosteroid treatment, although this effect was not sustained. Three trials showed shortened duration in fever with treatment versus placebo; however, the effects on other clinical symptoms such as fatigue and sore throat varied. Overall, as the authors concluded, there were insufficient data throughout these studies to support steroid use in the routine treatment of infectious mononucleosis. The studies were generally small (n = 24-94) and had variability in the type of corticosteroid used, route of administration, dose, duration, and outcome measures.2
The lack of clear evidence of benefit has led to universal recommendations indicating that steroids have no role in the routine use of treatment of infectious mononucleosis. However, despite this, steroids continue to be used somewhat liberally in uncomplicated cases, perhaps to hasten return to school and normal activities because of persistent symptoms, patient demand, or the physician’s personal experience, clinical judgment, or training.3 Steroids are not without adverse effects. Rare case reports have linked the use of steroids for routine mononucleosis with myocarditis, mostly mild and asymptomatic, but causing supraventricular tachycardia in one case,4 and neurologic complications including meningoencephalitis, seizures, and brachial plexus palsy.5,6 Furthermore, the potential that they may interfere with the immunobiology of the disease has also been theorized, adversely affecting latently infected lymphocytes and long-term immunity.7 In one study of corticosteroid therapy, lymphocytes from young adult patients treated with a 10-day prednisone taper were compared over time to those from untreated patients with severe EBV disease.8 For the first 2 weeks, lymphocyte totals and subsets were similar between treated and untreated patients, but between weeks 3 and 12 posttreatment, lymphocyte total numbers and subsets of B cells, helper T cells, and cytotoxic T cells were significantly lower in the prednisone-treated group. Although this reduction may contribute to improvement of immune-mediated symptoms, the authors expressed concern regarding the unknown effect of altering the T-lymphocyte response in steroid-treated subjects, as T cells are critical in long-term control of EBV infection in the host. For these reasons, avoidance of routine use of steroids is recommended.
Most patients with an acute EBV infection have a self-limited course and recover without sequelae. Rarely, however, severe complications can occur in both healthy and immonocompromised patients. It is during these times that the use of steroids may, indeed, be warranted. Airway obstruction or impending airway obstruction is due to tonsillar hypertrophy and occurs in approximately 3.5% of patients but has been reported to occur in as many as 25% of cases.9 Massive splenomegaly and splenic rupture are the other most commonly feared complications. Although mild splenomegaly is quite a common finding in acute mononucleosis, found in approximately 50% of patients, serious splenic complications are very rare, occurring in less than 1%. Splenic rupture usually is found to occur during the second and third weeks of illness, at the peak of splenomegaly. Neurologic complications occur in less than 1% of patients. Two of the most common neurologic complications are encephalitis and cranial nerve palsies. Other neurologic complications that have been reported are aseptic meningitis, acute disseminated encephalomyelitis, transverse myelitis, Guillain-Barré syndrome, optic neuritis, and Alice-in-Wonderland syndrome (a perceived distortion of object size).10 Other life-threatening complications reported include myocarditis, fulminant hepatitis, and liver failure, and hematologic manifestations such as hemolytic anemia, idiopathic thrombocytopenic purpura, and hemophagocytic lymphohistiocytosis. These, and other life-threatening complications, are all indications for use of steroid therapy. Steroids have been used anecdotally and in small case series for these indications, but no rigorous studies have been performed to confirm the benefit of steroid use in these situations. Nevertheless, it is expert opinion that steroids may be useful for these potentially life-threatening complications of EBV infection.
References
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