The average values reported for healthy adults depend substantially on the choice of methodology. De Odorico et al26 compared the results for 2D and 3D ultrasonography. They concluded that the 3D method was the more reliable of the 2 options, and gave systematically lower estimates, but that the need for multiple determinations made 2D data more practical in normal clinical practice. Radionuclide data generally indicate larger volumes than ultrasonography, and in some instances, the scintigraphic findings have been compromised by a failure to exclude emissions from adjacent organs such as the kidneys and lungs. Perhaps because of post-mortem changes in the shape of the spleen, autopsy values have tended to be smaller than the data obtained by ultrasonography. It is thus inappropriate to make comparisons of absolute dimensions across methodologies.
Because of problems in determining the absolute volume of what is an irregularly shaped organ, some authors have simply reported percentage changes in their initial estimate of splenic volume (Table 4).36–38 Others have gauged splenomegaly in terms of length rather than volume or have calculated an arbitrary volumetric “index.”39–41 A wide range of formulae have been proposed to estimate splenic volumes.30,31,33,42–46 Many of these formulae show a close correlation with the weights of resected spleens and can be used to judge changes in the size of an individual's spleen, but it is difficult to compare absolute values between authors.
Various texts have suggested that at ultrasonography, the normal length of the adult spleen is in the range 12 to 14 cm,47–49 although such estimates have often been based upon small and rather heterogeneous samples. Experimental values are summarized in Table 5.
The extent of splenomegaly must often be assessed in children, adolescents and athletes with unusual body builds. In children, splenic dimensions show moderately strong relationships to standing height, body mass, and age, commonly with correlation coefficients of 0.7 to 0.8 (Table 6).
Some observers have reported the modest effects of height in adults, particularly in tall athletes such as basketball players,35,53 but this seems only to be true if the sample includes extreme body types. Others have found correlation coefficients between body size and splenic dimensions were too weak (r < 0.03) to warrant any adjustments of norms.44,54
Challenges to the use of laboratory determinations of splenic size as a component in the diagnosis of IM include not only interindividual variation but also methodology-related differences in absolute values, and the wide variety of formulae that have been used to calculate the volume of a complex-shaped organ from its linear dimensions.
Some authors have claimed that in IM, the difference from normal data is large enough to allow a confident diagnosis of splenic enlargement. Thus, Dommerby et al55 claimed that at ultrasonography, all infected individuals showed a splenic enlargement of at least 25%, and 3 days after the first symptoms, spleen lengths and widths were on average 50% to 60% greater than that of in a control group with other throat infections; splenic dimensions progressively returned to normal over 4 weeks, as the IM abated. In contrast, Hosey et al56 found that in 7% of healthy university athletes, the sonographic length and breadth of the spleen were such that these individuals would have been classed as having splenomegaly. Although there was an average 33.6% increase in size of the spleen with infection,57 this was no more than the commonly reported SD of normal values (above). Moreover, the many other possible causes of splenomegaly must be considered in reaching a diagnosis (Table 7).
Peaking of splenomegaly occurs around the 12th day of infection, and a change in dimensions over serial measurements provides a clearer indication of infection. Serial measurements on healthy controls show intraindividual changes in spleen length of <10%.57
The effects of the disease process upon tissue structures make the enlarged spleen vulnerable to rupture,58 and the regression of splenomegaly is often used in guiding a return to normal athletic activity. Dommerby et al55 suggested that although the initial enlargements of the liver and spleen were unrelated to abnormal hepatic enzyme levels, regression of these 2 indicators occurred in parallel over the course of the following month, as the disease resolved. However, there remain uncertainties about the sensitivity of illness severity and splenic enlargement as measures of the risk of impending splenic rupture.12,59,60
Early splenectomy was once regarded as the safest option after splenic rupture, but this reflected an overestimation of the associated mortality.6 There are occasional fatalities after a “spontaneous” rupture,69–73 but such incidents are rare12 and do not warrant a hasty splenectomy. Removal of the spleen may compromise subsequent immune responses.74 Moreover, some reports have shown 1% of deaths from an overwhelming meningeal or pneumococcal septicemia at operation,61,75–77 although this risk can be attenuated by the preoperative administration of pneumococcal and other vaccines.78
Many authors now regard conservative treatment as a better option, provided that the condition of the patient is stable and blood transfusion can be limited to <4 units to minimize the risks of transmitting hepatitis and HIV infections.63,79–81 Arguments raised against conservative management include a slower return of the athlete to competition, the risks of repeated blood transfusion, and the danger that the enlarged spleen may still contain hematomas that will cause a second rupture.25,66,68,73,79,82,83
There have been suggestions that vigorous physical activity is both a risk factor for CFS and prolongs its course.84 If IM is indeed related to CFS, this could be a further argument for restricting activity during and immediately after infection.
During the postacute phase of IM, there are often complaints of persistent fatigue, daytime sleepiness and depression,11 and sometimes the characteristics of fatigue match the American Psychological Association criteria for the diagnosis of CFS,108 although the relationships of IM to CFS are inconsistent (Table 8).85–88 One major problem is that CFS seems to be a heterogeneous group of conditions, rather than a single entity.89 Epstein–Barr virus (EBV) is not universally detected in patients with CFS, but type 1 EBV in particular is present in a subset of cases who have previously experienced IM.90,91 Moreover, retrospective studies provide evidence of a prior illness resembling IM in many patients with CFS,92–94 and a prospective study of adolescents with IM found that 6 months later, 13% developed CFS.95,96 It remains unclear whether late complaints of fatigue indicate a lingering infection, as suggested by a continued elevation of proinflammatory cytokines19 or whether the infection triggered what is essentially a psychological disorder.85,97,98
A retrospective comparison of 47 CFS cases with matched controls found a greater number of the patients reporting exercise >3 times per week before onset of the disease (67% vs 40%),84 but the significance of this apparent difference (P < 0.02) was weakened by multiple (18) post hoc intergroup comparisons. In a prospective case–control study of 301 adolescents with IM, pedometer studies have found that CFS is usually associated with reduced levels of physical activity,99–101 but an increase of activity was again associated with an immediate worsening of symptoms.102 However, Huang et al95 found no differences of habitual activity between those who developed late fatigue and those who did not.
We may conclude that a small proportion of cases of IM do progress to CFS. More information is needed on the responses to exercise in such individuals, but as with other forms of CFS, it seems plausible that excessive physical activity may lead to worsening of condition.
The general management of the patient with IM is largely symptomatic. There is no evidence of benefit from the routine administration of either corticosteroids103–105 or antiviral medications such as acyclovir.106,107 However, corticosteroids may be indicated if there is severe edematous airway obstruction,12 and antiviral medication may prove helpful in the late treatment of a specific subset of patients with long-term fatigue.108,109
Most patients make an uneventful recovery after a period of modified bed rest, although 5% of patients develop serious complications.110 Penman111 collected reports of some 100 episodes of IM with fatal outcomes, including deaths attributed to neurological complications, respiratory obstruction, myocarditis, and liver failure. For athletes, the most serious issues are usually pharyngitis, splenomegaly with the potential for splenic rupture,61 and a possible progression of continuing fatigue to one variant of CFS in the later phases of the disease. However, the factors triggering a progression to CFS and the nature of this relationship remain controversial.1,87,103
One controlled study of university students noted a slightly faster recovery with ad libitum physical activity,112 and another study involving army cadets found no complications from a return to light training as soon as the patients were afebrile.113 However, vigorous activity is unwise while the virus is active. In addition to issues of splenic rupture and progression to CFS, there is a slight risk of developing myocarditis, with chest pain, electrocardiogram abnormalities, and the release of cardiac troponin.114,115
Decisions on a return to light, noncontact activity and progressive reconditioning after IM are guided by (1) the regression of symptoms, (2) the normalization of splenic size as monitored by serial ultrasonography (although ultrasonography is not always practiced, and the interpretation of data can be difficult with extreme body types),116 and (3) epidemiologic data on the likelihood of splenic rupture at various times after onset of the illness. Rutkow6 somewhat arbitrarily recommended against athletic participation for as long as 6 months after infection. More recently, most authors have opted for only 3 to 4 weeks of rest if the athlete is asymptomatic and ultrasound demonstrates normal splenic dimensions.1,60,83,103,117–120 Nevertheless, there have been occasional episodes of splenic rupture as late as 7 weeks after the onset of infection. Thus, some authors still advise avoiding contact sports and activities demanding the Valsalva maneuver for at least 2 months, and highly trained athletes may take as long as 3 months to regain their previous level of performance.12
Infectious mononucleosis is sufficiently prevalent among adolescents and young adults that the condition must be suspected if an athlete presents with fever, swollen glands, a sore throat, and tiredness. Careful assessment is important, as symptoms are nonspecific, and a positive diagnosis of IM will require several months of absence from full competition. Physical examination must be reinforced by laboratory tests, including demonstration of a lymphocytosis with abnormal lymphocytes, a heterophile-positive slide test, and the appearance of specific EBV antigens. Palpation and percussion are ineffective methods of detecting associated splenomegaly. Even with of laboratory data, evaluation must take account of methodology, the formulae used in calculating dimensions, and the individual's body size. Sonographic data usually demonstrate an enlarged spleen during the first few weeks of infection, but dimensions may remain within what is a broad normal range. Splenic dimensions are more useful in following the course of the disease and in advising on the athlete's return to physical activity. The main risks to the athlete are splenic rupture and a progression to CFS. By 3 to 4 weeks after the onset of infection, the risks of injury from contact trauma, a Valsalva maneuver, or spontaneous rupture are sufficiently low to allow a graded return to physical activity. Sudden onset abdominal pain should nevertheless arouse suspicions of a ruptured spleen. Debate continues on the merits of surgical versus conservative treatment of such an incident. Surgical intervention may trigger a dangerous septicemia, and splenectomy is also associated with an ongoing compromise of immune function. These risks must be weighed carefully against the disadvantages of conservative treatment: a longer absence from competition, the need for substantial blood transfusions, and the possibility of a recurrent rupture of the spleen. Discussion continues on the frequency with which IM progresses to a form of CFS and on the possible factors that provoke prolonged fatigue. However, for most athletes, IM offers no more than the inconvenience of 4 weeks of restricted activity with little risk to long-term health.
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