AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Pleurodynia is an uncommon complication of coxsackievirus B infection and is defined as the sudden occurrence of lancinating chest pain attacks, commonly associated with fever, malaise, and headaches. Coxsackievirus B is an RNA Enterovirus, which usually causes an asymptomatic or brief upper respiratory tract or gastroenteric infection. In rare cases, other severe sequelae of coxsackievirus B infection develop, including meningitis and carditis.

Pathophysiology

The striated muscle is the actual anatomic structure targeted by the coxsackievirus B and is responsible for the attacks of severe chest pain. Therefore, the term pleurodynia may be a misnomer because only some patients with the condition actually develop pleuritis (ie, inflammation of the pleural surface). In patients with pleurodynia, the striated intercostal muscles necrose, which explains the frequent elevations in serum creatine kinase levels. Some of the more chronic sequelae, such as myocarditis, dermato-polymyositis, chronic fatigue syndrome, and possibly, juvenile-onset diabetes type I, are believed to be immune mediated.

The virus has an incubation time of a week in the gastrointestinal tract and then, through hematogenous dissemination, involves the target organs, most commonly skeletal muscle but also the CNS (ie, meningitis, encephalitis) and myocardium (ie, carditis with or without associated pericarditis). The coxsackievirus B can be recovered in the stool or pharynx for up to 2 weeks after the resolution of the symptoms.

Frequency

United States

Coxsackievirus B was present in 24% of the 18,000 enteroviruses isolated and reported in the United States from 1970-1979. The estimated number of nonpolio enteroviral symptomatic infections is 5-10 million per year.

In regions of temperate climate, the infection is seasonal, with about 90% of infections occurring in the summer and early fall, and sometimes infections occur in epidemics.

The incidence of coxsackievirus B infection in neonates is 1 in 2000 live births.

International

Antibodies to coxsackievirus B serotypes are present in 75% of the population in developed countries. In the tropical and subtropical climate areas, the prevalence of the enteroviral infections is year-round.

Mortality/Morbidity

• The severity of the coxsackievirus B infection is highest in infants and children.
• Of infants who develop coxsackievirus B infection, 10% die, usually within the first 4 weeks of life and most commonly from cardiac involvement. Fulminant hepatic failure, sepsis syndrome, and severe CNS involvement with seizures and apnea are also potential complication in this age group.

Sex

Males are more commonly affected than females.

Age

Coxsackievirus B infection occurs most commonly in children younger than 15 years; half of these patients are younger than 5 years, and 30% are younger than 1 year. The disease is rare in patients older than 60 years. However, pleurodynia most commonly affects adults infected with the virus, with fewer than 10% of cases occurring in patients younger than 20 years. Of the 372 prospectively studied children aged 4-18 years with nonpolio enteroviral infections, only 3% developed pleurodynia. In contrast, 30 of the 78 mainly adult patients with coxsackievirus B–associated cardiac disease had pleurodynia. Therefore, the location of pain is believed to be predominantly thoracic in adults and abdominal in children.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

Onset of chest pain is acute; during attacks, the pain is severe, intense, and excruciating, lasting seconds to a minute. Pain is paroxysmal, occurring in attacks separated by minutes to hours. Severe attacks can result in difficulty breathing. The thoracic pain is usually over the lower ribs and is unilateral, but it can also occur over the front, back, or substernal area. Between attacks, patients usually have a constant, dull, pleuritic chest pain. The attacks usually persist for 3-5 days but rarely last for longer than a month and may go through phases of remission and exacerbation.

• Associated symptoms related to the viral infection may include the following:
• • Upper respiratory tract symptoms, including sore throat, rhinitis, and dry cough
  • Constitutional symptoms, including headaches (50%), fever, and malaise
  • GI symptoms, including nausea, vomiting, diarrhea (50%), and in children, abdominal pain (usually in the epigastric area)
  • Testicular pain (ie, orchitis) in 10% of males

Physical

• Fever (97%) and appropriate heart rate response (ie, tachycardia)
• Respiratory system findings - Pharyngitis (85%), including herpangina, visible splinting of the chest during attacks, localized chest wall tenderness in the same area of pain (25%), and pleural friction rub (25%)
• Other potential signs associated with the coxsackievirus B infection - Otitis (25%) and dermatitis (30%)

Causes

• The classic etiologic agent for pleurodynia is coxsackievirus B, serotypes B1, B2, B3, B4, and B5, which are small, nonenveloped RNA viruses, in which an icosahedral capsid encloses the single-stranded RNA genome.
• Other nonpolio enteroviruses, including echoviruses type 6 and 19, are also reported to cause syndromes very similar to that of coxsackievirus B infection, including pleurodynia.
• Humans are the only known reservoir of the enteroviruses; transmission occurs via the fecal-oral route. The incubation time usually is 2-5 days. Potential risk factors for the transmission of the enteroviruses are poor sanitation and overcrowding. Intrafamilial spread is common.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Pleurisy, viral or idiopathic
Sickle cell crisis
Fractured rib
Mediastinal emphysema
Other tumors of the pleural space, soft tissue sarcoma
Bronchiolitis obliterans with organizing pneumonia (BOOP)
Intercostal neuralgia
Hyperventilation syndrome
Myositis
Drug-induced myalgias (Esomeprazole has recently been involved in a case report of myalgia, cephalgia, and fever.) (Grattagliano, 2005)

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Viral cultures
• • Either primary monkey kidney cells or embryonic lung fibroblasts are the standard cells used for isolation of coxsackievirus B and diagnosis. Adding Buffalo green monkey kidney cells may increase the sensitivity of this method. Viral growth occurs in 1-4 days, causing a cytopathic effect on the host cells, resulting in rounded, refractile cells that eventually lyse. The cultures may be performed from various clinical specimens, dictated by the presence of clinical symptoms.
  • Throat viral cultures are more sensitive than urine viral cultures and confirm 33% of the enteroviral infections studied. Throat culture findings were positive for coxsackievirus B in 45% of the patients presenting with pleurodynia. Blood cultures are useful in children younger than 3 months. Stool cultures have a higher yield than rectal swabs. Having multiple culture specimens may also increase the yield of virus recovery in culture.
  • A positive enteroviral culture result must be interpreted in light of the clinical context and the history of polio immunization. After vaccination with the live attenuated oral polio vaccine, viral culture results from both throat and stool specimens may remain positive for enteroviruses for several months. Similarly, patients with asymptomatic infections may shed the virus for months after they acquire the infection.
• Fluorescent staining and neutralization assays: With specific antibodies, these tests are employed to further confirm and delineate the type of enteroviruses isolated from culture.
• Molecular diagnosis
• • Reverse transcriptase–polymerase chain reaction (RT-PCR) is a promising technique for the detection of viral nucleic acids from specimens with a low viral load, including the cerebrospinal fluid (CSF) and may be associated with false-negative viral cultures.
  • A commercial diagnostic kit has been developed and studied for this indication. In a study of enteroviral infection in a pediatric population, RT-PCR for throat specimens also was more sensitive than viral culture. Additional restriction fragment length polymorphism (RFLP) assay may provide a simple strategy to identify the virus subtype.
• Serologic studies for viral antigen detection: Specific antibodies against enteroviral groups and serotypes are commercially available, but their application has thus far been limited to fluorescent staining and detection of viral antigens in cell cultures, rather than clinical specimens.
• • Enzyme-linked immunosorbent assay (ELISA) is more sensitive than the neutralization test and can be used as a screening tool, followed by the neutralization test for confirmation.
  • ELISA using an enteroviruses group–specific monoclonal antibody may detect early immunoglobulin M (IgM) antibody secreted during coxsackievirus B infection. The test is more sensitive than the neutralization tests and can be used as a screening tool, followed by the neutralization test. The specificity is not extremely high because the antibodies cross-react with other enteroviruses such as hepatitis A virus.
  • The neutralization assay measures the ability of the serum to antagonize the viral infectivity in cell culture. Although the test is expensive and awkward, a more specific finding of a positive ELISA result followed by a negative neutralization test result usually signifies an enteroviral infection other than that caused by coxsackievirus B.
• Complement fixation test: This test is another laborious method of measuring antiviral antibodies used to diagnose coxsackievirus B infection.
• Serum creatine kinase is usually elevated because of muscle necrosis.
• The white cell count ranges from mild leukopenia to mild leukocytosis.
• Although seldom performed for the diagnosis of pleurodynia per se, tissue diagnosis can be made by direct detection of the viral antigen or by isolation of RNA virus–specific sequences.
• Depending on the clinical presentation and suspicion for serositis caused by systemic lupus erythematosus, an antinuclear antibody test can be performed.

Imaging Studies

• Chest radiography
• • A chest radiograph is usually obtained to exclude other causes of chest pain. In pleurodynia, the findings on chest radiography can be normal, or the radiograph may show a small amount of ipsilateral pleural effusion or adjacent atelectasis from splinting.
  • The atelectasis can be linear or in the form of bibasilar consolidation.
  • Infrequently, the coxsackievirus B infection causes pneumonia, with a radiographic pattern of fine perihilar opacities.

Histologic Findings

Necrosis of the striated intercostal muscles is visible. Rarely, adjacent pleural inflammation results in a small exudative pleural effusion.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

No specific treatment exists. Management is supportive and includes nonsteroidal anti-inflammatory drugs (NSAIDs) for pain and pleurisy (if present).

Aspirin should be avoided in children because of the potential to develop Reye syndrome.

Activity

As tolerated

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Nonsteroidal anti-inflammatory drugs and analgesics are used for the symptomatic relief of pleurodynia.

Drug Category: Nonsteroidal anti-inflammatory drugs (NSAIDs)

These agents have analgesic, anti-inflammatory, and antipyretic activities. Their mechanism of action is not known, but it may inhibit cyclooxygenase activity and prostaglandin synthesis. Other mechanisms may exist as well, eg, inhibition of leukotriene synthesis, lysosomal enzyme release, lipoxygenase activity, neutrophil aggregation and various cell membrane functions. They are used for symptomatic relief of pleurodynia.

Drug Name	Ketoprofen (Orudis, Oruvail, Actron)
Description	For relief of mild to moderate pain and inflammation. Small dosages are initially indicated in small and elderly patients and in those with renal or liver disease. Doses of more than 75 mg do not increase therapeutic effects. Administer high doses with caution and closely observe patient for response.
Adult Dose	25-50 mg PO q6-8h prn; not to exceed 300 mg/d
Pediatric Dose	25-50 mg PO q6-8h prn; not to exceed 300 mg/d
Contraindications	Documented hypersensitivity
Interactions	Coadministration with aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; may increase PT when taking anticoagulants (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; phenytoin levels may be increased when administered concurrently
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Category D in third trimester of pregnancy; caution in CHF, hypertension, and decreased renal and hepatic function; caution in anticoagulation abnormalities or during anticoagulant therapy

Drug Name	Naproxen (Naprelan, Naprosyn, Anaprox, Aleve)
Description	For relief of mild to moderate pain; inhibits inflammatory reactions and pain by decreasing activity of cyclooxygenase, which results in a decrease of prostaglandin synthesis.
Adult Dose	500 mg PO followed by 250 mg q6-8h; not to exceed 1.25 g/d
Pediatric Dose	<2 years: Not established >2 years: 2.5 mg/kg/dose PO; not to exceed 10 mg/kg/d
Contraindications	Documented hypersensitivity; peptic ulcer disease; recent GI bleeding or perforation; renal insufficiency
Interactions	Coadministration with aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; may increase PT when taking anticoagulants (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; phenytoin levels may be increased when administered concurrently
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Category D in third trimester of pregnancy; acute renal insufficiency, interstitial nephritis, hyperkalemia, hyponatremia, and renal papillary necrosis may occur; patients with preexisting renal disease or compromised renal perfusion risk acute renal failure; leukopenia occurs rarely, is transient, and usually returns to normal during therapy; persistent leukopenia, granulocytopenia, or thrombocytopenia warrant further evaluation and may require discontinuation of drug

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Outpatient Care

• Patients must receive follow-up care with their primary care providers to ensure that other potential coxsackievirus B–associated complications are diagnosed and managed in a timely manner.

Deterrence/Prevention

• Common hygiene measures aid in the prevention of the oral-fecal transmission of coxsackievirus B. An outbreak of pleurodynia among high school football players was traced to contaminated water; therefore, avoid direct oral contact with common drinking or ice containers in favor of individual water containers and ice packs.
• Coxsackievirus B is a small RNA virus that lacks a lipoprotein envelope, and, hence, may be resistant to physical and chemical inactivation. Good sterilization techniques that include ethylene oxide have been shown to inactivate the virus on electrophysiologic catheters.

Complications

• Direct complications of pleurodynia are rare. Splinting from pain may result in atelectasis and shortness of breath.
• A postviral syndrome, also called fatigue-dysphoria syndrome, is described in children who were seropositive for coxsackievirus B and who complained of fatigue, weakness, sore throats, and dysphoria. This syndrome may also complicate the patient's recovery.
• In rare cases, coxsackievirus B infection may be complicated by carditis, aseptic meningitis, constrictive pericarditis, orchitis, myalgic encephalomyelitis, hemorrhagic conjunctivitis, hepatitis, pancreatitis, and juvenile-onset diabetes mellitus.
• Dilated cardiomyopathy is a complication of viral myocarditis. It may be acute or related to severe muscle necrosis, or it may occur several years later, possibly due to chronic inflammation and fibrosis as a result of an immune-mediated process.

Prognosis

• The prognosis is good, with complete recovery in most cases. The return to normal health may be gradual after a period of weakness and fatigue. No deaths are reported as a direct result of pleurodynia.

Patient Education

• Encourage proper hygiene measures in the patient's household to avoid intrafamilial spread of the virus.
• For excellent patient education resources, visit eMedicine's Lung and Airway Center. Also, see eMedicine's patient education article Chest Pain.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to correctly diagnose life-threatening causes of acute severe onset of chest pain (see Differentials), including pulmonary embolism, myocardial infarction, or aortic dissection
• Failure to provide a thorough clinical evaluation followed by a proper investigative plan, which should (in most cases) aid in the appropriate diagnosis of such disorders

Special Concerns

• Coxsackievirus B may be transmitted to the fetus during pregnancy by transplacental route or during delivery. It may be associated with spontaneous abortions before 12 weeks' gestation. It may also be related to increased incidence of congenital heart defects, and early-onset insulin-dependent diabetes mellitus. Placental infection by the virus may lead to perinatal morbidity and death.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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Article Last Updated: Sep 20, 2006