Pleurodynia

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Background

Pleurodynia is an uncommon complication of coxsackievirus B infection. However, cases of pleurodynia secondary to other enteroviruses have been reported (eg, cytopathogenic human orphan [ECHO] virus). Pleurodynia is defined as the sudden occurrence of lancinating chest pain or abdominal 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.[1]

Also see the article Coxsackieviruses.

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

Epidemiology

Frequency

United States

Coxsackievirus B was present in 24% of the 18,000 enteroviruses isolated and reported in the United States from 1970-1979.[2] 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. In infants who develop coxsackievirus B infection, 10% die, usually within the first 4 weeks of life most commonly from cardiac involvement. Fulminant hepatic failure, sepsis syndrome, and severe CNS involvement with seizures and apnea are also potential complications in this age group.[3]

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 mostly 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.

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 eMedicineHealth's Lung Disease and Respiratory Health Center. 

History

Pleurodynia should be considered in all cases of acute and subacute chest pain that present in the ER or in internal medicine, cardiology, or cardiothoracic surgery outpatient clinics. The 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 and rarely last longer than a month and may go through phases of remission and exacerbation.

Associated symptoms related to the viral infection may include the following:

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, coxsackievirus A, and human parechovirus type 3 (HPeV3),[4] 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 is usually 2-5 days. Potential risk factors for the transmission of the enteroviruses are poor sanitation and overcrowding. Intrafamilial spread is common.

Laboratory Studies

Coxsackie B virus infection can be diagnosed by isolation of the virus in cell culture, detection of virus RNA via polymerase chain reaction (PCR) or serologic evaluation of viral antibodies.[5]

Imaging Studies

Chest radiography

Histologic Findings

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

Medical Care

No specific treatment exists. Management is supportive and includes nonsteroidal anti-inflammatory drugs (NSAIDs) for pain and pleurisy (if present) or peripheral nerve block (eg, intercostal nerve) with 1% lidocaine (Xylocaine) infusion.

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

Several experimental antiviral treatments have been tested in animal models, as follows:

Pregnancy considerations

Coxsackievirus B may be transmitted to the fetus during pregnancy by transplacental route or during delivery. During pregnancy, the outcomes of coxsackievirus B infection depend on the timing of infection during the age of gestation. Two independent studies reported higher prevalence of coxsackievirus B infection in women experiencing a miscarriage than in women delivering at term or receiving a voluntary termination before 13 weeks gestation. IgM antibody against coxsackie virus B1-5 or semi-nested RT-PCR positive for coxsackievirus B3 in the placental tissue were significantly higher, by 42% and 57.1%, respectively, than in women in the control group.[22, 23] It may also be related to increased incidence of congenital heart defects, and early-onset insulin-dependent diabetes mellitus. 

Transmission of ECHO virus to neonates has also been reported during delivery, by an orofecal route. Similarly to coxsackievirus B, it may cause severe systemic infection in the neonate, such as aseptic meningitis, hepatitis, gastroenteritis, and viral pneumonitis.[24]

Activity

Activity is as tolerated.

Complications

Direct complications of pleurodynia are rare.

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.[28]

Coxsackievirus B is a small RNA virus that lacks a lipoprotein envelope and, hence, may be resistant to physical and chemical inactivation, including 70% alcohol or 1% quaternary ammonium compounds. Sodium hypochlorite at a concentration of 3120 ppm, at a contact time of 5 minutes, was sufficient to completely inactivate different Enterovirus strains.[29]  Good sterilization techniques that include ethylene oxide have been shown to inactivate the virus on electrophysiologic catheters.[30]

Long-Term Monitoring

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.

Medication Summary

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

Ibuprofen (Motrin, Advil)

Clinical Context:  Exerts anti-inflammatory effect via inhibition of cyclooxygenase, resulting in decreased formation of prostaglandins and thromboxanes from arachidonic acid. Also may inhibit synthesis and/or actions of other local inflammatory mediators and leukocyte migration. Analgesic effect is thought to result from the drug's action on peripheral pain impulse transmission and on pain receptor modulation.

Ketoprofen (Orudis, Oruvail, Actron)

Clinical Context:  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.

Naproxen (Naprelan, Naprosyn, Anaprox, Aleve)

Clinical Context:  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.

Class Summary

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.[31]

Author

Irina Petrache, MD, Professor, Department of Medicine, Wollowick Chair in COPD Research, Chief, Division of Pulmonary, Critical Care, and Sleep Medicine, National Jewish Health

Disclosure: Nothing to disclose.

Coauthor(s)

Karina A Serban, MD, Assistant Professor of Medicine, Department of Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, National Jewish Health

Disclosure: Nothing to disclose.

Specialty Editors

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Zab Mosenifar, MD, FACP, FCCP, Geri and Richard Brawerman Chair in Pulmonary and Critical Care Medicine, Professor and Executive Vice Chairman, Department of Medicine, Medical Director, Women's Guild Lung Institute, Cedars Sinai Medical Center, University of California, Los Angeles, David Geffen School of Medicine

Disclosure: Nothing to disclose.

Additional Contributors

Helen M Hollingsworth, MD, Director, Adult Asthma and Allergy Services, Associate Professor, Department of Internal Medicine, Division of Pulmonary and Critical Care, Boston Medical Center

Disclosure: Nothing to disclose.

Acknowledgements

Gregg T Anders, DO Medical Director, Great Plains Regional Medical Command , Brooke Army Medical Center; Clinical Associate Professor, Department of Internal Medicine, Division of Pulmonary Disease, University of Texas Health Science Center at San Antonio

Disclosure: Nothing to disclose.

Ninotchka Liban Sigua, MD Fellow, Department of Pulmonary and Critical Care, Indiana University School of Medicine

Disclosure: Nothing to disclose.

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