Bornholm disease

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Arooj Naz, M.B.B.S

Bornholm disease or epidemic pleurodynia or epidemic myalgia is a disease caused by the Coxsackie B virus or other viruses.The lining around the lungs is called the pleura. Pleurodynia is a general term for pain from this lining, pain in the chest or upper abdomen when the patient breathes. Epidemic pleurodynia is an infection caused by one of several viruses. This type of infection can cause a similar type of pain as the pain that comes from the lining around the lungs. However, in epidemic pleurodynia, the pain comes from the muscles in the chest that join ribs together. Up until 1949, the underlying cause of the disease was undetermined.

In 1872, Daae-Finsen reported an epidemic of “acute muscular rheumatism” occurring in a community called Bamble, giving rise to the name “Bamble disease” in Norway. Subsequent reports, published only in Norwegian, referred to the disease by this name. In 1933, Ejnar Sylvest gave a doctoral thesis describing a Danish outbreak of this disease on Bornholm Island entitled, “Bornholm disease-myalgia epidemica”, and this name has persisted. Bornholm disease is named after the Danish island Bornholm where early cases occurred. Some notable outbreaks include those that occurred in Ohio (1936), Oxford (1951), Toronto (1958), and Singapore (1974). It is interesting to note that although the epidemics occurred individual of one another and were disperesed over time and geographical location, the disease pattern and seasonal factors were found to be similar in many cases.

Bornholm disease is a disease caused by one of the group B coxsackie viruses and is less often caused by a group A coxsackie virus or an echovirus, causing pain in the muscles of the chest that join ribs together. The virus is spread by contact and epidemics usually occur during warm weather in temperate regions and at any time in the tropics, primarily through  saliva and feces. From within the pharynx, the viruse multiplies in the throat and intestines, the muscles of the chest wall, abdominal muscles and diaphragm after which it enters the lymphatic tissues. The virus uses autophagy to increase viral replication.

Bornholm disease is often due to either the Coxsackie virus or echovirus. The most prevalent strains include Coxsackievirus B, especially B3 and B4, and Coxsackievirus A, including types 4, 6, 9 and 10. Echovirus types 1, 6, 8, 9 and 19 have also been implicated in some cases. Generally, Coxsackievirus B virus is more prevalent in regards to respiratory complaints compared to Coxsackievirus A strains. The clinical spectrum varies depending on age groups for the Coxsackievirus A and B strains of the virus. Although severe progression of the disease is rare, it has been associated in particular with the Coxsackievirus B3 virus.

Bornholm Disease has been referred to by various different names, some of which include Devil’s Grip, epidemic pleurodynia and epidemic myalgia, to name a few. Apart from the plethora of names presenting possible difficulty in its recognition, it is often a diagnosis that is not part of the initial differential diagnosis’ when a patient presents with chest pain. Because of the possibility of life-threatening conditions presenting with similar pain, it often requires extensive workup to exclude other diseases in medical settings. Conditions that should be rules out include Acute Coronary syndromes (ACS), Aortic dissection/ Ruptured aortic aneurysm, Pulmonary embolism, Tension pneumothorax, Pneumonia, Pleurisy/ Pleuritis, Acute appendicitis, Pancreatitis, Cholecystitis, Costochondritis, and Guillain-Barré Syndrome.

Up to 90% of epidemics occur in the summer and early fall. The illness most commonly strikes people younger than age 30, although older people also may be affected. According to the CDC, strains of the Coxsackie B4 virus were responsible for 1.9% of all enterovirus infections combined, which was equivalent to at least 54 cases in the United States alone. Bornholm disease is seemingly responsible for 20%-40% of all non-cardiac chest pain. Various paediatric studies done at the Chang Gung Memorial Hospital spanning from 2004-2012 found that of a total of 386 cases studied, 158 were due to the Coxsackie A4 virus, 145 were attributable to the Coxsackie B3 virus and only 83 were found to have been due to the Coxsackie B4 virus.

According to the U.S. Preventive Service Task Force (USPSTF), there is currently insufficient evidence to screen for Bornholm disease. Viral disease can be supported with physical examinations and laboratory findings.

Patients experience sudden chest pain that is often described as a sharp, cutting or knife-like sensation as well as a fever that often lasts about 4 to 7 day. Recovery is gradual and may take up-to 10 days with relapses being a common finding but the disease is rarely fatal. Complications are unlikely, but affect children more commonly. These include acute viral meningitis, orchitis, hepatic necrosisand coagulopathy, Pericarditis and disseminated intravascular coagulopathy, amongst others. The prognosis is generally very good, requiring symptomatic treatment for pain and bed rest. In cases including orchitis, suspensory bandages may prove useful.

The most common presenting symptoms include fever, which affects 70% of patients, which may last 4-7 days.The fever may be associated with headaches. Approximately 40% of patients experience severe, acute chest pain that is described as an iron grip around the rib cage and gives rise to the term referred to as ‘The Devil’s grip’. Poor oral intake, weakness and muscular fatigue are also commonly found. Although patients recover quickly, relapse is common.

Physical findings may vary amongst patients and may also vary according to the the underlying cause. If the disease is due to the Coxsackie virus, findings such as oral ulcerations, throat discomfort or pain, diarrhea as well as vomiting may be seen. For patients experiencing localized chest tenderness, abdominal rigidity and guarding may present difficulty performing a complete physical examination. The pain may result in tachycardia. Pulmonary symptoms include pleural effusion, cough, rhinorrhea and difficulty breathing. Fever may present with headaches and potentially progress to febrile seizures.

In many cases of Bornholm disease, Inflammatory biomarkers such as Erythrocyte sedimentation rate, C-reactive proteinand Creatine Kinase are found to be elevated. Changes in CBC have been found to vary according to the underlying causative strain. Although leukocytosis is a common finding, infection with the A4 strains can result in white cell counts ≥15000/µL. Comparatively, the Coxsackie B3 has been found to cause anemia and thrombocytopenia. Live function testsincluding AST and ALT may be elevated but changes in electrolytes have not been observed. In the event of respiratory or cardiac complications developing, Arterial Blood Gas and Pulse oximetry may be altered.

Due to the classic cardiac pain, patients presenting with Bornholm disease often have an ECG done to rule out life threatening diseases, such as myocardial infarction. Findings often include non-specific ECG findings may be seen; this includes T wave inversions that often resolve with resolution of the disease and MI can be ruled out due to the absence of ST changes.

In cases of Bornholm Disease, chest x-ray findings may be visible in the form of pulmonary infiltrates; such findings have been consistent in almost half of all cases. Some uncommon findings include patch consolidationand pleural effusions.

Bornholm disease is also referred to as epidemic myalgia. Muscle involvement may be visible on MRI, often as a patchy distribution of thickened fascia and hyper intense muscles.

Diagnostic findings are limited for Bornholm disease and, because it mimics classic chest pain, extensive testing is often done to rule out cardiac conditions. Other diagnostic studied include stool, blood and throat samples. All of these have been found to contain traces of causative virus strain. In fact, they have also been found in sewage and flies. MRI can reveal changes in the muscle and fascia. Normal nerve conduction studies may be used to differentiate the disease from Guillain-Barré syndrome.

Treatment includes the administration of nonsteroidal anti-inflammatory agents or the application of heat to the affected muscles. In healthy people, pleurodynia is a harmless infection that goes away on its own within a few days. To treat the muscle pain, your doctor probably will recommend over-the-counter pain relievers. If necessary narcotic pain medication can be used. Aspirin should not be given to children with pleurodynia because of the risk of Reye’s syndrome, a serious reaction causing brain and liver injury in children who take aspirin during certain viral illnesses.

As the disease is often self-limited and treated medically, surgical interventions are not required. Surgical intervention may be considered in the case of myocarditis if the patient is unresponsive to all other medical treatments and continues to deteriorate.

The goal of Primary prevention is to prevent the occurrence of an illness or a disease before it ever occurs. The viruses that cause epidemic pleurodynia can spread very easily among young children, who tend to put toys or fingers into their mouth. The disease is most likely to spread in day care centers. The best way to prevent infection is to wash hands thoroughly, especially before meals or after changing a diaper or using the bathroom. There is no vaccine to prevent pleurodynia.

Secondary prevention occurs once the disease has developed and aims to prevent progression and development of further complications. Viral meningitis can be prevented by strict isolation, frequent hand washing and appropriate hand hygiene especially after using the bathroom. The development of orchitis may be prevented by surgical correction of underlying UTI’s. Hepatitis is avoidable by the use of vaccines and safe eating habits. Pericarditis can be prevented by the concomitant use of aspirin and colchicine. Respiratory distress can be prevented by controlling various properties, including the tidal volume, PEEP, FiO2, and reducing the risk of aspiration by elevating the head end of bed and maintaining oral hygiene.

As the treatment is primarily symptomatic and can be controlled with NSAIDs, the treatment is relatively affordable. Because of their low cost, NSAIDs are amongst the most popular and effective drugs in controlling inflammatory induced pain. An average bottle of ibuprofen containing 30 tablets can be purchased for less than $14 in the United Sates.

The prevention of Bornholm disease focuses on preventing infections with Coxsackie virus, as it is the most common underlying cause. The Coxsackie virus can  persist for prolonged durations. The Coxsackie virus is an RNA virus that is non-enveloped, positive single stranded and has the ability to form an envelope by taking over host membranes which provides resistance. The relationship between Coxsackie viral infections and chronic disease is also of interest, especially autoimmune conditions. These include chronic myocarditis, diabetes and chronic inflammatory myopathy. Apart from studying the relationship between coxsackie virus and chronic conditions, the effects in utero are also being studied. Neonates may present with fetal myocarditis and neurodevelopmental delays, possibly due to meningitis and encephalitis.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Arooj Naz, M.B.B.S

Bornholm disease is named after the Danish island Bornholm where early cases occurred. Initially, the underlying cause of cases could not be identified but, in 1949, the Coxsackie virus was identified in many patients.

• In 1872, Daae-Finsen reported an epidemic of “acute muscular rheumatism” occurring in a community called Bamble, giving rise to the name “Bamble disease” in Norway.
• Subsequent reports, published only in Norwegian, referred to the disease by this name.
• In 1933, Ejnar Sylvest gave a doctoral thesis describing a Danish outbreak of this disease on Bornholm Island entitled, “Bornholm disease-myalgia epidemica”, and this name has persisted.
• In many early cases of the disease, there was no identifiable pathogen associated with it.
• It was in 1949 when the cases were thought to have been caused by the Coxsackie virus, particularly Coxsackievirus B3 and Coxsackievirus A9 strains, and, less frequently, an association with echovirus types 1, 6, 8, 9 and 19.
• Upon further investigation, attack rates were found to be higher amongst close contacts and family members, this may be attributable to viruses entering via the pharynx, proliferating in the lymphatic tissues and progressing to the muscles via the bloodstream.^[1]
• Clinically, patients often present with vague chest pain.^[2] Some notable outbreaks include Singapore (1974)^[3] and Toronto (1958-1959).^[4]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Arooj Naz, M.B.B.S

Bornholm disease is a disease caused by one of the group B coxsackie viruses and is less often caused by a group A coxsackie virus or an echovirus, causing pain in the muscles of the chest that join ribs together. The virus is spread by contact and epidemics usually occur during warm weather in temperate regions and at any time in the tropics, primarily through saliva and feces. From within the pharynx, the viruse multiplies in the throat and intestines, the muscles of the chest wall, abdominal muscles and diaphragm after which it enters the lymphatic tissues. The virus uses autophagy to increase viral replication.

Group B coxsackie viruses are transmitted from person to person by fecal-oral contamination, direct mouth-to-mouth contact or via droplet infection. ^[1] Other people become infected with the virus if they touch contaminated items then put their fingers in their mouth before washing them properly. Contaminated items can include soiled diapers, shared toys and toilets. Epidemic pleurodynia is contagious and occurs in clusters, meaning many people in an area get it around the same time.

The virus that causes devil’s grip is a picornavirus. It is spread by contact and epidemics usually occur during warm weather in temperate regions and at any time in the tropics. It can also be spread through saliva and feces.^[2] Once inside the body via the pharynx, the coxsackie viruses multiplies in the throat and intestines as well as within the muscles of the chest wall, abdominal muscles and diaphragm after which it enters the lymphatic tissues ^[3] and subsequently spreads into the bloodstream. At this point, the body’s immune defences often can limit the infection and prevent the person from developing symptoms. If the immune defences are less successful, the person starts developing symptoms.

Once viral cells are within host cells, it uses autophagy to increase viral replication. Reduced immunity in children may help explain the disease susceptibility in younger children.^[4]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Arooj Naz, M.B.B.S

Bornholm disease usually is caused by one of the group B coxsackie viruses and is less often caused by a group A coxsackie virus or an echovirus. The most prevalent Coxsackievirus virus strains included B3 and B4 followed by A4, A6, A9, and A10.

Bornholm disease is often due to either the Coxsackie virus or echovirus. The most prevalent strains include:

• Coxsackievirus B (CBV) types B3 and B4
• Coxsackievirus A (CAV) types 4, 6, 9 and 10
• Echovirus types 1, 6, 8, 9 and 19
• Although less common, there have been some cases associated with Human parechovirus type 3 (HPeV3)^[1]

Generally, Coxsackievirus B virus presents with more severe respiratory complaints compared to Coxsackievirus A strains. Apart from respiratory symptoms, the Coxsackievirus B virus has also presented with cases of aseptic meningitis, pericarditis, and orchitis as well as herpangina and tonsillitis/pharyngitis. The CB4 strain has also been associated with herpangina in children.^[2] The CB5 strains have been found to be particularly associated with myocarditis and pericarditis.^[3] The clinical spectrum varies depending on age groups for the Coxsackievirus A and B strains of the virus. Although severe progression of the disease is rare, it has been associated in particular with the Coxsackievirus B3 virus.^[4]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Arooj Naz, M.B.B.S

Bornholm Disease has been referred to by various different names, some of which include Devil’s Grip, epidemic pleurodynia and epidemic myalgia, to name a few. Apart from the plethora of names presenting possible difficulty in its recognition, it is often a diagnosis that is not part of the initial differential diagnosis’ when a patient presents with chest pain. Because of the possibility of life-threatening conditions presenting with similar pain, it often requires extensive workup to exclude other diseases in medical settings.

Bornholm disease presents with acute chest and or abdominal pain and requires a high degree of suspicion for diagnosis. The disease presents with a. clinical syndrome that can appear to mimic inflammation or injury of any organ within the thorax or abdomen and thus requires differentiation.^[1]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Arooj Naz, M.B.B.S

Up to 90% of epidemics occur in the summer and early fall. The illness most commonly strikes people younger than age 30, although older people also may be affected.

According to the CDC, strains of the Coxsackie B4 virus were responsible for 1.9% of all enterovirus infections combined, which was equivalent to at least 54 cases in the United States alone. Bornholm disease is seemingly responsible for 20%-40% of all non-cardiac chest pain; these statistics have been found to be similar in various countries, including Germany, USA, China, and Australia.^[1] Throughout history, there have been numerous epidemics of Bornholm disease, and it can be presumed that there were many other outbreaks that were not documented or remained unclassified as the cause of the disease was unknown till the 1950’s. Several prominent outbreaks that were documented include:

• 19th Century: Iceland and Norway^[2]
• 1888: United States of America^[3]

• 1936: Cincinnati, Ohio^[4]
• 1944: South-Pacific Islands^[5]
• 1950: Hoquiam, Washington State (50 cases within one month and a morbidity rate of about 5 per 1,000 population)^[6]
• 1951: Oxford (a total of 277 cases studied between the months of April and November; began abruptly)^[7]
• 1951: South-east Scotland^[8]
• 1958-1959: Toronto (strains of Coxsackie B5 virus isolated)^[9][10]
• 1974: Singapore (patients were further studied in groups of “typical Bornholm disease” and “atypical Bornholm disease”; the typical group included those with positive Coxsackie B3 virus)^[11]

Southeast Asia has reported fewer cases of Bornholm disease comparatively but a retrospective study performed at the National Taiwan University Hospital in 2005 yielded informative material. This included statistics such as:^[12]

• Chest wall pain and tenderness present in 14% of the patients studied
• 75% cases experiencing pleuritic chest pain
• Radiological evidence in the form of pulmonary infiltrates or pleural effusions found in 45% of the cases
• Uncommon findings included tonsillar exudates and urinary tract infection

Various paediatric studies done at the Chang Gung Memorial Hospital spanning from 2004-2012 found that of a total of 386 cases studied, 158 were due to the Coxsackie A4 virus, 145 were attributable to the Coxsackie B3 virus and only 83 were found to have been due to the Coxsackie B4 virus. ^[13]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Arooj Naz, M.B.B.S

Bornholm disease is often present in the summertime, therefore it is helpful to be aware of it during this time. The demographic most at risk of exposure includes children attending day-care centers and those under the age of 10 years old. Care should be taken to reduce exposure to already infected patients, and isolation is advised. Poor hand hygiene before meals and after using the bathroom may lead to a viral auto-infection. The virus can be shed in the stool for up to 6 weeks.

The incidence for Bornholm disease can be exacerbated with certain exposures and unhygienic practice. To prevent contracting the disease, it may be helpful to avoid any risk factors that predispose a patient to Coxsackie virus strains. The disease is common in children under the age of 10 during the summertime. Early recognition among children that may be at risk can help reduce the risk of complications. ^[1]Some risk factors include:)^[2]

• Exposure while in day-care centers through sharing toys with other children
• Close contact with already infected patients
• Poor hand hygiene before meals and after using the bathroom that may lead to a viral auto-infection (virus can be shed in the stool for uptown 6 weeks)

In some cases, the presence of other concomitant conditions can result in increased predisposition to disease. These include:

• Infections in children younger than one year
• Prolonged duration of fever (greater than 3 days)

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Arooj Naz, M.B.B.S

According to the U.S. Preventive Service Task Force (USPSTF), there is currently insufficient evidence to screen for Bornholm disease.

• According to the U.S. Preventive Service Task Force (USPSTF), there is currently insufficient evidence to screen for Bornholm disease.
• Viral disease can be supported with physical examinations and laboratory findings.

Template:WH Template:WS

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Arooj Naz, M.B.B.S

Patients experience sudden chest pain that is often described as a sharp, cutting or knife-like sensation as well as a fever that often lasts about 4 to 7 day. Recovery is gradual and may take up-to 10 days with relapses being a common finding but the disease is rarely fatal. Complications are unlikely, but affect children more commonly. These include acute viral meningitis, orchitis, hepatic necrosis and coagulopathy, Pericarditis and disseminated intravascular coagulopathy, amongst others. The prognosis is generally very good, requiring symptomatic treatment for pain and bed rest. In cases including orchitis, suspensory bandages may prove useful.

The chest pain associated with Bornholm disease often lasts about 4 to 7 days.The duration of disease often correlates with the duration of fever.^[1] Affected induviduals often experience a short prodromal period of generalized malaise that precedes the occurrence of chest pain, which is described as a sharp, cutting or knife-like sensation.^[2] Although the disease is rarely fatal, the chest pain persists. During recovery, the patient may experience weakness and recover gradually over a period of 10 days. Relapses during the weeks following the initial episode are a characteristic feature of this disease.

About 5% of people develop complications. These include:

• Acute viral meningitis as a complication of the coxsackievirus infection
• Adult males may develop orchitis

Less common complications include: ^[3]

• Hepatitis; HNC: Hepatic Necrosis and coagulopathy
• Pericarditis
• Myocarditis
• Disseminated Intravascular Coagulopathy (DIC)
• Respiratory distress ^[4]
• Benign lymphocytic meningitis ^[5]

Clinical studies have shown that children affected with the Coxsackie B3 strain had the highest rate of complication, approximately 9.2%. The most common complication complications included DIC followed by respiratory distress, shock and hepatic necrosis.^[6]

An unlikely complication included meningeal involvement, this was noted in an outbreak that occurred in Sweden with less than 10% of patients being affected.^[7]

The prognosis is very good as the disease often results in complete recovery with mostly supportive care.^[3]

• For male patients that experienced orchitis, treatment focused on bed rest as well as the use of suspensory bandages.^[8]

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