Coxsackie A virus

style="background:#Template:Taxobox colour;"|Coxsackie A virus
style="background:#Template:Taxobox colour;" | Virus classification
Group: Group IV ((+)ssRNA) Family: Picornaviridae Genus: Enterovirus Species: Human enterovirus A
Subtype
Coxsackie A virus

Template:Search infobox Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Usama Talib, BSc, MD [2]

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Overview

Coxsackie (virus) is a cytolytic virus of the picornaviridae family, an enterovirus (a group containing the polioviruses, coxsackieviruses, and echoviruses). There are 61 non-polio enteroviruses that can cause disease in humans, of which 23 are coxsackie A viruses (6 are coxsackie B viruses). Enterovirus are the second most common viral infectious agents in humans (after the rhinoviruses).

Historical Perspective

The coxsackie viruses were discovered in 1948-49 by Gilbert Dalldorf, a scientist working at the New York State Department of Health in Albany, New York. Dr. Dalldorf, in collaboration with Grace Sickles, had been searching for a cure for the dreaded disease polio. Earlier, Dalldorf had worked on monkeys suggesting that fluid collected from a non-polio virus preparation could protect against the crippling effects of polio. Using newborn mice as a vehicle, Dalldorf attempted to isolate such protective viruses from the feces of polio patients. In carrying out these experiments, he discovered viruses that often mimicked mild or nonparalytic polio. The virus family he discovered was eventually given the name coxsackie, for the town of Coxsackie, New York, a small town on the Hudson River where Dalldorf had obtained the first fecal specimens.

The Coxsackie viruses subsequently were found to cause a variety of infections, including epidemic pleurodynia (Bornholm disease), and were subdivided into groups A and B based on their pathology in newborn mice. (Coxsackie A virus causes paralysis and death of the mice, with extensive skeletal muscle necrosis; Coxsackie B causes less severe infection in the mice, but with damage to more organ systems, such as heart, brain, liver, pancreas, and skeletal muscles.)

The use of suckling mice was not Dalldorf's idea, but was brought to his attention in a paper written by Danish scientists Orskov and Andersen in 1947, who were using such mice to study a mouse virus. The discovery of the Coxsackie viruses stimulated many virologists to use this system and ultimately resulted in the isolation of a large number of so-called enteric viruses from the gastrointestinal tract that were unrelated to poliovirus, and some of which were oncogenic (cancer-causing).

The discovery of the Coxsackie viruses yielded further evidence that viruses can sometimes interfere with each other's growth and replication within a host animal. Other researchers found that this interference can be mediated by a substance produced by the host animal, a protein now known as interferon. Interferon has since become prominent in the treatment of a variety of cancers and infectious diseases.

Lately, in the media, there have been many cases of children dying in third world countries from Hand Foot and Mouth disease. Even in the US there have been cases of children dying from this.

Selected papers:

• 1948 An unidentified, filtrable agent isolated from the feces of children with paralysis. Science 108:61-62.
• 1949 A virus recovered from the feces of "poliomyelitis" patients pathogenic for suckling mice. J. Exp. Med. 89:567-82. With G. M. Sickles. Serologic differences among strains of the Coxsackie group of viruses. Proc. Soc. Exp. Biol. Med. 72:30-31. The Coxsackie group of viruses. Science 110:594.
• 1951 With R. Gifford. Clinical and epidemiologic observations of Coxsackie virus infection. N. Engl. J. Med. 244:868-73. The sparing effect of Coxsackie virus infection on experimental poliomyelitis. J. Exp. Med. 94:65-71.
• 1952 With R. Gifford. Adaptation of group B Coxsackie virus to adult mouse pancreas. J. Exp. Med. 96:491-97.
• 1954 With R. Gifford. Susceptibility of gravid mice to Coxsackie virus infection. J. Exp. Med. 99:21-27.
• 1955 With R. Gifford. The recognition of mouse ectromelia. Proc. Soc. Exp. Biol. Med. 88:290-92. With R. Albrecht. Chronologic association of poliomyelitis and Coxsackie virus infections. Proc. Natl. Acad. Sci. USA 41:978-82.
• 1956 With S. Kelly. Antigenic potency of poliovirus vaccines. Am. J. Hyg. 64:243-58.
• 1957 The neuropathogenicity of group A Coxsackie viruses. J. Exp. Med. 106:69-76.

Diseases

The most well known Coxsackie A disease is hand, foot and mouth disease (unrelated to foot and mouth disease), a common childhood illness, often produced by Coxsackie A16. In most cases infection is asymptomatic or causes only mild symptoms. In others, infection produces short-lived (7-10 days) fever and painful blisters in the mouth (a condition known as herpangina), on the palms and fingers of the hand, or on the soles of the feet. There can also be blisters in the throat, or on or above the tonsils. Adults can also be affected. The rash, which can appear several days after high temperature and painful sore throat, can be itchy and painful, especially on the hands/fingers and bottom of feet.

Other diseases include acute hemorrhagic conjunctivitis (A24 specifically), herpangina, and aseptic meningitis (both Coxsackie A and B viruses).

Coxsackie B viruses also cause infectious myocarditis, infectious pericarditis, and pleurodynia.

Differentiating Coxsackie A virus disease from other diseases

Different rash-like conditions can be confused with Coxsackie A virus and are thus included in its differential diagnosis. The various conditions that should be differentiated from Coxsackie A virus include:

Disease	Features
Impetigo	It commonly presents with pimple-like lesions surrounded by erythematous skin. Lesions are pustules, filled with pus, which then break down over 4-6 days and form a thick crust. It's often associated with insect bites, cuts, and other forms of trauma to the skin.
Insect bites	The insect injects formic acid, which can cause an immediate skin reaction often resulting in a rash and swelling in the injured area, often with formation of vesicles.
Kawasaki disease	Commonly presents with high and persistent fever, red mucous membranes in mouth, "strawberry tongue", swollen lymph nodes and skin rash in early disease, with peeling off of the skin of the hands, feet and genital area.
Measles	Commonly presents with high fever, coryza and conjunctivitis, with observation of oral mucosal lesions (Koplik's spots), followed by widespread skin rash.
Monkeypox	The presentation is similar to smallpox, although it is often a milder form, with fever, headache, myalgia, back pain, swollen lymph nodes, a general feeling of discomfort, and exhaustion. Within 1 to 3 days (sometimes longer) after the appearance of fever, the patient develops a papular rash, often first on the face. The lesions usually develop through several stages before crusting and falling off.
Rubella	Commonly presents with a facial rash which then spreads to the trunk and limbs, fading after 3 days, low grade fever, swollen glands, joint pains, headache and conjunctivitis. The rash disappears after a few days with no staining or peeling of the skin. Forchheimer's sign occurs in 20% of cases, and is characterized by small, red papules on the area of the soft palate.
Atypical measles	The symptoms commonly begin about 7-14 days after infection and present as fever, cough, coryza and conjunctivitis. Observation of Koplik's spots is also a characteristic finding in measles.
Coxsackievirus	The most commonly caused disease is the Coxsackie A disease, presenting as hand, foot and mouth disease. It may be asymptomatic or cause mild symptoms, or it may produce fever and painful blisters in the mouth (herpangina), on the palms and fingers of the hand, or on the soles of the feet. There can also be blisters in the throat or above the tonsils. Adults can also be affected. The rash, which can appear several days after high temperature and painful sore throat, can be itchy and painful, especially on the hands/fingers and bottom of feet.
Acne	It is typical of teenagers, usually appears on the face and upper neck, but the chest, back and shoulders may have acne as well. The upper arms can also have acne, but lesions found there are often keratosis pilaris, not acne. The typical acne lesions are comedones and inflammatory papules, pustules, and nodules. Some of the large nodules were previously called "cysts"
Syphilis	It commonly presents with gneralized systemic symptoms such as malaise, fatigue, headache and fever. Skin eruptions may be subtle and asymptomatic It is classically described as: Non-pruritic bilateral symmetrical mucocutaneous rash Non-tender regional lymphadenopathy Condylomata lata and Patchy alopecia.
Molluscum contagiosum	The lesions are commonly flesh-colored, dome-shaped, and pearly in appearance. They are often 1-5 millimeters in diameter, with a dimpled center. Generally not painful, but they may itch or become irritated. Picking or scratching the lesions may lead to further infection or scarring. In about 10% of the cases, eczema develops around the lesions. They may occasionally be complicated by secondary bacterial infections.
Mononucleosis	Common symptoms include low-grade fever without chills, sore throat, white patches on tonsils and back of the throat, muscle weakness and sometime extreme fatigue, tender lymphadenopathy, petechial hemorrhage and skin rash.
Toxic erythema	It is a common rash in infants, with clustered and vesicular appearance.
Rat-bite fever	It commonly presents with fever, chills, open sore at the site of the bite and rash, which may show red or purple plaques.
Parvovirus B19	The rash of fifth disease is typically described as "slapped cheeks," with erythema across the cheeks and sparing the nasolabial folds, forehead, and mouth.
Cytomegalovirus	The common symptoms include sore throat, swollen lymph nodes, fever, headache, fatigue, weakness, muscle pain and loss of appetite.
Scarlet fever	It commonly includes fever, punctate red macules on the hard and soft palate and uvula (Forchheimer's spots), bright red tongue with a "strawberry" appearance, sore throat and headache and lymphadenopathy.
Rocky Mountain spotted fever	The symptoms may include maculopapular rash, petechial rash, abdominal pain and joint pain.
Stevens-Johnson syndrome	The symptoms may include fever, sore throat and fatigue. Commonly presents ulcers and other lesions in the mucous membranes, almost always in the mouth and lips but also in the genital and anal regions. Those in the mouth are usually extremely painful and reduce the patient's ability to eat or drink. Conjunctivitis of the eyes occurs in about 30% of children. A rash of round lesions about an inch across, may arise on the face, trunk, arms and legs, and soles of the feet, but usually not on the scalp.
Varicella-zoster virus	It commonly starts as a painful rash on one side of the face or body. The rash forms blisters that typically scab over in 7-10 days and clears up within 2-4 weeks.
Chickenpox	It commonly starts with conjunctival and catarrhal symptoms and then characteristic spots appearing in two or three waves, mainly on the body and head, rather than the hands, becoming itchy raw pox (small open sores which heal mostly without scarring). Touching the fluid from a chickenpox blister can also spread the disease.
Meningococcemia	It commonly presents with rash, petechiae, headache, confusion, and stiff neck, high fever, mental status changes, nausea and vomiting.
Rickettsial pox	The first symptom is commonly a bump formed by a mite-bite, eventually resulting in a black, crusty scab. Many of the symptoms are flu-like including fever, chills, weakness and muscle pain but the most distinctive symptom is the rash that breaks out, spanning the person's entire body.
Meningitis	It commonly presents with headache, nuchal rigidity, fever, petechiae and altered mental status.

Treatment

Treatment is dependent on the disease process initiated by the virus.

Related Chapters

• Bornholm disease
• Coxsackie B