Coxsackie virus

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

Coxsackie Virus
Overview
Classification Coxsackie A virus Coxsackie B virus Coxsackie B4 virus
Differential Diagnosis

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)

Classification

Coxsackie viruses consist of coxsackie A virus and coxsackie B virus. Coxsackie B virus has 6 serotypes, one of the significant serotypes is called coxsackie B4 virus.

Differential Diagnosis

Coxsackie A virus and coxsackie B virus can cause multiple diseases in humans. The wide array of diseases caused by coxsackie viruses can be differentiated from one another easily on the basis of involvement of the organs systems, clinical presentation and diagnostic techniques.

Virus Type	Disease	Clinical Features	Diagnosis	Image
Coxscakie A virus	Hand foot and mouth disease	Fever Headache Loss of appetite Maculopapular or vesicular rash with very small blisters on hands, feet, and diaper area; may be tender or painful if pressed Sore throat Ulcers in the throat (including tonsils), mouth, and tongue	Throat and lesion swabs Tzanck test
	Acute hemorrhagic conjunctivitis	Rapidly progressive Infection starts ipsilaterally, but rapidly involves the fellow eye within 1 or 2 days Eyelids swelling Tearing Eye redness Severe eye pain Purulent discharge Subconjunctival hemorrhage	Positive conjunctival scraping for polymerase chain reaction (PCR) Positive viral culture of corneal epithelial cells for HSV
	Herpangina	Sudden fever Sore throat and dysphagia- May occur up to 24 hours before the appearance of the xanthem Vomiting Abdominal pain Myalgia Headache Pharyngeal lesions	Primarily clinical Pharyngeal viral cultures may be helpful Approximately 1 week after infection, type-specific antibodies appear in the blood
	Aseptic Meningitis	Headache Nuchal rigidity Fever Altered mental status	Clinical Lumbar puncture CSF analysis CT rarely
Coxsackie B virus	Pericarditis	Chest pain that radiates to the back, relieved by sitting up and leaning forward and is worsened by lying down. Deep inspiration and cough can increase the pain. Cough (either dry or productive) Fever Fatigue Anxiety Breathlessness	Clinical EKG Cardiac biomarkers Creatine kinase Cardiac troponin-I (cTnI) Serum LDH , serum myoglobin and SGOT (AST) Echocardiography and Percardiocentesis
	Myocarditis	Chest pain often described as stabbing, pleuritic or sharp in character Swelling of the feet Breathlessness Dyspnea on exertion Orthopnea Palpitations Syncope in setting of high grade AV block Fever (especially when infectious, e.g. in rheumatic fever) Joint pains Fatigue Cyanosis	Clinical Markers of Myonecrosis Creatine kinase (CK-MB) Cardiac troponin I (cTnI) or T (cTnT) are elevated more frequently than CK-MB (34-53% versus 2-6 %) as reported in two series. Lactate dehydrogenase (LDH) Alanine transaminase (ALT) Aspartate transaminase (AST)	Viral myocarditis
	Pericardial effusion	Chest pain Dyspnea Nonspecific chest discomfort	Clinical Thoracic X-ray showing the presence of an enlarged cardiac silhouette with clear lungs CT scan
	Pleurodynia	Fever Headache Attacks of severe pain in the lower chest, often on one side Pleuritic pain with the slightest movement of the rib cage Dyspnea Very few have classic muscle pain in the chest and upper abdomen May be accompanied by a panic attack	Clinical CXR
	Hepatitis	Abdominal pain or distention Gynecomastia Dark urine and pale or clay-colored stools Fatigue Fever, usually low-grade General itching Jaundice (yellowing of the skin or eyes) Loss of appetite Nausea and vomiting Weight loss	Liver function tests
	Sjogren's syndrome	Dry eyes Dry mouth Xerosis Raynaud phenomenon and vasculitis Joint and muscle abnormalities Interstitial lung disease Gastrointestinal manifestations CNS involvement	Clinical Autoantibodies Anti-Ro/SSA and anti-La/SSB antibodies Anti-centromere antibodies

Coxsackie virus oral lesions must be differentiated from other mouth lesions such as oral candidiasis and aphthous ulcer

Oral Involvement

Coxsackie virus infection must be differentiated from other diseases presenting with pain and blistering within the mouth such as gingivostomatitis and glossitis.

Disease	Presentation	Risk Factors	Diagnosis	Affected Organ Systems	Important features	Picture
Diseases predominantly affecting the oral cavity
Oral Candidiasis	Dysphagia or odynophagia White patches on the mouth and tongue	Newborn babies Denture users Poorly controlled diabetes As a side effect of medication, most commonly having taken antibiotics. Inhaled corticosteroids for the treatment of lung conditions (e.g, asthma or COPD) may also result in oral candidiasis which may be reduced by regularly rinsing the mouth with water after taking the medication. People with poor nutrition, specifically vitamin A, iron and folate deficiencies. People with an immune deficiency (e.g. as a result of AIDS/HIV or chemotherapy treatment). Women undergoing hormonal changes, like pregnancy or those on birth control pills. Organ transplantation patients	Clinical diagnosis Confirmatory tests rarely needed	Localized candidiasis Oral and esophageal candidasis Candida vulvovaginitis Chronic mucocutaneous candidiasis Invasive candidasis Candidaemia Candida endocarditis Candida osteoarticular disease	Oral candidiaisis is a benign self limiting disease unless accompanied by immunosuppression.	Tongue infected with oral candidiasis - By James Heilman, MD - Own work, CC BY-SA 3.0, httpscommons.wikimedia.orgwindex.phpcurid=11717223.jpg
Herpes simplex oral lesions	Fever Sore throat Painful ulcers	Stress Recent URTI Female sex	Physical examination Viral culture Tzanck smear	Orofacial Infection Anogenital Infection Ocular Infection Herpes Encephalitis Neonatal Herpes Herpetic Whitlow Herpes Gladiatorum	The symptoms of primary HSV infection generally resolve within two weeks	Oral herpes simplex infection - By James Heilman, MD - Own work, CC BY-SA 3.0, httpscommons.wikimedia.orgwindex.phpcurid=19051042.jpg
Aphthous ulcers	Painful, red spot or bump that develops into an open ulcer	Being a female Between the ages of 10-40 Family history of aphthous ulcers	Physical examination Diagnosis of exclusion	Oral cavity	Self-limiting , Pain decreases in 7 to 10 days, with complete healing in 1 to 3 weeks	By Ebarruda - Own work, CC BY-SA 3.0, httpscommons.wikimedia.orgwindex.phpcurid=7903358
Squamous cell carcinoma	Non healing ulcer, nodule, indurated plaque or mass May involve skin, lips, inside the mouth, throat or esophagus	Chronic sun or UV exposure Fair skin Elderly age (>45 yrs) Male sex Smoking	Physical exam Biopsy	Oral Cavity Floor of mouth Lateral tongue Throat Esophagus	Malignant Can spread to TMJ Some times associated with leukoplakia	Squamous cell carcinoma - By Luca Pastore, Maria Luisa Fiorella, Raffaele Fiorella, Lorenzo Lo Muzio - http://www.plosmedicine.org/article/showImageLarge.action?uri=info%3Adoi%2F10.1371%2Fjournal.pmed.0050212.g001, CC BY 2.5, https://commons.wikimedia.org/w/index.php?curid=15252632
Leukoplakia	White leathery spots on the mucous membranes of the tongue and inside of the mouth Lateral borders of tongue	Atypical Tobacco use Chronic irritation Immunodeficiency Bloodroot (sanguinaria)	Physical exam Diagnosis of exclusion Biopsy	Vulvar lesions occur independent of oral lesions	Associated with HIV Persistant white spots Benign but can progress to carcinoma after almost 10 years Oral proliferative verrucous leukoplakia is an aggressive sub type with multiple lesions and higher conversion to warts or carcinoma	Leukoplakia - By Aitor III - Own work, Public Domain, https://commons.wikimedia.org/w/index.php?curid=9873087
Melanoma	A lesion with ABCD Asymmetry Border irregularity Color variation Diameter changes Bleeding from the lesion	UV radiations Genetic predisposition Old age Male gender Family or personal history of melanoma Multiple benign or atypical nevi	ABCD characteristics Bleeding or ulceration may show malignancy Serum LDH may be elevated in case of malignancy Biopsy	Can metastasize All UV radiation or sun exposed areas can be effected independently 1-2 to hundreds of granules	Neural crest cell derivative Development begins with disruption of nevus growth control Progression involves MAPK/ERK pathway N-RAS or BRAF oncogene also involved	Oral melanoma - By Emmanouil K Symvoulakis, Dionysios E Kyrmizakis, Emmanouil I Drivas, Anastassios V Koutsopoulos, Stylianos G Malandrakis, Charalambos E Skoulakis and John G Bizakis - Symvoulakis et al. Head & Face Medicine 2006 2:7 doi:10.1186/1746-160X-2-7 (Open Access), [1], CC BY-SA 2.0, https://commons.wikimedia.org/w/index.php?curid=9839811
Fordyce spots	Rice-like granules or spots Small, painless, raised, pale, red or white 1 to 3 mm in diameter	Greasy skin types Some rheumatic disorders Hereditary nonpolyposis colorectal cancer Lower gingiva (gums) Vestibular mucosa	Physical exam Small keratin-filled pseudocysts May be seen on incidental mucosal biopsy Biopsy not done for them primarily	Oral cavity Vermilion border of the lips Oral mucosa of the upper lip Buccal mucosa in the commissural region often bilaterally Genitals	Benign neoplasms with sebaceous features Visible sebaceous glands No surrounding mucosal change Several adjacent glands may coalesce into a larger cauliflower-like cluster	Fordyce spots - Por Perene - Obra do próprio, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=19772899
Burning mouth syndrome	Burning or tingling on the lips, tongue, or entire mouth	Nutritional deficiencies Chronic anxiety or depression Diabetes type 2 Menopause Oral thrush or dry mouth, or damaged nerves transmitting taste Female gender Menopause	Presentation Physical exam	Oral cavity	Pain typically is low in the morning and builds up over the day Low dosages of benzodiazepines, tricyclic antidepressants or anticonvulsants may be effective
Torus palatinus	Bony growth on midline of the hard palate Nodular mass covered with normal mucosa	Genetic predisposition Autosomal dominant	Physical exam Types Flat tori Spindle tori Nodular tori Lobular tori	Hard palate	More common in Asian and Inuit populations Twice more common in females Repeated trauma can cause bleeding Surgery may be required in symptomatic	Torus palatinus - By Photo taken by dozenist, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=846591
Diseases involving oral cavity and other organ systems
Behcet's disease	Painful mouth sores Acne like skin lesions Headache, fever, poor balance, disorientation Abdominal pain, diarrhea or bleeding Uveitis Joint swelling and joint pain Genital sores wit pain and scaring Aneurysms	Over active immune system	Physical examination	Mouth Genitals GIT Eye Joints Skin Vascular system Brain	Outbreaks of exaggerated inflammation Affects smaller blood vessels	Behcet's disease - By Ahmet Altiner MD, Rajni Mandal MD - http://dermatology.cdlib.org/1611/articles/18_2009-10-20/2.jpg, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=17863021
Crohn's disease	Chronic, episodic diarrhea or constipation Abdominal pain Vomiting Weight loss or weight gain	Smoking Whites and European Jews Hormonal contraception Diets high in microparticles, sweet, fatty or refined foods Industrialized country	Typical history and symptoms Skip lesions on biopsy Anti-Saccharomyces cerevisiae antibodies (ASCA) Anti-neutrophil cytoplasmic antibodies (ANCA)	Eyes Joints Skin	May lead to Obstructions Abscesses Free perforation Hemorrhage
Agranulocytosis	Fever or chills Frequent infections Unusual redness, pain, or swelling around a wound Mouth ulcers Abdominal pain Burning sensation when urinating Sore throat	Medications Cytotoxic chemotherapy Hematologic malignancies Autoimmune disorders	Neutropenia <100 cells per micro litre Eosinopenia Basopenia	Oral cavity Skin GIT Urinary system Conjunctiva	Immunocompromization Types Drug-induced Malignant Autoimmune
Syphilis	Chancre Regional lymphadenopathy	Multiple sexual partners Illicit drug use Unprotected sex Men who have sex with men Residence in highly prevalent areas HIV infection Presence of other STIs Previous history of STIs Intravenous drug use	Darkfield microscopy Non treponemal tests like VDRL and RPR test) Treponemal testsFTA-ABS tests, (TP-PA) assay, enzyme immunoassays, and chemiluminescence immunoassays)	Oral cavity Penis Cervix Labia Anal canal Rectum CNS CVS	Primary syphilis Chancre Secondary syphilis Condylomata lata Latent syphilis Asymptomatic Tertiary syphilis Gummas Neurosyphilis	oral syphilis - By CDC/Susan Lindsley - http://phil.cdc.gov/phil_images/20021114/34/PHIL_2385_lores.jpg, Public Domain, https://commons.wikimedia.org/w/index.php?curid=2134349
Coxsackie virus	Fever Sores in the mouth Rash with blisters Aches	Pregnancy immunodeficiency	History and Physical exam Throat swabs Swabs from the lesion Tzanck test	Oral cavity Skin	Symptomatic treatment
Chicken pox	Conjunctival symptoms Catarrhal symptoms Characteristic spots on the trunk appearing in two or three waves Itching	Pregnancy Premature infants born to susceptible mothers All infants born at less than 28 weeks gestation or who weigh =1000 grams Immunocompromised	History and physical exam PCR to detect VZV in skin lesions (vesicles, scabs, maculopapular lesions)	Oral cavity Skin	Sodium bicarbonate in baths or antihistamines for itching Paracetamol (acetaminophen) for fever Prednisolone is contraindicated	Chickenpox - By James Heilman, MD - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=52872565
Measles	Fever Rash Cough Coryza (runny nose) Conjunctivitis (pink eye) Malaise Koplick spots in mouth	Unvaccinated individuals Crowded and/or unsanitary conditions Traveling to less developed and developing countries Immunocompromized Winter and spring seasons Born after 1956 and never fully vaccinated Health care workers	History and examination PCR for Measles-specific IgM antibody PCR for Measles RNA	Oral cavity Skin Respiratory tract Eyes Throat	Caused by Morbillivirus Primary site of infection is the respiratory epithelium of the nasopharynx Transmitted in respiratory secretions, via aerosol droplets containing virus particles	Koplick spots (Measles) - By CDC - http://phil.cdc.gov/PHIL_Images/20040908/4f54ee8f0e5f49f58aaa30c1bc6413ba/6111_lores.jpg, Public Domain, https://commons.wikimedia.org/w/index.php?curid=824483