Clinical presentation uniformly involves the appearance of a rash, but significant differences are exhibited between pathogens:

• Roseola infantum is characterized by sudden appearance of high fever in infants followed by rash after fever completely subsides, usually after a few days [2]. The rash is maculopapular in form and develops on the face and trunk, lasting 24-48 hours [1]. The rash spontaneously resolves, but febrile seizures may be seen in long-term follow-up, which is hypothesized to be caused by HHV-6.
• Rubella infection - After an incubation period of 14-21 days, a scarlatineform maculopapular rash develops accompanied with cervical lymphadenopathy and constitutional symptoms such as fever, malaise, fatigue and joint pain [3]. The rash appears on the trunk and extremities, lasting about 3 days. In children, the disease is self-limiting, but adults may develop more severe forms of infection.
• Measles is one of the most important viral exanthems as it produces a severe systemic illness that may be fatal. Usually, symptoms appear 8-12 days after infection and include very high fever accompanied by cough, coryza and conjuctivitis (3 C's). Symptoms tend to increase in intensity and after a few days, patognomonic Koplik spots appear - lesions found on mucous membranes that precede the appearance of a maculopapular rash [4]. The rash firstly appears behind the ears and then spread on the whole body [1]. Complications may include pneumonia and encephalitis in rare cases.
• Parvovirus B19 manifests with flu-like symptoms seen in other viral exanthems, but the distinguishing feature is the rash that starts on the cheeks approximately 4-14 days after the onset of symptoms [12]. The rash may last up to 3 weeks, but it may not always be present and joint pain may be the only symptom instead [12].
• Chickenpox, caused by VZV, is demarcated by simultaneous appearance of nonspecific symptoms and the characteristic papular, pustular and vesicular rash. A patognomonic feature of chickenpox is the appearance of rash on the scalp, which is not seen in other exanthems.
• Chikungunya virus presents with arthritis, high fever, headache and either a maculopapular or petechial rash that develops in patients that report recent travel to endemic areas.
• Molluscum contagiousum, unlike all other viral exanthems, includes a nodular to pearl-like rash that appear on the trunk and genitalia. Moreover, the incubation period for this virus is 2-8 weeks and a previous history of direct contact with infected persons is usually present.

• Splenomegaly

  Epstein-Barr virus (EBV) can also present as lymph node enlargement, yellow or gray tonsillar pseudomembrane, palatal petechiae, maculopapular or petechial eruption, splenomegaly, and hepatomegaly. [visualdx.com]

  Reserve testing of the hepatitis B surface antigen level for patients with a history of hepatitis B exposure, systemic symptoms (hepatomegaly, splenomegaly, diarrhea), elevated hepatic enzyme levels, or Italian or Japanese heritage. [contemporarypediatrics.com]

  Splenomegaly occurs in approximately 8-50% of patients 45-47 and often is undetected clinically. [ahcmedia.com]

  Splenomegaly occurs in approximately 8-50% of patients45-47 and often is undetected clinically. [reliasmedia.com]

  Splenomegaly is noted on occasion. Arthritis may occur and is more common in adults, especially women. [escholarship.org]

• Fever

  Roseola infantum is caused by human herpesvirus-6 and is distinguished from other viruses by the onset of fever and the rash after fever completely subsides. [symptoma.com]

  Lassa fever, besides constitutional symptoms such as fever, chills, headache and myalgia, can cause generalized petechial eruption and facial edema. [therapeutique-dermatologique.org]

  […] signs/symptoms -HHV6; infants, young kids -------------------------------------- Exanthem subitum (6th disease) -abrupt high fever but child looks well -fever abruptly disappears --> pale pink macular rash -leukopenia and abnormal lymphocytes Coxsackievirus [cram.com]

  […] followed by maculopapular rash in a centrifugal distribution on the second day of fever usually disappearing by the sixth day. [idoj.in]

• Malaise

  Exanthem is the medical name given to a widespread rash that is usually accompanied by systemic symptoms such as fever, malaise and headache. [dermnetnz.org]

  In all cases, a rash that is present all over the body occurs, often accompanied with fever, malaise, fatigue and joint pain. [symptoma.com]

  The prodrome symptoms include fever, cough, headache, malaise, abdominal pain, decreased appetite, muscle aches, joint pain, runny nose, swollen neck glands or eyelids. [niroginepal.com]

• Anemia

  This type of anemia leads to paleness, yellowing of the skin and whites of the eyes (jaundice), dark urine, fatigue, shortness of breath, and a rapid heart rate. [mymemory.translated.net]

  The risk of fetal death is between 2% and 6.5% when infection occurs during pregnancy.  Immunodeficiency • Can cause chronic erythroid hypoplasia with severe anemia  Chronic hemolytic anemias • B19 is the most common cause of transient aplastic crisis [slideshare.net]

  In pregnant women with recent parvovirus B19 infection, weekly (Doppler) ultrasound studies should be performed to exclude fetal anemia and fetal hydrops. [onlinelibrary.wiley.com]

  In the patients with chronic hemolytic anemias, a transient aplastic crisis manifested by anemia, reticulocytopenia, and red-blood-cell aplasia may result. [escholarship.org]

  Most of the time, this is a mild illness, but parvovirus B19 infection may lead to acute severe anemia if you have immune deficiencies or sickle-cell disease. It carries a small risk for fetal death during pregnancy. [healthcare-online.org]

• Pallor

  It is most commonly noted in patients between 4 and 10 years of age and involves a "slapped cheek" appearance of the cheeks with circumoral pallor. After 1-4 days, a lacy reticular eruption on extensor surfaces arises that lasts up to 3 weeks. [visualdx.com]

  In addition to this flushed appearance, there is usually a pale area around his mouth (circumoral pallor). Another finding is dark, hyperpigmented areas on the skin, especially in skin creases. These areas are called Pastia's lines or Pastia's sign. [atsu.edu]

  […] rash that feels like sandpaper As the rash fades peeling affects the fingertips, toes and groin area Distribution Typically the rash first appears on the chest and stomach, rapidly spreading to other parts of the body Flushing of the face and perioral pallor [pcds.org.uk]

  Punctate papular exanthem, cra‐ niocaudal spread, predominantly on joint flexures, perioral pallor 2. [onlinelibrary.wiley.com]

• Constitutional Symptom

  Lassa fever, besides constitutional symptoms such as fever, chills, headache and myalgia, can cause generalized petechial eruption and facial edema. [therapeutique-dermatologique.org]

  Click here to view full-size graphic The eruption resolves spontaneously over three to four weeks with residual desquamation, but may persist for as long as two months.3,4 Pruritus is uncommon.3 Variable constitutional symptoms may accompany Gianotti-Crosti [contemporarypediatrics.com]

  Human immunodeficiency virus (HIV) Early HIV infection may be asymptomatic or present with a variety of non-specific symptoms and signs, including constitutional symptoms, adenopathy, pharyngitis and frequently a rash. [racgp.org.au]

  Rubella infection - After an incubation period of 14-21 days, a scarlatineform maculopapular rash develops accompanied with cervical lymphadenopathy and constitutional symptoms such as fever, malaise, fatigue and joint pain. [symptoma.com]

• Rhinitis

  Condition Incubation period Prodrome Rash Other Dx features Measles (Rubeola) 9-14 days Fever Cough, Conjunctivitis Rhinitis Maculopapular – face to extremities Koplik spots in mouth Mumps (Parotitis) 12-25 days Pain/swelling in front of/below ear Rubella [smartypance.com]

  It is characterised by high fever lasting for 3-5 days, rhinitis, cough, irritability and tiredness. As the fever subsides a mild toxic erythema may appear on the face and trunk and persists for 1 to 3 days. [dermnetnz.org]

  5th disease – Erythema infectiosum 6th disease – Roseola Rubeola (Measles) Things you should know Highly contagious Respiratory droplet transmission I came in to see my physician assistant today because of… Fever greater than 104.0 Cough Runny nose – rhinitis [physicianassistantexamreview.com]

  One girl had history of allergic rhinitis, and another girl had a family history of atopic dermatitis and urticaria. Table. [jamanetwork.com]

  Patients should be asked about pruritus, painful lesions, the initial site of involvement, and any personal or family history of atopy (e.g., asthma, allergic rhinitis, childhood eczema). View/Print Table Table 1. [aafp.org]

• Abdominal Pain

  When to Seek Medical Care See your doctor if you have any of the following: A temperature over 101 degrees that lasts more than a day Severe headache, stiff neck, confusion, unconsciousness, or seizures Diarrhea and/or vomiting and severe abdominal pain [skinsight.com]

  You may have any of the following: Fever and chills A runny or stuffy nose Cough, sore throat, or hoarseness Headache, or pain and pressure around your eyes Muscle aches and joint pain Shortness of breath or wheezing Abdominal pain, cramps, and diarrhea [drugs.com]

• Koplik Spot

  In addition, mucosal patches, known as Koplik spots, are seen in the oral mucosa and are hallmarks of this viral exanthem. [symptoma.com]

  Condition Incubation period Prodrome Rash Other Dx features Measles (Rubeola) 9-14 days Fever Cough, Conjunctivitis Rhinitis Maculopapular – face to extremities Koplik spots in mouth Mumps (Parotitis) 12-25 days Pain/swelling in front of/below ear Rubella [smartypance.com]

  Rubeola (Measles) -general -signs/symptoms -Paramyxovirus; childhood illness -------------------------------------- -contagious 7 days before rash forms -fever, runny nose, conjunctivitis, cough -------------------------------------- Koplik's spots = [cram.com]

  Koplik's spots are ENANTHEMS that are typically found on the buccal and labial mucosa. [quizlet.com]

  These are called Koplik spots. 11 12. Another Example of Koplik Spots 12 13. Case One, Question 1  Based on the history and exam, what is the most likely diagnosis? a. Drug Eruption b. Erythema Infectiosum c. Measles d. Roseola e. Rubella 13 14. [slideshare.net]

• Jaundice

  This type of anemia leads to paleness, yellowing of the skin and whites of the eyes (jaundice), dark urine, fatigue, shortness of breath, and a rapid heart rate. [mymemory.translated.net]

  In Yellow fever, besides an intense jaundice, facial flushing, conjunctival hyperemia and petechiae can be observed. [therapeutique-dermatologique.org]

  Low Days Arthralgia more common than frank arthritis Hepatitis B Moderate Malaise, rash, jaundice Moderate Days/weeks Arthritis is abrupt in onset, in RA distribution preceding icteric phase Hepatitis C Moderate Malaise, jaundice Moderate Weeks, months [racgp.org.au]

  […] symptoms Fever Loss of appetite Sore throat Enlarged lymph nodes Muscle aches Fatigue Diarrhea Ulcers in the digestive tract, possible causing bleeding Hepatitis Encephalitis – inflammation of the brain Behavioral changes Neonatal signs and symptoms Jaundice [physicianassistantexamreview.com]

• Myalgia

  Lassa fever, besides constitutional symptoms such as fever, chills, headache and myalgia, can cause generalized petechial eruption and facial edema. [therapeutique-dermatologique.org]

  [Case Reports] Am J Forensic Med Pathol 2020; 41(1):48-51Reilly JM, Xing W, … Sathyavagiswaran LAJ Chikungunya is a mosquito-transmitted viral illness with clinical hallmarks of rash, fever, arthralgia, and myalgia. [unboundmedicine.com]

  Parlamendi ja nõukogu #. juuni #. aasta direktiiviga #/EÜ finantstagatiskokkulepete kohta, [#] en Common: lethargy dizziness shakiness or tremor nausea diarrhoea vomiting rash or skin eruptions (exanthema) pain in your joints (arthralgia) or muscles (myalgia [et.glosbe.com]

  Other nonspecific symptoms such as vomiting, headache, anorexia, exanthems, and myalgia may be also associated. [radiopaedia.org]

• Skin Rash

  Skin rash on belly. [shutterstock.com]

  Within all the people who go to their doctor with viral exanthem, 97% report having skin rash, 79% report having fever, and 40% report having cough. [symcat.com]

  Introduction An exanthem is any eruptive skin rash that may be associated with fever or other systemic symptoms. Causes include infectious pathogens, medication reactions and, occasionally, a combination of both. [medscape.com]

  A skin rash is an area of skin that has become swollen, inflamed, or irritated. Skin rashes can include skin bumps that look like pimples or sores; blotchy, scaly or red skin; and itchy or burning skin. [everydayhealth.com]

• Ulcer

  Herpangina -kids 3-10 (summertime) -vesicular enanthem on soft palate, tonsillar pillars --> ulcerates (2-6 lesions) [cram.com]

  Notably, very painful, >1 cm genital ulceration can be seen (Lipschütz ulcers) in pre-adolescent females, often with a necrotic appearance and violaceous borders, involving the labia majora, labia minora, or inner thighs. [visualdx.com]

  […] manifestations Heals on its own Coxsackievirus A type 16 Enterovirus 71 macular to vesicular w/ erythematous halo tender, fades w/o pigment vomiting and cns sx (rare) latent in ganglia mucocutaneous "Dewdrop on a rose petal" rapid rupture --> leaves gray-white ulcer [brainscape.com]

  After an incubation period of 3 to 5 days, flat small blisters appear on the hands and feet, and painful ulcers appear in the mouth. There may be a mild fever. Sometimes in young children there is a rash on the buttocks. [dermnetnz.org]

• Fussiness

  Monkey began experiencing a runny nose and mild cough last week, and became especially fussy as the weekend inched closer. [thetightropeblog.wordpress.com]

  Use acetaminophen for fever, fussiness or discomfort. In infants over 6 months of age, you may use ibuprofen instead of acetaminophen. Talk with your child's doctor before giving these medicines if your child has chronic liver or kidney disease. [fairview.org]

  […] the skin Bumps or wheals that appear like “hives,” with a purplish color Aching or swollen joints Red eyes Sores in the mouth, on the tongue, or on the gums A flat red or purplish rash that does not blanch (lose its color) when you press on it Extreme fussiness [kidemergencies.com]

• Seizure

  When to Seek Medical Care See your doctor if you have any of the following: A temperature over 101 degrees that lasts more than a day Severe headache, stiff neck, confusion, unconsciousness, or seizures Diarrhea and/or vomiting and severe abdominal pain [skinsight.com]

  1 dose vaccine greater than 50 yo HHV-6 Acute febrile illness w/ or w/o rash high fever --> rash --> fever resolves rash: neck/trunk --> extremities less than 3 yo: febrile seizures 95% adults ubiquitous assoc w/ Pitryiasis rosea --> Kaposi Sarcoma: vasc [brainscape.com]

• Confusion

  In developed countries where most children have received measles and rubella vaccinations, other viral exanthems are often confused with breakthrough measles or rubella. [cambridge.org]

  The lesions, when purpuric, may occasionally be confused with those of Henoch-Schönlein purpura. [contemporarypediatrics.com]

  When to Seek Medical Care See your doctor if you have any of the following: A temperature over 101 degrees that lasts more than a day Severe headache, stiff neck, confusion, unconsciousness, or seizures Diarrhea and/or vomiting and severe abdominal pain [skinsight.com]

• Febrile Seizures

  1 dose vaccine greater than 50 yo HHV-6 Acute febrile illness w/ or w/o rash high fever --> rash --> fever resolves rash: neck/trunk --> extremities less than 3 yo: febrile seizures 95% adults ubiquitous assoc w/ Pitryiasis rosea --> Kaposi Sarcoma: vasc [brainscape.com]

  The rash spontaneously resolves, but febrile seizures may be seen in long-term follow-up, which is hypothesized to be caused by HHV-6. [symptoma.com]

  Eyelid swelling Irritability Fever (can last three or four days) Abrupt high fever Febrile seizures (this is the most serious risk, particularly if the fever is very high.) Treatment: Treatment aims to reduce symptoms. [healthcare-online.org]

  Because of the high fever, febrile seizures can occur but are not common. Roseola rash. Click image for source. 3. Hand, foot, and mouth disease (HFMD). [thetightropeblog.wordpress.com]

  Roseola is spread via respiratory droplets during the febrile phase of the illness. The incubation period for roseola is approximately 9-10 days after exposure. Febrile seizures/convulstions may occur in 5-15% of infected children. [dermnetnz.org]

To make the diagnosis, specific clinical findings can distinguish between viral pathogens, but they often require additional tests. Serology is a useful method for viruses such as rubella, VZV, parvovirus B19 and measles, while PCR seems to be a superior method that confirms the presence of a viral DNA, but it is not used in the setting of suspected HHV-6 virus and rubella. Molluscum contagious may be diagnosed by clinical findings and subsequent biopsy of the lesion.

• Human Herpesvirus 6

  The first exanthema was caused by the measles virus, the third by the rubella virus, the second and fourth by bacterial toxins, the fifth by parvovirus, and the sixth by human herpesvirus-6 (HHV-6). [cambridge.org]

  […] herpesviruses B10.0 Other human herpesvirus encephalitis B10.01 Human herpesvirus 6 encephalitis B10.09 Other human herpesvirus encephalitis B10.8 Other human herpesvirus infection B10.81 Human herpesvirus 6 infection B10.82 Human herpesvirus 7 infection [icd10data.com]

  Human herpesvirus-6 infection in children. A prospective study of complications and reactivation. N Engl J Med 1994;331:432-8. 10. Abuhammour W, Abdel-Haq N, Asmar B. Picture of the month. Petechial eruption with parvovirus B19 infection. [ijdd.in]

  Measles (rubeola) German measles (rubella) Coxasackieviruses Scarlet fever (S. pyogenes) Herpes simplex (HSV) Erythema infectiosum (Fifth disease, parvovirus B19) Chickenpox (varicella, VZV) Roseola infantum (human herpesvirus 6, HHV6) Maculopapular: [quizlet.com]

• Staphylococcus Aureus

  It was described in 1900 and is postulated to be related to the bacterium Staphylococcus aureus.[9] In 1979 and 2001 a possible "seventh diease" was postulated following reports of a condition in Japan also referred to as acute febrile infantile mucocutaneous [en.wikipedia.org]

  This disease is caused by epidermolytic (exfoliative) toxin-producing strains of Staphylococcus aureus 2,3. However, others believe it to be a misdiagnosis of either scarlet fever or rubella and therefore a nonexistent disease entity 1. [atsu.edu]

  "Fourth disease" is still not widely accepted and is possibly related to the bacterium known as Staphylococcus aureus. 1. [healthcare-online.org]

  Large blisters can also be seen in varicella, often resulting from superinfection with Staphylococcus aureus. Hemorrhagic lesions may occur in patients with thrombocytopenia. Scarring is not unusual in uncomplicated varicella. [plasticsurgerykey.com]

Treatment for the majority of viral exanthems includes supportive measures only. Measles, rubella, Chikungunya, fifth disease and roseola infantum are all treated by fluid administration, antipyretics and analgesics, while severe cases with respiratory symptoms may necessitate assisted ventilation and oxygen therapy. In the case of chickenpox, however, antiviral therapy is available. Acyclovir is considered as a first-line therapy (especially in older children with an increased risk for severe varicella), while valacyclovir and famciclovir are advocated for use in adolescents and young adults [8]. Antiviral therapy has shown to reduce the duration of symptoms as well as the rash, but it is imperative to start treatment within 24h after the onset of rash. Regarding molluscum contagiosum, larger nodules may be surgically handled through either curettage or liquid nitrogen, but these lesions tend to resolve spontaneously in a matter of months.

The prognosis of viral exanthems has significantly improved in the past few decades, primarily due to wide-scale vaccination for rubella, measles and VZV. Other exanthems, such as chikungunya, roseola infantum and parvovirus B19 cause relatively mild and self-limited forms of infection and do not pose a major risk to patients.

There are numerous viral pathogens that can present with a rash [9], but the most significant ones include the five childhood exanthems (rubella, chickenpox, roseola infantum, measles, and parvovirus B19 infection or fifth disease), Chikungunya virus and molluscum contagiosum. Rubella and Chikungunya are single-stranded RNA viruses that share similar morphological characteristics, with one major distinctive feature. Namely, Chikungunya (CKV) is transmitted to humans by aedes mosquitoes, while rubella mandates human-to-human contact [1]. VZV and HHV-6, causes of chickenpox and roseola infantum, respectively, are double-stranded DNA viral pathogens that belong to the group of human herpes viruses, together with Epstein-Barr, herpes simplex 1 and 2 (HSV-1, HSV-2) and Cytomegalovirus (CMV). Parvovirus B19, the causative agent of fifth disease, contains a single-stranded DNA, whereas rubella (also known as German measles) is a single-stranded RNA virus. Significant differences between these pathogens exist in terms of morphology and disease mechanism, but all universally lead to development of a generalized rash, which is why they are classified as viral exanthems [10].

The majority of viral exanthems, apart from CKV, appear in early or late childhood, which is shown to be the single most important risk factor for all diseases. Additionally, the majority of viruses are highly contagious and are transmitted by respiratory route, meaning that crowded places such as kindergartens and schools are often sites of outbreaks. Despite marked reductions in mortality from viral exanthems, some of them are still a significant burden in various parts of the world. Measles virus kills 500,000 unvaccinated children every year and remains one of the most fatal childhood diseases [11]. It is estimated that more than 90% of children contract HHV-6 by the time they reach adulthood, while approximately 65% of the population is infected by parvovirus B19 [1]. Not all individuals, however, develop a symptomatic infection. Additionally, certain populations are shown to be at increased risk due to specific viral characteristics. For example, the only known site of parvovirus B19 replication is the erythroid progenitor and patients with increased hemoglobin degradation, such as hereditary spherocytosis and sickle cell disease are at increased risk for more severe forms of disease [12]. Moreover, molluscum contagiosum is shown to be most prevalent in immunocompromised individuals, such as those suffering from HIV infection, but immunosuppression may also be a precipitating factor in HHV-6 infection, as certain studies have shown its reactivation in the setting of organ transplantation [13]. CKV is restricted to endemic regions where the mosquito vector, aedes sp., is responsible for the transmission. Africa, Asia and the Americas are regions where this virus is encountered [14].

The pathogenesis of almost all viral exanthems, except for CKV, starts with respiratory transmission of the virus and subsequent viral proliferation in the pharynx and the upper respiratory tract. Once the viruses start replicating, variable times are needed to establish a viremia that is high enough to cause symptoms and the appearance of rash. Hence, incubation periods vary from a few days seen in measles to 2-3 weeks seen in rubella infection. At some point, the immune system, specifically the humoral system and antibody production is stimulated, leading to an intense inflammatory reaction that contributes to typical flu-like symptoms and rash, which is thought to be a result of viral and T-cell interaction.

Vaccination has revolutionized the battle against the majority of viral exanthems. Measles and rubella, together with mumps virus, constitute the measles-mumps-rubella (MMR) vaccine that proves to be virtually 100% effective, while VZV vaccination is also being conducted. Currently, no specific measures exist for fifth disease, roseola infantum, molluscum contagiousm and Chikungunya virus, but early recognition may be vital in reducing the risk for complications [15].

The appearance of a generalized rash that can occur due to bacterial, autoimmune, iatrogenic and viral causes is known as an exanthem. In the pediatric population, five viral exanthems are recognized [1]:

• Roseola infantum (known as exanthem subitum) is caused by human herpesvirus type 6 (HHV-6) [2], a virus that establishes an infection during early life by replicating in the salivary glands and lymphocytes. It is characterized by a sudden onset of high fever followed by a maculopapular rash that resolves within 24 to 48 hours. Additionally, HHV-6 is hypothesized to be one one of the most important factors in the pathogenesis of febrile seizures in infants.
• Rubella (German measles), an RNA virus belonging to the group of Togaviridae, causes a mild benign illness in infants after 7 days of infection, with the appearance of a scarlatineform maculopapular rash that lasts for about 3 days [3].
• Measles, caused by measles virus that belongs to Paramyxoviridae, was one of the most lethal diseases prior to introduction of vaccines and is one of the most contagious viral exanthems. After an incubation period of 8-12 days, very high fever appears together with cough, coryza and conjuctivitis (3 C's), soon followed by erythematous patches that initially develop retroauricularly [4]. In addition, mucosal patches, known as Koplik spots, are seen in the oral mucosa and are hallmarks of this viral exanthem.
• Chickenpox (or varicella) is caused by the Varicella zoster virus (VZV) and is one of the most common viral exanthems encountered in medical practice. Typical presentation involves a benign, self-limited generalized rash consisting of either oval or round macules, papules and vesicles that appear 1-2 days after infection [5]. Varicella is the only exanthem that presents with a rash on the scalp, in addition to the trunk and the extremities and this is deemed as one of its main distinguishing features.
• Erythema infectiosum (also known as fifth disease, named because of its discover after the previous four exanthems) is caused by a single-stranded DNA human parvovirus B19 that colonizes the upper respiratory tract. As a result of extensive viremia, flulike symptoms appear after a prodromal period of 4-14 days and are followed by a maculopapular rash that develops on the cheeks and spreads to the extremities.

In addition to these five common exanthems, two less frequent viral exanthems exist: The Chikungunya virus (belonging to the same group of viruses as rubella) is a mosquito-transmitted infection characterized by fever and rash that is restricted to tropical parts of the world, while molluscum contagiosum, which causes papular and nodular lesions, is associated with sexually active individuals [6] [7]. Rare causes include Epstein-Barr virus (as a part of infectious mononucleosis) and Coxsackie A virus. To differentiate between various viral pathogens in the diagnostic workup, advanced clinical experience is necessary to recognize distinguishing features. In addition, some viruses may be detected by serology and polymerase chain reaction (PCR), a procedure that detects viral DNA in patient samples. Treatment primarily focuses on symptomatic measures, except in the case of chickenpox, when acyclovir can be effectively used [8]. Because of significant advances in immunization, the burden of viral exanthems has significantly decreased in the past several decades, but deaths from these pathogens are still seen all over the world, particularly in poorly developed countries where vaccination is not readily conducted.

Viral exanthem is a term that demarcates a viral infection that has rash in its clinical presentation and several viruses are included in this group. There are five main childhood exanthems - Measles, roseola infantum, chickenpox, rubella and parvovirus B19 (fifth disease). Additionally, various other viral pathogens can cause a rash, such as Chikungunya virus (CKV), primarily seen in tropical regions due to its transmission by mosquitos, Epstein-Barr virus (EBV), the causative agent of infectious mononucleosis can present with a rash in rare cases and Molluscum contagiosum, which is seen mainly in immunocompromised patients. The pathogenesis of all viruses, except CKV, starts with transmission of the virus by either respiratory or direct route from an infected host, after which viral replication in the upper respiratory tract occurs. Once the virus establishes an infection, various symptoms appear as a result of immune system interaction with the virus. In all cases, a rash that is present all over the body occurs, often accompanied with fever, malaise, fatigue and joint pain. There are subtle, but very important differences in the appearance of rash across viral exanthems and may turn out to be the key finding that can help the physician to make the diagnosis. Measles is caused by the measles virus and can lead to very dangerous infections characterized by very high fever, a rash that starts behind the ears and patches in the oral mucosa, known as Koplik spots. Roseola infantum is caused by human herpesvirus-6 and is distinguished from other viruses by the onset of fever and the rash after fever completely subsides. Chickenpox is caused by Varicella zoster virus and it is one of the most common viral infections that present with a rash in childhood. The main feature is the distribution of rash on the scalp, in addition to the extremities and the trunk. On the other hand, the rash seen in Molluscum contagiosum primarily involves the genitalia, as risky sexual contact is the main risk factor. Fifth disease (caused by Parvovirus B19) produces a rash that involves the cheeks, in addition to fever and malaise. Rubella virus usually has a long period of symptoms such as fever, enlarged lymph nodes and joint pain before the onset of rash. These signs, together with laboratory studies that are available for some viruses, should be definite tools for making the diagnosis. Antibodies can be detected against varicella, measles, parvovirus and rubella, but the diagnosis mainly rests on clinical criteria. Treatment, apart form acyclovir against chickenpox, include supportive measures, as there is no therapy for the remaining viral exanthems. Fortunately, the majority of viral exanthems have a mild and benign clinical course. Measles, however, may cause severe complications, such as pneumonia and encephalitis. Much has been done in terms of prevention in the past several decades through the introduction of vaccination, as global incidence rates for several viral exanthems have dropped by almost 95%. But there are still areas of the world where vaccination is not being carried out and these pathogens present one of the most important causes of childhood death.

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