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Viral Exanthem

Viral Exanthemata

Viral exanthem is a term describing a viral infection that presents with a rash. Roseola infantum, rubella, parvovirus B19 (known as fifth disease), measles and varicella are five pediatric viral exanthems, while Chikungunya and molluscum contagiosum are other notable exanthems seen in adults. The rash may be macular, papular, vesicular or pustular and the diagnosis is made based on clinical criteria and laboratory studies. Treatment mainly involves symptomatic measures.


Presentation

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.
Fever
  • All cases showed gradual resolution of fever, rash and eventual normalisation of liver function test. A high index of suspicion was required before this uncommon syndrome can be recognised.[ncbi.nlm.nih.gov]
  • Roseola This viral exanthem is contagious and leads to rash and high fever, with the rash developing while the fever decreases.[healthcare-online.org]
  • (see Fever and children, below) Rapid breathing.[fairview.org]
  • Mother reports child has had a fever for 3 days as high as 103.1F PO. She has been giving Tylenol and Ibuprofen for fever but he appeared well and was eating and playing normally, so mother was not alarmed.[prezi.com]
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]
  • Learning objectives Be able to identify common specific viral exanthems Introduction An exanthem is a widespread erythematous rash that is accompanied by systemic symptoms such as fever , headache and malaise .[dermnetnz.org]
  • 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]
  • […] in Dermatology at the Lister Hospital, Stevenage, Hertfordshire and also the driving force behind the PCDS educational programme Introduction An exanthem is a rash, usually of viral origin, accompanied by systemic symptoms such as fever, headache and malaise[pcds.org.uk]
  • Following the incubation period of 3-6 days, a prodrome may occur with fever, malaise, cough, anorexia, and abdominal pain.[ahcmedia.com]
Exanthema
  • A little baby body cover with roseola infantum, exanthema subitum, sixth disease. human herpesvirus type 6(HHV6), human herpesvirus type 7 (HHV7).[shutterstock.com]
  • (see also Keratitis) 370.40 in exanthema (see also Exanthem) 057.9 [ 370.44 ][medicalcodesets.org]
  • exanthema can be misdiagnosed by a doctor.[hbj.sg]
  • Read on to know what is Viral exanthema and also find out about its causes, symptoms, diagnosis and treatment.[primehealthchannel.com]
Febrile Convulsions
  • Roseola - Wikipedia In rare cases, this can cause febrile convulsions (also known as febrile seizures or "fever fits") due to the sudden rise in body temperature, but in many cases the child appears normal.[bloginfinitylifestyle.xyz]

Workup

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.

Pyuria
  • . 69,80,82,88,102,105 Solomon and his co-workers 105 reported elevations in 37 of 43 cases, with 5 having values greater than 50 mm. per minute.Urinary abnormalities were noted in several reports. 69,82,105 In Boston 105 only 11 patients with slight pyuria[nejm.org]

Treatment

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.

Prognosis

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.

Etiology

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].

Epidemiology

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].

Sex distribution
Age distribution

Pathophysiology

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.

Prevention

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].

Summary

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.

Patient Information

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.

References

Article

  1. Murray PR, Rosenthal KS, Pfaller MA. Medical Microbiology. Seventh edition. Philadelphia: Elsevier/Saunders; 2013.
  2. Stone RC, Micali GA, Schwartz RA. Roseola infantum and its causal human herpesviruses. Int J Dermatol. 2014;53(4):397-403.
  3. Edlich RF, Winters KL, Long WB 3rd, Gubler KD. Rubella and congenital rubella (German measles). J Long Term Eff Med Implants. 2005;15(3):319-328.
  4. Perry RT, Halsey NA. The clinical significance of measles: a review. J Infect Dis. 2004;189(1):S4-16.
  5. Gershon AA, Gershon MD. Pathogenesis and Current Approaches to Control of Varicella-Zoster Virus Infections. Clinical Microbiology Reviews. 2013;26(4):728-743.
  6. Lo Presti A, Lai A, Cella E, Zehender G, Ciccozzi M. Chikungunya virus, epidemiology, clinics and phylogenesis: A review. Asian Pac J Trop Med. 2014;7(12):925-932.
  7. Chen X, Anstey AV, Bugert JJ. Molluscum contagiosum virus infection. Lancet Infect Dis. 2013;13(10):877-888.
  8. Gilbert DN, Chambers HF, Eliopoulos GN, Saag MS. The Sanford Guide to Antimicrobial Therapy 2015. 45th ed. Antimicrobial Therapy, Inc, Sperryville, VA; 2015.
  9. Carneiro SC, Cestari T, Allen SH, Ramos e-Silva M. Viral exanthems in the tropics. Clin Dermatol. 2007;25(2):212-220.
  10. Porter RS, Kaplan JL. Merck Manual of Diagnosis and Therapy. 19th Edition. Merck Sharp & Dohme Corp. Whitehouse Station, N.J; 2011.
  11. Salavastru CM, Stanciu AM, Fritz K, Tiplica GS. A burst in the incidence of viral exanthems. Indian Dermatology Online Journal. 2014;5(2):144-147.
  12. Weir E. Parvovirus B19 infection: fifth disease and more. CMAJ : Canadian Medical Association Journal. 2005;172(6):743.
  13. Mandell GL, Bennett JE, Dolin R. Mandel, Douglas and Bennett's Principles and Practice of Infectious Diseases. 8th ed. Philadelphia, Pennsylvania: Churchill Livingstone; 2015.
  14. Wertheim HFL, Horby P, Woodall JP. Atlas of Human Infectious Diseases. First edition. Blackwell Publishing, Oxford, UK; 2012.
  15. Nelson JS, Stone MS. Update on selected viral exanthems. Curr Opin Pediatr. 2000;12(4):359-364.

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Last updated: 2018-06-22 11:04