Synonyms of fifth disease: Erythema infectiosum, fifth’s disease, slapped cheek syndrome, erythema contagiosum, örtliche Rötheln, Megalerythema epidemicum, Mégalérythème épidémique, megalerythema epidemicum, exanthema variable, erythema simplex marginatum, erythema infantimi febrile, epidemische kinderrotlauf.
History of the numbered diseases
In 1900, Clement Dukes (1845-1925) attempted to number the paediatric exanthems to help differentiate the variably described and inaccurately labelled rashes of childhood. He noted sub-groups of these rashes and divided them based on clinical presentation into: measles (first), scarlet fever (second), rubella (third), and Filatov-Dukes (fourth). In 1905, Léon Cheinisse added erythema infectiosum (fifth), and in 1910 John Zahorsky added roseola infantum (sixth).
Overview of fifth disease
Erythema infectiosum (fifth disease), is a common manifestation of infection in children characterized by low-grade fever, malaise, facial rash, and later by the spread of a lacy maculopapular rash involving the trunk and limbs. The rash normally disappears within 1 week, although recrudescence can occur for several months after emotional or physical stress or exposure to sunlight or heat.
Caused by an Parvovirus (erythrovirus) B19, or EVB19, a single-stranded DNA virus targetting red cells in the bone marrow. It spreads via respiratory droplets, and has an incubation period of 7–10 days
Around 75% of children (50% of adults) who are infected develop the characteristic rash.
Three phases to rash (often overlapping)
- Facial erythema (‘slapped cheek’). Red papules on the cheeks which coalesce within hours to form a red, slightly oedematous, warm area, symmetric on both cheeks but sparing the bridge of the nose and the region around the mouth. The rash fades in about 4 days.
- Body rash resembles a ‘net’ or ‘lace’. Unique pattern and usually begins on the arms and legs around 2 days after the facial rash. The rash then extends to the trunk and buttocks and fades in 6-14 days.
- Rash Recurrence(s) usually occur of the following 2-3 weeks, or several months, and are often triggered by temperature changes, emotional upsets or sunlight. Eventually the rash fades without scaling or pigmentation
Parvovirus B19 (B19V) is a small non-enveloped single-stranded DNA (ssDNA) virus of the family Parvoviridae, the subfamily Parvovirinae, the genus Erythrovirus and Human parvovirus B19 type species. It is a common community-acquired respiratory pathogen
B19V infection is associated with a wide spectrum of clinical manifestations ranging from benign to life-threatening depending on the age, haematologic status, and immunologic status of the host.
- Polyarthropathy in infected adults
- Transient aplastic crisis is of particular concern in patients with either decreased red blood cell production or increased turnover (e.g. hereditary spherocytosis, autoimmune haemolytic anaemia, sickle cell disease)
- In pregnancy can cause foetal anaemia, non-immune foetal hydrops, spontaneous abortion and may lead to intrauterine death.
- Papular-purpuric gloves and socks syndrome (PPGSS) is an uncommon but distinctive viral rash in teenagers and young adults. It is characterised by painful redness and swelling of the feet and hands and most often caused by parvovirus B19.
- Cases of immune thrombocytopenic purpura, Henoch-Schönlein Purpura and haemophagocytic syndrome have been attributed to parvovirus B19. However, transient erythroblastopaenia of childhood and true aplastic anaemia are not associated with infection.
There is no specific treatment. Affected children may remain at school, as the infectious stage occurs before the rash is evident.
- Red blood cell transfusions and immunoglobulin therapy can be successful in chronic parvovirus infection or during an aplastic crisis.
- Hydrops fetalis due to parvovirus infection is treated by intrauterine transfusion.
History of fifth disease
1886 – Anton Tschamer reported from Graz an epidemic of thirtycases of an eruptive disease which he differentiated from typical rubella, but considered a modified form he called örtliche Rötheln. The appearance over the cheeks, eruption on the outer surface of the arms, absence over the neck and trunk, and duration of the eruption puzzled him. He recognized he was dealing with a very different type of eruption from rötheln, but came to the conclusion that his cases were an abortive form of German measles.
1896 – Adolf Tobeitz (1873-1938) read a paper “Zur Polymorphie und Differential der Rubella” before the 11th International Medical Congress in Moscow. He reported similar cases to Tschamer which showed “a distinct departure from the general course of rubella“. Theodor Escherich (1857-1911), in the discussion following Tobeitz’s paper, made the first claim that this form of eruption was not identical with rötheln, but was a disease sui generis.
1899 – Georg Sticker (1860-1960) first provided the name erythema infectiosum in his paper Die neue Kinderseuche in der Umgebung von Giessen. Escherich accepted the term provided by Sticker whilst studying the disease closely through two epidemics in Graz in 1897 and 1899. Adolf Schmid, one of his Escherich’s assistants, published a full description of the disease and its essential characteristics in 121 cases.
1900 – Clement Dukes numbered the paediatric exanthems to differentiate the variably described and inaccurately labelled rashes of childhood. He divided them based on clinical presentation into: rubeola (first), scarlet fever (second), rubella (third), and Filatov-Dukes (fourth).
1905 – Henry Larned Keith Shaw (1873-1941) aroused American interest and investigation with his essay concerning a Viennese series. Coloured drawings of the rash illustrate Shaw’s paper
1905 – Léon Cheinisse (1871-1924) in his publication Une Cinquième maladie éruptive, le Mégalérythème épidémique, coined the term ‘fifth disease‘ in deference to the four exanthematous diseases of childhood then acknowledged to be distinct on clinical and epidemiologic grounds.
à côté de ces quatre affections exanthématiques — rougeole, scarlatine, rubéole, pseudo-scarlatine épidémique – , il en est une cinquième qui, décrite d’abord, elle aussi, comme une variété de rubéole, a été ensuite érigée, par différents auteurs et sous des désignations diverses [érythème infectieux aigu, érythème infectieux morbilliforme, megalerythema epidemicum, erythema simplex marginatum, etc.], en entité morbide distincte et indépendante.
Alongside these four exanthematic affections—measles, scarlet fever, rubella, pseudo-epidemic scarlet fever – there is a fifth which, also first described as a variety of rubella, was later supported by different authors and under various designations [erythema infectiosum, erythema infectios morbilliforme, megalerythema epidemicum, erythema simplex marginatum, etc.], as a distinct and independent morbid entity.
Subsequently, American epidemics were recorded by Zahorsky (1924), Herrick (1926), Feeley (1928) and Lawton and Smith (1931). Photographs accompany those of Herrick and Lawton and Smith.
1957 – Werner et al detected A new viral agent associated with erythema infectiosum
(1) An epidemic of erythema infectiosum was studied during the spring of 1955 in Reading, Pa.
(2) A cytopathogenic transmissible agent was obtained from monkey kidney cultures inoculated with clinical material.
(3) The serological data from cases and contacts are suggestive of a relationship between the cytopathogenic agent and the disease erythema infectiosum in humans.Werner 1957
1975 – Australian virologist Yvonne Cossart (1934-2014) described parvovirus-like particles in the serum of blood donors during screening for hepatitis B virus. The serum sample, which contained parvovirus-like particles, was coded as panel B and number 19 and hence named “parvovirus B19”. The B19 virus is a member of the genus of autonomous parvoviruses referred to later as human parvovirus (HPV). The ‘orphan’ virus was frozen and stored awaiting a disease association.
1980 – John Pattison et al noted the association between aplastic crisis and B19 infection when B19 was detected in six sickle cell anaemia patients suffering aplastic crisis in London. Subsequently specific IgM antibody tests were-developed, confirming these diagnoses, and further cases of aplastic crisis found to share the same aetiology.
1983 – Mary Anderson et al investigated an outbreak of erythema infectiosum in North London investigating cases for evidence of human parvovirus infection
Parvovirus-specific IgM was detected in all sera from the 31 cases in children and 2 adolescents. Those sera taken soon after the onset of the rash were strongly positive and the amount of specific IgM diminished as the length of time between the rash and the serum specimen increased. On the basis of these preliminary results we propose that the human parvovirus is the hitherto elusive agent of erythema infectiosum.Anderson et al 1983
- Theodor Escherich (1857-1911)
- Clement Dukes (1845-1925)
- Georg Sticker (1860-1960)
- Henry Larned Keith Shaw (1873-1941)
- Léon Cheinisse (1871-1924)
- Yvonne Cossart (1934-2014)
- Tschamer A. Ueber örtliche Rötheln. Jahrbuch für Kinderheilkunde und physische Erziehung. 1889; 29: 372-379.
- Tobeitz A. Ueber Rubeola. XII Internationaler medicinischer Congress in Moskau. 1896
- Tobeitz A. Zur Polymorphie und differential Diagnose der Rubeola, Archiv für Kinderheilkunde. 1898; 25: 17.
- Sticker G. Die neue Kinderseuche in der Umgebung von Giessen (Erythema infectiosum). Zeitschrift für praktische Aerzte. 1899; 8(11): 353–358
- Pospischill D. Ein neues, als selbständig erkanntes akutes Exanthem. Wiener klinische Wochenschrift , 1899; 12(7): 181
- Schmid. Aus der Grazer pädiatrischen Klinik (Prof Escherich). Ueber Rötheln und Erythemepidemien. Wiener klinische Wochenschrift , 1899; 12(47): 1169-1173
- Escherich T. Variété d’erythéme infectieux chez les enfants, Congrès international de Médecine Comptes-rendus. 1900, p. 528.
- Shaw HLK. Erythema infectiosum. The American Journal of the Medical Sciences. 1905; 129: 16-22
- Cheinisse L. Une Cinquième maladie éruptive, le Mégalérythème épidémique. Semaine Médicale, Paris 1905; 25: 205-207
Eponymous term review
- Zahorsky J. An Epidemic of Erythema Infectiosum, American journal of diseases of children, 1924; 28(2): 261-262
- Herrick TP. Erythema Infectiosum, American journal of diseases of children. 1926; 31(4): 486-495
- Feeley JB. Erythema Infectiosum, Atlantic Medical Journal. 1928; 31: 752
- Lawton AL, Smith RE. Erythema infectiosum: A clinical study of an epidemic in Branford. Conn. Arch Intern Med (Chic). 1931; 47(1): 28-41.
- Werner GH, Brachman PS, Ketler A, Scully J, Rake G. A new viral agent associated with erythema infectiosum. Ann N Y Acad Sci. 1957 apr 19;67(8):338-45.
- Cossart YE, Field AM, Cant B, Widdows D. Parvovirus-like particles in human sera. Lancet. 1975 Jan 11;1(7898):72-3.
- Pattison JR, Jones SE, Hodgson J, Davis LR, White JM, Stroud CE, Murtaza L. Parvovirus infections and hypoplastic crisis in sickle-cell anaemia. Lancet. 1981 Mar 21;1(8221):664-5.
- Anderson MJ, Jones SE, Fisher-Hoch SP, Lewis E, Hall SM, Bartlett CL, Cohen BJ, Mortimer PP, Pereira MS. Human parvovirus, the cause of erythema infectiosum (fifth disease)? Lancet. 1983 Jun 18;1(8338):1378.
- Anderson MJ, Lewis E, Kidd IM, Hall SM, Cohen BJ. An outbreak of erythema infectiosum associated with human parvovirus infection. J Hyg (Lond). 1984 Aug;93(1):85-93.
- Anderson LJ. Role of parvovirus B19 in human disease. Pediatr Infect Dis J. 1987 Aug;6(8):711-8.
- Musiani M, Manaresi E, Gallinella G, Cricca M, Zerbini M. Recurrent erythema in patients with long-term parvovirus B19 infection. Clin Infect Dis. 2005 Jun 15;40(12):e117-9
- Rogo LD, Mokhtari-Azad T, Kabir MH, Rezaei F. Human parvovirus B19: a review. Acta Virol. 2014;58(3):199-213.
- Qiu J, Söderlund-Venermo M, Young NS. Human Parvoviruses. Clin Microbiol Rev. 2017 Jan;30(1):43-113.
the names behind the name
BSc, MD from University of Western Australia. Junior Doctor currently working at Sir Charles Gairdner Hospital with an interest in Dermatology and Obstetrics & Gynaecology.
Associate Professor Curtin Medical School, Curtin University. Emergency physician MA (Oxon) MBChB (Edin) FACEM FFSEM Sir Charles Gairdner Hospital. Passion for rugby; medical history; medical education; and asynchronous learning #FOAMed evangelist. Co-founder and CTO of Life in the Fast lane | Eponyms | Books | Twitter |