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

Clinical manifestations

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
Erythema infectiosum (fifth disease) 2
Slapped cheek appearance and lacy rash on the arms and torso
Parvovirus B19

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.

Treatment

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.

1899Georg 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).

1905Henry 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

1904 Erythema infectiosum Shaw and Henning
Erythema infectiosum. Shaw 1905

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.

Cheinisse 1905

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.

Cheinisse 1905

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.

Lawton Smith 1931 erythema infectiosum
Fig. 3 (case 64). Second day of rash. Left arm, extensor surface, showing cleared central area which appears as rash extends to flexor surface. Lawton, Smith 1931

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.

1980John 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.

1983Mary 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

Associated Persons

References

Historical references

Eponymous term review


Cite this article as: Tatiana Ninkov and Mike Cadogan, "Fifth disease," In: LITFL - Life in the FastLane, Accessed on September 24, 2022, https://litfl.com/fifth-disease/.

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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 |

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