APRIL 23, 1955 HAEMOLYTIC ANAEMIA IN PREGNANCY EJotm 1005

In this case the haemolytic process seems to be due to Older children and adults have been involved in other
overactivity of the normal mechanisms for the removal of series. The sexes are equally affected.
red cells from the blood stream. The nature of such Aetiology.-Although the infective nature of the disease
mechanisms is at present obscure. It is known, however, was accepted, proof was not established until Kempe et al.
that they are influenced by the sex hormones. Hyperhaemo- (1950) succeeded in transmitting the disease by injecting
lysis has been demonstrated in normal women during the serum from an 18-months-old child in the pre-eruptive stage
latter part of the menstrual cycle (Ashby, 1921 ; Berlin, into a 6-months-old susceptible baby kept in isolation, who
1951). These authors, while admitting the obscurity of the developed typical roseola infantum on the ninth day. In
nature of this hyperhaemolysis, conclude that it is due to young apes these workers produced a fever without a rash
hormone influences; Berlin also believes that the spleen after a similar period. While they consider the~ causal
plays no part in its production, as he found it to persist agent to be a virus, they have been unable to isolate it or
after splenectomy. Presumably, during a normal pregnancy to transmit it through any of the usual media. Hellstrom
the hyperhaemolysis is inhibited, to prevent the increased and Valquist (1951), at Upsala, have confirmed these findings
concentration of sex hormones following gestation from in a larger series of 14 human cases.
causing a haemolytic anaemia. In our case the inhibitory Epidemiology.-Although most cases arise sporadically,
mechanisms would appear to have failed. epidemics have been reported, and the cases which I noted
in my practice presented as a mild epidemic, although I can
Summary identify in recollection a number of sporadic cases over
A case of symptomatic haemolytic anaemia associated the years. American writers believe that it is endemic and
with pregnancy is described. The haemolytic process almost universal in infancy, but that in favourable circum-
occurred during a young woman's first two pregnancies stances it appears isininepidemic form. They find that the
and ceased spontaneously on both occasions during the highest incidence the spring and to a less degree in
puerperium. Neither circulating haemolysins nor thePathology.-No autumn.
have been reported. The blood
atypical agglutinins were demonstrated. The mechanism changes seem to bedeaths important-they are a neutrophil leuco-
of the hyperhaemolysis was obscure. We suggest that penia, appearing during the febrile stage and falling to a
it may be related to that occurring during the pro: total white-cell count as low as 2,000 per c.mm. This
gestational phase of the normal menstrual cycle. process is reversed as soon as the rash appears, and the
We are indebted to Dr. J. F. Wilkinson for advice and en- count returns to normal within a week. The incubation
couragement during the preparation of this paper. period is 5 to 15 days.
REFERENCES Clinical Course
Allibone, E. C., and Collins, D. H. (1951). J. clin. Path., 4, 412.
Ashby. W. (1921) J. exp. Med., 34, 127.
Berlin, R. (1951). J. clin. Path., 4, 286.
The individual case presents on the following lines. A
Dacie, J. V. (1950). Practical Ilaematology, 1st ed. Churchill, London. call is received to an infant who "has come out in a
King, E. J. (1946). Micro-analysis in Medical Biochemistry. London.
Lescher, F. G. (1942). Lancet, 2, 148.
rash all over. He's been feverish for a few days, and I
O'Grady, J. W., Riva, H. L., and Ritzenthaler, J. G. (1953). Amer. J. nearly sent for you yesterday, doctor. When I saw the
Obstet. Gynec., 65, 1338.
Varadi, S. (1951). J. din. Path.. 4, 221.
rash to-day I thought it must be measles, but he seems
Whitby, L. E. H., and Britton, C. J. C. (1950). Disorders of the Blood, better now." In fact, the child appears well apart from a
6th ed. Churchill, London.
Wintrobe, M. M. (1951). Clinical Haematology. Kimpton, London.
rash in the form of discrete rose-coloured macules, most
Zinkham, W. H., and Diamond, L. K. (1952). Blood, 7, 592. marked on the trunk but spreading on to the thighs and
upper arms, up to the neck and often behind the ears. In
severe rashes some coalescence may occur.
If the case is seen earlier the child has a fever extending
ROSEOLA INFANTUM over three to five days, the temperature rising to 101-102
13 CASES SEEN IN GENERAL PRACTICE F. (38.3-38.9 C.) or higher, with symptoms of inflamma-
tion and congestion of the nose and throat, and frequently
BY of the tympanic membranes. He is restless, may refuse
E. L. McQUITlY, M.B., Ch.B. feeds, and is obviously unwell. Examination of the fauces
shows redness of the tonsils and pharynx, and of one or
Very little has been published in Britain on this relatively both ear-drums. A cough may be present without signs in
the chest. With the appearance of the rash the child rapidly
common condition, also known as exanthem subitum improves, the catarrhal signs disappear, and normal lustre
or sixth disease. The British Medical Journal (1950) returns to the ear-drums. Posterior cervical and occipital
draws attention to this " common but little-known infec- lymph-node enlargement can nearly always be found: in
tious disease of young children which has received too my experience this is more obvious when the rash is severe,
little attention in the past." especially on the neck and behind the ears. The glands in
Nearly all the published accounts of the disease come the groins and armpits do not become palpable. All signs
from the U.S.A., where Zahorsky, of St. Louis, first disappear in a day or two in most cases, but occasionally
congestion of the nose or Eustachian tubes persists and
described it as a clinical entity and gave it the descrip- frank otitis media may develop (as in one of the present
tive name in 1910. Up to 1940 he had seen about 300 series).
cases in private practice (Zahorsky, 1940). Cases have Clemens (1945), in a series of 80 cases, reports a pre-
been reported from all over the world, including Brazil, eruptive enanthlem in 87%: this took the form of erythe-
Formosa (Itagaki, 1933), Canada, Germany (Fischhof, matous specks and streaks on the soft palate which preceded
1936), South Africa (Witkin,. 1937), Sweden, and the typical exanthem by 48 hours and coincided with the
Australia (Jackson, 1949). In Britain, only Schlesinger period of maximum tubotympanitis and faucial congestion.
(1937) refers to a few cases seen in London. I noted this in one case, but would be inclined to dismiss
it as part of the general congestion of the mucous mem-
The purpose of this paper is to show that, despite the brane of the palate.
paucity of references to it in the journals and textbooks,
it arises quite frequently in general practice. Differential Diagnosis
Age Incidence.-The disease affects infants between the In a clear-cut case the disease which is most like roseola
ages of 6 months and 2 years. The youngest in Clemens's infantum is rubella. In that condition the pyrexia and
(1945) series of 80 cases was 5 months old, but he quotes malaise coincide with the rash and are usually less pro-
one 2 rtionths old. My youngest patient was 4- weeks old nounced. There is not the three to five days' pre-eruptive
 1006 APRIL 23, 1955 ROSEOLA INFANTUM JBRu
JOL
fever and malaise, with a dramatic return to normality patients saw any cases of rubella. None of the older
invariably found with roseola. In rubella the rash is usually members of the families developed rubella, although I
marked on the face, as opposed to roseola infantum, in watched particularly for it. Cases 1 and 6 demonstrated the
which the face escapes, apart from a few faint rosy macules infectivity and incubation period. Case 1 was an adopted
on the forehead. The absence of cases of rubella among son aged 31 years, who developed the rash two days after
older children and adults suggests the correct diagnosis. his adopted sister, aged 18 days, was introduced into the
Scarlet fever may be suspected. The absence of circum- house from a maternity home outside the area. She
oral pallor, strawbe-rry tongue, tonsillar adenitis, and the developed the rash 12 days later. In all cases the rash was
rapid resohition of the rash in roseola infantum, together typical of roseola infantum. The last patient, whose ill-
with the age incidence, will help to exclude it. ness occurred at a much later date, lived out in the country.
The prodromal rash of measles, or the early stage of the The mother told me that two babies of about the same
eruption with a post-auricular rash, may also be suggested. age, in near-by cottages, had had a similar rash and fever,
Again, this doubt is soon resolved' by the absence of but I did not see these cases.
Koplik's spots and the course of the illness.
Since I have recognized the disease in practice I am Summary and Conclusion
certain that many rashes which were previously dismissed Roseola infantum is a distinct entity with characteristic
to the parents as "teethings" or " stomach upset" or " drug age incidence, epidemiology, signs, and symptoms which
rash" have in fact been roseola. The story of restlessness, should be more frequently diagnosed.
fever, and sweating may suggest miliaria, but the rash is
quite different. There are, too, the blood changes I have It has been obscured in the past by a tendency to dis-
already mentioned. miss unusual rashes in infants as teething, sweat rash,
Complications drug sensitivity, or even " slight measles " or " mild
Although most observers say that recovery is always com- scarlet fever," or, more excusably, German measles.
plete, Zahorsky reports several cases of suppurative otitis The alternative name of exanthem subitum-the un-
media and rhinitis following the illness, and one case in the expected rash-should not excuse our failure to think
present series developed an acute catarrhal. otitis media of it in any case of unexplained fever in the critical' age
three days after defervescence. groups. I personally prefer the more descriptive name
Jackson (1949), in Australia, had two cases in which con- originally bestowed by Zahorsky. Its recognition may
vulsions occurred in the feverish stage: no changes were prevent the unnecessary use of antibiotics or other
found in the C.S.F., and' he believes them to have been due drugs, and will certainly give reassurance to anxious
to the pyrexia. parents.
It has been suggested that deaths in convulsions may Treatment has not been mentioned, as this is purely
occur before the rash has had time to appear; this is
obviously difficult to prove. symptomatic unless the rare suppurative complications
arise.
Details of Cases REFERENCES
British Medical Journal, 1950, 2, 876.
Clemens, H. H. (1945). J. Pediat., 26, 66.
Case Age
Yearsin Sex ofDate
Rash Comments
Cmet Fischhof, P. (1936). Med. Klin., 32, 807.
Hellstrom, B.. and Valquist, B. (1951). Acta paediat. (Uppsala). 40, 189.
3* 15/1/54 Itagaki, T. (1933). Taiwan Igakkal Zasshi, 32, 137.
1 M Cough and cold preceding; cleared Jackson, D. C. (1949). Med. J. Aust., 2, 52.
rapidly afterwards. Post-auricular Kempe, C. H., et al. (1950). J. Pediat., 37, 561.
glands enlarged Schlesinger, B. (1937). British Medical Journal, 1, 298.
2 10, 12 M 23/1:54 Feverish preceding rash-normal after- Witkin, M. (1937). S. Afr. med. J., 11, 499.
wards. Lives in adjoining street to Zahorsky, J. (1940). Arch. pediat., 57, 405.
Case 1
3 10,12 F 23,1/54 Feverish preceding rash-normal after-
wards
4 10112 F 2311/54 Typical roseola-had been to same
Christmas party as Case 3, on 16/1154 The ways in which the two great Asian countries of India
5 11/12 M 27/1/54 Had tonsillitis 10 days previously-
apparent recurrence 3-4 days before
and Japan have struggled with their problems of excessive
rash, but subsided with rash population are reviewed by P. E. P. in "Population Poli-
6 44'52 F 27;1i 54 Adopted sister of Case 1. Cough and
nasal eatarrh. ? Pain on swallowing;
cies in India and Japan" (Planning Broadsheet No. 378).
fauces red. Better after eruption In India the need to feed adequately from domestic sources
7 11/12 F 4/2/54 Fever preceding-no cough or cold.
Better after rash
a population which increases by five million a year has been
8 11/12 M 15/2/54 Fever and tonsillar infection preceding met by an imaginative series of five-year-plans covering
eruption. Fine macular rash with
some coalescence. Occipital glands
industry, agriculture, and public services. In these, birth
enlarged. Brother aged 4 years control is integrated with a family service including sex
9 19/12 M 17'3,54
remained well
Rash to-day after 4 days' malaise.
education and marriage guidance. In 1951 Dr. Abraham
Now well Stone, for W.H.O., organized controlled experiments in the
10 23112 M 2113 '54 Feverish beforehand. Both T.M. very
red. Ear infection seemed to be
rhythm method, which is in some respects consonant with
settling when seen again 2 days after Indian thought and custom, but the results were disappoint-
rash, but flared up as typical acute
catarrhal otitis media after another
ing. The Indian Government, however, accepted most of
48 hours the recommendations of the Family Planning Research and
I1
12
12jl2
4/12
F
M
26/3!54
27/4/54
Typical rash with preceding fever Programme Committee for encouraging clinics, research,
13 9 12 F 25/8P54 Typical rash on trunk-preceded by and the setting up of voluntary as well as government
fretfulness and diarrhoea, which agencies. In Japan only American financial aid has in
stopped when rash appeared recent years buttressed the nation's economy against col-
lapse, says the report. Between 1945 and 1953 Japan's
population increased by 15 million. In 1948 a Eugenic
Present Series Protection Law facilitated the termination of pregnancy for
In the brief description of individual cases which follows physical and economic reasons, so that now over a million
I have included only the comments which I jotted down in abortions are procured each year; abortion replaces
my visiting diary. In view of the youth of the patients infanticide, the traditional method of population control
and the invariable recovery I did not feel justified in taking Last August, however, 'the Japanese Minister of Welfare's
blood samples to establish a leuc'openia followed by a Advisory Council on Population Problems announced that
return to normal. However, during the period discussed, birth control was preferable to abortion and advocated
no cases of measles were notified to the medical officer of government sponsored clinics. But these recommendations
health and none of my p3artners in a practice of over 10,000 have not yet been adopted as the official policy.