NON-VIRAL ICTERIC DISORDERS IN PREGNANCY
Jaundice in late Pregnancy
This group of icteric pregnant women forms the main body of the series, 38 patients, Cases 35 to 72. The term late pregnancy in the title of this chapter may appear to be somewhat misleading, in view of the fact that the onset in some cases occurred in a relatively early stage of pregnancy. Rut, although the group may not be uniform from the standpoint of aetiology, the clinical signs and symptoms in its different members are so similar that, for practical pur- poses, they are best described in the group as a whole. The title was suggested by the fact that the onset of jaundice occurred towards the end of pregnancy in the great majority of cases. Howerer, a closer analysis of the histories shows symptoms other than jaundice to have become manifest in several instances appreciably earlier in the course of gestation than one might hare expected. There is, in fact, no little difficulty in dating the onset of the condition exactly. The only source of information available is the history, which cannot be relied upon to the day. Dates may well be inaccurate by as much as a week or so in either direction. However, as will be illustrated in the following, this inaccuracy is of no importance whatsoever to a general interpretatioii of the condition.
CLINICAL SIGNS AND SYMPTOMS
Some of the signs and symptoms in each case are giren in Table 10 (mild symptoms are marked (+)). Their incidence is shown in Table 12. As these figures offer no indication from a qualitative standpoint, some comments are called for.
Lassitztde.-This symptom occurs commonly. I t is, however, extremely difficult to assess-not least when associated with pregnancy. Its diagnostic value may be considered small, but it is none the less of interest. In the authors experience of these patients, the fatigue is too extreme to be purely physiologic lassitude. Nor does the disturbance to sleep caused by pruritus offer a satisfactory ex- planation, though i t may be a contributory factor. The symptom may be so severe that, as in Case 51, the patient has not the strength to get up although
JAUNDICE IN PREGNANCY 65
the other symptoms are not particularly marked. It may also persist after delivery, for some months, as in Cases 36, 51, 60, 62 and 69. This is exemplified by Case 51 ; some 5 months after delivery the patient attended hospital for her fatigue. Examination showed both haematologic and hepatologic conditions to be fully normal. The lassitude is of the asthenic type so commonly found after other diseases of the liver-such as viral hepatitis-which may with reason be regarded as due to cerebral lesions ( THORLING 1950, 1950, and others).
Anorexia, Nausea and Vomiting.-Anorexia has not been found to any great extent and was frequently absent in patients with both the other symptoms. Nausea and vomiting have as a rule been coexistent. I n general these symptoms were only slight or very moderate. I n only one instance, Case 67, could their intensity be compared to that of the pernicious vomiting of pregnancy (for case report see page 77).
Epigastric Pain.-All grades and varieties of epigastralgia are represented in the 9 cases in which this symptom occurred. The pain is described in some instances as a dull ache, in others as laminating, in most mild. Severe pain appears to have been present only in Case 67. Typical biliary colic did not occur. I n a few cases, however, the pain was referred to the right shoulder or to the back and bile-duct disease was suspected-for a time a t least. Epigastric pain, then, may give rise to diagnostic problems.
Stools.-Tables 10 and 12 show diarrhoea to have occurred in 13 cases. The term diarrhoea, implying frequent loose stools, appears to be too drastic in the majority of the cases. I n no case were they of a character suggestive of a specific intestinal infection, and culture of the faeces was not thought to be indicated. They appear only in one case to have been spurting or as thin as water. Their colour is described as pale yellow or clay-coloured. This latter description is common even in cases in which diarrhoea did not occur. I n two such cases, bile pigments were demonstrated in the faeces; in view of this, and despite the history, one cannot assume them to be acholic stools suggestive of total obstruc- tion of the bile ducts. I n Case 60 the attacks of diarrhoea were clearly synchro- nized with meals, an example of the gastrocolic reflex. On the information avail- able, it is not possible to say whether or not this phenomenon is widespread.
Przwitus and the Skin.-In this, as in the two groups of patients described earlier, pruritus was an extremely common symptom. It was wholly absent in only 3 of 38 cases. In many of the patients it was very severe, and in some their immediate reason for seeking medical advice. Scratches were observed in 14 of the 35 patients; and in a further 16 instances, although there were no scratches, the patients sleep was disturbed. Thew figures give some indication of the intensity of the itching, and it seems quite clear that in these cases the condition was what might be called pathologic pruritus. The clinical features of this itching did not differ from those associated with various other types of internal diseases. It increased in intensity towards evening. It was usually
5 - 551613 Zeif Thorling
28 29 30 31 32
F F D F D
Table 10. Clinical Signs and Symptoms in 46 For group classifications
33 34 35
F F F
-_ -- 36 37 38 39 40 41
F F F F F F
42 43 44 45
F F F F
V I VI Month of pregnancy I Case number
Ti- I - T ( + : I (+: -
T (+: I ( + : -
I - - T I -
+ ( + I + + + + + ( + ) - + + -
+ - + t
+ - + - Lassitude
Arthralgia, Muscle pains ~~
Pruritus + + + + ( + I + [ + ) + - + - +
Fever - - ( + ) - - - + - - - ( + I - - 1 - + I -
Dark urine + + - + + + + + ? ? - + + I - + I + + + + + + + + ? ? + + - - - + - - ? ? -
- - + - - - I - ( + ) - - Palp. liver I -
Palp. spleen l - Liver tend. - -(+b - 1 - - I +
I I - I - - I - _ - _ _
situated on the hands-particularly between the fingers, the soles of the feet, the lower leg and the arms. Very frequently, however, it was generalized and the face was the only portion of the body on which the author failed to find it. This symptom usually appeared early in the course of the disease, as will be discussed -in more detail in the following.
JAUNDICE I N PREGNANCY
L6 47 48 49
F D F F
50 51 62 53 64 56 56 57 68 69 60
F F D F F D F B F F F
Pregnant Women with Non-Viral Icteric Disorders. 888 Table 6, p. 38. ( -t ) = mildness.
+ + + + + + + + + + + + - - + + + + - + + - + + - + + + + + I
VII I VIII I IX I x
+ + + + + + + + + + i. + - + + + + + + - + + + +
61 62 63 64 65 66 67 68 69 70 71 72
F F F F F B F F F F l- F F ? + + ? I + + + + + ? + + - ? + ? + + ? + - - + + ? - + - ? -
+ - - + + - - - - - - - + - - - + - - I + - - - + - - - - - -
+ + + - - ? + + + ( + I - + + + - - - ? + + + - I - + + + ( + I ( + ) - - + - - - + + - ( + ) - - - - - -
Apart from the scratches, in some cases combined with lichenization, other skin lesions were observed in only 3 cases. Transient urticaria was noted in Case 68; reddish papules the size of confetti with horny centres occurred in Case 54 ; and in case 37 papulo-vesicular efflorescences were disseminated over the trunk and extremities. In the latter case, the diagnosis of herpes gestationis
LEIF THORLING 68
I, 85 !I Fever . . . . . . 30 Sore throat. . . . 37 1 1 Pruritus . . . . . 34 I Dark urine . . . .
, Palpable liver . . . 0 ! Liver tenderness .
Palpable spleen . .
Table. 12. Incidence of Clinical Signs and Symptoms in 38 Women with 'Jaundice in Late Pegnancy'.
38 0 36 0 38 84 36 100 37 37 37
Symptoms and signs
Lassitude . . . . Anorexia . . . . . Nausea. . . . . . Vomiting. . . . . Arthralgia and/or muscle pains . . .
Epigastric pains . . Diarrhoea . . . .
33 37 38 38
30 38 38
Initial. per cent
61 19 21 21
0 18 16
per cent ' 1 course. I' Symptoms and signs Total
course. per cent
90 100 41 19
was considered, but the long duration of the condition and the favourable out- come for both mother and child afforded no confirmation. It may be of interest to note that the patient's mother and maternal aunt had both suffered intense itching during their pregnancies.
In every instance the itching subsided a t the time of, or shortly after, delivery and in some even before the onset of labour.
One might imagine the combination of pregnancy and liver disease to furnish ideal conditions for the manifestation of spider iiaevi (cf. BEAN 1945 and others). In the 16 patients whom the author examined personally and systemati- cally for such skin lesions, one single spider was found in two instances, Cases 51 and 72. The first of these patients could not say whether i t had been present earlier, and in the second i t appeared between two examinations. I n the remain- ing cases in the series there are occasional notes to the effect that lesions of this type were absent, otherwise they are not mentioned. However, the fact that repeated examinations were made of the skin for the presence of scratches, et cetera, leads one to suppose that spider naevi were absent in these cases too. The author feels justified in assuming this type of skin lesion not to be charac- teristic of the condition. The same appears to apply to palmar erythema, which was not observed in any of the 16 patients examined systematically.
While collecting the control series, a patient with numerous spider angiomata on the upper half of the trunk was found. She was in the 9th month of pregnancy and had observed these skin lesions one month previously. They had increased successively. As fa r as she could remember, no lesions of this type had attended her first pregnancy. She felt well, had no itching, no albuminuria, and her blood pressure was normal. The serum bilirubin level was 0.3 mg per cent, negative direct reaction; alkaline phosphatases 7 units; cephalin flocculation test 0; and the thymol turbidity test 0.04 ext. coeff., in other words, the values were fully normal. These observations should not necessarily be taken to indicate the presence of liver disease. The same view is expressed by BEAN (1945).
JAUNDICE IN PREGNANCY 69
Physical Abdominal Findings.-The positive palpatory findings in 16 cases may be taken as suggestive of enlargement of the liver. In these cases, the liver edge was usually felt immediately below the costal margin. I n Cases 51 and 52 the liver was felt digitally slightly more than 3 cm below the costal margin on examination the day after delivery. Negative palpatory findings do not, of course, rule out the presence of enlargement of the liver. This applies particu- larly in patients in the final stages of pregnancy. From the standpoint of diag- nosis, one may say only that a palpable liver may or may not be part of the syndrome. As regards liver diseases in general, i t is said that a palpable or percussible decrease in the size of the liver is an unfavourable prognostic sign. No such finding was made in the two cases of greatest clinical severity, Nos. 64 and 67. However, both the patients survived. There was no relation between the palpatory findings and the presence of pain in the abdomen.
Liver tenderness was not particularly marked. I n some instances there was slight tenderness in the epigastrium or under the right costal margin, occasion- ally brought on by jolts. In Case 51 the tenderness was definitely localized to the region of the gall-bladder, even after delivery. However, continued observa- tion and roentgen examination of the gall-bladder revealed no disease in that organ.
It will be seen in Table 10 that the spleen was not palpable in any case. This does not, of course, imply that the syndrome may not be attended by sple- nomegaly. Palpation and percussion of the spleen are difficult examinations, particularly so in late pregnancy. I n 6 cases, however, the spleen was also exam- ined roentgenographically. It was found to be of normal size in Cases 49, 52, and 72 on the 12th day after delivery. I n Case 64 the lower pole of the spleen was seen 2 cm below the costal margin, but the upper pole could not be deter- mined 17 days after delivery. I n Case 51, the size of the spleen was 17 X 6 cm 14 days after delivery; the lower pole lying 3 cm below the costal margin, On examination 5 months later, it measured 13 X 6 em. In the last two cases, one might reasonably suppose the spleen to be palapble. But, although the author was aware of the roentgenographic findings, palpation failed to verify them. This suggests that in such cases the spleen is soft. However, although i t appears possible that splenomegaly may attend the syndrome, its presence is not in- variable.
The greatest deviations from normal to these tests in each case are given in Table 13, and the figures are summarized in Table 14. The alkaline phosphatase values will be found in Fig. 10, with the exception of Case 51 in which the increase was so marked that it could not be fitted into the diagram.
70 LEIF THORLING
Table 13. Greatest Deviation from Normal in Laboratory
sented. It is of interest to note that the direct reaction in the 19 patients exam- ined was always positive, even in the case showing the smallest increase in serum bilirubin (1.3 mg per cent). Bilirubinuria was a common finding, al- though there were several exceptions. I n these, the histories contained reports of dark urine (two cases unknown). The duration of this symptom is, however, strikingly short and the result of an isolated laboratory test is of help only as an indication of the conditions that particular day. This is illustrated by some of the case reports in the following.
Flocculation Tests.-The reaction to the thymol turbidity test has invariably been negative on repeated examination (see case reports below). The same applies to the zinc sulphate turbidity test. The cephalin flocculation test gave a reaction of 3 + in only one of the 16 cases examined; this was Case 43, and 4 subsequent examinations gave wholly negative results. In the Takata-Ara test, slight flocculation occurred commonly in one or more tubes. Maximal flocculation in a t least one tube was observed in Cases 39 and 40.
Citric Acid of the Serum.-The citric acid content of the serum was within normal limits in all but one case (No. 57) , in which a slight increase was noted. The tests were not performed on serum taken during labour; according to LEKKER (1934) the serum a t that time may show an increase in citric acids.
Alkaline Yhospltatases.-As is seen in Fig. 10, an increa...