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Natural history of infantile eczema: Its incidence and course
158
The Journal of P E D I A T R I C S
January 1965
Natural history of infantile eczema." Its incidence a n d course
DR. SEDLIS. I shall take up first the accepted facts about eczema, then the contentious questions, a n d finally I shall describe a study we have in progress designed to throw light on some of these questions. T h e accepted facts. T h e r e is general agreem e n t t h a t eczema usually has its onset in the first half year of life a n d tends to clear with increasing age. T h e m e d i a n age at onset in our own cases was 2 ~ months; 75 per cent of the patients h a d their eczema by the age of 6 months. T h a t exacerbations and remissions occur without a p p a r e n t cause is our own experience as well as that of others. At times, of course, a cause for the change m a y be apparent. Approximately two thirds of our patients h a d a family history of m a j o r allergy (eczema, h a y fever, or a s t h m a ) ; this is an agreement with most of the data in the literature in which the incidence of a positive history in the immediate family ranges from 50 to 75 per cent. T h e incidence of positive skin tests as reported in the literature is between 43 and 72 per cent; in our series it has been about 50 per cent. T h e respiratory sequelae are among the wellaccepted facts; we shall present our own data on this point later. T h e contentious questions. These deal with both the incidence of the d~sease and its course. Breast feeding. T h e r e are claims that breastfed infants are less likely to suffer from eczema, notably the widely quoted study of Grulee a n d Sanford a2 carried out in infant welfare stations in Chicago some years ago. T h e interpretation of their results is open to question since other variables entered the picture. T h e mothers of the breast-fed babies were presumably not working mothers and m a y have been more conscientious in the care given their infants. O t h e r workers a2~, 232,233 have reported t h a t eczema is m o r e frequently seen a m o n g breast-fed infants. It would be difficult to carry out an adequately controlled study in the U n i t e d States at present with the virtually universal practice of introducing solid foods during the early m o n t h s of life. It might be m e n t i o n e d that in some studies 2~2, 23a the findings are not in agreement with those of
Grulee and Sanford. If indeed there is a difference in the incidence of eczema in breast-fed a n d artificially fed babies, I doubt if the difference is significant. T h e alleged lower incidence in the breast-fed baby has been attributed to several factors: (1) the low allergenicity of breast milk, (2) its lower protein content, and (3) the fact that it is given in the neonatal period, a time when immunologic tolerance can be established. Sex. A m o n g infants a n d snlall children males are said to be somewhat more frequently affected, whereas a m o n g older children and adults the reverse is said to be the case. ~3 In our own series of infants and small children the ratio of males to females was three to two. Seasonal incidence. T h e literature is conflicting on this point. I n our own experience flare-ups were somewhat more c o m m o n in cold weather. Geographical incidence. Eczema appears to be more c o m m o n in the so-called well-developed countries. This seems to be related to socioeconomic factors and possibly to nutrition r a t h e r than to race or geography. In Nigeria ~4 infantile eczema is said to b e confined to the wealthy u p p e r class Nigerians. T r a n s p l a n t a t i o n of primitive or semiprimitive groups to a sophisticated A m e r i c a n or E u r o p e a n u r b a n environment seems to be associated with a m a r k e d increase in the incidence of eczema. T h u s children of Chinese families transplanted from T a i w a n to Honolulu or San Francisco a~ are reported to suffer from
60
0
I
i 5
i ~O
L 15 YEARS
= L:'O AFTER
Z~
' :~O
= 35
f 4O
ONSET
Fig. 3. Persistence of infantile eczema (17 followup studies, 1,968 patients).
j. Pediat. January, 1965, part 2
Holt: Con[erence on in[antile eczema
1 59
/)
C Fig. 4. Grades of severity of infantile eczema. A, Upper left, 4 plus. B, Upper right, 3 plus. C, Lower left, 2 plus. D, Lower right, 1 plus.
Volume 66
Number 1 part 2
Natural history of eczema
PRESENT THERAPY ( based on cQses hospito.Hzed in University Hospitol 1958,1959,1960 ) 4+
:E UJ
g o AVERAGE RESULT
FL
BESTRESULT
, = = = ~ = v ; = = = -
2 DAYS
4
6 OF
8
IO
12
14
TREATMENT
Fig. 5. Severe eczema--immediate response to therapy.
3+
w
b_ o >F-
2+
m > m L+
I
12
I 24 AGE
I 56 iN
i 48
I 60
I 66
MONTHS
Fig. 6. Course of eczema--composite curve.
1958
16 1
eczema eight times as frequently as Chinese children in T a i w a n and more frequently t h a n Caucasian children in Honolulu a n d San Francisco. Likewise, children of J a m a i c a n families who have migrated to L o n d o n suffer more t h a n J a m a i c a n children in J a m a i c a a n d more t h a n British children in London. 16 One can only speculate about the explanation for these differences. Overnutrition. This is said to play a role in predisposing toward eczema. Certainly eczema is c o m m o n in well-nourished children a n d one is likely to be impressed, as U n d e r w o o d was, with the contrast between the state of the skin and the state of nutrition in such cases. However, w h e n we plotted the weights of our eczematous children on standard graphs for weight and age we found no striking deviation from the normal. O n the other hand, there are indications that underfed, underprivileged populations 17 suffer little from eczema. T h e r e is evidence that infantile eczema is decreasing in the U n i t e d States. Hill TM points out that in the 5 year period from 1930 to 1935 an average of 435 children a year with eczema were a d m i t t e d to the outpatient d e p a r t m e n t of the Boston Children's Hospital in contrast to 52 admitted during 1959. Some of our pediatric colleagues in the suburban New York area report a similar decrease in frequency. Hill suggests the increasing use of processed milk as a n explanation of this phenomenon. Natural history of the disease. Accurate information on this is needed if one is to evaluate therapy properly. Credit is often given to therapy t h a t should be given to nature. T h e literature on the course of the disease is most unsatisfactory in revealing the frequency with which infantile eczema persists into adult life. A m o n g 17 reasonably critical reports 19-3a which we have examined
1959
1960
1961
1962
Pt~ P,L
4+5+-
-X
/ i"-~,/'-%~
2+I+-
IYEAR
2 YEAR
3 YEAR
Fig. 7. Course of eczema--an individual case.
4 YEAR
5 YEAR
16 2
Holt: Con/erence on in/antile eczema
(Fig. 3 ) the figures for its persistence range from 3.5 to 82 per cent. I n general the higher figures come from the dermatologic literature, the lower ones from the pediatric literature. Errors of se-
IM CO
75
- 65.3
<~ o la_ o
%
PrIL' I~Z(50DILIL)' Z~ ~MODERATE LLI 25 EL INI.fTIAL ON OBSERVATI
18 24
36
- 50,6
48
60
%
3.8%
AGE IN MONTHS Fig. 8. Course of 26 severe cases of eczema (prospective study) followed from onset under 1 year through 5 years of age.
]anuary 1965
lection are likely to occur in both groups. T h e dermatologist who deals largely with adults is likely to see the persistent cases, while the pediatrician sees m a n y mild cases that clear readily and never reach the dermatologist. T h e r e are very few data on tong-term follow-up of well-studied cases in which the follow-up was carried out by examination r a t h e r t h a n by letter. T h e need for re-examination is a p p a r e n t from the data of Oehme, ~6 whose incidence of cure was 66 per cent based on correspondence, but only 45 per cent based on examination of the same patients. As far as I am aware no one has carried out a prospective study of eczema, a gap which we are attempting to fill. Since it seemed clear t h a t mild cases of infantile eczema tend to clear a n d that the persistent ones come from a group t h a t is initially severe, it appeared essential for a prognostic study to establish standards of severity. In order to obtain an objective standard of severity we used a photographic technique. Color photographs were m a d e of each patient on admission to the study and were graded 1 plus to 4 plus by m a t c h i n g t h e m against the standards shown in the accompanying figure (Fig. 4). T h e lesions were often graded by more t h a n one observer
\ 2- 9 MOS.
9 - 18 MOS.
18-36 MOS.
2 Fig. 9. Distribution of eczema in relation to age.
3-4 YRS.
OVER 4 YRS.
Volume 66
Number 1 part 2
with surprisingly close agreement. By plotting the severity of the lesion against time we can evaluate the immediate response to suppressive therapy as well as the long-term persistence of some measure of eczema. In the more chronic phases of the disease the photographic evaluation is somewhat less satisfactory since it does not reveal the amount of induration present. Fig. 5 illustrates the immediate response of a group of cases of 4 plus eczema to a form of local suppressive therapy that wiI1 be discussed elsewhere. Fig. 6 is a composite curve illustrating the course of eczema as we have observed it during the first 5 years of life. All degrees of initial severity are included. Being a composite curve, this does not show the peaks and remissions seen in individual cases. These are illustrated in Fig. 7, the graph of a single case observed intermittently for a 5 year period. The outcome of the initially severe cases is shown graphically in Fig. 8. Of 26 children with 3 plus to 4 plus eczema at the start, one case (4 per cent) remained severe at the end of 5 years, 8 (31 per cent) continued to show moderate activity, and 17 (65 per cent) had become quiescent. By quiescence I mean the complete absence of erythema and scaling, though not infrequently indurated patches persist at the sites of former activity. Mothers of such children, asked whether the child still has eczema or not, will usually reply in the negative.
Natural history o[ eczema
16 3
Our study illustrates the distribution of the lesions with increasing age (Fig. 9). Facial involvement with a tendency to generalization is the usual pattern between 2 and 9 months of age. When the extremities are involved the lesion usually consists of localized patches on the extensor surfaces. Between 9 and 18 months there is more generalized involvement of the extremities, a n d the flexor as well as the extensor surfaces are commonly affected. Involvement of the flexural surfaces becomes more marked thereafter and by the age of 4 years it is usually predominant. By this time involvement of the face is less frequent; at the age of 5 only 30 per cent of the patients show facial involvement as contrasted with 100 per cent of young infants. The prognosis for sequelae of eczema, notably asthma, is always a matter of concern. Figures reported in the literature vary widely, the range being from 20 to 80 per cent. One source of discrepancy is the lack of a clear differentiation between asthma and asthmatic bronchitis (infectious asthma). In our study we have grouped both together and have designated as having asthma any child who exhibited recurrent wheezing as a sequel of eczema. Dr. Pasternack and Mr. Cleary of the Department of Environmental Medicine have been kind enough to analyze our data from the statistical point of view which I shall now ask Dr. Pasternack to present.
The Journal of P E D I A T R I C S
January 1965
Natural history of infantile eczema." Its incidence a n d course
DR. SEDLIS. I shall take up first the accepted facts about eczema, then the contentious questions, a n d finally I shall describe a study we have in progress designed to throw light on some of these questions. T h e accepted facts. T h e r e is general agreem e n t t h a t eczema usually has its onset in the first half year of life a n d tends to clear with increasing age. T h e m e d i a n age at onset in our own cases was 2 ~ months; 75 per cent of the patients h a d their eczema by the age of 6 months. T h a t exacerbations and remissions occur without a p p a r e n t cause is our own experience as well as that of others. At times, of course, a cause for the change m a y be apparent. Approximately two thirds of our patients h a d a family history of m a j o r allergy (eczema, h a y fever, or a s t h m a ) ; this is an agreement with most of the data in the literature in which the incidence of a positive history in the immediate family ranges from 50 to 75 per cent. T h e incidence of positive skin tests as reported in the literature is between 43 and 72 per cent; in our series it has been about 50 per cent. T h e respiratory sequelae are among the wellaccepted facts; we shall present our own data on this point later. T h e contentious questions. These deal with both the incidence of the d~sease and its course. Breast feeding. T h e r e are claims that breastfed infants are less likely to suffer from eczema, notably the widely quoted study of Grulee a n d Sanford a2 carried out in infant welfare stations in Chicago some years ago. T h e interpretation of their results is open to question since other variables entered the picture. T h e mothers of the breast-fed babies were presumably not working mothers and m a y have been more conscientious in the care given their infants. O t h e r workers a2~, 232,233 have reported t h a t eczema is m o r e frequently seen a m o n g breast-fed infants. It would be difficult to carry out an adequately controlled study in the U n i t e d States at present with the virtually universal practice of introducing solid foods during the early m o n t h s of life. It might be m e n t i o n e d that in some studies 2~2, 23a the findings are not in agreement with those of
Grulee and Sanford. If indeed there is a difference in the incidence of eczema in breast-fed a n d artificially fed babies, I doubt if the difference is significant. T h e alleged lower incidence in the breast-fed baby has been attributed to several factors: (1) the low allergenicity of breast milk, (2) its lower protein content, and (3) the fact that it is given in the neonatal period, a time when immunologic tolerance can be established. Sex. A m o n g infants a n d snlall children males are said to be somewhat more frequently affected, whereas a m o n g older children and adults the reverse is said to be the case. ~3 In our own series of infants and small children the ratio of males to females was three to two. Seasonal incidence. T h e literature is conflicting on this point. I n our own experience flare-ups were somewhat more c o m m o n in cold weather. Geographical incidence. Eczema appears to be more c o m m o n in the so-called well-developed countries. This seems to be related to socioeconomic factors and possibly to nutrition r a t h e r than to race or geography. In Nigeria ~4 infantile eczema is said to b e confined to the wealthy u p p e r class Nigerians. T r a n s p l a n t a t i o n of primitive or semiprimitive groups to a sophisticated A m e r i c a n or E u r o p e a n u r b a n environment seems to be associated with a m a r k e d increase in the incidence of eczema. T h u s children of Chinese families transplanted from T a i w a n to Honolulu or San Francisco a~ are reported to suffer from
60
0
I
i 5
i ~O
L 15 YEARS
= L:'O AFTER
Z~
' :~O
= 35
f 4O
ONSET
Fig. 3. Persistence of infantile eczema (17 followup studies, 1,968 patients).
j. Pediat. January, 1965, part 2
Holt: Con[erence on in[antile eczema
1 59
/)
C Fig. 4. Grades of severity of infantile eczema. A, Upper left, 4 plus. B, Upper right, 3 plus. C, Lower left, 2 plus. D, Lower right, 1 plus.
Volume 66
Number 1 part 2
Natural history of eczema
PRESENT THERAPY ( based on cQses hospito.Hzed in University Hospitol 1958,1959,1960 ) 4+
:E UJ
g o AVERAGE RESULT
FL
BESTRESULT
, = = = ~ = v ; = = = -
2 DAYS
4
6 OF
8
IO
12
14
TREATMENT
Fig. 5. Severe eczema--immediate response to therapy.
3+
w
b_ o >F-
2+
m > m L+
I
12
I 24 AGE
I 56 iN
i 48
I 60
I 66
MONTHS
Fig. 6. Course of eczema--composite curve.
1958
16 1
eczema eight times as frequently as Chinese children in T a i w a n and more frequently t h a n Caucasian children in Honolulu a n d San Francisco. Likewise, children of J a m a i c a n families who have migrated to L o n d o n suffer more t h a n J a m a i c a n children in J a m a i c a a n d more t h a n British children in London. 16 One can only speculate about the explanation for these differences. Overnutrition. This is said to play a role in predisposing toward eczema. Certainly eczema is c o m m o n in well-nourished children a n d one is likely to be impressed, as U n d e r w o o d was, with the contrast between the state of the skin and the state of nutrition in such cases. However, w h e n we plotted the weights of our eczematous children on standard graphs for weight and age we found no striking deviation from the normal. O n the other hand, there are indications that underfed, underprivileged populations 17 suffer little from eczema. T h e r e is evidence that infantile eczema is decreasing in the U n i t e d States. Hill TM points out that in the 5 year period from 1930 to 1935 an average of 435 children a year with eczema were a d m i t t e d to the outpatient d e p a r t m e n t of the Boston Children's Hospital in contrast to 52 admitted during 1959. Some of our pediatric colleagues in the suburban New York area report a similar decrease in frequency. Hill suggests the increasing use of processed milk as a n explanation of this phenomenon. Natural history of the disease. Accurate information on this is needed if one is to evaluate therapy properly. Credit is often given to therapy t h a t should be given to nature. T h e literature on the course of the disease is most unsatisfactory in revealing the frequency with which infantile eczema persists into adult life. A m o n g 17 reasonably critical reports 19-3a which we have examined
1959
1960
1961
1962
Pt~ P,L
4+5+-
-X
/ i"-~,/'-%~
2+I+-
IYEAR
2 YEAR
3 YEAR
Fig. 7. Course of eczema--an individual case.
4 YEAR
5 YEAR
16 2
Holt: Con/erence on in/antile eczema
(Fig. 3 ) the figures for its persistence range from 3.5 to 82 per cent. I n general the higher figures come from the dermatologic literature, the lower ones from the pediatric literature. Errors of se-
IM CO
75
- 65.3
<~ o la_ o
%
PrIL' I~Z(50DILIL)' Z~ ~MODERATE LLI 25 EL INI.fTIAL ON OBSERVATI
18 24
36
- 50,6
48
60
%
3.8%
AGE IN MONTHS Fig. 8. Course of 26 severe cases of eczema (prospective study) followed from onset under 1 year through 5 years of age.
]anuary 1965
lection are likely to occur in both groups. T h e dermatologist who deals largely with adults is likely to see the persistent cases, while the pediatrician sees m a n y mild cases that clear readily and never reach the dermatologist. T h e r e are very few data on tong-term follow-up of well-studied cases in which the follow-up was carried out by examination r a t h e r t h a n by letter. T h e need for re-examination is a p p a r e n t from the data of Oehme, ~6 whose incidence of cure was 66 per cent based on correspondence, but only 45 per cent based on examination of the same patients. As far as I am aware no one has carried out a prospective study of eczema, a gap which we are attempting to fill. Since it seemed clear t h a t mild cases of infantile eczema tend to clear a n d that the persistent ones come from a group t h a t is initially severe, it appeared essential for a prognostic study to establish standards of severity. In order to obtain an objective standard of severity we used a photographic technique. Color photographs were m a d e of each patient on admission to the study and were graded 1 plus to 4 plus by m a t c h i n g t h e m against the standards shown in the accompanying figure (Fig. 4). T h e lesions were often graded by more t h a n one observer
\ 2- 9 MOS.
9 - 18 MOS.
18-36 MOS.
2 Fig. 9. Distribution of eczema in relation to age.
3-4 YRS.
OVER 4 YRS.
Volume 66
Number 1 part 2
with surprisingly close agreement. By plotting the severity of the lesion against time we can evaluate the immediate response to suppressive therapy as well as the long-term persistence of some measure of eczema. In the more chronic phases of the disease the photographic evaluation is somewhat less satisfactory since it does not reveal the amount of induration present. Fig. 5 illustrates the immediate response of a group of cases of 4 plus eczema to a form of local suppressive therapy that wiI1 be discussed elsewhere. Fig. 6 is a composite curve illustrating the course of eczema as we have observed it during the first 5 years of life. All degrees of initial severity are included. Being a composite curve, this does not show the peaks and remissions seen in individual cases. These are illustrated in Fig. 7, the graph of a single case observed intermittently for a 5 year period. The outcome of the initially severe cases is shown graphically in Fig. 8. Of 26 children with 3 plus to 4 plus eczema at the start, one case (4 per cent) remained severe at the end of 5 years, 8 (31 per cent) continued to show moderate activity, and 17 (65 per cent) had become quiescent. By quiescence I mean the complete absence of erythema and scaling, though not infrequently indurated patches persist at the sites of former activity. Mothers of such children, asked whether the child still has eczema or not, will usually reply in the negative.
Natural history o[ eczema
16 3
Our study illustrates the distribution of the lesions with increasing age (Fig. 9). Facial involvement with a tendency to generalization is the usual pattern between 2 and 9 months of age. When the extremities are involved the lesion usually consists of localized patches on the extensor surfaces. Between 9 and 18 months there is more generalized involvement of the extremities, a n d the flexor as well as the extensor surfaces are commonly affected. Involvement of the flexural surfaces becomes more marked thereafter and by the age of 4 years it is usually predominant. By this time involvement of the face is less frequent; at the age of 5 only 30 per cent of the patients show facial involvement as contrasted with 100 per cent of young infants. The prognosis for sequelae of eczema, notably asthma, is always a matter of concern. Figures reported in the literature vary widely, the range being from 20 to 80 per cent. One source of discrepancy is the lack of a clear differentiation between asthma and asthmatic bronchitis (infectious asthma). In our study we have grouped both together and have designated as having asthma any child who exhibited recurrent wheezing as a sequel of eczema. Dr. Pasternack and Mr. Cleary of the Department of Environmental Medicine have been kind enough to analyze our data from the statistical point of view which I shall now ask Dr. Pasternack to present.