A
Report
on
Sixty-Five
Patients
over
17 Years
of
Age
Harry Shwachman, M.D., Lucas L. Kulczycki, M.D., and Kon-Taik Khaw, M.D.
Children’s Hospital ?tfedical Center, Department of Medicine and Ditision of Clinical Laboratories, and Department of Pediatrics, Harvard Medical School
(Submitted january 15; accepted for publication February 19, 1965.)
Supported in part by a grant from National Institutes of Health (A6339) and from the National Cystic
Fibrosis Research Foundation.
ADDRESS: (H.S., and K-T.K.) Children’s hospital, 300 Longwood Avenue, Boston, Massachusetts
02115; (L.L.K.) Children’s Hospital, Washington, D.C.
STUDIES
IN CYSTIC
FIBROSIS
689
PEDIATRICS, Vol. 36, No. 5, November 1965
C
YSTIC FIBROSIS 15 110 longer a diseaseconfined to infancy and childhood.
In the past, tile occasional survival of a
child beyond the age of 10 years was
un-usual, and tilere were practically no
au-thenticated adult cases. The geneticist con-sidered cystic fibrosis a lethal disease. In 1954 McIntoshu reviewed the records of
the older patients seen at the Columbia-Presbyterian Medical Center and recorded
27 affected with cystic fibrosis above the age of 10; 23 were living at the time of
the report and tile oldest was 1792 years. We, too, have had a similar experience.
In January, 1954, 21 or 12.4% of our 169
living patients were over 10 years and 5
patients had previously succumbed after
attaining this age.2 It was clear that a
number of our patients were progressing satisfactorily and would grow into adult-hood and that the care of these patients would fall into the hands of the internist. A later report (1959) from McIntosh’s clinic
by di Sant’Agnese and AndersenI covered
the period from 1939 through 1958 and included a total of 550 cases of cystic fi-brosis. Tilere were
as
patients living beyondthe age of 10, the oldest 24 years and there
were 21 others who succumbed after
reach-ing 10 years. Numerous publications from
this and other countries indicate that cystic fibrosis does occur in the adult and is
being recognized with increased
fre-quency.428
Four developments account for the
in-creasing number of adult patients. They
are: (1) A greater awareness of cystic
fi-brosis, of its protean clinical
manifesta-tions, 1tfl(l t clearer understanding of the
pathogenesis of
tue
disease. Pancreaticin-sufficiency is no longer considere(l an es-sential feature in every 2 \Ve are no longer (lealing with a rare genetic disease.
(2) Improved diagnostic techniques,
liar-ticulary the introduction of a practical
sweat test in 19542 led to the detection of
many unrecognized cases. This work was stimulated
by
the observation of di Sant ‘Agnese et a!. of the sweat gland defect incystic fibrosis. (3) The intro(lulction of
effective therapeutic measures, notably an-tibiotics, which reduce niorhidity and
cx-tend life expectancy.1 (4) Tile realization
that mild manifestations of the disease may
exist throughout childhood and escape
proper identification.
During the past 25 years an estimated 1,700 patients with cystic fibrosis, exclud-ing meconiuni ileus, were seen in our in-stitution. Tell years ago we recognized only 3 patients be’ond 17 years, and the
oldest patient studied at postmortem up to that time was 14 years of age.
The present study is desiglled as a progress report on our older patients, i.e., those above 17 years of age, the majority
of whom Ilave been observed by us over many years. We are not including the 15 patients who succumbed beyond tile age of 17, as they will be dealt with in a separate paper.
CLINICAL
MATERIAL-RESULTS
Fifty-one of the 65 patients were diag-nosed ill our clinic and 14 were diagnosed
lrior to their initial visit to us. These
pa-tients are listed in Table I, in the order of
duration of tile follow-up period. They are divided into two groups. The first group
of 48 incitl(les those patients who were diagnosed prior to our application of the “bag” sweat test in 1954. In these cases
the diagnosis was made on the basis of
the clinical and family history, physical
examination, x-ray of the chest, and duo-denal fluid examination which included assay for trypsin in all cases, for viscosity
in 40 cases, and for lipase and amylase
ac-tivity ill many. Forty of these 48 I)atients
had absent to markedly reduced trypsin
in their duodenal secretion, whereas 8
pa-tients had varying degrees of tryptic ac-tivity from partial reduction to full activity.
The viscosity of the duodenal fluid was
in-creased in 40 of the 45 cases in which it was measured. Later, the diagnosis was
confirmed in these patients by the quantita-tive assay of sweat for sodium and chlor-ide in 46 of the 48 patients and by the posi-tive palm print in the 2 patients who re-fused either the bag test or pilocarpine iontophoresis. The second group (listed in
Table I) includes the 17 patients who were seen by us for the first time within the
past 7 years, or since we have placed so
much reliance on the quantitative sweat test. Sweat was collected by the “bag”
method prior to 1959 and by pilocarpine iontophoresis after that time. Our previous
criteria were employed, with the exception of the analysis of duodenal fluid which
was not done on every patient.
The age at which the diagnosis of cystic
fibrosis was made and the age of each
pa-tient, as of January 1, 1964, is listed in Table I. Patient No. 15 was diagnosed as having intestinal obstruction at 2 days of
age. He is the oldest survivor among our patients with surgically corrected
meco-nium ileus. Patient No. 8 was also seen with intestinal obstruction at 1 day of age. It
was felt that he had meconium ileus, and
his obstruction was relieved without
stir-gery. He was not seen again until he was
31 ( , years of age when the diagnosis of
cystic fibrosis was niadle. \Ve have liste(l his follow-up as exten(ling over 182 years from the time of diagnosis rather than from
birth, 22:- years ago. Tue oldest patient
(No. 56) ill our study is 329’2 years of age.
He was first seen when he was 28 years
old and has the distinction of being the oldest living patient in whom we made the diagnosis of cystic fibrosis. The recog-nition of his illness led us to the same diagnosis of cystic fibrosis in his
20-year-old sister, who had had bronchiestasis
since childhood. When seen by us she had severe pulmonary insufficiency and
was 4 months pregnant. She succumbed
approximately 9 months later, or 4 months
after giving birth to a normal healthy boy.
The postmortem findings confirmed the
diagnosis of cystic fihrosis.2
Table I includes a column for the
re-cording of affected siblings. Five patients had no siblings and one patient was adopted. Of the remaining 59 patients, 33 (56%) had affected siblings. There were four pairs of siblings, with brothers and sisters in three instances and two brothers in the fourth case. Three patients had first cousins who were known to he affected with cystic
fibrosis. At present, we shall not elaborate further on the family composition of our patients. In no instance did we find clinical or laboratory evidence of cystic fibrosis in the parents of these patients.
Table II shows an analysis of the
follow-up period. In determining the duration of this period the initial visit corresponds to the date of diagnosis in 51 patients. In 10 patients, the time elapsed between the
diagnosis and referral to our clinic was less than 1% years. The patient listed as No. 58 is of special interest as he was
diag-nosed 3 years prior to our contact with him. He is a French medical student who elicited a recording in the French
litera-ture. Since this patient spent over 2
months under our care while this report
was in preparation, he is included. The 2
follow-ARTICLES TABLE I I F ‘2 F 3 M 4 F 5 F
iorty-Eight Patients with Cystic Fibrosis Followed from 8 to 224 Years
+ + + + 0 78 62 64 58 57 (6.fl 19 11 6 6 (1 F 1 1’ (; 61 57 57 58 72 19 19112 18 18 18 17 17 17 17 17 16 16 16 15iI 151’s 15 14H 14H 14 1315 13 13 13 8 12 7 1 12 1015 (; 7 S 9 10 11 12 13 14 15 16 17 18 19 ‘2() ‘26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 M M M M F M M M M F M M M M M F F F F F “I F M Tsr F M M F 6wk ‘110 1-s ‘-14 1-s H H 10 1-s 2(layS 12 -4 4 Si’s 2 9 1544 4is 4H 6 10’s I2 6 IOH 12 104 114) 160 90 93 105 86 121 96 112 104 142 106 113 84 123 122 134 106 160 114 109 176 71 99 112 135 III 104 132 110 206 118 124 139 66 95 97 11(1 117 86 94 108 103 118 103 1’21 126 135 114 115 99 124 125 97 116 150 114 99 173 73 104 112 121 106 149 132 121 209 124 110 145 68 94 109 (1 4) 0 (1 + 4) 4) + 0 0 + + + 0 + + + + + + + + 0 0 + 0 + + 0 0 + + 0 44 4) 11) 18 17H 17 l7 ‘-10 ‘1-s 19 17 19i*s “1 I I
j-18 181’s 19h 23 ‘29k ‘-9 “I-s ‘23h 24f1 1811 1811 F (I (; (; (1 G G (I; C, F F (1 G F P G C (; C I C F C C (; F F C (-; F F F (; (; 51 94 54 71 87 74) 82 71) 78 65 57 63 76 71 75 58 46 50 47 75 45 95 55 68 65 84 50 62 86 86
Patient No. Sex Duration of Follow-up (yr) Age (yr) Jan. 1964 Age (yr) J)iagnosed Sibs. with C. F. Sweat Test Na Cl mEql Recent C’linical Score 41 42 43 44 45 46 47 48 Tsr F TsI Tsr F F F Tsr Follow-up 10 9 8 8115 20 19’ 19 19’ 21 13 10 13 10 10 I3 1114 + 0 + + 0 0 + 0 201 120 115 119 98 109 133 80 212 106 114 138 86 102 134 96 53 67 67 65 74 65 74 67
Seventeen Patients with
P P P P C C (; C
Cystic hbrosis Followed from 6 Months to 615 years
49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 TsL F Tsr F TsI Ts[ F Ts1 TsI TsI F Ts1 Ts[ F M 6h 6, 615 15 f-s 10 H 4t 4 1-s 3 - is -1-s 12 12 1-I 12 I7 1815 C)) 9 --1-s 1915 19 )‘ 10 -1-s 10215 2011 1814 24’s 17J4 17115 14’ 1215 17 17 1411s 16 ‘28 151’s 1615 18i15 1615 17 1611 0 0 + 0 0 + + + + 0 + + 0 0 0 + 0 64 111 154 118 119 139 I’S 107 123 114 137 118 107 81 104 77 93 67 113 14-2 120 125 131 136 99 112 118 131) 115 110 97 100 8-2 104 53 70 89 65 81 79 75 86 79 66 76 82 57 68 72 75 70 (; (; (; C (; I F C C C C F C C (; C C 62
TABLE I (Continued)
up, both girls, are college graduates
sue-cessfuliy employed and engaged to be mar-ried. From Table II we see that 20 patients
were followed for more than 16 years, 38
for over 12 years, and 48 patients for over 8 years.
Tile patients are grouped according to
age at time of diagnosis in Table III. Eight
patients were recognized in their first year,
and 52% of tile total group were diagnosed
tinder the age of 10. Three patients were
diagnosed after having attained 21 years.
The age of diagnosis in our select sample
of older patiellts may be compared with a
random group of new patients, i.e., the
total number seen in any one year as silown in Table lIlA. One is immediately
impressed with the large number of pa.
tients diagnosed in early life. In a total of 85 new patients seen in 1963 50% were
diagnosed tinder 1 year, 74% under 7 years, and 91% tinder 8 years.
Tile clinical rating as of January, 1964, as well as tile age and sex distribution of the patients, are shown in Table IV. One
notes a preponderance of male survivors.
Of tile 65 patients, 42 or 65% are male. This
tendency is noted at all ages of patients listed. In contrast, is tile equal sex
TABLE III
AGE AT DIAGNOSIS IN 65 1ATIENTS UNDER STUDY
7 patients (2 males and 5 females) who are
married. One marriage occurred 5 years
ago, anOtiler 3 years ago, and the rest
oc-curred over 1 year ago. None of the 5
female patients, nor the spouses of the 2
male patients, have become pregnant. The severity of disease is reflected in our
system of rating.3’ A patient with a rating
of over 85 is considered in excellent
condi-tion, as judged by his performance, his
physical examination, his nutritional status,
and tile appearance of tile cilest x-ray. He
would be in a position to compete
physi-cally with ilis healthy peers, he wouldi have minimal findings on physical examination, his nutrition would be good, and tile chest
film would sllO\V no or very minimal
in-volvement. Complications such as
cirrho-sis, portal hypertension, diabetes mellitus,
bronchiectasis, and other pulmonary
com-plications exclude patients from this
“excel-lent” category. We note from Table IV that 6 of the 7 excellent scores are in males.
Four of the 6 men in tilis category have
completed college and vork gainfully; one is a teacher, another a plant supervisor,
an-other a mathematician and tile fourth is a
salesman. The three others in this excellent
group are still in school. The physical and sex development of these patients appears to he normal. However, since none are
par-ents one must await further specific studies and time for assessment. Tilere are 19
pa-tients in tile “good” group and 29 in tile “mild” group. The 10 patients listed as moderately ill (Table IV) were limited in
,
%o, of
Iears
Patient.,
Percentage . of Patients
Accumulated
Percentage
-of Patient.,
Below 1 yr
i-S
4-5 6-9
10-is
13-16
17-20 Over 21
8
10
9 7
9
ii
8 3
6.5
12
15
U Ii
ii
17
iS 5
100
12
27
41 52
66
83 95
100
their activities, unable to hold a full-time job or attend school regularly and were found to tire easily after exertion. Most are underweight, have a chronic cough, with
evidence of chron ic pulmonary infection
both cliilically and by x-ray. As a general rule they showed retarded sex
develop-ment. The girls showed late and often ir-regular menses. The prognosis in these pa-tients is poor. None of the patients fell in
the “severe” category, as of January 1, 1964.
Further analysis of the clinical rating, in relation to age and sex (Table IV) reveals tilat patients with varymg degrees of ill-ness were noted in each of the age groups. In other words, patients in “excellent”
con-dition were found both in tile younger
and older age group. However, in the “moderate” grotip, there appeared to be a larger number of younger patients. Six of
TABLE lilA
AGE AT DIAGNOSIS OF 85 NEw CASES SEEN IN 1963
TABLE II
1)UIIAr!ox OF FoI.I.ow-FP
hears
No. of
.
Patients
Percentage
-of Patients
Over 20 2 3
16-19 18 28
12-15 18 28
8-11 10 15
3-7 ii 17
Less than 3 6 9
65 100%
.4ge at Diagnosis No. of
Patients
Percentage
of Patients
Accumulated
Percentage
of Patient,
Meconium Ileu iwk-Smo
6mo-iimo 12 mo-SI mci
Syr-Syr 4 yr-7 yr 8yr-9yr
10 yr-iS yr 13 yr-i6 yr
l7yr-SOyr
Over Si yr
8 25
9 9
11 iS S
I S
S
1
85
9 30 11
11
13 18 S
I S
S
1
100
39 50
61
74 91
694
TABLE IV
CLINICAL RATING OF 65 PATIENTS BY AGE AND SEX
Age Group 17-18 19-20-21 22-23 Totals
Sex M F T if F T if F T ii F T
Clinical Score
Excellent 2 1 3 0
(;ood 4 3 7 3
Tsrild 4 i s 12
Tsroderite 4 2 6 2
lotals 14 7 21 17
0 4 0 4 6 1 7
5 1 6 7 8 11 19
17 5 2 7 21 8 29
2 I 1 2 7 3 10
24 II 9 20 4-2 23 65
the 10 “moderately ill” patients were in the
group 17 through 18 years.
The concentration of the sweat sodium
and chloride in mEq/1 found in each pa-tient tested is shown in Table I. We shall
not attempt a detailed analysis of our re-stilts but wish to point out that all values for sodium and chloride are above 60
mEq/1 .3’
Patient No. 49 with the lowest values, namely, sodium of 64 mEq/l plus chloride
of 67 mEq/l, presented a diagnostic
prob-lem since there is no pancreatic component and tile family history is negative. However, he has typical upper and lower respiratory involvement clinically and by x-ray.
Numer-Otis sweat tests were performed and the values varied from high normal to the low cystic fibrosis range. Recent additional con-firmatory evidence obtained by analysis of
1115 fingernail clippings places him in the
cystic fibrosis group.33 His case, along with
a number of similar ones in younger
chil-dren vill be tile subject of a special report
which will consider the interpretation of
borderline sweat electrolyte values.
At attempt to assess tile type or
ade-quacy of follow-up care is given in Table
I. The present status of the patients in rela-tion to the type of follow-up is shown in
Table V. Forty-three or 66% of the patients liste(l fall in the category of “good”
follow-lii). This nieans Periolic checkups at 3- to
6-month intervals and a consistent program,
with adherence to medical advice. For the
most part, the parents as vell as tile
pa-tients are conscientious and fully
co-opera-tive and have a fairly good understanding
of the disease. Of these 43 patients, 5 now reside at such great distances that it would be impracticable for them to continue to
report to us regularly. These patients have
been referred to cystic fibrosis centers
near-est them for further care.
Thirteen patients are listed under “fair”
in the follow-up column. These patients
may occasionally skip appointments and
can be Coullted to come when acutely ill or vllen there is some other urgent medical
demand. We have found it difficuit to im-press upon the parent or patient the im-portance of preventive medicine. If a
pa-tient has not reported to us for a period of
about 2 years, at any time in his follow-up, he voti1d be placed in this “fair” cate-gory.
There are 9 patients with a “poor”
fol-low-up. This means that these individuals
were seen by us at infrequent intervals be-cause they left our clinic or moved to
TABLE V
RELATIONSHIP OF Ci-InsENT CIINw-AL STATUS TO
ADEQUACY OF FoI.I.ow-uP IN 65 CF PATIENTS
. .
Clinical
Status
Adequacy of Follou’-up
(;ood Fair Poor Totals
Excellent Good Tslild Tsloderale
‘rotals
6 14 17 6
43
1
4 5
3
13
0
1 7
1
9
7
19 29
10
Sinusitis C
Nasal polvposis C
Atelectasis C
Bronchiectasis C
Ilemoptysis 0
Pneumothorax 0
Subcutaneous
emphysema R
Pleural effusion ... .R
Cor pulmonale R
Heat prostration ... .R
Rectal prolapse ... .0
Cirrhosis 0
Portal hypertension . .R
Hvpersplenism R
Anemia R
Fecal impaction with intestinal
obstruction B
Cynecomastia 0
Diabetes mellitus . .. .H
Pancreatitis R
Sterility 0
TABLE VII
CORRELATION OF AGE AT DIAGNOSIS AND CURRENT CI.iNic&r. RATING IN 65 PATIENTS
Age at Diagnosis
Clinical Rating
Excellent Good
Mild
Moderate
Totals
<1
I
3 3
I
8
1-2
0
4
C) 1
10
3-.;
0
I
4 4
9
6-9 10-12
2 1
1) 1
3 6
2 1
7 9
1.3-16 17-20
2 4)
7 I
2 5
1 1)
1-2 6
>20
I
‘2
I
0
4
Total
7 19 29 10
65 TABLE VI
(‘ouuF:l.TIoN (IF 1)uu:uTIoN 0)’ Foi.i.ow-ui’ VITII
(‘i.ixici. R-I’INo IN 65 PArIENTS
I)uration of (‘liniral Rating
Follow-up
- -
----
---
------
Tolili(yr) !zccl1ent (;ood .‘sJild .Uoderate
--- -_;;---
-_-;
_-;_----
I8-iS S 1 7 0 10
13-17 I 9 8 7 55
:
-- -:::
allother community and were no longer
under otir immediate supervision. Four of the 9 patients live at considerable distances from Boston and are followed in other
cen-ters. Five of the 9 patients reside close to Boston, i.e.. within a 3-hotir drive, but re-fuse to attend our clinic or any other clinic. Ignorance, poverty, parental attitudes, emo-tional, social and other factors have made it difficult to provide them with continuous
medical supervision. Of these 5 patients,
3 attended our clinic regularly for a
num-ber of years, only to reject medical care of
any sort after reaching adolescence. The other 2, diagnosed in adolescence, have re-fused to recognize their disease and report
to us only when in serious physical diffi-culty.
The present clinical rating in relation to
the length of time we have observed these
patients is shown in Table VI. We note that the patients now show varying degrees of illness irrespective of tile total period treated. Twenty-six patients are now in
“good” or excellent’ condition, half ilaving
been treated less tilan 13 years and tile
other half for I)eriO(ls ranging from 13 to
23 years. Hovever, 9 of the 10 moderately
ill patients Ilave heeil seen for over 13 years. This suggests that spite of “good”
follow-tip a ilumber of patients became progress-ively worse over tile years and that tile
condition of many of the newly diagnosed older patients is relatively “mild.”
The correlation of the current clinical
condition of the 65 patients with tile age at
tile time of diagnosis is shown in Table VII. There are somewhat fewer recordings of “excellent” and “good” in patients
diag-nosed tinder 10 years (11 otit of 34 or 30%) when compared to patients diagnosed be-tween 10 and 20 years (12 out of 27 or 44%).
A number of complications have been observed in this group of patients. At times it is diffictllt to tell whether we are dealing
with a complication or a feature of the dis-ease. Rather than detail individtial case re-ports we prefer to list those encountered followed by tile letter indicatiiig frequency:
R = rarely, 0 = occasionally, C =
In a few instances we could account for
complications such as deep staining of teeth
following long-term tetracycline therapy, or
goiter following prolonged iodides. We have not encountered optic neuritis or
aplastic anemia in this series of patients,
complications felt by some to be induced
by chloramphenicol therapy. Another s
en-Otis complication, botryomycosis has been noted oniy in otir younger patients.
Osteo-arthropathy with elevation of tile
Ierios-teum seen in some of our severely ill older patients has not been detected in these
pa-tieilts.
COMMENT
The recognition of cystic fibrosis in
in-fancy is simple when symptoms of
pulmn-any and pancreatic involvement are
pnes-ent. Tile diagnosis is confirmed when lab-oratory evidence of pancreatic insufficiency is obtained by dtiodenal inttibation or with a number of other indirect tests; the sim-plest of these is the stool trypsin test.
How-ever, the detection of pancreatic enzyme activity in duodenal fluid does not exclude
tile diagnosis. Tile eSCilCC of
charactenis-tic cilailges in tile chest film may lend
sup-Iort to tile diagnosis. The finding of an
elevated! level of sweat sodium and/on
chloride is essential for the diagnosis. The diagnosi 5 becomes increasingly difficult
\vilen only respiratory tract symptoms are
present, when unustial manifestations of pancreatic insufficiency occtirs, when liver involvement predominates tile picture, or
\vilen symptoms are first noted beyond adolescence or \vilen the sweat test is bor-derline. Fortunately, borderline elevatioll of sweat electrolyte levels are rarely en-countered. A positive family history is help-ful in all cases but especially so in assessing doubtftil or borderline cases. Our newly
developed tecllniqties of determining tile
sodium and potassium concentration in nail clippings is of value in such cases.
The question must be raised as to why so many of the patients in this series were diagnosed late in life. Only 12% of the pa-tients were diagnosed under 1 year of age,
whereas today approximately 50% of pa-tients in our clinic are diagnosed under 1
year. In an attempt to answer this we mtist
appreciate the fact that this disease was
initially described by pathologists as a fatal disease of early life. All patients with me-conium ileus died. The early clinical
de-scniption of cystic fibrosis incltided only infants and children who had complete
pan-creatic insufficiency. Those still possessing pancreatic function did not show the ad-vanced nutritional failure which dominated
the early clinical descriptions. Indeed some of these children may grow normally and on rare occasion even exceed the growth
rate of tile average healthy child. The often made statement of tile past, ‘she looks too well to have cystic fibrosis” shotild forever be abandoned. Considerable attention was
also paid to the celiac syndrome with efforts to separate cystic fibrosis from tilis waste
basket group of entities. We now wonder how cystic fibrosis was so long confused with
celiac disease, and why some people still classify cystic fibrosis as a stibgrotip of the
celiac syndrome. With further clinical ex-perience came the appreciation that patients
with cystic fibrosis are affected differently, that one can actually assess severity by a nu-menical score and that complications of the disease may be the presenting complaints. The diagnosis prior to the establishment of the correct one in this series of patients included the following: chronic bronchitis,
asthmatic broncilitis, asthma, pneumonia or
recurrent pneumonia, bronchiectasis, pul-monary ttiberculosis, sinusitis, nasal poly-posis, celiac disease, rectal prolapse, hepatomegaly and portal hypertension, and heat prostration. In several instances ex-tensive stirgical and medical therapy had been employed and in a few instances pa-tients had been placed in tuberculosis
sani-tania prior to the correct diagnosis. Indeed the disease ran a mild course in the ma-jority of newly diagnosed older patients.
We believe our program of medical su-pervision had much to do with the large
number of survivors. We fully realize that
un-supervised and reach adulthood. To help
assess the wide variation in disease pattern we included data to indicate severity of
dis-ease as well as assessment of the adequacy of follow-up.
Our present plan of therapy is described in detail in a chapter in Shirkey’s text.37 Many of the meastires now employed were
not available when the majority of patients in this report were diagnosed. However,
dietary regulations with emphasis on low fat and high protein diet, witil pancreatic enzyme replacement, and muitivitamins were advocated from the beginning of tile
clinical recognition of this disease in our
institution in 1938 and 1939. The manage-ment of the pulmonary involvement which may be initiated by a diffuse obstructive process Witil secondary infection has al-ways presented the most difficult and
chal-lenging problem. Tile greatest single ad-vance came with the introduction of aureo-mycin in 1948 and otir convincing evidence to show that this agent was far superior to any previotisly available one, in tile
treat-ment of the chronic lung disease. Aerosol
therapy with penicillin was employed in some instances as early as 1946. Mist tent therapy was first used on occasion in the
home in 1954.’ Prior to 1956 attempts at physical tilerapy were sporadic and only
advanced cases of bronchiectasis were
re-ferred to our phvsiotilerapist. In 1957 all active physical therapy program was
in-stituted in our ciinic.3#{176} Aside from these
important advances in therapy a few minor changes which slowly evolved over the years may play a greater role than we are
able to quantitate. These are factors that
have to deal with the economic, emotional, and psychological problems of parents and
of growing children having a disease
ex-pensive to treat and with an unpredictable ftiture. Otir constant availability for guid-ance, the close and harmonious relationship
to the family physician or pediatrician, and
of highly skilled experts in otir medical
center, our attempt to secure financial as-sistance and to provide contintiotis long-term care by tile same group of individuals
regardless of age of patient, cotipled with
efforts to instruct otir parents and above
all our positive approach undoubtedly
con-tributes to the relative success of our pro-gram and survival of some of these
pa-tients beyond adolescence.
SUMMARY
The present report is an analysis of 65
patients with cystic fibrosis who are 17 years of age as of January 1, 1964. The
oldest patient in this series is 329, with a mean age of slightly over 20% years for the
entire group. It is tinique to have tile
op-portunity to follow a large group of pa-tients from early life beyond adolescence
in a pediatric center by the same group of physicians. The follow-up period varied from over 20 years in 2 patients to less tilan
3 years in 6 patients, with an average of over 113 years for the whole grotlp. The earliest diagnosis was made at 2 days in an infant with meconium ileus. This boy, now 17 years, is our oldest stirvivor of meconium
iieus corrected surgically.
The diagnosis was made in 8 patients in
tileir first year of life and 34 of the 65 pa-tients were diagnosed tinder 10 s-ears of
age. Fifty-one of the 65 patients were diag-nosed by us and 14 were diagnosed prior to referral. Forty-two or 65% of patients are male, whereas the sex incidence is equal in infancy and childhood. Of interest are
the 7 patients who are married. None have borne children. The present clinical status of these patients is excellent in 7, good in 19, mild in 29, and moderate in 10. The type of follow-tip care was considered good
in 43 cases, fair in 13, and poor in 9. Brief attention is given to changing concepts of
tile disease especially as it relates to diag-nosis and therapy. Since 1954 when the sweat test was iiltrodticed by us as a prac-tical method we ilave considered this the most reliable single diagnostic test. Prior
to 1954 all patients were subjected to duo-denal intuhation. These patients with no
have a positive sweat test. The changes in
therapy as it has evolved over the years are mentioned. The most important single
ad-vance noted was the introduction of broad spectrum antibiotics in 1948, followed in the last 10 years by a variety of measures
designed to keep the bronchopuimonary tree “clean.”
We feel tilat the early detection of this
disease, i)ltis the application of our ctirrent
modes of therapy, will not only prevent
numerous complications but will provide a
much better prognosis for life.
ADDENDUM
Since the analysis was made 13 addi-tional patients reached 17 years of age as of January 1, 1965. Four patients died in 1964. The number of patients over 17 as of January 1, 1965, is 74.
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2. Shwachman, H., Leubner, F!., Catzell, P.:
Mucoviscidosis. Adv. Pediat., 7:249, Year Book Publishers, 1955.
3. di Sant’Agnese, P. A., and Andersen, D. H.:
Cystic fibrosis of the pancreas in young
adults. Ann.
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case in a twenty-year-old female. New EngI.
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5. Baumgartner, U., and de Voogd, K. K. : Zwei
Falle von Mucoviscidosis im
Erwachsenen-alter. Schweiz. Med. Wschr., 89:130, 1959.
6. Burnard, E. D.: Congenital pancreatic fibrosis:
Report of survival in young adults. New
Zeal. Med. J., 52:395, 1953.
7. Caldwell, D. NI., and McNamara, D. H.:
Fibrocystic disease of the pancreas and
diabetes in an adult with unusual pulmonary
manifestations. Calif. Med., 89:280, 1958.
8. Cece, J. D., Henry, j. P., and Toigo, A.:
Pan-creatic cystic fibrosis in an adult. J.A.M.A.,
181:31, 1962.
9. Dalifino, C.: La rnucoviscidosi deli’ adulto. Rivista sintetica t contributo casistico. Med. Clin. Sptr., 12:403, 1962.
10. de 1-Ialk’r, H., and Siegenthaler, P.:
Muco-viscidose de ladulte. Rev. Med. Suisse
Horn., 82:42, 1962.
11. Desmond, F. B.: Pancreatic fibrosis and
bron-chiectasis in an adult. New Engi. J. Med.,
62:380, 1963.
12. di Sant’Agnese, P. A., and Jones, W. 0.: Cystic fibrosis of the pancreas. Amer. Intern.
Med., 54:782, 1961.
13. Dubach, U. C. : Die NIucoviscidose des
Er-wachsenen. Schweiz. Med. Wschr., 92:783,
1962.
14. Fanconi, A. : Postneonataler Kotiieus hem
cvsti-scher Pancreasfibrose. 1-Ielv. Paediat., Acta
15:566, 1960.
15. Frischauf, A. : Zvstische Pancreasfibrose bei
ciner 16 johnigen. \Vein. KIm. Woch., 64:
504, 1952.
16. Hendrix, R. C., and Cood, D. N!. :
Fibro-cystic disease of the pancreas after
child-hood : Case report with necropsy at age 17
years. Ann. Intern. Med., 44:166, 1956.
17. Israel-Asselain, R., Chebat, J., and Lechien,
J.: Un cas de mucoviscidose. A
determin-ation bronchique predominante et a
evolu-tion prolongee chez un jeune adulte.
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Franc. Med. Chir. Thorac., 15:457, 1961.
18. King, R. : Fibrocystic disease of the pancreas
in an adolescent with minimal pulmonary
involvement. Arch. Dis. Child., 31:270, 1956.
19. Kohl, H. W/. : Fibrocystic disease. Arizona
Med., 5:47, 1948.
20. Lepore, M. J.: Cystic fibrosis of the pancreas
in the adult. Castroenterologv, 44:696,
1963.
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aged 46. Lancet, i:365, 1960.
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with chronic pulmonary disease and
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26. Siegenthaler, P., and de Hailer, B.: La
muco-visci(lose de iadulte, maladie rare. Schweiz. Med. Wschr., 93:1528, 1963.
27. Trever, R. W., and Abrahams, I. W.: Cystic
fibrosis of the Pancreas: Clinical features
ill adolescence and early adult life. Arch.
Int-rn. Nied., 106:253, 1960.
28. Weiner, J.: See Ref. 2, pp. 267-268.
29. Shwachman, ii.: Progress in the studs- of
30. di Sant’Agnese, P. A., Darling, R. C., Perera,
C. A., and Shea, E.: Abnormal electrolyte composition of sweat ill cystic fibrosis (If
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and Patterson, P. H.: Aureomvcin therapy
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the pancreas; report of a case. Obstet.
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33. Shwachrnan, H., and Kulczycki, L. L.: A
report of one hundred and five patielits
with cystic fibrosis of the pancreas studied
over a five to fourteen year period. J. Dis.
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34. Shwachman, I-i., and Antonowicz, I.: The
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K. 1., Shwachrnan, II.: Studies in cystic
fIbrosis: Analysis of nail clippings for sodium an(l potassium. New EngI. j. \Ie(I., 272:504,
1965.
:36.Katzuelsen, D., Vass ter, C. F., Foley, C. F.,
and Shwachrnan, II.: Botryornycosis, a
com-plication in cystic fibrosis. Report of 7 cases. j. of Pediat., 65:525, 1964.
37. Shwachman, H., and Khaw, K. T.: In
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38. Denton, B.: The clinical use of continuous
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39. Doyle, B.: Physical therapy in the treatment of cystic fibrosis. Physical Tiler. Rev., 39: 24, 1959.
RHEUMATIC FEVER DIAGNOsIs,
MANAGE-MENT AND PREVENTION, by Milton Marko-witz and Ann Gayler Kuttner.
Philadel-phia: W. B. Saunders, 1965, 242 pp.,
$7.50.
Although the mortality from acute
rheuma-tic fever has steadily declined during the last
few decades, this disease still remains a serious problem for the practitioner. Rhetimatic fever
is a challenge because the diagnosis is some-times difficult, the pathogenesis not clear, and the drtigs used ill its treatment stippressive
rather than curative.
This well-written book offers the reader
more than it promises in the title; it covers the
etiology, pathogenesis, pathology, diagnosis,
management, and prevention of i-hetlnlatic
fever as well as the biology of the beta
hemo-lytic streptococctis. The general practitioner
and pediatrician will benefit from reading this book; the physician engaged in research will
find the volume of value because it provides
an imposing amotint of data and an extensive bibliography comprising close to 500
refer-ences.
It is a pity that in a few instances the au-thors seem biased in summarizing conclusions
drawn from the literattlre. A case in point is to
be fotind in the chapter concerning the
treat-ment of severe rheumatic carditis. We feel that the authors do not sufficiently emphasize the life-saving effect of the steroids in patients
with severe rheumatic carditis and congestive
heart failtire or pericardial effusion. They do
ilot mention that the majority of physicians
fa-miliar with rheumatic fever feel it obligatory to
prescribe ACTH or steroids in such cases. The
practicing physician cotild be misled if ile
were to follow the suggestions of the authors
aild might even imperil the life of the severely
sick rheumatic fever patient if he were to use
steroids only 111 severely ill patients with rheumatic mvocarditis of recent oliset’ or
should delay its adnlinistration and give “a short course of ster&ds” only if the disease of
the myocardium becomes “life threatening
during the acute stage of the illness.”
The illustrations of electrocardiograms and
roentgenograms are veli chosen and are of
ex-celient (1ality. Especially’ impressive are the
roentgenograms of the chest showing the
dra-matic effect of “suppressive therapy” on
rheu-matic pericardial effusion. The rapid change ill
the size of the heart silhouette shown in these
picttires is striking. \Ve think the practitioner
would like to know which of the “suppressive
agents produced SO dramatic an effect. We suspect it was one of the steroids because we
do Ilot see such a dramatic response to
actyl-salicyiic acid. If this is the case, why do the
authors not specify the “suppressive agent in
the subtitle of the chest films? Is the enigmatic
stibtitle another sign of the prejudice the au-thors cherish against steroids?
In summary, this volume is highly
