Harry Shwachman, M.D., Lucas L. Kulczycki, M.D., Harry L.
Mueller, M.D., and Carlyle G. Flake, M.D.
The Division of Clinical Laboratories, the Departments of Medicine and Otolaryngology, Children’s
Hospital Medical Center, and the Departments of Pediatrics and Surgery of the Harvard Medical School
Supported in part by the Children’s Cystic Fibrosis Association of Connecticut, Inc., and by Grant
E1560 from the National Institutes of Health, U. S. Public Health Service. Submitted for publication November 17, 1961; accepted May 22, 1962.
ADDRESS: (H.S.) 300 Longwood Avenue, Boston 15, Massachusetts.
PEDIATRICS, September 1962
NASAL
POLYPOSIS
IN
PATIENTS
WITH
CYSTIC
FIBROSIS
389
I
N REcENT YEARS, nasal polyposis has beenobserved with an impressive frequency
in patients with cystic fibrosis. The
in-creased longevity of patients with this
dis-ease, due to improved therapeutic measures
and the recognition of mild forms of the
disease, or of its partial expression in some
patients, provides an opportunity to observe
new manifestations or complications.13
Nasal polyposis is one such manifestation
which may occur at any age beyond
in-fancy in the course of the disease. Since
nasal polyps are unusual in children, their
occurrence in patients with cystic fibrosis
may be of particular significance. The
pur-pose of this report is to present clinical and
laboratory observations made during the
past 4 years on patients with cystic fibrosis
found to have nasal polyps. The generally
accepted belief that nasal polyps are a
manifestation of respiratory gy45 also
was considered in these studies.
CLINICAL MATERIAL
The diagnosis of cystic fibrosis was
es-tablished by clinical and laboratory
ex-aminations. The clinical manifestations of
pancreatic insufficiency or of pulmonary
in-volvement, either alone or combined, were
present in all patients. Laboratory studies
included a quantitative assay of sweat for
sodium, potassium, and chloride. Values of
sodium and chloride above 60 meq/l were
considered significant, whether sweating
was induced by the bag method, or by
pilocarpine iontophoresis.”6 Duodenal
intu-bation and enzyme assay for pancreatic
enzymes was done in a large number of
patients, including a few patients who did
not have a sweat test. The general plan of
management of patients with cystic fibrosis
has been reviewed recently. Whenever
physical examination disclosed nasal polyps,
the patient was seen in consultation by a
staff otolaryngologist. In addition, each
pa-tient with nasal polyps was seen in the
Allergy Clinic, where the allergic history
was reviewed and scratch tests with 76
allergens performed. Nasal smears and
cul-tures were done on the majority of patients.
A correlation of skin test results and
clini-cal symptoms was attempted in each case.
All 50 patients had rotengenograms of the
chest, and 44 of the 47 living patients with
nasal polyps had roentgenograms of their
paranasal sinuses. The tissues removed at
operation were examined in the Department
of Pathology by Dr. Gordon Vawter.
Se-lected polyps were studied in mammalian
cell culture by Dr. C. E. Foley, The
Chil-dren’s Cancer Research Foundation.
CLINICAL OBSERVATIONS AND RESULTS
During the past 4 years 50 (6.7%) of 742
patients with cystic fibrosis were found to
have nasal polyposis. In Table I, these
pa-tients are grouped according to age at the
time of diagnosis of cystic fibrosis, age at
diagnosis of nasal polyposis, and
chrono-logical age as of April 1, 1961. The
diag-nosis of cystic fibrosis was made before 1
year of age in 20 patients and before 4
years of age in 30 of the 50 patients. In
43 (86%) of the patients, polyps were
de-tected between the ages of 4 and 13 years.
TABLE I
Firrv PATIENTS WITH CYSTIC FIBROSIS AND NASAL
POLYPOSIS: AGE AT DIAGNOSIS AND AT FOLLOW-UP
<1
‘2- 3
4- 6
7- 9
10-1’2
13-15 16-19
5: ‘20
Number of Patients with
Polyps Notei*
Before Diagnosis After Diagnosis
ofC.F. of CF.
Time interval
(i,r)
* In one additional patient nasal polyposis and cystic
Age
yr)
NUMBER OF PATIENTS IN AGE Guouc
At Diagno.is
yslec asat
.
r ioiosis 011/7)0818
Al loilnw-np
.
on April 7, 196l
0 0 .
10 ‘2 ..
6 13 6
6 18 12(1)
‘2 P2 14(1)
‘2 1 4
‘2 3 7
‘2 1 4(1)
* Numbers in parentheses refer to the three patients
who died.
patients. During tile period of this study,
three patients witil polyps died. It should
he noted (Table I) that the majority of
pa-tients with nasal polyps are, at this writing,
more than 10 years of age.
The time relation between tile diagnosis
of nasal polyposis and cystic fibrosis is
mdi-cated in Table II. In one patient, the
diag-nosis of nasal polyposis and cystic fibrosis
were made simultaneously, on the initial
visit. Nasal polyps had been noted in eight
patients prior to the diagnosis of cystic
fibrosis. The diagnosis of cystic fibrosis was
TABLE II
INCIDENCE OF POLYPOSIS WITH RESPECT TO
DIAGNOSIS OF CvsTIe FIBItoSIS
0 5 <‘2
4 13 3-5
1 P2 6-8
‘2 7 9-11
1 4 12
Total8 41 ..
established in four of these patients
be-tween 3 and 5 years after tile recognition
of nasal polyps, and in one instance the
time interval was more than 12 years. In
the 41 remaining patients, nasal polyps first
appeared after the diagnosis of cystic
fibrosis had been established; and again, in
four instances, polyps were first noted as
long as 12 years or more after the
diag-nosis of cystic fibrosis had been made.
Allergic Investigation
These 50 patients with nasal polyposis
could be divided into two groups, based on
the presence or lack of evidence of allergy.
In 24 patients no evidence of allergy could
be elicited. Although 18 of these patients
(Table Ill-A) had either nasal obstruction,
discharge and stuffiness, or wheezing, none
of these symptoms could be establisiled as
due to allergy, and all could be adequately
explained as symptoms of cystic fibrosis and
nasal polyposis. The remaining 26 patients
were considered to be atopic, and are listed
in Table Ill-B in order of the severity of
their cystic fibrosis, as adjudged by a
sys-tern of clinical evaluation in use for the past
6 years.2 In this scoring system, 100 is the
maximum score. Four categories are
evalu-ated, each with a maximum assigned value
of 25 points: (1) general condition and
ac-tivity of the patient; (2) physical findings;
(3) nutritional status; and (4) evaluation of
the chest roentgenogram. According to this
system of rating, a patient with a score
above 85 is considered to be in excellent
condition, and those between 71 and 85 to
be in good condition. Scores between 56
and 70 indicate mild, between 41 and 55
moderate, and 40 or below, severe disease
activity. At the present time, none of the
47 surviving patients fall in the group with
severe disease on the basis of clinical
evalu-ations made within 4 months prior to April
1961. In addition to this clinical evaluation,
the ages of these patients as of April 1,
1961, age at diagnosis of cystic fibrosis, age
at diagnosis of nasal polyposis, evaluation
of the allergic investigation, and the
con-centration of electrolytes in sweat are
391
The patients in the atopic group had
positive results of skin tests and the
follow-ing symptoms; sneezing, itchy noses, runny
noses, and occasional wheezing, which were
not adequately explained by cystic fibrosis
and nasal polyposis. These patients
pre-sented one or more of the following
addi-tional criteria of atopy: (1) response to
anti-allergic medication; (2) correlation with
skin tests; (3) response to hyposensitization;
and (4) response to elimination. Seven of
these patients had been diagnosed as having
nasal polyposis on an allergic basis by their
own physicians prior to referral and
inclu-sion in these studies. The three patients who
died were among these seven patients. The
26 atopic patients (Table Ill-B) may be
sub-divided into two groups; 15 of these
pa-tients show a good correlation between
al-lergic symptoms and skin tests, and a
num-ber of these individuals are responding to
anti-allergic therapy, while there appears
to be no correlation between results of the
skin tests and allergic symptoms in the
re-maining 11 patients. It is evident, by
corn-paring the data summarized in Tables Ill-A
and Ill-B that age distribution, range of
severity of disease, and concentration of
sweat electrolytes are generally similar.
However, there is a striking difference in
sex distribution. Of the 24 nonallergic
pa-tients, only 9 were males, whereas of the
26 atopic individuals, 19 were males. This
preponderance in the incidence of atopy
among male children is, of course, well
known.
Other Observations
The facial appearance of children with
nasal polyposis is often characteristically
distorted as a result of prolonged chronic
nasal obstruction, with depression and
wid-ening of the nasal bridge (Fig. 1).
Roent-genograms of the paranasal sinuses were
obtained in all but three living patients.
In every case of nasal polyposis theme was
evidence of ethmoidal and maxillary sinus
involvement. In the older patients in whom
the frontal sinuses were developed,
opaci-fication of these sinuses was also noted.
The appearance of the maxillary and
eth--‘.4
j
FIG. 1. Patient 18, at 10i years of age. Note widened and depressed nasal bridge.
moid sinuses on the x-ray film may be hazy,
and suggests, in addition to the swelling of
the mucosa, the presence of fluid or
exu-date. Bone destruction or sclerosis, and
otitis media, deafness, and anosmia may
occur. One patient has suffered from
recur-rent otitis media for more than 10 years,
with frequent need for draining of the
mid-die ear.
Nasal smears prepared with Hansel’s stain
were studied in 28 cases. Sixteen patients
were in the nonallergic group; of these, 14
showed no eosinophils on a single nasal
smear. One patient had a 4-plus eosinophilia
on one occasion and no eosinophils on
me-peat smears. One other patient had 1-plus
eosinophilia on one occasion, and of the
12 patients studied from the atopic group,
3 showed occasional eosinophils, and 9
showed none. In one patient the peripheral
blood smear revealed an 8% eosinophilia,
with only a few eosinophils in the smear
of the nasal mucosa.
Nasopharyngeal cultures were obtained
392
ot-s,.I o,xo
Si
- #{149}1 - - #{149}IS--- ei -
-J
: , “ “‘ -o-. #{149}..oot- t-.t---, . . . . . .t- . t-.o#{248} t-o-
.-t , -Q o,
- I e,-e,©
*o-t- ,I - - © t- t- ,, ., ,, - © -p #{149}00 t- t- t- t- . t- t- t- t- t- t. ‘0 ‘
. . .5 C ,) V -p o C ; -,0 t-t-C . “ ,-; -P , - 0t-:h ‘3 l 00--X0G0-0F-- t--P z B a z B E-4 z a c) S S .2 .2
z
r12 S B I, -3 a.4 -3 1)z
B I’ z B I, a.4 c4 z a a I, S B .3 .2I
., p
j
i o 0 . 0 0 t- t- t- .0G4 ‘.4 4 ‘.4 ‘. 4 4 4 ‘ ,
-: ui C .! -,‘ . .-
--ic
Z ZZZZZZZZZZZZZ ZZZZ ZZ ZZ
.;
C
. . . . .‘ .
- . .
-. C ‘.z C.
‘: :::::::::;: ::::
‘;‘;
‘:;:
,..% ‘ . “I#{149} 0 :;0 t-000040020 00P0
?
#{149}B.
V.)
‘
w -‘.oo oo
- -
-000 00 t-”
C
,
X0
z: 2’ ‘2
B C 0 -C -C .d c) C ‘C 0 C C 0 z C 0 E .0 0 C I’
.
00-’.) ‘C
0G)
#{149}
‘C-I
00 *)00
00
#{149}
0 - 00 00 00: :
4
0., 000 0’0-’0
C,-p $ owo
#{149}
#{149}
#{149}000-p004
#{149}
0040lO4.0
t-t-t- t-’o’o
00 0 4 00 0 4 00 0 00
‘C0- 0’00P-P-P- ---0’C 0,-0 -00t’-t’-0000 04G,,, 00-04 ‘O
0000 -pG’ 0 -t-*t0 pO ©
. #{149}00 V00C
0000
#{149}-
“ ! 00‘0000 ‘0 0 00’C000 00 04
oGiGi :-
.
040 “ 0.,_0- 04S,
#{149}
000004 -) 0-p t- 00 t- t- t- - t- ‘C
00 00 00 - - 0- - t- ‘- t- 00 00 ‘0
- - 0 - 0 ‘C ‘C 0- 0 00 00 * C) -‘
-p 0 0 - G X 0- t- 0 0- 00 0
040404
4---p0 0_ -0’C’C t- ‘C -P
04044 4
.,, . 0 0 -p S 0 0 G4 0 0 00 00
04 01 04 04 4 4 04 04 GI 04 04 04 4 ‘
-C
i:.1i
.
000 0000 0000 00 0
0a0I, IOM Z
.s
- s-“ . C 0 0 -Co ‘3 #{149}2 C :: .5 c..)
.
.C 0 ‘2 .5 C.
0.
Cc.) I. P4 Co 0 I.-C 0 -C S C-C S B Co S -a c) C -4 Co 0 B C -C C C-C.,J 8 .‘
. .
.5 .5 .5 .5_C
V
‘.B C .d. .s .i
#{149}
‘.‘4: OV.’ .0 .- -0
.
z Z&3u ZZ ZZ Cl) )
ss ‘‘‘ C 8 C 0 C -C 0 C 0 .0 -C .0 C C C C C z C C U .0 C .0 C z C .0 . V .0 ,; #{149} C
000 t-000 000000 0 00 0
2:2 0000t- 000t-- e
00 0 0 4 t- 00 0 4 -‘ ‘P 00 ‘0 0
‘0 G4 00 0 -P 0 00 0 00 0 00
G4 - -
-t- - 00 #{149}0 0 00 0 ‘ 04
00 00 0 00 00 0 04 00 00 00 04 00 *0 00 0-_*) c4,
a
zz ZCI2ZZZZCIDZ 00-00 0000000G400 -p=’0 0-000-004 P000 --P0 G4000G4040- ) - -P 0- 00 4 -.00 00
000 00000000-a
coo S4
‘0000- 000
30
15 (6 mucoid strains)
8 5 5 4 3 1 1
1
treated with broad spectrum antibiotics.
The most widely used agents were
chlom-tetracycline, erythromycin,
chiorampheni-col, novobiocin, sulfisoxazole (Gantrisin),
and acetyl sulfamethoxypyridazine (Kynex).
In addition, a few patients had received
aerosol therapy with neomycin, or with a
mixture of penicillin and streptomycin. The
micro-organisms isolated from the
naso-pharynx of these 45 patients are as follows:
Micro-organLs-m Patients (no.)
Micrococcus pyogenes var
aureus
Pseudomonas aeruginosus
Streptococcus “viridans”
(unclassified)
Hemophilus influenzae
Neisseria catarrhalis
Candida (unclassified)
C. coli
Proteus (unclassified)
Micrococcus tetragenes
Diplococcus pneumoniae “Diphtheroids”
Cell Cultures
Six surgical specimens of nasal polyps
were cultured in the mammalian cell
cul-ture media described by Eagle.9 Foley et
a!.’#{176}isolated cells from all of these
speci-mens in vitro, and established five of the
six cultures as serially propagated cell lines.
These cell lines thus far are
indistinguisha-ble from one another nutritionally and
his-tochemically, and in general, resemble the
majority of other “normal” mammalian cell
lines maintained in serial culture. The
sig-nificance of these observations cannot be
assessed at this time, since there is as yet
no means of determining the precise
histo-logical origins of such cell lines. Cell lines
so derived from surgical specimens of
polyps from patients with cystic fibrosis
may have had no distinguishing
physiolog-ical function in vivo, or physiological
func-tion may have been lost or suppressed by
serial propagation in vitro.
Clinical Course
The child may have no complaints, or
he may have obstructive symptoms with
or without nasal discharge, prior to the
detection of nasal poiyps. The nasal mucous
membranes and turbinates may be so
edematous and pale as to suggest allergic
rhinitis, for which such patients may have
been treated. Investigation of nasal
ob-struction may reveal nasal mucosal
poly-poid formation with extensive sinus
involve-ment. Examination by an experienced
phy-sician revealed polyps which, in a
num-ber of instances, had not been detected for
a considerable time. Tonsillectomies and
adenoidectomies had been done in an effort
to relieve the obstruction in a number of
these patients.
Nasal polyps may be single but are more
often multiple on either side or bilaterally. In
the 50 patients considered here were 29 cases
of bilateral polyposis. Polyps arise from the
sinus mucous membranes and often
pro-trude from the middle and inferior
turbin-ates. Where obstruction occurs, the
thera-peutic procedure has been a simple
polypec-tomy. This provides temporary relief for
varying periods of time. The polypoid tissue
removed from a 6-year-old patient is
illus-trated in Figure2. Regrowth occurred within
3 weeks in a few instances, although in many
cases no significant regrowth has occurred
over a number of years. Thirty-one patients
had polypectomies; 18 on one occasion, 2 on
two occasions, 3 on three to six occasions, and
in 8 patients polypectomy was done more
than six times. Four older patients had
sufficient discomfort to require
polypec-tomies as often as every month to several
times per year for a number of years.
Nine-teen patients have not had sufficient
ob-structive symptoms to require polypectomy.
The suppressive effect of oral therapy with broad spectrum antibiotics on the rate of regrowth of the nasal polyps is
impres-sive. In the four patients requiring frequent
polypectomies, the intervals between
surgi-cal intervention lengthened as soon as daily
antibiotic therapy was instituted. The local application of agents such as antthistamines,
hydrocortisone, astringents, and antibiotics
have provided slight transitory relief. One
‘
gl1Iuifi I
“1k1
I
U1flU
‘Al
i”IJI
I
i1L”
, FIG. 2. Case 3. Nasal polyps removed from 6-year-old child.unwise because of extensive bronchiectasis
was provided some relief and shrinkage of
polyps by the use of nasal hydrocortisone
drops.
A summary of the observations on 47
living patients is presented in Table IV.
CASE REPORTS
Three case reports are presented to
illus-trate some of the problems encountered.
Case 1
H.S. was born in Connecticut on April
9, 1931. His growth and development were
considered excellent during infancy and
childhood. At 6 years he moved to
Tennes-see, where he lived for 12 years, except for
one year in Texas (between ages 9 and 10),
where he was ill with heat prostration. He
complained of nasal obstruction at 11 years
of age. Nasal polyposis and paranasal
sinu-sitis were noted at 16 years. At 18 2/12
years he had bilateral Caldwell Luc
opera-tion and left transantral ethmoidectomy. Six
months later he developed an acute
respira-tory infection and soon afterwards was told
he had multiple allergies. His response to
dust vaccine and a special diet was poor.
The nasal obstruction reappeared,
intra-nasal windows were enlarged on both sides,
and polypoid material was removed. At 22
years, the left ethmoid region was again
filled with multiple polyps and purulent
dis-charge. The above changes, together with
paranasal sinusitis, persisted until the
pres-ent time, requiring repeated drainage and
polypectomies. He has relatively clear lungs
and no clinical evidence of pancreatic
in-sufficiency or hepatic involvement. He
served in the Army and was considered to
be in good health. However, a diagnosis of
gastric ulcer was made at this time. He is
TABLE IV
OBSERVATIONS ON FORTY-SEVEN LIVING PATIENTS WITH CYSTIC FiBRosis AND NASAL POLYPOSIS
Chronic paranasal sinusitis
by roentgenogram
Positive family history for
allergy
Sex incidence
1 (100%) 6 (100%)
1’2 (57.1%) 9 males
(4.9%) Negative to 76 allergens
16
‘2
P2
9 14 4
4
‘20 ‘23
20 ‘23
1 13
5
‘2 21 Non-atopic
Type of Observation Patients 6 Ato pie
Patients
Skin tests
Correlation of skin tests with symptoms
Nasal smears for eosinophils
(a) examined (b) positive Bilateral nasal polyps
Unilateral nasal polyps
Polypectomies More than twice
Incidence in the same (am-ily (3 families with sib-lings in each)
Partial pancreatic involve-ment
Abnormal sweat electrolytes
Tested Positive
Clinical status of patients Excellent
Good Mild Moderate
may explain in restrospect the episode of
heat prostration. The diagnosis of cystic
fi-brosis in this man led to a family
investiga-tion, with the discovery of cystic fibrosis
in his younger sister, who had been treated
for bronchiectasis since early childhood.
Case 2
V.S., now nearly 15 years of age, was
21 (80
.
8%) given a diagnosis of cystic fibrosis when she(73.1%) was 3 4/12 years of age, on the basis of a
Positive duodenal fluid assay. A younger sibling was
known to have cystic fibrosis. The
pa-tient had large, foul stools, with frequent
15 (57.7%) rectal prolapse, in infancy. Since her lungs
P2 were clear she received antibiotics only
‘2 with each respiratory infection. At 11%
15 years of age she complained of intermittent
I 1 nasal obstruction, and nasal polyps were
1: noted. Two years later, the right nasal
air-way was completely obstructed. X-mays
me-vealed ethmoidal sinusitis and minimal
pul-i; monary changes. Many polyps were
me-S moved from the might side, including a
large one hanging down into the
naso-pharynx. The left nasal cavity was free of
polyps. During the subsequent 2 years, the
patient’s pulmonary condition improved to
1 such an extent that chest films have been
9 interpreted as nearly normal. However, se-S vere paranasal sinusitis, with secondary
ob-struction and opacification of all sinuses,
persisted. This patient is now in good
health. The family history is negative for
allergy. Two younger siblings have cystic
fibrosis.
This case lends support to the impression
that nasal polyps may occur in such
pa-tients, regardless of the severity of the
pul-monary process. In this patient, pulmonary
involvement was mild and was favorably influenced by removal of the nasal obstruc-tion.
His younger sister was first seen at the age of 20 years, when she was 4 months pregnant. She had extensive bronchiectasis and a positive sweat test, with a sodium concentration of 74 meq/l and a chloride value of 79.8 meq/l. She delivered a healthy infant, who has shown no evidence of cystic
fibrosis. She succumbed to secondary
pul-monary infection and insufficiency a number
of months after the baby was bom.hl
This patient illustrates the occurrence of
nasal polyps and sinusitis in an adolescent
whose basic disorder was not uncovered because of lack of pulmonary disease and
overt signs of pancreatic insufficiency. The
availability of the sweat test established the
diagnosis of cystic fibrosis, and incidentally
Case 17
C.C. (Fig. 3) was born on April 27, 1955,
weighing 8 lb 7 oz (3,827 gm). Slle Ilad a
ravenous appetite, gained weight slowly,
thick, greenish pus. This was removed with
suction, and the medial wall of the orbit
then came into view. Theme were a few
polyps present. The polypoid mucous
mem-brane was cut from the upper portion of
the inferior turbinate and from the edge of the middle tumbinate, leaving a large
opening into the middle meatus on this side.
No operation on the left side was done
be-cause of considerable bleeding and the
length of time required to perform the
oper-ative procedure.
One
month
later
a bilateral
nasal
poly-pectomy was done and a huge number of
polyps and polypoid mucous membrane
were removed (predominantly from the
right) from each side of the nose. At the
conclusion of the operation the nose on
each side was clear. In this patient, the
polyps megrew at an exceeding rapid rate
in spite of adequate antibiotic therapy.
Steroid therapy was instituted in an
at-tempt to prevent or reduce regrowth.
Tn-amcinalone was given for a 3%-month
pe-nod. No regrowth of the polyps has
oc-curred thus far.
COMMENT
Although the occurrence of nasal
poly-posis in patients with cystic fibrosis has
been known for many years, this report
represents the first attempt to gather and
evaluate the relevant clinical data. Lurie
(1959) called attention to this condition and
POLYPECTOMI ES
BiIatsr Right BiotsraI
,1,L,i,
No Rscurrsnce5/15 S1 7/28 BIIot#{149}rol Noscl
Polyposks
ChronIc
p AII.rglc
RNnItis
Nasal Stuffiness
MOUTh BreathIng
SnorIng
Dx
1%
hacking’ cough at 3 months of age and
appeared to sweat excessively. At about 4
months of age, her family physician
sus-pected cystic fibrosis and prescribed
pan-creatin and multivitamins. Antibiotics were
given intermittently. She gained weight to 26
lb (11.8 kg) at 1 7/12 years of age, when her
health began to fail. At 1 11/12 years she
was referred to the Children’s Hospital
Medical Center. The diagnosis of cystic
fi-brosis in a younger sibling who had more
severe manifestations had already been
made. The diagnosis of cystic fibrosis was
confirmed and a constant medical regimen
instituted. She began to gain weight, and
her cough diminished, with improvement in
her pulmonary status. At 3% years of age she
had a constant nasal discharge and was a
mouth breather. Nasal drops and sprays
produced no relief. Skin tests for allergy
were negative. X-ray films revealed chronic
maxillary and ethmoid sinusitis. It was not
until the third ear-nose-throat examination
(
within 6 weeks) that masses of nasalmucoid polyps were discovered bilaterally.
Four months later, several polyps were
me-moved from each side of the nose. Two
weeks later, a second polypectomy was
per-formed because of rapid regrowth of
polyps.
After the removal of a number of polyps
from the right side of the nose, it became
apparent to tile surgeon that the entire
ethmoid area on this side was filled with
3yrs 3”trs. 4yvs 4J’yrs. 5yrs.
‘:.
E-I CHLOROMYCET1N t25mqms BID
J
FIG. 3. Case 17. Patient required multiple polypectomies. Her response to triamcinalone was very
398
reported three cases before the American
Laryngological Association.12
The over-all incidence of polyps in the
patient population considered here is 6.7%,
but if those patients under 6 years of age are excluded, the incidence of nasal
poly-posis in those over 6 years of age would be
nearly doubled. The age distribution of
the 742 patients with cystic fibrosis seen
during the 4-year period included in this
study is as follows: under 4 years, 166; 4
to 6 years, 155; 6 to 10 years, 167; 10 to 16
years, 194; and over 16 years, 60 patients.
Furthermore, a more careful examination
of the nasal airway might reveal polyps in
some patients with cystic fibrosis who are
now considered to be polyp-free, and there
may be other patients in whom there are
early mucosal changes which could be
diag-nosed as “pnepolypoid” by experienced
otolaryngologists. The obvious question is:
“Why is polyp formation so common in
pa-tients with cystic fibrosis and so rare in
other respiratory diseases in childhood?”
Genetic and/or constitutional factors may be
implicated, and the occurrence of polyps
may indeed be related to the abnormal
func-tion of the mucous membranes and secretory
glands as part of a generalized mucus gland
14 Two additional factors may
play a significant role: infection, which is
al-most always present, and allergy, which
is present in a significant number of
pa-tients with cystic fibrosis.
In a recent study of respiratory allergy
in a series of 266 patients with cystic
fibro-sis seen over a 2-year period, the incidence
of allergy was 16.6%,8 indicating that the
incidence of allergy in patients with cystic
fibrosis is not in excess of that in the general
population, or in patients with other
disom-ders, such as rheumatic fever, leukemia, or
nephrosis.16 In the group of 266 patients
mentioned above,8 there were 15 patients
who had nasal polyps, of whom 7 fulfilled
the criteria of atopic individuals. These 7
pa-tients were among 44 in this series who
had respiratory allergy, and they represent an incidence of 16% in such patients,
whereas the remaining 8 patients with nasal
polyps were in the larger group of 222
pa-tients who presented no evidence of allergy.
Thus, only 3.6% of patients without allergy
had polyps, as contrasted to an incidence
of 16% among those with allergy. It is
evi-dent that the occurrence of polyps is not
limited to atopic patients.
Previous investigators5’ ‘ ‘
‘
18 havepointed out that the occurrence of nasal
polyps is common in patients with allergic
conditions of the respiratory tract. The
hy-pothesis that nasal polyps are related to
tile allergic state, and that infection alone
in the absence of an underlying atopy’
usually does not lead to the formation of
nasal polyps19 has been published. In Van
Metre’s studv20 of allergy in cystic fibrosis,
the mere presence of polyps was taken as
evidence of allergy. Pennington,21 in a
paper entitled “Paranasal Sinus Changes in
Fibrocystic Disease of the Pancreas” has
mentioned neither nasal polyposis nor
al-lergy. However, in all of the cases of cystic
fibrosis in this study, chronically diseased
paranasal sinuses were observed.
Penning-ton2’ recognized that the high mortality rate
among young children with cystic fibrosis
in the past perhaps had not allowed nasal
symptoms to become manifest in many
cases. Routine sinus films have not been
taken on all patients with cystic fibrosis in
the present study. However, in
approxi-mately 80 such examinations in older
chil-dren without nasal polyps, 93% presented
x-ray involvement of the sinuses.
Histologi-cal examination reveals changes
character-istic of those seen in the bronchi of
pa-tients with cystic fibrosis in the mucosal
lining of the sinuses, including dilatation of
the mucus secreting glands and the
dis-charge of viscid secretion, often with
evi-dence of secondary infection (Fig. 4A). The
histological appearance of a polyp removed
from a patient with severe allergy is shown
in Figure 4B for comparison. It is probable
that changes may occur in the mucosa of
the nasal and paranasal sinuses more
corn-monly than is recognized, and that
“sub-clinical” alterations may evolve over a
.;cs;L:f
-F4J -.
‘‘:“
‘C sr1I:;i1::
-4
. ,..>..
;k- .
‘‘?#{149}._‘
.,
V#{149}‘.;‘‘.; I
,
-::
-r-: : #{149}.4.
s’_
..‘.. ‘.‘.
.74
tllis pathological process involving the
mucous membrane structures is multiple
polyposis, with partial or complete
obstruc-tiori of the nasal airway. Tile examination
of nasal smears was not helpful in
distin-guishing between those patients with no
obvious allergy and those witil respiratory
allergy.
Is.
l,
r
-:A’
-“1..
;
.
. . ..t,.. . - . 4._ - .s #{149} -.
- .‘.. ‘j ‘:.
. .-
,
. . 1’o.. - .. :,,.
-
:....-: . ._::.‘tt1c1 ? s:,!:
,,
...:.1 -.:-.--
#{149}
:#{149}. F#{231}’.-’;.. , -.C _- .
:
“‘-b , ‘ #{149}9% 4
0 ‘ 4_4_) .-: ‘. -.
‘1
‘. #,. C _-. (:t
.
. : . : : . t’ .:, p - ,.‘:--I- , #{149}
:
‘ - ‘ .?‘*- -.. ‘C ;.1’- .. -a’- 1. ...
-‘ - - 0
-V
_
‘ -“ ‘. ii_____Fic. 4A. Microscopic appearance of polyp removed from Patient 3 (Fig. 1) (S60-1827). Note large cystic gland in the center filled with mucus and deeply staille(l eosinophilic
coagulum. This lesion is the most characteristic feature of the nasal polyp in cystic fibrosis. Other histologic features present, such as edema, increased vascularity, and mixed leukocyte infiltration, are nonspecific or may be seen in other forms of nasal polyposis. Cystic degeneration of stroma is usually not a feature. (Toluelene blue eosin
NASAL POLYPOSIS
:#{149}
!
.
_‘.. . .,*
._. 0.#{149}
..
family history, together with an
acquaint-ance with the clinical features of cystic
fi-brosis, in addition to a quantitative sweat
test, may prove rewarding.
SUMMARY !
o
f’p’.e . #{149}‘I ‘
4
S #{149})% #{149}
. . \
\C .
.. ... C “
P ‘ ,,, .. ‘ .#{149}.; .
:,
.,.
a- ‘t .#{149}*?.4.1-s t ,, * ‘ #{149}‘C,
#{149},
. -
1IaI :‘#{149}. - : #{149}
s.fs
:‘.
Y:’
“ .*
,%. ,
;w .
r
*
:C -. -
_________
-FIG. 4B. Microscopic appearance of polyp removed from an allergic individual who did
not have cystic fibrosis (S50-88). The hyaline basement membrane is thickened, there is considerable eosinophilia as well as edema and swelling of vascular walls, changes which may be seen in allergic polyposis. No glandular tissues are necessarily present. When present, the glands do not show the typical change seen in Figure 4A. (x400, approx.)
The present studies call attention to the
high incidence of nasal polyposis among
patients with cystic fibrosis in the older age
groups. The physician should be alerted to
the possibility of cystic fibrosis as the
studied during the past 4 years, 50 (or 6.7%)
were found to have nasal polyposis. Polyps
were noted in patients of all ages, the
youngest being 23 years of age.
Roentgeno-grams of the sinuses showed evidence of
paranasal sinusitis in each case studied. An
allergic investigation was conducted in each
of the 50 patients with nasal polyposis.
Twenty-four patients presented no evidence
of allergy. The clinical severity of the basic
disease (cystic fibrosis) was the same in
both the allergic and nonallergic group.
A brief description of the clinical course
of the patient with nasal polyps is
pre-sented. The polyps are often multiple, may
cause complete nasal obstruction, and tend
to regrow. Their course is beneficially
in-fluenced by the administration of
broad-spectrum antibiotics or systemic steroids.
However, polyps did appear in many
pa-tients while on constant broad spectrum
an-tibiotic therapy. Conservative management
is suggested. Simple polypectomy is carried
out when nasal obstruction is complete. In
a small number of patients, repeated
poly-pectomies have been necessary over a
num-ber of years. The severity of the pulmonary
lesion is not reflected by the degree of
al-teration of the mucosal linings of the
pama-nasal sinuses. Patients with nasal polyposis,
regardless of the presence or absence of
allergy, should be examined for evidence of
cystic fibrosis, including family history,
pul-monary evaluation, and appropriate
laboma-tory tests.
REFERENCES
1. Shwachxnan, H., Leubner, H., and Catzell, P.:
Mucoviscidosis, in Advances in Pediatrics, Vol. 7, edited by S. Z. Levine. Chicago, Year Book Publishers, 1955, p. 249. 2. Shwachnian, H., and Kulczycki, L. L. :
Long-term study of one hundred five patients with cystic fibrosis. J. Dis. Child, 93:228, 1957.
3. Rosan, R. C., Shwachman, H., and Kulczycki,
L. L.: Diabetes mellitus and cystic fibrosis
of the pancreas : laboratory and clinical ob-servations. Amer. J. Dis. Child. To be pub-lished.
4. Hansel, F. K.: Clinical and histopathological
studies of the nose and sinuses in allergy.
1.
Allergy, 1 :43, 1930.5. Kern, B. A., and Shenck, H. P. : Allergy a
constant factor in the etiology of so-called
mucous nasal polyps. J. Allergy, 4:485, 1933.
6. Shwachman, H., Elian, E., and Antonowicz, I.:
Sweat test in cystic fibrosis. Exhibit
pre-pared for the LX International Congress of
Pediatrics, Montreal, July, 1959.
7. Shwachman, H. : Therapy of cystic fibrosis of
the pancreas. PEDIATRICS, 25: 155, 1960. 8. Kulczycki, L. L., Mueller, H., and
Shwach-man, H. : Respiratory allergy in patients with cystic fibrosis. J.A.M.A., 175:358, 1961.
9. Eagle, H. : The specific amino acid
require-ments of a mammalian cell (strain “L”) in
tissue culture. J. Biol. Chem., 214:839, 1955.
10. Foley, C. E., et al.: Isolation and serial
prop-agation of malignant and normal cell in
semi-defined media: origins of CCRF cell lines. Cancer Res., 20:930, 1960.
11. Siegel, B., and Siegel, S. : Pregnancy and
de-livery in a patient with cystic fibrosis of the
pancreas: report of a case. Obstet. Gynec.,
16:438, 1960.
12. Lurie, M. H. : Cystic fibrosis of the pancreas and nasal mucosa, Annals of Otology,
Rhi-nology, and Laryngology, 68:478, 1959. 13. Farber, S.: Pancreatic function and disease in
early life. Arch. Path., 37:238, 1944.
14. Farber, S.: Some organic digestive
disturb-ances in early life. J. Michigan Med. Soc.,
44:587, 1945.
15. Samter, M. : Nasal polyps (an inquiry into the mechanism of formation). Arch. Otolaryng., 73:334, 1961.
16. Mueller, H. : Personal communication.
17. Semenov, H. : The pathology of the nose and paranasal sinuses in relation to allergy. Trans. Amer. Acad. Ophthal. Otolaryng., 56:121, 1952.
18. Blumstein, G. I., and Tuft, L. : Allergy
treat-ment in recurrent nasal polyposis: Its
im-portance and value. Amer. J. Med. Sci., 234:
269, 1957.
19. Chait, R. A.: Allergic rhinitis and nasal polyps.
New York J. Med., 56:2405, 1956.
20. Van Metre, E., Jr., et al.: Evidence of allergy
in patients with cystic fibrosis of the
pan-creas. J. Allergy, 31 : 141, 1960.
21. Pennington, C. L. : Paranasal sinus changes in fibrocystic disease of the pancreas. Arch. Otolaryng., 63:576, 1956.
Acknowledgment
We should like to thank Drs. Charles Ferguson and John Trakas, of the Otolaryngology Depart-ment for their assistance; Dr. E. D. B. Neuhauser
and his staff for the radiological examinations and
interpretation of the films. We also wish to thank
Dr. Sidney Farber for his constant guidance and
