MAY, 1966

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PNEUMOCYSTIS CARINII PNEUMONIA*

By MARIE A. CAPITANIO, M.D., and JOHN A. KIRKPATRICK, JR., M.D.
PHILADELPHIA, PENNSYLVANIA

‘1’ HE first case of Pneumocystis Carinii ported by Chagas in 1909, and then by
pneumonia was reported in this coun- Canini in 1910, for whom the organism was
try by Lunseth et al.’5 in 1955. Since then a named.8 The characteristic pulmonary pa-
number of cases have been reported in the thology was first described in 1938 by
American medical literature. Because the Ammich in Europe, although the clinical
roentgen examination ofthe chest may play state had been recognized earlier in Ger-
a role in the presumptive diagnosis of the many. Vanek, in I 95 I , described Pneumo-
disease, 6 cases are discussed (Table i) cystis Caninii in the lungs of infants who
with emphasis on the roentgen manifesta- had the clinical and histologic features of
tions. plasma cell pneumonia and considered this
organism to be the probable etiologic
ETIOLOGY
agent,16 although it has not been possible
Pneumocystis Caninii pneumonia is be- to confirm fully Koch’s postulates. The
lieved to be caused by the organism, Pneu- proof that Pneumocystis is the causal agent
mocystis Caninii, which is thought to be a in plasma cell pneumonia to date is mdi-
protozoon but may possibly be a fungus rect, but, nevertheless, rather convincing,
and occurs predominantly in patients in as the organism has been found in all pa-
whom there is an alteration in the immune tients with this disease. The organism can
mechanism. The disease was observed first be identified in microscopic sections of tis-
in Central Europe in epidemic form in sue by utilizing various staining techniques;
institutionalized infants to 4 months of e.g., the McManus-Hotchkiss method;
age who were born prematurely or who Masson’s tnichnome method; and with
were debilitated. Since then, cases have Giemsa as well as with Rio-Hortega’s silver
been reported from all pants of the world in stain.2 Sheldon2#{176} was able to stimulate the
both epidemic and endemic form. In the growth of the organisms already present in
United States, Canada, and England, the lungs of rabbits by the administration
Pneumocystis Caninii infection appears of cortisone which he thought produced an
endemic and has been associated with dis- alteration in the host-parasite relationship.
turbances of the immune mechanism such The organism has been noted as an mci-
as hypogammaglobulinemia,6”6 Wiskott- dental finding in the lungs of children and
Aldrich syndrome,22 cytomegalic inclusion adults who have died of unrelated causes,
disease,’#{176} leukemia and lymphomas,’ and which suggests that Pneumocystis can be
more recently osteopetrosis.’ It has been present in human lungs in the absence of
reported in children of all ages and in clinical symptoms until an alteration in the
adults.22 The increased incidence at to 4 resistance of the host permits the disease to
months of age, as reported in the Euro- evolve and become clinically manifest.’7
pean literature, coincides with that period
PATHOLOGY
in life when the gamma globulins are be-
lieved to be at their lowest physiologic The lungs are large, heavy, firm, pearl
level. gray, and almost airless. Histologically, the
The pnotozoon is a saprophyte found in lungs show an extensive mononuclear cellu-
the lungs of many animals, e.g., the rat, the lan infiltration. In the reports from Europe,
mouse, the rabbit, the dog.2 It was first re- the interstitial cellular infiltrate has been

a From the Departments of Pediatrics and Radiology, Temple University School of Medicine, and St. Christopher’s Hospital for
Children, Philadelphia, Pennsylvania.

I 74
 VOL. 97, No. i Pneumocystis Caninii Pneumonia ‘75
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TABLE I

Patient Age Race Sex Underlying J)isease Treatment Survival

I. R.S. mo. N F Wiskott-Aldrich Tetracycline Expired

syndrome Prednisone days after
Vancomycin admission

P.S. 6 mo. W NI Hypogammaglobu- Gammaglobulin Expired 19

linemia Tetracycline days after
Methecillin admission

3. J.S. 4 mo. W M None demonstrated Tetracycline Expired 4

Dexamethasone months after
admission

4. E.V. 6 yr. W F Acute lymphatic Prednisone Expired 4

leukemia Gammaglobulin days after
Penicillin admission

5’ M.McD. 6 mo. W F Hypogammaglobu- Gammaglobulin Expired 3

linemia Hydroxystilbamine days after
admission

6. AG. 10 mo. \v M Hypogammaglobu- Gammaglobulin Expired i

linemia Hydroxystilbamine months after
Penicillin admission
Tetracycline

Note: All patients were proven to have Pneumocystis Carinii pneumonia by biopsy of the lung and/or at postnorten examination
(see Figures I through 6).

described as being composed predominantly demonstrated the presence of mature cysts

of plasma cells, but this has not been the with characteristic nuclear-like “cyst bod-
case in this country or in those countries ies” as well as mans’ crescent forms which
outside of Europe. Some believe these to be seem to be typical for human Pneumocvstis
histiocytes and/or cells intermediate be- infections. The cysts have a thick wall with
tween plasma cells and histiocytes. There an inner and outer membrane. Each cyst
are few polymorphonuclear leu kocy tes and
lymphocytes. The alveoli are filled with a
characteristic foamy or “soap bubble”
exudate in which the organisms can be
identified.’#{176}
Electron microscopy of ultra-thin sec-
tions of alveolar fluid from human lungs
infected with Pneumocvstis Caninii has

FIG. I. R.S., female, months of age. There are

diffuse interstitial and penibronchial infiltrates
throughout both lungs with peripheral and inter-
stitial emphysema. Nei ther hilar lymphadeno-
path)’ nor pleural disease is present.
 I 76 Marie A. Capitanio and John A. Kirkpatrick, Jr. MAY, 5966
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CLINICAL PICTURE

The most characteristic finding is

r
,- ‘S. tachypnea Wi th pen-oral and peri-orbi tal
cyanosis. In spite of the severe respiratory
distress, the lungs are frequently normal to
auscultation and percussion. Occasionally,
fine crepitant rales on coughing or deep
breathing, slightly impaired resonance, and
bronchial breath sounds are evident over
some areas of the lungs. This discrepancy
between the severity of the pulmonary
symptoms and the physical findings is typ-
ical. Fever is not usually a factor, the tem-
perature rarely going above ioo0 F. unless

I
tllere is a superimposed bacterial infection.
The onset of the disease is usually slow and
insidious with restlessness or languor and
FIG. P.S., 2. male, 6 months of age. The lungs are poor feeding. The duration of the disease is
over-aerated and there is extensive parenchymal
from to 6 weeks, although at times only a
disease. An air bronchogram is seen behind the
few days elapse prior to death. The reported
heart on the left. The diftuse density of the lungs is
consistent with an intra-alveolar exudate. Volume mortality rate varies from 20 to 50 per cent,
loss involving the left lung is manifested by the but it is difficult to ascertain accurately as
shift of the heart and mediastinum to the left. it is likely tilat there are sub-clinical
cases.2’’#{176}’#{176}’’9
contains several nuclear-like bodies. These
bodies ilave a complex lamellar or tubular
LABORATORY FINDINGS
structure in tileir interior and seem to be
enveloped in a distinct membrane wiliCh Laboratory data are of limited help in
ilas two or more contours.5 making the diagnosis. The white blood cell

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 VOL. 97, No. i Pneumocystis Caninii Pneumonia I 77
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*r

#{149}5 #{149}

A B I

Pr::* . :
lI(;. 4 l.V., feniale, 6 y ears ot age. (.1) there
is a ranuIar j)tttern of tl)nornhal densi tv
throtzhout both lungs. (B) One s eek liter,
there is au increase in the generalited .rrtn_
ular Jensi tv throughout loth lungs. (C )
weeks later, there is almost coi#{236}iplete
(i)IC1fiCltiOfl of the In ogs.

I \/.
.

IC

count is normal or only slightly elevated be found when Pneunlocvstis Caninii illfec-

and associated with a normal differential tioll iS secondary.

count or sligllt lleutropililia. Slight to
ROENTGENOGRA1HIC FINDINGS
marked eosinopllilia llas been observed.
There ilave been reports of tile plasnla The roentgenograpilic appearance of tile
calcium levels being as high as 20 rug. per chest is similar in all patients. There is a
100 ml., but tilis ilas Ilot been a consistellt fine, almost homogeneous, granular pattern
finding. Plasma proteins are usually witilin of density throughout the pulmonary pa-
the range of normal.’#{176} Abnormalities con- renchyma, which presents first in the hilar
sistent with the underlying disease are to regions and then progresses to the periph-
 178 Marie A. Capitanio and John A. Kirkpatrick, Jr. lA , 1966
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:
,, “,“
#{149}“

11G. 5. M.NIcD.,
volves both lungs.
female,
Air
6 months
bronchograms
of age. (4) A granular,
are seen in both lungs.
almost homogeneous density
The lungs are over-aerated.
is present
Hilar k rnilu-
mn in-
4
opathy and pleural disease are absent. (B) Nine days later, the lungs are almost homogeneous in their
opacity.

erv (Fig. 4, A, B and C; and , A and B). present. The parenchymal iii ltcincnt
The peripheral portions of the lungs are progresses toward the periphery to invl\ c
enlphvsematous (Fig. 3, A and B). In ad- all of the lungs and to become more in-
dition to interstitial enspllvsema, pneumo- fluent until frequently the thorax is ci-
thorax and pneumonlediastinum may be pletely opacified. Usually, all lobes are
involved, but not necessanil’ so; at times
the infiltrates may be subsegmental in dis-
tnibution with over-aeration of the rcmim ;ii ii-
ing portions of lung (Fig. , 2, and . In
spite of the extensive involvement f the
‘_.i4’ ‘. lung, pleural reaction and hilan lvmiplia-
denopathy are absent. An air lmnchran
is usually present as one would e\pccr to
find in the presence of intra-alveolar mntil-
tnates of any etiolog’.7’8’#{176}
Atelectasis is not an uncommon featmi mc
and, in spite of obvious loss of \()ltimnc of
portions of the lung, emphysema ill be
evident as manifested by the low rsmtin
of the diaphragm and the wide intcrcstml
spaces (Fig. 2 and 6).
Roentgenographic abnormalities ma’ be
present early in the disease before simss of
severe respiratory distress become n ;mn i -
FIG. 6. .A.G., male. io months ofage. There is diffuse
disease throughout all lobes with the exception of fest. Several patients proven to have i’nem-
the right middle lobe which is emphysematous. mocystis Caninii pneumonia have hccn
 VOL. 97, No. Pneumocystis Caninii Pneumonia I 79
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cured of the disease and have been followed ise. There are not sufficient cases in which
roentgenographically. The changes wi thin these drugs have been used to adequately
the lungs were shown to clean within 6 estimate their value.’6
weeks, although i patient has been reported Treatment has, for the most part, been
in whom complete resolution did not take directed toward reducing the symptoms
place until 2 years after the onset.8 with oxygen and mist, resulting in consider-
Other entities to be considened in differ- able relief from respiratory distress. Broad
ential diagnosis on the basis of the roentgen spectrum antibiotics are utilized when so-
appearance are the reticuloendothelioses, penimposed bacterial pneumonia is present.
idiopathic pulmonary hemosidenosis, giant The use of cortisone has been deleterious
cell pneumonia, alveolar proteinosis, and, and is believed to enhance the spread of the
in the early stages, lipoid pneumonia, le- infectious process.
sions responsible for obstruction to pulmo-
nary venous return, and, at times, the SUMMARY
Hamman-Rich syndrome. Pneu mocvstis Can nii pneu moni a most
often occurs in debilitated infants and
DIAGNOSIS
children on those with more specific altera-
Though roentgenognaphic alterations are tions of the immune mechanism. The cilar-
not specific with respect to the etiology, actenistic clinical picture is one of progres-
they should, when the clinical findings of sive respiratory distress and cyanosis, with
progressive respiratory distress and cyano- relatively few physical findings pertaining
sis are taken into consideration, strongly to the thorax. The roentgen findings are
suggest the diagnosis. The definitive diag- those of diffuse, granular pulmonary infil-
nosis, however, is made by the demonstra- trates which progress from the hili toward
tion of the pneumocysts. They may be re- the periphery of the lung, becoming more
covered either from bronchial secretions on and more confluent. Interstitial emphy-
from biopsy of the lung. Since it may be sema may be present and, not infrequently,
difficult to demonstrate the pneumocysts pneu mothonax and pneu momedi asti nu m.
in bronchial washings, biopsy of the lung Pleural reaction and hilan lymphadeno-
offers the best method for diagnosis. This pathy are absent. Although the roentgen
may be performed by either needle aspira- findings are not specific
with respect to the
tion or open biopsy. Open biopsy is prob- etiologic agent, when they are correlated
ably the preferred method because it results with the clinical picture, the presumptive
in a large sample of tissue for evaluation diagnosis of pneumonia due to Pneumocys-
by the pathologist.’0 tis Carinii may be made.
A complement fixation test, utilizing
Marie A. Capitanio
extract from the lungs of affected infants,
Department of Radiology
has been reported by Vivell, Buhn, and St. Christopher’s Hospital for Children
Lips in 1956. According to them, a titer of 2600 North Lawrence Street
I to may be regarded as positive for Philadelphia, Pennsylvania 19133

pneumocyst antibodies, but a rising titer

is more conclusive. A positive reaction REFERENCES

usually occurs during the second week of I. AHERNE, W. Case of osteopetrosis (Albers
illness.’6 Schonberg) wi th in tercurren t Pneumocystis
pneumonia. Arch. Dis. Childhood, 1960, 35,
TREATMENT 495502.
2. AHVENAINEN, E. K. Interstitial plasma cell
There is no specific treatment to date,
pneumonia. Pediat. C/in. North America, I 957,
though early reports on the use of the 4, 203-214.
aromatic diamidines and pentavalent anti- 3. ALLIBONE, E. C., GOLDIE, W., and MARMION,
mony compounds have shown some prom- B. P. Pneumocystis Carinii pneumonia and
 i 8o Marie A. Capitanio and John A. Kirkpatrick, Jr. MAY, 1966
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progressive vaccinia in siblings. Arch. Dis. pneumonia. Am. 7. C/in. Path., 1962,38, 40!-
Childhood, 1964,39, 26-34. 405.
4. BOMMER, W. Pneumocystis Carinii in interstitial 14. HENNIGAR, G. R., VINIJCHAIKUL, K., ROQUE,
plasma-cell pneumonia: studies of organism. A. L., and LYONS, H. A. Pneumocystis
A.M.A. Am. 7. Dis. Child, 1961, 102, 375- Carinii pneumonia in adult: report of case.
391. Am. 7. C/in. Path., 1961,35, 353-364.
5. BOMMER, W. Pneumocystis Carinii from human 15. LUN5ETH, J. H., KIRMSE, T. W., PREZYNA,

lungs under electron microscope. A.M.A. Am. A. P., and GERTH, R. E. Interstitial plasma
:i. Dis. Child., 1962, 104, 657-66 I. cell pneumonia. 7. Pediat., 1955, 46, 137-145.
6. BURKE, B. A., KROVETZ, L. J., and GooD, R. A. 16. MARSHALL, W. C., WESTON, H. J., and BODIAN,
Occurrence of Pneumocystis Carinii pneu- M. Pneumocystis Carinii pneumonia and con-
monia in children with agammaglobulinemia. genital hypogammaglobulinaemia. Arch. Dis.
Pediatrics, 1961,28, 196-205. Childhood, 1964,39, 18-25.
7. COHEN, W. N., and MCALISTER, W. H. Pneu- 17. PosT, C., DUTZ, W., and NASARIAN, I. Endemic
mocystis Carinii pneumonia: report of four Pneumocystis Carinii pneumonia in South
cases. AM. J. ROENTGENOL., RAD. THERAPY & Iran. Arch. Dis. Childhood, 1964, 39, 35-40.
NUCLEARMED., 1963,89, 1032-1037. i8. ROWE, C. W. Pneumocystis Carinii pneumonia.
8. FALKENBACH, K. H., BAcHMANN, K. D., Radiology, 1960, 75, 257-261.
and O’LAUGHLIN, B. J. Pneumocystis Carinii 19. SHELDON, W. H. Pulmonary Pneumocystis
pneumonia. AM. J. ROENTGENOL., RAD. Carinii infection. 7. Pediat., 1962, 61, 780-791.
THERAPY & NUCLEAR MED., 1961, 85, 706- 20. SHELDON, W. H. Experimental pulmonary Pneu-
713. mocystis Carinii infection in rabbits. 7. Exper.
9. lEINBERG, S. B., LESTER, R. G., and BURKE, Med., ‘959, 110, 147-160.
B. A. Roentgen findings in Pneumocystis 2!. STERNBERG, S. D., and ROSENTAL, J. H. Inter-
Carinii pneumonia. Radiology, 1961, 76, 594- stitial plasma cell pneumonia. 7. Pediat.,
600. ‘955, 46, 380-393.
10. GAJDU5EK, D.C. Pneumocystis Carinii-etio- 22. WEINTRAUB, H. D., and WILSoN, W. J. Pneu-
logic agent of interstitial plasma cell pneu- mocystis Carinii pneumonia in Wiskott-
monia of premature and young infants. Aldrich syndrome. A.M.A. Am. 7. Dis. Child.,
Pediatrics, 1957, 19, 543-565. 1964, zo8, 198-200.
I I. GERRARD, J. W. Pneumocystis pneumonia. 23. WHITE, W. F., SAXTON, H. M., and DAWSON,
Pediat. C/in. North America, i 958, 5, 3 27-335. I. M. P. Pneumocystis-pneumonia: report of
12. HAMPERL, H. Variants of Pneumocystis pneu three cases in adults and one in child with dis-
monia. :i. Path. & Bact., 1957, 74, 353-356. cussion of radiological appearances and pre-
13. HENDRY, W. S., and PATRICK, R. L. Observations disposing factors. Brit. M. 7., 1961, 2, 1327-
on thirteen cases of Pneumocystis Carinii 1331.