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The schilling blood count as an aid in the diagnosis of acute appendicitis in children
T H E S C H I L L I N G B L O O D COUNT AS A N A I D IN T H E D I A G N O S I S OF A C U T E A P P E N D I C I T I S IN C H I L D R E N M.D. NEw YORK, N. Y.
J U L I & N L . ROG•TZ,
blood s m e a r w i t h special a t t e n t i o n to S TtheU D Ii EmSm aoft u r ethe, p odifferential l y m o r p h o n u c l e a r leucocytes, in p r a c t i c a l l y all the k n o w n p a t h o l o g i c states, h a v e led to the conclusion t h a t in the absence of infection t h e r e can be no a p p r e c i a b l e increase in the p e r c e n t a g e of i m m a t u r e white cells in the blood. R e p o r t s on m a n y thousands of cases h a v e confirmed Schilling% original contention t h a t " a real failu r e " of the differential s m e a r to indicate the presence of infection in the b o d y " i s u n t h i n k a b l e . ' ,1 Otherwise stated, an absolutely n o r m a l s m e a r w i t h no increase in the i m m a t u r e neutrophiles enables one to rule out the presence of an acute infectious process in the b o d y with r e a s o n a b l e accuracy. I f rep e a t e d counts are normal, there is no acute infection present. This premise, which is v i t a l to the v a l i d i t y of t h i s work, has been a m p l y proved.i, e, 3 D o u b t f u l cases of " a p p e n d i c i t i s " f r e q u e n t l y occur with a b d o m i n a l pain a n d localized tenderness, w i t h or w i t h o u t vomiting, with n o r m a l t e m p e r a t u r e a n d n o r m a l total leucocyte count, in which it is difficult to m a k e a positive diagnosis. The usual white a n d differential blood counts v a r y g r e a t l y and are of no real significance. These guides are especially unreliable in children. W i t h i m p r o v e d , modern, o p e r a t i v e technic, r a t h e r t h a n r i s k costly delay a n d the r u p t u r e of an acutely inflamed a p p e n d i x , the surgeon feels it s a f e r a n d wiser to p e r f o r m an a p p e n d e c t o m y in all d o u b t f u l cases at the risk of finding a n o r m a l appendix, which, as a m a t t e r of fact, occurs in a b o u t f r o m 30 to 40 per cent of cases o p e r a t e d on for acute appendicitis. 4' ~ I f it were possible, in such u n c e r t a i n cases, to rule out definitely acute infection, some other e x p l a n a t i o n of s u g g e s t i v e s y m p t o m s m i g h t be sought, a n d m a n y u n n e c e s s a r y a p p e n d e c t o m i e s avoided. O p e r a t i v e technic is not u n i f o r m l y good, and the d a n g e r s of unskilled s u r g e r y at inconvenient times are got negligible. A c a r e f u l e x a m i n a t i o n of the blood s m e a r b y the Schilling method, which is not difficult, should u n e q u i v o c a l l y indicate the absence of an acute i n f l a m m a t o r y process in the a p p e n d i x and t h e r e b y minimize u n n e c e s s a r y surgery. F r o m the A. J~eobi I)ivision for C hi l dre n of t he L e n o x H i l l I-Iospital; service of ]Dr. J e r o m e S. Leopold. 757
758
T[IE JOURNAL
OF P E D I A T R I C S
This can be done only, however, w h e n the p e r c e n t a g e of i m m a t u r e white cells in the s m e a r is n o r m a l (10 per cent or less in children). [['he presence of f r o m 10 p e r cent to 15 per cent of these y o u n g f o r m s indicates a mild, acute or s u b a c u t e c a t a r r h a l process. More t h a n 15 per cent of the y o u n g cells is definite evidence of infection s o m e w h e r e in the body. Since the blood differential is not specific, it does not determine the n a t u r e of the i n f l a m m a t o r y process, whose presence, once indicated, m u s t be located b y other signs. R E V I E W OF L I T E R A T U I C E
Efforts to develop a highly p r a c t i c a l application of the Schilling count b y establishing the absence of an acutely inflamed a p p e n d i x in the presence of false, t h o u g h suggestive, signs led to a s t u d y of a series of cases as t h e y a p p e a r e d in the p e d i a t r i c wards. W h e n this w o r k was begun, there were no r e p o r t s of a similar n a t u r e in the literature. Since then, however, several observers have published the results of t h e i r studies on the Schilling index in acute appendicitis, mostly in adults. My observati6ns in children corroborate those which have r e c e n t l y a p p e a r e d and should be followed b y other studies. I f these faets can be repeatedly verified, they are of great practical value. Y a g u d a * r e v i e w e d a series of 671 cases (the ages are not given, b u t some children m u s t h a v e been included in this n u m b e r ) on which appendectomies h a d been p e r f o r m e d . The blood smears h a d been examined b y the usual m e t h o d a n d filed. T h e y were r e e x a m i n e d according to the Schilling classification, and these counts were comp a r e d with the histologic findings in each case. These results are of g r e a t interest a n d significance. T h e y are briefly s t a t e d as follows: 1. N o r m a l appendices (no evidence of acute inflammation), 277 cases (41 p e r cent), showed f r o m 2 p e r cent to 8 p e r cent stab f o r m s ( a v e r a g e 4.3 p e r cent). 2. C a t a r r h a l appendices ( i n f l a m m a t o r y process limited to the mueosa) showed 7 per cent to 14 p e r cent stab cells ( a v e r a g e 10.2 p e r cent). 3. Acute, diffuse, s u p p u r a t i v e appendicitis w i t h o u t p e r f o r a t i o n showed 14 p e r cent to 28 p e r cent stabs ( a v e r a g e 17.8 p e r cent). 4. Acute, diffuse, s u p p u r a t i v e appendicitis with p e r f o r a t i o n and peritonitis showed 32 per cent to 47 per cent stabs ( a v e r a g e 39.5 p e r cent). Y a g u d a concluded t h a t a n o r m a l p e r c e n t a g e of i m m a t u r e neutrophile ceils ruled out acute appendicitis. H e r z s f o u n d t h a t in 161 cases diagnosed appendicitis it was possible to establish some other diagnosis in sixty-one cases. I n thirty-five cases of a p p e n d e c t o m y with histologic specimens, eleven were normal.
ROGATZ:
SCHILLING
BLOOD
COUNT
759
H e c o n c l u d e d t h a t t h e S c h i l l i n g c o u n t is i n v a l u a b c a n d w i t h it one c a n o f t e n a v o i d o p e r a t i o n . A n a c u t e case of a p p e n d i c i t i s n e v e r occurs with a normal blood picture. I n a s m a l l e r series, c o n t a i n i n g t e n a c u t e cases a n d t h i r t y n o n a c u t e cases, six of t h e e n t i r e g r o u p b e i n g c h i l d r e n , Gooda]e a n d M a n n i n g ~ f o u n d t h a t i n cases w h e r e t h e a p p e n d i c e s s h o w e d a g e n e r a l , p o ] y m o r -
phonuclear infiltration, with or without pus in the lumen, there is a definite left shift. Normal cases showed no increase in the immature white cells. They concluded that the Schilling index renders a more accurate picture of the pathology in the appendix than the ordinary differential count. L u c k 7 d e s c r i b e d t h e b l o o d p i c t u r e i n a p p e n d i c i t i s i n t e n a d u l t %~ses a n d n o t e d t h a t t h e Schil]ing~ C o u n t is v a l u a b l e to d e t e r m i n e t h e presence or a b s e n c e of a n i n f e c t i o n i n t h e b o d y . H e e n c o u n t e r e d n o i n f e c t i o n of a n y s e v e r i t y i n t h 4 " a b s e n c e of a s h i f t to t h e left, r e g a r d l e s s of t h e c l i n i c a l s y m p t o m s or t h e t o t a l l e u c o c y t e a n d p o ] y m o r p h o n u c l e a r count. P r o c h n o w 8 f o u n d the use of the S c h i l l i n g h e m o g r a m h i g h l y s a t i s f a c t o r y d i a g n o s t i c a l l y i n a c u t e a p p e n d i c i t i s a m o n g adu]ts. H e n o t e d a m a r k e d l e f t s h i f t w i t h i n c r e a s i n g ' s e v e r i t y of t h e i n f e c t i o n .
METs
AND OBSEI~VATIONS
On admission a total white cell count and a Schilling differential count were made in every case, prior to operation. Wright's stain was used in preparing' the blood smears. If the smears are thin and of even quality, so that there is no clumping or overlapping of erythrocytes, the leucocytes will be well formed and easy to distinguish in any portion of the smear. In a properly prepared specimen crushed elements are only occasional. It is impossible to classify cells with any accuracy in thick preparations, and failure is often due to this fault. The white cells were tabulated horizontally in the form of a hemogram, as basophiles, eosinophiles, myelocytes, juveniles, stabs, segments, lymphocytes, and monocytes (see Tables I and II). The rarely seen myelocytes, the infrequent juvenile cells, and the common, deTABLE ~ONACUT~ CASE
5 6 13 16
20
DATE
1/3/32 5/28/32 3/ 7/30 3/]8/33 5/ 2/33
I AGE IN[ u B E
s 11 10 1t 11
1-31 - 3 [- 1 - I 5 -
I CASES
j ~ -s~ L~ON' ]~AT~OT~OaIC ~EPO~T ] 1 55- ~ Normal 6 37[ 50 4 Normal appendix. 5 45 44 3 Chronic , thickened macosa. 11 72 ]4 2 Chronic, kinked, nonacute. ]0 62 26 2 Mild, chronic appendicitis. - 7 38 45 4 Chronic. Serosa smooth.
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THE JOURNAL OF PEDIATRICS TABLE
II
ACUTE CASES
~E~OG~A~ I PATIIOLOGIC REPORT M J ST S L M0~ - - 19 52 25 4 ~Early acute appendicitis. 4 Chronic, catarrhal, retrocecal; no~-12 29 5I acutely inflamed. 4 12/19/31 t4 7 Acute, exudative; many white blood 26 47 19 corpuscles. 7 8/ 6/32 12 Acute, hemorrhagic; necroses. 16 40 40 4 8 8/ 9/32 Acute fibrinous exudate at tip. 7 30 52 15 4 9 12/10/32 Ruptured; peritonitis. 5 1 68 26 4 1 10 1'2/29/32 12. Acute empyema of appendix. 1 21 66 8 4 11 1/10/33 Gangrenous, perforated; free pus, 31 52 5 11 8 adhesions, peritonitis. 12 2/ s/33 3 High retroceca], acute, covered with 40 47 10 8 fibrin. 14 3/]0/33 10 -20 62 14 4 Acute, inflamed, thickened. 15 3/12/33 10 ] 4 51 32. 9 3 Acute, suppurative, perforated. 17 3/30/33 8 2 31 35 24 7 Acffte, inflamed appendix. 18 4/12/33 5 32 53 11 2 2 Acute, inflamed, ruptured. 19 4/13/33 2 39 44 8 7 I~uptured ; free pus, 7 2,1 5/17/33 12 17 29 49 2 Chronic, catarrhal; serosa injected. 22 5/18/33 S 7 34 41 ]5 3 Ruptured; acute peritonitis. 23 511~/33! 9 - - 36 34 24 G Acute suppurative appe~diMtis. 24 7/21/33i :[3 15 77 8 0 Acute congestion; necroses; wMte blood corpuscles in mueosa section. 25 8/10/33 4 35 21 39 5 Retrocecal, appcndiceal abscess. 26 8/23/33 7 39 50 3 8 Acute~ suppm'ative; necroses. 27 8/23/33 12 2 40 28 28 2 Acute, ruptured during removal. 28 8/25/33 12 47 35 11 7 Acute, suppurative; necroses. 29 8/26/33 8 7 Acute, suppurative; necroses. 37 49 7 3O 9/12/33 9 3 32 52 9 4 Empyema of appendix. Abbreviations: ]3, basolohiles; E, eosinophiles; IV[, myeloeytes; J, juveniles; ST. stabs; S, segments; L. lymlJhocytes; MON, monocytes. AGEI: CASE DATE YEAR Y R 2 11/ 5/31 3 12/10/31 7
-
g e n e r a t e d s t a b or b a n d f o r m s c o m p r i s e t h e i m m a t u r e p o l y m o r p h o nuclear leucocytes with nonsegmented nuclei and represent varying d e g r e e s of i m m a t u r i t y . A n i n c r e a s e i n t h e p e r c e n t a g e of t h i s g r o u p of cells over n o r m a l c o n s t i t u t e s a " s h i f t to t h e ]eft. ''9 I n i n f e c t i o n s of m o d e r a t e s e v e r i t y t h e s t a b f o r m s w e r e i n c r e a s e d o v e r n o r m a l . As t h e i n f e c t i o n p r o g r e s s e d , a f u r t h e r i n c r e a s e i n s t a b f o r m s w a s f o l l o w e d b y t h e a p p e a r a n c e of j u v e n i l e cells a n d , i f a l l o w e d to c o n t i n u e u n t r e a t e d , r e s u l t e d i n t h e a p p e a r a n c e of o c c a s i o n a l m y e l o cytes i n the p e r i p h e r a l blood. T h o u g h t h e d e g r e e of s h i f t w a s app r o x i m a t e l y p r o p o r t i o n a l to t h e s e v e r i t y of the p a t h o l o g y f o u n d , one could n o t i n v a r i a b l y j u d g e t h e e x t e n t of d a m a g e i n t h e a p p e n d i x f r o m t h e a m o u n t of shift. I t is i m p o r t a n t to note, h o w e v e r , t h a t a n i n c r e a s e i n t h e i m m a t u r e w h i t e cells n e v e r f a i l e d to i n d i c a t e the p r e s e n c e of infection. The segments (the familiar, mature, po]ymorphonue]ear leucocytes w i t h t w o or m o r e lobes c o n n e c t e d b y h a i r l i k e f i l a m e n t s f o r m i n g t h e n u c l e u s ) w e r e u s u a l l y d e c r e a s e d d u r i n g t h e a c u t e s t a g e of i n f e c t i o n a n d b e c a m e m o r e n u m e r o u s d u r i n g c o n v a l e s c e n c e . A n a b n o r m a l increase of the s e g m e n t s w i t h a n o r m a l p e r c e n t a g e of s t a b s u s u a l l y in-
ROGATZ:
SCHILLING BLOOD COUNT
761
dieated a chronic infection. I t is for this r e a s o n t h a t a high percenta g e of p o t y m o r p h o n u c l e a r cells m u s t be e x a m i n e d to determine the n u m b e r of i m m a t u r e , n o n s e g m e n t e d f o r m s present. One m a y not assume t h a t a high p o l y m o r p h o n u c l e a r count m e a n s a high stab count. Unless acute infection is present, t h e r e will be no a b n o r m a l increase in stab forms. This i m p o r t a n t i n f o r m a t i o n can only be obtained by g r o u p i n g the cells according to the presence or absence of filaments in the nuclei2 REPORT OF CASES
I n this series of t h i r t y appendectomies, six cases showed normal his~ tologie specimens. I n each of these cases t h e opinion was v e n t u r e d t h a t a normal, or at least a n o n a e u t e l y inflamed, a p p e n d i x would be f o u n d a n d t h a t a p p e n d e c t o m y w a s not u r g e n t l y indicated. The total white count is omitted in the tables since it p l a y e d no p a r t in determining the presence or absence of infection. I n several instances it was n o r m a l in the presence of severe p a t h o l o g y a n d was therefore reg a r d e d as unreliable. A m o n g the nonaeute cases, p a t i e n t s 1 and 13 showed stab counts of 11 p e r cent. This slight increase over n o r m a l was not deemed sufficient evidence of acute infection. Case 13 s h o w e d 83 per cent polym o r p h o n u c l e a r cells, of which 72 p e r cent w e r e m a t u r e segments, indicating as the microscopic sections showed, a chronically inflamed organ, b u t n o acute infection. T h o u g h Case 3, with a high normal figure of 12 p e r cent stabs was omitted f r o m the nonaeute group, it w a s felt t h a t no u r g e n c y for o p e r a t i o n existed t h o u g h the a p p e n d i x m i g h t be chronically inflamed and b e t t e r removed. IIistologie section indicated this. CASE 1 . - - P a t i e n t , aged e i g h t years, gave a h i s t o r y of p a i n in the r i g h t u p p e , q u a d r a n t , of t w e n t y - f o u r h o u r s ' d u r a t i o n , g r o w i n g worse a n d a p p e a r i n g in the l e f t lower q u a d r a n t . T h e r e was no v o m i t i n g . T h e r e w a s t e n d e r n e s s in the r i g h t lower quadrant, O t h e r e x a m i n a t i o n was n e g a t i v e . The t e m p e r a t u r e was 99 ~ F, The t o t a l leucocyte c o u n t was 12~400. T h e Schilling s m e a r showed ]1 per cent stabs, a n d o p e r a t i o n w a s d e e m e d u n n e c e s s a r y , as i n f e c t i o n w a s n o t shown to be present. A p p e n d e c t o m y w a s performed~ a n d a n o r m a l a p p e n d i x was removed. CASE 6 . - - P a t i e n t , a g e d eleven years, w a s ill for six d a y s with p a i n in t h e r i g h t a b d o m e n . T h e p a t i e n t was n a u s e o u s b u t did n o t v o m i t d u r i n g this period. T h e bowels were regular. There was no fever. T h e r e w a s s l i g h t t e n d e r n e s s a n d s p a s m over t h e r i g h t r e c t u s muscle. T h e t o t a l white cell c o u n t w a s ]1,000. T h e r e were 5 p e r cent s t a b s i n t h e smear. W i t h this c o u n t t h e r e could be no acute or s u b a c u t e i n f e c t i o n in t h e b o d y a n d operation was deemed u n n e c e s s a r y . The p a t h o l o g i s t r e p o r t e d a t h i c k e n e d m u c o s a w i t h no necroses a n d m a d e a diagnosis o f chronic appendicitis. CASE 1 3 . - - P a t i e n t j a g e d t e n years~ complained of p a i n in the r i g h t ~idc f o r two weeks. T h e r e was no v o m i t i n g . E x a m i n a t i o n revealed m a r k e d t e n d e r n e s s on m o d e r a t e p r e s s u r e i n the r i g h t lower ,quadrant, especially over M e B u r n e y ' s point. T h e reetM e x a m i n a t i o n was negative. T h e t e m p e r a t u r e w a s 100 ~ F. T h e child
762
THE J O U R N A L OF PEDIATRICS
w a s a p p r e h e n s i v e a n d neurotic. W i t h t h e t e m p e r a t u r e a p p r o x i m a t e l y n o r m a l a n d no other a p p a r e n t cause f o r t h e pain, t h e s t a b count was u s e f u l in i n d i c a t i n g t h e absence of an a c u t e i n f l a m m a t o r y process. T h e s m e a r showed 11 p e r cent s t a b s - a h i g h normal. T h e r e were, however, 72 per cent s e g m e n t s as well, s u g g e s t i n g a s u b a e u t e process. A s l i g h t l y i n j e c t e d a p p e n d i x was removed. Section showed two small, superficial ulcerations w i t h o u t i n f l a m m a t o r y i n f i l t r a t i o n - - c o n s i d e r e d s u b a c u t e . T h o u g h this a p p e n d i x w a s u n d o u b t e d l y b e t t e r out of the body, t h e count correctly i n d i c a t e d no a c u t e i n f l a m m a t i o n at t h e time of operation, a n d no s u r g i c a l a b d o m e n . CAs~ 2 0 . - - A girl, a g e d eleven years, h a d p a i n in the r i g h t lower a b d o m e n a n d n a u s e a w i t h o u t v o m i t i n g f o r t h r e e d a y s b e f o r e admission. T h i s p a i n h a d r e c u r r e d a t i n t e r v a l s f o r t h e p a s t t h r e e weeks, b u t t h e p r e s e n t a t t a c k was t h e m o s t severe, a n d t h e child could h a r d l y sit or stand. T h e t e m p e r a t u r e w a s 99 ~ F. T h e r e w a s definite t e n d e r n e s s on m o d e r a t e p r e s s u r e over M c B u r n e y ' s point. Rectal e x a m i n a tion verified this t e n d e r n e s s on t h e r i g h t side. T h e white c o u n t was 16,000. T h e r e Were only 7 p e r cent stabs, however. A d i a g n o s i s of acute a p p e n d i c i t i s w a s m a d e despite t h e n o r m a l differentia], t h o u g h it was a r g u e d there could be no acute process w i t h this count. A p p e n d e c t o m y was p e r f o r m e d a f e w h o u r s a f t e r admission, a n d a g r o s s l y n o r m a l a p p e n d i x was removed. T h e p a t h o l o g i s t r e p o r t e d a chronic c a t a r r h a l a p p e n d i c i t i s with a smooth, g l i s t e n i n g serosa a n d a s l i g h t l y i n j e c t e d m u e o s a intact. CO!ViMENT
I t can thus be seen f r o m these findings and other r e p o r t e d cases t h a t a count of the immature, nonsegmented, p o l y m o r p h o n u e l e a r leucocytes in the d i f f e r e n t i a l blood s m e a r is p a r t i c u l a r l y useful in ruling out a c u t e appendicitis a n d the need f o r i m m e d i a t e s u r g e r y in cases w i t h false s y m p t o m s a n d signs, w h e r e the t e m p e r a t u r e is normal. I n the presence of f e v e r t h e r e is u s u a l l y an increase in the stab forms, a n d one cannot k n o w w h e t h e r the a p p e n d i x or some other p a r t of t h e b o d y is responsible f o r the shift. R e g a r d l e s s of the t o t a l white cell count or other suspicious signs, a n o r m a l p e r c e n t a g e of stab cells indicates the absence of acute i n f l a m m a t i o n in the b o d y and relieves the p a t i e n t of the need f o r u r g e n t l a p a r o t o m y . I t has been shown t h a t in over 30' per cent of the a p p e n d e c t o m i e s p e r f o r m e d , n o r m a l appendices h a v e been r e m o v e d f o r w a n t of an a c c u r a t e guide as to the actual presence of inflammation. These unn e c e s s a r y operations can be s a f e l y obviated b y a more general use of the Schilling index. I n practice, if a case with suggestive signs shows a count of m o r e t h a n 10 per cent stab cells, one should ignore the count and follow the signs. There m a y be acute appendicitis present. I f it shows less t h a n 10 per cent stabs, acute appendicitis is h a r d l y possible. SU3/I IV[ARY
T h i r t y cases diagnosed as acute appendicitis and operated on f o r this condition are described a n d discussed with speeiaI r e f e r e n c e to the signifieanee of the p e r c e n t a g e of i m m a t u r e , nonsegmented, p o l y m o r -
phonuelear leucocytes in the blood stream.
ROGATZ :
SCI-IILLING .BLOOD COUNT
763
Of these t h i r t y cases, histologic specimens in six were those of normal or n o n a c u t e l y inflamed appendices, a c c u r a t e l y judged by the Schilling count before operation. A table of the whole series with the h e m o g r a m and i m p o r t a n t pathologic findings in each case is given. T h o u g h this group of eases is small, similar results have been described in adults. The p r a c t i c a l importance of tile conclusions arrived at j u s t i f y f u r t h e r observations on the correctness of these results. CONCLUSIONS
The Schilling differential smear is accurate in determining the absence of acute appendicitis in the presence of falsely suggestive symptoms and signs where the t e m p e r a t u r e is normal, regardless of the total white count. In so f a r as this information cannot be obtained with the o r d i n a r y examination of the blood smear, the Schilling method is far more valuable and should replace t h e older count. The routine use of the Schilling index in the f u t u r e should materially reduce unnecessary appendectomies and the consequent risk incurred. REFERENCES 1. Schilling, Victor, and Gradwoh], R. B. It. : The :Blood Picture, ed. 7 and 8, p. 254, St. Louis, 1929, C. V. Mosby Co. 2. Nussbaum, S.: Arch. Pedlar. 49: 207, 1932. 3. Weiss, A.: Am. J. M. So. 174: 45, 1927. 4. u A.: Am. J. Clln. Path. 1: 39, 1931. 5. tIerz, O.: Monatschr. f. ]~inderh. 49: 309, 193]. 6. Goodale, R., and Manning, M.: J. Lab. & Clin. Med. 16: 386, ]931. 7. Luck, J. V.: Am. J. Surg. 19: 275, 1933. 8. Proatmow, F . : Arch. f. klin. Chlr. 166: 160, ]93]. 9. Rogatz, J. L.: Am. J. Dis. Child. 40: 70, 1930. 1070 PARK AVENUE
J U L I & N L . ROG•TZ,
blood s m e a r w i t h special a t t e n t i o n to S TtheU D Ii EmSm aoft u r ethe, p odifferential l y m o r p h o n u c l e a r leucocytes, in p r a c t i c a l l y all the k n o w n p a t h o l o g i c states, h a v e led to the conclusion t h a t in the absence of infection t h e r e can be no a p p r e c i a b l e increase in the p e r c e n t a g e of i m m a t u r e white cells in the blood. R e p o r t s on m a n y thousands of cases h a v e confirmed Schilling% original contention t h a t " a real failu r e " of the differential s m e a r to indicate the presence of infection in the b o d y " i s u n t h i n k a b l e . ' ,1 Otherwise stated, an absolutely n o r m a l s m e a r w i t h no increase in the i m m a t u r e neutrophiles enables one to rule out the presence of an acute infectious process in the b o d y with r e a s o n a b l e accuracy. I f rep e a t e d counts are normal, there is no acute infection present. This premise, which is v i t a l to the v a l i d i t y of t h i s work, has been a m p l y proved.i, e, 3 D o u b t f u l cases of " a p p e n d i c i t i s " f r e q u e n t l y occur with a b d o m i n a l pain a n d localized tenderness, w i t h or w i t h o u t vomiting, with n o r m a l t e m p e r a t u r e a n d n o r m a l total leucocyte count, in which it is difficult to m a k e a positive diagnosis. The usual white a n d differential blood counts v a r y g r e a t l y and are of no real significance. These guides are especially unreliable in children. W i t h i m p r o v e d , modern, o p e r a t i v e technic, r a t h e r t h a n r i s k costly delay a n d the r u p t u r e of an acutely inflamed a p p e n d i x , the surgeon feels it s a f e r a n d wiser to p e r f o r m an a p p e n d e c t o m y in all d o u b t f u l cases at the risk of finding a n o r m a l appendix, which, as a m a t t e r of fact, occurs in a b o u t f r o m 30 to 40 per cent of cases o p e r a t e d on for acute appendicitis. 4' ~ I f it were possible, in such u n c e r t a i n cases, to rule out definitely acute infection, some other e x p l a n a t i o n of s u g g e s t i v e s y m p t o m s m i g h t be sought, a n d m a n y u n n e c e s s a r y a p p e n d e c t o m i e s avoided. O p e r a t i v e technic is not u n i f o r m l y good, and the d a n g e r s of unskilled s u r g e r y at inconvenient times are got negligible. A c a r e f u l e x a m i n a t i o n of the blood s m e a r b y the Schilling method, which is not difficult, should u n e q u i v o c a l l y indicate the absence of an acute i n f l a m m a t o r y process in the a p p e n d i x and t h e r e b y minimize u n n e c e s s a r y surgery. F r o m the A. J~eobi I)ivision for C hi l dre n of t he L e n o x H i l l I-Iospital; service of ]Dr. J e r o m e S. Leopold. 757
758
T[IE JOURNAL
OF P E D I A T R I C S
This can be done only, however, w h e n the p e r c e n t a g e of i m m a t u r e white cells in the s m e a r is n o r m a l (10 per cent or less in children). [['he presence of f r o m 10 p e r cent to 15 per cent of these y o u n g f o r m s indicates a mild, acute or s u b a c u t e c a t a r r h a l process. More t h a n 15 per cent of the y o u n g cells is definite evidence of infection s o m e w h e r e in the body. Since the blood differential is not specific, it does not determine the n a t u r e of the i n f l a m m a t o r y process, whose presence, once indicated, m u s t be located b y other signs. R E V I E W OF L I T E R A T U I C E
Efforts to develop a highly p r a c t i c a l application of the Schilling count b y establishing the absence of an acutely inflamed a p p e n d i x in the presence of false, t h o u g h suggestive, signs led to a s t u d y of a series of cases as t h e y a p p e a r e d in the p e d i a t r i c wards. W h e n this w o r k was begun, there were no r e p o r t s of a similar n a t u r e in the literature. Since then, however, several observers have published the results of t h e i r studies on the Schilling index in acute appendicitis, mostly in adults. My observati6ns in children corroborate those which have r e c e n t l y a p p e a r e d and should be followed b y other studies. I f these faets can be repeatedly verified, they are of great practical value. Y a g u d a * r e v i e w e d a series of 671 cases (the ages are not given, b u t some children m u s t h a v e been included in this n u m b e r ) on which appendectomies h a d been p e r f o r m e d . The blood smears h a d been examined b y the usual m e t h o d a n d filed. T h e y were r e e x a m i n e d according to the Schilling classification, and these counts were comp a r e d with the histologic findings in each case. These results are of g r e a t interest a n d significance. T h e y are briefly s t a t e d as follows: 1. N o r m a l appendices (no evidence of acute inflammation), 277 cases (41 p e r cent), showed f r o m 2 p e r cent to 8 p e r cent stab f o r m s ( a v e r a g e 4.3 p e r cent). 2. C a t a r r h a l appendices ( i n f l a m m a t o r y process limited to the mueosa) showed 7 per cent to 14 p e r cent stab cells ( a v e r a g e 10.2 p e r cent). 3. Acute, diffuse, s u p p u r a t i v e appendicitis w i t h o u t p e r f o r a t i o n showed 14 p e r cent to 28 p e r cent stabs ( a v e r a g e 17.8 p e r cent). 4. Acute, diffuse, s u p p u r a t i v e appendicitis with p e r f o r a t i o n and peritonitis showed 32 per cent to 47 per cent stabs ( a v e r a g e 39.5 p e r cent). Y a g u d a concluded t h a t a n o r m a l p e r c e n t a g e of i m m a t u r e neutrophile ceils ruled out acute appendicitis. H e r z s f o u n d t h a t in 161 cases diagnosed appendicitis it was possible to establish some other diagnosis in sixty-one cases. I n thirty-five cases of a p p e n d e c t o m y with histologic specimens, eleven were normal.
ROGATZ:
SCHILLING
BLOOD
COUNT
759
H e c o n c l u d e d t h a t t h e S c h i l l i n g c o u n t is i n v a l u a b c a n d w i t h it one c a n o f t e n a v o i d o p e r a t i o n . A n a c u t e case of a p p e n d i c i t i s n e v e r occurs with a normal blood picture. I n a s m a l l e r series, c o n t a i n i n g t e n a c u t e cases a n d t h i r t y n o n a c u t e cases, six of t h e e n t i r e g r o u p b e i n g c h i l d r e n , Gooda]e a n d M a n n i n g ~ f o u n d t h a t i n cases w h e r e t h e a p p e n d i c e s s h o w e d a g e n e r a l , p o ] y m o r -
phonuclear infiltration, with or without pus in the lumen, there is a definite left shift. Normal cases showed no increase in the immature white cells. They concluded that the Schilling index renders a more accurate picture of the pathology in the appendix than the ordinary differential count. L u c k 7 d e s c r i b e d t h e b l o o d p i c t u r e i n a p p e n d i c i t i s i n t e n a d u l t %~ses a n d n o t e d t h a t t h e Schil]ing~ C o u n t is v a l u a b l e to d e t e r m i n e t h e presence or a b s e n c e of a n i n f e c t i o n i n t h e b o d y . H e e n c o u n t e r e d n o i n f e c t i o n of a n y s e v e r i t y i n t h 4 " a b s e n c e of a s h i f t to t h e left, r e g a r d l e s s of t h e c l i n i c a l s y m p t o m s or t h e t o t a l l e u c o c y t e a n d p o ] y m o r p h o n u c l e a r count. P r o c h n o w 8 f o u n d the use of the S c h i l l i n g h e m o g r a m h i g h l y s a t i s f a c t o r y d i a g n o s t i c a l l y i n a c u t e a p p e n d i c i t i s a m o n g adu]ts. H e n o t e d a m a r k e d l e f t s h i f t w i t h i n c r e a s i n g ' s e v e r i t y of t h e i n f e c t i o n .
METs
AND OBSEI~VATIONS
On admission a total white cell count and a Schilling differential count were made in every case, prior to operation. Wright's stain was used in preparing' the blood smears. If the smears are thin and of even quality, so that there is no clumping or overlapping of erythrocytes, the leucocytes will be well formed and easy to distinguish in any portion of the smear. In a properly prepared specimen crushed elements are only occasional. It is impossible to classify cells with any accuracy in thick preparations, and failure is often due to this fault. The white cells were tabulated horizontally in the form of a hemogram, as basophiles, eosinophiles, myelocytes, juveniles, stabs, segments, lymphocytes, and monocytes (see Tables I and II). The rarely seen myelocytes, the infrequent juvenile cells, and the common, deTABLE ~ONACUT~ CASE
5 6 13 16
20
DATE
1/3/32 5/28/32 3/ 7/30 3/]8/33 5/ 2/33
I AGE IN[ u B E
s 11 10 1t 11
1-31 - 3 [- 1 - I 5 -
I CASES
j ~ -s~ L~ON' ]~AT~OT~OaIC ~EPO~T ] 1 55- ~ Normal 6 37[ 50 4 Normal appendix. 5 45 44 3 Chronic , thickened macosa. 11 72 ]4 2 Chronic, kinked, nonacute. ]0 62 26 2 Mild, chronic appendicitis. - 7 38 45 4 Chronic. Serosa smooth.
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THE JOURNAL OF PEDIATRICS TABLE
II
ACUTE CASES
~E~OG~A~ I PATIIOLOGIC REPORT M J ST S L M0~ - - 19 52 25 4 ~Early acute appendicitis. 4 Chronic, catarrhal, retrocecal; no~-12 29 5I acutely inflamed. 4 12/19/31 t4 7 Acute, exudative; many white blood 26 47 19 corpuscles. 7 8/ 6/32 12 Acute, hemorrhagic; necroses. 16 40 40 4 8 8/ 9/32 Acute fibrinous exudate at tip. 7 30 52 15 4 9 12/10/32 Ruptured; peritonitis. 5 1 68 26 4 1 10 1'2/29/32 12. Acute empyema of appendix. 1 21 66 8 4 11 1/10/33 Gangrenous, perforated; free pus, 31 52 5 11 8 adhesions, peritonitis. 12 2/ s/33 3 High retroceca], acute, covered with 40 47 10 8 fibrin. 14 3/]0/33 10 -20 62 14 4 Acute, inflamed, thickened. 15 3/12/33 10 ] 4 51 32. 9 3 Acute, suppurative, perforated. 17 3/30/33 8 2 31 35 24 7 Acffte, inflamed appendix. 18 4/12/33 5 32 53 11 2 2 Acute, inflamed, ruptured. 19 4/13/33 2 39 44 8 7 I~uptured ; free pus, 7 2,1 5/17/33 12 17 29 49 2 Chronic, catarrhal; serosa injected. 22 5/18/33 S 7 34 41 ]5 3 Ruptured; acute peritonitis. 23 511~/33! 9 - - 36 34 24 G Acute suppurative appe~diMtis. 24 7/21/33i :[3 15 77 8 0 Acute congestion; necroses; wMte blood corpuscles in mueosa section. 25 8/10/33 4 35 21 39 5 Retrocecal, appcndiceal abscess. 26 8/23/33 7 39 50 3 8 Acute~ suppm'ative; necroses. 27 8/23/33 12 2 40 28 28 2 Acute, ruptured during removal. 28 8/25/33 12 47 35 11 7 Acute, suppurative; necroses. 29 8/26/33 8 7 Acute, suppurative; necroses. 37 49 7 3O 9/12/33 9 3 32 52 9 4 Empyema of appendix. Abbreviations: ]3, basolohiles; E, eosinophiles; IV[, myeloeytes; J, juveniles; ST. stabs; S, segments; L. lymlJhocytes; MON, monocytes. AGEI: CASE DATE YEAR Y R 2 11/ 5/31 3 12/10/31 7
-
g e n e r a t e d s t a b or b a n d f o r m s c o m p r i s e t h e i m m a t u r e p o l y m o r p h o nuclear leucocytes with nonsegmented nuclei and represent varying d e g r e e s of i m m a t u r i t y . A n i n c r e a s e i n t h e p e r c e n t a g e of t h i s g r o u p of cells over n o r m a l c o n s t i t u t e s a " s h i f t to t h e ]eft. ''9 I n i n f e c t i o n s of m o d e r a t e s e v e r i t y t h e s t a b f o r m s w e r e i n c r e a s e d o v e r n o r m a l . As t h e i n f e c t i o n p r o g r e s s e d , a f u r t h e r i n c r e a s e i n s t a b f o r m s w a s f o l l o w e d b y t h e a p p e a r a n c e of j u v e n i l e cells a n d , i f a l l o w e d to c o n t i n u e u n t r e a t e d , r e s u l t e d i n t h e a p p e a r a n c e of o c c a s i o n a l m y e l o cytes i n the p e r i p h e r a l blood. T h o u g h t h e d e g r e e of s h i f t w a s app r o x i m a t e l y p r o p o r t i o n a l to t h e s e v e r i t y of the p a t h o l o g y f o u n d , one could n o t i n v a r i a b l y j u d g e t h e e x t e n t of d a m a g e i n t h e a p p e n d i x f r o m t h e a m o u n t of shift. I t is i m p o r t a n t to note, h o w e v e r , t h a t a n i n c r e a s e i n t h e i m m a t u r e w h i t e cells n e v e r f a i l e d to i n d i c a t e the p r e s e n c e of infection. The segments (the familiar, mature, po]ymorphonue]ear leucocytes w i t h t w o or m o r e lobes c o n n e c t e d b y h a i r l i k e f i l a m e n t s f o r m i n g t h e n u c l e u s ) w e r e u s u a l l y d e c r e a s e d d u r i n g t h e a c u t e s t a g e of i n f e c t i o n a n d b e c a m e m o r e n u m e r o u s d u r i n g c o n v a l e s c e n c e . A n a b n o r m a l increase of the s e g m e n t s w i t h a n o r m a l p e r c e n t a g e of s t a b s u s u a l l y in-
ROGATZ:
SCHILLING BLOOD COUNT
761
dieated a chronic infection. I t is for this r e a s o n t h a t a high percenta g e of p o t y m o r p h o n u c l e a r cells m u s t be e x a m i n e d to determine the n u m b e r of i m m a t u r e , n o n s e g m e n t e d f o r m s present. One m a y not assume t h a t a high p o l y m o r p h o n u c l e a r count m e a n s a high stab count. Unless acute infection is present, t h e r e will be no a b n o r m a l increase in stab forms. This i m p o r t a n t i n f o r m a t i o n can only be obtained by g r o u p i n g the cells according to the presence or absence of filaments in the nuclei2 REPORT OF CASES
I n this series of t h i r t y appendectomies, six cases showed normal his~ tologie specimens. I n each of these cases t h e opinion was v e n t u r e d t h a t a normal, or at least a n o n a e u t e l y inflamed, a p p e n d i x would be f o u n d a n d t h a t a p p e n d e c t o m y w a s not u r g e n t l y indicated. The total white count is omitted in the tables since it p l a y e d no p a r t in determining the presence or absence of infection. I n several instances it was n o r m a l in the presence of severe p a t h o l o g y a n d was therefore reg a r d e d as unreliable. A m o n g the nonaeute cases, p a t i e n t s 1 and 13 showed stab counts of 11 p e r cent. This slight increase over n o r m a l was not deemed sufficient evidence of acute infection. Case 13 s h o w e d 83 per cent polym o r p h o n u c l e a r cells, of which 72 p e r cent w e r e m a t u r e segments, indicating as the microscopic sections showed, a chronically inflamed organ, b u t n o acute infection. T h o u g h Case 3, with a high normal figure of 12 p e r cent stabs was omitted f r o m the nonaeute group, it w a s felt t h a t no u r g e n c y for o p e r a t i o n existed t h o u g h the a p p e n d i x m i g h t be chronically inflamed and b e t t e r removed. IIistologie section indicated this. CASE 1 . - - P a t i e n t , aged e i g h t years, gave a h i s t o r y of p a i n in the r i g h t u p p e , q u a d r a n t , of t w e n t y - f o u r h o u r s ' d u r a t i o n , g r o w i n g worse a n d a p p e a r i n g in the l e f t lower q u a d r a n t . T h e r e was no v o m i t i n g . T h e r e w a s t e n d e r n e s s in the r i g h t lower quadrant, O t h e r e x a m i n a t i o n was n e g a t i v e . The t e m p e r a t u r e was 99 ~ F, The t o t a l leucocyte c o u n t was 12~400. T h e Schilling s m e a r showed ]1 per cent stabs, a n d o p e r a t i o n w a s d e e m e d u n n e c e s s a r y , as i n f e c t i o n w a s n o t shown to be present. A p p e n d e c t o m y w a s performed~ a n d a n o r m a l a p p e n d i x was removed. CASE 6 . - - P a t i e n t , a g e d eleven years, w a s ill for six d a y s with p a i n in t h e r i g h t a b d o m e n . T h e p a t i e n t was n a u s e o u s b u t did n o t v o m i t d u r i n g this period. T h e bowels were regular. There was no fever. T h e r e w a s s l i g h t t e n d e r n e s s a n d s p a s m over t h e r i g h t r e c t u s muscle. T h e t o t a l white cell c o u n t w a s ]1,000. T h e r e were 5 p e r cent s t a b s i n t h e smear. W i t h this c o u n t t h e r e could be no acute or s u b a c u t e i n f e c t i o n in t h e b o d y a n d operation was deemed u n n e c e s s a r y . The p a t h o l o g i s t r e p o r t e d a t h i c k e n e d m u c o s a w i t h no necroses a n d m a d e a diagnosis o f chronic appendicitis. CASE 1 3 . - - P a t i e n t j a g e d t e n years~ complained of p a i n in the r i g h t ~idc f o r two weeks. T h e r e was no v o m i t i n g . E x a m i n a t i o n revealed m a r k e d t e n d e r n e s s on m o d e r a t e p r e s s u r e i n the r i g h t lower ,quadrant, especially over M e B u r n e y ' s point. T h e reetM e x a m i n a t i o n was negative. T h e t e m p e r a t u r e w a s 100 ~ F. T h e child
762
THE J O U R N A L OF PEDIATRICS
w a s a p p r e h e n s i v e a n d neurotic. W i t h t h e t e m p e r a t u r e a p p r o x i m a t e l y n o r m a l a n d no other a p p a r e n t cause f o r t h e pain, t h e s t a b count was u s e f u l in i n d i c a t i n g t h e absence of an a c u t e i n f l a m m a t o r y process. T h e s m e a r showed 11 p e r cent s t a b s - a h i g h normal. T h e r e were, however, 72 per cent s e g m e n t s as well, s u g g e s t i n g a s u b a e u t e process. A s l i g h t l y i n j e c t e d a p p e n d i x was removed. Section showed two small, superficial ulcerations w i t h o u t i n f l a m m a t o r y i n f i l t r a t i o n - - c o n s i d e r e d s u b a c u t e . T h o u g h this a p p e n d i x w a s u n d o u b t e d l y b e t t e r out of the body, t h e count correctly i n d i c a t e d no a c u t e i n f l a m m a t i o n at t h e time of operation, a n d no s u r g i c a l a b d o m e n . CAs~ 2 0 . - - A girl, a g e d eleven years, h a d p a i n in the r i g h t lower a b d o m e n a n d n a u s e a w i t h o u t v o m i t i n g f o r t h r e e d a y s b e f o r e admission. T h i s p a i n h a d r e c u r r e d a t i n t e r v a l s f o r t h e p a s t t h r e e weeks, b u t t h e p r e s e n t a t t a c k was t h e m o s t severe, a n d t h e child could h a r d l y sit or stand. T h e t e m p e r a t u r e w a s 99 ~ F. T h e r e w a s definite t e n d e r n e s s on m o d e r a t e p r e s s u r e over M c B u r n e y ' s point. Rectal e x a m i n a tion verified this t e n d e r n e s s on t h e r i g h t side. T h e white c o u n t was 16,000. T h e r e Were only 7 p e r cent stabs, however. A d i a g n o s i s of acute a p p e n d i c i t i s w a s m a d e despite t h e n o r m a l differentia], t h o u g h it was a r g u e d there could be no acute process w i t h this count. A p p e n d e c t o m y was p e r f o r m e d a f e w h o u r s a f t e r admission, a n d a g r o s s l y n o r m a l a p p e n d i x was removed. T h e p a t h o l o g i s t r e p o r t e d a chronic c a t a r r h a l a p p e n d i c i t i s with a smooth, g l i s t e n i n g serosa a n d a s l i g h t l y i n j e c t e d m u e o s a intact. CO!ViMENT
I t can thus be seen f r o m these findings and other r e p o r t e d cases t h a t a count of the immature, nonsegmented, p o l y m o r p h o n u e l e a r leucocytes in the d i f f e r e n t i a l blood s m e a r is p a r t i c u l a r l y useful in ruling out a c u t e appendicitis a n d the need f o r i m m e d i a t e s u r g e r y in cases w i t h false s y m p t o m s a n d signs, w h e r e the t e m p e r a t u r e is normal. I n the presence of f e v e r t h e r e is u s u a l l y an increase in the stab forms, a n d one cannot k n o w w h e t h e r the a p p e n d i x or some other p a r t of t h e b o d y is responsible f o r the shift. R e g a r d l e s s of the t o t a l white cell count or other suspicious signs, a n o r m a l p e r c e n t a g e of stab cells indicates the absence of acute i n f l a m m a t i o n in the b o d y and relieves the p a t i e n t of the need f o r u r g e n t l a p a r o t o m y . I t has been shown t h a t in over 30' per cent of the a p p e n d e c t o m i e s p e r f o r m e d , n o r m a l appendices h a v e been r e m o v e d f o r w a n t of an a c c u r a t e guide as to the actual presence of inflammation. These unn e c e s s a r y operations can be s a f e l y obviated b y a more general use of the Schilling index. I n practice, if a case with suggestive signs shows a count of m o r e t h a n 10 per cent stab cells, one should ignore the count and follow the signs. There m a y be acute appendicitis present. I f it shows less t h a n 10 per cent stabs, acute appendicitis is h a r d l y possible. SU3/I IV[ARY
T h i r t y cases diagnosed as acute appendicitis and operated on f o r this condition are described a n d discussed with speeiaI r e f e r e n c e to the signifieanee of the p e r c e n t a g e of i m m a t u r e , nonsegmented, p o l y m o r -
phonuelear leucocytes in the blood stream.
ROGATZ :
SCI-IILLING .BLOOD COUNT
763
Of these t h i r t y cases, histologic specimens in six were those of normal or n o n a c u t e l y inflamed appendices, a c c u r a t e l y judged by the Schilling count before operation. A table of the whole series with the h e m o g r a m and i m p o r t a n t pathologic findings in each case is given. T h o u g h this group of eases is small, similar results have been described in adults. The p r a c t i c a l importance of tile conclusions arrived at j u s t i f y f u r t h e r observations on the correctness of these results. CONCLUSIONS
The Schilling differential smear is accurate in determining the absence of acute appendicitis in the presence of falsely suggestive symptoms and signs where the t e m p e r a t u r e is normal, regardless of the total white count. In so f a r as this information cannot be obtained with the o r d i n a r y examination of the blood smear, the Schilling method is far more valuable and should replace t h e older count. The routine use of the Schilling index in the f u t u r e should materially reduce unnecessary appendectomies and the consequent risk incurred. REFERENCES 1. Schilling, Victor, and Gradwoh], R. B. It. : The :Blood Picture, ed. 7 and 8, p. 254, St. Louis, 1929, C. V. Mosby Co. 2. Nussbaum, S.: Arch. Pedlar. 49: 207, 1932. 3. Weiss, A.: Am. J. M. So. 174: 45, 1927. 4. u A.: Am. J. Clln. Path. 1: 39, 1931. 5. tIerz, O.: Monatschr. f. ]~inderh. 49: 309, 193]. 6. Goodale, R., and Manning, M.: J. Lab. & Clin. Med. 16: 386, ]931. 7. Luck, J. V.: Am. J. Surg. 19: 275, 1933. 8. Proatmow, F . : Arch. f. klin. Chlr. 166: 160, ]93]. 9. Rogatz, J. L.: Am. J. Dis. Child. 40: 70, 1930. 1070 PARK AVENUE