• No results found

THE BACTERIOLOGIC FINDINGS, STREPTOCOCCAL IMMUNE RESPONSE, AND RENAL COMPLICATIONS IN CHILDREN WITH IMPETIGO

N/A
N/A
Protected

Academic year: 2020

Share "THE BACTERIOLOGIC FINDINGS, STREPTOCOCCAL IMMUNE RESPONSE, AND RENAL COMPLICATIONS IN CHILDREN WITH IMPETIGO"

Copied!
14
0
0

Loading.... (view fulltext now)

Full text

(1)

THE

BACTERIOLOGIC

FINDINGS,

STREPTOCOCCAL

IMMUNE

RESPONSE,

AND

RENAL

COMPLICATIONS

IN

CHILDREN

WITH

IMPETIGO

Milton Markowitz, M.D., H. David Bruton, M.D., Ann G. Kuttner, M.D.

and Leighton E. Cluff, M.D.

Streptococcal Disease Laboratory, Department of Pediatrics, Sinai Hospital; the Harriet Lane Home

Service and Department of Pediatrics, Children’s Medical and Surgical Center; and the Department

of Medicine, The Johns Hopkins Hospital

Clinical Material

A total of 303 children seen at the

Har-(Submitted August 19; revision accepted for publication November 18, 1964.)

This study was supported in part by Grant HE 05555, National Institutes of Health, Public Health

Service, Bethesda, Maryland, and by a contract with the Armed Forces Epidemiological Board, Com-mission on Streptococcal and Staphylococcal Diseases.

ADDRESS: (MM.) Sinai Hospital of Baltimore, Belvedere Avenue at Greenspring, Baltimore, Mary-land 21215.

PEDIATRICS, March 1965

393

S

UPERFICIAL skin infections, especially

impetigo, occur commonly in

chil-dren. These infections are of special

inter-est because they are often associated with

acute glomerulonephritis. 4 Streptococci

have l)een isolated frequently from

impeti-ginous lesions, but they have not been

ade-quately studied and their role in patients

‘ith renal complications is not understood.

A prospective systematic study of 303

chil-dren with impetigo was undertaken in

which the following aspects of the problem

were investigated: (1) The incidence of

group A streptococci in the skin lesions;

(2) concommitant studies of the bacteriology

of the nasopharnyx; (3) routine urine

ex-aminations; (4) streptococcal antibody

re-sponse.

Recent knowledge of the bacteriology of

impetigo is based mainly on the excellent

studies by Parker et ai., and by Barrow.

Group A streptococci isolated from

im-petiginous lesions were found by these

in-vestigators to fall into a small number of

characteristic agglutination patterns.

Fur-thermore, these observers also found that a

single phage-type of staphylococci

pre-dominated in impetigo. In view of this

find-ing observations on staphylococci as well as

on streptococci were included in this study.

PLAN OF STUDY

net Lane Home Out-Patient Department

over a 10-month period (July, 1963, through

April, 1964) with skin infections were

in-eluded in the study. The majority of the

children (86%) had typical impetigo

con-tageosum. The remainder had

miscellane-ous pyogenic skin conditions, chiefly

in-fected eczema. A separate analysis of data yielded no significant differences between

the impetigo and the other pyogenic skin

infections.

There were 146 males and 157 females.

Ninety-five per cent of the children were

Negro. There were 95 patients in the 0-2-year age group, 107 in tile 3-5-age group

and 101 in the 6-14-age group.

At the time of the initial visit, a history

was taken of the duration of the skin

le-sions, their presence in other members of

the family and previous treatment. On

physical examination the number and

char-acter of the skin lesions were noted. The

presence of associated physical findings

such as nasal discharge, pharyngitis,

and regional lymphadenopathy were

re-corded. Cultures of the skin, nares, and

pharynx and a urine specimen were

oh-tamed (see Laboratory Methods). The

pa-tients were asked to return one and three

weeks following the initial visit. Two

hun-dred and thirty patients (77%) returned. On

follow-up visits, an evaluation was made of

the clinical response to local treatment

(2)

394 STREPTOCOCCAL IMPETIGO

parenteral penicillin. The nares, throat, and skin lesions were recultured, and another

urine specimen obtained.

Laboratory Methods

Cultures were obtained from the skin

lesions, nares, and pharynx with sterile

swabs which were inoculated immediately

onto 5% sheep blood agar plates. Open skin lesions or lesions from which the crust was removed were selected for culture. The

plates were incubated aerobically for 18

to 24 hours at 37#{176}Cand thereafter were examined for beta hemolytic streptococci and hemolytic staphylococci. Colonies of beta hemolytic streptococci and hemolytic

staphylococci were picked, subeultured for

purity, and transferred to blood broth. Beta

hemolytic streptococci were grouped and

typed by the precipitin reaction. A

num-ber of the strains, which could not be typed in this manner were sent to Dr. Armine T.

Wilson and Dr. M. T. Parker for typing

by the slide-agglutination technique. The staphylococci isolated were tested for

co-agulase activity. Coagulase-positive strains

were typed with bacteriophage at routine

test dilutions (RTD) using the standard set

of phages according to the method of Blair

and Carr.7 When not typable with RTD

phage types, tests were performed with 1,000 RTD. The phages used were Group

I: 29, 52, 52A, 79 and 80; Group II: 3A,

3B, 3C, 55, and 71; Group III: 6, 7, 42E, 47, 53, 54, 75, 77, and 83 (VA4); Group IV:

42D; Misc.: 81 and 187.

Blood was drawn aseptically, the serum

separated and stored in the frozen state

without preservative. Specimens from each

patient were tested in sequence

simulta-neously for antistreptolysin 0 antibodies.

Staphylococci were tested for penicillin sen-sitivity, using discs containing 2 units of

penicillin. The indirect bactericidal test was

used to detect type-specific antibodies. The

details of this method have been ouflined

in a previous publication.8

The specific gravity of the urine was re-corded and the protein content determined

by sulfosalicylic acid method. Fifteen ml

were spun for five minutes at 2,500 RPM and examined microscopically. Results were

reported as cells per high power field. If

pyuria was present, clean catch urine

cul-tures were obtained. In every Negro child

with hematuria the presence of hemoglobin S was ruled out by hemoglobin electro-phoresis.

Treatment

At the time of the initial visit the par-ents of all patients were instructed to

cleanse the skin lesions with a warm, soapy

wash cloth four times daily followed by the application of a thin layer of 3%

am-moniated mercury ointment. Every patient

with a history number ending in an odd

digit received one intramuscular injection

of 600,000 units of procaine penicillin

com-bined with 600,000 units of benzathine

penicillin C.

RESU LTS

Bacteriologic Findings

Streptococcus pyogenes and

coagulase-positive Staphylococcus aureus were the

two bacterial species studied in cultures

from the skin and nares. Beta hemolytic streptococci were the only organisms

iso-lated from the pharynx which were investi-gated. The skin lesions were positive for either staphylococci or streptococci or both in 172 of 303 children (57%). The

percent-age of patients in the total group and in

different age groups from whom these or-ganisms were cultured from skin lesions is

shown in Figure 1.

Smiivrococcus PYOGENES: Fifty children

had pure cultures of streptococci and 18

had mixed cultures of streptococci and

staphylococci. Beta hemolytic streptococci were found in a total of 68 patients (22%).

Of the 68 strains isolated from the skin

lesions, 53 were Group A and one was

Group C. The remaining 14 were

non-groupable. Typing of the Group A strains

by the precipitin test was successful in only

four instances. It has been repeatedly

ob-served that streptococci isolated from the

(3)

00%

90

80.

70

60.

50.

40

30.

20.

l0

L

395

* Not tested.

P

1

Staphylococcus aureus

Streptococcus pyogenes

________ Staphylococcus aureus and

Streptococcus pyogenes

L

Total group 0-2 Years 2-5 Years 6-14 Years

(303) (95) (107) (101)

FIG. 1. The percentage of patients in the total group and in different age groups from whom S. aureus

and S. pyogenes were isolated from skin lesions. The number of patients in each group is shown in

parenthesis.

technique. Dr. Armine T. Wilson and Dr.

M. T. Parker kindly typed 21 strains by

the slide-agglutination method. The results

of typing by slide-agglutination and

pre-cipitin tests arc shown in Table I. Of the

four strains which were typable by the

precipitin method two were Type 6, one

Type 2 and one Type 28. Among the strains

typed by the slide-agglutination technique,

one was Type 28. The remainder fell into

the following agglutination patterns : 4

Types 3/13/3319, 4 Types 5127144, 7 Type

14, and 5 Types 812511mp. 19.

Beta hemolytic streptococci were

iso-lated from the nasopharynx in 26 of the

303 patients (8%) : 16 from the nares and

10 from the pharynx. Of the 26 strains, 15

were Group A and one was Group C. Only

one strain was typable (Type 6). Of the

total group of 68 children with positive

cultures from

the

skin lesions, beta

hemo-lytic streptococci were found in the nares

or pharynx as well as in the skin in 18

pa-tients. Seventeen of the 18 cultures could

not be typed by the precipitin reaction.

The only typable strains, identified as Type

6, were isolated from the nares and skin of

the same child.

STAPHYLOCOCCUS AUREUS :

Coagulase-positive staphylococci were isolated from

the skin lesions of 122 children (40%), 104

in pure culture and 18 in mixed cultures

of staphylococci and hemolytic

strepto-cocci.

TABLE I

SEROTYPE DISTRIBUTION OF 25 STRAINS OF

STREPTO-COCCUS PYOGENaS ISOLATED FROM SKIN LESIONS OF PATIENTS WITH IMPETIGO

Serologic Type

No. Strains

Precipitin Test

Slide- Agglutina-tion

Type2 Type6 Type28

Type 3/13/33/9

Type 5/27/44 Type 14 (T antigen)

Types 8/25/Imp 19

1

2

2

4 4 7

5

1

2

1 .. .. .. ..

..‘

..

1

4

4

7

(4)

TABLE II

RESULTS OF P1IAGE-TYPING OF Staphylococcus Aureus

ISOLATED FROM CULTURES OF TIlE SKIN AND NOSE IN

ChILDREN WITH IMPETIGO

isolated

and the

GrOUp

Source of Culture

Skin Nose

I II

Type 71 only

Type 71 +other phages III

Untypable Mixed groups

Total no. strains

12 32

9 21 11 36

8

99

9 34

8 21 9 26

8

86

Ninety-nine of the 122 strains

from the skin were phage-typed

results are shown in Table II. Sixty-three

strains (62%) were typable and 32 of the

typable strains were lysed by one or more

phages in Group II (3A, 3B, 3C, 55, 71). Of the 32 strains in Group II, 31 were lysed

either by phage-type 71 alone (9 strains) or

Type 71 in combination with one or more

other phages in Group II (22 strains).

S. aureus was isolated from the nose in

114 of the 303 patients (38%). Eighty-six of

the 114 strains were phage-typed and the

results are shown in Table II. Sixty strains

(70%)

were typable and of these 35 were

lysed by phages in Group II. Of the 35

strains lysed by Group II phages, 28 were

lysed by either phage-type 71 alone (8

strains) or with other phages in Group II

(21 strains).

Of the 122 children in whom S. aureus

was cultured from the skin lesions, in 58

(47%) this organism was also present in the

nares. To determine whether patients with

phage-typable staphylococci in the skin

were carrying similar types in the nose, a

comparison was made of the phage-types

in 32 of these children. Sixteen of the 32

patients had the same phage-type in the

nose and the skin, and 14 of the 16 were

phage-type 71.

The penicillin sensitivity of 117 strains of

S. aureus was studied. Among 56 strains

isolated from skin lesions, 25 (44%) were

found to be resistant. A smaller number of

strains isolated from the nares were also

resistant to penicillin, 19 of 61 (31%). In

the combined group of 44 resistant strains,

20 were phage-type 71.

Clinical Features and Bacteriologic Findings

The clinical findings in children with

pure cultures of hemolytic streptococci and

of S. aureus as well as patients in whom

neither organism was isolated are shown

in Table III.

It is generally believed that bullous

thin-skinned lesions are more likely to be caused

by staphylococci and that thick-crusted

le-sions are usually streptococcal. In this

se-ries no clinical distinction could be made

from the appearance of the lesion,

prob-ably because the skin infections were rarely

observed in their early stages. Open lesions

were present with equal frequency in the

streptococcal and staphylococcal groups.

Negative cultures occurred most frequently

in children without open lesions.

The incidence of streptococcal impetigo

TABLE III

A COMPARISON OF CLINICAL FINDINGS IN CHILDREN WITH PYOGENIC SKIN DISEASE BASED ON THE

BACTERI-OLOGY OF TIlE SKIN L.sIoNs

Bacteriology of Skin Lesion S. S. Neither pyogenes aureus Organism Number of Patients 50 104 1’9

Age distribution, yr

O- 14 3 30

2-5 30 33 39

6-14 56 33 31

Duration of lesion

Less than one week 60 33 7

More than one week 40 67 73

Type of lesion

Impetigo 89 53 8.5

Infected eczema s 7 3

Other 6 10 10

Open lesions Sl 80 36

Severity

1-lOlesions 37 61 40

More than 10 lesions 48 39 60

Purulent nasal discharge 11 15 7

Pharyngitis 10 14 5

(5)

<2Yrs. (48pts.) 2-5 Yrs. (36 pts.)

o.#{149} I

0

000

6-14 Yrs. (67 pts.)

0

II

01111111

I

I

625

500

UI

C 2250

w

i.-. 166

>-c

0

a)

100.

z

50

12

0 Nasopharynx - beta strep. #{149}Nosopharynx - no beta strep.

Fic. 2. ASO titers of different age groups in a Well Child Clinic Population. The solid line represents the upper limit of normal for each age group.

III

I..

II

I.

I I I

III

III

oIl III III III

IIIIIIII

0111111

II 11111111

0111

III

1111111

01

1111111111

III. III..

I IllIll III.... 1111111

was lower in the infant age group (14%)

than in children over 6 years of age (56%).

Staphylococcal infection, on the other hand,

occurred with about equal frequency in all

age groups. Streptococci were cultured

more frequently from lesions of recent

on-set, while staphylococci were isolated more

commonly from children with impetigo of

longer duration. Three-fourths of the

chil-dren who had negative cultures had had

lesions for several weeks before they were

examined. Additional physical findings such

as nasal discharge, pharyngitis, and regional

lymphadenopathy occurred with the same

frequency in both bacterial groups.

Serologic Findings

Further evidence of streptococcal

infec-tion in children with impetigo was sought

by studying the antistreptolysin 0 titers at

the time of the initial examination. In

addition, serial determinations were

ob-tained in 230 children who returned

for follow-up 7 and 21 days after the first

visit. Since ASO titers vary with age,

socio-economic conditions, geographical area, and

other factors, it seemed desirable to

deter-mine titers in various age groups in a

popu-lation similar to the one from which the

impetigo patients were drawn.

ANTISTREPTOLYSIN 0 (ASO) TITERS:

CON-TROL GRoup: ASO titers were determined in

151 well infants and children randomly

selected from a population similar to the

study group. A nasopharyngeal culture was

taken at the same time. The titers are shown

in the form of a scattergram (Fig. 2). The

geometric mean titer ‘as determined for

each age group (Table IV). The antibody

titer established as the upper limit of the

normal range was defined as two tube

dilutions above the geometric mean titer:

100 units for infants less than 2 years, 125

units for the 2-5-year age group and 250

units for children 6-14 years. In the control

population, 21 of the 151 children (14%)

had an antibody level above the normal

(6)

hemolyt-TABLE IV

PERCENTAGES OF PATIENTS WITH ELEVATED ASO TITERS ANI) TIlE GEo\I:TuIC MEAN TITERS

IN NORMAL CONTROLS AND CIuInREN WITH IMPETIGO

Age Groups (}ears)

0-2 2-5

(;-(‘etlegory

_______--

_--________

-

---

-.

---7CElerated Geomstric % Elevated (,‘eomelric % IJer(z1ed (r’eomelric

ASO Titer Mean Titer ufSO Titer Mean Tiler A So Tiler 1eon ‘I’itcr

Normal controls 5 18 units 2 47 units 16 1i7 units

Impetigo group 20 35 units 39 76 units i8 175 uiiits

ic streptococci in their nasopharynx at the ANTISTREPTOLYSIN 0 TIrEns: IMPETIGO

time that the serum for the determination GROUP: The distribution of the initial ASO

of the ASO titer was obtained and in 7 of titers in 303 children with skin infections is

these 12 children, the antibody level was shown for each age group in Figure 3.

elevated. Eighty-six of the 303 patients (28%) had a

< 2 Yrs. (95 pts.) 2-5 Yrs.(lO7pts.) 6-14 Yrs. (101 pts.)

1250 a

833 I a

625 .

LI

LIII

500.

I IlIl . #{163}1111

UI

g333.

IlIl . LALIIIIII

::::::::::

250. 66111 LOIIIIIIII #{163}

LIllIllIll

>166LIIIII O..IIIIIIIg::::::::

125 II 661 #{163}6611111

Z IIIIIIIIII

100 #{163} aaaIIIII

#{163}IIIIII LLIIIIIIII

50 titlIllIll t’IIIIIII

IIIIIIIIII 1111111111 alIll

12

t:t&a111

#{163} 111111 #{163}6601111

IIIIIIIIII

1111 11111 I

1111111111 ________________ ________________

#{163}Skin - beta strep. Skin and nasopharyx - beta strep.

0 Nasopharynx-b’eta strep. Skin-no beta strep.

S Skin ond nasopharynx-no beta strep.

Fic. 3. Distribution of anti-streptolysin 0 titers among 303 patients with skin infections. The solid line

(7)

TABLE VI

SKIN LFsIoNs: FoLww-uP RESULTS IN 140 CHILDREN EFFECT OF THERAPY* AS RELATED TO BACTERIOLOGY

68 25

76

titer greater than normal, the smallest

num-ber (18) occurring in children under 2 years

of age and the remainder were spread fairly

evenly between the other age groups.

Strep-tococci were isolated from the skin lesions

in 19 of the 86 children with elevated titers.

A comparison of the percentage of

cliii-dren with increased titers and the geometric

mean titers between the impetigo group and

the control population are shown in Table

IV. In each age category both the

percent-age of patients with high titers and the

geometric mean titers are greater in the

impetigo patients than in the control

popu-lation.

Serial determinations of the ASO titers

were obtained in 230 patients who returned

for follow-up examination 7 and 21 days

after the initial visit. A change in titer of

two or more tube dilutions in sera tested

sequentially at the same time was

con-sidered indicative of a recent streptococcal

infection. A significant change in titer

oc-curred in 42 of the 230 patients. In 33 of

these 42 children, there was other evidence

of streptococcal infection based on either

a positive skin cuture or an initial elevated

ASO titer.

An elevated ASO titer was found in 19

of the 68 children with streptococci in the

skin lesion. Six additional patients with

positive cultures subsequently showed a rise

in ASO titer. Thus 25 of the 68 children

(37%) from whom streptococci was isolated

from the skin lesion had serologic evidence

of a streptococcal infection. Thirty-nine of

the 104 children (37%) with pure cultures

of staphylococci in the skin also had an

TABLE V

NUMBER OF PATIENTS WITh BAcFERIOLOGIC AND

SEII0-LOGIC EVIDENCE OF STREPTOCOCCAL INFECTION AMONG

303 CHILDREN WITH PYOGENIC SKIN INFECTION

Category Number of Patients

Total patients studied 1. Positive skin cultures

a) Plus serologic evidence 2. Serologic evidence, negative

skin culture

Total bacteriologic or serologic

evi-dence

Penicillin

Therapy

.

No Penzczllzn

.

Bacteria No.of No. Pts.

.

Lesions Cleared after

1 Week No.

Pt..

.

Lesions

Cleared

after

1 Week

S. aurens 83 45 27 38 15

S. pyogenes 42 18 16 24 12

Both organisms 15 8 4 7 4

SPatients in both treatment groups received 3% ammoniated

mercury ointment locally. Penicillin dosage: a single intramuscular

injection of 600,000 units procaine and 600.000 unit. benzathine penicillin.

elevated ASO titer, suggesting that they had had streptococcal as well as staphy-lococcal infections.

A summary of the bacteriologic and

serologic evidence of streptococcal

infec-tion is shown in Table V. As has been

noted previously, there were 68 patients

with positive cultures. Of the children with

negative cultures, 76 had either an elevated

ASO level or a significant change in titer. Therefore 144 of the 303 patients (48%) had either positive bacteriologic findings or

serologic evidence of a streptococcal

infec-tion associated temporally with pyogenic skin disease.

Treatment

The effect of therapy on the course of

impetigo was studied in 140 patients with

cultures of the skin lesion who returned for re-examination within one week after

treat-ment was instituted. Pure cultures of

staph-ylococci were recovered from 83, pure

cul-tures of streptococci from 42, and mixed

cul-tures of these two organisms from 15. The

effect of penicillin randomly allocated in

these three groups is presented in Table VI.

In the staphylococcal group 45 received

penicillin. The lesions were completely

303 healed and follow-up cultures were

nega-tive in 26 of the 45 children after one week.

In the remaining 19 who still had active

lesions, the skin cultures remained positive

in 5. Fifteen of 38 children, who had

(8)

had negative cultures after one week. In

3 of the 23 patients with persistent lesions

the cultures remained positive. Penicillin

sensitivity was determined in 46 of the 83

strains of staphylococci. While a number

of strains tested were resistant (21 of 46)

no correlation was found between

penicil-lin sensitivity and the response to

treat-ment.

Among the 42 patients with pure

cul-tures of streptococci, 18 received penicillin.

After one week, follow-up cultures in these

18 children were negative and in 16

heal-ing was complete. Of the 24 children who

received local treatment only, one

follow-up culture was positive and in 12 the

le-sions had cleared. In 15 patients with

mixed cultures, there was no significant

difference in the healing of the lesions in

children who received penicillin and in

those who did not.

Urinary Findings

The complications associated with im-petigo were limited to the kidney. None of

the children developed furuncles,

ab-scesses, cellulitis, or other pyogenic

infec-tions.

At the time of the first examination, 6 of the 303 children with impetigo had

evi-dence of acute glomerulonephritis. Four

had the classical clinical and urinary

find-ings of this disease. One had mild edema

and one had mild hypertension. Hematuria

and proteinuria were present in both mild

cases. Twenty-two additional patients had

microscopic hematuria: 8 at the first

exami-nation and 14 at a follow-up visit 7 to 21

days after the initial visit. The physical

examination and the blood urea nitrogen

were normal, and urine cultures were

nega-tive in the group of patients with

micro-scopic hematuria.

The duration and severity of the skin

in-fections did not differ in the patients with

acute glomerulonephritis or with

micro-scopic hematuria from that observed in

pa-tients without urinary complications. In 5

of 14 children with normal urinary findings

initially who subsequently developed

mi-croscopic hematuria, the impetigo was

treated with parenteral penicillin at least

one week before the red cells appeared. Bacteriologic or serologic evidence of a

streptococcal infection was present in 5 of

6 children with nephritis. Among the 22

patients with microscopic hematuria, 9 had

beta hemolytic streptococci in the skin. Serologic evidence (elevated ASO titers)

was obtained in 6 other children in whom

no streptococci were isolated from the skin

lesions. Bactericidal antibodies against

Type 12 streptococcus were determined in

15 of the 22 patients with microscopic

hematuria. Type-specific antibodies were

found in 7 of 15 patients. Type 12

anti-bodies were also determined in 15 children with impetigo who did not have hematuria.

Type-specific antibodies were present in 3

of these patients.

Percutaneous renal biopsies were per-formed in 2 patients with microscopic

hematuria. In one child the changes in the

glomeruli were slight and non-specific, and

were interpreted as probably within

nor-mal limits. In the second child there was a slight increase in the indigenous nuclei and

a prominence of the mesangium. These

changes were definite but minimal and

their significance is not known. None of

the 22 children with transient microscopic

hematuria showed any additional evidence of renal disease on follow-up examinations.

COMMENT

The patients with pyogenic skin

infec-tions reported in this series were unselected

sporadic cases seen in the children’s out-patient department of the Johns Hopkins Hospital and are probably representative

of a general pediatric clinic experience.

Among the 303 infants and children, beta

hemolytic streptococcus was isolated in 50 (16%) coagulase-positive S. aureus in 104

pa-tients (34%), and both organisms in 18 (6%).

Parker and Williams9 found varying

pro-portions of these organisms from year to

year, but in their over-all series,

(9)

staphy-lococcal four times more frequently than streptococci.

The variations in the frequency of the

organisms isolated are probably related

to differences in the populations studied.

The staphylococcus appears to be the more

common organism isolated from infected

skin lesions. However, in this study the

re-suits of the ASO determinations obtained

suggest that streptococcal infection may be

more frequently associated with pyogenic

skin disease in children than the

bacterio-logic findings indicate. One-third of the

pa-tients with pure cultures of staphylococci

had an elevated ASO titer. This finding

suggested that mixed infections may be

common, and that infection with

staphy-lococci might have been secondary in these

patients. The observation that streptococci

were isolated more frequently from lesions

cultured early than in those of longer

dura-tion was in accord with this possibility.

It is generally believed that in

strepto-coccal impetigo the source of the infecting

organism is the nasopharynx. Data

pre-sented in this study do not support this

concept. Streptococci were uncommon in

the nasopharynx of patients who had these

organisms in the skin lesions. It seems

pos-sible therefore that the skin may be the

portal of entry.

In contrast to findings in streptococcal

impetigo, nasal carriage of staphylococci

occurred in almost 50% of the patients with

staphylococcal impetigo. Furthermore,

phage-type 71 was present in both nose

and skin cultures in many instances. Similar

findings were reported by Barrow.6 This

in-vestigator found that in the nares of healthy

controls, while phage-type of staphylococci

other than 71 were common, phage-type 71

was rarely isolated. In impetigo therefore

Barrow suggested that staphylococci might

be transferred from the skin to the nose and

not vice versa.

The incidence of nephritis associated

with impetigo reported by different

ob-servers has varied greatly, from 7 to

68%.1,3, Most of the studies were

retro-spective and do not include adequate

bac-teriologic and serologic data. In the only

prospective study previously published,

Burnett10 found that among 42 children

with bacteriologic or serologic evidence of

streptococcal infection two patients had

nephritis, an incidence of 4.76%.

In this study among 144 children who had bacteriologic or serologic evidence of

streptococcal infection 5 cases of nephritis

occurred, an incidence of 3.4%. In 3 of these

patients, the findings were typical of

classi-cal acute glomerulonephritis. In the other

2 children the clinical manifestations were

so mild that they might have been

over-looked if urine examinations had not been

done routinely on every patient. One other child had typical nephritis in the absence of any evidence of streptococcal infection. In the total group of 303 patients 6

chil-dren had nephritis, an incidence of 1.9%.

In addition to the 6 patients with glom-erulonephritis, there were 22 children with

transient microscopic hematuria. The

sig-nfficance of this finding in these

asympto-matic patients is not clear. Fifteen of the

22 children had bacteriologic or serologic

evidence of a streptococcal infection. It is

well known that transient urinary

abnor-malities may occur following hemolytic

streptococcal infections and these findings

are considered to have little or no clinical

significance.1’ Siegal and coworkers12 have

reported that transient hematuria occurred

more commonly in children known to have

had infections with nephritogenic strains

of streptococci in previous years. In this

study, specific antibodies against a

nephrit-ogenic strain (Type 12) were found in 7

of 15 patients with microscopic hematuria

and indicates that a past infection with

Type 12 had occurred in a significant

num-ber. While only a small group of patients

were studied, Type 12 antibodies occurred

more frequently in the hematuria group

than in impetiginous children with normal

urinary findings, or among children in the

general pediatric population.8 Of the two

patients in whom kidney biopsies were

ob-tained, the findings were normal in one

(10)

STREPTOCOCCAL IMPETIGO

Long-term follow-up of the children with microscopic hematuria is planned, since

it is possible that such patients may be

among those who subsequently develop

chronic glomerulonephritis without a his-tory of an acute episode.

It is now well established that nephritis

usually follows upper respiratory infections

due to Group A streptococci, Types 12, 4,

25, and 49. With the exception of Type 49,

most of these studies were done in adults

in whom skin infections are uncommon. In an outbreak of 63 cases of acute glom-erulonephritis in an Indian reservation

de-scribed by Kleinman,13 two-third of the

children had skin infections. Skin cultures were positive for Group A streptococci in

7 of 12 patients studied and these

organ-isms were subsequently shown to be Type

4914,15

No systematic studies of the occurrence

of the nephrotoxic types found in impetigi-nous lesions have been published, probably

because these strains are usually not

typ-able by the precipitin reaction. In Europe,

streptococci are comonly typed by the slide

agglutination method. With this technique, Parker and co-workers#{176} and Banow in England showed that streptococci isolated ifom impetiginous lesions fell in one of

three distinctive agglutination patterns,

3/13/B3264, 5/11/12/27/44, and 8/25/Imp.

19. The English workers noted that these agglutination patterns were rarely en-countered among streptococci isolated from the nasopharynx. These investigators were the first to suggest that streptococcal im-petigo might be due to special types char-acterized by a few characteristic agglutin-ating patterns. Recently Parkerl6 has found that a number of strains isolated from

im-petigo react with Type 14 antisera and may

form still another distinct group. This group

is of special interest because it has been

found to be associated with nephritis in the

U.S.A. and in Europe.

In this study of 68 strains of streptococci,

the types of only 4 could be identified by

the precipitin reaction. The types identified were other than the known nephritogenic

ty pes. Twenty-one strains were typed by

the slide agglutination technique. Four of the 21 strains were identified as 5/27/44,

4 as 3/13/33/9, 5 as 8/25/Imp 19, and 7

as Type 14. In 2 patients with

microhema-tuna, streptococci of type 5/27/44 were

isolated. Although 7 of the strains were

identified as Type 14, none of these patients had renal complications. The relationship of these special strains of streptococci

iso-lated from skin lesions to renal

complica-tions requires further study.

Studies on staphylococci isolated from the skin lesions of impetigo patients indicate that these infections may also be due to special types of these organisms. Among

100 strains of S. aureus isolated from

im-petigo, Barrow6 found that 63 were

phage-type 71. Similar findings were reported by

Spittlehousel7 and Parker and co-workers.

Barrow’s findings that staphylococcus Type

71 is rarely found in other pyogenic

staphy-lococcal infections such as boils, abscesses, or osteomyelitis is further evidence that

impetigo strains may represent a special

group limited to superficial skin infections.

Furthermore, in contrast to most strains of

staphylococci, with the exception of those

encountered in hospital infections, staphy-lococcus phage-type 71 are usually

peni-cilhin resistant. Our findings support the

view of Barrow#{176}and Parker et al. that

staphylococcal impetigo is caused mainly by one phage-type.

The effect of one injection of penicillin (600,000 units procaine penicillin and

600,000 units benzathine penicillin) on the

course of impetigo varied with the

bacterio-logic findings. While the group of children

with pure cultures of streptococci who

re-ceived penicillin appeared to improve more

rapidly than those who received only local treatment, the number of children in each

treatment group was too small to warrant

conclusions. No difference was noted in patients who had mixed cultures of strep-tococci and staphylococci, or in those with staphylococci only in their skin lesions.

Penicillin sensitive as well as penicillin

(11)

from these patients. The failure to respond

to therapy therefore did not appear to be

due solely to the prevalence of

penicillin-resistant staphylococci.

It has been suggested by Stetson” and

co-workers that early penicillin treatment of

streptococcal infections reduced the

mci-dence of acute glomerulonephritis.

Four-teen who had no abnormal urinary findings

when first seen subsequently developed

transient microscopic hematuria. Five of

these 14 children had received penicillin

one week prior to the occurrence of

ab-normal urinary findings. Since none of these

patients had proven glomerulonephritis, and

the significance of transient hematuria is

not known, no data on the value of penicillin

therapy in streptococcal impetigo for the

prevention of renal complications were

obtained.

Classical glomerulonephritis and acute

rheumatic fever both follow in the wake

of scarlet fever or streptococcal pharyngitis.

Nephritis, however, is also associated with

streptococcal impetigo, whereas rheumatic

fever rarely if ever follows streptococcal

skin infections. Streptococci isolated from

epidemics followed by a high incidence of

rheumatic fever are usually rich in the

type-specific M antigen and are readily

typable. Rheumatic fever is most likely to

occur in individuals in whom the magnitude

of the antibody rise is greatest.18 On the

other hand, streptococci isolated from

im-petigo are often deficient in type-specific M

antigen and evoke only a mild immune

response. Also, unlike rheumatic fever, the

incidence of glomerulonephritis is not

re-lated to the degree of increase in ASO

titer.19 It is possible that rheumatic fever

does not follow streptococcal skin infections

because these organisms cause only

super-ficial infections and evoke very little

im-mune response. It is also possible that

post-impetigo renal complications may be related

to special strains of streptococci.

SUMMARY

1. Cultures of the skin, nares, and

phar-ynx were examined in 303 children with

impetigo. One hundred and seventy-two

skin cultures were positive: 50 for beta

hemolytic streptococci, 104 for

coagulase-positive staphylococci, and 18 for both

organisms. Beta hemolytic streptococci were

present in nasopharyngeal cultures of 26

children, 18 of whom also had these

or-ganisms in the skin. Staphylococci were

found in 114 cultures of the nares and in

58 children these bacteria were also present

in the skin culture.

2. Of the 68 strains of beta hemolytic

streptococci cultured from the skin, 53 were

group A, one was group C, and 14 could

not be grouped.

3. Only 4 of the group A strains were

typable by the precipitin reaction. None of

the strains were known nephrotoxic types.

Twenty-one strains were typed by slide

agglutination: 20 showed agglutination

patterns considered to be characteristic of

impetigo strains.

4. Twenty-five of 68 children with

strep-tococci in the skin lesion had an elevated

ASO titer. In 76 children with negative

skin cultures, there was serologic evidence

of streptococcal infection. On the basis of

combined bacteriologic and serologic

find-ings, 144 children (48%) with impetigo had

evidence of streptococcal infection.

5. Ninety-nine of the 122 strains of

staph-ylococci isolated from the skin and 86 of

114 strains cultured from the nose were

phage-typed. Phage-type 71 was the most

common typable strain from both sources.

6. At the first visit, 6 children had acute

glomerulonephritis and 8 had microscopic

hematuria. An additional 14 patients showed

transient hematuria on follow-up

examina-tion. Five of the 6 patients with

glomerulo-nephritis and 15 of 22 with transient

mic-rohematuria had evidence of a streptococcal

infection. Kidney biopsies were performed

in 2 patients with microscopic hematuria:

one was normal and the other showed

minimal changes of questionable

signifi-cance.

7. The group of children with pure

cul-tures of streptococci who received penicillin

(12)

STREPTOCOCCAL IMPETIGO

those who received only local treatment.

On the other hand, in patients with mixed

cultures of streptococci and staphylococci

as well as those with pure cultures of

staphylococci, there was no difference in

response in those given penicillin as

corn-pared with those treated with ammoniated

mercury.

8. In 5 children, microhematuria was not

prevented by the administration of

penicil-un 7 to 10 days before the appearance of

the abnormal urinary findings.

9. The strains of group A streptococci

isolated from skin lesions showed several

distinctive patterns by the slide

agglutina-tion technique similar to those observed

by other workers. Also in accord with

English investigators, one phage-type of

staphylococcal predominated in the strains

isolated from the skin lesions.

10. Abnormal urinary findings are

corn-mon in children with impetigo, but are

usually not associated with infection with

the known nephrotoxic types of group A

streptococci.

REFERENCES

1. Addis, T.: Glomerular nephritis. Diagnosis

and Treatment. New York: Macmillan, 1948. 2. Futcher, P. H.: Role of skin infections in the

etiology of acute glomerulonephritis. Arch. Intern Med., 65:1192, 1940.

3. McCullough, C. C., Coffee, J. Y., Trice, P. A.,

Stone, J. J., and Crandall, H. L.: Acute glomerulonephritis: Impetigo as an

etiolog-ical factor. J. Pediat., 38:346, 1951.

4. Blumberg, R. \V., and Feldman, D. B.: Ob-servations on acute glomerulonephritis

as-sociated with impetigo. J. Pediat., 60:677, 1962.

5. Parker, M. T., Tomlinson, A. J., and Williams,

R. E.: Impetigo contagiosa: The association

of certain types of S. Aureus and of Strep-tococcus pyogenes with superficial skin in-fection. J. Hyg. (Lond.), 53:458, 1955.

6. Barrow, G. I.: Clinical and bacteriologic

as-pects of impetigo contagiosa. J. Hyg. (Lond.),

53:495, 1955.

7. Blair, J. E., and Carr, M.: The techniques

and interpretation of phage typing of

staphy-lococci. J. Lab. Clin. Med., 55:650, 1960.

8. Markowitz, M. : Studies on type-specific strep-tococcal antibodies as indicators of previous streptococcal infections in rheumatic and

nonrheumatic children. J. Clin. Invest., 42:

409, 1963.

9. Parker, M. T. and Williams, R. E. : Further

observations on the bacteriology of impetigo

and permphigus neonatorum. Acta Paediat.,

50:101, 1961.

10. Burnett, J. W. : Management of pyogenic cut-aneous infections. New Engi. J. Med., 266: 164, 1962.

11. Stetson, C. A., Rammelkamp, C. H., Jr., Krause, R. M., Kohen, R. J., and Perry, W. D. : Epidemic acute nephritis: Studies on etiology, natural history and prevention.

Medicine, 34:431, 1955.

12. Siegel, A. C., Rammelkamp, C. H., Jr., and

Griffeath, H. I.: Epidemic nephritis in a

school population; The relation of hematuria

to group A streptococci. PEDIATRICS, 15:33,

1955.

13. Kleinman, H. : Epidemic acute

glomerulone-phritis at Red Lake. Minnesota Med., 37: 479, 1954.

14. Reinstein, C. R. : Epidemic nephritis at Red Lake, Minnesota. J. Pediat., 47:25, 1955.

15. Updyke, E. L., Moore, M. S., and Conroy, E.:

Provisional new type of Group A

strepto-cocci associated with nephritis. Science, 121:

171, 1955.

16. Parker, M. T. : Personal communication. 17. Spittlehouse, K. E. : Phage-types of

staphy-lococcus pyogenes isolated from impetigo

and sycosis barbae. Lancet, 11:378, 1955.

18. Taranta, A., Wood, H. F., Feinstein, A. R., Simpson, R., and Kleinberg, E.: Rheumatic

fever in children and adolescents. Ann.

In-tern Med., Supp. 5, No. 2, Part II, 60:47, 1964.

19. Earle, D. P., and Seegal, D.: Natural history

of glomerulonephritis. J. Chron. Dis., 5:3,

1957.

Acknowledgmen’c

This study was undertaken at the suggestion of

Dr. Robert E. Cooke, Professor of Pediatrics, The

Johns Hopkins School of Medicine, and we are

indebted to him for his interest and support. The

authors gratefully acknowledge the excellent tech-nical assistance of Myra Roseman, Goldie Pelovitz, and Patricia Perlman. We thank Mary Hammond

for clerical help and invaluable aid in the

(13)

1965;35;393

Pediatrics

Milton Markowitz, H. David Bruton, Ann G. Kuttner and Leighton E. Cluff

AND RENAL COMPLICATIONS IN CHILDREN WITH IMPETIGO

THE BACTERIOLOGIC FINDINGS, STREPTOCOCCAL IMMUNE RESPONSE,

Services

Updated Information &

http://pediatrics.aappublications.org/content/35/3/393

including high resolution figures, can be found at:

Permissions & Licensing

http://www.aappublications.org/site/misc/Permissions.xhtml

entirety can be found online at:

Information about reproducing this article in parts (figures, tables) or in its

Reprints

http://www.aappublications.org/site/misc/reprints.xhtml

(14)

1965;35;393

Pediatrics

Milton Markowitz, H. David Bruton, Ann G. Kuttner and Leighton E. Cluff

AND RENAL COMPLICATIONS IN CHILDREN WITH IMPETIGO

THE BACTERIOLOGIC FINDINGS, STREPTOCOCCAL IMMUNE RESPONSE,

http://pediatrics.aappublications.org/content/35/3/393

the World Wide Web at:

The online version of this article, along with updated information and services, is located on

American Academy of Pediatrics. All rights reserved. Print ISSN: 1073-0397.

References

Related documents

This indicates that firms which increased capital expenditures during the availability of 50% bonus depreciation experienced positive cumulative abnormal returns in general

So, a study is required to implement closed-loop speed control of a 3- phase, brushless, permanent magnet in-wheel motor for a hybrid electric vehicle using

aureus causes the lesions of bullous impetigo and staphylococcal scalded skin

The perspective-n-point problem is discussed with details in this chapter because it is the most fundamental algorithm in map-based visual odometry (and this why the topic was

During authentication (recognition), the features of new test iris image is compared with the features of iris stored in database during enrollment.. Fig 2: Block Diagram of

Dumont CP , Himmelman JH, Russell MP ( 2004 ) Size-specific movement of green sea urchins Strongylocentrotus droebachiensis on urchin barrens in eastern Canada.. In:

Arpita Chatterjee(2013) The Therapeutic Value of Indian Classical, Folk and Innovative Dance Forms, rupkatha Journal on Interdisciplinary Studies in Humanities,