Probable Toxic Shock Syndrome Without Shock and Multisystem Involvement

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PEDIATRICS Vol. 70 No. 2 August 1982 279

Probable

Toxic

Shock

Syndrome

Without

Shock

and

Multisystem

Involvement

Col James W. Bass, MC, USA, Lt Col Lewis B. Harden, MC, USA,

and Capt John H. Peixotto, MC, USA

From the Section on Pediatric Infectious Diseases, Department of Pediatrics, Walter Reed Army Medical Center, Washington, DC, and Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland

ABSTRACT. Three menstruating adolescents using tam-pons colonized with Staphylococcus aureus developed high fever, vomiting, diarrhea, and abdominal pain

fol-lowed by conjunctival injection and a sunburn-like rash. Two girls had transient orthostatic hypotension but none

developed shock or evidence of multiple organ injury.

They are reported as having probable toxic shock

syn-drome without shock or multiple organ system

involve-ment. Pediatrics 70:279-281, 1982; toxic shock syndrome,

Staphylococcus aureus.

required to establish the diagnosis and they could

be considered a forme fruste. Treatment may have

modified their illness, or some cases of TSS may be relatively mild and self-limited. We report these

cases as probable TSS without shock or multiple

organ system involvement.

CASE REPORTS

Case 1

The criteria for diagnosis of toxic shock syndrome

(TSS), as defined by the Centers for Disease

Con-trol (CDC) are: (1) fever (temperature 38.9 C [102 F]), rash (diffuse macular erythroderma), (3)

des-quamation, one to two weeks after the onset of

illness, particularly of palms and soles, (4) hypoten-sion or orthostatic syncope, (5) involvement of three or more organ systems (gastrointestinal, muscular,

mucous membrane, renal, hepatic, hematologic, and

central nervous system) and (6) if obtained, nega-tive cultures of the blood, throat, and cerebrospinal

fluid as well as serologic tests for Rocky Mountain

spotted fever, leptospirosis, or measles.’ We

re-centiy treated three young female adolescents

whose illness fulfilled most of these criteria and was recognized as probable TSS. The patients recovered

rapidly after prompt treatment with intravenous fluids and antibiotics. Although they apparently

had TSS, there illness did not meet all ofthe criteria

Received for publication June 29, 1981; accepted Aug 19, 1981.

The views expressed herein are those of the authors and do not necessarily reflect the views of the US Army or the Department

of Defense.

Reprint requests to (J.W.B.) Tripier Army Medical Center,

Tripter AMC, HA 96859.

American Academy of Pediatrics.

A 17-year-old white girl was hospitalized with a

three-day history of high fever, nausea, vomiting, lower

abdom-mat

pain, headache, and dizziness. She had developed a

sunburn-like rash several hours previously. Her

men-strual period had started seven days earlier and she was

using tampons (Playtex and OB).

Examination revealed the following: an oral tempera-ture of 40.4 C; pulse rate of 120 beats per minute;

respi-rations, 38/mm; and blood pressure, 1 15/64 mm Hg in a

supine position and 85/45 sitting erect. Her condition was

moderately toxic and her conjunctiva were injected. A bright pink, erythematous rash was present over her

abdomen, knees, thighs, and arms. The abdomen was

diffusely tender, and a pelvic examination revealed a

profuse, purulent, bloody discharge and a mildly tender

cervix. The rest of the examination was within normal

limits.

Laboratory data were as follows: hematocrit, 37.7%; WBC count, 8.5/cu mm with 61% segmented neutrophils, 26% band cells, 11% lymphocytes, and 2% monocytes. The sedimentation rate was 21 mm/hr. The urine specific

gravity was 1.029, and there were 10 to 20 WBCs and 2 to 4 RBCs per high power field (HPF). The urine culture

was negative. The cervical Gram stain revealed numerous polymorphonuclear leukocytes and many Gram-positive

cocci in clusters. Both the cervical and vaginal cultures produced a heavy growth of penicillin-resistant Staphy-lococcus aureus. The throat culture grew S aureus but

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280 TOXIC SHOCK SYNDROME phosphokinase (CPK) yielded normal values.

Treatment was initiated with nafcillin administered

intravenously, 200 mg/kg/day, in 20-minute infusions at six-hour intervals and gentamicin, 5 mg/kg/day

admin-istered intramuscularly in three divided doses at eight-hour intervals. During the first 12 hours the patient

received 3 liters of Ringer’s lactate. Orthostatic hypoten-sion without syncope persisted throughout this period. The patient’s condition began to improve and she was

afebrile after 24 hours; she was discharged after seven days of intravenously administered nafdillin.

Desquama-tion over the hands and feet was observed one week later.

Case 2

A 16-year-old white girl was hospitalized with a

one-day history of headache, myalgia, abdominal pain, and

fever to 40.5 C. Several hours prior to admission she developed a bright red, sunburn-like rash over her legs

and arms. She was in the sixth day of her menstrual

period and was using tampons (Playtex).

Examination revealed the following: oral temperature, 39.8 C; pulse rate, 120 beats per minute; respirations, 28/

mm; and blood pressure, 100/52 mm Hg with no

ortho-static changes. She was in a moderately toxic condition and had injected conjunctiva and a diffuse erythroderma around the elbows and on the lower extremities. Pelvic examination was normal except for hyperemic mucosa.

Laboratory data were as follows: hematocnt, 34.7%; WBC, 24.3/cu mm including 76% segmented neutrophils, 8% band cells, 12% lymphocytes, and 4% monocytes. Urine specific gravity was 1.015, and there were eight to ten WBCs/HPF. No RBCs were noted, but bacteria were

seen in the urine sediment. The urine culture grew more

than three organisms, none of which was predominant.

Endocervical and vaginal cultures grew

penicfflin-sensi-tive S aureus and group B fl-hemolytic streptococci. The throat culture was negative for group A $-hemolytic

streptococci. Measurement of serum electrolytes, BUN, creatinine, glucose, biirubin, SGOT, SGPT, LDH, and

CPK yielded normal values.

Initially the patient was presumed to have urinary tract infection, and treatment was initiated with intrave-nous fluids and ampicillin. Intravenous infusions of 500

mg were given over a 20-minute period every six hours.

She remained normotensive with no orthostatic changes

in blood pressure. The patient became afebrile overnight and all other symptoms abated. The erythroderma faded

after 24 hours, and the patient was discharged after three days and was told to complete a two-week course of oral

ampicillin. On follow-up examinations she failed to show

any evidence of desquamation.

Case 3

A 16-year-old girl was hospitalized with a four-day

history of arthralgia, myalgia, malaise, and fever to 39 C.

On the day of admission she began vomiting and

experi-encing chills. She was in the sixth day of her menstrual

period and had been using tampons (Tampax).

Her past medical history was significant for two similar episodes that were managed elsewhere. The first had occurred seven months previously and consisted of

vom-iting, diffuse abdominal pain, fever, conjunctivitis, and a sunburn-like rash which desquamated over the fingers and toes after being treated with a course of oral penicil-lin. The original diagnosis of scarlet fever was changed to mild toxic shock syndrome when vaginal cultures

pro-duced a heavy growth of S aureus and no group A

f-hemolytic streptococci were recovered from the vagina or

from the throat culture. A second episode occurred one month later, again with fever, vomiting, and a rash which did not desquamate. Both of these previous episodes occurred late in her menstrual period and were associated

with tampon use.

Examination revealed the following: an oral

tempera-ture of39.2 C, a pulse of 130 beats per minute, respirations

of 20/min, and blood pressure of 98/42 mm Hg with the patient supine without orthostatic change. Her condition was moderately touc and she had bilateral conjunctival

injection. There was mild edema and minimal erythro-derma of the skin over the fingers and toes. There was

diffuse abdominal tenderness, and pelvic examination

revealed a clear vaginal discharge. The rest of the exam-ination was normal.

The following laboratory values were obtained:

hema-tocnt, 36.5%; WBC, 4.7/cm mm with 35% segmented

neutrophils, 45% band cells, 18% lymphocytes, 2%

mono-cytes. The urine specific gravity was 1.021, and there were

WBCs too numerous to count. Bacteria were noted in the

urine sediment. A catheterized specimen had eight to ten

WBCs and four to six RBCs per HPF. Three voided urine specimens were cultured and had no growth. Gram stain of the endocervical and vaginal discharge showed

numer-ous Gram-negative rods and Gram-positive cocci, and

culture produced a heavy growth of S aureus sensitive to

penicillin. A throat culture was negative for group A

1G-hemolytic streptococci. The serum SGOT was 412 IU,

the SGPT 190 IU, and the I.DH was 482 IU.

Measure-ment of serum electrolytes, BUN, creatimne, glucose,

biirubin, and CPK yielded normal values.

Because the patient was without a distinct skin rash and was normotensive, antibiotics were not given. Within six hours after admission a diffuse erythroderma devel-oped over the lower extremities, abdomen, and hands, and a significant orthostatic drop in blood pressure with syncope occurred. Intravenous fluids were administered along with nafcillin, 150 mg/kg/day intravenously at six-hour intervals in 20-minute infusions. During the first 24

hours the patient received 2.4 liters of 0.3% saline in 5% dextrose and water. After 12 hours she became afebrile

and free of other symptoms. The erythroderma faded after 24 hours. Intravenous nafdilhin therapy was

contin-ued for three days; the patient was discharged on a

regimen of oral cioxacillin for a ten-day course of therapy. One week later she experienced desquamation of the skin over the hands and feet.

COMMENT

These three patients did not meet the essential criteria for the diagnosis of TSS and therefore were not reported to the Centers for Disease Control. All

were young, menstruating adolescents using

tam-pons that were colonized with S aureus. After a

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ARTICLES 281 characteristic two- to three-day period ofhigh fever,

headache, vomiting, diarrhea, and abdominal pain,

they developed marked conjunctival injection and

a sunburn-like rash, but in only two patients was

there subsequent desquamation. None had shock

or orthostatic syncope. One patient did have an

orthostatic drop in blood pressure on admission and

another developed this shortly after admission, but

neither had syncope. None of the three patients

met the criteria requiring involvement of three or

more organ systems. Although all three girls did

have severe gastrointestinal symptoms and two had

muscular involvement as indicated by the symptom of myalgia, with the exception of transient elevation

of the SGOT, SGPT, and LDH levels in the third

patient there was no evidence of renal, hepatic,

hematologic, or CNS involvement. We doubt that

the multiorgan system involvement in TSS is

ac-tually a primary effect of the disease and suspect that it is the consequence of inadequate organ

pro-fusion brought about by shock. In a recently

re-ported series of patients with TSS,2 it was noted

that patients without overt shock but with ortho-static hypotension and syncope tended to have less

involvement of muscular, renal, hepatic, hemato-logic, and CNS organ systems.

Culture and serologic tests to rule out Rocky

Mountain spotted fever, leptospirosis, and measles

were not performed in our patients; however, we

feel that the clinical illness in these patients is more

consistent with a diagnosis of mild toxic shock

syndrome without shock and multiple organ system

involvement.

An informal survey of other physicians suggests that patients similar to these are being seen but not

reported. We feel that TSS has a much wider

din-ical spectrum than adherence to CDC criteria would

dictate. Those patients reported to date may

rep-resent the “tip of the iceberg” and TSS may be a

far more common and varied disease entity than is

presently appreciated by clinicians. It is probable that formes frustes occur with spontaneous resolu-tion. These episodes may ultimately be diagnosed only by detection of TSS-associated toxin with

spe-cific antibody response as recently reported by

Bergdoll and associates (enterotoxin F)3 or

Schliev-ert and co-workers (pyrogenic exotoxin C).4

We propose that the criteria for the diagnosis of

TSS be modified to include a subset with clinical features similar to those of the patients presented in this paper. This would result in the

documenta-tion of mild episodes and might lead to a better

understanding of the disease.

REFERENCES

1. Center for Disease Control: Follow-up toxic shock

syn-drome-United States. Morbidity Mortality Weekly Rep 29:297, 1980

2. Tofte RW, Williams DN: Toxic shock syndrome: Clinical and laboratory features in 15 patients. Ann Intern Med 94:149, 1981

3. Bergdoll MS, Reiser RF, Crass BA, et al: A new

staphyto-coccal enterotoxin, enterotoxin F, associated with

toxic-shock syndrome Staphylococcus aureus isolates. Lancet

1:1017, 1981

4. Schlievert PM, Shands KN, Dan BB, et al: Identification and characterization of an exotoxin from Staphylococcus

aureus associated with toxic shock syndrome. J Infect Dis

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1982;70;279

Pediatrics

James W. Bass, Lewis B. Harden and John H. Peixotto