Lymphadenitis as the Dominant Manifestation of Kawasaki Disease Julie Kim Stamos, Kathleen Corydon, James Donaldson and Stanford

T. Shulman Pediatrics 1994;93;525

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PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly publication, it has been published continuously since 1948. PEDIATRICS is owned, published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois, 60007. Copyright 1994 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.

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6. Balatskii mothorax

AV, Rusinovich lul, Reshetnikova luK. in a child with multiple cartilaginous

Case of traumatic heexostoses. Pediatriia.

CASE

REPORTS

197352:82-84 DJ, Glicklich five study. Pediatrics. 8. Fleischer GR, Fichman usual cause of chest 9. Wang AA, Patterson

7. Driscoll

LB, Galen WJ. Chest pain in children: a prospec1976;57:648-651 KR, Honig PJ. Hemothorax in a child. An unpain. Clin Pediatr (Phila). 1978;17:300-302 HS, Hemstreet MP, et al. Hemothorax in a patient

We retrospectively reviewed the medical charts of I I KD patients for whom medical attention was sought specifically because of marked cervical lymphadenopathy (Table 1). Patients were identified from review of divisional records from January 1983 to December 1992, encompassing approximately 450 patients with

KD diagnosed

during

that

period.

Patients

ranged

from

2 to 9

with asthma. Ann Allergy. 1990;64:55-57 10. Banadio WA, Hailmich T. Post-traumatic pulmonary contusion in children. Ann Sung. 1989;18:1050-1052 11. Bender TM, Oh KS, Medina JL, et al. Pediatric chest trauma. J Thorac Imaging. 1987;2:60-67 12. Laurin 5, Aronson S, Schuller H, et al. Spontaneous hemothorax from bronchopulmonary sequestration. Unusual angiographic and pathologic-anatomic findings. Pediatr Radiol. 1980;10:54-56 13. Johnson DE, Miller LC, Iverson S, et al. The health of children adopted from Romania. JAMA. 1992;268:3446-3451 14. Kendig EL Jr. Early diagnosis of tuberculosis in childhood. AJDC. 1956;
92:558-561 15. Leung AN, Muller NL, Pineda PR, et al. Primary tuberculosis in 1992;

childhood: radiographic 16. Starke JR. Childhood 13:343-353

17. 18. Solomon L. Hereditary RC, Unni

manifestations. Radiology. 1992;182:87-91 tuberculosis during the 1990s. Pediatr Rev.

multiple KK, McLeod exostoses. RA,

Bone

Joint

Surg.

1963;45:
arising in

292-304
Garrison et al. Chondrosarcoma

Cancer. 1982;49:1890-1897 19. Sponseller PD, Tolo VT. Bone, joint and muscle problems. In: Oski FA, DeAngelis CD, Feigin RD. et al, eds. Principles and Practice of Pediatrics, 1990. Philadelphia: J.B. Lippincott Company; 1990 20. Madigan R, Worrall T, McClain EJ. Cervical cord compression in hereditary multiple exostoses. Review of the literature and report of a case. J Bone Joint Surg. 1974;56:401-404 21 . Holvelius L. Aneurysm of popliteal artery causes by a cartilaginous exostosis. Orthop Scand. 1975;46:836-838 22. Hanrahan PS, Edelman J, Brash S. Spontaneous hemarthrosis associated with an exostosis of the talus. J Rheumatol. 1987;14:171
osteochondroma.

years (median = 5 years), and eight were boys. Chief complaints at initial examination were fever and neck mass or torticollis. The initial diagnosis in 10 of I I patients was bacterial cervical lymphadenitis. Cervical masses ranged in size from 3 X 2 cm to 5 X 7 cm on examination and were usually described as erythematous, tender to palpation, but nonfluctuant. On admission, one patient had only fever and lymphadenopathy; the remainder initially manifested two or more other major KD diagnostic criteria. Eight of 11 patients eventually developed at least four major KD criteria. The other three patients fulfilled three major KD criteria, and all three developed coronary abnormalities. Computed tomography of the neck was performed in 5 of 11 patients because of concern about the magnitude of cervical swelling (Table 2). Findings included enlarged cervical and parapharyngeal lymph nodes, increased retropharyngeal space, and impingement by nodes on the oropharynx and major cervical blood vessels (Figs I and 2). One patient had a low-density region within the cervical mass suggesting necrosis or abscess formation. Five of 11 patients underwent needle aspiration of the lymph node or retropharyngeal space because of a suspected suppurative process. In each case, fluid was unobtainable or the scant amount obtained was negative on routine bacterial culture. In two patients, aspiration procedures were performed under general anesthesia. Parenteral antibiotics were given to nine patients for presumed bacterial lymphadenitis, without benefit. The diagnosis of KD was delayed in most cases, being established at a median of 9 days (maximum = 15 days) after the onset of fever. Intravenous

gammaglobulin

and

aspirin

were

administered

to nine

patients
signs and swelling.

who responded with symptoms, including

rapid resolution of fever and other dramatic subsidence of cervical

Lymphadenitis Manifestation

as the Dominant of Kawasaki Disease

Kawasaki disease (KD) is an acute febrile illness primarily affecting infants and young children. Its importance relates to the fact that 20% to 25% of untreated patients develop coronary abnormalities that can lead to myocardial infarction or even to death.1 KD is a leading cause of acquired heart disease in children in many regions, including the United States.2 Because there are no specific diagnostic tests for KD, the diagnosis is established by the presence of fever and four of five criteria without other explanation for the illness: (1) nonexudative conjunctival injection; (2) oral mucosal changes; (3) changes of the peripheral extremities; (4) rash, primarily truncal; and (5) cervical lymphadenopathy. Cervical adenopathy is the least constant diagnostic criterion, present in approximately 50% of patients, whereas each of the other four criteria is found in almost 90% of patients with classic KD.3 We describe 1 1 children with KD brought to medical attention primarily or solely because of fever and striking cervical lymphadenopathy.
Fig
Received for publication Jun 28, 1993; accepted Oct 17, 1993. PEDIATRICS (ISSN 0031 4005). Copyright 1994 by the American emy of Pediatrics.

.,

1. Patient

3, illness

day 10. Computed

tomography

scan dem-

Acad-

onstrates on the muscle carotid

numerous matted hypopharynx (H), (5), and compressing arteries (CA).

left cervical nodes (arrows) impinging displacing the sternocleidomastoid the internal jugular vein (IJ) and

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525

TABLE Patient

1.

Clinical

F eatures

of Kawasaki

Disease

(KD)

Patients

Who

Have

Severe

Cervical Other

Lymphadenopathy KD Criteria
(D.n))

Age,

yr

Sex

Initial

Complaint
(Date

Diagnosis,
Day of Illness 4

of Development

Fever Painful, Fever Torticollis, Fever Warm,

Rash

(D.2)

red, 6 x 4 cm neck

mass

Conjunctival injection (D.4) Peripheral erythema and edema

Conjunctival injection (D.3)

(D.4)
5

large

neck

mass

Peripheral erythema Red lips (D.3); Rash

Rash (D.10) Conjunctival injection Peripheral erythema Red lips (D.10) Conjunctival Peripheral Rash (0.2) Rash (D.3) Peripheral Conjunctival injection erythema

and pain (D.5)

(D.10) (D.10) (D.2) (0.2)

(D.3)
10

red

6 x 3 cm

neck

mass

Fever Tender,

red

7 x 4 neck

mass

Fever Neck pain and swelling Difficulty swallowing Fever Torticollis

9 edema (0.8) injection (D.8) 15

Red lips (0.8)

Peripheral edema (D.6) Peeling rash (D.15)

7 x 5 cm tender 7 5 M
Fever

neck

mass
Rash (D.2) 13

Torticoffis
Large, 8 9 6 2 M M Fever Neck Fever
Torticoffis

Conjunctival neck mass

Oral Rash Rash mucosal (0.6) (0.8)

injection
changes

(D.6)
(0.6) 11 10

painful mass

Oral mucosal
mass tender neck mass Conjunctival Rash (0.5) Conjunctival

changes
injection injection

(D.9)
(0.9) 5 (0.4) 6

Neck 10 5 M

Fever 3 x 2 cm Fever Tender,

Peripheral
11 3 M 4 x 4 cm neck mass Rash (0.5) Conjunctival Peripheral

edema

(D.5)

injection (0.4) edema (0.4)

Two

patients

developed

giant

coronary

aneurysms

as sequelae

of

KD; patient 8 had been treated with IVGG on illness day 11, and KD was diagnosed in patient 7 in 1983, before the use of IVGG. Two other patients developed transient mild coronary dilatations; patient 6, in whom KD was diagnosed on illness day 15, was treated with aspirin alone, and patient 9 was given IVGG and aspirin on illness day 10.

DISCUSSION

Although cervical adenopathy (at least 1 .5 cm diameter) is a major criterion for KD, it is the least common and is present in only about 50% of cases. Adenopathy is typically unilateral but may be bilateral. The nodes are usually firm and somewhat tender. They may be erythematous but are nonfluctuant. Pathologic lymph node findings in KD are fairly nonspecific and include focal areas of necrosis with microthrombi in adjacent small vessels,4 hyperplasia of T-zones, and macrophage infiltration of B-zones.5 Our patients were unusual in that they all had very marked lymphadenopathy, usually in association with erythema and tenderness, and because fever and lymphadenopathy were present several days before other manifestations of KD were noted. Eight of 11 patients eventually developed at least four major KD criteria. Although the remaining three fulfilled only three criteria, each developed typical echocardiographic evidence of coronary changes. Therefore, the diagnosis of KD is reasonably certain in all these patients. Cloney et a16 reported an autopsy-diagnosed case of KD similar to our patients. Because therapy in our patients was directed toward bacterial lymphad-

Fig 2. Patient 6, illness day 15. Computed tomography scan demonstrates very enlarged right cervical and parapharyngeal nodes (arrows) somewhat displacing the lateral wall of the hypopharynx and compressing the internal jugular vein (IJ). The retropharyngeal space (RP) is widened.

526

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TABLE Patient

2.

Course Antibiotic (No.

of

Kawasaki

Disease

(KD) Computed

Patients

Who

Have

Severe Procedures

Cervical

Lymphadenopathy KD Therapy (Illness Day)

Therapy

Sequelae

of Days)
(7)

Tomography
Findings

I 2 3

Cefadyl

NIY ND

ND ND
cervical

WGG P/CC IVGG

(4) and

ABA ABA ABA

None

None
NafCillin dime, mycin

(5) and (10) and

None None

and

ceftazi-

Enlarged
paratracheal nodes

and
lymph

ND

then dinda(total 12)

4 5

Cefuroxinie Cefador,
taxime, penem Nafcillin, mycin then

(1)
cefo-

ND
ND

ND
General

IVGG
anesthesia; aspiration; negative IVGG

(2) and
(9) and

ABA ABA

None None

then then
(total

imidlinda13)
cefaIncreased retropharyngeal space with marked adenopathy ND

needle
culture

(total 8)

Needle ture Needle

tare

aspiration; negative aspiration;

negative

cul-

ABA

(15)

Dilation artery Giant

rysms

(R) coronary

Cefador,
mandole,

then

cul-

ABA

(13)

then

cm-

coronary (LAD

aneuand

damycin and gentamicin (total 12)

RCA)
Increased retropharyngeal space with General

Oxaciffin,
mycin

then
(total

dlinda9)

marked

adenopathy

anesthesia, needle aspiration retropharyngeal space; culture tive

WGG
of
nega-

(11) and

ABA

Giant coronary rysms (LAD

aneu-

and

RCA)

Cefador,

then cefamandole and dindamydn (total 8)

(4)

Adenopathy extending from external ear to

(R) retropharyngeal

ND

1VGG

(10) and ABA

Mild dilation LAD coronary artery

space
10

Penicillin

(L) Cervical
thy with

adenopaextension

Needle
fluid

aspiration;
obtained

no

IVGG

(5) and

ABA

None

to supradavicular area and superior mediastinum 11

*

Amoxicillin

(3) intravenous

ND gammaglobulin; ABA,
aspirin;

ND
LAD, left anterior

IVGG
descending

(6) and
RCA,

ABA

None coronary artery; L, left; R,

ND,

not done;

IVGG,

right

right.

enitis, the diagnosis of KD was delayed in most, to at least the tenth day of illness in five patients. All four of our patients who developed coronary abnormalities had a delayed diagnosis of KD and were treated on or after the tenth day of ifiness. April et a17 noted that KD patients with cervical adenopathy were significantly older than those without adenopathy, speculating that the greater maturity of the mucosal immune system in older patients may lead to a more intense inflammatory response. Likowise,
Qgreater

antibiotics. the need antibiotic therapy

leviate ment, with

spite

Earlier
for

diagnosis
unnecessary

of KD should
procedures

aland

and

lead
risk

to more
for

timely

KD treatcoronary

a lowered

developing

abnormalities.
Jun#{128} KiM STAMOS, MIY
KATHLEEN JAMES STANIORD
CORYDON,

DONALDSON,

RN, MD

BSN

the

median
than the

age

of our
age

patients
of KD KD

(5 years)
patients include

was
in the

median rarely

T. Siuuwi, MD Loyola University Medical Center Maywood, IL Northwestern University Medical Schools
Chicago, IL

Chicago
normalities

area

(2.25 years).3
reported

Other
in

otolaryngologic and severe

of

abnecrotic

pharyngitis,
tis

peritonsifiar

cellulitis,

uvuli1. Kato H, Ichinose

REFERENCES
E, Yoshioka F, et aL Fate of coronary aneurysms in disease: serial coronary angiography and long-term followup study. Am I Candiol. 1982;49:1758-1766 Taubert KA, Rowley MI, Shulman ST. A U. S. nationwide survey of Kawasaki disease and acute rheumatic fever. JPediatr. 1991;119:2:79-82. Rowley AR, Gonzalez-Crussi F, Shulman ST. Kawasaki syndrome. Rev Infect Dis. 1988;10:1-15 Giesker DW, Krause PJ, Pastuazak WT, et aL Lymph node biopsy for early diagnosis in Kawasaki disease. Am I Sung Pathol. 19826:493-501 Corbeel L, Delmotte B, Standaert L, Casteels-Van Daele M,Eeckels R. Kawasaki disease in Europe. Lancet. 1977;1:797 Cloney DL, Teja K, LOhrJA. Fatal case of atypical Kawasaki syndrome. Pediatr Infect Dis J. 1986;6:297-299 Kawasaki

and supraglottitis.8-1#{176} Although the differential

diagnosis

cervical
2. 3.

lymphadenopathy

in children

is broad,

prolonged

high fever, nonexudative bulbar conjunctival injection, erythema and fissuring of the lips, rash, or swelling of the hands and feet should suggest KD. Physicians should be aware that patients with KD initially may have findings that strongly suggest bacterial lymphadenitis. Patients should be observed closely for development of other KD criteria when they continue to be febrile and show little improvement do-

4.
5.

6.

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527

7. April 8. Brion

MM,

Burns

JC,

Newburger

JW,

et al

lymphadenopathy.
L, Courtoy

Arch

Otolanyngol

Head

Kawasaki Neck Sung.

disease cervical 1989;115:512-514

D, et aL Mucocutaneous lymph node Eun J Pediatn. 1980;135:111-116 9. Korkis JA, Stillwater LB. An unusual otolaryngological problem: mucocutaneous lymph node syndrome (Kawasakis syndrome) case report. I Otolaryngol. 1985;14:257-260 10. Kazi A, Gauthier M, Label MH, et aL UVU11tiS and supraglottitis: early manifestations of Kawasaki disease. Pediatr Infect Dis I. 1992;120: 564-567 M, Bachelart

Syndrome

with necrotic pharyngitis.

dren, aged 2 to 18 years (median 8.5 years), are roported in this study. The most common manifestation was recurrent attacks of acute pancreatitis, followed by chronic diarrhea. Laboratory data showed normal serum electrolyte, calcium, cholesterol, and liver enzyme levels (aspartate aminotransferase, alanine aminotransferase). The significant clinical symptoms and laboratory investigations are summarized in the Table . An association of hereditary pancreatitis with diabetes rnsipidus was found in one child at age 7 (Fig 1).

Hereditary Children

Pancreatitis in the of West Virginia

DISCUSSION Hereditary pancreatitis (HP) is a chronic disease which ultimately leads to pancreatic insufficiency. The most common manifestation is repeated attacks of acute pancreatitis. All our pediatric patients have manifested the disease in this manner, resulting in multiple admissions. Five of seven patients had clinical symptoms of malabsorption and had abnormal pancreatic stimulation tests. Pancreatic insufficiency was diagnosed in two patients before the age of 3 years. All five patients responded to pancreatic enzyme supplementation. Pancreatic pseudocysts occur commonly in HP, with an estimated incidence in up to 50% of patients.6 In our series, only one child (family H, Fig 1) had three pancreatic pseudocysts which had regressed spontaneously. The estimated rate of regression of pseudocysts of all etiologies is 20%. Excluding our eight patients, the pedigrees reprosent a total of 38 members who had hereditary pancreatitis. Seven patients (Figs 1 and 2) had a partial or total pancreatectomy, or other pancreatic drainage procedure. Diabetes mellitus and recurrent abdominal pain were diagnosed in several other members. The outcomes of previous generations suggest that children with HP wifi be prone to significant future morbidity due to pancreatic outlet obstruction and/or pseudocyst formation that may require surgery. Unfortunately, endocrine/exocrine pancreatic insufficiency and pancreatic malignancy (estimated 5%) is the long-term course of the disease.1 The molecular defect in HP is as yet unknown. De

Hereditary pancreatitis is the second most common cause of chronic pancreatitis in children.1 In this entity, pancreatitis is clustered in families and inherited throughout the generations, involving many family members. The disease is transmitted as an autosomal dominant trait which is not sex-linked and has limited penetrance.1 Unfortunately, the etiology of this familial disease is unknown. The most common symptom in hereditary pancreatitis is recurrent attacks of abdominal pain due to repeated episodes of acute pancreatitis, which later may result in exocrine and/or endocrine pancreatic insufficiency. In cases in which pancreatic histology had been reported, normal pancreatic tissue was replaced by diffuse fibrosis and chronic inflammation.2 West Virginia seems to be an endemic area for hereditary pancreatitis. Perhaps due to intrafamilial marriage, the gene pool for this disease apparently has been present in this region for generations. Data published from this area in 1973 identified three family pedigrees with this disease.3 In this study, we present our experience with four additional family pedigrees and the children who have hereditary pancreatitis.
MATERIALS AND

METHODS
families not previously rewere followed up in our peHuntington, WV. Their charts clinical findings, labora-

Patient
Eight

Population
with
children from hereditary gastrointestinal

four

different

ported
diatric

pancreatitis clinic in

were reviewed retrospectively tory results, and treatment.

for their

TABLE.

Clinical

and Laboratory

Data

Laboratory
Pancreatic

Investigation
function

was evaluated by the secretin stimulation test (five patients) as described by Madrazo-de la Garza et al4 or by the bentiromide test5 if endoscopy was refused (two patients). One patient refused both tests. Four-hour glucose tolerance tests were performed in all patients. Diabetes insipidus was diagnosed by the water deprivation test.

CliniCal symptoms Diarrhea, foul

stool + recurrent pancreatitis

Abdominal
Growth

pain
(>5%tile)

3/8 8/8
8/8

(37%) (100%)
(100%)

Polyuria
Laboratory data Elevated amylase/lipase Hypercalcemia Hyperlipidemia Abdominal ultrasound

1/8 8/8 0/8 0/8

8/8

(12.5%)
(100%)

RESULTS

(100%)

The four family pedigrees represent a total affected members, of whom seven had pancreatic gery (Figs 1 and 2). Five male and three female
Received for publication Jun 24, 1993; accepted Sep 15, 1993. PEDIATRIcS (ISSN 0031 4005). Copyright C 1994 by the American emy of Pediatrics.

of 46 surchil-

Edema
Dilated Cysts Calculi Pancreatic

duct

1/8 1/8 1/8 0/8 test tolerance

test test

(12.5%) (12.5%) (12.5%)

function

Abnormal
Acad-

Abnormal Abnormal

glucose secretin
bentiromide

test (4 h)

0/8 4/5 2/2

(80%)
(100%)

528

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Lymphadenitis as the Dominant Manifestation of Kawasaki Disease Julie Kim Stamos, Kathleen Corydon, James Donaldson and Stanford T. Shulman Pediatrics 1994;93;525
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PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly publication, it has been published continuously since 1948. PEDIATRICS is owned, published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois, 60007. Copyright 1994 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.

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