Open Journal of Pediatrics, 2012, 2, 250-252 OJPed
http://dx.doi.org/10.4236/ojped.2012.23039 Published Online September 2012 (http://www.SciRP.org/journal/ojped/)
Kawasaki disease, Mycoplasma pneumoniae infection and
anaplastic large cell lymphoma: An uncommon association
Jalel Chemli1, Saida Hassayoun1, Soumaya Ketata2, Ajmi Houda1, Moncef Mokni3, Noura Zouari1,
Saoussen Abroug1, Abdelaziz Harbi1
1Department of Paediatrics, Sahloul Hospital, Sousse, Tunisia
2Laboratory of Bacteriology-Virology, Sahloul Hospital, Sousse, Tunisia
3Department of Cytopathology, Farhat Hached Hospital, Sousse, Tunisia
Received 20 October 2011; revised 13 February 2012; accepted 19 July 2012
Kawasaki disease (KD) is an acute febrile systemic
vasculitis occurring predominantly in young children
less than 5 years of age. Although imperfectly known,
the aetiopathogenesis of KD would be secondary to
immunological abnormalities that could constitute a
favourable terrain for neoplasms. We report on a
case in a 2-year-old girl who presented clinical mani-
festations compatible with Kawasaki disease compli-
cated by coronary aneurysm. Aetiopathological in-
vestigations revealed M. pneumoniae infection as spe-
cific IgM were present in the serum (Elisa). The pa-
tient was initially treated by intravenous immu-
noglobulins (IVIG) and aspirin to anti-inflammatory
dose. Following a few days of desquamation, resolu-
tion of the symptomatology occurred. Four weeks
later she developed disseminated tumorous syndrome.
Lymph node biopsy revealed massive infiltration by
large cells lymphomatous proliferation. Histologic
and immunophenotypic findings were characteristic
of ALK-1+ anaplastic large cell lymphoma. Four
weeks later, the patient died from a severe nosocomial
infection complicated by septic shock. Our observa-
tion is the first cases describing the association be-
tween anaplastic large cell lymphoma, KD and M.
pneumoniae. Immunologic disorder due to KD and M.
pneumoniae infection may play probably a central
role for malignancy .
Keywords: Kawasaki Disease; Mycoplasma
pneumonia e; Anaplastic Large Cell Lymphoma;
Kawasaki disease (KD) is a systemic vasculitis that oc-
curs predominantly in infants and young children, first
described in Japan in l967 by Tomisaku Kawasaki .
The etiology and pathogenesis of KD still remain un-
known. However, immunological abnormalities in the
acute phase of KD are well documented and may be
pathogenic in the known cardiac and noncardiac compli-
cations of the disease. Despite the well-known associa-
tion between acquired immunodeficiency states and neo-
plasia, there are only a few reports of malignant neo-
plasms accompanying or following the onset of this dis-
ease [2-4]. We report here an exceptional case of KD
associated with Mycoplasma pneumoniae infection and
complicated by anaplastic large cell lymphoma in a
2. CASE REPORT
A 2-year-old Tunisian girl was diagnosed with Kawasaki
disease after presenting with a 10-day history of fever,
bilateral nonexudative conjunctivitis, erythema of the
lips and oral mucosa, swelling and erythema of the palms
and soles, rash, and cervical lymphadenopathy. Labora-
tory investigation revealed an haemoglobin concentration
of 6 g/dL, white blood cell count of 15,700/mm3 (with
72% neutrophils, 24% lymphocytes and 3% monocytes)
and platelet count of 750 × 103 cells/L. C-reactive protein
was elevated to 102 mg/L and erythrocyte sedimentation
rate to 65mm in the first hour. Visceral laboratory invest-
tigations (renal and hepatic function, muscular enzyme)
revealed no abnormalities. Chest X-ray revealed bron-
chial syndrome associated with diffuse alveolar opacities.
Echocardiogram showed coronary artery ectasia (left
main coronary artery 5 mm, left anterior descending ar-
tery 3.4 mm and right coronary artery 3.2 mm). Aetio-
logical investigations revealed M. pneumoniae infection
as specific IgM were present in the serum (Elisa, DRG
Diagnostic, Allemagne). Serologic tests for Epstein-Barr
virus (EBV), rubella and cytomegalovirus (CMV) were
negative. The patient was treated with intravenous im-
munoglobulin (IV-IG) 2 g/Kg single infusion and started
on aspirin 100 mg/Kg/day and erythromycin (50 mg/
J. Chemli et al. / Open Journal of Pediatrics 2 (2012) 250-252 251
Kg/day). Following a few days of desquamation, com-
plete resolution of the symptomatology occurred. Four
weeks later, she developed tumorous syndrome with
moderate hepatosplenomegaly and palpable left cervical
and profound lymph adenopathies detected by the ultra-
sonography of the abdomen and the chest computed to-
mography. Examination of the bone marrow revealed
only granulous hyperplasia without tumorous infiltration.
Lymph node biopsy revealed massive infiltration by
large cells lymphomatous proliferation. The neoplastic
elements were immunoreactive for leukocyte common
antigen, CD30, ALK-1 and ep ithelial membrane antigen.
These histologic and immunophenotypic findings were
characteristic of ALK-1+ anaplastic large cell lymphoma.
A combination chemotherapy with methotrexate, idaru-
bicin, cytarabine and thiotepa was started.
Two weeks later, the patient died from a severe noso-
comial infection complicated by septic shock.
Although coronary artery involvement is the feature re-
sponsible for most of the morbidity in KD, other com-
plications can also occur.
Our observation is particular by the associatio n of KD
with M. pneumoniae infection and anaplastic large cell
lymphoma never described at to day. However, if linking
M. pneumoniae to KD is actually considered that is a
possible trigger [5-9], relationship between KD and ma-
lignancies remains unclear and controversial. The hy-
pothesis that there may be an unrecognized peri-malig-
nant syndrome of signs and symptoms is discussed by
Murray et al. . Clinicians must rely on the presence of
specific clinical criteria and laboratory data, excluding
other illnesses that can mimic the disease . In this
situation the strict diagnostic criteria of Kawasaki disease
are required. However, some patients do not fulfil all
major clinical criteria of the disease and are diagnosed
based on echocardiogram findings. Because of the pro-
longed history of unexplained fever, bilateral nonexuda-
tive conjunctivitis, erythema of th e lips and oral mucosa,
swelling and erythema of the palms and soles, rash, and
cervical lymphadenopathy, KD was considered in our
patient and confirmed sonographically with coronary ar-
te ry ectasia.
Inaba et al.  reported one case of anaplastic large
cell lymphoma associated with Sjogren’s syndrome sug-
gesting that the association of vasculitis with malignancy
The aetiology of KD is unclear. The hypothesis that
Kawasaki disease is related to a bacterial superantigenic
toxin has been suggested because of the reported selec-
tive expansion of V
2 and V
8 T-cell receptor families,
but this theory remains controversial. Mycoplasma ar-
thritis has been shown to produce superantigen, and it is
therefore possible that other Mycoplasma organisms may
do likewise. However, the relationship between KD and
malignancies remains unclear. There are only a few re-
ports of malignant neoplasms associated with KD [2-4].
This association sugg ests that there may be a relationship
between immunological disorder in KD and the devel-
opment of malignancy. In the Japanese literature eight
patients (6 males and 2 females) with history of KD de-
veloped neoplasm . The interval between KD and de-
velopment of neoplasm is variable: 4 weeks to 14 years.
Four of them died. The nature of the neoplasm is also
variable: 3 cases of acute lymphocytic leukemia, 1 case
of Hodgkin’s disease, 1 case of schwannoma, 1 cases of
giant cell tumor of th e tendon sheath, 1 case of osteosar-
coma and 1 case of malignant reticuloma. Seven of the
eight KD patients who developed neoplasms, were treated
with high-dose intravenous immunoglobulin (IVIG). It is
noteworthy that lymphoid malignancies developed in
five cases very shortly after the onset of KD. This sug-
gests that lymphoid malignancies might have developed
in the bone marrow and/or lymphoid tissues at the onset
of KD . Physiopathology of development malignancy
after KD remains unclear. However, it actually admitted
that immunological disorder may play probably a central
Striking immune perturbations occur in acute KD, in-
cluding marked cytokine cascade stimulation and endo-
thelial cell activation. Both HLA-DR+ CD3 + (activated T
cells) and DR+ CD4+ cells (activated helper T cells) were
significantly increased in the lamina propria of patients
with acute Kawasaki disease as compared with controls.
In contrast, CD8+ cells (suppressor/cytotoxic T cells)
were significantly reduced in both the epitheliu m and the
lamina propria of individuals with Kawasaki disease as
compared with controls .
Polyclonal activation of T cells in KD as manifested
by increased interleukins, tumor necrosis factor-
) and increased level HLA-DR+ CD3+ (activated T cells)
and DR+ CD4+ cells (activated helper T cells) is well
documented . Moreover, many growth factors such
as G-CSF (granulocyte colony-stimulating factor), M-CSF
(macrophage colony-stimulating factor) , VEGF
(Vascular endothelial growth factor)  in the acute
phase of KD, might accelerate the development of lym-
phoid malignancies . This immunological disorder
present in the acute phase of KD may persist for a long
The role of infectious factor is not excluded. However,
patients with conditions causing aberration of lympho-
cyte function such as EBV infection, human immunode-
ficiency virus infection (HIV) and post morrow trans-
plantation appear to be a favourable terrain for theses
neoplasms. Our patient presented M. pneumoniae infec-
tion. Extrapulmonary manifestations in M. pneumoniae
Copyright © 2012 SciRes. OPEN ACCESS
J. Chemli et al. / Open Journal of Pediatrics 2 (2012) 250-252
Copyright © 2012 SciRes. OPEN ACCESS
 Wang, J.N., Wang, S.M., Liu, C.C. and Wu, J.M. (2001)
Mycoplasma pneumoniae infection associated with Ka-
wasaki disease. Acta Paediatrica, 90, 594-595.
infection may occur through immune dysregulation .
But relationship between this type of infection and ma-
lignancy remains unclear and not well documented yet.
Our observation is the first case describing the associa-
tion between anaplastic large cell lymphoma, KD and M.
pneumonia e. Immunologic disorder due to KD and M.
pneumonia e infection may play probably a central role
for malignancy and especially for anaplastic large cell
 Lee, M.N., Cha, J.H., Ahn, H.M., Yoo, J.H., Kim, H.S.,
Sohn, S. and Hong, Y.M. (2011) Mycoplasma pneumo-
niae infection in patients with Kawasaki disease. Korean
Journal of Pediatrics, 54, 123-127.
 Newburger, J.W., Takahashi, M., Gerber, M.A., Gewitz,
M.H., Tani, L.Y., Burns, J.C., et al. (2004) Diagnosis,
treatment, and long-term management of Kawasaki dis-
ease: A statement 158 for health professionals from the
Committee on Rheumatic Fever, Endocarditis and Ka-
wasaki Disease, council on cardiovascular disease in the
young, American Heart Association. Circulation, 110,
Further, more detailed epidemiolog ical studies may be
required to clarify the relationship between malignancy,
KD and M. pneumoniae infection.
REFERENCES  Inaba, H., Kawasaki, H., Nakamura, S., Yamamoto, H.,
Kaneko, Y., Satake, N., Komada, Y., Ito, M. and Sakurai,
M. (1998) Anaplastic large cell lymphoma associated
with Sjögren’s syndrome. Leukemia and Lymphoma, 32,
 Kawasaki, T. (1967) Acute febrile mucocutaneous syn-
drome with lymphoid involvement with specific desqua-
mation of fingers and toes in children: Clinical observa-
tion of 50 cases. Japanese Journal of Allergology, 16,
178-222.  Nagata, S., Yamashiro, Y., Maeda, M., Ohtsuka, Y. and
Yabuta, K. (1993) Immunohistochemical studies on small
intestinal mucosa in Kawasaki disease. Pediatric Re-
search, 33, 557-563.
 Murray, J.C., Bomgaars, L.R., Carcamo, B. and Mahoney,
D.H. Jr. (1995) Lymphoid malignancies following Ka-
wasaki disease. American Journal of Hematology, 50,
 Nakamura, Y., Yanagawa, H., Harada, K., Kato, H. and
Kawasaki, T. (2002) Mortality among 139 persons with a
history of Kawasaki disease in Japan. The fifth look. Ar-
chives of Pediatrics & Adolescent Medicine, 156, 162-
 Brogan, P.A., Shah, V., Clarke, L.A., Dillon, M.J. and
Klein, N. (2008) T cell activation profiles in Kawasaki
syndrome. Clinical & Experimental Immunology, 151,
 Igarashi, H., Hatake, K., Tomizuka, H., Yamada, M., Gunji,
Y. and Momoi, M.Y. (1999) High serum levels of M-CSF
and G-CSF in Kawasaki disease. British Journal of Hae-
matology, 105, 613-615.
 Suzuki, H., Takeuchi, T., Minami, T., Shima, Y., Iwaha-
shi, S., Shibuta, S., Uemura, S., Kounami, S., Aoyagi, N.
and Yoshikawa, N. (2005) Neoplasms in three patients
following Kawasaki disease. Pediatrics International, 47,
217-219.  Terai, M., Yasukawa, K., Narumoto, S., Tateno, S., Oana,
S. and Kohno, Y. (1999) Vascular endothelial growth fac-
tor in acute Kawasaki disease. American Journal of Car-
diology, 83, 337-339.
 Chemli, J., Hassayoun, S., Ketata, S., Ajmi, H., Ayeche,
H., Zouari, N., Abroug, S., Boujaafar, N. and Harbi, A.
(2010) Kawasaki disease and Mycoplasma pneumoniae
infection. Medecine et Maladies Infectieuses, 40, 717-719.
 Merlin, E., Al Fatuhi, H. and Crost, P. (2004) Kawasaki
syndrome and Mycoplasma pneumoniae infection. Ar-
chives of Pediatrics & Adolescent Medicine, 11, 972-979.
 Coussens, L.M. and Werb, Z. (2002) Inflammation and
cancer. Nature, 420, 860-867. doi:10.1038/nature01322
 Mizukane, R., Kadota, J., Yamaguchi, T., Kiya, T., Fu-
kushima, H., Nakatomi, M. and Kohno, S. (2002) An eld-
erly patients with hemophagocytic syndrome due to se-
vere Mycoplasma pneumonia with marked hypercytoki-
nemia. Respiration, 69, 87-91. doi:10.1159/000049377
 Vitale, E.A., La Torre, F., Calcagno, G., Infricciori, G.,
Fede, C., Conti, G., Chimenz, R. and Falcini, F. (2010)
Mycoplasma pneumoniae: A possible trigger of Kawasaki
disease or a mere coincidental association? Report of the
first four Italian cases. Minerva Pediatric a, 62, 605-607.