is a frequent major complication that affects the prognosis
Henoch-Schönlein
Purpura in a Child
With Guillain-Barré
Syndrome
Tatsuo Fuchigami, MD, PhD*†,
Maki Hasegawa, MD*†,
Koji Hashimoto, MD, PhD*†,
Yukihiko Fujita, MD, PhD†,
and Yasuji Inamo, MD, PhD*†
A case of Henoch-Schönlein purpura with Guillain-
Barré syndrome in a 3-year-old-girl is presented. This
association is extremely rare. During the course of Guil-
lain-Barré syndrome, a decrease in plasma factor XIII
activity was noted. When the Guillain-Barré symptoms
improved, the factor XIII activity returned to normal.
In the present case of Henoch-Schönlein purpura com-
plicated by Guillain-Barré syndrome, the factor XIII
level was measured, a novel feature of this study. The
findings suggest the involvement of factor XIII, which
is characteristically involved in Henoch-Schönlein
purpura, also is involved in the associated Guillain-
Barré syndrome. Ó 2010 by Elsevier Inc. All rights re-
served.
Fuchigami T, Hasegawa M, Hashimoto K, Fujita Y,
Inamo Y. Henoch-Schönlein Purpura in a child with Guil-
lain-barré syndrome. Pediatr Neurol 2010;43:431-434.
Introduction
Henoch-Schönlein purpura is an autoimmune disorder
that preferentially affects children. It is characterized
clinically by punctate hemorrhages, arthralgia, and gastroin-
testinal symptoms; histologic examination reveals systemic
necrotizing vasculitis of small vessels. Glomerulonephritis
From the *Department of General Pediatrics, Nihon University Nerima
Hikarigaoka Hospital, Nihon University School of Medicine, and
†
Department of Pediatrics and Child Health, Nihon University School of
Medicine, Tokyo, Japan.
Ó 2010 by Elsevier Inc. All rights reserved.
doi:10.1016/j.pediatrneurol.2010.06.008  0887-8994/$—see front matter
[1]. Infrequently, neurologic manifestations are seen in
patients with Henoch-Schönlein purpura. Central nervous
system involvement is uncommon [2,3], and involvement
of the peripheral nervous system is even rarer [3]. In the
present case, the extremely rare [4-6] occurrence of
Guillain-Barré syndrome, also known as acute inflamm-
atory demyelinating polyradiculoneuropathy, appeared in
association with Henoch-Schönlein purpura.
Plasma factor XIII activity is decreased in more than 70%
of patients with Henoch-Schönlein purpura, particularly in
those with severe abdominal symptoms [7]. Kaneko et al.
[8] reported that measurement of plasma factor XIII, a clot-
ting factor, was helpful in the diagnosis of Henoch-Schön-
lein purpura even before development of the characteristic
rash. Reported here is a case of Guillain-Barré syndrome
complicating Henoch-Schönlein purpura in a 3-year-old
girl in whom Guillain-Barré syndrome was thought to
have been related to a decrease in factor XIII.
Case report
A 3-year-old girl was admitted with abdominal pain, lower limb pain,
arthralgia, and difficulty walking. There was no recent drug exposure or
immunization, and her family history was unremarkable. Two weeks
before admission, she had acute pharyngitis and acute otitis media, for
which she was treated at a family clinic. Three days before admission,
she developed bilateral knee joint pain. One day later, severe leg pain
and difficulty standing developed. Because her leg pain did not improve,
she was admitted to the Department of General Pediatrics at Nihon Univer-
sity Nerima Hikarigaoka Hospital with suspected arthritis. On admission,
she was unable to stand or sit up unassisted. She also had vomiting and
abdominal pain.
Examination on admission revealed no swelling or redness of joints over
the upper and lower extremities; however, all movements of her legs
caused stabbing pain. The pain was severe, occurring with even the slight-
est movement. Thus, muscle weakness and deep tendon reflexes could not
be checked. There was no cranial nerve involvement. The patient was
96 cm tall (+1.08 S.D.) and weighed 14.0 kg (+0.64 S.D.). Her axillary
body temperature was 36.6 C, her pulse rate was 120/min, and her blood
pressure was 120/78 mmHg. There was mild abdominal tenderness and di-
minished bowel sounds, but no distention. Purpura was not evident.
Initial laboratory tests indicated mild leukocytosis (white blood cells,
12,900/mL, with 73.0% neutrophils), no anemia (hemoglobin, 13.7 g/dL),
normal platelet count (42.1  104/mL), normal prothrombin time of 12.8
s, normal activated partial thromboplastin time of 25.0 s, normal D-dimer
0.8 mg/mL, and normal thrombin-antithrombin III complex of 1.3 ng/mL.
There were no abnormalities on coagulation testing. Factor XIII activity
was 86% (normal, 70-140%). C-reactive protein was normal (0.18 mg/
dL), and C3 and C4 complement factors were increased (C3, 156 mg/dL;
C4, 50 mg/dL). Immunoglobulin G was 1193 mg/dL, immunoglobulin A
Communications should be addressed to:
Dr. Fuchigami; Department of General Pediatrics; Nihon University
Nerima Hikarigaoka Hospital; Nihon University School of Medicine;
2-11-1 Hikarigaoka; Nerima-ku; Tokyo 179-0072, Japan.
E-mail: tfuchi@med.nihon-u.ac.jp
Received February 5, 2010; accepted June 8, 2010.
Fuchigami et al: HS Purpura and Guillain-Barré 431
was 48 mg/dL, and immunoglobulin M was 118 mg/dL. Biochemical stud-
ies revealed normal levels for electrolytes, blood urea nitrogen, creatinine,
and transaminase. Urinalysis was negative for protein and occult blood.
The Guaiac test for fecal occult blood was positive. The admission chest ra-
diograph was normal. Abdominal x-ray revealed only a constipated colon.
Bacterial cultures from the throat and stool grew no pathogenic bacteria.
Eight days after onset, the patient developed Quincke edema on her
lower back, and purpura on her lower extremities and earlobes. Laboratory
tests at that time indicated decreased factor XIII activity (54%) and
increased thrombin-antithrombin III (474 ng/mL). With a diagnosis of
Henoch-Schönlein purpura, prednisolone (2 mg/kg per day) and tranexa-
mic acid were started because of gastrointestinal involvement. After
prednisolone was started, her abdominal symptoms began to improve,
and purpura had also disappeared. Her leg pain and difficulty standing
did not improve, however, and progressive weakness in both arms and
legs, lack of deep tendon reflexes as a hallmark sign, dysphagia, dysarthria,
and dyspnea were recognized.
Twelve days after onset, a lumbar puncture indicated a protein level of
189 mg/dL and white blood cells at 3/mL; however, there were no oligoclo-
nal bands. Serum anti-GQ1b and GM1 antibodies were not detected.
At this time, with a diagnosis of Guillain-Barré syndrome, she received
400 mg/kg per day of intravenous g-globulin for 5 consecutive days.
Nerve conduction studies indicated delayed motor nerve conduction
velocity of the tibial nerve (38.9 m/s), and decreased M wave amplitude
decreased (0.433 mV) at 13 days after onset. (Later, at 26 days after onset,
tibial motor nerve conduction velocity was even more delayed: 18.6 m/s.)
Fourteen days after onset, sagittal and axial T1-weighted magnetic
resonance images were obtained prior to and following the administration
of gadolinium-diethylenetriamine pentaacetic acid. The post-contrast
images demonstrated abnormal enhancement of the cauda equina and
lumbosacral nerve roots (Fig 1). Serial imaging was performed. The nerve
root enhancement resolved as her clinical symptoms improved.
Twenty days after onset, the patient was started on rehabilitation. Factor
XIII activity decreased further (to 34%), and thrombin-antithrombin III
Figure 1. T1-weighted images after gadolinium injection reveal enhancement of multiple anterior and posterior nerve roots at the level of the conus
medullaris (arrows). (A) Sagittal image. (B) Axial image. [R] indicates right side.
432 PEDIATRIC NEUROLOGY Vol. 43 No. 6
normalized (2.2 ng/mL). By 35 days after onset, she could sit alone.
Nonetheless, factor XIII activity continued to be low (53%). By 60 days
after onset, the patient could roll over, but a low factor XIII level (59%)
continued. At 90 days, the patient could walk with support, and factor
XIII activity returned to normal (74%). At 100 days after onset, she could
walk unassisted, and factor XIII activity was normal (84%). Thus, at
approximately 15 weeks after the onset of symptoms, her neurologic
function had returned to almost normal. Decreased factor XIII activity
continued for several months and normalized when neurologic function
returned to almost normal.
The child’s parents gave their consent for the publication of this case
report.
Discussion
The diagnosis of Guillain-Barré syndrome is based on
characteristic signs and symptoms, with confirmation from
laboratory and electromyographic studies. The characte-
ristic laboratory findings are an elevated cerebrospinal fluid
protein in the absence of a pleocytosis. Electromyographic
features supportive of Guillain-Barré syndrome include
nerve conduction slowing, conduction block, prolonged dis-
tal latencies, and prolonged or absent F waves. The patient
in the present report fulfilled the modified criteria proposed
by an ad hoc committee of the U.S. National Institute of
Neurological Disorders and Stroke [9]. After injection of
gadolinium-diethylenetriamine pentaacetic acid, magnetic
resonance imaging revealed enhancement of the cauda
equina in this patient. This imaging observation may also
help confirm the diagnosis of Guillain-Barré syndrome [10].
Table 1. Comparison of cases of Guillain-Barré syndrome occurring in association with Henoch-Schönlein purpura

Henoch-Schönlein Purpura Guillain-Barré Syndrome

Gastrointestinal Renal Motor Sensory Respiratory
Case Age, yr Purpura Involvement Involvement Weakness Abnormalities Involvement References

1 41 + Quadriplegia + Sanghvi and Sharma, 1956 [4]

2 35 + + + Quadriplegia + Moreau et al., 1988 [5]
3 10 + + + Paraplegia + Goraya et al., 1998 [6]
4 3 + + Quadriplegia + + Present case

The patients in all four cases were female.

Activity of factor XIII (fibrin-stabilizing factor) has been
investigated in children with Henoch-Schönlein purpura
and found to be decreased. Children with Henoch-Schönlein
purpura who have factor XIII levels less than 50% of normal
experience complications earlier, and normalization of fac-
tor XIII levels heralds recovery [11]. Dalens et al. [11] sug-
gested that the mechanism of factor XIII deficiency is
specific for Henoch-Schönlein purpura, because these
abnormalities are not found in patients with hepatic failure
(defective synthesis), nephropathy (urinary loss), or other
vasculitides (local proteolysis). In the present patient, factor
XIII activity was reduced to as low as 34%. A report has
suggested that the factor XIII level may be decreased in
Crohn’s disease or infectious colitis [12]. For reasons
already given, the present patient did not have any of these
diagnoses. Serum factor XIII levels, although not specific
for Henoch-Schönlein purpura, are characteristically
depressed in Henoch-Schönlein purpura.
Involvement of the peripheral nervous system in
Henoch-Schönlein purpura is extremely rare. Table 1 gives
the salient features of the four reported cases of Henoch-
Schönlein purpura with Guillain-Barré syndrome. Among
these, the present patient is the youngest, and only the
second child; all four patients were female. We speculated
that the severe pain and sensory abnormalities in the present
case were due to inflammation and entrapment of the nerve
roots and to alteration in the function or spontaneous
discharges in the demyelinated sensory nerves [13].
The pathogenesis of Guillain-Barré syndrome in
Henoch-Schönlein purpura is not clearly understood.
An allergic or hypersensitivity mechanism was initially
proposed [4]. Immunoglobulin A immune complexes
were seen on neuromuscular biopsy in the case described
by Moreau et al. [5]. Deposits of immunoglobulin A and
complement C3 in dermal capillaries on skin biopsy were
also identified [6]. In the present case, during the course
of the Guillain-Barré syndrome, a decrease in plasma factor
XIII activity was noted. When the symptoms of Guillain-
Barré syndrome improved, factor XIII activity returned to
normal. Because factor XIII level did not recover after
resolution of Henoch-Schönlein purpura, it is reasonable
to conclude that factor XIII is associated with Guillain-
Barré syndrome.
Coagulation factor XIII is a plasma transglutaminase that
crosslinks fibrin, the final step of the coagulation system,
and serves also as a connective tissue factor that contributes
to the healing of wounds [12].
Autoantibody production signifies a breakdown of
immune tolerance to self-antigens and is an important
feature of many autoimmune disorders. In celiac disease, an
autoimmune enteropathy with multiple extraintestinal mani-
festations, autoantibody reactivity to transglutaminase 2
has been shown to closely correlate with the acute phase of
the disease. Immune reactivity to other autoantigens,
including factor XIII and transglutaminase 3, which is one
of the transglutaminase isozymes, has also been reported in
celiac disease [14]. Although anti-factor XIII antibody leads
to a decline of transglutaminase functions, factor XIII defi-
ciency in Henoch-Schönlein purpura is thought rarely to exert
a similar pathogenic role as in celiac disease. Recent reports
have described in some patients with celiac disease the
presence of idiopathic peripheral neuropathies, such as Guil-
lain-Barré syndrome [15]. These findings suggest that even
a factor XIII insufficiency in Henoch-Schönlein purpura
may cause impaired synthesis of ganglioside, and intensify
the activity of autoimmune diseases such as Guillain-Barré
syndrome.
The present case is novel as the only reported case of
Henoch-Schönlein purpura complicated by Guillain-Barré
syndrome in which factor XIII levels were measured. The
findings suggest the involvement of factor XIII, which is
characteristic of Henoch-Schönlein purpura, also in the
associated Guillain-Barré syndrome.
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