Antinuclear antibodies in children with chronic nonspecific complaints

Children who are chronically complaining nonspecific symptoms such
as headache, fatigue, abdominal pain, and low grade fever are
commonly seen in daily pediatric outpatient clinics. Some of
them are unable to go to school and are diagnosed as school
refusal by physicians or educational staff. On the other hand,
there are children who do not fulfill any criteria of collagen
diseases and whose anti-nuclear antibodies (ANA) are found to
be positive. Some of these children have chronic nonspecific
complaints. We prospectively studied the prevalence of ANA in
children who visited a pediatric outpatient clinic because of
chronic nonspecific complaints. Surprisingly, 74 out of 140
symptomatic children (52.4%) were positive for ANA, while only
5 out of 82 healthy control children (6.1%) were positive (p <
0.0001). 39 of 74 ANA positive patients (52.1%) have low ANA
titers < or = 1:80, nevertheless 36 patients (47.9%) have high
ANA titers > or = 1:160. ANA fluorescent patterns were
homogeneous and speckled in 75.3%, speckled in 17.6% and
others in 6.8%.

ANA positive patients tended to have general
fatigue and low grade fever, while gastrointestinal problems
such as abdominal pain and diarrhea and orthostatic
dysregulation symptoms were commonly seen in ANA negative
patients. Children who were unable to go to school more than 1
day a week were seen significantly more in ANA positive
patients than in negative patients. Autoantibody analysis
using Western immunoblot revealed that 26 out of 63 ANA
positive sera (41.3%) had antibodies to the 62 kD protein
which had not been previously noticed. These data suggest that
autoimmune mechanism may play a role in childhood chronic
nonspecific symptoms. We therefore propose a new disease
entity of the autoimmune fatigue syndrome in children. When
chronically complaining children visit a pediatric out-patient
clinic, immunological approaches should be considered before
they are discriminated as school refusal or having psychogenic

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