ORIGINAL ARTICLE
Inflammatory Myopathy and Celiac Disease
Alexa
Adams, MD1, Karen B. Onel, MD2, and Thomas Lehman1
1, 3 Hospital for Special Surgery
2La Rabida Childrens’ Hospital/University of
Corresponding Author:
Thomas J.A. Lehman, M.D.
Chief, Division of Pediatric Rheumatology
Hospital for Special Surgery
535 East 70th Street
New York, NY 10021
Office (212) 606-1151
Fax (212) 606-1938
ABSTRACT
We report two children with inflammatory
myopathy who were found to have celiac disease:, a 10 year old female with
dermatomyositis and an 8 year old female with polymyositis. The association
between inflammatory myopathy and celiac disease has been reported in adults,
but is not well recognized in children. Celiac disease is being diagnosed with
increasing frequency in patients of all ages, and we believe that the
possibility of celiac disease must be considered in children presenting with
idiopathic inflammatory myopathy even in the absence of significant gastrointestinal
complaints.
Case 1
A 10-year-old female presented
at age 6 years with a one month history of weakness, knee pain, and a rash over
the eyelids. Her physical examination was significant for a bilateral
heliotrope rash on her eyelids. Mild capillary nail fold abnormalities were
noted, without evidence of Gottron’s papules. Her muscle strength was 3/5 in
the lower extremities with a positive Gower’s sign. Laboratory testing revealed
a CPK of 228 IU/L (30-135 IU/L) and an aldolase of 29.9 IU/L (1.2-8.8 U/L
IU/L). The SGOT and SGPT were elevated at 125 and 50 IU/L (both 0-45 IU/L)
respectively, with an LDH of 2866 IU/L (313-618). The serum chemistry panel was
otherwise unremarkable. She was anemic with a hemoglobin of 10 g%, her platelets
were 470,000 cells/mm3, and her ESR was 58 mm/hour. The MRI with T2
imaging was markedly abnormal.
She was started on Prednisone 1
mg/kg/day (20 mg daily) for treatment of juvenile dermatomyositis. The
prednisone was weaned off over the next year, and she did well with only an
occasional arthritis episode that was treated successfully with NSAIDs.
Two years after presentation
she developed significant muscle weakness. Her CPK was 300 IU/L and her
aldolase 30 IU/L. An MRI of the thighs demonstrated patchy but diffuse edema of
the bilateral thighs consistent with recurrent dermatomyositis. Prednisone was
restarted and methotrexate added. She
was growing poorly and complained of abdominal pain. She was found to be tissue
translgutaminase, anti-endomysial antibody, and anti-gliaden antibody
positive. A biopsy of the small
intestine was performed, and the pathological report was consistent with celiac
disease. She is currently off all
medications and is asymptomatic on a gluten free diet.
Case
2
An 8-year-old
Caucasian female presented with a 4 month history of bilateral finger pain and
stiffness, and a seven month history of fatigue with reduced participation. She
had gel effect and morning stiffness. NSAIDs had been given without improvement.
She did not have fever, rash, or joint swelling. She had no evidence of other
overlap syndrome features with characteristics of SLE or scleroderma. Her
medical and family histories were otherwise unremarkable. She had always been
small for her age, growing along the 5th percentile. Because of a
history of asthma and slow growth a sweat test was done which was negative.
On examination she was thin with
diffuse swelling and tenderness of the MCP and PIP joints, elbows, knees, and
ankles. Muscle strength was normal and there were no rashes or skin lesions.
Laboratory testing revealed an elevated antinuclear antibody titer at 1:640
with a speckled pattern. The anti-DNA, anti-Sm, anti-Ro, anti-La, anti-RNP,
anti-Scl-70, and anti-centromere antibody titers were all negative. The C3 and
C4 were normal. The anti-cardiolipin titers were negative. A total T3 was high
at 363 ng/dl (127-221 ng/dL). TheT4 and TSH were normal. The IgM rheumatoid
factor and HLA-B27 antigen were negative.
Lyme and parvovirus titers were
negative. The patient had a normal IgA level. The complete blood count,
sedimentation rate, complete metabolic panel, urinalysis and lactic
dehydrogenase were all within normal limits. A creatine phosphokinase was
within normal limits, but the aldolase was found to be elevated at 11.9 U/L
(1.2-8.8 U/L). She was tissue transglutaminase positive. Her anti-endomysial,
anti-gliaden IgA, anti-reticulin IgA, and anti-gliaden IgG antibodies were all
negative.
A MRI with T2 imaging of the pelvis, bilateral
lower extremities, and the right shoulder were significant for diffuse
inflammatory changes consistent with polymyositis. We then considered her to
have probable polymyositis on the basis of the arthritis, elevated aldolase,
and abnormal muscle MRI. Due to her poor growth, the possibility of celiac
disease was considered. A biopsy of the duodenum demonstrated classic
histologic findings of celiac disease. She was started on a gluten free diet
and prednisone 1 mg/kg/day with significant improvement.
DISCUSSION
Celiac disease, also
known as gluten-sensitive enteropathy, is an inflammatory condition of the
small intestine precipitated by the ingestion of gluten in genetically
predisposed individuals. Clinical manifestations classically include
malabsorption, weight loss, and abdominal pain. The varied clinical
manifestations of this disease may delay diagnosis leaving patients vulnerable
to inadequately treated symptoms and the long-term effects of
malabsorption.
If celiac disease is
suspected in a child, the rheumatologist should order a tissue transglutaminase
and an endomysial antibody test.
Anti-gliadin antibody titers may be falsely elevated. If these tests are positive, consultation of
a gastroenterologist for a small intestinal biopsy is necessary. For the
definitive diagnosis of celiac disease, the biopsy must show the typical
lesions with villous flattening, crypt hyperplasia, and intra-epithelial
lymphocytes. These biopsy findings should resolve with the institution of a
gluten-free diet and recur with the re-introduction of dietary gluten.
While classic celiac
disease has traditionally been diagnosed in infants and young children with
malabsorption, extra-intestinal associations of celiac disease are being
recognized with increasing frequency, including associated neurologic,
dermatologic, hematologic, endocrinologic, and rheumatologic diseases. For
example, it is well known that celiac disease occurs with increased frequency
in patients with IgA deficiency and autoimmune diseases such as Type 1 diabetes
mellitus, and thyroiditis. [1-2] In addition, an increased incidence of celiac
disease has been reported among children with juvenile chronic arthritis. [3]
It is likely that celiac disease remains under-diagnosed in the
Early institution of
a gluten-free diet alleviates the symptoms of celiac disease and avoids the
long-term effects of chronic malabsorption that includes anemia, vitamin
deficiencies, failure to thrive, short stature and osteoporosis. Additionally,
the prompt diagnosis and treatment of celiac disease may spare patients
prolonged trials of ineffective medications, and even unnecessary treatment
with corticosteroids. In order to identify those patients at risk for celiac
disease, it is necessary to maintain a high index of suspicion for its varied
clinical manifestations. In adult patients, there have been reports of
polymyositis and dermatomyositis occurring in the setting of celiac disease. [5,6,7] However, to our knowledge, there have been no
reports of celiac-associated
polymyositis in the pediatric population, though celiac disease has been
reported in association with juvenile dermatomyositis [8]. Polymyositis is rare in childhood, and we
believe that this may represent an extension of the spectrum of atypical celiac
disease and idiopathic inflammatory myopathies of childhood.
In summary, the
diagnosis of celiac disease should be considered in children presenting with the
clinical picture of dermatomyositis, polymyositis, and other rheumatic diseases
with poor growth, even in the absence of clinical malabsorption or frank
abdominal complaints. If abdominal pain is present, coexistent celiac disease
should be considered as well as NSAID and other drug gastrointestinal toxicity,
inflammatory bowel disease, vasculitis, and other causes of abdominal pain in
these special children. If celiac disease is found to be present, these
children can do much better with the institution of a gluten-free diet.