An unusual cause of weakness

By Brian Branchford, MD, Michael Weisgerber, MD, and Jennifer Freeto, MD

A six-year-old previously healthy male presented with a six-week history of progressive weakness. He developed fatigue and bilateral leg pain on a hiking trip in Tennessee, one month prior to admission. He stated that his legs occasionally "felt like breaking." He began to have progressive difficulty riding his bike and walking long distances. Over the last week he struggled to climb stairs and get out of bed. By the time of hospital admission, he had difficulty lifting his arms to feed himself. There was no history of trauma. When parents reflected back further, they noticed decreased energy levels when hiking and playing sports. Four months ago he participated in his first T-ball season and seemed to have diminished base-running ability compared to his peers, which parents attributed to his shy nature. The patient's father also reported an episode in his own childhood of weakness and rash, which improved after steroid therapy.

On admission, the patient's weight was 25 kg (95^th percentile), temperature was 36.8 degrees Celsius, heart rate 117 beats per minute, respiratory rate 28 breaths per minute and blood pressure 121/65. His right parietal scalp exhibited a small (1-2 cm) erythematous patch of alopecia. He had two erythematous macules behind both ears. One cm mobile, nontender lymph nodes were noted in the right posterior auricular and right anterior cervical areas. His heart had a 2/6 systolic murmur at the left sternal border that did not radiate. S1 and S2 were normal. Capillary refill time was brisk, and distal pulses were 2+ in all extremities. His abdomen was soft and nondistended. His liver protruded approximately 2 cm below the R costal margin. Cranial nerves were intact, as was sensation. Muscle strength was symmetric and 3/5 in neck flexion and upper and lower extremities proximally, and 4/5 distally. He complained of bilateral arm pain and could not extend his arms at the shoulder joint beyond parallel to the ground when lifting his hands away from his body in the lateral plane. He had difficulty standing up from a low seat. Deep tendon reflexes were 1+ symmetrically. He walked with a wide-based, hobbling gait.

Review of laboratory results from his primary doctor's office showed that lyme titers, ANA, C-reactive protein and rheumatoid factor were normal. EBV antibodies and antigen as well as parvovirus antibodies were elevated. AST was elevated at 124, ALT was elevated at 85, and CK was elevated at 1800. 

Initial hospital laboratory evaluation yielded an elevated ANA titer, at 160, with a speckled pattern. Anti-double stranded DNA testing was negative. C3, C4, CH50 levels were within normal limits. The AST and ALT were elevated at 238 and 100, respectively.  LDH level was increased at 1842. Creatine kinase was elevated at 2,228. Aldolase level also was elevated. Lead level was normal. His thyroid stimulating hormone level was normal at 2.62. Computed tomography of his head and magnetic resonance imaging studies of his brain and spine were all normal, as was cerebral spinal fluid analysis.

Hospital course and treatment

The patient had significant proximal weakness of bilateral upper and lower extremities. Laboratory results were consistent with myositis. His skin findings were felt to be nonspecific.

Muscle biopsy was obtained, and microscopic examination of the frozen tissue showed deposition of C5b9 (membrane attack complex) on multiple small intramuscular capillaries, some in a perifascicular pattern, coupled with characteristic staining pattern on ULEX stain, and increased B-cell populations. These results confirmed a diagnosis of juvenile dermatomyositis. Intravenous methylprednisolone was administered for three days prior to discharge.

At the time of discharge the patient was able to ambulate, but still remained significantly weak. He was discharged home on prednisolone and methotrexate, with plans to return to rheumatology clinic for follow-up.

Discussion

The differential diagnosis of progressive proximal weakness includes dermatomyositis,  polymyositis, toxin ingestion, paraneoplastic syndrome, guillan-barre syndrome, late-presenting mitochondrial disorder, CNS tumor or CNS infection. With a normal MRI of the brain and spine, normal CSF and a negative toxicology screen, a muscle biopsy was required to make the diagnosis of juvenile dermatomyositis in this patient.

Juvenile dermatomyositis, although the most common of the pediatric inflammatory myopathy, still is relatively uncommon, with an incidence of approximately three cases per million children. Most children report a history of infection in the preceeding months before disease onset, often upper respiratory or gastrointestinal symptoms. Coxsackie virus B and group A streptococcus are frequently identified pathogens associated with disease onset or flares.

Nearly three-quarters of affected patients are white, and twice as many girls as boys are diagnosed. The average age of disease onset is approximately 7 years, with one-quarter of children affected at less than 4 years of age. There is some association with familial autoimmune disease. Pathogenesis is related to tumor necrosis factor activation and increased natural killer cell activity leading to cytotoxicosis.

Clinical manifestations include progressive proximal weakness, dermatologic manifestations, fever and respiratory symptoms in children less than 6 years of age, and arthritis, dysphagia, headaches and musculoskeletal complaints in older children.  Dermatologic manifestations may include: 1) heliotropic (violet) rash in the periorbital, malar or nasal bridge areas, 2) edema of the periorbital area or scalp, occasionally with alopecia, 3) Gottron papules (palpable, erythematous lesious over the metacarpal and proximal interphalangeal joints), and 4) capillary looping at the nailfolds with periungual avascularity. Proximal weakness begins insidiously, and often is not recognized until it has progressed to the point where it is difficult to climb stairs, comb hair, raise head from bed, transfer in or out of bed, chair or car. A Gowers sign may be noted, as the child is required to "walk hands upward" along their lower body in order to rise from a seated position. Inflamed muscles often are tender to palpation. Signs of dangerous progression include dysphagia, hoarseness or difficulty handling secretions. Other manifestations may be gastrointestinal (constipation, diarrhea, abdominal pai or bleeding), cardiac (conduction abnormality or dilated cardiomyopathy) or orthopedic (osteopenia and increased fracture risk) in nature.

Laboratory findings often include elevated levels of muscle-derived enzymes, such as creatine kinase, aldolase and lactate dehydrogenase. Antinuclear antibody with speckled pattern can be present in more than half of patients, while anti-double stranded DNA is negative. Erythrocyte sedimentation rate is usually normal. 

When significant weakness is present, prompt intervention with high-dose intravenous methylprednisolone may be effective and should be continued until symptoms improve and inflammatory indicators (vWf:Ag, neopterin, and CD19 B cell percentage) normalize. Methotrexate and cycophosphamide are sometimes used when inadequate response occurs with steroids. Physical and occupational therapy provide passive stretching early in the disease course and later direct reconditioning of muscles to regain strength and range of motion. Weight bearing improves bone density.

Prior to corticosteroid use, one-third of patients died and another one-third were permanently disabled, but mortality now is approximately 1 percent. Children with dermatomyositis appear able to repair their vascular or muscular damage. Prognosis for this disease has improved significantly recently with aggressive immunosuppression and monitoring of inflammation.

References

Miller, Marc L. "Clinical Manifestations of Juvenile Dermatomyositis and Polymyositis," UpToDate online® Version 15.2, 2007.

Miller, Marc L. "Treatment of Juvenile Dermatomyositis and Polymyositis," UpToDate online® Version 15.2, 2007.

Pachman, Lauren M. "Juvenile Dermatomyositis," in Nelson's Textbook of Pediatrics, 17^th ed. Edited by Behrman, R, Kliegman, R, and Jenson, H. 2004;149:813-816.

Brian Branchford, MD, is a pediatric resident at Children's Hospital of Wisconsin.
Michael Weisgerber, MD, is a hospitalist at Children's Hospital, an assistant professor of Pediatrics (Hospitalist Medicine) at the Medical College of Wisconsin and a member of Children's Specialty Group.
Jennifer Freeto, MD, is a pediatric hospitalist at Children's Hospital, an assistant professor of Pediatrics (Hospitalist Medicine) at the Medical College and a member of Children's Specialty Group.

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