CHICAGO—A slate of pediatric rheumatologists recounted a series of interesting cases, ranging from a teenage track athlete with mysterious fatigue to a young adult with worsening headache, memory changes and a complex medical history, in ACR Convergence 2025’s Pediatric Thieves Market, in which the audience decided which case was most compelling.
All of the cases involved a winding road to diagnosis and left clinicians with important lessons to share in their presentations.
15-Year-Old Track Star
Drayton Harvey, PhD, a fourth-year medical student in the MD-PhD program at the University of Southern California, Los Angeles, and the California Institute of Technology, Pasadena, discussed the case of a 15-year-old track star who could run a 5.5-minute mile in the 1600-meter race. At a track meet, he’d only been able to jog and had been exhausted by the end. It was later learned he’d been having trouble keeping up with his family on a ski trip a few months earlier.
He was found to have a creatine kinase of 30,000 u/L (reference range: 10–205 u/L) and was hospitalized, then discharged after a week with a rhabdomyolysis diagnosis. But he was soon hospitalized again with worsening weakness. On a neuromuscular test, he was found to have mostly normal strength but was hyperreflexic. He had a positive Gower sign, a sign of weakness in the hips and thighs. A genetic panel was unremarkable, and he was sent home to rest and get additional work up as an outpatient.
After being unable to tie his shoes or get through a half day of school, he was hospitalized again. An expanded myositis panel was sent out, he was found to have oropharyngeal dysphagia that he was able to clear with throat clearing.
After a five-day steroid pulse, he regained strength and consistently met his occupational and physical therapy goals.
The results of the muscle biopsy showed scattered degenerating and regenerating fibers and few lymphocytes or spare macrophages on hematoxylin and eosin (H&E) staining; MHC-1 staining showed patchy sarcolemmal positivity; and he had positive LC3 staining.
The diagnosis was a rare case of immune-mediated necrotizing myositis (IMNM). Dr. Harvey said part of what made the case vexing was the lack of cutaneous abnormalities, which are often seen in IMNM. He said IMNM can get confused with limb girdle muscular dystrophy (MD) because MD can present in such a heterogeneous way.
“Most importantly,” Dr. Harvey said, “we sent an expanded myositis panel and that is about the only way for us to get antibody positivity in these cases. It’s not on your traditional, more narrow myositis panel.”
16-Year-Old Female with Ankle & Calf Pain
Another case, presented by Rachel Guess, MD, assistant professor of pediatrics, rheumatology and immunology at Washington University in St. Louis, involved a 16-year-old female who was active in sports and healthy who presented on a few visits with ankle pain, then calf pain. She then has severe left hip pain, for which she went to the emergency room.
Her inflammatory markers had steadily increased and her hemoglobin had decreased. When she got short of breath during a blood transfusion, she was admitted to the hospital, where she got a magnetic resonance imaging (MRI) scan.
The left-hip MRI showed two large, rim-enhancing, diffusion-restricting fluid collections in the muscles, which were favored to represent intramuscular abscesses. Extensive muscle and soft tissue inflammation was also seen.
The orthopedics team was able to drain fluid but the patient had hemoptysis, and she needed to be intubated and received a norepinephrine drip.
A chest computed tomography (CT) scan showed diffuse alveolar opacification, a rapid change from the chest X-ray two days before, with small right pleural effusion and small volume ascites.
She was negative on a variety of tests, including Blastomyces, leptospira, a heavy metals panel, anti-nuclear antibody (ANA) and antiphospholipid antibodies. But she was positive for anti-neutrophil cytoplasmic antibody (ANCA), specifically anti-proteinase 3 antibody. She was diagnosed with ANCA-associated vasculitis and granulomatosis with polyangiitis (GPA).
Necrotizing myositis is sometimes seen as a manifestation of GPA, but not a particularly high percentage of the time. A systematic review of 395 patients with muscle vasculitis found that GPA was seen in 19 of the patients and microscopic polyangiitis in 57 of the patients, for a total of about 19%.1
A muscle biopsy has been shown to be helpful, said Dr. Guess, whose case won the competition.
“This actually might be a path towards making the diagnosis, by a relatively low-risk biopsy,” she said. One study showed biopsy done without image guidance yielded a positivity rate of 58%.2
12-Year-Old Female with Multiple Joint Contractures
In another presentation, Johnson Nameirakpam, MD, of the Jawaharlal Nehru Institute of Medical Sciences in Manipur, India, discussed a 12-year-old female with multiple joint contractures and deformities, who had normal inflammatory markers. She had a history of fractures after seemingly trivial trauma.
On X-ray, she was found to have interosseous membrane and metaphyseal expansion of the arms, and hypertrophic callus, and, upon further testing, osteoporosis. Her father had similar contracture and was diagnosed with osteosarcoma.
On genetic testing, the girl was found to have a variant of the IFITm5 gene, which can cause osteogenesis imperfecta V, a disease in which bones are susceptible to easy fracture.
She was managed with zoledronate, calcium and vitamin D supplements.
Dr. Nameirakpam said the disease can mimic inflammatory arthritis, so caution is needed.
“So don’t go into your knee-jerk reflex of starting DMARDs [disease-modifying anti-rheumatic drugs] when we have some arthritis or arthritis-like picture,” he said.
19-Year-Old Male with a Worsening Headache
Rasha Elrefai, MD, a pediatric rheumatology fellow at Baylor College of Medicine, Houston, discussed a 19-year-old male with a worsening headache and vision and memory issues whose health challenges began early in life. He had Evans syndrome and recurrent infections at age 2; erythema nodosum and necrotizing granuloma on lymph node biopsy at age 3; enteritis, colitis, immune dysregulation and T cell lymphopenia at age 15; and panuveitis and bilateral cataracts at age 17.
A physical exam showed short stature, flexion deformities in both hands, an eczematous rash along the elbows and a right-sided visual field deficit. His inflammatory markers were elevated, with mild leukocytosis, as well as lymphopenia and thrombocytopenia.
A brain MRI showed left posterior circulation artery infarction, which was concerning for stroke. A CT angiography of the head showed chronic injury with encephalomalacia in the posterior inferior left parietal lobe.
He was positive for antiphospholipid antibodies and began to have clinical seizure episodes, and he was given triple antiepileptic therapy, Dr. Elrefai said.
After a rheumatology consult, hydroxychloroquine was started and his mycophenolate mofetil dosing was optimized.
He was found to have immunodeficiency 71 with inflammatory disease and congenital thrombocytopenia (IMD-71), a rare disorder caused by a mutation in the ARPC1B gene, which is critical for regulating the actin cytoskeleton in immune cells. Deficiency of this gene leads to impaired T cell and B cell function, Dr. Elrefai said. Hematopoietic stem cell transplant is considered feasible and effective for the condition, she said.
She said the disorder can initially resemble systemic lupus erythematosus.
“Molecular diagnostics,” Dr. Elrefai said, “are crucial for distinguishing monogenic immune dysregulation disorders from acquired or idiopathic autoimmune conditions, fundamentally altering treatment approaches.”
Thomas R. Collins is a freelance medical writer based in Florida.
References
- Conticini E, d’Alessandro M, Al Khayyat SG, et al. Inflammatory muscle involvement in systemic vasculitis: A systematic review. Autoimmun Rev. 2022 Mar;21(3):103029.
- Lacou M, Leroy M, Lan NL, et al. Muscle biopsy in anti-neutrophil cytoplasmic antibody-associated vasculitis: Diagnostic yield depends on anti-neutrophil cytoplasmic antibody type, sex and neutrophil count. Rheumatology (Oxford). 2021 Feb 1;60(2):699–707.