This is the second reported case of granulomatous myositis associated with sarcoidosis in a pediatric patient, and the first to present with a chief complaint of leg pain. While the histopathology results eventually confirmed the diagnosis, we first considered many other diagnoses given the unusual presentation of pain and inflammation localized to bilateral calves in a child.

The differential diagnosis for myositis in children includes rheumatic diseases (e.g. juvenile dermatomyositis/polymyositis, vasculitis, eosinophilic fasciitis, systemic lupus erythematosus, or IgG4-related disease), as well as infection, malignancy, paraneoplastic syndromes, and genetic, metabolic, neurologic, or toxic myopathies. Of all these conditions, only rare distal muscular dystrophies and inclusion body myositis are known to cause isolated lower leg myositis and inclusion body myositis is almost exclusively found in adults. When present in adults, symptomatic lower leg myositis is typically unilateral and involves the gastrocnemius, vastus lateralis, and adductor muscles [20, 21]. Systemic rheumatologic diseases such as juvenile dermatomyositis and polymyositis are often more proximal in nature, while vasculitis typically includes systemic symptoms and would be unlikely to cause regional muscle inflammation isolated to symmetric regions. Infectious myopathies are also unlikely to present in symmetric areas. Concern for IgG4-related disease was raised given her prior peri-orbital inflammation; however, staining of both biopsies excluded this. Her peri-orbital muscle inflammation and granulomatous myositis of her lower extremities also raised concern for granulomatosis with polyangiitis; however, she had no signs of vasculitis on histopathology, imaging, or exam and negative anti-neutrophil cytoplasmic antibodies [22]. Lastly, the intermittent nature of her flares over the years was unusual for any of these diagnoses - though given the degree of atrophy seen, it is likely that some inflammation persisted between presentations.

As demonstrated, a diagnosis of sarcoidosis requires consideration of a multitude of diagnoses. In these diagnostic dilemmas, a thorough laboratory evaluation must assess for signs of inflammation (CBC, ESR, CRP, IgG) and muscle injury (CK, LDH, AST, and aldolase). Unfortunately, results in this patient were non-specific and her significantly elevated IgG raised concern for monoclonal gammopathy or multiple myeloma initially, though SPEP was reassuring. While she did have a positive lupus anticoagulant, this finding has low specificity and she lacked other antiphospholipid antibodies, signs and/or symptoms of thrombosis, or markers of systemic lupus erythematosus. Ultimately, tissue biopsy was deemed necessary and led to a diagnosis of granulomatous myositis. While granulomatous myositis can be seen in the context of infections (such as tuberculosis), inflammatory bowel disease, vasculitis, malignancy, thymoma, and myasthenia gravis, [23] her presentation, negative staining for infectious pathogens, and lymphohistiocytic infiltrate with CD4 + T cell predominance confirmed the diagnosis of sarcoid myositis. With this knowledge, re-evaluation of her prior periorbital biopsy further supported a diagnosis of sarcoidosis.

There are 3 clinical patterns of sarcoid myositis reported in the literature: acute inflammatory myositis with myalgia (typically presents early on and in young patients), chronic myopathy with progressive weakness (typically presents late and is the most common pattern), and nodular myopathy with palpable muscle nodules. Our patient presented with acute inflammatory myositis with myalgia that progressed toward chronic myopathy. It is important to note that markers of sarcoidosis (angiotensin converting enzyme and lysozyme) are often negative in children. Additionally, markers of muscle inflammation may be normal in sarcoid myositis, as seen in our patient.

Interestingly, our patient had no other features of sarcoidosis, apart from elevated inflammatory markers and her histopathology, despite almost a decade of disease activity affecting various muscles. This is in contrast to the one previously reported pediatric case of sarcoid myositis in which a child presented at 16 years of age with hypercalcemia and renal insufficiency and was subsequently found to have non-caseating epithelioid granulomas and calcium oxalate crystals in her skeletal muscle after abnormalities were noted on exam and imaging [24].

Little is known about the optimal treatment of sarcoidosis in children, including sarcoid myositis. While sarcoidosis typically responds to glucocorticoids, the response of sarcoid myositis to glucocorticoids is unpredictable [7, 10, 12, 15, 25, 26]. Both our patient and the previously reported pediatric patient responded well to prednisone and methotrexate with relapse upon glucocorticoid withdrawal. The 16-year-old went into remission with the addition of adalimumab while our patient was lost to follow-up. There are reports of successful treatment of adults with sarcoid myositis with glucocorticoids [10, 27] with or without methotrexate [28] as well as other immune modulating agents, including TNF-antagonists.

In summary, sarcoid myositis is an underrecognized manifestation of sarcoidosis with very little known regarding its presentation and course in children. In this patient, sarcoid presented as bilateral lower leg myositis, a rare distribution of myositis that required a broad differential diagnosis and targeted work-up. This patient also fell into the rare subgroup of patients with symptomatic muscle involvement [12]. Further characterization of sarcoid myositis in children and its management will enhance care for children with this potentially devastating disease.