Additional Investigations After the Muscle Biopsy Diagnosis

The patient’s serum angiotensin-converting enzyme (ACE) level was normal. Computerized tomography (CT) of the chest, abdomen, and pelvis was unremarkable.

Final Diagnosis

Isolated granulomatous myositis.

Patient Follow-up

The patient was started on Prednisone 60 mg once daily. She also underwent physical therapy. Two months after the treatment, she showed improvement in her muscle strength. The dose of Prednisone was gradually tapered down to 20 mg once daily. She tolerated the treatment well. One year after the treatment, she only showed mild stable weakness in the wrist and finger extensors (4/5) and intrinsic hand muscles (4+/5). She was subsequently followed by her local neurologist.

Discussion

Granulomatous myositis is a rare muscle biopsy diagnosis. In a large series of 2,985 muscle biopsies, only 12 (0.4%) showed granulomatous inflammation [1]. Although muscle granulomas have been reported in association with many medical conditions , including sarcoidosis, infections, Crohn disease, lymphoma, thymoma, graft-versus-host-disease, anti-PD-1 therapy and others, the condition can be present in isolation [1–12]. It is most commonly seen in association with systemic sarcoidosis followed by idiopathic with no causes identified [1, 13].

Muscle involvement is not uncommon in systemic sarcoidosis; however, it is mostly asymptomatic with muscle granulomas found in autopsy or random muscle biopsy [14]. Patients with symptomatic muscle involvement can present with palpable muscle nodules, acute myositis, or much more commonly chronic myopathy [5, 14, 15]. Chronic myopathy caused by sarcoidosis usually has symptom onset after 50 years of age with a female predominance. The disease manifests symmetrical, proximal, lower limb weakness. With time, some patients may develop weakness in the upper limbs and distal limb muscles, and some patients may also have dysphagia [5, 8, 16]. The clinical presentation of our patient is seemingly different. The initial symptoms in our patient were mainly distal with foot drop and finger and wrist drop. She developed mild weakness in the deltoid muscles late in the course. Her muscle involvement was more broad and severe in the upper limbs than in the lower limbs. This pattern is mostly seen in isolated granulomatous myositis [5, 8].

Due to the rarity of granulomatous myositis, there has been no large-scale comparison study to fully characterize the clinical features of sarcoid chronic myopathy and isolated granulomatous myositis. Only a few retrospective small series studies have been published [5, 8]. It is not entirely clear whether isolated granulomatous myositis is a distinct entity or a special presentation of sarcoidosis. At present, the diagnosis of isolated granulomatous myositis is made based on the clinical presentation, the presence of granulomatous myositis on muscle biopsy, and the absence of identifiable causes especially the symptoms and findings of systemic sarcoidosis. Sarcoidosis is an immune-mediated multiorgan disorder of unknown cause. It typically involves lungs, skin, lymph nodes, eyes, and parotid glands. Nervous system involvement is uncommon, and symptomatic muscle involvement is exceedingly rare [17, 18]. The diagnosis is established by imaging studies and tissue pathology. Given the common involvement of mediastinal lymph nodes and lungs, chest CT is important in the diagnostic evaluation. Serum ACE level can be elevated, but it is neither sensitive nor specific [19]. Gallium 67 scan is not as sensitive as fluorodeoxyglucose positron emission tomography (FDG-PET) in detecting occult systemic disease [20]. Our patient did not have any symptoms or signs to suggest systemic sarcoidosis. Her CT scan of the chest, abdomen, and pelvis did not reveal abnormalities in other organs, although she did not have gallium 67 scan or FDG-PET scan. Given her clinical presentation, granulomatous myositis shown on her muscle biopsy, and lack of symptoms, signs or CT findings of other organ involvement, the diagnosis for her was isolated granulomatous myositis.

It has been shown that isolated granulomatous myositis and sarcoid chronic myopathy are not different in age at onset, serum CK, EMG, or muscle biopsy findings [5, 8]. Both are late-onset, predominantly affecting people above 50 years of age. Both have normal or mildly elevated serum CK levels. EMG in both mostly shows irritable myopathic changes in the affected muscles. Muscle biopsies in both reveal non-caseating granulomas in endomysium or perimysium with epithelioid histiocytes mixed with T lymphocytes. Multinucleated giant cells may also be present. Our patient had all these features. Due to the late disease onset, prominent distal limb involvement, and additional proximal limb involvement at a late stage, isolated granulomatous myositis can mimic sporadic inclusion body myositis (sIBM) [21] or motor neuropathy. sIBM predominantly affects knee extensors and finger flexors. Our patient shows prominant wrist, finger and foot drop but no significant weakness in the finger flexors or knee extensors, which is atypical for sIBM. EMG is important for differentiating a myopathic condition from a neurogenic condition. Muscle biopsy is essential for establishing the diagnosis of granulomatous myositis. Muscle biopsy in sIBM usually does not show granulomas but shows a constellation of endomysial inflammation, red-rimmed vacuole, tubulofilamentous inclusions, and increased number of COX-deficient fibers. Our patient’s muscle biopsy did not show these features.

There are no controlled studies to guide the treatment of isolated granulomatous myositis or sarcoid chronic myopathy. According to the anecdotal reports [5, 8], the first-line treatment is oral Prednisone, and the treatment response is mixed. Adding a chronic immunosuppressant or immune modulating therapy is usually ineffective. But in general, isolated granulomatous myositis is milder with little disability.

Pearls