The coexistence of systemic lupus erythematosus (SLE) and muscle‑specific tyrosine kinase (MuSK) antibody‑positive myasthenia gravis (MG) is extremely rare, with no previous reports available. This overlapping condition often causes diagnostic confusion, especially in distinguishing primary autoimmune MG from hydroxychloroquine (HCQ)‑related myopathy or myasthenia. In addition, long‑term glucocorticoid use complicates therapeutic management due to comorbidities such as osteopenia. This study aims to present the clinical features, diagnosis, treatment and follow‑up outcomes of a unique patient with SLE, secondary Sjögren’s syndrome (SS) and MuSK‑MG, and to explore rational immunotherapeutic strategies for this rare overlap syndrome.

We present a case report of a 42-year-old female patient with a 5-year history of autoimmune disease. She was initially diagnosed with undifferentiated connective tissue disease, and later fulfilled the 2019 EULAR/ACR classification criteria for systemic lupus erythematosus (SLE). During follow-up, she developed fluctuating ptosis, diplopia, dysphagia and neck weakness. Combined with electrophysiological examination and positive anti-MuSK antibody, she was diagnosed with MuSK-positive myasthenia gravis (MG). Clinical and serological evaluations, including QMG, MG-ADL, SLEDAI-2K and ESSDAI scores, were performed to assess disease activity and therapeutic response. The clinical course, diagnosis, treatment and follow-up outcomes were systematically summarized and analyzed.

When MuSK‑MG was first diagnosed approximately five months before admission, the patient was classified as MGFA Class IIb, with a baseline QMG score of 11 and MG‑ADL score of 4, indicating prominent bulbar and ocular impairment. At admission, systemic disease activity was relatively low. The patient had xerostomia lasting more than three months, myalgia, abdominal distension, and approximately 10 kg weight loss. Laboratory evaluation showed low C4, trace proteinuria with normal 24‑hour urine protein. SLEDAI‑2K was 2 and ESSDAI was 1, consistent with mild disease activity of SLE and secondary SS. The patient received 500 mg intravenous rituximab with initial clinical improvement, followed by a second 500 mg dose one month later, with a third dose planned at six months. HCQ and MMF were maintained at stable doses throughout treatment, and prednisone was kept at 22.5 mg/day at discharge. At the two‑month follow‑up, all MuSK‑MG symptoms resolved completely, with QMG and MG‑ADL scores decreasing to 0. SLEDAI‑2K and ESSDAI scores also fell to 0, indicating remission of both SLE and SS. Prednisone was successfully tapered to 15 mg/day, with planned gradual reduction to a maintenance dose of 5 mg/day. Notably, myasthenic remission was achieved despite ongoing HCQ treatment, effectively excluding HCQ‑induced myasthenia. No severe adverse events related to rituximab were observed.

The concurrent presentation of SLE, secondary SS, and MuSK‑MG is an extremely rare autoimmune overlap phenotype with no prior reported cases. For SLE patients with new‑onset fluctuating ocular or bulbar weakness, especially with negative AChR antibodies, anti‑MuSK antibody testing should be performed promptly to avoid misdiagnosis as drug‑induced myopathy. This case confirms that MuSK‑MG in this setting represents an independent autoimmune process rather than a complication of HCQ. Low‑dose rituximab provides rapid and sustained remission of both neuromuscular and systemic autoimmunity via B‑cell depletion, enables effective glucocorticoid tapering, and allows continuation of HCQ without exacerbating myasthenia. This regimen represents a mechanistically rational and clinically valuable steroid‑sparing strategy for this challenging overlap syndrome.