In January 2018 a 43-year-old woman presented with progressive back pain, limb stiffness, painful spasms, and gait impairment. Neurological examination showed increased tone in knee and ankle muscles, brisk reflexes, preserved strength without fatigable weakness, and normal sensory testing. Serum anti-GAD65 antibodies were positive at a dilution of 1:100 while cerebrospinal fluid testing was negative. Needle EMG demonstrated continuous motor unit activity (CMUA) in agonist and antagonist lower-limb muscles with superimposed stimulus-triggered bursts; these abnormal discharges were abolished by diazepam.
Routine laboratory and broad autoantibody panels were unremarkable or negative. The patient met established clinical and electrophysiological criteria for stiff person syndrome (SPS) and improved after treatment with IVIG, high-dose methylprednisolone and an oral steroid taper, plus symptomatic agents (clonazepam, eperisone). After corticosteroid discontinuation she relapsed in August 2018 and again improved with IVIG and prednisolone.
In March 2022 the patient developed fluctuating limb weakness and intermittent ptosis, initially noted after COVID-19 vaccination. By October 2022 examination revealed fatigable ocular and limb weakness. Serology showed markedly positive anti-acetylcholine receptor (anti-AChR) antibodies (29 nmol/L) and positive anti-titin antibodies. Repetitive nerve stimulation produced a significant decremental response consistent with a postsynaptic neuromuscular transmission defect, establishing a diagnosis of myasthenia gravis (MG).
Chest CT identified an anterior mediastinal mass. Pyridostigmine and two sessions of plasma exchange produced symptomatic improvement (MG-ADL from 7 to 2; QMG from 16 to 8). The patient underwent thymectomy; histopathology confirmed a WHO type B2 thymoma.
Postoperative radiotherapy was completed in February 2023. Later that month the patient contracted SARS-CoV-2 infection and subsequently developed worsening fatigue, severe ptosis, generalized weakness, and progressive respiratory failure without recurrence of SPS pain or stiffness. In March 2023 she presented in myasthenic crisis (MGFA class V), requiring non-invasive ventilation and ICU care. At that time MG-ADL was 16 and QMG 28; anti-AChR titer had risen to 55.28 nmol/L.
During the myasthenic crisis the patient received two additional plasma exchanges, a course of IVIG (0.4 g/kg/day for 5 days), and high-dose intravenous methylprednisolone (1 g/day for 3 days) with gradual tapering, but clinical response was inadequate. Given infectious complications and concern for immunosuppression risks, low-dose rituximab was administered (100 mg and 500 mg on consecutive days), yet the patient’s respiratory symptoms and limb weakness persisted.
Because conventional immunotherapies failed to produce satisfactory improvement, treatment with efgartigimod (an FcRn inhibitor) was started on April 15, 2023 at 10 mg/kg weekly for four consecutive weeks.
The patient experienced marked improvement in respiratory function and muscle strength after efgartigimod induction, allowing discontinuation of ventilatory support and restoration of independent ambulation. Clinical scores improved after the first cycle: MG-ADL decreased from 16 to 7 and QMG from 28 to 15. Laboratory changes included a reduction in total serum IgG to 4 g/L and a decline in anti-AChR titer to 26.21 nmol/L. By July 2023 she reached minimal symptom expression (MSE) with MG-ADL 0 and QMG 3.
Based on induction tolerability and clinical benefit, an off-label maintenance approach was adopted beginning July 10, 2024 (efgartigimod 10 mg/kg every two weeks). During follow-up through December 2025 there were no further MG exacerbations, myasthenic crises, or recurrence of SPS-related stiffness and pain. Serum anti-GAD65 antibodies became undetectable while anti-AChR antibodies remained positive (29.6 nmol/L in November 2024).
This case describes sequential onset of SPS with low-titer anti-GAD65 and later anti-AChR-positive MG associated with WHO type B2 thymoma, supporting the concept that thymic pathology may contribute to broader autoimmune dysregulation. The report highlights several points:
Thymoma has been reported in a substantial proportion of previously described SPS–MG overlap cases, suggesting disrupted central tolerance and generation of multiple autoreactive clones as plausible mechanisms.
The patient’s low serum anti-GAD65 titer (1:100) is below typical diagnostic thresholds and was not corroborated by CSF; nonetheless, the combination of clinical SPS features, thymoma, and later anti-AChR-positive MG indicates multi-system autoimmunity.
Environmental triggers may have influenced disease course: onset of MG symptoms followed COVID-19 vaccination and myasthenic crisis followed SARS-CoV-2 infection, consistent with a potential two-hit model of peripheral immune activation on a background of thymoma-related tolerance defects.
Therapeutically, this report documents a rapid and substantial clinical response to efgartigimod after failure of plasma exchange, IVIG, high-dose steroids, and rituximab. As an FcRn inhibitor, efgartigimod selectively reduces circulating IgG and plausibly lowers pathogenic autoantibody levels, which correlated here with clinical improvement. This is the first reported use of periodic efgartigimod in a patient with overlapping SPS and MG and thymoma in this case series; further studies are needed to define safety, optimal dosing, and long-term outcomes in larger cohorts.
Clinicians should maintain long-term vigilance for thymic pathology and the emergence of additional autoimmune neurological disorders in patients with SPS. In cases of thymoma-associated, treatment-refractory MG—particularly when standard therapies fail—FcRn inhibition with efgartigimod may be considered as a therapeutic option, recognizing that evidence beyond this case is limited. Multidisciplinary management and sustained follow-up are essential to monitor disease activity, treatment response, and evolution of autoantibody profiles.