In this case report, we describe the clinical features, paraclinical findings, and treatment response to various immunosuppressive agents in a patient diagnosed with Anti-SRP myopathy. Anti-SRP myopathy is a subtype of immune-mediated necrotizing myopathy (IMNM), characterized histopathologically by muscle fiber necrosis at different stages, scattered distribution, sparse lymphocytic infiltration, and deposition of C5b-9 membrane attack complexes on the sarcolemma [1,4]. This is a rare disease, first described in 2004, accounts for approximately 3–6% of patients with IIM. According to the 2017 EULAR/ACR classification criteria, Anti-SRP autoantibodies are not included, and IIM is divided into four major subgroups: polymyositis, dermatomyositis, amyopathic dermatomyositis, and inclusion body myositis. IMNM is not classified as a separate entity but is instead included under polymyositis, which is problematic due to the distinct histopathology of IMNM compared to polymyositis. A study by Shogo Komaki et al on the clinical features of IMNM indicated that approximately 20% of Anti-SRP myopathy patients are not classified as autoimmune myositis based on the EULAR/ACR 2017 criteria [5]. These findings highlight the diagnostic challenges clinicians face when identifying and diagnosing Anti-SRP myopathy. Indeed, before a definitive diagnosis was made, our patient had been experiencing leg weakness since March 2022, but was initially diagnosed with compression neuropathy due to uterine fibroids and underwent surgery. Furthermore, when applying the EULAR/ACR 2017 criteria, the patient’s total score was 5.8, classifying the case only as probable IIM, due to the lack of Anti-SRP autoantibody in the criteria. Recognizing IMNM as a distinct disease entity, the European Neuromuscular Centre (ENMC) issued diagnostic guidelines in 2018 with three main criteria: elevated muscle enzymes, proximal muscle weakness, and positive anti-SRP antibodies [1]. Our patient met the ENMC diagnostic criteria.

Our female patient presented with progressive proximal lower limb muscle weakness over 3 years, impaired activities of daily living, elevated muscle enzymes, and thigh muscle atrophy developing within only 7 months after disease onset. Throughout the disease, the patient did not experience fever or signs of infection. Regarding her medical history, she had not used any medications affecting muscle function over the past 3 years, did not consume alcohol, and had no exposure to toxins. Paraclinical investigations, including lumbar MRI, excluded spinal cord and lumbar root pathology. Electromyography of the lower limbs showed no peripheral neuropathy. Electrolyte levels, thyroid function tests, and blood glucose were all within normal limits. Autoimmune tests revealed a high positivity for anti-SRP antibodies. Therefore, the clinical and paraclinical features of our case are consistent with those reported in the literature [1,2]. Anti-SRP myopathy is more common in women than in men (with a 3:1 ratio) and typically affects middle-aged individuals. These patients usually present with rapid, symmetrical proximal muscle weakness, severe muscle pain, significantly elevated muscle enzymes, and ultimately muscle atrophy and disability if not treated promptly. Furthermore, these patients tend to recover poorly, with only half achieving near-normal or full muscle strength after 4 years of immunosuppressive therapy. Approximately 19% of patients with Anti-SRP myopathy develop pulmonary involvement on chest CT, primarily exhibiting a non-specific interstitial pneumonia (NSIP) pattern [6,7]. While most of these cases present with mild to moderate symptoms and slow disease progression, this patient cohort frequently experiences a higher incidence of interstitial lung disease and respiratory failure compared to those with Anti-HMG-CR myopathy [6]. This is particularly true when diagnosis and initiation of immunosuppressive therapy are delayed. For our patient, the extended duration of the diagnostic workup and the subsequent delay in treatment initiation directly contributed to the rapid development of exertional dyspnea and significant lung lesions on chest CT within merely four months of a definitive diagnosis. Therefore, Anti-SRP myopathy remains one of the most debilitating autoimmune myopathies, which underscores the importance of early diagnosis and intervention.

In this case, muscle biopsy of the proximal lower limbs was not performed due to the patient concerns about potential complications. It is important to note that while histopathological findings can be suggestive, they are not entirely specific for anti-SRP myopathy [1,3]

In our patient, treatment was initiated with a combination of prednisolone (1 mg/kg) and methotrexate, starting at 10 mg/week and increasing to 15 mg/week due to the severity and rapid progression of muscle weakness. Subsequently, the treatment regimen was switched to mycophenolate mofetil and cyclophosphamide (5 cycles), respectively, as there was no improvement in muscle strength, mobility, and muscle enzyme levels continued to rise. The challenges in treating Anti-SRP myopathy have been documented in other reports [8,9]. In a study of 100 patients in Japan, half of the patients were refractory to treatment, and the other half relapsed when corticosteroid or conventional immunosuppressive doses were reduced. Since Anti-SRP myopathy is a rare disease, there have been no randomized controlled trials conducted to date, and no official treatment guidelines exist for Anti-SRP myopathy.

However, there has been increasing interest in the role of B lymphocytes, given the success of Rituximab, a monoclonal antibody targeting CD20 on B cells, in treating refractory autoimmune diseases [4]. Rituximab initiates B cell lysis through complement activation and antibody-dependent cell-mediated cytotoxicity. Furthermore, several features of Anti-SRP myopathy suggest a role for humoral immunity in its pathogenesis, including deposition of membrane attack complexes on sarcolemma and small blood vessels in muscle fascicles, non-inflammatory small vessel damage, and the correlation between autoantibody levels and disease activity. These findings imply that humoral immune responses, with B cells as the primary cellular component, play a significant role in the disease's pathogenesis. Indeed, in a case series by Ritu Valiyil et al, eight patients with Anti-SRP myopathy who did not respond to initial treatment with corticosteroids and conventional immunosuppressive agents showed significant improvement in muscle strength and enzyme levels following rituximab infusion [10]. In our case, after discussion with the patient and obtaining consent, rituximab was administered in combination with corticosteroid pulse therapy, given over two cycles, 2 weeks apart. The follow-up visit revealed significant clinical improvement (in muscle strength and HAQ-DI score) and a decrease in muscle enzyme levels (Figure 2).