Anti-SRP immune-mediated necrotizing myopathy from childhood to adulthood: A case series highlighting rituximab-responsive disease

Abstract

Objectives

Anti-signal recognition particle (SRP) myositis is a rare subset of immune-mediated necrotizing myopathy (IMNM). It is characterized by proximal muscle weakness, markedly elevated serum creatine kinase (CK) levels, and poor response to conventional therapies. Evidence for optimal management remains limited, particularly regarding the long-term outcomes of rituximab treatment.

Method

We retrospectively reviewed anti-SRP myositis patients who received rituximab at Seoul National University Hospital. Diagnosis was based on clinical features, elevated CK levels, and positivity for anti-SRP antibodies. Demographic, clinical, laboratory, radiological, histopathological, and treatment data were collected.

Results

Five patients, aged between 4 and 71 years, exhibited proximal muscle weakness, elevated CK levels, and variable disease severity. Rituximab induction followed by maintenance therapy led to a significant improvement in muscle strength and normalization of CK and aldolase levels. In patients with mild or subclinical phenotypes, aldolase elevations often preceded clinical relapses. Relapses during follow-up were managed with rituximab re-administration, which restored muscle strength and biochemical markers. MRI, EMG, and muscle biopsy findings were consistent with myopathic changes.

Conclusions

This case series highlights the heterogeneity in age, disease severity, and clinical course of anti-SRP myositis and the efficacy of rituximab in refractory and relapsing cases. Multimodal monitoring, including CK, aldolase, CD19+ B-cell counts, and clinical assessment, is essential for the early detection of relapses. Our findings support rituximab as a valuable component of individualized treatment strategies for anti-SRP myositis, though larger studies are warranted to establish standardized protocols and clarify long-term outcomes.

Highlights

• • Wide clinical diversity and onset ages emphasize the need for suspicion and screening of anti-SRP antibody

• • Rituximab induction and maintenance therapy provide effective disease control for refractory anti-SRP myositis

• • CK, aldolase, CD19+ B-cell counts, and clinical monitoring is essential for early detection of relapse

Introduction

Idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of immune-mediated diseases primarily affecting skeletal muscle, with potential involvement of the skin and lungs. Advances in clinicopathological understanding and autoantibody profiling have led to a refined classification of IIMs. The classification framework has been a subject of ongoing debate and continues to evolve. While multiple classification frameworks have been proposed, a broadly used approach recognizes several major subtypes including dermatomyositis, polymyositis, immune-mediated necrotizing myopathy (IMNM), inclusion body myositis, and overlap myositis. Notably, anti-synthetase syndrome (ASyS) is increasingly recognized as a distinct clinical entity within the IIM spectrum, characterized by the presence of anti-aminoacyl-tRNA synthetase antibodies and a constellation of features including myositis, interstitial lung disease, arthritis, and mechanic’s hands.^1,2 Autoantibody profiles play a key role in defining the IIM subsets. Myositis-specific autoantibodies (MSAs), such as anti-Mi-2 or anti-SRP, are highly distinctive for IIMs, while myositis-associated autoantibodies (MAAs), such as anti-Ro52 or anti-Ku, are commonly shared across systemic autoimmune diseases. Anti-SRP antibodies were discovered in 1986, and newer autoantibodies are still being found, with the latest anti-tRNA synthetase antibodies discovered in 2023. ³ These profiles guide not only diagnosis, but also prognosis and therapeutic strategies. ⁴

IMNM is characterized by rapid-onset, symmetrical proximal muscle weakness, markedly elevated serum creatine kinase (CK) levels, and poor response to steroids alone, often necessitating early and aggressive immunosuppressive therapy.^4–6 Three serologic subgroups of IMNM are recognized; anti-SRP-associated, anti-HMGCR-associated, and seronegative IMNM. ⁵ Anti-SRP myositis is a distinct IMNM form and accounts for approximately 2-39% of clinically diagnosed myositis cases, although the prevalence varies widely by clinical or histological criteria.^7–10

Patients with anti-SRP myositis generally demonstrate limited responses to standard therapies for inflammatory myopathies.^5–7,11 Although combination immunotherapy has shown potential benefits, clinical evidence remains insufficient, and no standardized treatment protocols are currently available. Therefore, additional data on treatment strategies and outcomes are required to better inform clinical practice. Here, we describe the disease course of five patients diagnosed with anti-SRP myositis and report the outcomes of the treatment strategies.

Methods

Patients with anti-SRP myositis who visited Seoul National University Hospital between 2020 and 2025 were identified through two complementary approaches. First, we reviewed patients in whom anti-SRP antibody positivity had been confirmed by a research-based myositis-specific antibody (MSA) assay covering 17 autoantibodies. Second, to ensure that no eligible patients were missed, we performed a systematic search of the hospital Clinical Data Warehouse (CDW) for patients who had undergone the institutionally established MSA panel, which was introduced during the study period and covers 11 autoantibodies. The diagnosis of anti-SRP myositis was based on clinical features, elevated CK levels, and positivity for anti-SRP antibodies. The MSA panel has been available for use in our hospital since 2020.

Demographic, clinical and laboratory data, including age at symptom onset, presenting symptoms, manual muscle testing (MMT) grades based on the Medical Research Council (MRC) muscle power scale, serum CK, and aldolase, were collected and reviewed longitudinally. Muscle magnetic resonance imaging (MRI), muscle biopsy, and electromyography (EMG) data were analyzed when available. Relapse was defined as a decline of one or more scale in the MRC scale from the previously maintained level, or any regression in activities of daily living. Subclinical relapse was defined as a two-fold or greater increase in laboratory markers from baseline in the absence of measurable decline in MRC scale. This study was approved by the Institutional Review Board (IRB) of Seoul National University Hospital (IRB Nos. 2004-042-1116 and 1101-110-353).

Serum samples were tested for MSAs and MAAs, including autoantibodies for Mi-2α, Mi-2β, TIF1γ, MDA5, NXP2, SAE1, Ku, PM-Scl100, PM-Scl75, Jo-1, SRP, PL-7, PL-12, EJ, OJ, and Ro-52, using a line immunoassay (EUROIMMUN kit) according to the manufacturer’s instructions. Positivity was determined based on the EUROLineScan signal intensity, which was categorized as follows: 0–5, negative; 6–10, borderline; 11–25, positive (+); 26–50, positive (++); and greater than 50, strong positive (+++). Patients with “+” or stronger results were considered positive for the respective autoantibodies.

Skeletal muscle biopsies, performed in line with diagnosis journey, specifically from the vastus lateralis, were obtained from the available patients. Immunohistochemical analyses to assess immunological features and inflammatory infiltrates were performed in available specimen, using antibodies against CD4, CD8, CD56, C5b-9, and p62 proteins.

Results

The research-based assay identified five patients with confirmed anti-SRP myositis, all of whom were included in this case series. The complementary CDW search of patients tested with the institutional MSA panel retrieved six patients, of whom two overlapped with the research-based cohort, yielding four additional candidates. Thus, a total of nine patients with anti-SRP myositis were identified at our institution during the study period.

The four additional patients identified through the CDW search were excluded for the following reasons: three had insufficient follow-up or received rituximab before the diagnosis of anti-SRP myositis, and one did not receive rituximab. Consequenctly, the final study cohort comprised five patients with research-confirmed anti-SRP myositis, all of whom received rituximab and had adequate follow-up. The clinical course and treatment history of all five patients are summarized in the Supplementary Table.

Case 1 – Subacute onset with rapid progression

A 53-year-old woman presented with a 4-month history of myalgia and developed rapidly progressive proximal muscle weakness within one month. Initial CK and aldolase levels were markedly elevated, exceeding 6,000 IU/L and 80.6 U/L, respectively (Figure 1). Muscle biopsy revealed features of immune-mediated necrotizing myopathy, including necrosis of myofibers, degenerating and regenerating myofibers with minimal inflammatory cell infiltration, size variation of myofibers and characteristic fine granular pattern in sarcoplasm with p62 positivity and staining of CD56 in regenerating myofibers (Figure 2). A gene panel for myopathies was negative at the referring hospital. At our clinic, she became unable to climb the stairs within a month. Considering the subacute and rapid progressive course, inflammatory myopathy was considered more likely. An MSA and MAA panel revealed the presence of anti-SRP (+++) and anti-Ro52 (+++) antibodies. Prior to the identification of anti-SRP antibody positivity, the patient had received high-dose intravenous methylprednisolone at the referring hospital. Following the confirmation of anti-SRP antibody, intravenous immunoglobulin (IVIG) therapy was initiated, resulting in modest clinical improvement. Subsequently, she received rituximab loading, 1g twice with 2-week interval, followed by maintenance rituximab every 6 months in combination with oral prednisone 5mg daily, which stabilized her CK and aldolase levels and preserved muscle strength. Six months after initiating therapy, CK and aldolase levels decreased significantly, with muscle strength improving to MRC grade IV+ (Figure 1).

Figure 1.

Timeline (in months) of patients 1 to 5 with CK, aldolase, B cell recovery, medications and relapses.

Figure 2.

Muscle biopsy of patient 1. (A) Hematoxylin and eosin-stained sections showing degeneration of myofibers (black arrowheads) and regeneration (black arrows). (B) Muscle fibers show prominent size variation (asterisks) without significant lymphocytic inflammation (pauci-immune). (C) CD56 (neural cell adhesion molecule) staining showing regenerating multinucleated myofibers (purple arrow). (D) p62 staining (brown) showing a fine granular pattern in the sarcoplasm. (E, F) Electron microscopy showing disrupted myofibrillar structure (red arrowhead) and autophagosome vacuoles (red arrows).

Twenty-eight months after the transfer, oral mycophenolate mofetil was introduced, allowing rituximab dosing intervals to be extended beyond every 6 months. By the time of the fifth maintenance infusion, her hip and shoulder girdle muscles had improved to grade V. Despite continued low-dose prednisone 2.5mg daily and mycophenolate 500mg twice daily, serial laboratory tests demonstrated a rising trend in CK and aldolase levels. In the context of persistent enzyme elevation accompanied by difficulty climbing up stairs, a seventh cycle of rituximab was administered, after which both enzyme levels and CD19+ B cells, which are known to produce antibodies, declined again (Figure 1).

Case 2 – Subacute onset with rapid progression

A 71-year-old woman presented with rapidly progressive muscle weakness. Her initial symptoms included myalgia and chronic fatigue, but within weeks, her proximal strength declined to grade II. Muscle MRI showed signal changes in the rectus femoris and vastus muscles in the anterior compartment, adductor magnus in the medial compartment, gluteus maximus (not shown), and biceps long head in the posterior compartment (Figure 3(A) and Table 1). EMG demonstrated myopathic changes, characterized by low amplitude polyphasic motor unit action potentials (MUAPs) without denervation potentials. Respiratory muscle involvement led to respiratory failure and intensive care unit (ICU) admission and she received tracheostomy. Her initial CK level exceeded 10,000 IU/L. First‐line high‐dose corticosteroids and IVIG failed to produce meaningful improvement, so plasma exchange was performed, followed by a second IVIG course. This lowered CK to two-fold and aldolase to the normal range, but only partial improvement in strength, reaching MRC grade III, was achieved. Following the transfer to our center, co-positivity for anti-SRP antibody and anti-Ro52, both at an intensity of +++, was identified, and she received a loading dose of rituximab infusions, 1g twice in 2-week interval. A month after rituximab loading, the patient was able to breathe, feed, and move independently. Six months later, her motor strength recovered to grade IV, and both CK and aldolase levels normalized. Rituximab infusions of 1g were administered every 6 months, and after the second maintenance dose, her strength further improved to grade V.

Figure 3.

Fat-suppressed protocol of thigh MRIs in patient 2 (A) and patient 5 (B) showing fat infiltration and atrophy of the rectus femoris (yellow arrowhead) in the anterior compartment and adductor magnus (red arrowhead) in the medial compartment.

Table 1.

Involved muscles detected with lower extremity MRI.

​	Time interval between symptom onset to MRI (months)	Anterior compartment	Medial compartment	Posterior compartment
Patient 1	5	Sartorius (proximal) Rectus femoris Vastus muscles	Obturator externus/internus Adductor longus Adductor brevis Adductor magnus* Gracilis (proximal)	Gluteus maximus Biceps femoris long head Semimembranosus*(short head, semitendinosus relatively preserved) Soleus Gastrocnemius
Patient 2	3	Sartorius Rectus femoris* Vastus muscles	Adductor magnus*	Gluteus maximus Biceps femoris long head Semimembranosus (short head, semitendinosus preserved) Posterior compartment of lower leg (excluding gastrocnemius)
Patient 3	4	Rectus femoris	Obturator externus/internus Adductor magnus (left) Gracilis (left)	Gluteus maximus (left) Biceps femoris short head
Patient 4	31	-	-	-
Patient 5	16	Sartorius (proximal) Rectus femoris*	Adductor longus Adductor brevis Adductor magnus* Gracilis	Gluteus maximus Biceps femoris* long head, short head Semimembranosus* Semitendinosus*

*The muscles highlighted in bold represent those consistently affected in all patients, showing signal changes. Muscle involvement indicates edema unless otherwise specified; muscles with fatty infiltration are explicitly denoted with an asterisk (*).

During the subsequent two years of rituximab maintenance, her CK and aldolase levels remained within normal limits, and her muscle strength was sustained at grade V. Therefore, rituximab was discontinued. However, both enzyme levels showed a gradual increase, and by month 45, this coincided with a decline in muscle strength to grade IV. Therefore, a fifth rituximab maintenance dose was administered. CK and aldolase levels peaked and declined to normal by month 50, with muscle strength returning to grade V (Figure 1). The patient was identified as an HBV carrier on pre-treatment screening, and prophylactic antiviral therapy was administered throughout the course of rituximab treatment; HBV reactivation did not occur.

Case 3 – Subacute progressive course

A 44-year-old woman presented with chronic fatigue, lower-extremity weakness, and dysphagia. Four months prior to the visit, she experienced diffuse myalgia, easy fatigability and a transient skin rash lasting one week. Initial laboratory tests at another hospital showed markedly elevated CK and aldolase levels. A myopathy gene panel was negative. Neurological examination at our hospital revealed proximal muscle weakness of MRC grade IV. Muscle biopsy demonstrated p62 positivity, C5b-9 positivity, and MHC class I upregulation, findings consistent with immune-mediated necrotizing myopathy. Given the atypical presentation, an MSA and MAA panel was performed, which revealed anti-SRP (+++) and anti-Ro52 (+++) antibodies. She was treated with high-dose intravenous methylprednisolone 1g daily for three consecutive days, followed by oral prednisone tapering from 30mg daily to 10mg daily over 3 months; however, the clinical response was inadequate. Rituximab was administered as a loading dose of 1g twice at a 2-week interval. One month later, CK levels normalized and aldolase levels decreased. By six months, her muscle strength had improved from MRC grade IV to V, and both enzymes remained within the normal range. Mycophenolate mofetil was introduced to reduce the relapse risk, and she remained clinically stable thereafter.

Maintenance therapy with mycophenolate mofetil 500mg twice daily, along with gradual tapering of low-dose prednisone from 5mg to complete discontinuation was sufficient to preserve muscle strength, and no further rituximab cycles were required for the next 18 months of maintenance. However, serial measurements showed a mild and gradual rise in CK and aldolase levels beginning at 28 months. In response to this subclinical relapse, oral prednisone 5mg daily was re-initiated at 35 months, resulting in decreased enzyme levels without rituximab re-administration (Figure 1).

Case 4 – Episodic weakness and paralysis

A 29-year-old man presented with myalgia, recurrent transient paralysis and weakness for three months. Episodes of weakness occurred monthly, usually upon waking in the morning. The severity of the symptoms fluctuated, and both weakness and paralysis resolved spontaneously in a few days. His initial aldolase level was elevated, while CK level was normal. Extensive work-up—including gene panels for periodic paralysis, neuromuscular channelopathies, and hereditary myopathies—was unrevealing. Empirical treatment with muscle relaxant afloqualone for symptomatic control of stiffness and sodium channel blockers, often beneficial in periodic paralysis, did not result in meaningful improvement. After a prolonged diagnostic journey, including whole-exome and genome sequencing, no genetic cause was identified. However, an MSA and MAA panel revealed anti-SRP autoantibody positivity in the serum at an intensity of ++. Therefore, he received high-dose methylprednisolone 1g for three consecutive days as first-line immunotherapy, followed by loading doses of rituximab, 1g twice in 2-week interval. A month after rituximab loading, his subjective myalgia and proximal lower extremity weakness resolved. Oral immunosuppression with prednisone 5mg daily was maintained, and azathioprine 150mg daily was later added to allow steroid tapering. Six months after starting immunotherapy, his muscle strength gradually improved from MRC grade IV+ to V. Maintenance therapy with rituximab infusions every 6 months, along with daily prednisone 5mg daily and azathioprine 200mg daily, effectively sustained muscle strength, and aldolase levels were within the normal range, and rituximab was stopped after 2 years.

Despite ongoing treatment with prednisone and azathioprine, routine laboratory tests revealed normal CK levels but slightly increased aldolase levels along with clinical relapse presenting a decline in muscle strength to IV+ and myalgia at 48 months. Consequently, a fifth rituximab maintenance dose was given. By 51 months, both enzyme levels had decreased to the normal range, and his muscle strength was stable at grade V (Figure 1).

Case 5 – Chronic progressive course

A 4-year-old boy presented with progressive lower extremity weakness lasting approximately three months. One month after the initial evaluation, he experienced difficulty in elevating his arms. His symptoms rapidly progressed within months, with the development of dysarthria and neck flexion weakness. His CK level was increased to 30-fold, raising suspicion for inherited muscle diseases, including muscular dystrophy and myopathies. Multiple genetic evaluations, including Duchenne muscular dystrophy multiplex ligation-dependent probe amplification, and a targeted gene panel for limb-girdle muscular dystrophy, yielded negative results. Fourteen months after the first presentation, the patient had lost the ability to ambulate independently.

MRI of the lower extremities showed signal changes and atrophy in multiple muscle groups, including the rectus femoris, adductor magnus, and gluteus maximus (Figure 3(B)). Muscle biopsy findings showed prominent myofiber necrosis including degeneration and regeneration, size variation of muscle fibers, without infiltration of lymphocytes, raising suspicion of muscular dystrophy. EMG was indicative of a myopathic process.

Atypically early onset, rapidly deteriorating course, and early involvement of the upper extremities suggest an immune-mediated pathophysiology. Twenty-four months after initial presentation, anti-SRP antibody positivity was identified at an intensity of +++ in serum. Rituximab loading doses of 500mg administered twice at a 2-week interval resulted in a reduction of CK levels from ten-fold to 1.5-fold the upper limit of normal within two months. Although he remained unable to walk, a trial of IVIG subsequently led to improvements in his hand grip strength and head control. IVIG was administered every 1–2 months. At 60 and 80 months, the patient’s proximal muscle power remained poor (motor grade II in the upper and grade III in the lower extremities) with elevated aldolase level by 1.5-fold, prompting reloading of rituximab, which was later maintained every 6 months. Currently, 88 months after his initial presentation, the boy remains wheelchair bound with grade III muscle strength of upper extremities. His current regimen at age 12 includes prednisone 5mg daily, mycophenolate mofetil 250mg twice daily, and rituximab 500mg every 6 months (Figure 1).

Discussion

Our study illustrates the clinical heterogeneity of anti-SRP myositis, spanning from episodic mild weakness to life-threatening respiratory failure. The age of onset was equally diverse, ranging from 4 to 71 years. Pediatric anti-SRP myositis is rare,^12,13 and our study added a case of a 4-year-old child. All five patients in this series fulfilled the ENMC 2018 diagnostic criteria for seropositive IMNM, as each presented with proximal muscle weakness and elevated serum CK levels, with confirmed anti-SRP antibody positivity. Three female patients demonstrated concurrent anti-Ro52 positivity alongside anti-SRP antibodies, a finding that has been previously reported predominantly in East Asia, raising the possibility that this pattern may be ethnicity-related.^14–17 Further large-scale, multi-ethnic studies are warranted to determine whether concomitant antibodies are an ethnicity-specific phenomenon or a more universal feature of the disease. Of the 5 patients, three underwent muscle biopsy as part of diagnostic workup, all of which demonstrated diffuse myofiber necrosis and regeneration. Additionally, four who underwent EMG showed signal changes indicating myopathy. Notably, 80% of our cohort was initially suspected of having genetic myopathy, and various genetic evaluations were prescribed, resulting in negative findings. As prompt suspicion of IMNM and prescription of MSA panels are the key to shortening the time needed for diagnosis, thus leaving more muscle mass for recovery,^9,18 we want to highlight the suspicion of IMNM in patients with features of limb-girdle muscular dystrophy.^6,7,9

A key observation in our patients was the pivotal role of rituximab treatment. Induction therapy with rituximab led to decreased CK levels and improved muscle strength in all patients. Patients continued maintenance therapy with rituximab at intervals ranging from 6 months to 1 year, except for patient 3, who received mycophenolate mofetil as the primary immunotherapy. Rituximab has emerged as a valuable treatment option for anti-SRP myositis, particularly in patients with refractory disease or frequent relapses. In Patient 5, the time lag between symptom onset and rituximab initiation likely contributed to incomplete muscle power recovery, as prolonged disease activity may have resulted in irreversible structural muscle damage prior to the commencement of effective immunotherapy. According to the 224th ENMC International Workshop, glucocorticoids remain the mainstay of initial therapy, but early addition—either simultaneously or within one month—of a second-line immunosuppressant such as methotrexate or rituximab is strongly recommended to prevent long-term disability. ⁶ The initial steroid regimen consisted of high-dose intravenous methylprednisolone (1 g/day or 30mg/kg/day for 3 to 5 consecutive days), followed by oral corticosteroid tapering over approximately 1 to 3 months to a maintenance dose of 2.5–10 mg/day, depending on the clinical response. Rituximab can be administered as 1 g on days 1 and 14 as loading doses, with further cycles of maintenance repeated every 6 months for 2 years. Regarding adverse events, none of our patients experienced severe infections or other significant complications attributable to rituximab during the treatment course. Prophylactic vaccination was not considered prior to rituximab administration, ¹⁹ because delaying treatment for this purpose in patients with subacute or rapidly progressive muscle weakness does not appear to be a clinically reasonable decision.

Data from multiple cohort studies support this finding. In a US cohort of 37 patients with 380 clinic visits, rituximab administration was associated with strength improvement, but symptoms tended to recur after 6–9 months, consistent with the expected biological duration of B cell depletion. ¹¹ Notably, among the 17 evaluable patients treated with rituximab, 13 demonstrated a positive response, although the duration of the effect varied significantly, with some requiring frequent re-administration, while others remained stable for over two years. A Brazilian cohort of 14 patients also reported favorable responses to rituximab in refractory cases, with improvements in strength and biochemical markers, allowing the reduction or discontinuation of steroids and other immunosuppressants. ²⁰ High relapse rates (70%) during glucocorticoid tapering or reduction of immunosuppressants justify the use of rituximab. Similarly, recent Chinese data revealed 25% of patients experienced relapses when immunotherapy was tapered or discontinued, indicating that ongoing immunosuppression may be necessary to maintain disease control. ²¹ Together, these findings suggest that rituximab offers an effective option for relapse control and long-term disease suppression, particularly when used as part of an early and proactive treatment strategy.

Another important finding from our cohort is that aldolase levels appeared to reflect clinical relapses earlier than CK levels, particularly during episodes of worsening muscle weakness. Aldolase elevation consistently preceded or paralleled symptom aggravation in patients 3, 4, and 5, suggesting its potential role as a sensitive biomarker of disease activity. Previous studies have primarily focused on CK as a surrogate marker of muscle damage.^5,8,11 However, CK levels may not always parallel clinical severity, particularly in cases with active inflammation but minimal necrosis or in advanced atrophic stages. ²² In contrast, aldolase and transaminases have shown similar trends to CK but have consistently failed to reach statistical significance in previous studies. ¹¹ In our patients, transaminase levels frequently remained within the normal range despite significant CK elevation, and abnormal values were observed only when CK levels were markedly elevated, further supporting their limited sensitivity as markers of muscle disease activity in anti-SRP myopathy. In contrast, aldolase appeared to fluctuate in closer temporal association with clinical disease activity than CK in certain patients. However, we are unable to draw definitive conclusions regarding the relative superiority of aldolase over CK as a biomarker of disease activity, due to the small sample size and retrospective observational nature of this study. We present this as a preliminary observation that warrants further investigation in larger, prospective cohorts. These observations suggest that serial assessment of aldolase, alongside other monitoring parameters, may complement existing strategies for detecting subclinical or emerging disease activity, though further research is needed to clarify its role in multimodal monitoring approaches.^4,7

A notable finding of our study was one patient with only mild symptoms. Case 4 presented with myalgia and intermittent, spontaneously resolving episodes of paralysis. Notably, thigh muscle MRI revealed normal signal intensity, initially leading physicians to consider nonmuscular causes. However, the patient reported significant improvement in symptoms following immunotherapy. Similar cases have been reported in prior cohorts, where patients initially presented with isolated myalgia or exhibited minimal or no weakness at the onset.^7,11 In one case report, a patient initially experienced isolated finger weakness, which later progressed to both upper and lower extremities. ²² These observations align with the findings of a recent Japanese cohort study evaluating the performance of the EULAR/ACR classification criteria for IMNM. ¹ The study found that approximately 20% of anti-SRP patients fell into the “less than possible” category, failing to meet even the minimum probability threshold for IIM classification. Compared with patients in the “possible” or “definite” categories, the “less than possible” group had milder clinical presentations, lower serum CK and aldolase levels, and subtler abnormalities on muscle biopsy. Despite these differences, MRI and EMG findings were not significantly different, suggesting that tissue-level or electrophysiological involvement may precede overt clinical deterioration. The authors proposed that such patients may have been captured early in the course. These findings highlight the importance of clinical follow-up in patients presenting with myalgia and normal or mildly elevated CK levels, with particular attention to the early signs of proximal muscle weakness. Patient education is crucial to ensure timely reassessment in the event of progressive weakness.

Prolonged surveillance remains important in anti-SRP myositis, even after achieving clinical stability following two years of rituximab maintenance. In line with current recommendations, we attempted to discontinue rituximab in patients of well-controlled disease after two years. ⁶ However, during subsequent follow-up, the patients exhibited signs of relapse, including muscle weakness, elevated serum aldolase and/or CK levels, and increase in circulating CD19+ B-cell counts. In these instances, rituximab was re-administered to preserve muscle strength and prevent further functional decline. Additionally, this is the first case series to confirm the efficacy of rituximab in an Asian population. The patients in this series exhibited a wide range of clinical manifestations, highlighting the diverse spectrum of symptoms associated with anti-SRP myositis. Notably, all patients demonstrated a positive response to rituximab treatment.

MRI of the lower extremities shows high sensitivity in detecting signal changes and locating lesions, with limitations in specifying disease entities among various IIMs. ² All four patients with MRI signal changes in the muscles were observed in the rectus femoris, adductor magnus, and gluteus maximus. The sartorius, vastus, biceps long head, and semimembranosus were also commonly affected in our patients. Comparing thigh MRIs between patients with IMNM and other IIMs, more extensive and severe muscle edema (reflecting active inflammation), fatty replacement, and muscle atrophy were observed. ²³ The posterior thigh muscles and adductors of the medial thigh were affected in patients with IMNM, whereas patients with DM had predominant lesions in the anterior thigh.^4,24 Interestingly, rectus femoris involvement was observed in all patients except Patient 4, whose near-normal MRI findings were likely attributable to early imaging performed prior to the development of significant muscle edema. Whether rectus femoris involvement represents a characteristic feature of anti-SRP myopathy remains to be determined, and further studies with larger patient cohorts are needed.

Muscle biopsy is not necessary for diagnosis but can be helpful in some cases. The hallmark histological feature is scattered myofiber necrosis with regeneration, often without significant lymphocytic infiltration.^2,25 Necrotic fibers are typically distributed across different stages, while regenerating fibers are abundant and widely distributed. Biomarkers of regeneration, such as CD56 (neural cell adhesion molecule) and neonatal myosin, may aid in histological evaluation. Notably, the pattern of fine granular sarcoplasmic staining of p62 is a distinctive feature of IMNM, different from the coarse vacuolar staining of subsarcolemmal or perinuclear regions seen in IBM. ²⁶ C5b-9 deposition appears in a granular pattern on the sarcolemma but not in the perifascicular areas, unlike dermatomyositis.^4,6 A study by Zhao et al. showed characteristic expression of BAFF receptors and CD19 in patients with anti-SRP myositis, which was higher in refractory patients. ²⁷ The application of specialized staining techniques, including C5b-9, MHC class I, and p62 immunohistochemistry, may provide further diagnostic clarity and potentially support earlier diagnosis in some patients. ²⁸ Therefore, a more systematic approach to muscle biopsy incorporating these specialized staining protocols could enhance diagnostic precision in anti-SRP myopathy. Although the types of existing antibodies show different histological features, ²⁶ they are not sufficient to diagnose subtypes. ⁶ Thus, muscle MRI, EMG, and biopsy can guide the diagnosis of IIM, but serologic evidence of antibodies is critical for prognosis and identifying associated diseases. ²

Although this case series provides valuable clinical insights, there are certain limitations that must be acknowledged. First, the small sample size of five patients limits the generalizability of the findings, which should be interpreted with caution. Moreover, as our institution serves as a tertiary referral center, some patients had received initial treatment at outside hospitals prior to transfer, resulting in variability in corticosteroid regimens, concomitant immunosuppressive therapies, and timing of rituximab initiation across cases, which may have influenced the individual responses to rituximab. The potential impact of prior treatment should be considered when interpreting these outcomes. As high-dose corticosteroids, IVIG, and rituximab were initiated in close succession due to insufficient response, it is difficult to attribute the clinical improvement to any single agent, given that this aggressive combination approach was employed with the goal of achieving best outcomes in a rapidly progressive disease. Finally, the quantification of anti-SRP antibody levels was not performed, and the changes in antibody levels following rituximab treatment were not assessed. Monitoring anti-SRP antibody levels may provide valuable information regarding disease activity and response to treatment. Further research is warranted to determine the optimal treatment approach for individual patients based on their specific clinical characteristics.

In conclusion, this case series contributes to the understanding of anti-SRP myositis and highlights rituximab as a treatment option for refractory or relapsing cases. The diverse clinical manifestations observed emphasize the heterogeneity of the disease. Given that anti-SRP myositis is a treatable condition, it should be actively considered, and antibody testing should be performed in a broader range of patients presenting with unexplained myopathy. Further research with larger sample sizes and long-term follow-up is needed to confirm these findings and to optimize treatment strategies for patients with anti-SRP myositis.

ORCID iDs

Seon-Jae Ahn https://orcid.org/0000-0003-0520-7812

Jee Min Kim https://orcid.org/0000-0003-1583-2224

Seungbok Lee https://orcid.org/0000-0002-3145-8714

Narae Kim https://orcid.org/0000-0001-9173-922X

Hye Jin Yoo https://orcid.org/0000-0002-9704-7870

Eun Na Kim https://orcid.org/0000-0003-2992-7881

Jae-Kyung Won https://orcid.org/0000-0003-1459-8093

Jangsup Moon https://orcid.org/0000-0003-1282-4528