Introduction
Knowledge about Idiopathic Inflammatory Myopathies (IIM) has significantly increased in recent years. The IIM subtypes such as inclusion body myositis, dermatomyositis and polymyositis are now relatively well-characterized. Over the past decade, the entity of Immune-Mediated Necrotizing Myopathy (IMNM) has also been recognized as a distinct form of IIM [1], which is characterized by relatively severe proximal weakness, myofiber necrosis with minimal inflammatory cell infiltrate on muscle biopsy, and infrequent extra-muscular involvement [2]. Clinical features of acute or progressive onset, symmetrical proximal limb weakness, Creatine Kinase (CK) elevation, and myopathic change in electromyography and histopathology may be characterized by muscle fiber necrosis and regeneration, as well as lymphocyte infiltration of individual in histopathologic exam [3]. 
So far, two different autoantibodies have been described in IMNM patients: those targeting 3hydroxy-3-methylglutaryl-CoA reductase (HMGCR) and those targeting Signal-Recognition Particle (SRP), and their role in IMNM pathogenesis is the subject of ongoing research [1]. In this study. we report a rare case of necrotizing myopathy with increased Creatine Phosphokinase (CPK) and positive SRP.

Case Presentation
The case was a 67-year-old male patient referred to Firozgar hospital affiliated to the Iran University of Medical Science, Tehran, Iran in June 2018 with a main complaint of pain in proximal lower extremities. Eight months before admission, the proximal lower extremity pain without progression had been seen, which developed to distal lower extremity weakness later, and gradually progressed to proximal weakness after six months. Lower extremity weakness was on the left side. In physical examination, according to Medical Research Council Scale for muscle strength, the motor function of proximal upper extremities, the distal of upper extremities, the proximal of lower extremities, and the distal of lower extremities were 4/5, 5/5, 3/5, 4/5, respectively. Deep tendon reflex of extremities was +1 with downward two-sided plantar reflex. Sensory examination result was normal and Gower’s sign was positive which is associated with the weakness of proximal muscles of lower extremities. The posture was normal, but gait was waddling.

Lab data
The patient’s laboratory findings are presented in Table 1.

After admission, serological markers such as anti-SRP autoantibodies were evlauated which was positive.

Muscle biopsy
Open muscle biopsy was performed after freezing of the muscle using isopentane cooled in liquid nitrogen. The myopathic atrophy with multiple necrotic and many degenerative/regenerative fibers was associated with mild endomysial fibrosis, and no inflammation were found. After muscle biopsy, tumor marker tests, paraneoplastic panel, SRP, JO1, MF2, and β-Hydroxy β-methylglutaryl-CoA reductase were measured. 

Nerve conduction study and electromyography
According early recruitment with small polyphasic motor unit action potential with spontaneous activity in biceps and deltoid muscles and also in lower limbs muscles, the patient’s electrodiagnosis was compatible with proximal>distal polymyopathy with denervating feature (irritative).

Treatment
Two gram per kg Intravenous Immunoglobulin (IVIG) was administrated after diagnosis of IMNM. Prednisone 50 mg/day orally, calcium vitamin D daily, pantoprazole 40 mg/day, physiotherapy, and occupational therapy were administrated after discharge.

Discussion
The IMNM is rare; therefore, clinical trials are very difficult to conduct in patients with IMNM. In this rgeard, case reports are very important to unveil the effects of potential new treatments [4]. The current study used the European NeuroMuscular Centre criteria for diagnosing IMNM [5]. The hallmark feature of patients with IMNM is the presence of proximal muscle weakness. In Malartre et al.’s study, it was shown that IMNM patients have more severe muscle weakness predominantly affecting the lower limbs [6]. This is consistent with the current study. In Yamada et al.’s study, a 40-year-old man with a 3-month history of progressive weakness of four limbs were presented. In examinations, the weakness of hip abductor was marked. During walking, shoulder sway was noted as compensation for hip abductor weakness. Blood tests showed a marked elevation of CK level and the presence of SRP antibodies. They suggested that physicians should consider the possibility of anti-SRP antibody-positive myopathy in patients with hip abductor weakness in a subacute onset [7].
Diagnosis of IMNM is based on the clinical features and muscle biopsy. Other parameters such as CK level are often more than 10 times above the normal level at the time of the onset of muscle weakness. Magnetic resonance imaging may show diffuse or patchy edema within muscles [8]. In our case report, it was not seen. As mentioned in Allenbach et al.’s study, anti-HMGCR and anti-SRP myositis-specific autoantibodies are crucial for defining IMNM when muscle biopsy is absent [9]. Abusharar et al. presented a patient with IMNM secondary to simvastatin use. The patient had proximal myopathy, dysphagia, and elevated CK levels, and was subsequently found to have anti-HMGCR autoantibodies with a necrotizing process on muscle biopsy. The patient was further complicated by sequelae of multiple disease processes, ultimately leading to deterioration of the patient health [10]. In current study, the patient had no such problems after 2 year of follow-up. 
Benveniste et al. showed that the level of anti-SRP antibodies is correlated with disease activity, suggesting a pathogenic role for these autoantibodies [11]. In Shelly et al.’s study, of six patients tested for IMNM antibodies, only one patient had anti-SRP positive [12]. Therefore, we can divide IMNM to three sub-categoreis of anti-SRP-positive, anti-HMGCR-positive, and seronegative IMNM. The discovery of specific autoantibodies, increased understanding of the risk factors and clinical characteristics, treatment options, and development of novel classification criteria are significant advances in understanding IMNM.

Conclusion
Reporting a case of anti-SRP associated IMNM and its related pathophysiology, diagnosis and treatment options can help increase the physicians’ knowledge of this rare and debilitating condition.

Ethical Considerations
Compliance with ethical guidelines
All study procedures were in compliance with the ethical guidelines of the Declaration of Helsinki, 2013.

Funding
This research did not receive any grant from funding agencies in the public, commercial, or non-profit sectors.

Authors' contributions
Investigation: Seyed Mohammad Masoud Hojati, Payam Saadat; Writing-original draft: All authors; Writing-review & editing: Payam Saadat, Shayan Alijanpour.

Conflict of interest
The authors declared no conflict of interest. 

Acknowledgements
The authors thank the Clinical Research Development Unit of Rouhani Hospital.


References

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