1 Introduction

Polymyositis (PM) is an established subgroup of Idiopathic inflammatory myopathies (IIMs) which usually manifest as muscular weakness and soreness in proximal limbs. PM had inflammatory cell infiltration between muscular tissues which would be related to immunopathogenic pathways[1]. Rhabdomyolysis (RML) is a rare complication of PM which has exactly similar clinical manifestation except potential severe kidney damage. The patient also has a history of strenuous exercise. In this study, we present a patient who was diagnosed with RML secondary to PM clinically.

2 Case Report

A 26-year-old female, with one month history of muscle discomfort and progressive oliguria, was admitted to the intensive care unit (ICU) of the second hospital of Anhui medical university. The patient had been in good health before the onset of this disease. The medical history demonstrated that the patient had a history of vigorous exercise (slimnastics) 1 month ago. One week after exercise, this patient has been suffered from progressive muscle weakness and pain. What is more, 2 weeks later, she began to have a fever.

On admission to our hospital, her temperature was 38.4 ℃, the pulse was 133 beats per minute, the blood pressure was145/82 mmHg, and the respiratory rate was18 breaths per minute. Physical examination revealed severe non-pitting peripheral edema with no apparent skin lesions. The breath sounds of both were coarse, and moist rales would be heard. On the Medical Research Council scale, the motility of her limbs was significantly decreased, the proximal and distal muscle were 0/5 and 1/5, respectively. The knee and Achilles tendon reflexes were weak, and the pathological signs were negative. Her consciousness was clear, but her spirit was not good. Laboratory studies showed that white blood cell count (14.17 × 109/L) was high with the neutrophil predominance of 88.8%. Levels of C-reactive protein (89.9 mg/L) and procalcitonin (1.330 ng/mL) were elevated, and the serum creatinine (134 µmol/L) and myoglobin levels (>4140ngm/L) were unnormal. The muscle enzymes were abnormally elevated, especially creatine kinase (143,250 U/L). A urine test revealed red blood cell (2+) and protein (3+) levels. Her basic immunological tests were normal and had no relevant family history of autoimmune disease. In addition, except for antinuclear antibodies (titer 1:320, speckled pattern), the results of rheumatic immunological test were negative. The computed tomography scan (CT scan) showed a flaky high-density plot area with an air bronchogram in the lower lobes of both lungs; the changes of pulmonary interstitium were not obvious (Fig. 1).

Fig. 1
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The patient’s CT

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She was diagnosed with rhabdomyolysis (RML), a systemic myopathy affecting striated muscles throughout the body. As the urine output of this patient decreased, and creatinine index increased, the patient was considered acute kidney injury (AKI). Therefore, continuous renal replacement therapy (CRRT) was started immediately to maintain the fluid output state (CVVDHF mode), and low molecular weight heparin sodium was used for anticoagulation. Hemoperfusion (HP) therapy was also performed to eliminate myoglobin to minimize kidney injury. In addition, combined with the blood culture of another hospital showing Staphylococcus saprophyticus, we immediately gave her an anti-infective medication (linezolid) when she arrived at our hospital. However, the temperature of this patient remained elevated. Candida albicans were found in urine but not in blood. After adjusting the anti-infective medication to cefoperazone sulbactam and fluconazole, her temperature gradually stabilized.

However, the treatment of regular therapy has little effect on this patient. The improvement of the patient's renal function, peripheral edema, and muscular strength was not obvious (CK 25,890 U/L; Cr 101 μmol/L). We examined other possible causes of her disorder, especially autoimmune diseases, which can be similar in clinical manifestation. The result of the antinuclear antibodies test was positive on admission. Based on this finding, the patient received intravenous methylprednisolone at 80 mg daily on hospital day 8. The diagnosis of polymyositis (PM) was confirmed 2 days after hormone therapy for Myositis Autoantibody had positive results (NXP2+++) and no special cutaneous involvement. Though electromyogram (EGM) and muscle biopsy were not tested, the symptoms of the patient, antibodies test results, and the effective diagnostic treatments all together confirmed the diagnosis of PM. In addition to CRRT and HP, plasma exchange (PE) and double filtration plasmapheresis (DFPP) were used to remove many autoantibodies, complements, immune complexes and inflammatory factors. Simultaneously, the hormone dosage, the treatment course, and the occurrence of adverse reactions were reduced. The patient’s physical condition and spirit improved gradually after those adjustments, and muscle enzymes reexamined were significantly lower than those on admission (ALT 92 U/L, AST 251 U/L, LDH 738 U/L, CK 2486 U/L, CK-MB 80 U/L).

On hospital day 17, the patient's tachypnea worsened abruptly, labored breathing developed, and the temperature elevated. Tracheal intubation was performed and high-dose methylprednisolone pulse treatment (800 mg/day) was used. Considering the frequency of pulmonary interstitial involvement in patients with NXP2 antibody inflammatory myopathy and her state, we applied for a bedside chest X-ray (Fig. 2), which showed increased bilateral lung markings without significant parenchymal lesions. In addition, in combination with the patient's tumor markers and chest CT on admission, no abnormal space-occupying lesions in the lung were found. Thus, we thought the greater worsening of respiratory symptoms might be related to the increased muscle weakness of the respiratory muscles and the marked edema of the face and neck. Three days later, methylprednisolone was changed to the dose of 80 mg/day for 1 month and a half, then followed by oral dexamethasone for a week. After discontinuing dexamethasone, she maintained oral prednisone daily and adjusted dose to control symptoms. Four intravenous tocilizumab during the late hospital stay for consolidation therapy (on day 24, day 51, day 77 and day 89 since admission, single dose of 320 mg) (Fig. 3). In light of a sputum culture that revealed candida tropicalis and gram-positive cocci infection, we quickly changed antibiotics to meropenem and carpofunnet acetate. On hospital day 31, the patient accepted tracheotomy to prevent further pulmonary infection. Sputum culture and bronchoalveolar lavage showed multi-drug resistant Klebsiella pneumonia many times in the late stage of ICU treatment. The drug sensitivity test results show that the original antibiotics could cover the pathogenic bacteria. What is more, we added fluconazole for the preventive treatment of antifungal.

Fig. 2
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The patient’s X-ray

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Fig. 3
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The patient’s therapy of PM

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The patient's temperature and inflammatory index levels decreased steadily, the respiratory muscle strength improved gradually, the lung lesions were absorbed significantly, and the tracheotomy was extubated safely 32 days later. The patient's renal function recovered 43 days after receiving intermittent CRRT therapy and she was transferred to the general ward for treatment 56 days later. Her muscle enzymes roughly recovered to normal (ALT 48 U/L, AST 39 U/L, LDH 529 U/L, CK 113 U/L) and the muscle strength of the limbs was improved 4 months later. She was discharged to a rehab facility and her condition remained stable during the follow-up.

3 Discussion

PM is an autoimmune disorder characterized by non-pyogenic inflammatory changes with lymphocytic infiltration. The lesions of non-pyogenic inflammation occur in the proximal limbs and patients usually manifest as muscular weakness and soreness. Most cases have subacute or chronic onset. Bohan et al. [2] proposed objective diagnostic criteria for PM (Table 1) in 1975. Patients with this disorder rarely suffer from AKI but often manifest as chronic glomerulonephritis with normal renal function. However, this patient progressed to anuria from brown urine 1 week before admission and her renal function indexes were abnormal (Cr 134 µmol/L; BUN 13.25 mmol/L). What is more, her MYO and CK were elevated extremely (MYO >4140 ng/mL; CK 25,890 U/L), which are not common features of PM. Muscle biopsy and EMG could not be carried out subject to her physical condition, and the positive rate of autoantibody is not significant. Therefore, those patients' symptoms did not clearly point to PM.

Table 1 Objective criteria of polymyositis
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RML relates to a skeletal muscle cell damage, which results in the release of toxic intracellular substances into the systemic circulation, usually manifested as a triad of muscle weakness, muscle pain, and brown urine. Serum creatine phosphokinase elevates five times, higher than the limit of normal levels (>1000 U/L), used for the diagnosis of RML. Kidney injury is common in patients with RML. It is reported that AKI occurred in about 13%­50% of patients with RML, and the proportion goes up as high as 81.4% in severe cases [3,4,5]. The mechanisms may be related to renal vasoconstriction, direct myoglobin toxicity, and intraluminal cast formation [6,7,8,9,10]. All of these characteristics are consistent with this patient's presentation.

RML commonly occurs in the large muscle groups of the thigh, pelvis or paraspinal region, which progresses more rapidly. Serum CK returns to normal over days or weeks after fluid therapy and urine alkalinization. Patients with RML could have renal involvement due to nephrotoxic substances and serum CK level could predict acute renal failure (ARF). In a study, when serum CK was greater than 15,000 IU/L, the quantification of the risk of ARF increased to 70% [11]. Unlike RML, PM has a slow progression and high serum CK does not decrease until specific treatment. Specific treatments comprehensively include glucocorticoids, immunosuppressants, immunoglobulin, even biological agents. Except serum CK, as MRI is sensitive to soft tissue, magnetic resonance imaging (MRI) is another significant diagnostic technique. Type 1 RML mainly refers to exertional RML, the homogeneous signal on T1-weighted, T2-weighted, and STIR images caused by muscle edema is similar to the one in myositis. However, there is the heterogeneous signal in type 2 RML and "stipple sign" are seen in the affected muscle's focus edge related to direct trauma, vascular obstruction, drug or alcoholism [12, 13]. Limited by the patient's own conditions, MRI was not performed. However, given the ineffectiveness of standard RML treatment and the likelihood of primary PM, we administered methylprednisolone as a diagnostic treatment, and the patient's overall health gradually improved after hormone therapy. In the past, it was always thought that myositis was a rare etiology of RML. Recent research about idiopathic inflammatory myopathies (IIMs) suggests that about one-fifth of patients have RML [14]. A research evaluated 475 patients with RML demonstrated that 21 patients were diagnosed with PM in 27 patients with IIMs [15]. Therefore, it is important to maintain a high suspicion of inflammatory myopathies in a patient with typical clinical features.

To date, 21 cases (14 males and 7 females) of PM with RML were able to be retrieved on PubMed, CNKI, and WanFang Date (Table 2). The average age was 47.57 years (22–73). All patients received hormone therapy, most of them used methylprednisolone at the initial dose of 1 mg/(kg day). There were 6 patients have had a poor response to glucocorticoid, they were treated combined with immunosuppressants such as methotrexate and azathioprine. Four patients were treated combined with immunoglobulin (IVIG). Research showed that in a trial with 35 patients with PM, treatment with IVIG was associated with a significant clinical improvement in 70% patients [16]. One refractory myositis was combined with infliximab, a monoclonal antibody to CD20, to reduce CK levels and improve lung function. Biological agents such as infliximab and rituximab (RTX) have emerged as a novel treatment option [17]. All patients accepted aggressive fluid management to prevent the deterioration of renal function. In 11 patients who developed renal impairment, 9 patients accepted dialysis and most of them improved steadily. However, a patient died of renal failure after abandoning dialysis.

Table 2 literature review
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PM complicated with RML is a rare disorder. All probable etiologies should be considered when diagnosing RML. It is irrational to diagnose exertional RML based solely on a clinical history of strenuous exercise without a differential diagnosis. Auto-immune disorders must be considered in the etiology of non-traumatic rhabdomyolysis. In RML, serum CK falls to normal within days to weeks, whereas in myositis, serum CK remains high until special treatment is initiated. On the other hand, PM patients with extremely high serum CK, RML and AKI must be highly guarded. Early detection of serum MYO, the monitor of urine volume, routine urine, renal function, and electrolytes can help avoid the missed diagnosis of RML. Otherwise, patients' conditions may be delayed due to a misdiagnosis. EMG, muscle biopsy, and myositis antibodies should all be tested if the hospital and patients' conditions allow. The management of PM complicated with RML focuses on treating the protopathy and supporting the renal function. It is critical to utilize glucocorticoids to normalize serum muscle enzymes, and severe cases can be combined with immunosuppressants or immunoglobulin. Biotherapy, PE and DFPP can be considered in refractory myositis. In terms of conventional treatment, maintain the electrolyte and acid–base balance through prompt and aggressive fluid management in conjunction with urine alkalization. Studies have shown that up to 78% of patients with idiopathic inflammatory myopathy (IIM) were found to have interstitial lung disease [39]. It is necessary to be alert to interstitial lung disease for patients with rapid respiratory deterioration. Doctors should monitor oxygen saturation and oxygenation index during treatment, regularly reexamine HRCT and perform pulmonary function tests for differential diagnosis if conditions permit. In addition, Hill et al. showed a standardized incidence ratio of tumors is 1.3 in patients with PM. Recent epidemiology also showed that patients with IIM have a higher risk of malignancy than the general population, especially in the first year after diagnosis [40,41,42]. Patients with anti-NXP2, anti-TIF1 or anti-SAE should be paid a special attention [43]. Routine cancer screening should be widely carried out in the first year of confirmation, and long-term follow-up for latent malignancies should be carried out after discharge.

4 Conclusion

This case reports the clinical symptoms, diagnosis, therapy and follow-up highlights of PM complicated with RML. The disease diagnosis is determined mainly by typical clinical manifestations, biochemical criteria, and special examination of muscles. Importantly, we conclude that this disorder should take the comprehensive measure. It is necessary to make physicians recognize this disease and provide appropriate treatment immediately to improve the prognosis and survival rates.