Case description
A 71-year-old male was admitted to tongji hospital, Tongji Medical College, Huazhong University of Science and Technology on April 9, 2022 and complained of chest tightness, wheezing, cough for more than 3 months. Biopsy and brushing were performed at the upper left lobar bronchial opening by electronic bronchoscopy on April 12, 2022. Histopathological diagnosis was small cell lung carcinoma. Immunohistochemistry showed that PCK (weak+), CK8/18 (weak+), CD56(+), Syn (partially weak+), CgA (partially weak+), INSM1 (partially+), NKX2.2 (partially weak+), SSTR2(-), TTF-1(-), RB1(+), CD20(-), CD20 (positive control(+), CD3 (2V6) (-), LCA(-), P53 (diffuse strong+, suggesting mutation), Ki-67(LI about 90%).
After the patient provided written informed consent, he received the first cycle of EP (etoposide, 100mg/m2, D1-D3 + nedaplatin, 80mg/m2, D1) regimen chemotherapy starting on April 20. On April 22, the patient developed chest tightness, weakness, wheezing, palpitation, increased blood pressure and decreased oxygen saturation, so chemotherapy on the third day was suspended. He underwent a lung enhanced CT examination showing a mass shadow in the left upper lobe, considering a neoplastic lesion with involvement of the left pulmonary artery with atelectasis in the left upper lobe; Micro-nodules in the upper lobe of the right lung and the lower lobe of both lungs; Left pleural effusion, left lung insufficiency; Aortic wall calcification; Gallstones. An electrocardiogram revealed sinus bradycardia and frequent ventricular premature beats. On April 24, color doppler echocardiography showed no abnormal heart structure or valve activity. The symptoms improved after treatment with oxygen inhalation and cardio-protective therapy, but the patient refused to continue chemotherapy and was discharged on April 27.
After discharge, the patient developed a general feeling of fatigue, which gradually worsened within the next week, so that he could not stand up and walk on his own, accompanied by shoulder pain that gradually developed into a general feeling of muscle pain and tightness of the four limbs. On May 21, he was admitted to a local hospital for emergency treatment. Laboratory tests showed: creatine kinase(CK) 11002U/L (normal range, 59–248U/L); myoglobin(Mb) >2000ng/ml (normal range, ≤154.9ng/ml); alanine aminotransferase(ALT) 165U/L (normal range, ≤41U/L); aspartate aminotransferase(AST) 518U/L (normal range, ≤40U/L); lactate dehydrogenase(LDH) 846U/L (normal range, 135–225U/L). After rehydration and diuretic treatment, levels of serum CK,Mb,ALT,AST and LDH were markedly elevated to 14947U/L, >2000ng/ml, 325U/L, 1146 U/L and 1236U/L respectively on May 24. Physicians at the local hospital recommended that the patient should be transferred to the higher-level hospital for further diagnosis and treatment.
Therefore, the patient was admitted to our hospital in May 24, with complaints of a progressed generalized muscle pain and weakness after chemotherapy for small cell lung cancer. The patient was a smoker but had no history of hypertension, diabetes mellitus, autoimmune disease or renal disease and no relevant family history. He did not have any history of infection, trauma, hyperthermia, myopathies (myositis, dystrophy, and others) or taking lipid-lowering agents prior to admission. He began to feel difficulty swallowing food or drinking water and his urine was dark yellow at admission. At that time, his height, weight, blood pressure, heart rate, temperature, respiratory rate and SpO2 were 180cm, 73 kg, 135/75mmHg, 71 beats/min, 36.1℃,20 breaths/min, and 95% on room air, respectively. Laboratory tests on admission showed substantially increased serum CK, Mb, ALT, AST and LDH (Table 2). In addition, renal function and myocardial is abnormal: cardiac troponin I (cTnI) 46.5 pg/mL, blood urea nitrogen(BUN) 11.70mmol/l, serum creatinine (Scr) 105 μmol/l, uric acid (UA) 508.0μmol/l. Autoimmune myositis-associated antibodies (anti-Ro-52, anti-Jo-1, anti-Mi-2, anti-Ku, anti-PM-Scl100, anti-PM-Scl75, anti-SRP, anti-PL-7, anti-PL-12, anti-EJ antibodies), vasculitis-associated autoantibodies (anti-pANCA, anti-cANCA, anti-MPO, anti-PR3), rheumatism autoantibody(anti-ANA, anti-dsDNA, anti-ENA, anti-RNP A, anti-RNP 68, anti-Sm/nRNP, anti-Sm, anti-SS-A, anti-SS-B, anti-Scl-70) were negative and thyroid function tests (thyroid-stimulating hormone and free thyroxine) were normal. In order to exclude infection-induced rhabdomyolysis, IgM antibody tests for pathogens (mycoplasma pneumoniae, chlamydia pneumoniae, coxsackievirus, adenovirus, respiratory syncytial virus, cytomegalovirus) were negative. Surprisingly, the lung CT scan showed that the lung mass was significantly smaller than that before chemotherapy (Figure 1). We suggested a muscle biopsy and electromyogram to rule out myopathies, but it was rejected by patients and his families. According to the Naranjo Scale of adverse drug reactions, the score is 5, which indicates that adverse events are probable adverse drug reactions (Table 3) [2]. The patient was diagnosed with severe rhabdomyolysis induced by chemotherapy.
A large amount of intravenous fluids was administered to prevent acute kidney injury and intravenous methylprednisolone (40mg/day) were started immediately for rhabdomyolysis. Seven days later, intravenous methylprednisolone was changed to 30mg/day. The serum CK, ALT, AST and LDH gradually declined within 2 weeks (Table 2). The symptoms of fatigue and myalgia have improved. After the 17 day of hospitalization, CK levels decreased to 941U/L, and he requested discharge back to local hospital for further rehabilitation (Figure 2). Methylprednisolone was continued during the hospitalization and upon discharge. On June 10, he was discharged from our hospital with an oral dose of methylprednisolone 20 mg/day, and the dosage was gradually reduced. The serum CK normalized 2 weeks after discharge with an oral dose of methylprednisolone 10 mg/day, however, the symptoms of fatigue and myalgia improvement still slowly. Therefore, chemotherapy has not been restarted until now.