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.