We describe the case of a 46-year old woman who was diagnosed with locally invasive breast cancer in September 2019. The patient had no other known diseases or usual medication and was currently being treated with neoadjuvant chemotherapy, having received the 6th cycle of paclitaxel on April 3rd, 2020.
According to local guidelines following the outbreak of the coronavirus pandemic (SARS-CoV-2), she was subjected to a SARS-CoV-2 polymerase chain reaction (PCR) screening test (nasopharyngeal swab) prior to the following chemotherapy administration and had tested positive. She was asymptomatic and reported no recent history of fever, cough, dyspnea or gastrointestinal manifestations. She was admitted to an isolation ward in the Santa Maria University Hospital in Lisbon, Portugal, due to absence of isolation conditions at home.
Medical examination and blood tests at admittance were unremarkable (Table 1). During the first 15 days of hospital stay, the patient complained of occasional nausea and diffuse myalgia; however, beginning on May 2nd, she presented with vomiting, abdominal pain and new-onset fever. Physical examination revealed no significant findings and her oxygen saturation remained >95 %. Laboratory tests revealed de novo lymphopenia, slight thrombocytopenia, as well as an increase in CRP, amylase, transaminases, LDH and GGT levels. CK at the time was normal. Urine sediment analysis had unspecific alterations. An abdominal ultrasound was performed the same day, with no significant liver or biliary findings. She was given paracetamol and metoclopramide, with symptomatic relief. Over the following two days, she presented with diarrhea and a new-onset dry cough.
On May 5th, 19 days after admission, chest X-ray (Fig. 1) revealed a significant bilateral infiltrate with upper left lung consolidations. CT-scan (Fig. 2) confirmed the presence of diffuse bilateral ground-glass opacities with predominantly left lung nodular infiltrates in less than 50 % of lung parenchyma and showed no evidence of structural pancreatic disease. Blood work revealed a marked increase in CK (87,456 U/liter), LDH (2750 U/liter), ferritin (1795 ng/mL) and Il-6 (80 pg/mL), as well as further increase in CRP, transaminases, GGT, amylase and lipase. Total bilirubin, troponin, urea and creatinine remained at normal values. There was no hyperuricemia, lactic acid increase, or arterial blood gas and ion changes. Serology for SARS-CoV-2 revealed antibody response (Positive IgG: 6.92 UA/mL, equivocal IgM). Acute cytomegalovirus and Epstein-Barr virus (EBV) infections, as well as human immunodeficiency virus (HIV) and hepatitis B (HBV) infections were ruled out. Nasopharyngeal swab was still positive for SARS-CoV-2 RNA.
Other than paracetamol and metoclopramide, the patient had not been given any drugs and one month had passed since the last administration of paclitaxel. She also exhibited no muscle rigidity, hyperpyrexia, altered consciousness or autonomic instability that may have pointed to metoclopramide-induced malignant neuroleptic syndrome; nevertheless, metoclopramide was discontinued. She confirmed no personal or family history of rhabdomyolysis.
Considering the strong possibility of a cytokine-mediated response in the wake of post-chemotherapy immune reconstitution, immune-modulating therapy was proposed. According to internal guidelines, she was not eligible for tocilizumab and was administered 80 mg methylprednisolone once daily as well as hydroxychloroquine. She also received intravenous bicarbonate on the first day. In order to avoid worsening of lung disease, fluid administration was closely titrated to achieve neutral fluid balance.
Over the following 48 h, the patient experienced marked relief of myalgia, asthenia and diarrhea. Her cough became less intense and her fever resolved. Blood work showed recovery of lymphocyte counts as well as decreasing CK (36,807 U/liter), LDH, CRP and liver enzymes. Lipase and amylase remained stable. Ferritin peaked at 2753 ng/mL, beginning descent on the 3rd day of methylprednisolone. Chest x-ray showed infiltrate improvement. It was then decided to wean off methylprednisolone (10 mg decrease every 3 days, switch to oral prednisolone after 20 mg, followed by a 5 mg decrease every 3 days) and to stop hydroxychloroquine after 10 days.
Further investigation of alternative causes for rhabdomyolysis revealed normal thyroid hormone levels and a negative auto-immune myositis panel.
The patient agreed to a deltoid muscle biopsy performed after 10 days of methylprednisolone treatment. No viral RNA was detected in the muscle sample and pathology revealed no inflammatory infiltrates or signs of muscle damage.
The patient was discharged on the 10th day of corticosteroid treatment, having experienced no kidney damage or hypoxemia, with CK < 500 U/liter; she resumed paclitaxel administrations 10 days later, with no complications.