Dermatomyositis as a paraneoplastic manifestation of ovarian cancer: A case report
Dermatomyositis is a rare idiopathic inflammatory myopathy characterized by proximal skeletal muscle weakness, muscle inflammation and distinct cutaneous eruptions. While the pathogenesis of dermatomyositis is poorly understood, the condition is believed to be caused by altered cellular and humoral immunity.1
An association between inflammatory myopathy and cancer has been recognized since 1916.2 The increased frequency of cancer in patients with inflammatory myopathy is consistent with paraneoplastic processes linked to oncogenesis and autoimmunity.3 Diagnosis is based on a characteristic clinical picture and is confirmed by biochemistry, electromyogram, nerve conduction velocity studies and/or biopsy of skin and muscle. Treatment is mainly by steroids, immunosuppressive drugs and management of underlying malignancy. Recurrence of dermatomyositis symptoms is often the first sign of cancer relapse. The prognosis of ovarian cancer in the context of dermatomyositis is generally poor.
In this case report, we describe a postmenopausal woman with skin and muscle symptoms consistent with dermatomyositis. She was started on high-dose immunosuppressive therapy, which did not result in resolution of symptoms, and she was subsequently diagnosed with stage IIIc ovarian cancer. Eventually, the manifestations of dermatomyositis regressed in synchrony with effective surgical removal of the tumour followed by systemic chemotherapy.
Case presentation and history
In January 2020, a 57-year-old G4P3A1 Chinese female consulted a private health clinic for an eruption of a dusky red rash on her cheeks, eyelids, forehead, neck and knuckles, with scaly and dry skin. She was otherwise healthy and had no history of food or drug allergy. She received as-needed treatment for skin allergy, but her symptoms did not improve. She noticed progressive symmetrical muscle pain and weakness in her upper arms and hips, with swelling in her hands, and subsequently became bedridden.
She was taken to a private hospital, where electromyogram and nerve conduction velocity studies showed changes consistent with dermatomyositis. She was started on mycophenolate mofetil 750 mg BID, prednisolone 25 mg daily, and hydroxychloroquine 200 mg daily. Laboratory tests showed elevated creatine kinase (4,729 U/L) along with elevated tumour markers, cancer antigen 15-3 (CA15-3; 222 U/mL) and CA-125 (2,426 U/mL). Serum autoantibodies were negative. Gynaecology examination revealed a pelvic mass. CT scan and transvaginal ultrasound showed bilateral ovarian tumours, with free fluid in the pouch of Douglas. Colonoscopy and panendoscopy findings were unremarkable.
Treatment and response
The patient was transferred to our government hospital in April 2020. Prior to surgery, mycophenolate mofetil, hydroxychloroquine and prednisolone were withheld. Exploratory laparotomy was performed, with intraoperational findings revealing suspicious extensive abdominal metastases including the diaphragm, peritoneum, mesentery and omentum, with a moderate amount of bloody ascites.
In view of the patient’s refusal to undergo colostomy, the surgical extent was compromised to avoid intestinal perforation. Partial omentectomy, excision of left adnexa and of suspicious metastases in the mesenterium and peritoneum, as well as pelvic and abdominal lavage were performed. A stress dose of intravenous (IV) hydrocortisone was given during surgery and tapered over 72 hours postoperatively, while prednisolone 25 mg daily and hydroxychloroquine 200 mg daily were resumed after recovery from surgery.
Cytology of the abdominal lavage fluid showed carcinoma cells. Final pathology confirmed a high-grade serous adenocarcinoma of the ovary with omental metastasis, classified as International Federation of Gynecology and Obstetrics stage IIIC ovarian cancer. The patient denied any family history of breast or ovarian malignancy. She received induction chemotherapy with IV carboplatin (area under the curve, 5 mg/mL/min) and paclitaxel (175 mg/m2). Prednisolone was tapered to 10 mg daily. Her muscle power improved after the first cycle of chemotherapy, and she became able to walk with confidence without aid. Her facial rash resolved, and CA-125 decreased from 1,974 U/mL on the day of chemotherapy initiation (day 120) to 881 U/mL after the third cycle of chemotherapy (day 167) and 497 U/mL just before the fourth cycle of chemotherapy (day 181). (Figures 1 and 2) The patient was still receiving treatment at the time of writing this report.
Dermatomyositis is a rare disease with an incidence of 0.96 per 100,000 in the general population.4 Its clinical significance lies in its association with paraneoplastic processes in some patients. A large retrospective study showed that up to 15 percent of dermatomyositis patients had underlying malignancies.5 Ovarian, lung and colorectal cancers were frequently diagnosed both before and after the diagnosis of dermatomyositis,6 suggesting that these cancers could be associated with the disease.
In a recent propensity score analysis based on medical records of 23 consecutive patients with concurrent ovarian cancer and dermatomyositis, and 115 patients diagnosed with ovarian cancer alone, researchers in China found a correlation and a parallel clinical course between the two diseases.7 While the concurrence of ovarian cancer and dermatomyositis as a paraneoplastic syndrome was rare, the prognosis was poor. The risk for patients to be diagnosed with dermatomyositis was the highest within 3 years before or after ovarian cancer diagnosis.
In the US, researchers reported the cases of two premenopausal women with dermatomyositis, who received high-dose immunosuppressive therapy without resolution of symptoms, and were subsequently diagnosed with stage III ovarian cancer.8 The patients’ symptoms associated with dermatomyositis resolved after debulking surgery and adjuvant chemotherapy.
These reports suggest that clinicians should have a high degree of clinical suspicion for underlying ovarian cancer in women of all ages diagnosed with dermatomyositis. Dermatomyositis patients are often immunosuppressed, which may present unique challenges at the time of surgery for ovarian cancer. In addition, symptoms of dermatomyositis can be used to evaluate treatment response and recurrence of ovarian cancer.
The severity, diagnostic challenges and clinical significance of dermatomyositis manifestations as a paraneoplastic effect in patients with ovarian cancer have been described in a recent case report from the UK.9 In another earlier case series, researchers from Israel reported that the diagnosis of dermatomyositis preceded that of ovarian cancer in most cases, with a mean interval of 10.9 months.10 Delayed diagnosis could be due to the insidious onset and slow progression of dermatomyositis, as well as the limitations of imaging studies. In the case series, 94 percent of patients were diagnosed with stage III or IV ovarian cancer, rendering their prognosis extremely poor.10 In another case series from the US, the death rate of patients with ovarian malignancies associated with dermatomyositis was 100 percent, and the mean survival time from diagnosis was 11 months (range, 0–28 months).11 Gynaecologists should therefore be aware of the significance of the association between these two conditions.
Cases of dermatomyositis presenting after an established diagnosis of ovarian cancer have also been reported recently.12 However, consistent with our patient case, ovarian cancer may also be diagnosed shortly after the diagnosis of dermatomyositis.13 While the risk of cancer was the highest during the first year after diagnosis of dermatomyositis and dropped substantially thereafter, the risk of ovarian cancer remained above the expected population risk for up to 5 years after the established diagnosis of dermatomyositis.14 A thorough physical examination, pelvic ultrasound and serum CA-125 assay should thus be performed at the time of dermatomyositis presentation and patients should be followed closely for several years thereafter.
In our patient, manifestations of dermatomyositis regressed in synchrony with effective treatment of the tumour. Although dermatomyositis may follow a paraneoplastic course, or may follow its own course independent of treatment of the tumour, health practitioners should be vigilant for the recurrence of muscle weakness and cutaneous manifestations that are associated with relapse of the malignant disease in most cases.
In summary, the association between dermatomyositis and ovarian cancer should be clearly emphasized. As ovarian cancer is one of the most lethal gynaecologic malignancies, health practitioners should perform timely screening to detect occult cancer in patients with dermatomyositis, particularly in female patients above the age of 40 years. With prompt detection, disability from myositis can be alleviated when the ovarian cancer is well managed, even if mortality cannot be prevented in these patients.