When Myopathy Strikes in a Cancer Patient

CASE REPORT

A 54-year-old white woman was diagnosed with moderately differentiated stage IIIC adenocarcinoma of the colon in July 2006, for which she underwent right hemicolectomy. She was started on adjuvant chemotherapy with FOLFOX6 (folinic acid/5-fluorouracil/oxaliplatin). Oxaliplatin was discontinued after the first six cycles due to a rise in hepatic enzymes (aspartate aminotransferase [AST] 256 U/L and alanine aminotransferase [ALT] 815 U/L). She was then started on capecitabine, which was discontinued due to the development of pruritic rash. Infusional 5-FU was administered for the remaining cycles.

Five months after her initial diagnosis and while receiving infusional 5-FU, the patient complained of generalized weakness and mild tingling and numbness of the fingers and toes. Her symptoms were initially attributed to a previous diagnosis of fibromyalgia, degenerative joint disease, and possibly neuropathic side effects of oxaliplatin-based chemotherapy. One month later the patient complained of increasing weakness—she could not dress herself or stand from a sitting position, which suggested proximal muscle weakness of upper and lower extremities. She denied arthralgias. On examination she had a diffuse erythematous, maculopapular rash on her face, upper chest, thighs, trunk, and extensor surface of both arms (Figure 1). She also had nodules on the back of her hand. Her muscle strength was 3/5 in proximal muscle group of both upper and lower extremities with no sensory loss. Clinical diagnosis of dermatomyositis was suspected and appropriate workup was performed.

Figure 1.

Erythematous maculopapular rash on face, hand and lower back.

On laboratory evaluation sedimentation rate was 36 mm/hr, C-reactive protein 4.74 mg/dL, antinuclear antibody negative, anti-Jo-1 (histidyl tRNA synthetase) 16 U/L, white blood cells 3.9/nL, platelets 209/nL, hemoglobin 13.9 g/dL, hematocrit 43.5%, AST 156 U/L, ALT 127 U/L, creatinine phosphokinase (CPK) 1,274 U/L, aldolase 26.9 U/L (1.5 – 8.1), carcinoembryonic antigen (CEA) 0.9 U/L. Her serum creatinine level was normal, and she was negative for anti-SSA, anti-SSB, anti-Sm, and anti-RNP. Magnetic resonance imaging (MRI) of the cervical spine revealed no abnormalities. Nerve conduction studies showed bilateral median neuropathies at the wrist. Electromyography sampling of selected proximal and distal muscles in the arms and legs showed clear myopathic changes in the left deltoid, quadriceps, and tibialis anterior muscles. Muscle biopsy of the left proximal quadriceps was performed. Alkaline phosphatase stain showed capillaries in peri- and endomysium, and esterase stain showed inflammatory cells consistent with dermatomyositis (Figure 2).

Figure 2.

Alkaline phosphatase stain showed capillaries in peri- and endomysium, and esterase stain showed inflammatory cells.

Treatment with high-dose prednisone was initiated; methotrexate was later added and the prednisone dose was tapered. Dramatic clinical resolution of her symptoms occurred, with improvement in muscle strength. Within 2 months, her CPK level returned to normal. Her skin lesions also improved significantly. The patient underwent computed tomography (CT) scans of the chest, abdomen, and pelvis to rule out recurrent colon cancer. Her CA-125 was normal and transvaginal ultrasound revealed no evidence of cancer recurrence. Our patient remains disease-free at 3 years and continues to be followed for colon cancer.

DISCUSSION

Bohan and Peter’s criteria describe dermatomyositis as an inflammatory myositis with dermatologic features—Gottron’s papules, heliotrope rash over the eyelids, scaly erythematous rash over the dorsum of hands or with involvement of knees, elbows, and medial malleoli, face, neck, and upper torso.^1–5 The association between dermatomyositis and cancer was first suggested in 1916 and has been recognized for nearly a century,^4,6,7 though the exact risk and incidence is controversial.^8,9 Multiple epidemiologic studies have confirmed the association and also revealed the temporal relationship between the two entities.^2,10 Malignant disease may occur before the onset of dermatomyositis, concurrently with myositis, later as a paraneoplastic syndrome, or it may follow its own course independent of the treatment of malignant disease.^1,11

A population-based cohort study performed in 2001 on the incidence of malignant disease in biopsy-proven inflammatory myopathy suggested an overall increased incidence in the first 3 years after diagnosis of myositis,⁴ though other studies report that the risk is apparent for 5 years after diagnosis.^1,10 The prevalence of cancer at dermatomyositis diagnosis is significant among persons older than 50 years and portends a poorer prognosis.¹⁰ Dermatomyositis is associated with adenocarcinomas of the ovaries, lung, stomach, and colorectum.^2,10,13,14 It is more often a harbinger to the diagnosis of a malignant tumor;⁷ however, cases have been reported where myositis emerges after cancer has been diagnosed, as in our case.

A model of paraneoplasia focusing on common autoantigen expression and immune targeting between cancer tissue and muscle tissue in myositis has been suggested.⁶ The occurrence of malignancies both before and at the time of diagnosis of dermatomyositis supports the concept of causal relation between these diseases and may be a sign of compromised immune function.¹² It also supports the hypothesis that dermatomyositis may be a paraneoplastic syndrome and that the two are related.¹⁵ The disappearance of skin and muscular signs after treatment of the tumor and recurrence with further metastasis reinforces the possible paraneoplastic nature of dermatomyositis.^16–22

Suspicion of malignancy and prompt screening is critical in patients with dermatomyositis.²³ Indeed, all patients with dermatomyositis should be assessed for the presence of malignant disease. ^1,4 Since the risk of malignancy remains high for many years after a diagnosis of dermatomyositis, disability from myositis could be alleviated if cancers are detected and treated early enough.²⁴ The evaluation of patients with myositis for the presence of possible occult tumor is one of the more difficult and controversial aspects of care of these individuals, as there has been no prospective, case-controlled study to establish the appropriate extent of such a workup.

Experts recommend that otherwise asymptomatic patients with dermatomyositis undergo an age-specific examination for occult malignancy, but the value of more exhaustive screening has also been emphasized.^25,26 The type of assessment should be age- and sex-specific, as the likelihood and possible sites of malignancy increase and vary with increasing age.¹ Thorough clinical examination, including routine laboratory screening, chest CT, fecal occult blood testing, abdominal ultrasound or CT, mammography, pelvic CT or transvaginal ultrasound, gynecologic examination, and serum CA-125^27,28 have been used to screen for cancers in the first 3 years after diagnosis due to overrepresentation of cancer in first 3 to 5 years.^17,29 Upper and lower endoscopic studies of the gastrointestinal tract should be conducted according to the patient’s age to rule out colorectal malignancies associated with dermatomyositis. ³⁰,³¹

CONCLUSION

Our case report describes a rare presentation of dermatomyositis after an initial diagnosis of colon cancer. Recommendations in the literature call for workup for detection of occult malignancy after the diagnosis of dermatomyositis, but it remains a challenge when dermatomyositis presents a few months after the diagnosis of colon cancer. It could also signal relapse of cancer and, thus, the presence of micrometastatic disease. Current American Society of Clinical Oncology (ASCO) guidelines recommend CEA testing every 3 months and CT scans every year after adjuvant chemotherapy for stage II and III colon cancer. Since the risk of occult malignancy is high in patients presenting with dermatomyositis, these guidelines may pose a real challenge in terms of surveillance. Thus far, our patient has not experienced a recurrence of colon cancer or developed a new primary. We did perform clinical examinations every 3 months as recommended by ASCO, but we performed CT scans every 4 to 6 months for the first 3 years. We believe that surveillance for these patients should include closer follow-up and even more frequent CT scans.

Neuropathic symptoms are commonly seen with oxaliplatin-based chemotherapy, which is considered standard of care for stage III colon cancer. It causes predominantly sensory neuropathy; therefore, a thorough neurologic examination is required when a patient complains of new neurologic symptoms while undergoing chemotherapy. It is important to distinguish myopathy from neuropathy when a cancer patient has received a chemotherapeutic agent that can cause peripheral neuropathy. We also emphasize the importance of appropriate evaluations for this association between colon cancer and dermatomyositis, which can help reduce morbidity and mortality in these patients.