Real Time Clinical Question: Rheumatology

February 13, 2009

think.jpgCommentary by Jon-Emile Kenny MD, PGY- 2 

Faculty Peer Reviewed

At morning report, the case of a 55 F with known dermatomyositis (DM), and interstitial lung involvement who had presented to the hospital with increasing dyspnea was presented.  The discussion of the case opened with the cardinal manifestations of DM including proximal muscle weakness as diagnosed with EMG, cutaneous manifestations such as the heliotrope rash, the shawl sign, Gottron’s papules, Reynaud’s, and ‘Mechanics Hand’, and the systemic manifestations such as interstitial lung disease.

We then turned to the differential diagnosis basic laboratory work up. As clinical symptoms and signs may stem from a multitude of etiologies secondary to rhabdomyolysis, iatrogenesis, viruses and endocrine pathology, testing for CPK, aldolase, ANA, TSH in addition to EMG and skin biopsy are frequently required to narrow the differential; we discussed the relative unimportance of anti-Jo 1 antibodies. During the discussion of pertinent investigations in DM, the topic of malignancy screening was raised and the following clinical question was posed:

For newly diagnosed dermatomyositis, what cancer-screening investigations should be undertaken and at what repeat intervals?

As the risk of malignancy in DM is 5 to 7 fold higher than the general population (1), the diagnosis should prompt timely, age-appropriate malignancy screening. Indeed, some studies have indicated that the risk of concurrent or future malignancy in patients with DM may be as high as 30-40%. Adenocarcinomas of the cervix, lung, ovaries, pancreas, bladder, and stomach account for approximately 70 percent of the cancers associated with inflammatory myopathies (2). While there is no clear evidence to support the following, cancer screening based on age and gender should include the following (2):

• Complete blood count
• Erythrocyte sedimentation rate and serum C-reactive protein
• Serum chemistry panel
• Serum prostate-specific antigen
• Urinalysis with microscopic examination for blood
• Serum CA125 and CA19-9
• Stools for occult blood
• CXR.

In addition, a French study found that there is an increased yield for blind intra-abdominal malignancy investigation with CT scan and that the following are associated with increased risk of malignancy in DM: constitutional symptoms, a rapid onset of DM or polymyositis (PM), the lack of Raynaud phenomenon, and a higher mean erythrocyte sedimentation rate and creatine kinase level (3). Although no official recommendations have been made, many practitioners elect to act on this information by obtaining a CT scan of the abdomen/pelvis, and in some cases the chest as well, as part of the initial DM malignancy work-up.

Notably a large population-based study in Sweden found that the peak incidence of malignancy occurs either 2 years prior to or 2 years following the diagnosis of an inflammatory myopathy (4) and this was also seen in the aforementioned French analysis (3). This suggests that more frequent cancer surveillance beyond 3 years of diagnosis is less likely to be cost effective. One caveat may be ovarian cancer as it can occur five years after the presentation of DM; therefore screening female DM patients biannually with serum CA125 and annual pelvic exam with transvaginal ultrasound for up to five years after the diagnosis of DM’s recommended (2).

Faculty Comments by Michael Pillinger, MD, Associate Professor of Medicine and Pharmacology, NYU Division of Rheumatology:

The connection between dermatomyositis and malignancy is well-established, but the mechanisms through which the two are related remain mysterious. It would be tempting to consider dermatomyositis as a paraneoplastic syndrome, but cause and effect is almost impossible to establish, and in many cases the dermatomyositis precedes the malignancy, sometimes by years. Nonetheless, the frequency with which dermatomyositis patients turn out to have concurrent malignancy demands that we as physicians look carefully for malignancy in any patient diagnosed with dermatomyositis.

How should one evaluate the dermatomyositis patient for malignancy? The piece by Dr. Kenny provides an evidence-based start. We begin with ensuring that routine malignancy screening is up to date and we add simple blood tests to look for the footprints of liver, prostate and ovarian cancer. Most rheumatologists would, at minimum, add to that work up a chest radiograph—not because the evidence has established its value, but because it is inexpensive, easily obtained, low risk and may provide insight into unappreciated lung tumors. Unfortunately, we all know that by the time a tumor is visible in the lung the cow may already be out of the barn. We are therefore left to ask if more aggressive screening might more likely to uncover treatable malignancies early. As a physician, I find that I tend the follow the “what if it were my relative?” strategy in these situations, and find it hard to deprive the patient of CT imaging of the chest, abdomen and pelvis, ideally with contrast. The literature does not rigorously support this strategy, but given the relative rarity of the disease, the literature is not particularly satisfactory in this regard. Art, rather than science, must supervene where the data is thin.

Another question is, how long must the vigilance continue? Once again, I would argue beyond the data, which suggests that the peak incidence of new malignancy (in patients who initially present with dermatomyositis without malignancy) may come within the first two years. While undoubtedly true, malignancies have been documented as long as five years after the dermatomyositis presentation. I would not advocate for a full work up on a regular basis, but aggressive routine screening, along with careful attention to the possible appearance of new symptoms, is certainly warranted for an extended period.

Finally, I would point out that dermatomyositis is not the only inflammatory muscle disease to be accompanied by malignancy. Although the association is less strong, patients with polymyositis also appear to develop malignancy at an excessive rate. While these individuals may not warrant quite the extensive workup of the patients with dermatomyositis, they do deserve attention, close follow-up and a high index of suspicion.

1. Barnes BE; Dermatomyositis and malignancy. Ann Intern Med 1976 Jan;84(1):68-76.
2. Miller, M. Malignancy in Dermatomyositis and polymyositis. Up To Date Online: Accessed 10/9/2008.
3. Sparsa A; Routine vs. extensive malignancy search for adult dermatomyositis and polymyositis: a study of 40 patients. Arch Dermatol 2002 Jul;138(7):885-90.
4. Sigurgeirsson B; Risk of cancer in patients with dermatomyositis or polymyositis. A population-based study. N Engl J Med 1992 Feb 6;326(6):363-7.