PRATO, Italy— Mild-to-moderate knee monoarthritis may be a harbinger of non-small-cell lung cancer (NSCLC) in heavy smokers, according to a new study published online in the Annals of the Rheumatic Diseases.¹ The study authors urge rheumatologists to consider lung cancer as a possible cause of joint pain in all heavy smokers who are HLA-B27 negative; present with mild-to-moderate isolated knee monoarthritis; and have no history of psoriasis, spondyloarthropathy, or radiological features suggestive of knee osteoarthritis or chondrocalcinosis.

The next step is to aspirate the joint to rule out inflammation and to exclude other potential causes of joint fluid collection, according to lead author Fabrizio Cantini, MD, with the Hospital Misericordia a Dolce, in Prato, Italy.

"As in our patients when the most common causes of knee monoarthritis are ruled out, a chest radiograph is recommended as a first level investigation," Dr. Cantini says.

Early NSCLC diagnosis may improve survival as well as helping knee pain

The addition of knee monoarthritis to the list of paraneoplastic syndromes came after the researchers reviewed the clinical records of 6654 new outpatients with isolated knee monoarthritis seen from January 2000 to December 2005 at a single tertiary care center.

Of these patients, 296 (4.4%) presented with isolated monoarthritis of the knee. In five out of 296 (1.7%) patients this feature represented the initial manifestation of NSCLC. All five patients were middle-aged males, with a long history of heavy cigarette smoking, who had a nonerosive, isolated knee monoarthritis, with mild articular fluid collection of noninflammatory type. The lung cancer was diagnosed at stages 1A or 1B and the tumors were resectable in all patients. This form of lung cancer is typically only diagnosed early in 45% of the cases. In all five cases, knee monoarthritis-remitted patients were disease-free, with a median follow-up of 41 months.

Is knee pain an early sign of lung cancer?

"Although not frequent, awareness of the main clinical characteristics of this manifestation may help to facilitate proper diagnoses," the researchers conclude.

E. Neil Schachter, MD, professor of medicine and community medicine and the medical director of the respiratory care department at the Mount Sinai Medical Center, in New York City, called this an "interesting article." He commented that "the authors argue that non-small-cell lung cancer is associated with a number of bone disorders, including hypertrophic pulmonary osteoarthropathy (HOA) and bone metastases. They now describe a presentation of lung cancer which follows monoarticular knee arthritis, [and] the interesting association which they describe suggests that in these patients the tumor appears to be generally treatable," he told CIAOMed. "If this association holds up it might help identify early, treatable lung cancer."
 
He suggested that the findings could reflect the hypothesis that an inflammatory state of the body underlies lung cancer and many other chronic diseases.
 
"What remains to be seen is whether or not this is a true syndrome in the sense of HOA, [and] a case control study would be the way to resolve this issue," Dr. Schacter ended.

Reference

1.   Cantini F, Niccoli L, Nannini C, et al. Isolated knee monoarthritis heralding resectable non-small cell lung cancer. a paraneoplastic syndrome not previously described. Ann Rheum Dis. 2007; doi: 10.1136/ard.2007.075333 [Epub ahead of print].