These distinctive syndromes have known associations with malignancy. In most cases, their appearance should prompt a search for an underlying cancer.
Hypertrophic Pulmonary Osteoarthropathy
- Triad of polyarthritis, clubbing, and periostitis.
- Rapid progression of symptoms.
- Association with intrathoracic malignancies.
Clinical Findings & Treatment
Hypertrophic pulmonary osteoarthropathy may exist in a primary form or in a secondary form associated with infectious diseases (eg, lung abscess) or malignancy. This syndrome is associated most commonly with intrathoracic malignancies (eg, adenocarcinoma of the lung, mesotheliomas, lymphomas) but has also been described in association with other cancers. It may appear several months prior to detection of the associated neoplasm.
Hypertrophic pulmonary osteoarthropathy is characterized by painful polyarthritis, clubbing of the fingers and toes, and periostitis of the long bones. Rapidly progressive symptoms are a feature of paraneoplastic hypertrophic pulmonary osteoarthropathy. The polyarthritis can resemble rheumatoid arthritis in its joint distribution but elicits noninflammatory synovial effusions. The periostitis commonly causes severe pain and tenderness of the long bones of the legs, usually in association with characteristic radiographic and scintigraphic findings. Nonsteroidal anti-inflammatory drugs may improve joint pain. Treatment of the underlying neoplasm often leads to remission of the syndrome.
Palmar Fasciitis-Polyarthritis Syndrome
The development of polyarthritis and rapid progression of palmar fasciitis with flexion contractures of the hands is clearly linked with ovarian cancer but also has been described in patients with gastric, lung, colon, and pancreatic cancer. The syndrome is refractory to treatment, and the prognosis is poor.
Remitting Seronegative Symmetric Synovitis with Pitting Edema (RS3PE)
RS3PE is characterized by the presence of a symmetric synovitis of the small joints of the hands in association with pitting edema of the hands and feet. Serum rheumatoid factor is negative. Treatment with low-dose systemic glucocorticoids is usually effective. Although there are idiopathic forms of the syndrome, RS3PE can herald the development of hematologic malignancies or a variety of solid tumors. Treatment of the underlying neoplasm with surgery or chemotherapy can lead to resolution of RS3PE.
Patients with pancreatitis or with pancreatic cancer can present with the combination of arthritis and panniculitis. The arthritis is inflammatory and ranges from a monoarthritis to a polyarthritis. The panniculitis begins as tender red subcutaneous nodules, usually on the lower extremities, that initially mimic erythema nodosum but that later liquify and may drain a yellowish material. Release of pancreatic lipase likely plays a role in the pathogenesis of the syndrome.
Erythromelalgia manifests as recurrent attacks of pain and erythema involving the feet and, sometimes, the hands. The reversible acral erythema bears a resemblance to Raynaud phenomenon, but the effect of ambient temperature is the converse of that of Raynaud phenomenon: heat exacerbates and cold ameliorates the symptoms of erythromelalgia. Erythromelalgia can be idiopathic but a substantial minority have an underlying myeloproliferative disorder, particularly essential thrombocytosis and polycythemia rubra vera. Approximately 50% of patients with essential thrombocytosis have erythromelalgia.
Atypical Polymyalgia Rheumatica
Renal cell carcinoma, other solid tumors, and multiple myeloma can cause a pain syndrome that resembles polymyalgia rheumatica but that fails to respond promptly to low doses of glucocorticoids. Other features that point to a paraneoplastic syndrome rather than true polymyalgia rheumatica include unilateral symptoms, distal extremity pain, and the presence of clubbing.
Dermatomyositis & Polymyositis (See Chapter 27)
Compared with the general population, the incidence ratio of malignancy has been reported to be as high as 6.2 for dermatomyositis and 2.4 for polymyositis at the time of diagnosis. Although the incidence of malignancy appears to be highest at the time of diagnosis, an increased risk of malignancy may be present for 2–5 years after the diagnosis has been made. A number of clinical features correlate with the presence of malignancy in association with inflammatory myositis. These include older age, fever, substantial weight loss (greater than 5%), and rapid onset of disease (defined as diagnosis within 2 months of symptoms). Dermatomyositis with cutaneous necrosis of the trunk is also associated with malignancy.
Although the distribution of malignancies seen with the inflammatory myopathies is similar to the general population, there are several specific associations with dermatomyositis and polymyositis. Cancer of the ovaries, lungs, and the gastrointestinal tract is reported most frequently in association with dermatomyositis. Non-Hodgkin lymphoma and cancer of the lung as well as bladder cancer are frequently described in patients with polymyositis. Asian patients with inflammatory myositis have a high incidence of nasopharyngeal cancer.
At a minimum, age-appropriate cancer screening is indicated for patients with dermatomyositis and polymyositis. Although no guidelines exist, some clinicians advocate additional screening, at least in certain circumstances. For example, transvaginal ultrasonography and CA-125 are warranted in women with dermatomyositis, given the high incidence of ovarian cancer. Because the risk of ovarian cancer may be elevated for up to 5 years, some experts argue that screening should continue annually during this time.