- Indian Rheumatology association
Rheumatic diseases and malignancies have a bidirectional relationship with many rheumatic diseases having an increased risk of malignancy and vice versa. Drug induced neoplastic disorders, rheumatic manifestations of chemotherapeutic agents and paraneoplastic manifestations are also to be watched for.
Of all the rheumatic diseases, Sjogren’s disease has the strongest association with malignancy with a 13-15 times higher risk of developing lymphomas.
Table 1 : Risk of malignancy with rheumatic diseases
Rheumatic disease | Standardised incidence ratio | Increased incidence | Decreased incidence | Red flag signs |
SLE | 1.14 – 4.13 | Vulva, lung, thyroid, and hematologic cancers, particularly non Hodgkin lymphoma | Prostate cancer, cutaneous melanoma, breast and endometrial cancer | |
Primary Sjogren’s syndrome | 1.5 – 2.17 | Haematological malignancy including Non Hodgkin Lymphoma, Hodgkin lymphoma, multiple myeloma, leukemia and solid tumors including lung cancer, thyroid cancer, Non Melanoma Skin Cancer, kidney/ urinary tract cancer, liver cancer and prostate cancer | High disease activity at diagnosis, parotid enlargement, low complement levels, and cryoglobulinemia | |
Systemic Sclerosis | 1.24–4.20 | Lung cancer, haematological malignancy | RNA polymerase III antibodies | |
RA | 1.64 and 2.46 respectively | Lung cancer, Lymphoma | Colorectal cancer, breast cancer | |
ANCA associated vasculitis | 1.6 -2.0 | Haematological, urinary tract malignancy, non-melanoma skin cancer | ||
Inflammatory myositis Dermatomyositis> Polymyositis | Adenocarcinomas of the ovaries, GI tract, lung, or breast | Anti-TIF1γ antibody positivity, Anti-NXP2 antibody positivity, age >40 years at the time of IIM onset, features of persistent high disease activity despite immunosuppressive therapy (including relapse of previously controlled disease), dysphagia (moderate to severe) and cutaneous necrosis or ulceration |
The optimal approach to screen for malignancy in rheumatic diseases is still unclear.
(IMACS) has developed recommendations for inflammatory myositis, but for other rheumatic diseases, there is insufficient data to draw conclusions. Basic screening would include CT of the chest and abdomen, mammography, gynecologic examination, pelvic ultrasonography, and tumor marker analysis. Based on the disease and underlying subtype, specific malignancies may be screened for. A whole body PET CT may be considered when basic screening is non-contributory.
Most of the Indian guidelines for cancer screening are extrapolated from international data. Considering the health infrastructure and medical system in our country, they are not easily executed. There is a need for developing Indian guidelines for malignancy screening and specifically for those with rheumatic diseases. Delayed diagnosis leads to higher stage of cancer at diagnosis and poorer remission rates. Continued screening at every visit is necessary, when the initial screening at the time of diagnosis is negative.
A 60-year old lady was diagnosed to have ILD (UIP pattern) and referred for evaluation. She had no co-morbidities and physical examination did not suggest any CTD. The Myositis profile was strongly positive for anti-OJ antibodies and borderline positive for NXP-2. A basic screen including ultrasonography of the abdomen, chest radiograph and routine labs were normal. Immunosuppression with corticosteroids and Mycophenolate was begun for the ILD but she was non-compliant due to various logistics. A year later, she presented with acute lower limb DVT and complained of a vaginal infection. A gynecologist opined it as lichen planus with secondary infection. As it was a non-healing ulcer, a punch biopsy was done and revealed a vulval squamous cell carcinoma. Due to her advanced ILD, she was deemed to be a high-risk candidate for radical vulvectomy and is on palliative radiation therapy. The effect of radiation on her ILD remains a concern. This case opens up important issues like – was there a window of opportunity for early detection of malignancy, what further screening could have been done, do borderline values of NXP-2 or TIF1-γ warrant extensive evaluation, the importance of regular screening at every visit, and being watchful for paraneoplastic manifestations of malignancy.
