What diseases, aside from Kikuchi-Fujimoto disease, are patients with Systemic Lupus Erythematosus (SLE) at increased risk of developing when presenting with lymphadenopathy?

SLE-Associated Lymphadenopathy: Disease Risks Beyond Kikuchi-Fujimoto

Patients with SLE presenting with lymphadenopathy face significantly elevated risks of hematologic malignancies (particularly non-Hodgkin lymphoma with 3-5 fold increased risk), infections (especially with immunosuppressive therapy), and other cancers including lung and cervical malignancies. 1, 2

Primary Malignancy Risks

Hematologic Malignancies

• Non-Hodgkin lymphoma represents the most critical concern, with a 3-5 fold increased incidence compared to the general population. 2
• The overlap between SLE clinical features and lymphoma manifestations creates diagnostic challenges, requiring heightened clinical suspicion when evaluating persistent or atypical lymphadenopathy. 3
• Lymphoproliferative diseases occur at substantially higher rates in SLE patients, necessitating careful pathological evaluation of concerning lymph nodes. 3

Solid Organ Malignancies

• Lung cancer incidence is significantly elevated, particularly in SLE patients who smoke. 1, 2
• Cervical cancer and dysplasia occur more frequently, with up to 16% of SLE patients showing abnormal cervicovaginal cytology, especially those exposed to cyclophosphamide. 1, 2
• Hepatobiliary cancers demonstrate increased incidence in the SLE population. 2
• Breast cancer rates are elevated compared to age-matched controls. 1

Infectious Complications

Opportunistic Infections

• Cytomegalovirus (CMV) antigenaemia occurs in 18-44% of SLE patients, with higher rates in those receiving pulse methylprednisolone or cyclophosphamide. 1
• CMV infection can mimic active SLE flares, making differentiation challenging when lymphadenopathy is present—testing for CMV antigenaemia should be considered in patients on high-dose glucocorticoids. 1

Endemic Infections

• Tuberculosis frequency ranges from 2.5-13.8% in endemic areas and 0-1.4% in low-incidence regions, substantially higher than background population rates. 1
• TB testing before initiating glucocorticoids and immunosuppressive therapy is recommended per CDC guidelines, particularly relevant when lymphadenopathy develops. 1

Viral Hepatitis Reactivation

• While baseline HIV, HBV, and HCV infection rates are not increased in SLE, reactivation risk following immunosuppressive therapy necessitates screening before treatment initiation in patients with risk factors. 1

Critical Diagnostic Approach

When to Pursue Lymph Node Biopsy

• Persistent lymphadenopathy despite treatment, rapidly enlarging nodes, constitutional symptoms (fever, weight loss, night sweats), or atypical features warrant biopsy to exclude malignancy or infection. 3
• Biopsy becomes essential when clinical features overlap between SLE activity, infection, and lymphoma, as serologic markers alone cannot reliably differentiate these entities. 3

Laboratory Evaluation

• Obtain complete blood count (looking for cytopenias suggesting marrow involvement or hemophagocytic syndrome), serum creatinine, urinalysis, complement levels (C3/C4), and anti-dsDNA antibodies to assess SLE activity. 4
• Consider CMV antigenaemia testing in patients on high-dose immunosuppression presenting with lymphadenopathy and systemic symptoms. 1

Common Pitfalls to Avoid

• Do not assume all lymphadenopathy in SLE represents benign reactive changes or disease activity—SLE patients undergo cancer screening less frequently than the general population despite higher risk. 1, 2
• Avoid attributing all constitutional symptoms to SLE flare without excluding infection, particularly CMV and tuberculosis in immunosuppressed patients. 1
• Do not delay biopsy when clinical suspicion for lymphoma exists, as the considerable overlap between SLE and lymphoma features can lead to delayed diagnosis. 3
• Recognize that cyclophosphamide exposure increases cervical cancer risk, requiring vigilant gynecologic screening. 1, 2

Screening Recommendations

• All SLE patients should follow general population cancer screening guidelines at minimum (mammography, cervical cytology, fecal occult blood testing), with consideration for more intensive surveillance given elevated cancer risks. 1, 2
• Development of SLE-specific cancer screening protocols should be considered given the unique epidemiologic profile of this population. 2