Fever with generalised lymphadenopathy is an extremely common presentation in clinical practice. There are several causes of this, the most common being tuberculosis, sarcoidosis, lymphoma, human immunodeficiency virus and infectious mononucleosis.
A degree of lymphadenopathy is frequently a characteristic of established systemic lupus erythematosus (SLE), but it is rarely the primary presenting feature. Studies have shown the most common sites of lymphadenopathy in SLE include cervical (43%), mesenteric (21%), axillary (18%), and inguinal (17%).1
Hilar and mediastinal lymph node enlargement due to SLE is very rare.2
The presentation of generalised lymphadenopathy with blocks of enlarged retrosternal, mesenteric and retroperitoneal nodes has not been previously described as the initial clinical manifestation of the disease.
Precise differentiation between lupus lymphadenopathy and viral or bacterial infections entails negative serological tests for viruses and negative blood, urine and tissue cultures for bacterial infections. In this case, a careful search for viral and bacterial infections did not reveal an infection.
The absence of granulomata with or without caseation in the inguinal lymph node biopsy, as well as the negative tissue cultures, made tuberculosis and sarcoidosis unlikely.
Palpable lymph nodes in SLE can be bulky enough to mimic lymphoma. However, lymphadenopathy related to lymphoproliferative disorders (LPD) requires the existence of neoplastic lymphoid cells in bone marrow or lymph node biopsies. In this case neither bone marrow nor lymph node biopsies uncovered the presence of any neoplastic disorder.
Anti-dsDNA antibodies assay
Anti-double stranded (ds) DNA antibodies are predominantly seen in SLE; however, they are negative in 30% of cases, whereas they appear in only 0.5% of people without SLE.
This patient had lupus nephritis with anti-dsDNA antibodies and rising anti-dsDNA titres along with hypocomplementaemia, particularly a low C3, which frequently points towards active lupus glomerulonephritis.3
His anti-dsDNA was initially negative. However, it was retested only a few days later using a different assay and was found to be positive. Studies have described cases where patients may be negative in one but not another assay.4
The initial assay was performed using a crithidia luciliae immunofluorescence test (CLIF). The second test used an enzyme linked immunosorbent assay (ELISA).
Research has compared ELISA versus CLIF tests for the effectiveness of anti-dsDNA detection in SLE. ELISA sensitivity was 64% and specificity 95%. For CLIF these values were 39% and 97%, respectively. ELISA therefore has a greater sensitivity than CLIF and thus may explain our findings. Some workers have consequently recommended that ELISA be used in preference to the CLIF test.5,6
Lymphadenopathy and SLE disease severity
Generalised lymphadenopathy is a non-specific sign and is typically not troublesome. It rarely causes immediate danger to the patient. However, it has been found that patients suffering from SLE with lymphadenopathy demonstrate more constitutional symptoms such as tiredness, pyrexia and weight loss, more SLE cutaneous manifestations, higher anti-dsDNA antibodies titres, and diminished complement levels.7
This patient had an early onset of cutaneous symptoms, bilateral pleural effusion, microcytic anaemia, recurrent fever, high titres of ANA, and low complement levels.
Furthermore, among patients with SLE and lymphadenopathy, disease activity calculated using the British Isles Lupus Assessment Group (BILAG) index has been shown to be greater and a higher dose of corticosteroids has been shown to be required to control the disease. Some authors have suggested that lymphadenopathy should be incorporated as one of the clinical findings indicative of disease activity in SLE patients.8
In summary, generalised lymph node enlargement can be caused by active SLE and its presence may be an indication of higher disease severity in these patients. This case demonstrates that in patients with fever and lymphadenopathy, SLE should be considered in the differential diagnosis even if anti-dsDNA antibodies are not found, as the systemic manifestations of lupus can predate, follow, or occur concurrently with generalised lymphadenopathy.
- Extensive lymphadenopathy as the first clinical manifestation of systemic lupus erythematosus (SLE) is rare.
- SLE should be considered in patients presenting with lymphadenopathy when other causes cannot be found.
- Generalised lymphadenopathy may reflect disease severity in SLE.
- Patients may have a negative anti-dsDNA antibody test using one assay, but not when using another.