What is the likely diagnosis and appropriate work‑up for a 30‑year‑old woman with intermittent cervical lymphadenopathy, mild transaminase elevation, positive antinuclear antibody with homogeneous pattern, slightly elevated lactate dehydrogenase, and negative anti‑double‑stranded DNA antibodies?

Likely Diagnosis and Workup

Most Likely Diagnosis

This clinical presentation is most consistent with early or incomplete systemic lupus erythematosus (SLE), with lupus lymphadenopathy as a prominent feature. 1 The combination of intermittent cervical lymphadenopathy, positive ANA with homogeneous pattern, mildly elevated transaminases, and negative anti-dsDNA antibodies in a young woman strongly suggests SLE, though she does not yet meet full diagnostic criteria.

Key Diagnostic Considerations

Why SLE is Most Likely

• Lupus lymphadenopathy occurs in 5-7% of patients at disease onset and can present as isolated cervical lymphadenopathy, even before other SLE manifestations develop 1
• The homogeneous ANA pattern is characteristic of SLE and correlates with anti-dsDNA and anti-histone antibodies 1
• Mildly elevated liver enzymes occur commonly in SLE patients and can represent autoimmune hepatitis or lupus hepatitis 2, 3
• Negative anti-dsDNA does not exclude SLE, as only 70% of SLE patients are anti-dsDNA positive; this patient may have early disease 1
• The intermittent nature of the lymphadenopathy is typical of lupus lymphadenopathy, which fluctuates with disease activity 1

Alternative Diagnoses to Exclude

Kikuchi-Fujimoto disease (KFD) must be considered, as it presents with cervical lymphadenopathy, fever, and leukopenia in young women and is associated with SLE in up to 30% of cases 4. KFD can precede, coincide with, or follow the diagnosis of SLE 4.

Autoimmune lymphoproliferative syndrome (ALPS) is less likely because it requires persistent lymphadenopathy for >6 months affecting ≥2 nodal chains plus elevated TCR α/β double-negative T cells (≥1.5% of total lymphocytes or ≥2.5% of T lymphocytes) 5. Your patient's intermittent lymphadenopathy and lack of mention of DNT cells make this diagnosis unlikely.

Recommended Workup Algorithm

Immediate Laboratory Testing

Complete the SLE serologic panel:

• Anti-Smith antibodies (highly specific for SLE) 1
• Anti-Ro/SSA and anti-La/SSB antibodies 1
• Complement levels (C3, C4, CH50) – low levels suggest active SLE 1
• Complete blood count with differential to assess for cytopenias (anemia, leukopenia, thrombocytopenia) 1, 4
• Direct and indirect Coombs test if anemia is present to evaluate for autoimmune hemolytic anemia 1
• Urinalysis with microscopy and urine protein-to-creatinine ratio to screen for lupus nephritis 1

Evaluate the transaminase elevation:

• Repeat liver function tests including ALT, AST, alkaline phosphatase, bilirubin, and albumin 2, 3
• Fasting lipid profile and glucose to assess for metabolic syndrome/nonalcoholic fatty liver disease 3
• Hepatitis B surface antigen and hepatitis C antibody 2, 3
• Serum iron, ferritin, and total iron-binding capacity to exclude hemochromatosis 2, 3
• If initial workup is unremarkable, consider anti-smooth muscle antibody, anti-liver/kidney microsomal antibody type 1, and anti-mitochondrial antibody to evaluate for autoimmune hepatitis or primary biliary cholangitis 2

Additional inflammatory markers:

• Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) 5, 6
• Lactate dehydrogenase (LDH) – you mention it is 210, which is mildly elevated and can be seen in SLE, lymphoma, or hemolysis 6, 1

Imaging Studies

Contrast-enhanced CT of neck, chest, abdomen, and pelvis to:

• Characterize the extent and distribution of lymphadenopathy 7, 6
• Exclude malignancy (lymphoma) 7, 6
• Assess for hepatosplenomegaly or other organ involvement 1

Tissue Diagnosis

Excisional lymph node biopsy is strongly recommended because:

• Fine-needle aspiration has limited utility in distinguishing lupus lymphadenopathy from Kikuchi-Fujimoto disease and lymphoma 7, 6
• Excisional biopsy has >95% diagnostic yield and allows for comprehensive histopathology and immunohistochemistry 7, 6
• Lupus lymphadenopathy shows reactive follicular hyperplasia with scattered plasma cells, immunoblasts, and varying degrees of coagulative necrosis; Bcl2 is negative, excluding lymphoma 1
• Kikuchi-Fujimoto disease shows histiocytic necrotizing lymphadenitis without neutrophils 4
• Lymphoma must be definitively excluded, requiring immunophenotyping and flow cytometry 7, 6

Critical Pitfalls to Avoid

Do not prescribe multiple courses of antibiotics without clear signs of bacterial infection (warmth, erythema, localized tenderness, fever, recent URI or dental problem), as this significantly delays diagnosis of underlying systemic disease or malignancy 7, 6. Your patient's intermittent lymphadenopathy without infectious signs does not warrant antibiotics.

Do not assume negative anti-dsDNA excludes SLE. Anti-dsDNA is present in only 70% of SLE patients, and lupus lymphadenopathy can be the sole presenting feature before other criteria develop 1.

Do not delay biopsy. Lymphadenopathy persisting ≥2 weeks or >1.5 cm in a patient with systemic symptoms and positive ANA requires tissue diagnosis to exclude lymphoma and establish the specific etiology 7, 6.

Management Considerations

If lupus lymphadenopathy is confirmed on biopsy and additional SLE criteria are met, treatment typically includes hydroxychloroquine, corticosteroids (prednisone), and potentially steroid-sparing agents such as mycophenolate mofetil, with close monitoring for development of lupus nephritis or other organ involvement 1.

If Kikuchi-Fujimoto disease is diagnosed, treatment is supportive with NSAIDs and corticosteroids for symptomatic relief, as the disease is self-limited; however, close follow-up is essential because KFD is associated with subsequent development of SLE in up to 30% of cases 4.