A 47-year-old woman with a long-standing history of systemic lupus erythematosus (SLE) comes to the office due to a month of worsening fatigue and low-grade fevers. She has lost 4.6 kg (10 lb) during this time but has no joint pain, cough, dyspnea, or chest pain. Other medical conditions include hypertension, hypothyroidism, and anemia of chronic disease. The patient takes hydroxychloroquine for SLE and uses glucocorticoids intermittently for acute symptom flares. Temperature is 37.5 C (99.5 F), blood pressure is 132/84 mm Hg, pulse is 78/min, and respirations are 14/min. Physical examination shows no scleral icterus, oral ulcers, or skin rashes. The cervical and axillary lymph nodes are enlarged. The lungs are clear on auscultation, and heart sounds are normal. The abdomen is soft and nontender with no organomegaly. There is no extremity edema or joint tenderness. Laboratory results are as follows:
| Complete blood count | |
| Hemoglobin | 11 g/dL |
| Mean corpuscular volume | 82 µm3 |
| Platelets | 225,000/mm3 |
| Leukocytes | 6,200/mm3 |
| Serum chemistry | |
| Blood urea nitrogen | 14 mg/dL |
| Creatinine | 1.1 mg/dL |
| Lactate dehydrogenase, serum | 828 U/L |
| TSH | 2.2 µU/mL |
Which of the following is the most likely cause of this patient's current condition?
This patient with long-standing systemic lupus erythematosus (SLE) has fatigue, low-grade fevers, and lymphadenopathy. Although these symptoms can be seen in the setting of an acute SLE flare, additional manifestations of the disease (eg, joint symptoms, rash, oral ulcers, serositis) are usually present. Furthermore, patients with well-controlled SLE rarely have significant weight loss and elevated lactate dehydrogenase (LDH) levels. Given this constellation of findings, the most likely diagnosis is non-Hodgkin lymphoma (NHL).
Patients with chronic autoimmune diseases (eg, SLE, Sjögren syndrome) are at increased risk for NHL due to persistent B-cell stimulation, immune dysregulation, and exposure to immunosuppressive agents (eg, hydroxychloroquine). NHL often presents with progressive, painless lymphadenopathy and B symptoms (eg, weight loss, fever, night sweats). Laboratory evaluation often reveals elevated LDH, likely due to tumor burden, liver involvement, or occasional hemolysis. Confirmation is usually made by excisional lymph node biopsy.
(Choice A) Although the risk of most lymphoproliferative disorders is elevated in patients with autoimmune disease, acute lymphoblastic leukemia generally manifests in children, not adults. Bone pain is often a prominent complaint. In addition, complete blood count usually shows significant neutropenia and thrombocytopenia, with a white blood cell count that can be decreased or markedly elevated.
(Choice B) Infectious mononucleosis often causes peripheral lymphadenopathy, fatigue, and low-grade fever, but most patients have a sore throat/pharyngitis. Furthermore, significant weight loss and LDH elevation would be atypical.
(Choice C) Certain medications (eg, phenytoin) can cause painless peripheral lymphadenopathy with or without signs of serum sickness (eg, fever, rash, arthralgia). However, hydroxychloroquine does not typically cause these manifestations.
(Choice E) Tuberculosis is a leading cause of peripheral lymphadenopathy in the developing world. Although it is more likely to arise in those taking immunosuppressive agents, patients with tuberculosis lymphadenopathy rarely have systemic manifestations such as fevers or weight loss. Those with disseminated tuberculosis usually have pulmonary symptoms.
Educational objective:
Patients with chronic autoimmune diseases are at increased risk for lymphoproliferative disorders such as non-Hodgkin lymphoma (NHL) due to chronic B-cell stimulation, immune dysregulation, and use of immunosuppressive agents. NHL often presents with painless lymphadenopathy and B symptoms.