A 76-year-old woman comes to the office for evaluation of leukopenia. The patient came to the United States to visit her son a month ago and was seen at an urgent care clinic 2 weeks ago for acute sinusitis, where she was found to have leukopenia. She was prescribed an oral antibiotic, and a repeat blood test was advised. The patient has had 2 episodes of skin infections over the past 3 months. She also has had pain and swelling in the joints of her hands and knees for the past several years. The patient does not use tobacco, alcohol, or illicit drugs. Temperature is 37.2 C (98.9 F), blood pressure is 130/80 mm Hg, and pulse is 74/min. Physical examination shows normal heart and lung sounds, moderate splenomegaly, generalized lymphadenopathy, no sinus tenderness, and well-healing lower extremity ulcerations. The small joints of the hands are swollen and deformed. Laboratory results are as follows: Additional evaluation of this patient is most likely to reveal which of the following?

Question

A 76-year-old woman comes to the office for evaluation of leukopenia.  The patient came to the United States to visit her son a month ago and was seen at an urgent care clinic 2 weeks ago for acute sinusitis, where she was found to have leukopenia.  She was prescribed an oral antibiotic, and a repeat blood test was advised.  The patient has had 2 episodes of skin infections over the past 3 months.  She also has had pain and swelling in the joints of her hands and knees for the past several years.  The patient does not use tobacco, alcohol, or illicit drugs.  Temperature is 37.2 C (98.9 F), blood pressure is 130/80 mm Hg, and pulse is 74/min.  Physical examination shows normal heart and lung sounds, moderate splenomegaly, generalized lymphadenopathy, no sinus tenderness, and well-healing lower extremity ulcerations.  The small joints of the hands are swollen and deformed.  Laboratory results are as follows:  Additional evaluation of this patient is most likely to reveal which of the following?

Quizplus · Accepted Answer

11ec25c8_d520_dba8_bc81_a54c636194bf_MD0003_00 This patient with swollen, deformed hand joints and an elevated erythrocyte sedimentation rate likely has untreated inflammatory polyarthritis. The presence of concurrent neutropenia and splenomegaly raise strong suspicion for Felty syndrome, an uncommon but serious complication of long-standing, erosive rheumatoid arthritis (RA). Felty syndrome is marked by the formation of autoantibodies against neutrophil components and granulocyte colony-stimulating factor, leading to neutropenia (ie, absolute neutrophil count <2,000/mm³) and an increased risk of recurrent bacterial infection (particularly of the skin and sinuses). Neutrophils coated with antibodies are also trapped in the spleen, which usually results in splenomegaly. Most patients also have extraarticular manifestations of RA such as lymphadenopathy, rheumatoid nodules, and/or necrotizing skin lesions. The diagnosis is made based on clinical features but is supported by the presence of high-titer rheumatoid factor and anticitrullinated peptide antibodies (both of which are usually elevated in RA). Most patients are also HLA-DR4 positive (indicating a genetic susceptibility). Other causes of neutropenia should be ruled out with bone marrow biopsy and peripheral smear prior to establishing the diagnosis. Symptoms generally improve with treatment of the underlying RA. (Choice B) Vitamin B₁₂ deficiency can cause pancytopenia due to increased hematopoietic cell apoptosis and impaired DNA maturation. However, patients usually have macrocytic (not normocytic) anemia, and significant neutropenia/recurrent infection would be atypical. This patient's normocytic anemia is likely due to anemia of chronic disease from her joint inflammation. (Choice C) Aplastic anemia is marked by diffusely hypocellular bone marrow due to injury to hematopoietic stem cells. Patients typically have significant reductions in all 3 cell lines (not normal platelet count), and splenomegaly is atypical. (Choice D) Chronic myeloid leukemia is associated with the BCR-ABL1 fusion gene, commonly due to a chromosome 9/22 translocation (Philadelphia [Ph¹] chromosome). Patients often develop splenomegaly and lymphadenopathy but usually have dramatic leukocytosis (often >100,000/mm³), not leukopenia. ¹ (Choice E) Multiple myeloma is a plasma cell neoplasm characterized by production of a monoclonal immunoglobulin. It can present with systemic symptoms, recurrent infection, and normocytic anemia but is also commonly associated with bone pain, renal insufficiency, and hypercalcemia. In addition, splenomegaly is atypical. Educational objective: Felty syndrome is a complication of seropositive rheumatoid arthritis (RA) characterized by neutropenia and splenomegaly. Most patients have high-titer rheumatoid factor and anticitrullinated peptide antibodies (both of which are usually elevated in RA). Risk of recurrent bacterial infection is significantly increased due to neutropenia. References: Felty's syndrome, insights and updates. (http://www.ncbi.nlm.nih.gov/pubmed/25614773) Felty's syndrome without rheumatoid arthritis? (http://www.ncbi.nlm.nih.gov/pubmed/23292482)

A 76-Year-Old Woman Comes to the Office for Evaluation of Leukopenia