Background The large granular lymphocyte leukemia (LGG) is a rare lymphoproliferative disorder characterized by neutropenia, splenomegaly and infection, which is associated with rheumatoid arthritis (RA) up to 36% of cases. This clinical picture is similar to Felty's syndrome (FS), a rare complication of RA that may also present LGG proliferation by up to 40%, so both may be considered as part of the same spectrum of disease.
Objectives To describe the clinical, immunological and outcome characteristics of patients with LGG proliferative syndromes associated with RA in a Spanish tertiary hospital.
Methods All the patients with LGG proliferative syndromes associated with RA diagnosed during the period 1999-2013 were included. Demographic, clinical, immunological, therapeutic and outcome data were obtained by reviewing medical records.
Results A total number of 6 cases (SF 4, LGG leukemia 2) were diagnosed during this period, half of them were women, and mean age at diagnosis was 58.5 years (range: 51-84 years). AR was previously diagnosed in 4 patients, with mean disease duration of 14.2 years. In the other 2 cases the LGG syndrome was detected concomitantly to AR diagnosis and duration of joint symptoms was 6 months and 5 years, respectively. All the patients fulfilled 2010 ACR/EULAR classification criteria but the case with shorter disease duration did not meet 1988 ACR criteria due to the absence of radiographic changes. At the time of diagnosis of LGG syndrome, 3 patients had active synovitis, 5 joint sequelae, 2 splenomegaly, and 1 rheumatoid nodules and lower extremity hyperpigmentation. The manifestation that led to the diagnosis was the occurrence of severe or recurrent infections in 5 cases. All of them had elevated acute phase reactants, persistent neutropenia (range: 0-550 neutrophils/mL) and showed LGG in blood smears. Rheumatoid factor test was positive in 5 cases, and anti-CCP antibodies in 3 cases. Hypergammaglobulinemia was detected in all patients and was monoclonal in 2 of them. Immunophenotyping in peripheral blood showed a clonal expansion of aberrant CD8+ T lymphocytes in 4 cases (FS 2, LGG leukemia 2), and was polyclonal in the other 2 cases. The bone marrow biopsy showed LGG infiltration only in the cases of leukemia. All patients were initially treated with glucocorticoids, 5 with concomitant administration of granulocyte colony-stimulating factor due to severe neutropenia. Methotrexate was administered at doses of 15 mg/week in 3 cases, with partial improvement. Patients with LGG leukemia needed chemotherapy regimens, achieving remission in 1 case and partial response in the other. Mean follow-up was 4.6 years and during this period 2 patients (FS 1, LGG leukemia 1) continued having recurrent infections and a patient with FS died of septic shock.
Conclusions Patients with FS and LGG leukemia have similar profiles of clinical and immunological manifestations. Although usually they appear as a late complication of RA, in some patients these syndromes may coincide with the onset of joint disease. The course of these disorders is chronic, indolent, and the prognosis is determined by recurrent infections, which are the leading cause of mortality in these patients.
Disclosure of Interest None declared