Felty syndrome

Rheumatoid arthritis (RA) is an inflammatory disease typically affecting the joints, but the systemic inflammatory process may involve other tissues and organs. Many extra-articular manifestations are recognized, which are related to worse long outcomes. Rheumatoid nodules are the most common extra-articular feature, found in about 30% of patients. Secondary Sjögren's syndrome and pulmonary manifestations are observed in almost 10% of patients, also in the early disease. Active RA with high disease activity has been associated with an increased risk of such features. Male gender, smoking habit, severe joint disease, worse function, high pro-inflammatory markers levels, high titer of rheumatoid factor, and HLA-related shared epitope have been reported as clinical predictors of occurrence of these rheumatoid complications. In addition, there is a little evidence deriving from randomized controlled trials in this field, thus the therapeutic strategy is mainly empiric and based on small case series and retrospective studies. However, considering that these extra-articular manifestations are usually related to the more active and severe RA, an aggressive therapeutic strategy is usually employed in view of the poor outcomes of these patients.

The extra-articular features of RA remain, despite the improvement of joint damage, a major diagnostic and therapeutic challenge, since these are associated with a poor prognosis and need to be early recognized and promptly managed.

Les leucémies à grands lymphocytes granuleux (LGL) désignent des hémopathies caractérisées par la prolifération monoclonale de grands lymphocytes riches en granulations azurophiles, de phénotype T CD3⁺CD57⁺ ou Natural Killer (NK) CD3^–CD56⁺. La classification de l’Organisation mondiale de la santé (OMS) distingue ainsi trois entités : les leucémies LGL T, les expansions chroniques à cellules NK et les leucémies agressives à cellules NK. Les leucémies LGL T et les expansions chroniques à cellules NK ont une évolution indolente, principalement marquée par l’existence d’une cytopénie ou d’une pathologie auto-immune associée. Leur pronostic est conditionné par l’existence de complications infectieuses secondaires à la neutropénie. Le traitement repose en première intention sur les immunosuppresseurs (méthotrexate, ciclosporine, cyclophosphamide). Les leucémies agressives à cellules NK se présentent sous la forme d’un syndrome tumoral qui fait rapidement suspecter l’hémopathie sous-jacente. Il s’agit d’hémopathies peu chimiosensibles dont le pronostic est réservé. Les progrès récents dans la connaissance de la physiopathologie de ces hémopathies ont permis de préciser les mécanismes à l’origine de la pérennisation du clone LGL et d’identifier de nouvelles cibles thérapeutiques.

Large granular lymphocyte leukemia (LGL) is a hematologic disorder characterized by a monoclonal expansion of large lymphocytes containing azurophilic granules with a T CD3⁺CD57⁺ or Natural Killer (NK) CD3^–CD56⁺ phenotype. The World Health Organization (WHO) classification identifies three entities: the T LGL, the chronic lymphoproliferative disorder of NK-cells, and the aggressive NK-cell leukemia. T LGL and chronic lymphoproliferative disorder of NK-cells are indolent diseases frequently associated with cytopenias and a wide spectrum of auto-immune manifestations. Neutropenia can lead to recurrent bacterial infections, which represent an indication of initiating a treatment in most of the cases. Immunosuppressive therapies are usually used in this context. In contrast, aggressive NK-cell leukemia follows a fulminant course with a poor prognosis because patients are refractory to most of the treatments. There is now a considerable interest in the pathophysiology of the disease with the perspective of new therapeutic options.

Rheumatoid arthritis (RA) is a chronic inflammatory systemic disorder of unknown etiology. This disease affects about 0.5–1% of the population worldwide, most commonly middle-aged women. In many cases, ongoing synovitis of diarthrodial joints leads to destruction of articular cartilage and juxtaarticular bone. The aetiology of RA remains elusive, although it appears that genetic, infectious, environmental, and hormonal factors are all involved in complex, interrelated ways. Extra-articular manifestations can be detected in almost any organ system, causing considerable disease-related morbidity and interference with quality of life. Cutaneous manifestations of RA include three principal reaction patterns: (i) extravascular palisading granulomatous inflammation, (ii) interstitial and or subcuticular neutrophilia, and (iii) active vasculopathy encompassing lymphocyte-dominant, neutrophil-rich, and granulomatous vasculitis. The most widely recognized skin lesion is the rheumatoid nodule, but various cutaneous lesions can be observed either related to the disease itself or to the commonly used drugs.

Rheumatoid arthritis is a chronic inflammatory arthritis with significant extra-articular manifestations. Of note are unique cutaneous manifestations that the dermatologist may encounter. This article will make the dermatologist more cognizant of these skin findings in patients with this systemic inflammatory disorder. It examines rheumatoid arthritis, focusing on the general nonspecific and disease-specific rheumatoid arthritic skin changes. Classic rheumatoid nodules, accelerated rheumatoid nodulosis, rheumatoid nodulosis, rheumatoid vasculitis, Felty syndrome, pyoderma gangrenosum, interstitial granulomatosus dermatitis with arthritis, palisaded neutrophilic and granulomatosis dermatitis, rheumatoid neutrophilic dermatitis, juvenile rheumatoid arthritis, and adult-onset Still disease are reviewed. Understanding the cutaneous expressions of rheumatoid arthritis may lead to early diagnosis, prompt treatment, and lower morbidity and mortality for the affected persons.

At the completion of this learning activity, participants should be able to describe rheumatoid arthritis in terms of its epidemiology, etiology, pathogenesis, and general and specific cutaneous manifestations.

Felty's syndrome (FS) comprises a triad of rheumatoid arthritis (RA), neutropenia and splenomegaly, occurring in less than 1% of RA patients. Clinically it is characterized by severe joint destruction contrasting with moderate or absent joint inflammation and severe extra-articular disease, including a high frequency of rheumatoid nodules, lymphadenopathy, hepatopathy, vasculitis, leg ulcers, skin pigmentation etc. Recurrent bacterial infections are mostly due to the severe, otherwise unexplained neutropenia. The cause of neutropenia lies in both decreased granulopoiesis and increased peripheral destruction of granulocytes. Recurrent infections may lead to increased mortality. Spontaneous remission of the syndrome also occurs.

Over 95% of FS patients are positive for rheumatoid factor (RF), 47–100% are positive for antinuclear antibody (ANA), and 78% of patients have the HLA-DR4*0401 antigen. Some 30% of FS patients have large granular lymphocyte (LGL) expansion. LGL expansion associated with uncomplicated RA is immunogenetically and phenotypically very similar to but clinically different from FS. Neutropenia of FS can be effectively treated with disease-modifying anti-rheumatic drugs (DMARDs), the widest experience being with methotrexate (MTX). Results of treatment with granulocyte colony-stimulating factor (G-CSF) are encouraging, but there is no experience with other biological agents.

Splenectomy results in immediate improvement of neutropenia in 80% of the patients, but the rate of infection decreases to a lesser degree.