Mrs P is 64 years old and has had seropositive rheumatoid arthritis (RA) for 30 years. She has never been particularly compliant with her medication and has persistently refused to take DMARDs in the past.
She came to see me one afternoon with symptoms of a chest infection. She had been coughing up purulent, offensive sputum for the preceding five days and was feeling very lethargic and feverish.
On reviewing her notes, I discovered she had been treated with antibiotics three times in the past three months, for another chest infection, for cellulitis and for a UTI.
I prescribed antibiotics and arranged for her to have routine blood tests and a chest X-ray.
I reviewed Mrs P 10 days later, with her results. Although she had improved clinically after taking the course of antibiotics, I was surprised to find that her FBC revealed her to be neutropenic. I referred her urgently to the rheumatology department and she was subsequently diagnosed with Felty's syndrome.
Felty's syndrome, first described in 1924, is a specific subcategory of RA characterised by the triad of RA, severe extra-articular disease and unexplained neutropenia.
It only occurs in patients who are both rheumatoid factor positive and positive for anticyclic citrullinated peptide antibodies.
Felty's syndrome is very uncommon, affecting less than 1% of patients with RA.
It occurs in those who have had RA for at least 10 years and affects women three times more than men. It has become even more uncommon since the advent of DMARDs for patients with RA.
The prevalence is difficult to assess because many patients with Felty's syndrome are asymptomatic.
Owing to severe neutropenia, patients with the condition are susceptible to skin ulcer formation and sepsis.
On examination, patients usually have severe deformities in their joints and may also have rheumatoid nodules. In addition to splenomegaly, some patients may also have hepatomegaly.
Presenting symptoms may include:
- Recurrent infections.
- Weight loss.
- Left upper quadrant pain.
Felty's syndrome is a clinical diagnosis - there is no single investigation that can diagnose it.
In addition to neutropenia, many patients will have anaemia of chronic disease. An ultrasound scan is usually undertaken to assess splenomegaly and hepatomegaly.
A bone marrow biopsy may be performed in some patients in whom the diagnosis is in doubt.
The main differential diagnoses are haematological malignancies. Many experts consider that Felty's syndrome is the same as T-cell large granular lymphocytic leukaemia.1
There is no consensus on the best management for patients with Felty's syndrome. Several DMARDs have been used, with varying success.2
Methotrexate is usually the first choice. If it is not tolerated or is contraindicated, other DMARDs can be given, for example, hydroxychloroquine or sulfasalazine.
Some studies have shown good results with biological agents, especially rituximab.3 This is most commonly used second-line in patients with refractory Felty's syndrome.4
Treatment of the neutropenia depends on the patient's clinical situation and prevention or treatment of the underlying infection.5
Granulocyte colony-stimulating factor is effective in improving neutropenia and thereby reducing the risk of subsequent infections.
It is very important for these patients to receive the pneumococcus vaccination and to have annual influenza vaccinations.
Infections in these patients need to be treated promptly with antibiotics, usually before a swab or sputum result is available. Those with serious life-threatening infections need to be admitted to hospital.
In some patients with Felty's syndrome, the neutropenia will spontaneously improve. However, they remain at increased risk of developing infections.
The amount of activity and exercise undertaken by these patients depends on the infection risk and the spleen size. In general, patients should avoid any activity that could result in blunt trauma to the left upper quadrant, to minimise the risk of splenic injury.
- Dr Newson is a GP in the West Midlands
1. Bockorny B, Dasanu CA.
Autoimmune manifestations in large granular lymphocyte leukemia. Clin Lymphoma Myeloma Leuk 2012; 12(6): 400-5.
2. Heylen L, Dierickx D, Vandenberghe P et al. Targeted therapy with rituximab in Felty's syndrome: a case report. Open Rheumatol J 2012; 6: 312-14.
3. Sarp U, Ataman S. A beneficial long-term and consistent response to rituximab in the treatment of refractory neutropenia and arthritis in a patient with Felty syndrome. J Clin Rheumatol 2014; 20(7): 398.
4. Narvaez J, Domingo-Domenech E, Gomez-Vaquero C et al. Biological agents in the management of Felty's syndrome: a systematic review. Semin Arthritis Rheum 2012; 41(5): 658-68.
5. Newman KA, Akhtari M. Management of autoimmune neutropenia in Felty's syndrome and systemic lupus erythematosus. Autoimmun Rev 2011; 10(7): 432-7.