Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

all patients

1st line – methotrexate

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ACUTE
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all patients
1st line – 

methotrexate

Choice of agent is determined by prior effectiveness, adverse-effect profile, and physician experience with the various agents.

Methotrexate is the first-line agent in FS.[3] It increases granulocyte count and decreases erythrocyte sedimentation rate 4 to 8 weeks after start of therapy.

Data from a small retrospective cohort suggest that the effect of methotrexate persists for up to 1 year, and that the frequency of intercurrent infections tends to decrease.[16]

Usually combined with folic acid to minimise adverse effects.

A low starting dose is recommended, with small increases every month until the neutrophil count returns to normal. Usually, a dose of 15 mg a week is sufficient. This dose is lower than the current dose used for treating rheumatoid arthritis.

Primary options

methotrexate: 5 mg orally once weekly on the same day of each week initially, increase by 2.5 mg/dose increments at monthly intervals according to response, maximum 15 mg/week

and

folic acid: 5 mg orally once weekly

2nd line – rituximab

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ACUTE
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2nd line – 

rituximab

May be useful in patients who are unresponsive to or intolerant of methotrexate. Rituximab is preferred over other biologic or synthetic disease-modifying agents. Case reports of rituximab-treated patients with FS have found sustained neutrophil response (14 months after initial treatment in one patient), and reduced rheumatoid factor, synovitis, and pain score.[18][19][20][21]

Primary options

rituximab: consult specialist for guidance on dose

3rd line – sulfasalazine or leflunomide

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ACUTE
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all patients
3rd line – 

sulfasalazine or leflunomide

Choice of agent is determined by prior effectiveness, adverse-effect profile, and physician experience with the various agents.

Results from case reports suggest that leflunomide and sulfasalazine can be used as add-on therapy to methotrexate, or for patients with FS who are intolerant of or have an inadequate response to methotrexate.[22][23]

Sulfasalazine has been shown to reduce neutrophil-bound immunoglobulin G.[23]

Primary options

sulfasalazine: 0.5 to 1 g/day orally initially, increase by 0.5 g/day increments once weekly according to response, maximum 3 g/day given in 2-3 divided doses

OR

leflunomide: 10-20 mg orally once daily

4th line – colony-stimulating factors

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4th line – 

colony-stimulating factors

Most useful in patients with severe neutropenia, recurrent infections despite other treatment, or those who require a rapid rise in neutrophil count (e.g., patients undergoing surgery).[4][24]​

Granulocyte colony-stimulating factor (G-CSF or filgrastim) and granulocyte-macrophage colony-stimulating factor (GM-CSF or sargramostim) are effective within 2 weeks of treatment and raise neutrophil counts, stimulate neutrophil function, and reduce infection.[4][17][24]​ Neutrophil levels fall on therapy withdrawal.

Long-term G-CSF in patients with recurrent infections exacerbates arthritis and can cause a leukocytoclastic vasculitis.

The lowest dose should be used that maintains neutrophil counts >1 x 10⁹/L (>1000/microlitre).[3][4] White blood cell (WBC) count should be monitored twice a week in the first 3 weeks of treatment and weekly thereafter.[25]

Primary options

filgrastim: consult specialist for guidance on dose

OR

sargramostim: consult specialist for guidance on dose

5th line – splenectomy

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ACUTE
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5th line – 

splenectomy

Should be considered as a last resort.

Leads to a rapid increase in granulocytes granulocyte count within hours.[17] Granulocytopenia recurs in about 24% of patients following splenectomy, and only 45% of patients remain free of infection.

Moreover, an increased WBC count after splenectomy is not necessarily associated with reduced infection rates. Patients with recurrent infections before surgery usually continue to have infections.[17][25]

Splenectomy may improve synovitis temporarily and lead to leg ulcer healing.[26]

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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