RESEARCH - Sinus problems in rheumatoid arthritis patients

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Introduction

Sinus problems, whose symptoms are primarily associated with fatigue and

increased pain (1;2), are common in the general population and may be

increased in persons with immune disorders (3;4). In addition, clinical

trials suggest an increase in sinus symptoms in anti-TNF treated persons

with RA (5).

In the current study we had several aims: 1) to determine that rate of sinus

problems and whether they occurred more frequently in persons with RA; 2) to

determine which clinical symptoms were associated with sinus problems; 3) to

determine if anti-TNF therapy or other DMARD therapy was associated with

sinus problems; and 4) to determine the incidence rate of hospitalization

for sinus disease in persons with RA.

Sinus Disorders in Rheumatoid Arthritis: Prevalence and Treatment Effects

Kaleb Michaud and Fred Wolfe -- National Data Bank for Rheumatic Diseases,

Wichita, KS, USA

Abstract

PURPOSE: Sinus problems are common in the population. In rheumatoid

arthritis randomized clinical trials (RCT) the incidence of sinus infection

was increased among patients receiving anti-TNF therapies compared with

persons not on such therapies. Patients with RA might be at increased risk

for sinus disorders because of rheumatoid arthritis (RA) or because of

immuno-modulatory therapies. The purpose of this study is to determine if

rates of sinus disease are increased in RA and whether RA treatments alter

the risk of sinus disease.

METHODS: As part of a longitudinal study of rheumatic disease outcomes,

7,243 patients with RA, 1,667 with osteoarthritis (OA) and 447 with

fibromyalgia were evaluated in 2003 as to sinus problems. We determined

medical visits and prescription medication use for sinus problems, and

defined an important sinus problem as one that required a physician visit.

RESULTS: The lifetime prevalence of sinus disorders diagnosed by a physician

was 42.9%. During the previous 6 months 22.4% of RA patients, 24.0% of OA

patients and 25.1 % of fibromyalgia patients visited a physician for a sinus

problem (p = 0.181) and 22.3%, 24.0% and 25.1% received a prescription

medication for a sinus problem (p = 0.184). After adjustment for age and

sex, the rate of physician visits was significantly lower for RA patients

(22.1%) compared with OA patients (24.8%), p = 0.021. We developed a

predictive multivariable model for sinus problem physician visits in RA

patients (Table 1). The strongest predictor of sinus problems was a history

of allergies and younger age. Sinus problems were also more common in whites

and among those with an asthma history. Etanercept (odds ratio 1.2 (95%

C.I.: 1.0 to 1.4) increased the risk of sinus problems while leflunomide (OR

0.8 (0.8 to 1.0)) and sulfasalazine (OR 0.7 (0.5 to 0.9)) were associated

with reduced risk. Other (non-significant) variables are omitted from Table

1. In contradistinction to the modest associations of treatment with

outpatient medical visits, a strong association was seen for hospitalization

for sinus disease with prior (lagged) prednisone therapy (OR 10.7 (95% C.I.:

3.1 to 36.4)) but not with lagged DMARD or biologic therapy, after

controlling for age, sex and allergies.

CONCLUSIONS: Medical visits for sinus problems are not increased in RA

compared to OA and fibromyalgia. Among RA patients etanercept is a modest

risk factor for sinus problems, and sulfasalazine and leflunomide appear to

reduce the risk. Antecedent prednisone substantially increases the risk of

hospitalization for sinus surgery. However, as prednisone may have been used

as a sinus treatment, it is not possible to say if prednisone is causally

linked to sinus surgery.

Discussion (cont.)

Upper respiratory and sinus infections are more common in anti-TNF treated

patients than in control subjects in clinical trials (5), with very slight

increases in those treated with adalimumab and for sinusitis in those

treated with infliximab (12% vs. 6%) (5). In clinical trials, upper

respiratory infections and sinusitis were the most frequently reported

infections in patients receiving etanercept or placebo, and the rate of

upper respiratory tract infections was 17% in placebo group and 22% in

etanercept group. There were no increases in the rates of serious infections

(requiring hospitalization) (19).

However, the data of the current study indicate that sinus problems are not

increased in persons with RA, and after adjustment for age and sex are even

slightly reduced compared with OA, although the difference, though

statistically significant, is small (24.8% vs. 22.1%). We found that

sulfasalazine, although use by few patients (5.8%) has a protective effect

on sinus problems, OR 0.62 (95% C.I.: 0.47-0.82). This reduction might be

related to its anti-bacterial effect (20;21). We also found that leflunomide

had a reduced association with sinus problems (OR 0.83 (95% C.I.:

0.77-0.99).

Persons receiving etanercept had an increased risk of sinus infections in

age and sex adjusted analyses of Table 2 (OR 1.21 (95% C.I.: 1.04-1.41)).

The effect was decreased in multivariate analyses of Table 3 (OR 1.16 (95%

C.I.: 0.99-1.36). However, compared with infliximab the increased risk

remained: OR 1.23 (95% C.I.: 1.03-1.48).

In summary, sinus problems are not increased in RA compared with patients

with OA and fibromyalgia. Slight protective effects on sinus problems are

noted with sulfasalazine and leflunomide, and a slight increase in risk of

sinus problems is noted with etanercept.

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