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To the Editors:

We read with great interest the article by Nikpour et al, recently published in Arthritis Care & Research, concerning the frequency of flares and persistently active disease (PAD) in patients affected with systemic lupus erythematosus (SLE) (1). In recent years, the introduction of several new therapeutic agents for SLE patients required the use of specific indices for the evaluation of disease activity and response to therapy. Moreover, clinicians and researchers felt the necessity, especially in clinical trials, of establishing the conditions to define chronic disease activity and flare occurrence. In their study, Nikpour et al evaluated SLE patients who were seen in the Lupus Clinic of Toronto University and assessed at least twice per year (in 2004 or 2005) with a minimum interval of 2 months between clinic visits (1). According to the literature, flare was defined as an increase in the SLE Disease Activity Index 2000 update (SLEDAI-2K) score of ≥4 from the previous visit (2). PAD was defined as a SLEDAI-2K score of ≥4, excluding serology alone, on ≥2 consecutive visits. The authors found that of the 417 SLE patients studied in 2004, 35.3% had ≥1 flare episode, whereas 52.3% had PAD during the year. Similarly, in 2005, of the 458 SLE patients studied, 28.0% had ≥1 flare episode, whereas 46.1% showed PAD. No major differences were observed in the organ systems involvement between flares and PAD. In rank order, immunologic, cutaneous, renal, musculoskeletal, and neurologic were the most common occurring manifestations. The authors concluded that the periods of PAD were more common than flare episodes, PAD was present in nearly half of the patients, and that such incidence was maintained within the 2 years of study (1).

We would like to report our experience with SLE patients who were referred to the Lupus Clinic of the Rheumatology Unit, Sapienza University of Rome. We evaluated 116 consecutive patients during a 1-year followup from September 2008 to September 2009. Patients provided written informed consent at the time of their first visit. At each visit, the patients underwent a complete physical examination, and the clinical and laboratory data were collected in a standardized, computerized, and electronically-filled form, which included demographics, past medical history with date of diagnosis, comorbidities, and previous and concomitant treatments.

A blood sample for evaluation of serum complement C3 and C4 levels and determination of antinuclear and anti–double-stranded DNA antibody titers (assessed with indirect immunofluorescence according to standard methods) was also obtained. A urine protein analysis was performed in patients with renal involvement. Disease activity was assessed using the SLEDAI-2K and the European Consensus Lupus Activity Measure scores, while chronic damage was measured by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index score (2–4). All the patients were seen at least twice per year, even if most of the patients were evaluated 4 times per year (every 3 months). Selected patients could be seen more often, with a minimum interval of 2 months between visits.

Of the 116 SLE patients, 63 (54.3%) were assessed at least twice per year and were included in the study. Patients were primarily women (n = 59 [93.6%]), the mean ± SD age was 41.3 ± 10.6 years, and the mean ± SD disease duration was 147 ± 99.1 months. Five (7.9%) of these 63 patients experienced ≥1 flare episode, whereas 9 (14.3%) of the patients experienced PAD during the year. The musculoskeletal system was the most frequently involved organ system at the time of flare or during a period of PAD, while the renal system was more frequently involved in patients who experienced PAD (3 of 9 [33.3%]) (Table 1). In our population we observed a lower frequency of flares and PAD as compared with patients seen in the Lupus Clinic of Toronto University, but with similar organ system involvement. Considering PAD, a lower incidence of renal involvement was observed in our cohort compared with Nikpour et al (33.3% versus 51.8%).

Table 1. Demographic characteristics of SLE patients (n = 63), and flares and PAD occurrence frequency*
  • *

    Values are the number (percentage) of patients unless otherwise indicated. SLE = systemic lupus erythematosus; PAD = persistently active disease.

Age, mean ± SD years41.3 ± 10.6
Disease duration, mean ± SD months147 ± 99.1
Flare5 (7.5)
 Musculoskeletal2 (40.0)
 Skin2 (40.0)
 Immunologic5 (100.0)
 Hematologic2 (40.0)
PAD9 (14.3)
 Musculoskeletal4 (44.4)
 Skin3 (33.3)
 Renal3 (33.3)
 Immunologic2 (22.2)
 Hematologic1 (11.1)
 Neurologic1 (11.1)

The findings of a lower incidence of flares and PAD in our population as compared with Nikpour and colleagues might be explained by the smaller cohort, the shorter period of observation, or by ethnic differences. According to Nikpour and colleagues, we can conclude that flares and PAD may be considered as useful parameters of clinical evaluation in patients affected with SLE in the monitoring of the disease activity and progression, as well as the response to therapies. However, especially in the case of clinical trials, the very low and diverging incidence between populations might reveal biases. Larger studies are needed to confirm these issues.

  • 1
    Nikpour M, Urowitz MB, Ibanez D, Gladman DD. Frequency and determinants of flare and persistently active disease in systemic lupus erythematosus. Arthritis Rheum 2009; 61: 11528.
  • 2
    Gladman DD, Ibanez D, Urowitz MB. Systemic Lupus Erythematosus Disease Activity Index 2000. J Rheumatol 2002; 29: 28891.
  • 3
    Mosca M, Bencivelli W, Vitali C, Carrai P, Neri R, Bombardieri S. The validity of the ECLAM index for the retrospective evaluation of disease activity in systemic lupus erythematosus. Lupus 2000; 9: 44550.
  • 4
    Gladman DD, Urowitz MB, Goldsmith CH, Fortin P, Ginzler E, Gordon C, et al. The reliability of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index in patients with systemic lupus erythematosus. Arthritis Rheum 1997; 40: 80913.

Fabrizio Conti MD*, Fulvia Ceccarelli MD*, Carlo Perricone MD*, Laura Massaro MD*, Francesca Romana Spinelli MD*, Guido Valesini MD Professor*, * Sapienza Università di Roma, Rome, Italy.