Arthritis Care & Research Vol. 66, No. 7, July 2014, pp 1127–1128 © 2014, American College of Rheumatology
LETTERS DOI 10.1002/acr.22243
Clinical predictors in chronic articular adult-onset Still’s disease: comment on the article by Ichida et al To the Editor: We read with great interest the article by Ichida et al published recently in Arthritis Care & Research regarding the clinical manifestations of a large cohort of patients with adult-onset Still’s disease (AOSD) (1). We fully agree with the authors, and we would like to make a brief comment on both the possibility of erosive arthritis and the need for reliable clinical predictors of outcome to treat arthritis aggressively as soon as possible. The evolution of AOSD may be self-limited, intermittent, and chronic (2); the latter having the worst prognosis quoad valetudinem because of the erosion associated with articular involvement. In contrast to rheumatoid arthritis (RA), erosions are not an early event. The characteristics of osteoarticular involvement in AOSD are both erosions and joint space narrowing (JSN). Because of this, we focused on this topic using the Simple Erosions Narrowing Score (SENS) (3); in particular, we observed that an active polyarthritis persisting over 6 months from the onset, irrespective of the involved joints, was strongly (P ⬍ 0.001) associated with the development of a chronic course of the disease. This could be considered tautological, but it is worth considering that, as in early RA, the persistence of joint symptoms over time is the most reliable chronicity index. Contrary to what was claimed by Ichida et al, in our study, higher levels of ferritin were significantly (P ⬍ 0.002) associated with a chronic disease course. Moreover, comparing serum ferritin levels in patients with a chronic systemic and chronic articular course at the time of diagnosis and 6 months later, we concluded that the persistence of high ferritin levels after appropriate treatment may predict a chronic articular course (4). In our study, we also identified factors associated with the rate of progress of the articular disease, as measured with the SENS. The mean annual increase in the SENS was associated with ferritin level (P ⬍ 0.001) and the Disease Activity Score in 28 joints (P ⬍ 0.001); in particular, the SENS increased faster for higher levels of these 2 predictors. The same applied separately to erosions (P ⬍ 0.001 and P ⬍ 0.08, respectively) and JSN (P ⬍ 0.001 for both). The mean annual increase slowed down with time (measured by the number of years following diagnosis) for JSN (P ⬍ 0.001) and the SENS (P ⫽ 0.002). As far as our study is concerned (3), the clinical findings not only exhibited some inconsistencies with the case series by Ichida et al, but also with previous studies. Some possible explanations include a selection bias and also different genetic backgrounds. As far as treatments with biologic agents are concerned,
according to our experience and data from studies in the literature, we would like to point out that anti–tumor necrosis factor ␣ (anti-TNF␣) medications may be helpful in controlling both systemic and articular symptoms of refractory AOSD. TNF␣ blockade would not be as effective in slowing down the articular damage as in improving systemic and osteoarticular symptoms. This leads to the awareness that anti-TNF␣ agents should not be a conceivable first-line therapy in AOSD. Owing to a more targeted action and a more reassuring safety profile, as well as more evidence-based effectiveness, the interleukin-1 and interleukin-6 receptor antagonists anakinra and tocilizumab could actually be considered a first-choice therapy in AOSD patients. Matteo Colina, MD, PhD Ospedale Santa Maria della Scaletta Imola, Italy Francesco Trotta, MD University of Ferrara Ferrara, Italy 1. Ichida H, Kawaguchi Y, Sugiura T, Takagi K, Katsumata Y, Gono T, et al. Clinical manifestations of adult-onset Still’s disease presenting with erosive arthritis: association with low levels of ferritin and interleukin-18. Arthritis Care Res (Hoboken) 2014;66:642– 6. 2. Cush JJ, Medgser TA Jr, Christy WC, Herbert DC, Cooperstein LA. Adult-onset Still’s disease: clinical course and outcome. Arthritis Rheum 1987;30:186 –94. 3. Colina M, Zucchini W, Ciancio G, Orzincolo C, Trotta F, Govoni M. The evolution of adult-onset Still disease: an observational and comparative study in a cohort of 76 Italian patients. Semin Arthritis Rheum 2011;41:279 – 85. 4. Colina M, Ciancio G, Govoni M. Adult-onset Still’s disease: still a long way to go [letter]. Clin Exp Rheumatol 2012;30:143.
DOI 10.1002/acr.22242
Reply To the Editor: We appreciate the comments by Colina and Trotta and their interest in our article on the clinical manifestations of 2 subsets of patients with AOSD. Because of the retrospective nature of our study, various treatments were included, depending upon the particular rheumatologist treating the patients. We understand that the levels of serum ferritin and interleukin-18 are a good indicator of the severity of several clinical features, including polyarthritis in patients with AOSD, as reported previously. Patients with high levels of ferritin are frequently subject to complication with extraarticular manifestations, including macrophage activation syndrome. Therefore, these patients might be treated with a high dose of prednisolone, with immunosuppressants as the first therapy. Conversely, patients with low levels of ferritin (⬍1,500 ng/ml) are usually treated with a low dose of prednisolone as the first therapy. This bias regarding the first therapy treatment was a 1127
LETTERS DOI 10.1002/acr.22243
Clinical predictors in chronic articular adult-onset Still’s disease: comment on the article by Ichida et al To the Editor: We read with great interest the article by Ichida et al published recently in Arthritis Care & Research regarding the clinical manifestations of a large cohort of patients with adult-onset Still’s disease (AOSD) (1). We fully agree with the authors, and we would like to make a brief comment on both the possibility of erosive arthritis and the need for reliable clinical predictors of outcome to treat arthritis aggressively as soon as possible. The evolution of AOSD may be self-limited, intermittent, and chronic (2); the latter having the worst prognosis quoad valetudinem because of the erosion associated with articular involvement. In contrast to rheumatoid arthritis (RA), erosions are not an early event. The characteristics of osteoarticular involvement in AOSD are both erosions and joint space narrowing (JSN). Because of this, we focused on this topic using the Simple Erosions Narrowing Score (SENS) (3); in particular, we observed that an active polyarthritis persisting over 6 months from the onset, irrespective of the involved joints, was strongly (P ⬍ 0.001) associated with the development of a chronic course of the disease. This could be considered tautological, but it is worth considering that, as in early RA, the persistence of joint symptoms over time is the most reliable chronicity index. Contrary to what was claimed by Ichida et al, in our study, higher levels of ferritin were significantly (P ⬍ 0.002) associated with a chronic disease course. Moreover, comparing serum ferritin levels in patients with a chronic systemic and chronic articular course at the time of diagnosis and 6 months later, we concluded that the persistence of high ferritin levels after appropriate treatment may predict a chronic articular course (4). In our study, we also identified factors associated with the rate of progress of the articular disease, as measured with the SENS. The mean annual increase in the SENS was associated with ferritin level (P ⬍ 0.001) and the Disease Activity Score in 28 joints (P ⬍ 0.001); in particular, the SENS increased faster for higher levels of these 2 predictors. The same applied separately to erosions (P ⬍ 0.001 and P ⬍ 0.08, respectively) and JSN (P ⬍ 0.001 for both). The mean annual increase slowed down with time (measured by the number of years following diagnosis) for JSN (P ⬍ 0.001) and the SENS (P ⫽ 0.002). As far as our study is concerned (3), the clinical findings not only exhibited some inconsistencies with the case series by Ichida et al, but also with previous studies. Some possible explanations include a selection bias and also different genetic backgrounds. As far as treatments with biologic agents are concerned,
according to our experience and data from studies in the literature, we would like to point out that anti–tumor necrosis factor ␣ (anti-TNF␣) medications may be helpful in controlling both systemic and articular symptoms of refractory AOSD. TNF␣ blockade would not be as effective in slowing down the articular damage as in improving systemic and osteoarticular symptoms. This leads to the awareness that anti-TNF␣ agents should not be a conceivable first-line therapy in AOSD. Owing to a more targeted action and a more reassuring safety profile, as well as more evidence-based effectiveness, the interleukin-1 and interleukin-6 receptor antagonists anakinra and tocilizumab could actually be considered a first-choice therapy in AOSD patients. Matteo Colina, MD, PhD Ospedale Santa Maria della Scaletta Imola, Italy Francesco Trotta, MD University of Ferrara Ferrara, Italy 1. Ichida H, Kawaguchi Y, Sugiura T, Takagi K, Katsumata Y, Gono T, et al. Clinical manifestations of adult-onset Still’s disease presenting with erosive arthritis: association with low levels of ferritin and interleukin-18. Arthritis Care Res (Hoboken) 2014;66:642– 6. 2. Cush JJ, Medgser TA Jr, Christy WC, Herbert DC, Cooperstein LA. Adult-onset Still’s disease: clinical course and outcome. Arthritis Rheum 1987;30:186 –94. 3. Colina M, Zucchini W, Ciancio G, Orzincolo C, Trotta F, Govoni M. The evolution of adult-onset Still disease: an observational and comparative study in a cohort of 76 Italian patients. Semin Arthritis Rheum 2011;41:279 – 85. 4. Colina M, Ciancio G, Govoni M. Adult-onset Still’s disease: still a long way to go [letter]. Clin Exp Rheumatol 2012;30:143.
DOI 10.1002/acr.22242
Reply To the Editor: We appreciate the comments by Colina and Trotta and their interest in our article on the clinical manifestations of 2 subsets of patients with AOSD. Because of the retrospective nature of our study, various treatments were included, depending upon the particular rheumatologist treating the patients. We understand that the levels of serum ferritin and interleukin-18 are a good indicator of the severity of several clinical features, including polyarthritis in patients with AOSD, as reported previously. Patients with high levels of ferritin are frequently subject to complication with extraarticular manifestations, including macrophage activation syndrome. Therefore, these patients might be treated with a high dose of prednisolone, with immunosuppressants as the first therapy. Conversely, patients with low levels of ferritin (⬍1,500 ng/ml) are usually treated with a low dose of prednisolone as the first therapy. This bias regarding the first therapy treatment was a 1127
