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Spleen Calcifications in Connective Tissue Disorders
LETTERS Spleen Calcifications in Connective Tissue Disorders
W
e read with great interest the report from Tan Tieng and coworkers about the first description of diffuse calcifications of the spleen in systemic lupus erythematosus (SLE) (1). The in-depth review of their own and literature cases emphasized that splenic calcifications are less frequent than other spleen abnormalities in SLE, such as splenomegaly, spleen infarction, and hyposplenism (2). However, the authors suggest that the described calcification pattern— discrete, small, round, diffuse but sparing the capsular and subcapsular area—might be specific of SLE. This aspect is thought to be unique without overlap with patterns known in other diseases. In addition, the more linear, tubular, or ovoid morphology of many of the observed calcifications suggests a vascular distribution. This finding supports that calcified splenic nodules in SLE may represent calcification in the “onion-skin lesions,” characterized by at least 3 separated layers of periarterial fibrosis and regarded as pathognomonic of SLE (3). Considering these novel findings, we aimed to assess whether spleen calcifications might be a characteristic feature of other connective tissue disorders in which spleen calcifications have not yet been described. We decided to
The authors have no conflicts of interest to disclose. Address reprint requests to Yannick Allanore, Service de Rhumatologie A, Hôpital Cochin, 27 Rue du Faubourg St Jacques, 75014 Paris, France. E-mail: yannick. [email protected]
focus on (1) systemic sclerosis (SSc), an orphan and incurable disorder, characterized by an increased frequency of soft-tissue calcifications (4-7); and (2) rheumatoid arthritis (RA), a chronic systemic inflammatory disorder with possible splenic involvement; in particular, spontaneous splenic rupture, abnormal splenic function, and Felty’s syndrome (2). Thus, we systematically analyzed thoracic computed tomographic (CT) scans performed in our cohorts of patients with SSc (N ⫽ 96) and RA (N ⫽ 64) during their regular follow-up, as already reported for SSc patients (8). Their main characteristics are summarized in Table 1. The latest available CT scan in our PACS (Picture Archiving and Communication System), from February 2006 to December 2009, was reviewed by a single experienced radiologist, blinded for the diagnosis. The spleen was screened for calcium-density images in bone and abdominal contrast windows. The aspect, distribution, and number of calcifications were noted. After careful and systematic analysis of the whole sample of CT scans, we found 7 patients with spleen calcifications: 2 patients having SSc (2.1%) and 5 having RA (7.7%). Most were isolated and small, unlike the diffuse calcifications observed in SLE. Only a 64-year-old woman with RA displayed a pattern of 15 to 20 roundand rod-shaped calcifications with variable sizes (Fig. 1). However, they were fewer, less dense, and closer to the capsular region than those found in SLE. This patient had
Table 1 Characteristics of Patients with Rheumatoid Arthritis (RA) and Systemic Sclerosis (SSc)
Age, mean ⫾ standard deviation, SD Females, n (%) Disease duration (yr), mean ⫾ SD Limited/diffuse cutaneous subset, n (%) Subcutaneous calcinosis Positive antinuclear antibodies, n (%) Positive anticentromere antibodies, n (%) Positive antitopoisomerase-1 antibodies, n (%) Positive rheumatoid factors, n (%) Positive anti-CCP antibodies, n (%) Associated autoimmune diseases Sjögren’s syndrome, n (%) Thyroiditis, n (%) Primary biliary cirrhosis, n (%) Systemic lupus erythematosus, n (%) Inflammatory myositis, n (%)
Rheumatoid Arthritis (RA) (n ⫽ 64)
Systemic Sclerosis (SSc) (n ⫽ 96)
57 ⫾ 12.4 56 (87.5) 13 ⫾ 11.5 NA NA 19 (29) 0 (0) 0 (0) 53 (82.1) 54 (84.3) 17 (26.5) 9 (14) 3 (4.6) 1 (1.5) 1 (1.5) 5 (7.8)
59 ⫾ 11.4 77 (80) 7 ⫾ 9.58 60/36 (62.5/37.5) 24 (25) 85 (88) 21 (21.9) 28 (29.2) 12 (12.5) 4 (4.2) 25 (26) 12 (12.5) 4 (4.2) 5 (5.2) 1 (1) 4 (4.2)
NA, not applicable. 0049-0172/12/$-see front matter © 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.semarthrit.2011.04.009
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Letters
association between SLE and diffuse splenic calcifications and their pathological significance. Josep A. Farras Jerome Avouac Marine Meunier Yannick Allanore Paris Descartes University, Rheumatology A Department Cochin Hospital, APHP Paris, France
REFERENCES
Figure 1 Splenic calcifications in a patient with rheumatoid arthritis. (Color version of figure is available online.)
no history compatible with other known causes of splenic calcification. Altogether, these data suggest a low frequency of calcifications of the spleen in a sizable sample of SSc and RA patients. We acknowledge that the availability of lung CT scans for our cohort only allowed a partial evaluation of the spleen (at least 1/3 of the volume). However, the calcification pattern described in SLE patients was diffuse so we assume that the obtained partial evaluation should have been sufficient to detect such lesions. Therefore, our results strengthen the conclusions of Tan Tieng and coworkers on the specificity of diffuse splenic calcifications to SLE. Further studies are now warranted to confirm our data as well as the
1. Tan Tieng A, Sadow CA, Hochsztein JG, Putterman C. Diffuse calcifications of the spleen: A novel association with systemic lupus erythematosus. Semin Arthritis Rheum 2010 Dec 22 [Epub ahead of print]. 2. Fishman D, Isenberg DA. Splenic involvement in rheumatic diseases. Semin Arthritis Rheum 1997;27:141-55. 3. Kaiser IH. The specificity of periarterial fibrosis of the spleen in disseminated lupus erythematosus. Bull Johns Hopkins Hosp 1942;71:31-43. 4. Avouac J, Guerini H, Wipff J, Assous N, Chevrot A, Kahan A, et al. Radiological hand involvement in systemic sclerosis. Ann Rheum Dis 2006;65:1088-92. 5. Avouac J, Mogavero G, Guerini H, Drapé JL, Mathieu A, Kahan A, et al. Predictive factors of hand radiographic lesions in systemic sclerosis: a prospective study. Ann Rheum Dis 2011;70:630-3. 6. La Montagna G, Baruffo A, Tirri R, Buono G, Valentini G. Foot involvement in systemic sclerosis: a longitudinal study of 100 patients. Semin Arthritis Rheum 2002;31:248-55. 7. Koutaissoff S, Vanthuyne M, Smith V, De Langhe E, Depresseux G, Westhovens R, et al. Hand radiological damage in systemic sclerosis: Comparison with a control group and clinical and functional correlations. Semin Arthritis Rheum 2010 Sep 21 [Epub ahead of print]. 8. Gilson M, Zerkak D, Wipff J, Dusser D, Dinh-Xuan AT, Abitbol V, et al. Prognostic factors for lung function in systemic sclerosis: Prospective study of 105 cases. Eur Respir J 2010;35:112-7.
Reply to Letter to the Editor
W
e thank Dr Farras and colleagues for their interest in our article describing a unique splenic calcification pattern in patients with systemic lupus erythematosus. Their further investigation assessing whether a similar pattern of splenic calcification might be found in a large series of patients with other connective tissue diseases, namely systemic sclerosis and rheumatoid arthritis, was insightful given the known association with soft-tissue calcifications and splenic involvement, respectively. A broader association of rheumatologic diseases with splenic calcifications would indeed have important diagnostic and
Address reprint requests to Chaim Putterman, MD, Division of Rheumatology, Albert Einstein College of Medicine, Forchheimer Building, Room 701N, 1300 Morris Park Avenue, Bronx, NY 10461. E-mail address: .
therapeutic implications. It would be interesting to know whether dedicated imaging of the total spleen [instead of just the partial view afforded by the chest computed tomographic (CT) scanning] would have further increased the incidence reported by Farras and coworkers. Nevertheless, as they suggest, the lack of similar findings in these other connective tissue diseases further supports our claim that this calcification pattern may be pathognomonic for systemic lupus erythematosus. After discovery of the index case in our series, a database search was performed for other patients with a similar calcification pattern. The search was limited to radiography and fluoroscopy, covering the area of the spleen (both chest and abdominal exams) rather than including CT; this was an attempt to exclude the very common finding of scattered small calcifications seen in patients with a
W
e read with great interest the report from Tan Tieng and coworkers about the first description of diffuse calcifications of the spleen in systemic lupus erythematosus (SLE) (1). The in-depth review of their own and literature cases emphasized that splenic calcifications are less frequent than other spleen abnormalities in SLE, such as splenomegaly, spleen infarction, and hyposplenism (2). However, the authors suggest that the described calcification pattern— discrete, small, round, diffuse but sparing the capsular and subcapsular area—might be specific of SLE. This aspect is thought to be unique without overlap with patterns known in other diseases. In addition, the more linear, tubular, or ovoid morphology of many of the observed calcifications suggests a vascular distribution. This finding supports that calcified splenic nodules in SLE may represent calcification in the “onion-skin lesions,” characterized by at least 3 separated layers of periarterial fibrosis and regarded as pathognomonic of SLE (3). Considering these novel findings, we aimed to assess whether spleen calcifications might be a characteristic feature of other connective tissue disorders in which spleen calcifications have not yet been described. We decided to
The authors have no conflicts of interest to disclose. Address reprint requests to Yannick Allanore, Service de Rhumatologie A, Hôpital Cochin, 27 Rue du Faubourg St Jacques, 75014 Paris, France. E-mail: yannick. [email protected]
focus on (1) systemic sclerosis (SSc), an orphan and incurable disorder, characterized by an increased frequency of soft-tissue calcifications (4-7); and (2) rheumatoid arthritis (RA), a chronic systemic inflammatory disorder with possible splenic involvement; in particular, spontaneous splenic rupture, abnormal splenic function, and Felty’s syndrome (2). Thus, we systematically analyzed thoracic computed tomographic (CT) scans performed in our cohorts of patients with SSc (N ⫽ 96) and RA (N ⫽ 64) during their regular follow-up, as already reported for SSc patients (8). Their main characteristics are summarized in Table 1. The latest available CT scan in our PACS (Picture Archiving and Communication System), from February 2006 to December 2009, was reviewed by a single experienced radiologist, blinded for the diagnosis. The spleen was screened for calcium-density images in bone and abdominal contrast windows. The aspect, distribution, and number of calcifications were noted. After careful and systematic analysis of the whole sample of CT scans, we found 7 patients with spleen calcifications: 2 patients having SSc (2.1%) and 5 having RA (7.7%). Most were isolated and small, unlike the diffuse calcifications observed in SLE. Only a 64-year-old woman with RA displayed a pattern of 15 to 20 roundand rod-shaped calcifications with variable sizes (Fig. 1). However, they were fewer, less dense, and closer to the capsular region than those found in SLE. This patient had
Table 1 Characteristics of Patients with Rheumatoid Arthritis (RA) and Systemic Sclerosis (SSc)
Age, mean ⫾ standard deviation, SD Females, n (%) Disease duration (yr), mean ⫾ SD Limited/diffuse cutaneous subset, n (%) Subcutaneous calcinosis Positive antinuclear antibodies, n (%) Positive anticentromere antibodies, n (%) Positive antitopoisomerase-1 antibodies, n (%) Positive rheumatoid factors, n (%) Positive anti-CCP antibodies, n (%) Associated autoimmune diseases Sjögren’s syndrome, n (%) Thyroiditis, n (%) Primary biliary cirrhosis, n (%) Systemic lupus erythematosus, n (%) Inflammatory myositis, n (%)
Rheumatoid Arthritis (RA) (n ⫽ 64)
Systemic Sclerosis (SSc) (n ⫽ 96)
57 ⫾ 12.4 56 (87.5) 13 ⫾ 11.5 NA NA 19 (29) 0 (0) 0 (0) 53 (82.1) 54 (84.3) 17 (26.5) 9 (14) 3 (4.6) 1 (1.5) 1 (1.5) 5 (7.8)
59 ⫾ 11.4 77 (80) 7 ⫾ 9.58 60/36 (62.5/37.5) 24 (25) 85 (88) 21 (21.9) 28 (29.2) 12 (12.5) 4 (4.2) 25 (26) 12 (12.5) 4 (4.2) 5 (5.2) 1 (1) 4 (4.2)
NA, not applicable. 0049-0172/12/$-see front matter © 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.semarthrit.2011.04.009
e1
e2
Letters
association between SLE and diffuse splenic calcifications and their pathological significance. Josep A. Farras Jerome Avouac Marine Meunier Yannick Allanore Paris Descartes University, Rheumatology A Department Cochin Hospital, APHP Paris, France
REFERENCES
Figure 1 Splenic calcifications in a patient with rheumatoid arthritis. (Color version of figure is available online.)
no history compatible with other known causes of splenic calcification. Altogether, these data suggest a low frequency of calcifications of the spleen in a sizable sample of SSc and RA patients. We acknowledge that the availability of lung CT scans for our cohort only allowed a partial evaluation of the spleen (at least 1/3 of the volume). However, the calcification pattern described in SLE patients was diffuse so we assume that the obtained partial evaluation should have been sufficient to detect such lesions. Therefore, our results strengthen the conclusions of Tan Tieng and coworkers on the specificity of diffuse splenic calcifications to SLE. Further studies are now warranted to confirm our data as well as the
1. Tan Tieng A, Sadow CA, Hochsztein JG, Putterman C. Diffuse calcifications of the spleen: A novel association with systemic lupus erythematosus. Semin Arthritis Rheum 2010 Dec 22 [Epub ahead of print]. 2. Fishman D, Isenberg DA. Splenic involvement in rheumatic diseases. Semin Arthritis Rheum 1997;27:141-55. 3. Kaiser IH. The specificity of periarterial fibrosis of the spleen in disseminated lupus erythematosus. Bull Johns Hopkins Hosp 1942;71:31-43. 4. Avouac J, Guerini H, Wipff J, Assous N, Chevrot A, Kahan A, et al. Radiological hand involvement in systemic sclerosis. Ann Rheum Dis 2006;65:1088-92. 5. Avouac J, Mogavero G, Guerini H, Drapé JL, Mathieu A, Kahan A, et al. Predictive factors of hand radiographic lesions in systemic sclerosis: a prospective study. Ann Rheum Dis 2011;70:630-3. 6. La Montagna G, Baruffo A, Tirri R, Buono G, Valentini G. Foot involvement in systemic sclerosis: a longitudinal study of 100 patients. Semin Arthritis Rheum 2002;31:248-55. 7. Koutaissoff S, Vanthuyne M, Smith V, De Langhe E, Depresseux G, Westhovens R, et al. Hand radiological damage in systemic sclerosis: Comparison with a control group and clinical and functional correlations. Semin Arthritis Rheum 2010 Sep 21 [Epub ahead of print]. 8. Gilson M, Zerkak D, Wipff J, Dusser D, Dinh-Xuan AT, Abitbol V, et al. Prognostic factors for lung function in systemic sclerosis: Prospective study of 105 cases. Eur Respir J 2010;35:112-7.
Reply to Letter to the Editor
W
e thank Dr Farras and colleagues for their interest in our article describing a unique splenic calcification pattern in patients with systemic lupus erythematosus. Their further investigation assessing whether a similar pattern of splenic calcification might be found in a large series of patients with other connective tissue diseases, namely systemic sclerosis and rheumatoid arthritis, was insightful given the known association with soft-tissue calcifications and splenic involvement, respectively. A broader association of rheumatologic diseases with splenic calcifications would indeed have important diagnostic and
Address reprint requests to Chaim Putterman, MD, Division of Rheumatology, Albert Einstein College of Medicine, Forchheimer Building, Room 701N, 1300 Morris Park Avenue, Bronx, NY 10461. E-mail address: .
therapeutic implications. It would be interesting to know whether dedicated imaging of the total spleen [instead of just the partial view afforded by the chest computed tomographic (CT) scanning] would have further increased the incidence reported by Farras and coworkers. Nevertheless, as they suggest, the lack of similar findings in these other connective tissue diseases further supports our claim that this calcification pattern may be pathognomonic for systemic lupus erythematosus. After discovery of the index case in our series, a database search was performed for other patients with a similar calcification pattern. The search was limited to radiography and fluoroscopy, covering the area of the spleen (both chest and abdominal exams) rather than including CT; this was an attempt to exclude the very common finding of scattered small calcifications seen in patients with a