- Email: [email protected]
computed tomography in dermatomyositis
Letters to the editor / Joint Bone Spine 75 (2008) 506e512
508 Table 1 Laboratory markers Serum parameter (normal values)
References Bone alkaline Osteocalcin, CTX, ng/ml IGF-1, ng/ml phosphatase, ng/ml (3e13) (0.15e0.50) (54e336) mg/ml (3e15)
Before pamidronate 2 After pamidronate 8
5 4
0.32 0.26
292 289
T-score, þ1.5; lumbar Z-score, þ2.2; femoral T-score, þ0.8; and femoral Z-score, þ1.5). Calcium and phosphate levels were normal. A diagnosis of Schnitzler’s syndrome was given. The symptoms failed to respond to nonsteroidal antiinflammatory drugs, systemic glucocorticoid therapy, methotrexate, thalidomide, interferon alpha, and cyclosporine. Narcotic analgesics were needed to control the bone pain. Pamidronate was given in an effort to reduce the bone pain, in a dosage of 60 mg intravenously for 6 consecutive months. Although improvements were slow to occur, 4 months after the last pamidronate infusion a 66% decrease in bone pain severity was noted, despite discontinuation of the narcotics. Pain relief was sustained 1 year later, and no systemic episodes had occurred. Laboratory markers for bone turnover were unchanged after pamidronate therapy, compared to baseline (Table 1).
[1] Soubrier M. Schnitzler syndrome. Joint Bone Spine 2008;75(3):263e6. [2] Lipsker D, Veran Y, Grunenberger F, et al. The Schnitzler syndrome. Four new cases and review of the literature. Medicine 2001;80:37e44. [3] Schartz NE, Buder S, Sperl H, et al. Report of a case of Schnitzler’s syndrome treated successfully with interferon alpha 2b. Dermatology 2002;205:54e6. [4] Thonhofer R, Uitz E, Graninger W. Schnitzler syndrome e exacerbation after anti-TNF treatment. Rheumatology 2007;46:1041e2. [5] De Koning HD, Bodar EJ, Simon A, et al. Beneficial response to anakinra and thalidomide in Schnitzler’s syndrome. Ann Rheum Dis 2006;65:542e4. [6] Almerigogna F, Giudizi MG, Cappelli F, et al. Schnitzler’s syndrome: what’s new? J Eur Acad Dermatol Venereol 2002;16:214e9.
Daniel Wendling* Cle´ment Prati Rheumatology Department, Jean Minjoz Teaching Hospital, Franche-Comte´ University, boulevard Fleming, 25030 Besanc¸on Cedex, France *Corresponding author. Tel.: þ33 3 81 66 82 41; fax: þ33 3 81 66 86 86. E-mail address: [email protected] (D. Wendling) Bruno Hoen Infectious Diseases Department, St Jacques Teaching Hospital, Besanc¸on, France Eric Toussirot Ge´rald Streit Rheumatology Department, Jean Minjoz Teaching Hospital, Franche-Comte´ University, boulevard Fleming, 25030 Besanc¸on Cedex, France
2. Discussion The combination in our patient of urticaria, monoclonal IgM, bone pain and radiographic hyperostosis, and intermittent episodes of systemic inflammation with leukocytosis indicate a diagnosis of Schnitzler’s syndrome, as shown by current criteria [1,2]. Severe bone pain was a prominent feature in our patient. Bone pain has been reported in 59% of cases and diffuse radiographic osteosclerosis in 56% of cases [2]. Our patient had normal values of markers for both bone formation (bone alkaline phosphatase, osteocalcin, and IGF-1) and bone resorption (serum CTX) and, consequently, the pathogenesis of the hyperostosis remains unclear. The absence of changes in bone turnover markers also fails to provide clues regarding the mechanism underlying the analgesic effect of pamidronate therapy. No treatment guidelines are available for Schnitzler’s syndrome. The choice of treatments depends largely on the clinical presentation. Nonsteroidal anti-inflammatory drugs, immunosuppressants, colchicine, disulone, and thalidomide have been used [2]. Biotherapies tried to date include rituximab [1], interferon alpha [3], and adalimumab [4]; this last agent worsened the manifestations. Administration of anakinra to induce IL-1 inhibition may hold promise [1,5]. Our patient experienced marked and sustained pain relief after pamidronate therapy. Two similar cases have been reported [2,6], suggesting that pamidronate should be considered in patients who have severe bone pain due to Schnitzler’s syndrome.
Gilles Dumoulin Renal and Metabolic Functional Testing Department, Jean Minjoz Teaching Hospital, Franche-Comte´ University, 25030 Besanc¸on Cedex, France 12 December 2007 Available online 19 May 2008 1297-319X/$ - see front matter Ó 2008 Elsevier Masson SAS. All rights reserved. doi:10.1016/j.jbspin.2007.12.005
18
Fluorine fluorodeoxyglucose-positron emission tomography/computed tomography in dermatomyositis
1. Introduction Dermatomyositis (DM) is a rare multisystemic autoimmune disease that primarily affects the skin and skeletal muscle, and the diagnosis is confirmed by muscle biopsy [1]. The biopsy could be limited as well as during early stage localization and follow-up to detect exact active areas within the muscle. 18 Fluorine fluorodeoxyglucose-positron emission tomography (FDG-PET) is emerging as an imaging modality for the detection of malignancy and inflammation [2e4]. The recent advent
Letters to the editor / Joint Bone Spine 75 (2008) 506e512
of dual-modality PET/computed tomography (PET/CT) imaging systems has added unprecedented diagnostic capability by revealing the precise anatomical localization of metabolic information and metabolic characterization of normal and abnormal structures [5]. This application has an increasing value in both early detection of disease and its relapse than other conventional imaging methods. We report a case of DM with sudden upper extremity and thigh weakness; the FDG-PET/CT images exhibited a strongly elevated FDG uptake in the bilateral deltoids, the infraspinatus, and the sartorius. 2. Case report A 57-year-old male patient was admitted for progressive proximal muscle weakness that had initiated 3 months ago. The patient had specific cutaneous lesions such as typical
509
heliotrope eyelid rash, shawl sign and Gottron’s papules on both the hands. Physical examination revealed motor weakness at his shoulders, upper arms, and thighs [1]. DM was confirmed as the diagnosis by muscle biopsy. The biopsy sample was obtained from the upper medial part of right thigh, a region where the patient experienced the most severe myalgia and weakness. For the evaluation of contemporary malignancy, PET/CT and other cancer screening tests were performed. The patient fasted for at least 6 h before the PET/CT study. Scanning was commenced 60 min after injecting 555 MBq of 18F-FDG intravenously. The images revealed high signal of FDG uptake, indicating inflammatory hypermetabolism in the bilateral deltoids, the infraspinatus, and the sartorius. This finding was concordant to the inflammatory changes of DM revealed by muscle biopsy, which was performed to detect the active area (Fig. 1). The examinations did not reveal any accompanying malignancy. 3. Discussion FDG-PET/CT is a powerful molecular imaging technique that enables the detection of areas with different pathologies such as malignant neoplasm and active inflammation [2e5]. Particularly in the old age, DM associated with malignancy is an important clinical finding [6,7]. This clear association emphasizes the need for early recognition of malignancy, the onset of which may precede, coincide with, or follow the diagnosis of DM. With regard to skeletal abnormalities such as inflammatory change and accompanying malignancy, this approach appears to be extremely useful because it combines the advantages of functional data sets and biopsy guidance for the detection of inflammatory lesions in DM [2,8,9]. Here, we presented a case of DM, which was confirmed by muscle biopsy; the findings of biopsy were compatible with the inflammatory hypermetabolism revealed by FDG-PET/ CT. The clinical impact of FDG-PET/CT as a routine imaging technique is yet uncertain. However, FDG-PET/CT is a potential and valuable method to screen the musculoskeletal inflammation and contemporary malignancy in DM. References
Fig. 1. Whole body 18F-fluorodeoxyglucose (18F-FDG)-PET/CT revealed hypermetabolic activity in the proximal muscles. Selected PET images obtained 1 h after the intravenous injection of 555 MBq 18F-FDG are shown. These areas of uptake corresponded to the patient’s clinical proximal muscle weakness and reflected the degree of inflammation present due to dermatomyositis. Other foci of intense activity are not seen in these images. (A) There is symmetrical hypermetabolic activity involving the proximal muscles, namely, bilateral deltoids (indicated by the arrow) and the infraspinatus (indicated by the arrowhead). (B) In the lower extremities, the right sartorius muscle (indicated by the arrow) showed the strongest FDG uptake, and this finding corresponded to the clinical muscle weakness and was confirmed by muscle biopsy.
[1] Callen JP. Dermatomyositis. Lancet 2000;355:53e7. [2] Duet M, Pouchot J, Liote´ F, et al. Role for positron emission tomography in skeletal diseases. Joint Bone Spine 2007;74:14e23. [3] Yamada S, Kubota K, Kubota R, et al. High accumulation of fluorine18-fluorodeoxyglucose in turpentine-induced inflammatory tissue. J Nucl Med 1995;36:1301e6. [4] Zhao S, Kuge Y, Tsukamoto E, et al. Fluorodeoxyglucose uptake and glucose transporter expression in experimental inflammatory lesions and malignant tumours: effects of insulin and glucose loading. Nucl Med Commun 2002;23:545e50. [5] Horger M, Bares R. The role of single-photon emission computed tomography/computed tomography in benign and malignant bone disease. Semin Nucl Med 2006;36:286e94. [6] Hill CL, Zhang Y, Sigurgeirsson B, et al. Frequency of specific cancer types in dermatomyositis and polymyositis: a population-based study. Lancet 2001;357:96e100.
510
Letters to the editor / Joint Bone Spine 75 (2008) 506e512
[7] Buchbinder R, Hill CL. Malignancy in patients with inflammatory myopathy. Curr Rheumatol Rep 2002;4:415e26. [8] Berner U, Menzel C, Rinne D, et al. Paraneoplastic syndromes: detection of malignant tumors using [(18)F]FDG-PET. Q J Nucl Med 2003;47:85e9. [9] Liau N, Ooi C, Reid C, et al. F-18 FDG PET/CT detection of mediastinal malignancy in a patient with dermatomyositis. Clin Nucl Med 2007;32: 304e5.
Hyun-Sook Kim Division of Rheumatology, Department of Internal medicine, Chosun University College of Medicine, Gwangju, Republic of Korea Chung Ho Kim Young Ha Park Department of Radiology, St. Vincent Hospital, College of Medicine, The Catholic University of Korea, 93-6 Ji-dong Paldal-gu, Suwon 442-723, Republic of Korea Wan-Uk Kim* Division of Rheumatology, Department of Internal Medicine, St. Vincent Hospital, College of Medicine, The Catholic University of Korea, 93-6 Ji-dong Paldal-gu, Suwon 442-723, Republic of Korea *Corresponding author. Tel.: þ82 31 249 8158; fax: þ82 31 253 8898. E-mail address: [email protected]
Table 1 Changes in the erythrocyte sedimentation rate (ESR), serum C-reactive protein level (CRP), and bath ankylosing spondylitis disease activity index (BASDAI) during rituximab therapy
Baseline 3 Months 6 Months
ESR mm/h
CRP mg/L
BASDAI points/100
27 39 33
32 49 36
92 78 79
1. Case-report A woman was diagnosed with AS in 1990, when she was 26 years of age. She had pure axial disease with bilateral stage 4 radiological sacroiliitis. She was HLA B27-positive and met modified New York criteria for AS. Her treatment consisted of anti-inflammatory nonsteroidal drugs, sulfasalazine, pulse glucocorticoid therapy, and intravenous pamidronate. Marked disease activity despite these medications, with BASDAI values greater than 80, prompted treatment with TNFa antagonists in the dosages recommended for patients with AS. Infliximab was tried first (3 infusions), followed by etanercept (for 24 months) then by adalimumab (for 14 months). No major improvements were seen with any of these agents. Adalimumab therapy was discontinued when infiltrated papules developed over the lower limbs. A biopsy of a papule established the diagnosis of leukocytoclastic vasculitis. Rituximab therapy was given, as two 1-g intravenous infusions at a 2-week interval. The skin lesions cleared within 2 weeks. In contrast, the signs and symptoms of AS were unchanged after 3 and 6 months (Table 1). 2. Discussion
17 December 2007 Available online 2 May 2008 1297-319X/$ - see front matter Ó 2008 Elsevier Masson SAS. All rights reserved. doi:10.1016/j.jbspin.2007.12.002
Lack of short-term efficacy of rituximab upon symptoms of ankylosing spondylitis treated for an associated vasculitis Keywords: Ankylosing spondylitis; Rituximab; Treatment
Rituximab, a chimeric monoclonal antibody against CD20, is licensed for use in patients with rheumatoid arthritis who have failed treatment with 1 or more TNFa antagonists. There is evidence that rituximab may be effective in a number of other autoimmune diseases [1]. No therapeutic trials or anecdotal reports are available on the potential effects of rituximab in ankylosing spondylitis (AS). Immunohistological studies of specimens removed during spinal surgery for AS have shown significantly increased numbers of CD20 þ B cells within joints exhibiting persistent inflammatory lesions, most notably facet joints, in correlation with MRI findings [2,3]. We managed a patient with severe AS who required rituximab therapy to treat vasculitis.
Our patient had severe AS with an inadequate response to 3 TNFa antagonists. The occurrence of vasculitis during TNFa antagonist therapy has been reported previously [4]. There is some evidence that rituximab therapy may improve vasculitis [1,5]. In our patient, rituximab therapy had no impact on the signs or symptoms of AS after 3 and 6 months, in apparent contradiction with immunohistological arguments supporting a beneficial effect of anti-B-cell agents in AS [2]. The occurrence of conditions that require rituximab therapy in patients with AS provides an opportunity for assessing the effects of this drug on the concomitant joint disease. References [1] Saraux A, Devauchelle V, Jousse S, et al. Rituximab in rheumatic diseases. Joint Bone Spine 2007;74:4e6. [2] Appel H, Kuhne M, Spiekermann S, et al. Immunohistologic analysis of zygapophyseal joints in patients with ankylosing spondylitis. Arthritis Rheum 2006;54:2845e51. [3] Appel H, Loddenkemper C, Grozdanovic Z, et al. Correlation of histopathological findings and magnetic resonance imaging in the spine of patients with ankylosing spondylitis. Arthritis Res Ther 2006;8:R143. [4] Saint-Marcoux B, De Bandt M. Vasculitides induced by anti TNFa antagonists: a study in 39 patients in France. Joint Bone Spine 2006;73: 710e3.
508 Table 1 Laboratory markers Serum parameter (normal values)
References Bone alkaline Osteocalcin, CTX, ng/ml IGF-1, ng/ml phosphatase, ng/ml (3e13) (0.15e0.50) (54e336) mg/ml (3e15)
Before pamidronate 2 After pamidronate 8
5 4
0.32 0.26
292 289
T-score, þ1.5; lumbar Z-score, þ2.2; femoral T-score, þ0.8; and femoral Z-score, þ1.5). Calcium and phosphate levels were normal. A diagnosis of Schnitzler’s syndrome was given. The symptoms failed to respond to nonsteroidal antiinflammatory drugs, systemic glucocorticoid therapy, methotrexate, thalidomide, interferon alpha, and cyclosporine. Narcotic analgesics were needed to control the bone pain. Pamidronate was given in an effort to reduce the bone pain, in a dosage of 60 mg intravenously for 6 consecutive months. Although improvements were slow to occur, 4 months after the last pamidronate infusion a 66% decrease in bone pain severity was noted, despite discontinuation of the narcotics. Pain relief was sustained 1 year later, and no systemic episodes had occurred. Laboratory markers for bone turnover were unchanged after pamidronate therapy, compared to baseline (Table 1).
[1] Soubrier M. Schnitzler syndrome. Joint Bone Spine 2008;75(3):263e6. [2] Lipsker D, Veran Y, Grunenberger F, et al. The Schnitzler syndrome. Four new cases and review of the literature. Medicine 2001;80:37e44. [3] Schartz NE, Buder S, Sperl H, et al. Report of a case of Schnitzler’s syndrome treated successfully with interferon alpha 2b. Dermatology 2002;205:54e6. [4] Thonhofer R, Uitz E, Graninger W. Schnitzler syndrome e exacerbation after anti-TNF treatment. Rheumatology 2007;46:1041e2. [5] De Koning HD, Bodar EJ, Simon A, et al. Beneficial response to anakinra and thalidomide in Schnitzler’s syndrome. Ann Rheum Dis 2006;65:542e4. [6] Almerigogna F, Giudizi MG, Cappelli F, et al. Schnitzler’s syndrome: what’s new? J Eur Acad Dermatol Venereol 2002;16:214e9.
Daniel Wendling* Cle´ment Prati Rheumatology Department, Jean Minjoz Teaching Hospital, Franche-Comte´ University, boulevard Fleming, 25030 Besanc¸on Cedex, France *Corresponding author. Tel.: þ33 3 81 66 82 41; fax: þ33 3 81 66 86 86. E-mail address: [email protected] (D. Wendling) Bruno Hoen Infectious Diseases Department, St Jacques Teaching Hospital, Besanc¸on, France Eric Toussirot Ge´rald Streit Rheumatology Department, Jean Minjoz Teaching Hospital, Franche-Comte´ University, boulevard Fleming, 25030 Besanc¸on Cedex, France
2. Discussion The combination in our patient of urticaria, monoclonal IgM, bone pain and radiographic hyperostosis, and intermittent episodes of systemic inflammation with leukocytosis indicate a diagnosis of Schnitzler’s syndrome, as shown by current criteria [1,2]. Severe bone pain was a prominent feature in our patient. Bone pain has been reported in 59% of cases and diffuse radiographic osteosclerosis in 56% of cases [2]. Our patient had normal values of markers for both bone formation (bone alkaline phosphatase, osteocalcin, and IGF-1) and bone resorption (serum CTX) and, consequently, the pathogenesis of the hyperostosis remains unclear. The absence of changes in bone turnover markers also fails to provide clues regarding the mechanism underlying the analgesic effect of pamidronate therapy. No treatment guidelines are available for Schnitzler’s syndrome. The choice of treatments depends largely on the clinical presentation. Nonsteroidal anti-inflammatory drugs, immunosuppressants, colchicine, disulone, and thalidomide have been used [2]. Biotherapies tried to date include rituximab [1], interferon alpha [3], and adalimumab [4]; this last agent worsened the manifestations. Administration of anakinra to induce IL-1 inhibition may hold promise [1,5]. Our patient experienced marked and sustained pain relief after pamidronate therapy. Two similar cases have been reported [2,6], suggesting that pamidronate should be considered in patients who have severe bone pain due to Schnitzler’s syndrome.
Gilles Dumoulin Renal and Metabolic Functional Testing Department, Jean Minjoz Teaching Hospital, Franche-Comte´ University, 25030 Besanc¸on Cedex, France 12 December 2007 Available online 19 May 2008 1297-319X/$ - see front matter Ó 2008 Elsevier Masson SAS. All rights reserved. doi:10.1016/j.jbspin.2007.12.005
18
Fluorine fluorodeoxyglucose-positron emission tomography/computed tomography in dermatomyositis
1. Introduction Dermatomyositis (DM) is a rare multisystemic autoimmune disease that primarily affects the skin and skeletal muscle, and the diagnosis is confirmed by muscle biopsy [1]. The biopsy could be limited as well as during early stage localization and follow-up to detect exact active areas within the muscle. 18 Fluorine fluorodeoxyglucose-positron emission tomography (FDG-PET) is emerging as an imaging modality for the detection of malignancy and inflammation [2e4]. The recent advent
Letters to the editor / Joint Bone Spine 75 (2008) 506e512
of dual-modality PET/computed tomography (PET/CT) imaging systems has added unprecedented diagnostic capability by revealing the precise anatomical localization of metabolic information and metabolic characterization of normal and abnormal structures [5]. This application has an increasing value in both early detection of disease and its relapse than other conventional imaging methods. We report a case of DM with sudden upper extremity and thigh weakness; the FDG-PET/CT images exhibited a strongly elevated FDG uptake in the bilateral deltoids, the infraspinatus, and the sartorius. 2. Case report A 57-year-old male patient was admitted for progressive proximal muscle weakness that had initiated 3 months ago. The patient had specific cutaneous lesions such as typical
509
heliotrope eyelid rash, shawl sign and Gottron’s papules on both the hands. Physical examination revealed motor weakness at his shoulders, upper arms, and thighs [1]. DM was confirmed as the diagnosis by muscle biopsy. The biopsy sample was obtained from the upper medial part of right thigh, a region where the patient experienced the most severe myalgia and weakness. For the evaluation of contemporary malignancy, PET/CT and other cancer screening tests were performed. The patient fasted for at least 6 h before the PET/CT study. Scanning was commenced 60 min after injecting 555 MBq of 18F-FDG intravenously. The images revealed high signal of FDG uptake, indicating inflammatory hypermetabolism in the bilateral deltoids, the infraspinatus, and the sartorius. This finding was concordant to the inflammatory changes of DM revealed by muscle biopsy, which was performed to detect the active area (Fig. 1). The examinations did not reveal any accompanying malignancy. 3. Discussion FDG-PET/CT is a powerful molecular imaging technique that enables the detection of areas with different pathologies such as malignant neoplasm and active inflammation [2e5]. Particularly in the old age, DM associated with malignancy is an important clinical finding [6,7]. This clear association emphasizes the need for early recognition of malignancy, the onset of which may precede, coincide with, or follow the diagnosis of DM. With regard to skeletal abnormalities such as inflammatory change and accompanying malignancy, this approach appears to be extremely useful because it combines the advantages of functional data sets and biopsy guidance for the detection of inflammatory lesions in DM [2,8,9]. Here, we presented a case of DM, which was confirmed by muscle biopsy; the findings of biopsy were compatible with the inflammatory hypermetabolism revealed by FDG-PET/ CT. The clinical impact of FDG-PET/CT as a routine imaging technique is yet uncertain. However, FDG-PET/CT is a potential and valuable method to screen the musculoskeletal inflammation and contemporary malignancy in DM. References
Fig. 1. Whole body 18F-fluorodeoxyglucose (18F-FDG)-PET/CT revealed hypermetabolic activity in the proximal muscles. Selected PET images obtained 1 h after the intravenous injection of 555 MBq 18F-FDG are shown. These areas of uptake corresponded to the patient’s clinical proximal muscle weakness and reflected the degree of inflammation present due to dermatomyositis. Other foci of intense activity are not seen in these images. (A) There is symmetrical hypermetabolic activity involving the proximal muscles, namely, bilateral deltoids (indicated by the arrow) and the infraspinatus (indicated by the arrowhead). (B) In the lower extremities, the right sartorius muscle (indicated by the arrow) showed the strongest FDG uptake, and this finding corresponded to the clinical muscle weakness and was confirmed by muscle biopsy.
[1] Callen JP. Dermatomyositis. Lancet 2000;355:53e7. [2] Duet M, Pouchot J, Liote´ F, et al. Role for positron emission tomography in skeletal diseases. Joint Bone Spine 2007;74:14e23. [3] Yamada S, Kubota K, Kubota R, et al. High accumulation of fluorine18-fluorodeoxyglucose in turpentine-induced inflammatory tissue. J Nucl Med 1995;36:1301e6. [4] Zhao S, Kuge Y, Tsukamoto E, et al. Fluorodeoxyglucose uptake and glucose transporter expression in experimental inflammatory lesions and malignant tumours: effects of insulin and glucose loading. Nucl Med Commun 2002;23:545e50. [5] Horger M, Bares R. The role of single-photon emission computed tomography/computed tomography in benign and malignant bone disease. Semin Nucl Med 2006;36:286e94. [6] Hill CL, Zhang Y, Sigurgeirsson B, et al. Frequency of specific cancer types in dermatomyositis and polymyositis: a population-based study. Lancet 2001;357:96e100.
510
Letters to the editor / Joint Bone Spine 75 (2008) 506e512
[7] Buchbinder R, Hill CL. Malignancy in patients with inflammatory myopathy. Curr Rheumatol Rep 2002;4:415e26. [8] Berner U, Menzel C, Rinne D, et al. Paraneoplastic syndromes: detection of malignant tumors using [(18)F]FDG-PET. Q J Nucl Med 2003;47:85e9. [9] Liau N, Ooi C, Reid C, et al. F-18 FDG PET/CT detection of mediastinal malignancy in a patient with dermatomyositis. Clin Nucl Med 2007;32: 304e5.
Hyun-Sook Kim Division of Rheumatology, Department of Internal medicine, Chosun University College of Medicine, Gwangju, Republic of Korea Chung Ho Kim Young Ha Park Department of Radiology, St. Vincent Hospital, College of Medicine, The Catholic University of Korea, 93-6 Ji-dong Paldal-gu, Suwon 442-723, Republic of Korea Wan-Uk Kim* Division of Rheumatology, Department of Internal Medicine, St. Vincent Hospital, College of Medicine, The Catholic University of Korea, 93-6 Ji-dong Paldal-gu, Suwon 442-723, Republic of Korea *Corresponding author. Tel.: þ82 31 249 8158; fax: þ82 31 253 8898. E-mail address: [email protected]
Table 1 Changes in the erythrocyte sedimentation rate (ESR), serum C-reactive protein level (CRP), and bath ankylosing spondylitis disease activity index (BASDAI) during rituximab therapy
Baseline 3 Months 6 Months
ESR mm/h
CRP mg/L
BASDAI points/100
27 39 33
32 49 36
92 78 79
1. Case-report A woman was diagnosed with AS in 1990, when she was 26 years of age. She had pure axial disease with bilateral stage 4 radiological sacroiliitis. She was HLA B27-positive and met modified New York criteria for AS. Her treatment consisted of anti-inflammatory nonsteroidal drugs, sulfasalazine, pulse glucocorticoid therapy, and intravenous pamidronate. Marked disease activity despite these medications, with BASDAI values greater than 80, prompted treatment with TNFa antagonists in the dosages recommended for patients with AS. Infliximab was tried first (3 infusions), followed by etanercept (for 24 months) then by adalimumab (for 14 months). No major improvements were seen with any of these agents. Adalimumab therapy was discontinued when infiltrated papules developed over the lower limbs. A biopsy of a papule established the diagnosis of leukocytoclastic vasculitis. Rituximab therapy was given, as two 1-g intravenous infusions at a 2-week interval. The skin lesions cleared within 2 weeks. In contrast, the signs and symptoms of AS were unchanged after 3 and 6 months (Table 1). 2. Discussion
17 December 2007 Available online 2 May 2008 1297-319X/$ - see front matter Ó 2008 Elsevier Masson SAS. All rights reserved. doi:10.1016/j.jbspin.2007.12.002
Lack of short-term efficacy of rituximab upon symptoms of ankylosing spondylitis treated for an associated vasculitis Keywords: Ankylosing spondylitis; Rituximab; Treatment
Rituximab, a chimeric monoclonal antibody against CD20, is licensed for use in patients with rheumatoid arthritis who have failed treatment with 1 or more TNFa antagonists. There is evidence that rituximab may be effective in a number of other autoimmune diseases [1]. No therapeutic trials or anecdotal reports are available on the potential effects of rituximab in ankylosing spondylitis (AS). Immunohistological studies of specimens removed during spinal surgery for AS have shown significantly increased numbers of CD20 þ B cells within joints exhibiting persistent inflammatory lesions, most notably facet joints, in correlation with MRI findings [2,3]. We managed a patient with severe AS who required rituximab therapy to treat vasculitis.
Our patient had severe AS with an inadequate response to 3 TNFa antagonists. The occurrence of vasculitis during TNFa antagonist therapy has been reported previously [4]. There is some evidence that rituximab therapy may improve vasculitis [1,5]. In our patient, rituximab therapy had no impact on the signs or symptoms of AS after 3 and 6 months, in apparent contradiction with immunohistological arguments supporting a beneficial effect of anti-B-cell agents in AS [2]. The occurrence of conditions that require rituximab therapy in patients with AS provides an opportunity for assessing the effects of this drug on the concomitant joint disease. References [1] Saraux A, Devauchelle V, Jousse S, et al. Rituximab in rheumatic diseases. Joint Bone Spine 2007;74:4e6. [2] Appel H, Kuhne M, Spiekermann S, et al. Immunohistologic analysis of zygapophyseal joints in patients with ankylosing spondylitis. Arthritis Rheum 2006;54:2845e51. [3] Appel H, Loddenkemper C, Grozdanovic Z, et al. Correlation of histopathological findings and magnetic resonance imaging in the spine of patients with ankylosing spondylitis. Arthritis Res Ther 2006;8:R143. [4] Saint-Marcoux B, De Bandt M. Vasculitides induced by anti TNFa antagonists: a study in 39 patients in France. Joint Bone Spine 2006;73: 710e3.