- Email: [email protected]
No serological evidence that fibromyalgia is linked with exposure to human parvovirus B19
592
Letters to the Editor / Joint Bone Spine 72 (2005) 591–595
The presumed mechanism of bone alterations in myelofibrosis suggests a role for bisphosphonate therapy. A few cases of osteosclerosis treated with bisphosphonates in myelofibrosis patients have been reported. In one patient, etidronate therapy ensured complete relief from pain, as well as hematological improvements after 14 months [6]. In five pain-free transfusion-dependent patients, clodronate therapy induced decreases in the fibrosis visible on bone marrow biopsies with concomitant improvements in blood cells counts, which lasted up to 8 months [7]. The beneficial effects of bisphosphonate therapy may stem from multiple mechanisms including decreased bone resorption [8], fibroblast inhibition with decreased osteosclerosis [5,6,8], and an antitumor effect similar to that seen in myeloma and osteolytic bone metastases from breast cancer [9,10]. The good safety profile of bisphosphonate infusions in patients with myelofibrosis and the absence of proven treatments for the bone lesions related to this disease suggest a role for bisphosphonate therapy. In this setting, bisphosphonates may relieve pain, prevent fractures, and inhibit tumor growth. Controlled trials are needed.
References [1]
Taillant B, Ferrari E, Garnier G, Vinti H, Pesce A, Dujardin P. Hypercalcemia and diffuse osteolytic lesions in the acute phase of myeloid splenomegaly. Clin Rheumatol 1992;11:580. [2] Poullin P, Gabriel B. Primary myelofibrosis and osteolytic lesions. Rev Rhum 1994;61:560–2. [3] Tefferi A. Myelofibrosis with myeloid metaplasia. N Engl Med 2000; 342:1263–5. [4] Canalis E, Mc Carthy T, Centrella M. Growth factors and the regulation of bone remodeling. J Clin Invest 1988;81:277–81. [5] Diamond T, Smith A, Schnier R, Manoharan A. Syndrome of myelofibrosis and osteosclerosis: a series of case reports and review of the literature. Bone 2002;30:498–501. [6] Froom P, Elmalah I, Braester A, Aghai E, Quitt M. Clodronate in myelofibrosis: a case report. Am J Med Sci 2002;323:115–6. [7] Sivera P, Cesano L, Guerrasio A, Camaschella C, Mazza U. Clinical and haematological improvement induced by etidronate in a patient with idiopathic myelofibrosis. Br J Haematol 1994;86:397–8. [8] Ash P, Loulit JF, Townsend KMS. Osteoclasts derived from haematopoietic stem cells. Nature 1980;283:669–70. [9] Shipman CM, Rogers MJ, Apperley JF, Russell RG, Croucher PI. Bisphosphonates induce apoptosis in human myeloma cell lines: a novel anti-tumour activity. Br J Haematol 1997;98:665–72. [10] Diel IJ, Solomayer EF, Costa SD, Gollan C, Goerner R, Wallwiener D, et al. Reduction in new metastases in breast cancer with adjuvant clodronate treatment. N Engl J Med 1998;339:357–63.
Noémie Assous * Violaine Foltz Bruno Fautrel Sylvie Rozenberg Fabien Etchepare Pierre Bourgeois Rheumatology Department, Pitié-Salpêtrière Teaching Hospital, 47-83, boulevard de l’Hôpital, 75013 Paris, France E-mail address: [email protected] (N. Assous).
Received 20 July 2004; accepted 29 March 2005 Available online le 19 August 2005 * Corresponding author. Tel.: +33 1 53 16 41 14. 1297-319X/$ - see front matter © 2005 Elsevier SAS. All rights reserved. doi:10.1016/j.jbspin.2005.03.017
No serological evidence that fibromyalgia is linked with exposure to human parvovirus B19 Keywords: Fibromyalgia; Parvovirus B19
Fibromyalgia (FM) is a common condition characterized by chronic diffuse musculoskeletal pain, fatigue, sleep disturbances and a number of tender points to palpation. Its aetiology and pathogenesis remains unknown. Different theories have been proposed and besides genetic, neuroendocrine, psychologic and traumatic causes, infections have also been implicated. Among infections, the association of FM with some viruses has been the object of multiple studies due to its relation and similarities with the chronic fatigue syndrome (CFS) [1,2]. In this sense, many individual descriptions of association between infection with the human parvovirus B19 and FM or CFS has been reported during recent years, suggesting that parvovirus B19 may cause or trigger both conditions [3–6]. Since its discovery, a number of reports have suggested that human parvovirus B19 may be involved in the pathogenesis of various rheumatic diseases including rheumatoid arthritis, juvenile idiopathic arthritis, systemic lupus erythematosus, giant cell arteritis, dermatomyositis, CFS and FM [7–9]. However, it is critical to know if the reported associations with parvovirus B19 are due to chance or if they indicate a cause–effect association. Serological surveys carried out in European countries show that a large part of the population becomes exposed to parvovirus B19 during lifetime with seroprevalence increasing with age, to between 65% and 80% in adulthood [10,11]. Because parvovirus B19 infection is relatively common, it might coexist with FM by chance alone. Moreover, despite these reports implicating B19 virus in the pathogenesis of certain cases of FM, no systematic investigation of the seroprevalence for parvovirus B19 in epidemiologically defined FM populations has previously been performed to our knowledge. In order to clarify this question, we performed a study to determine whether there might be an association between parvovirus B19 infection and FM. For this purpose, we prospectively determined the prevalence of B19 infection in a series of 60 patients with FM, and compared it with the seroprevalence in the general population reported in the same period of time. Despite its limitations, a similar study design has been
Letters to the Editor / Joint Bone Spine 72 (2005) 591–595
previously used to investigate this possibility in other rheumatic conditions [11–13]. Available information on the extent of parvovirus B19 infection in Spain comes from three major studies of the seroprevalence of antibodies against B19 in a random sample of blood donors [14] and on a representative sample of healthy individuals selected at random from the general population [15,16]. In these studies the seroprevalence of B19 infection ranged from 53% to 65%. As in other areas, the prevalence increases with age, to between 76% and 90.9% in subjects older than 40 years [14–16]. Serum IgM and IgG antibodies against B19 VP1/VP2 antigens were measured by ELISA in all FM patients at the time of clinical diagnosis; in those cases in which IgM was positive, it was planned to test the DNA of the virus by polymerase chain reaction (PCR) in order to confirm the infection. Differences between prevalence rates were assessed by the Chi-square test. Statistical significance was defined as P ≤ 0.05. Binomial proportion test was also calculated for completeness. The study group consisted of 60 cases of primary FM consecutive diagnosed from 1998 to April 2004. These patients were evaluated at an outpatient rheumatology clinic and were routine referrals from general practitioners. All patients met the 1990 American College of Rheumatology classification criteria used for the diagnosis of FM [17]. The presence of other diseases that could explain the symptoms different that B19 infection excluded the inclusion in the study. All patients were women with a mean age at time of diagnosis of 40 ± 12 years (mean ± standard deviation; range 21–58 years). None had hematological cytopenias. Twenty of the 60 patients (33%) recalled an acute onset of the disease with “flu-like” symptoms. None of the included patients showed evidence of recent B19 infection (IgM antibodies), whereas the titers of specific IgG antibodies, indicating previous infection, were positive in 48.3% (28/60) of cases. The prevalence of antibodies against parvovirus B19 in the general Spanish population, in the group of women between 15 and 45 years of age, ranges from 43.3% [14] to 72.1% [13]. When we compared the seroprevalence in the group of FM patients with the one in the general population, no statistically significant difference was found (p> 0.05). Of interest, we neither observed differences when we only considered the group of patients with FM who recalled an acute onset with “flu-like” symptoms (40% [8/20]). A note of caution should be added in the interpretation of our results, especially regarding to the absence of IgM antibodies, since the samples tested in the study were performed at clinical diagnosis, and we can not assure that clinical diagnosis necessarily coincide with the beginning of the disease in all patients. Thus, our study does not exclude the possibility that parvovirus B19 might be a trigger of FM in a minor subset of FM patients [3]. However, the main conclusion is that in the general population parvovirus B19 is unlikely to be of aetiological importance for FM. Our findings are in close agreement with Berg et al. [18] who neither observed an etiologic association between B19 infection (searched with serol-
593
ogy and PCR to detect B19 DNA) and FM in a preliminary study conducted in 15 patients with FM. Longer studies in other populations with larger number of patients are necessary to confirm these results.
References [1] [2] [3] [4]
[5]
[6]
[7] [8] [9] [10]
[11]
[12] [13]
[14]
[15]
[16]
[17]
[18]
Goldenberg DL. Do infection trigger fibromyalgia? Arthritis Rheum 1993;36:1489–92. Goldenberg DL. Fibromyalgia syndrome a decade later. Arch Intern Med 1999;159:777–85. Leventhal LJ, Naides SJ, Freundlich B. Fibromyalgia and parvovirus infection. Arthritis Rheum 1991;34:1319–24. Kerr JR, Bracewell J, Laing I, Mattey DL, Bernstein RM, Bruce IN, et al. Chronic fatigue syndrome and arthralgia following parvovirus B19 infection. J Rheumatol 2002;29:595–602. Kerr JR, Coyle PV, DeLeys RJ, Patterson CC. Follow-up study of clinical and immunological findings in patients with acute parvovirus B19 infection. J Med Virol 1996;48:68–75. Acobson SK, Daly JS, Thorne GM, M-cIntosh K. Chronic parvovirus B19 infection resulting in chronic fatigue syndrome. Clin Infect Dis 1997;24:1048–51. Kerr JR. Pathogenesis of human parvovirus B19 in rheumatic diseases. Ann Rheum Dis 2000;59:672–83. Young NS, Brown KE. Parvovirus B19. N Engl J Med 2004;350:586– 97. Meyer O. Parvovirus B19 and autoimmune diseases. Joint Bone Spine 2003;70:6–11. Cohen BJ, Buckley MM. The prevalence of antibody to human parvovirus B19 in England and Wales. J Med Microbiol 1988;25: 151–3. Bengtsson A, Widell A, Elmstahl S, Sturfelt G. No serological indications that systemic lupus erythematosus is linked with exposure to human parvovirus B19. Ann Rheum Dis 2000;59:64–6. Peris P. Polymyalgia rheumatica is not seasonal and is unrelated to parvovirus B19 infection. J Rheumatol 2003;30:2624–6. Harrison B, Silman A, Barret E, Symmons D. Low frequency of recent parvovirus infection in a population-based cohort of patients with early rheumatoid arthritis. Ann Rheum Dis 1998;57:375–7. Muñoz S, Alonso MA, Fernández MJ, Muñoz JL, GarcíaRodriguez JM. Seroprevalence versus Parvovirus B19 in blood donors. Enferm Infecc Microbiol Clin 1998;16:161–2. De Ory F, Pachón I, Ramirez R, Echevarria JM. Antibodies against human parvovirus B19 in the Madrid community. Enferm Infecc Microbiol Clin 1999;17:364–5. Güerri ML, Prior C, Merina R, Zapico R. Regional seroprevalence of parvovirus B19, and its age and sex distribution. Enferm Infecc Microbiol Clin 2000;18:243–4. Wolfe F, Smythe H, Yunnus MB, Bennett RM, Bombardier C, Goldberg DL, et al. The American College of Rheumatology 1990 criteria for the classification of fibromyalgia. Report of the multicenter criteria committee. Arthritis Rheum 1990;33:160–72. Berg AM, Naides SJ, Simms RW. Established fibromyalgia syndrome and parvovirus B19 infection. J Rheumatol 1993;20:1941–3.
Javier Narváez * Joan-Miquel Nolla José Valverde Department of Rheumatology, Hospital Universitario de Bellvitge – IDIBELL, Hospitalet de LLobregat, Barcelona, Spain E-mail address: [email protected] (J. Narváez).
594
Letters to the Editor / Joint Bone Spine 72 (2005) 591–595
Received 17 August 2004; accepted 8 November 2004 Available online 22 March 2005 * Corresponding author. Department.of Rheumatology (Planta 10-2), Hospital, Universitario de Bellevitge, Feixa Llarga s/n, Hospitalet de LLobregat 08907, Spain. Fax: +34 93 414 16 30
The diagnosis was osteomalacia caused by renal tubular acidosis complicating tubulointerstitial nephritis as part of Sjögren’s syndrome. A corticosteroid, alkalinization, and an antimalarial were given, as well as vitamin D and calcium supplements. The clinical features and laboratory test abnormalities improved.
2. Discussion 1297-319X/$ - see front matter © 2005 Elsevier SAS. All rights reserved. doi:10.1016/j.jbspin.2004.11.004
Osteomalacia revealing Sjogren’s syndrome Keywords: Sjogren’s syndrome; Osteomalacia; Renal tubular acidosis
Renal dysfunction is not uncommon in patients with Sjögren’s syndrome. Tubulointerstitial nephritis is the usual pattern and may lead to renal tubular acidosis, which in turn may cause osteomalacia. Nevertheless, osteomalacia rarely occurs as the presenting manifestation of Sjögren’s syndrome. We report a case.
1. Case-report A 34-year-old woman was admitted for a 2-year history of diffuse bone pain, myalgia, inflammatory polyarthralgia, and a decline in general health. At admission, she had no fever but was markedly underweight (39 kg, 1.60 m). She had a waddling gait and reported pain upon palpation of the bones. There was no joint pain or evidence of arthritis. Neuromuscular function was normal. Radiographs disclosed multiple fractures of the thoracolumbar spine, ribs, and pubic rami. No evidence of joint destruction was seen on radiographs of the hands and feet. Laboratory tests showed severe inflammation (erythrocyte sedimentation rate, 109 per h; C-reactive protein, 48 mg/l; and polyclonal hypergammaglobulinemia, 24 g/l). Decreases were found in serum calcium (81 mg/l) and phosphate (22 mg/l) and in urinary calcium (40 mg/24 h) and phosphate (140 mg/24 h), whereas serum alkaline phosphatase was increased (322 UI/l), strongly suggesting osteomalacia. Serum 25-OH-vitamin D and parathyroid hormone levels were normal. Serum electrolyte assays disclosed metabolic acidosis with low potassium and high chloride. Urinary pH was 7.14. No glucose or proteins were found in the urine. Renal function was satisfactory. Findings were negative from urine cytology and microbiology. Ultrasonography of the kidneys was normal. Rheumatoid factors were present in a high titer (384 IU/ml) and antinuclear antibodies in a titer of 1/80 with a homogeneous fluorescence pattern. Tests were negative for anti-SSA and anti-SSB. A lip salivary gland biopsy revealed Chisholm stage 4 lesions.
Renal involvement is not rare in patients with Sjögren’s syndrome, although rates vary widely across studies [1]. Chronic tubulointerstitial nephritis is the usual pattern [2]. The pathophysiological mechanisms remain unclear, and the possible role for lymphocyte infiltration of the renal interstium is hotly debated. Cell apoptosis may play a part [3]. Studies have also suggested a key role for the Fas/Fas ligand system in the gland destruction that characterizes Sjögren’s syndrome [4]. Distal tubular acidosis is the most common clinical manifestation of tubulointerstitial nephritis related to Sjögren’s syndrome. The underlying mechanism is deficient H+-ATPase pump function. Osteomalacia caused by renal tubular acidosis rarely occurs as the presenting manifestation of Sjögren’s syndrome. Furthermore, osteomalacia is far more common with proximal than with distal tubular acidosis [5]. The present patient is our second reported case of inaugural osteomalacia in Sjögren’s syndrome [6]. The mechanisms leading to osteomalacia may include bone buffer release in response to metabolic acidosis and acidosis-induced dampening of osteoblast alkaline phosphatase activity [5]. Corticosteroid therapy has been used successfully in patients with osteomalacia related to renal tubular acidosis [3,7]. However, correcting the acidosis by giving alkalinizing agents without supplemental vitamin D may be sufficient [5,8]. Our case-report is a valuable reminder that osteomalacia can reveal Sjögren’s syndrome. High-dose corticosteroid therapy may improve renal involvement by Sjögren’s syndrome, although far larger numbers of patients would be needed to confirm this.
References [1]
[2] [3]
[4]
Goules A, Masouridi S, Tzioufas AG, Ionnidis JP, Skopouli FN, Moutsopoulos HM. Clinically significant and biopsy-documented renal involvement in primary Sjögren syndrome. Medicine (Baltimore) 2000;79:241–9. Kenouch S, Mery J. Les atteintes de l’interstitium rénal au cours des maladies systémiques. Nephrologie 1988;9:61–5. Saeka Y, Ohshima S, Ishida T, Shima Y, Umeshita-Sasai M, Nishioka K, et al. Remission of the renal involvement in a patient with primary Sjogren’s syndrome after pulse high-dose corticosteroid infusion therapy. Clin Rheumatol 2001;20:225–8. Matsumura R, Umemiya K, Kagami M, Tomioka A, Tanabe E, Sugiyama T, et al. Glandular and extraglandular expression of the Fas–Fas ligand and apoptosis in patients with Sjogren’s syndrome. Clin Exp Rheumatol 1998;16:561–8.
Letters to the Editor / Joint Bone Spine 72 (2005) 591–595
The presumed mechanism of bone alterations in myelofibrosis suggests a role for bisphosphonate therapy. A few cases of osteosclerosis treated with bisphosphonates in myelofibrosis patients have been reported. In one patient, etidronate therapy ensured complete relief from pain, as well as hematological improvements after 14 months [6]. In five pain-free transfusion-dependent patients, clodronate therapy induced decreases in the fibrosis visible on bone marrow biopsies with concomitant improvements in blood cells counts, which lasted up to 8 months [7]. The beneficial effects of bisphosphonate therapy may stem from multiple mechanisms including decreased bone resorption [8], fibroblast inhibition with decreased osteosclerosis [5,6,8], and an antitumor effect similar to that seen in myeloma and osteolytic bone metastases from breast cancer [9,10]. The good safety profile of bisphosphonate infusions in patients with myelofibrosis and the absence of proven treatments for the bone lesions related to this disease suggest a role for bisphosphonate therapy. In this setting, bisphosphonates may relieve pain, prevent fractures, and inhibit tumor growth. Controlled trials are needed.
References [1]
Taillant B, Ferrari E, Garnier G, Vinti H, Pesce A, Dujardin P. Hypercalcemia and diffuse osteolytic lesions in the acute phase of myeloid splenomegaly. Clin Rheumatol 1992;11:580. [2] Poullin P, Gabriel B. Primary myelofibrosis and osteolytic lesions. Rev Rhum 1994;61:560–2. [3] Tefferi A. Myelofibrosis with myeloid metaplasia. N Engl Med 2000; 342:1263–5. [4] Canalis E, Mc Carthy T, Centrella M. Growth factors and the regulation of bone remodeling. J Clin Invest 1988;81:277–81. [5] Diamond T, Smith A, Schnier R, Manoharan A. Syndrome of myelofibrosis and osteosclerosis: a series of case reports and review of the literature. Bone 2002;30:498–501. [6] Froom P, Elmalah I, Braester A, Aghai E, Quitt M. Clodronate in myelofibrosis: a case report. Am J Med Sci 2002;323:115–6. [7] Sivera P, Cesano L, Guerrasio A, Camaschella C, Mazza U. Clinical and haematological improvement induced by etidronate in a patient with idiopathic myelofibrosis. Br J Haematol 1994;86:397–8. [8] Ash P, Loulit JF, Townsend KMS. Osteoclasts derived from haematopoietic stem cells. Nature 1980;283:669–70. [9] Shipman CM, Rogers MJ, Apperley JF, Russell RG, Croucher PI. Bisphosphonates induce apoptosis in human myeloma cell lines: a novel anti-tumour activity. Br J Haematol 1997;98:665–72. [10] Diel IJ, Solomayer EF, Costa SD, Gollan C, Goerner R, Wallwiener D, et al. Reduction in new metastases in breast cancer with adjuvant clodronate treatment. N Engl J Med 1998;339:357–63.
Noémie Assous * Violaine Foltz Bruno Fautrel Sylvie Rozenberg Fabien Etchepare Pierre Bourgeois Rheumatology Department, Pitié-Salpêtrière Teaching Hospital, 47-83, boulevard de l’Hôpital, 75013 Paris, France E-mail address: [email protected] (N. Assous).
Received 20 July 2004; accepted 29 March 2005 Available online le 19 August 2005 * Corresponding author. Tel.: +33 1 53 16 41 14. 1297-319X/$ - see front matter © 2005 Elsevier SAS. All rights reserved. doi:10.1016/j.jbspin.2005.03.017
No serological evidence that fibromyalgia is linked with exposure to human parvovirus B19 Keywords: Fibromyalgia; Parvovirus B19
Fibromyalgia (FM) is a common condition characterized by chronic diffuse musculoskeletal pain, fatigue, sleep disturbances and a number of tender points to palpation. Its aetiology and pathogenesis remains unknown. Different theories have been proposed and besides genetic, neuroendocrine, psychologic and traumatic causes, infections have also been implicated. Among infections, the association of FM with some viruses has been the object of multiple studies due to its relation and similarities with the chronic fatigue syndrome (CFS) [1,2]. In this sense, many individual descriptions of association between infection with the human parvovirus B19 and FM or CFS has been reported during recent years, suggesting that parvovirus B19 may cause or trigger both conditions [3–6]. Since its discovery, a number of reports have suggested that human parvovirus B19 may be involved in the pathogenesis of various rheumatic diseases including rheumatoid arthritis, juvenile idiopathic arthritis, systemic lupus erythematosus, giant cell arteritis, dermatomyositis, CFS and FM [7–9]. However, it is critical to know if the reported associations with parvovirus B19 are due to chance or if they indicate a cause–effect association. Serological surveys carried out in European countries show that a large part of the population becomes exposed to parvovirus B19 during lifetime with seroprevalence increasing with age, to between 65% and 80% in adulthood [10,11]. Because parvovirus B19 infection is relatively common, it might coexist with FM by chance alone. Moreover, despite these reports implicating B19 virus in the pathogenesis of certain cases of FM, no systematic investigation of the seroprevalence for parvovirus B19 in epidemiologically defined FM populations has previously been performed to our knowledge. In order to clarify this question, we performed a study to determine whether there might be an association between parvovirus B19 infection and FM. For this purpose, we prospectively determined the prevalence of B19 infection in a series of 60 patients with FM, and compared it with the seroprevalence in the general population reported in the same period of time. Despite its limitations, a similar study design has been
Letters to the Editor / Joint Bone Spine 72 (2005) 591–595
previously used to investigate this possibility in other rheumatic conditions [11–13]. Available information on the extent of parvovirus B19 infection in Spain comes from three major studies of the seroprevalence of antibodies against B19 in a random sample of blood donors [14] and on a representative sample of healthy individuals selected at random from the general population [15,16]. In these studies the seroprevalence of B19 infection ranged from 53% to 65%. As in other areas, the prevalence increases with age, to between 76% and 90.9% in subjects older than 40 years [14–16]. Serum IgM and IgG antibodies against B19 VP1/VP2 antigens were measured by ELISA in all FM patients at the time of clinical diagnosis; in those cases in which IgM was positive, it was planned to test the DNA of the virus by polymerase chain reaction (PCR) in order to confirm the infection. Differences between prevalence rates were assessed by the Chi-square test. Statistical significance was defined as P ≤ 0.05. Binomial proportion test was also calculated for completeness. The study group consisted of 60 cases of primary FM consecutive diagnosed from 1998 to April 2004. These patients were evaluated at an outpatient rheumatology clinic and were routine referrals from general practitioners. All patients met the 1990 American College of Rheumatology classification criteria used for the diagnosis of FM [17]. The presence of other diseases that could explain the symptoms different that B19 infection excluded the inclusion in the study. All patients were women with a mean age at time of diagnosis of 40 ± 12 years (mean ± standard deviation; range 21–58 years). None had hematological cytopenias. Twenty of the 60 patients (33%) recalled an acute onset of the disease with “flu-like” symptoms. None of the included patients showed evidence of recent B19 infection (IgM antibodies), whereas the titers of specific IgG antibodies, indicating previous infection, were positive in 48.3% (28/60) of cases. The prevalence of antibodies against parvovirus B19 in the general Spanish population, in the group of women between 15 and 45 years of age, ranges from 43.3% [14] to 72.1% [13]. When we compared the seroprevalence in the group of FM patients with the one in the general population, no statistically significant difference was found (p> 0.05). Of interest, we neither observed differences when we only considered the group of patients with FM who recalled an acute onset with “flu-like” symptoms (40% [8/20]). A note of caution should be added in the interpretation of our results, especially regarding to the absence of IgM antibodies, since the samples tested in the study were performed at clinical diagnosis, and we can not assure that clinical diagnosis necessarily coincide with the beginning of the disease in all patients. Thus, our study does not exclude the possibility that parvovirus B19 might be a trigger of FM in a minor subset of FM patients [3]. However, the main conclusion is that in the general population parvovirus B19 is unlikely to be of aetiological importance for FM. Our findings are in close agreement with Berg et al. [18] who neither observed an etiologic association between B19 infection (searched with serol-
593
ogy and PCR to detect B19 DNA) and FM in a preliminary study conducted in 15 patients with FM. Longer studies in other populations with larger number of patients are necessary to confirm these results.
References [1] [2] [3] [4]
[5]
[6]
[7] [8] [9] [10]
[11]
[12] [13]
[14]
[15]
[16]
[17]
[18]
Goldenberg DL. Do infection trigger fibromyalgia? Arthritis Rheum 1993;36:1489–92. Goldenberg DL. Fibromyalgia syndrome a decade later. Arch Intern Med 1999;159:777–85. Leventhal LJ, Naides SJ, Freundlich B. Fibromyalgia and parvovirus infection. Arthritis Rheum 1991;34:1319–24. Kerr JR, Bracewell J, Laing I, Mattey DL, Bernstein RM, Bruce IN, et al. Chronic fatigue syndrome and arthralgia following parvovirus B19 infection. J Rheumatol 2002;29:595–602. Kerr JR, Coyle PV, DeLeys RJ, Patterson CC. Follow-up study of clinical and immunological findings in patients with acute parvovirus B19 infection. J Med Virol 1996;48:68–75. Acobson SK, Daly JS, Thorne GM, M-cIntosh K. Chronic parvovirus B19 infection resulting in chronic fatigue syndrome. Clin Infect Dis 1997;24:1048–51. Kerr JR. Pathogenesis of human parvovirus B19 in rheumatic diseases. Ann Rheum Dis 2000;59:672–83. Young NS, Brown KE. Parvovirus B19. N Engl J Med 2004;350:586– 97. Meyer O. Parvovirus B19 and autoimmune diseases. Joint Bone Spine 2003;70:6–11. Cohen BJ, Buckley MM. The prevalence of antibody to human parvovirus B19 in England and Wales. J Med Microbiol 1988;25: 151–3. Bengtsson A, Widell A, Elmstahl S, Sturfelt G. No serological indications that systemic lupus erythematosus is linked with exposure to human parvovirus B19. Ann Rheum Dis 2000;59:64–6. Peris P. Polymyalgia rheumatica is not seasonal and is unrelated to parvovirus B19 infection. J Rheumatol 2003;30:2624–6. Harrison B, Silman A, Barret E, Symmons D. Low frequency of recent parvovirus infection in a population-based cohort of patients with early rheumatoid arthritis. Ann Rheum Dis 1998;57:375–7. Muñoz S, Alonso MA, Fernández MJ, Muñoz JL, GarcíaRodriguez JM. Seroprevalence versus Parvovirus B19 in blood donors. Enferm Infecc Microbiol Clin 1998;16:161–2. De Ory F, Pachón I, Ramirez R, Echevarria JM. Antibodies against human parvovirus B19 in the Madrid community. Enferm Infecc Microbiol Clin 1999;17:364–5. Güerri ML, Prior C, Merina R, Zapico R. Regional seroprevalence of parvovirus B19, and its age and sex distribution. Enferm Infecc Microbiol Clin 2000;18:243–4. Wolfe F, Smythe H, Yunnus MB, Bennett RM, Bombardier C, Goldberg DL, et al. The American College of Rheumatology 1990 criteria for the classification of fibromyalgia. Report of the multicenter criteria committee. Arthritis Rheum 1990;33:160–72. Berg AM, Naides SJ, Simms RW. Established fibromyalgia syndrome and parvovirus B19 infection. J Rheumatol 1993;20:1941–3.
Javier Narváez * Joan-Miquel Nolla José Valverde Department of Rheumatology, Hospital Universitario de Bellvitge – IDIBELL, Hospitalet de LLobregat, Barcelona, Spain E-mail address: [email protected] (J. Narváez).
594
Letters to the Editor / Joint Bone Spine 72 (2005) 591–595
Received 17 August 2004; accepted 8 November 2004 Available online 22 March 2005 * Corresponding author. Department.of Rheumatology (Planta 10-2), Hospital, Universitario de Bellevitge, Feixa Llarga s/n, Hospitalet de LLobregat 08907, Spain. Fax: +34 93 414 16 30
The diagnosis was osteomalacia caused by renal tubular acidosis complicating tubulointerstitial nephritis as part of Sjögren’s syndrome. A corticosteroid, alkalinization, and an antimalarial were given, as well as vitamin D and calcium supplements. The clinical features and laboratory test abnormalities improved.
2. Discussion 1297-319X/$ - see front matter © 2005 Elsevier SAS. All rights reserved. doi:10.1016/j.jbspin.2004.11.004
Osteomalacia revealing Sjogren’s syndrome Keywords: Sjogren’s syndrome; Osteomalacia; Renal tubular acidosis
Renal dysfunction is not uncommon in patients with Sjögren’s syndrome. Tubulointerstitial nephritis is the usual pattern and may lead to renal tubular acidosis, which in turn may cause osteomalacia. Nevertheless, osteomalacia rarely occurs as the presenting manifestation of Sjögren’s syndrome. We report a case.
1. Case-report A 34-year-old woman was admitted for a 2-year history of diffuse bone pain, myalgia, inflammatory polyarthralgia, and a decline in general health. At admission, she had no fever but was markedly underweight (39 kg, 1.60 m). She had a waddling gait and reported pain upon palpation of the bones. There was no joint pain or evidence of arthritis. Neuromuscular function was normal. Radiographs disclosed multiple fractures of the thoracolumbar spine, ribs, and pubic rami. No evidence of joint destruction was seen on radiographs of the hands and feet. Laboratory tests showed severe inflammation (erythrocyte sedimentation rate, 109 per h; C-reactive protein, 48 mg/l; and polyclonal hypergammaglobulinemia, 24 g/l). Decreases were found in serum calcium (81 mg/l) and phosphate (22 mg/l) and in urinary calcium (40 mg/24 h) and phosphate (140 mg/24 h), whereas serum alkaline phosphatase was increased (322 UI/l), strongly suggesting osteomalacia. Serum 25-OH-vitamin D and parathyroid hormone levels were normal. Serum electrolyte assays disclosed metabolic acidosis with low potassium and high chloride. Urinary pH was 7.14. No glucose or proteins were found in the urine. Renal function was satisfactory. Findings were negative from urine cytology and microbiology. Ultrasonography of the kidneys was normal. Rheumatoid factors were present in a high titer (384 IU/ml) and antinuclear antibodies in a titer of 1/80 with a homogeneous fluorescence pattern. Tests were negative for anti-SSA and anti-SSB. A lip salivary gland biopsy revealed Chisholm stage 4 lesions.
Renal involvement is not rare in patients with Sjögren’s syndrome, although rates vary widely across studies [1]. Chronic tubulointerstitial nephritis is the usual pattern [2]. The pathophysiological mechanisms remain unclear, and the possible role for lymphocyte infiltration of the renal interstium is hotly debated. Cell apoptosis may play a part [3]. Studies have also suggested a key role for the Fas/Fas ligand system in the gland destruction that characterizes Sjögren’s syndrome [4]. Distal tubular acidosis is the most common clinical manifestation of tubulointerstitial nephritis related to Sjögren’s syndrome. The underlying mechanism is deficient H+-ATPase pump function. Osteomalacia caused by renal tubular acidosis rarely occurs as the presenting manifestation of Sjögren’s syndrome. Furthermore, osteomalacia is far more common with proximal than with distal tubular acidosis [5]. The present patient is our second reported case of inaugural osteomalacia in Sjögren’s syndrome [6]. The mechanisms leading to osteomalacia may include bone buffer release in response to metabolic acidosis and acidosis-induced dampening of osteoblast alkaline phosphatase activity [5]. Corticosteroid therapy has been used successfully in patients with osteomalacia related to renal tubular acidosis [3,7]. However, correcting the acidosis by giving alkalinizing agents without supplemental vitamin D may be sufficient [5,8]. Our case-report is a valuable reminder that osteomalacia can reveal Sjögren’s syndrome. High-dose corticosteroid therapy may improve renal involvement by Sjögren’s syndrome, although far larger numbers of patients would be needed to confirm this.
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