these cells. Calprotectin also correlated with the fatigue scores FSS, VAS, and SF-36 vitality (Table 2) and may represent other aspects of inflammation than ESR and CRP. S100A12 correlated with the focus score (Table 2). This might indicate that S100A12 is of value as a biomarker of more active disease, although firm conclusions cannot be drawn. We expected that patients with joint affection might have higher levels of calprotectin and S100A12, but found no support for this. The statistical power may have been too low for analysis of this subgroup. ERAC is a novel protein complex and its threedimensional structure is not known. However, it is known to contain at least two S100A12 antigenic epitopes reacting with both rabbit polyclonal and mouse monoclonal antibodies (2). We found only four ERACpositive patients out of 140, while none of the controls were positive (Table 1). The four were all ANA positive and three of these had a biopsy with a focus score of three, four, and seven, respectively. Although this is a low number of patients, it is noteworthy because the median focus score was only one in the whole patient group. We found a higher focus score (p ¼ 0.025) and IgG (p ¼ 0.021) in ERAC-positive patients than in ERAC-negative patients. ERAC correlated with ESR (p ¼ 0.002), ANA (p ¼ 0.01), anti-SSA (p ¼ 0.03), anti-SSB (p ¼ 0.02), and IgG (p ¼ 0.009) (data not shown). It is conceivable that ERAC positivity may be associated with high disease activity in some pSS patients. Studies of these proteins with a longitudinal design and on subgroups of patients with pSS are needed for more definite conclusions to be drawn.
References 1. Foell D, Roth J. Proinflammatory S100 proteins in arthritis and autoimmune disease. Arthritis Rheum 2004;50:3762–71. 2. Fagerhol MK, Larsen A, Brun JG, Hammer HB, Angel K, Kvien TK, et al. Large molecular size EDTA-resistant complexes containing S100A12, ERAC, in serum during inflammatory conditions. Scand J Clin Lab Invest 2012;72:129–36. 3. Kuruto R, Nozawa R, Takeishi K, Arai K, Yokota T, Takasaki Y. Myeloid calcium binding proteins: expression in the differentiated HL-60 cells and detection in sera of patients with connective tissue diseases. J Biochem 1990;108:650–3. 4. Cuida M, Halse AK, Johannessen AC, Tynning T, Jonsson R. Indicators of salivary gland inflammation in primary Sjögren’s syndrome. Eur J Oral Sci 1997;105:228–33. 5. Soyfoo MS, Roth J, Vogl T, Pochet R, Decaux G. Phagocytespecific S100A8/A9 protein levels during disease exacerbations and infections in systemic lupus erythematosus. J Rheumatol 2009;36: 2190–4. 6. Brun JG, Cuida M, Jacobsen H, Kloster R, Johannesen AC, Hoyeraal HM, et al. Sjögren’s syndrome in inflammatory rheumatic diseases: analysis of the leukocyte protein calprotectin in plasma and saliva. Scand J Rheumatol 1994;23:114–18. 7. Kristinsson J, Roseth A, Fagerhol MK, Aadland E, Schjonsby H, Bormer OP, et al. Fecal calprotectin concentration in patients with colorectal carcinoma. Dis Colon Rectum 1998;41:316–21. 8. Larsen A, Bronstein IB, Dahl O, Wentzel-Larsen T, Kristoffersen EK, Fagerhol MK. Quantification of S100A12 (EN-RAGE) in blood varies with sampling method, calcium and heparin. Scand J Immunol 2007;65:192–201. 9. Frosch M, Metze D, Foell D, Vogl T, Sorg C, Sunderkotter C, et al. Early activation of cutaneous vessels and epithelial cells is characteristic of acute systemic onset juvenile idiopathic arthritis. Exp Dermatol 2005;14:259–65. 10. Katz J, Stavropoulos F, Bhattacharyya I, Stewart C, Perez FM, Caudle RM. Receptor of advanced glycation end product (RAGE) expression in the minor salivary glands of patients with Sjögren’s syndrome: a preliminary study. Scand J Rheumatol 2004;33:174–8. 11. Stewart C, Cha S, Caudle RM, Berg K, Katz J. Decreased levels of soluble receptor for advanced glycation end products in patients with primary Sjögren’s syndrome. Rheumatol Int 2008;28:771–6.
Acknowledgements We thank M Eidsheim for technical assistance with the analyses of ERAC and A Larsen for the analyses of calprotectin and S100A12. This study was supported by GC Rieber Funds, the Broegelmann Foundation, the Marie and Else Mustad Legacy and the Norwegian Rheumatism Association.
Hilde Haugedal Nordal, Broegelmann Research Laboratory, Department of Clinical Science, University of Bergen, Postboks 7804, N-5020 Bergen, Norway. E-mail: [email protected]
Accepted 23 September 2013
Systemic myositis due to Campylobacter infection Y Fujiki1, T Kotani1, T Takeuchi2, S Makino2 1 Department of Rheumatology, Internal Medicine, Yodogawa Christian Hospital, Higashi Yodogawa-ku, and 2Department of Internal Medicine (I), Osaka Medical College, Takatsuki, Osaka, Japan
Myositis is classified into two subgroups: idiopathic myositis and infectious myositis. Idiopathic myositis includes connective tissue disease, vasculitis, granulomatous myositis, eosinophilic myositis, and inclusion-body myositis. Infectious myositis is
caused by viruses, bacteria, protozoa, parasites, and fungi (1). Campylobacter species are curved, microaerophilic, gram-negative rods with a characteristic darting motility. Campylobacter jejuni is the most common cause of human bacterial enteritis,
accounting for 5–14% of all diarrhoeal diseases (2). We report the very rare case of a patient with systemic myositis due to Campylobacter infection. A 78-year-old man ate raw chicken on 26 July 2012. Three days later he developed watery diarrhoea, nausea, muscle pain over his entire body, and weakness of the limbs. The muscle pain and weakness increased to the extent that he could not get out of bed, and so he visited our hospital on 31 July. He had no history of having pets or travelling abroad. On admission, he had a fever of 37.6 C and lower abdominal pain. Muscle pain predominantly affecting the proximal muscles of the limbs and decreased muscle strength (manual muscle test: upper limbs, 4; lower limbs, 3+) were observed. There was no sensory disturbance in the limbs. No skin eruption was observed. Laboratory examinations showed a white blood cell count (WBC) of 5700/μL (neutrophils, 78%; lymphocytes, 15%; eosinophils, 0%), platelet count (PLT) 125 000/μL, glutamate oxaloacetate transferase (GOT) 738 U/L, lactate dehydrogenase (LDH) 1052 U/L, creatine phosphokinase (CPK) 40 860 U/L, and aldolase 195.6 U/L, revealing an increase in myogenic enzymes. His electrolyte levels and thyroid function were normal, as were his immunoglobulin (Ig) and complement levels. Antinuclear antibody was negative, and other diseasespecific autoantibodies including anti-Jo-1 antibody were not detected. Magnetic resonance imaging (MRI) of the right upper arm where the muscle pain was strongest revealed diffuse swelling and oedematous changes in the muscles in the right arm and shoulder girdle, and a diagnosis of myositis was made (Figure 1A). Abdominal computed tomography (CT) showed thickening of the ascending colon wall, and a stool culture was positive for C. jejuni. His nausea and diarrhoea improved after fasting and fluid replacement following admission. After 10 days, his muscle pain and weakness had improved, and the myogenic enzyme levels had decreased and normalized. He was discharged on the 12th hospital day. MRI of the right upper arm performed on the 30th day after onset of illness revealed that the myositis findings had disappeared (Figure 1B). Muscle biopsy was not performed in this patient. However, there were no findings of idiopathic myositis, including collagen vascular disease, or other findings clearly indicating myopathies, neurological disorders, or endocrine/metabolic disorders. In addition, the onset of enteritis was synchronized with that of the myositis, the activities of both diseases changed concurrently, and the myositis improved after the improvement in enteritis. Based on these findings, a diagnosis of myositis due to Campylobacter infection was made. Among the bacteria, spirochetes, leptospira, tuberculosis, mycoplasma, streptococci, and staphylococcus have been reported to induce myositis (1). Campylobacter is a common cause of human bacterial enteritis. However, to our knowledge there has been only one report of a patient with myositis due to Campylobacter, namely that reported by Dawson and Davidson of a 14-year-old female with focal left calf myositis due to
1B; DAY 30
1A; DAY 0 A
Figure 1. MRI of the right upper arm. (A) Coronal T2-weighted MR image of the right arm at admission showing extensive, diffuse, highintensity lesions in the right arm and shoulder girdle. (B) Coronal T2-weighted MR image of the right upper arm on the 30th day after onset of illness showing the lack of inflammatory findings in these areas.
Campylobacter (3). Myositis occurred following bloody diarrhoea persisting for 5 days and improved after 6 weeks. Our patient’s case was similar to this case, but ours is the first reported case of systemic myositis due to Campylobacter infection. The pathogenesis of myositis due to Campylobacter infection is unclear. However, Campylobacter infection has been reported to induce immune diseases such as Guillain–Barré syndrome (4), reactive arthritis (5), and IgA-vasculitis, including Henoch–Schönlein purpura (6, 7). As types of pathogenesis, the abnormal production of proinflammatory cytokines due to the action of Campylobacter as an exogenous antigen (8), immunocomplex formation (9, 10), and molecular mimicry (5) have been suggested. Similar mechanisms could be considered in our case. In summary, Campylobacter infection is a common disease. Although there have been only two reported cases, including that of the present case, of myositis due to Campylobacter infection, other cases may have been overlooked. Therefore, attention should be paid to detect this infection, and its pathology further clarified.
References 1. Targoff IN. Polymyositis and dermatomyositis in adult. In: Maddison PJ, Isenberg DA, Woo P, Glass DN, editors. Oxford textbook of rheumatology, 2nd edn. Oxford: Oxford University Press, 1993:794–821. 2. Rautelin H, Hänninen ML. Campylobacters: the most common bacterial enteropathogens in the Nordic countries. Ann Med 2000;32:440–5. 3. Dawson JK, Davidson JE. Focal myositis due to Campylobacter infection. Rheumatology (Oxford) 2001;40:704–6.
80 4. Rees JH, Soudain SE, Gregson NA, Hughes RA. Campylobacter jejuni infection and Guillain–Barré syndrome. N Engl J Med 1995;333:1374–9. 5. Pope JE, Krizova A, Garg AX, Thiessen-Philbrook H, Ouimet JM. Campylobacter reactive arthritis: a systematic review. Semin Arthritis Rheum 2007;37:48–55. 6. Carter JE, Cimolai N. IgA nephropathy associated with Campylobacter jejuni enteritis. Nephron 1991;58:101–2. 7. Apostolopoulos P, Vafiadis-Zouboulis E, Delladetsima I, Charalambopoulos D, Archimandritis A, Katsilambros N. HenochSchönlein purpura associated with Campylobacter enterocolitis. J Clin Gastroenterol 1999;29:346–7. 8. Lim A, Lydia A, Rim H, Dowling J, Kerr P. Focal segmental glomerulosclerosis and Guillain-Barre syndrome associated with Campylobacter enteritis. Intern Med J 2007; 37:724–8.
Letters 9. Tomino Y, Sakai H, Miura M, Endoh M, Nomoto Y. Detection of polymeric IgA in glomeruli from patients with IgA nephropathy. Clin Exp Immunol 1982;49:419–25. 10. André C, Berthoux FC, André F, Gillon J, Genin C, Sabatier JC. Prevalence of IgA2 deposits in IgA nephropathies: a clue to their pathogenesis. N Engl J Med 1980;303:1343–6.
Takuya Kotani, Department of Rheumatology, Internal Medicine, Yodogawa Christian Hospital, 1-7-50 Kunijima, Higashi Yodogawaku, Osaka 533-0024, Japan. E-mail: [email protected]
Accepted 19 September 2013
Effects of wearing high heels on the forefoot: an MRI evaluation W Stomp1, A Krabben2, AHM van der Helm-van Mil2, M Reijnierse1 1
Departments of Radiology and 2Rheumatology, Leiden University Medical Centre, Leiden, The Netherlands
Rheumatoid arthritis frequently involves inflammation of the forefoot. Magnetic resonance imaging (MRI) is being used increasingly, mostly for research purposes, to detect inflammation. Given the sensitivity of MRI, a relevant issue is to discern pathology from normal variations because abnormalities have been observed in healthy persons (1–4). In particular, it is not known whether regular physical exercise or wearing a particular shoe type affects MRI results. Bone marrow oedema has been described
Figure 1. (A) The high-heel shoes worn by the three subjects. (B, C) Sagittal T2-weighted fat-suppressed image at the level of the second metatarsal bone (B) before and (C) after a day of high-heel wearing shows subcutaneous oedema at the plantar and dorsal side. Note the proximal location to the MTP joints on the plantar side (arrows).
(sometimes asymptomatic) in athletes (5). As wearing high heels shifts pressure from the heel to the heads of the metatarsal bones (6–8), we hypothesized that this might result in acute abnormalities of the forefoot similar to changes secondary to trauma or repetitive stress. We performed a single-blind crossover study to determine this. Three healthy females (age 17–18 years) underwent 1.5T MRI examinations of the dominant foot before (0800 h) and after (1700 h) a school day, with provoked walking distance and visual analogue scale (VAS) pain score. Activity, pain, and symptoms were recorded twice every hour. Flat shoes were worn on day 1 and high heels (mean height 9.48 cm) on day 2. Subjects wore flat shoes for 1 week before both examinations. MRI of the forefoot included T1-weighted and T2-weighted fat-suppressed scans, both in three orthogonal directions. Evaluation was performed by two readers independently who were blinded to the study day. In case of disagreement, a third reader, a musculoskeletal radiologist, made the judgement. The study was approved by the Institutional Review Board and all participants gave their written informed consent. The three subjects walked 6.7, 6.1, and 6.5 km respectively on day 1 and 8.1, 7.0, and 7.1 km respectively on day 2, including 15 min of stair climbing. VAS pain scores remained low (range 0–2) on day 1 but increased to 5–8 at the end of day 2. Pain was predominantly located in the forefoot area. One subject (a fanatic gymnast) had extensive bone marrow oedema of the medial sesamoid bone adjacent to the first metatarsophalangeal (MTP) joint, which was unchanged over all four MRI scans. No other abnormalities were seen on all MRI scans at 0800h, or on the forefoot MRI at 1700 h on
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