LETTERS TO THE EDITOR *MRC Dunn Nutrition Laboratory, Accepted 31 July 1991
Cambridge CB4 1XJ
1. Barnes MJ, Kodicek E. Biological hydroxylations and ascorbic acid with special regard to collagen metabolism. Vitam Horm 1972;30:l^l3. 2. Peterkofsky B, Udenfriend S. Enzymatic hydroxylation of proline in microsomal polypeptide leading to formation of collagen. Proc Natl Acad Sci USA 1965;53:335-42. 3. Hyams DE, Ross EJ. Scurvy, megaloblastic anaemia and osteoporosis. Br J Clin Pract 1963; 17:332^0. 4. Schorah CJ, Morgan DB. Nutritional deficiencies in the elderly. Hosp Update 1985;ll:353-60. 5. Vuilleumier JP, Keck E. Fluorometic assay of vitamin C in biological materials using a centrifugal analyser with fluorescence attachment. J Micromtr Anal 1989;5:25-34. Are Nodules in RA the Result of Manual Work?
J. G. JONES
Director of Rheumatology, Queen Elizabeth Hospital for Rheumatic Disease and Rehabilitation, P. O. Box 1342, Whakaue Street, Rotorua Accepted 25 September 1991 1. Thompson PW, Pegley FS. A comparison of disability measured by the Stanford health assessment questionnaire disability scales in male and female rheumatoid outpatients. Br J Rheumatol 1991 ;30:298-300.
2. De Haas WHD, De Boer W, Griffioen F, Oosten-Elst P. Rheumatoid arthritis of the robust reaction type. Ann Rheum Dis 1974;33:81-5. 3. Harris ED. Clinical features of rheumatoid arthritis. In: Kelley WN, Harris ED Jr, Ruddy S, Sledge CH, eds. Textbook of rheumatology. Philadelphia: WB Saunders, 1989;Ch.55;972. 4. Ebringer A. Rheumatoid arthritis as an infectious disease. Br MedJ 1991;303:524. Assessment of Ankylosing Spondylitis
SIR—We read with interest the editorial [1] and accompanying articles [2-4] in the October 1991 British Journal of Rheumatology, on assessment of disease activity and outcome in ankylosing spondylitis (AS). It is recognized that the assessment of patients with AS is difficult [3]. We agree it is important to distinguish between disease activity (process measures) and disease severity (outcome measures) [1]. Taylor et al. [3] show a good correlation between spinal flexion, chest expansion, finger-floor distance, and occiput-to-wall distance and corresponding lack of correlation with pain and stiffness, supporting the notion that the former are measures of disease severity or deformity (outcome) whilst the latter is a measure of disease activity (process). We would agree there are problems in choosing disease activity indicators in the absence of a single accurate measure [1-4]. If multiple process measures are used to assess disease activity, each should reflect independent facets of the disease [5], be reliable, valid and potentially reversible [2], i.e. in the face of a real change, the measure itself changes in the same direction [1]. As no single measure, however, reflects the disease activity in AS a composite index of inflammation, as in rheumatoid arthritis, may resolve some of the difficulties. Variables chosen to derive a disease activity score should be selected by careful, clinical reasoning and validated on large numbers of patients. The large number of variables potentially available for use in a composite index could be reduced to those reflecting the overall variation in the data set by use of principal components analysis. This topic was discussed at the 2nd Special Interest Group Meeting on Seronegative Spondyloarthropathies at the British Society for Rheumatology Eighth Annual General Meeting (18-20 September 1991). Cross-sectional measures of disease activity appear unrelated to outcome. Longitudinal measures may do so; this could be addressed using serial measures of activity as suggested by Mathews etal. [6]. We support the proposal of developing indices of activity and outcome as suggested and feel these should be evaluated at multiple centres on large numbers of patients over a prolonged time period [4]. By developing standards methods a better understanding of the natural history with identification of subgroups and evaluation of therapeutic measures can be performed. K. ZUKOVSKIS*, M. J. DAVlSt, P. T. DAWESf, P. JONESf *Senior 1 Physiotherapist Research, Haywood Hospital, Burslem, Stoke-on-Trent ST6 TAG tStaffordshire Rheumatology Centre, Stoke-on-Trent ST6 7AG tMathematics Department, Keele University, Staffordshire Accepted 30 October 1991 1. Rigby AS, Silman AJ. Outcome assessment in clinical trials of ankylosing spondylitis. Br J Rheumatol 1991 ;30:321—2. 2. Laurent MR, Buchanan WW, Bellamy N. Methods of assessment used in ankylosing spondylitis clinic trials: a review. Br J Rheumatol 1991;30:326-9.
Downloaded from http://rheumatology.oxfordjournals.org/ at Lakehead University on April 5, 2015
SIR—I was stimulated by one of Thompson and Pegley's observations in their comparison of the characteristics of males and females with rheumatoid arthritis [1]. They noted a significant difference in the percentage of males with nodules (50% of 22 patients) when compared with females (19% of 63 patients), and observed that this was in keeping with the findings of De Haas et al. who attributed nodules to the effects of manual work [2]. I sense this suggestion (made in 1974) that women eschew manual work will engender indignation in the bosoms of today's femininist sorority, and I have always felt empathy with the old adage of the Welsh valleys that 'Hard work never hurt no-one'. I find it difficult to accept that nodules are purely the result of manual work and am tempted to look for another explanation. If the percentages are unscrambled it will be seen that the number of males (11) is similar to the number of females (12). This finding could be explained on the grounds that nodular 'rheumatoid arthritis' is a disease sui generis which affects males and females equally. Support for this concept comes from rheumatological folklore which states that the presence of nodules is associated with 'more severe disease' [3] and clinical experience backs this up. If this group of patients is separated from those at present classified as having 'rheumatoid arthritis', we are left with the anodular patients. Most of these are female. In the study in question the female: male ratio is approximately 5:1. This suggests that factors like sex hormones or recurrent Proteus mirabilis infection of the susceptible female urinary tract [4] exert a major pathogenic influence in this type of disease. If nodular and anodular rheumatoid arthritis are different diseases, it is conceivable that their response to second-line drug treatment is different. Could this then help to explain why the outcome of the drug treatment of rheumatoid arthritis is so unpredictable? This thought of course does nothing to belittle the important influence the different social and cultural roles and psychological make up of the sexes have on the outcome of chronic inflammatory arthritis.
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3. Taylor HG, Wardle T, Beswick EJ, Dawes PT. The relationship of clinical and laboratory measurements to radiological change in ankylosing spondylitis. Br J Rheumatol 1991;30:330-5. 4. Goodacre JA, Mander M, Dick WC. Patients with ankylosing spondylitis show individual patterns of variation in disease activity. Br J Rheumatol 1991;30:336-8. 5. Davis MJ. Indices de actividad en la artritis reumatoide. Rev Esp Rewnatol 1991 ;18:45-6. 6. Mathews JNS, Altman DG, Campbell MJ, Royston P. Analysis of serial measurements in medical research. Br Med J 1990,29:111-15. Confusional Syndrome as the Presenting Form of Calcium Pyrophosphate Dihydrate Deposition Disease
A. ARAG6N, M. A. SEPULVEDA, A. CER6N*
Rheumatology Unit, Hospital Virgen de la Salud and * Geriatric Section, Hospital Virgen del Valle, Toledo, Spain Accepted 4 November 1991 1. McCarty D. Crystals, joints and consternation. Ann Rheum Dis 1983;42:243-53. 2. Rahman MU, Shenberger KN, Schumacher HR. Initially unrecognized calcium pyrophosphate dihydrate deposition disease as a cause of fever. Am J Med 1990:89:115-16. 3. Berger RG, Levitin PM. Febrile presentation of calcium pyrophosphate dihydrate deposition disease. J Rheumatol 1988;15:642-3. 4. Masuda I, Ishikawa K. Clinical features of pseudogout attack. A survey of 50 cases. Clin Orthop 1988:229:173-81. 5. Dayer JM, Evequoz V, Zavadil-Grob C, et al. Effect of synthetic calcium pyrophosphate and hydroxyapatite crystals on the interaction of human blood mononuclear cell with chondrocytes, synovial cells and fibroblasts. Arthritis Rheum 1987 ;30:1372-81. 6. Shoam S, Davenu D, Cady AB, Dinarello CA. Krueger JM. Recombinant human TNF and IL-1 induce slow wave sleep in rabbits. Am J Physiol 1987:253:12142.
Downloaded from http://rheumatology.oxfordjournals.org/ at Lakehead University on April 5, 2015
SIR—In 1983 McCarty [1] described and classified the forms of manifestation of calcium pyrophosphate deposition disease (CPDD). One of them, pseudogout, is an acute inflammatory process of single or multiple joints, which lasts days or a few weeks, the knees being the most frequent site of involvement. Often it is associated with systemic involvement and high fever [2, 3]. Rarely, as in the case described here, does CPDD appear as a confusional syndrome, a neurological abnormality which disappeared with the resolution of the joint process. A 72-year-old female suffering from high blood pressure treated with atenolol and complaining of occasional joint pains without clear signs of inflammation that was alleviated by NSAIDs, was admitted to our hospital. A few hours before her admission she started suffering impairment of her consciousness, which gradually worsened. Her family denied the existence of other symptoms: fever, chills, seizures or other neurological impairment. She was being treated only with atenolol for high blood pressure, with no evidence of her having taken any other medication during the last few weeks. Upon physical examination her body temperature was 37.5°C. She was stuporous and disoriented in time and space upon neurological examination. Laboratory examination showed an erythrocyte sedimentation rate of 102 mm/h and leucocytosis, mainly neutrophils. Tests made to find an infectious focus, including culture of urine, blood and stool and a lumbar puncture, were negative. A cranial CT scan was normal. Rheumatoid factor, C-reactive protein and antinuclear antibodies were all normal. Treatment with antibiotics was begun at her admission. After a careful joint examination 3 days later, inflammatory signs in both knees, right elbow and metacarpophalangeal joints of the right hand were observed. Forty ml of synovia! fluid were aspirated from the right knee, for which culture and Gram stain were negative, but characteristic calcium pyrophosphate dihydrate crystals were identified. An X-ray examination of both knees showed evidence of
chondrocalcinosis. At the third day after admission we stopped antibiotic treatment, we started treatment with colchicine, and then the joint process stopped and the confusional syndrome disappeared after 2 days. Joint involvement is the characteristic initial finding of CPDD. Often some patients have systemic involvement and high fever which are sometimes the most evident findings, even more than joint disorder, and they are a cause of fever of unknown origin and of high erythrocyte sedimentation rate in the elderly [3]. Exceptionally, as in the above cited case, confusional syndrome is the main or the most important symptom. In a recent review of 50 patients with pseudogout [4], 25 had some fever and five suffered mental impairment, including disorientation, confusion and visual disorder. These neurological features can interact with the testing of the joint disorder and hinder the diagnosis. Polyarticular sepsis may occur in people with established joint disease. Nevertheless, the short duration of the joint process and the rapid response to the colchicine makes it unlikely. Fever in these patients has been attributed to interleukin-1 produced by monocytes, the latter being stimulated by calcium pyrophosphate crystals [5]. Interleukin-1 also produces disorders of the central nervous system by the production of slow sleep waves and somnolence [6], which could explain the symptoms of our patient. In conclusion it is emphasized that joint involvement in CPDD is not always the main finding, thus hindering the diagnosis. As in the case of the above patient, confusional syndrome may be a presenting feature.
Cambridge CB4 1XJ
1. Barnes MJ, Kodicek E. Biological hydroxylations and ascorbic acid with special regard to collagen metabolism. Vitam Horm 1972;30:l^l3. 2. Peterkofsky B, Udenfriend S. Enzymatic hydroxylation of proline in microsomal polypeptide leading to formation of collagen. Proc Natl Acad Sci USA 1965;53:335-42. 3. Hyams DE, Ross EJ. Scurvy, megaloblastic anaemia and osteoporosis. Br J Clin Pract 1963; 17:332^0. 4. Schorah CJ, Morgan DB. Nutritional deficiencies in the elderly. Hosp Update 1985;ll:353-60. 5. Vuilleumier JP, Keck E. Fluorometic assay of vitamin C in biological materials using a centrifugal analyser with fluorescence attachment. J Micromtr Anal 1989;5:25-34. Are Nodules in RA the Result of Manual Work?
J. G. JONES
Director of Rheumatology, Queen Elizabeth Hospital for Rheumatic Disease and Rehabilitation, P. O. Box 1342, Whakaue Street, Rotorua Accepted 25 September 1991 1. Thompson PW, Pegley FS. A comparison of disability measured by the Stanford health assessment questionnaire disability scales in male and female rheumatoid outpatients. Br J Rheumatol 1991 ;30:298-300.
2. De Haas WHD, De Boer W, Griffioen F, Oosten-Elst P. Rheumatoid arthritis of the robust reaction type. Ann Rheum Dis 1974;33:81-5. 3. Harris ED. Clinical features of rheumatoid arthritis. In: Kelley WN, Harris ED Jr, Ruddy S, Sledge CH, eds. Textbook of rheumatology. Philadelphia: WB Saunders, 1989;Ch.55;972. 4. Ebringer A. Rheumatoid arthritis as an infectious disease. Br MedJ 1991;303:524. Assessment of Ankylosing Spondylitis
SIR—We read with interest the editorial [1] and accompanying articles [2-4] in the October 1991 British Journal of Rheumatology, on assessment of disease activity and outcome in ankylosing spondylitis (AS). It is recognized that the assessment of patients with AS is difficult [3]. We agree it is important to distinguish between disease activity (process measures) and disease severity (outcome measures) [1]. Taylor et al. [3] show a good correlation between spinal flexion, chest expansion, finger-floor distance, and occiput-to-wall distance and corresponding lack of correlation with pain and stiffness, supporting the notion that the former are measures of disease severity or deformity (outcome) whilst the latter is a measure of disease activity (process). We would agree there are problems in choosing disease activity indicators in the absence of a single accurate measure [1-4]. If multiple process measures are used to assess disease activity, each should reflect independent facets of the disease [5], be reliable, valid and potentially reversible [2], i.e. in the face of a real change, the measure itself changes in the same direction [1]. As no single measure, however, reflects the disease activity in AS a composite index of inflammation, as in rheumatoid arthritis, may resolve some of the difficulties. Variables chosen to derive a disease activity score should be selected by careful, clinical reasoning and validated on large numbers of patients. The large number of variables potentially available for use in a composite index could be reduced to those reflecting the overall variation in the data set by use of principal components analysis. This topic was discussed at the 2nd Special Interest Group Meeting on Seronegative Spondyloarthropathies at the British Society for Rheumatology Eighth Annual General Meeting (18-20 September 1991). Cross-sectional measures of disease activity appear unrelated to outcome. Longitudinal measures may do so; this could be addressed using serial measures of activity as suggested by Mathews etal. [6]. We support the proposal of developing indices of activity and outcome as suggested and feel these should be evaluated at multiple centres on large numbers of patients over a prolonged time period [4]. By developing standards methods a better understanding of the natural history with identification of subgroups and evaluation of therapeutic measures can be performed. K. ZUKOVSKIS*, M. J. DAVlSt, P. T. DAWESf, P. JONESf *Senior 1 Physiotherapist Research, Haywood Hospital, Burslem, Stoke-on-Trent ST6 TAG tStaffordshire Rheumatology Centre, Stoke-on-Trent ST6 7AG tMathematics Department, Keele University, Staffordshire Accepted 30 October 1991 1. Rigby AS, Silman AJ. Outcome assessment in clinical trials of ankylosing spondylitis. Br J Rheumatol 1991 ;30:321—2. 2. Laurent MR, Buchanan WW, Bellamy N. Methods of assessment used in ankylosing spondylitis clinic trials: a review. Br J Rheumatol 1991;30:326-9.
Downloaded from http://rheumatology.oxfordjournals.org/ at Lakehead University on April 5, 2015
SIR—I was stimulated by one of Thompson and Pegley's observations in their comparison of the characteristics of males and females with rheumatoid arthritis [1]. They noted a significant difference in the percentage of males with nodules (50% of 22 patients) when compared with females (19% of 63 patients), and observed that this was in keeping with the findings of De Haas et al. who attributed nodules to the effects of manual work [2]. I sense this suggestion (made in 1974) that women eschew manual work will engender indignation in the bosoms of today's femininist sorority, and I have always felt empathy with the old adage of the Welsh valleys that 'Hard work never hurt no-one'. I find it difficult to accept that nodules are purely the result of manual work and am tempted to look for another explanation. If the percentages are unscrambled it will be seen that the number of males (11) is similar to the number of females (12). This finding could be explained on the grounds that nodular 'rheumatoid arthritis' is a disease sui generis which affects males and females equally. Support for this concept comes from rheumatological folklore which states that the presence of nodules is associated with 'more severe disease' [3] and clinical experience backs this up. If this group of patients is separated from those at present classified as having 'rheumatoid arthritis', we are left with the anodular patients. Most of these are female. In the study in question the female: male ratio is approximately 5:1. This suggests that factors like sex hormones or recurrent Proteus mirabilis infection of the susceptible female urinary tract [4] exert a major pathogenic influence in this type of disease. If nodular and anodular rheumatoid arthritis are different diseases, it is conceivable that their response to second-line drug treatment is different. Could this then help to explain why the outcome of the drug treatment of rheumatoid arthritis is so unpredictable? This thought of course does nothing to belittle the important influence the different social and cultural roles and psychological make up of the sexes have on the outcome of chronic inflammatory arthritis.
143
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BRITISH JOURNAL OF RHEUMATOLOGY VOL. XXXI NO. 2
3. Taylor HG, Wardle T, Beswick EJ, Dawes PT. The relationship of clinical and laboratory measurements to radiological change in ankylosing spondylitis. Br J Rheumatol 1991;30:330-5. 4. Goodacre JA, Mander M, Dick WC. Patients with ankylosing spondylitis show individual patterns of variation in disease activity. Br J Rheumatol 1991;30:336-8. 5. Davis MJ. Indices de actividad en la artritis reumatoide. Rev Esp Rewnatol 1991 ;18:45-6. 6. Mathews JNS, Altman DG, Campbell MJ, Royston P. Analysis of serial measurements in medical research. Br Med J 1990,29:111-15. Confusional Syndrome as the Presenting Form of Calcium Pyrophosphate Dihydrate Deposition Disease
A. ARAG6N, M. A. SEPULVEDA, A. CER6N*
Rheumatology Unit, Hospital Virgen de la Salud and * Geriatric Section, Hospital Virgen del Valle, Toledo, Spain Accepted 4 November 1991 1. McCarty D. Crystals, joints and consternation. Ann Rheum Dis 1983;42:243-53. 2. Rahman MU, Shenberger KN, Schumacher HR. Initially unrecognized calcium pyrophosphate dihydrate deposition disease as a cause of fever. Am J Med 1990:89:115-16. 3. Berger RG, Levitin PM. Febrile presentation of calcium pyrophosphate dihydrate deposition disease. J Rheumatol 1988;15:642-3. 4. Masuda I, Ishikawa K. Clinical features of pseudogout attack. A survey of 50 cases. Clin Orthop 1988:229:173-81. 5. Dayer JM, Evequoz V, Zavadil-Grob C, et al. Effect of synthetic calcium pyrophosphate and hydroxyapatite crystals on the interaction of human blood mononuclear cell with chondrocytes, synovial cells and fibroblasts. Arthritis Rheum 1987 ;30:1372-81. 6. Shoam S, Davenu D, Cady AB, Dinarello CA. Krueger JM. Recombinant human TNF and IL-1 induce slow wave sleep in rabbits. Am J Physiol 1987:253:12142.
Downloaded from http://rheumatology.oxfordjournals.org/ at Lakehead University on April 5, 2015
SIR—In 1983 McCarty [1] described and classified the forms of manifestation of calcium pyrophosphate deposition disease (CPDD). One of them, pseudogout, is an acute inflammatory process of single or multiple joints, which lasts days or a few weeks, the knees being the most frequent site of involvement. Often it is associated with systemic involvement and high fever [2, 3]. Rarely, as in the case described here, does CPDD appear as a confusional syndrome, a neurological abnormality which disappeared with the resolution of the joint process. A 72-year-old female suffering from high blood pressure treated with atenolol and complaining of occasional joint pains without clear signs of inflammation that was alleviated by NSAIDs, was admitted to our hospital. A few hours before her admission she started suffering impairment of her consciousness, which gradually worsened. Her family denied the existence of other symptoms: fever, chills, seizures or other neurological impairment. She was being treated only with atenolol for high blood pressure, with no evidence of her having taken any other medication during the last few weeks. Upon physical examination her body temperature was 37.5°C. She was stuporous and disoriented in time and space upon neurological examination. Laboratory examination showed an erythrocyte sedimentation rate of 102 mm/h and leucocytosis, mainly neutrophils. Tests made to find an infectious focus, including culture of urine, blood and stool and a lumbar puncture, were negative. A cranial CT scan was normal. Rheumatoid factor, C-reactive protein and antinuclear antibodies were all normal. Treatment with antibiotics was begun at her admission. After a careful joint examination 3 days later, inflammatory signs in both knees, right elbow and metacarpophalangeal joints of the right hand were observed. Forty ml of synovia! fluid were aspirated from the right knee, for which culture and Gram stain were negative, but characteristic calcium pyrophosphate dihydrate crystals were identified. An X-ray examination of both knees showed evidence of
chondrocalcinosis. At the third day after admission we stopped antibiotic treatment, we started treatment with colchicine, and then the joint process stopped and the confusional syndrome disappeared after 2 days. Joint involvement is the characteristic initial finding of CPDD. Often some patients have systemic involvement and high fever which are sometimes the most evident findings, even more than joint disorder, and they are a cause of fever of unknown origin and of high erythrocyte sedimentation rate in the elderly [3]. Exceptionally, as in the above cited case, confusional syndrome is the main or the most important symptom. In a recent review of 50 patients with pseudogout [4], 25 had some fever and five suffered mental impairment, including disorientation, confusion and visual disorder. These neurological features can interact with the testing of the joint disorder and hinder the diagnosis. Polyarticular sepsis may occur in people with established joint disease. Nevertheless, the short duration of the joint process and the rapid response to the colchicine makes it unlikely. Fever in these patients has been attributed to interleukin-1 produced by monocytes, the latter being stimulated by calcium pyrophosphate crystals [5]. Interleukin-1 also produces disorders of the central nervous system by the production of slow sleep waves and somnolence [6], which could explain the symptoms of our patient. In conclusion it is emphasized that joint involvement in CPDD is not always the main finding, thus hindering the diagnosis. As in the case of the above patient, confusional syndrome may be a presenting feature.
