Idiopathic Inflammatory Myopathies
Ashok Kumar
Ashok Kumar
Definition
The idiopathic inflammatory myopathies (IIM) are
non-suppurative muscle disorders which are characterised by symmetrical,
proximal muscle weakness, decreased muscle endurance and chronic inflammation
in muscle tissue.1
Epidemiology
IIMs are rare disorders (estimated incidence: 5 to
10 per million per year). A bimodal age of onset (10-15 years and 45-60
years) has been reported. Female to male ratio is 2:1 except in inclusion-body
myositis where it is reversed. Prevalence of the disease is the highest
in the Japanese and the lowest in blacks. HLA associations include B8,
DR3 and DRW52
Pathophysiology
The molecular basis of muscle weakness in myositis is not yet known. Even the degree of inflammation observed histopathologically bears no direct relation with the extent of weakness.2,3 The significance of replacement of muscle tissue by fat is also not clear.4 Role of factors other than inflammation is strongly suspected because of abnormalities of energy metabolism as revealed by reduced levels of phosphocreatine (PCr) and adenosine triphosphate (ATP) on magnetic resonance spectroscopy.5-7
The molecular basis of muscle weakness in myositis is not yet known. Even the degree of inflammation observed histopathologically bears no direct relation with the extent of weakness.2,3 The significance of replacement of muscle tissue by fat is also not clear.4 Role of factors other than inflammation is strongly suspected because of abnormalities of energy metabolism as revealed by reduced levels of phosphocreatine (PCr) and adenosine triphosphate (ATP) on magnetic resonance spectroscopy.5-7
Diagnostic criteria
The generally accepted criteria for diagnosis of IIM include:8
1. Proximal muscle weakness
2. Elevated levels of muscle enzymes (CPK, LDH, aldolase, AST, ALT)
3. Myopathic changes demonstrated on electromyography
4. Muscle biopsy evidence of inflammation.
The addition of a skin rash (Criterion 5) allows the diagnosis of dermatomyositis
The generally accepted criteria for diagnosis of IIM include:8
1. Proximal muscle weakness
2. Elevated levels of muscle enzymes (CPK, LDH, aldolase, AST, ALT)
3. Myopathic changes demonstrated on electromyography
4. Muscle biopsy evidence of inflammation.
The addition of a skin rash (Criterion 5) allows the diagnosis of dermatomyositis
Differential Diagnosis
Although classical presentation of dermatomyositis hardly has any differential diagnosis, a long list of conditions needs to be considered in the differential diagnosis of polymyositis. These include drug-induced myopathies, endocrinopathies, paraneoplastic myopathy, pyomyositis, parasitic myositis, muscle dystrophies, metabolic myopathies, myasthenia gravis, Lambert-Eaton syndrome, Guillaine-Barre syndrome, spinal muscular atrophies, amyotrophic lateral sclerosis, etc. Important drugs which are known to cause myopathy include glucocorticoids, d-penicillamine, zidovudine, cholesterol-lowering drugs (clofibrate and statins) and chloroquine.
Although classical presentation of dermatomyositis hardly has any differential diagnosis, a long list of conditions needs to be considered in the differential diagnosis of polymyositis. These include drug-induced myopathies, endocrinopathies, paraneoplastic myopathy, pyomyositis, parasitic myositis, muscle dystrophies, metabolic myopathies, myasthenia gravis, Lambert-Eaton syndrome, Guillaine-Barre syndrome, spinal muscular atrophies, amyotrophic lateral sclerosis, etc. Important drugs which are known to cause myopathy include glucocorticoids, d-penicillamine, zidovudine, cholesterol-lowering drugs (clofibrate and statins) and chloroquine.
Professor of Medicine & Head, Clinical
Immunology and Rheumatology Service, AIIMS, New Delhi - 110 029.
Classification
Table 1 gives the clinical classification currently favoured. Another classification, based on myositis-specific autoantibodies (MSAs) is given in Table 2. MSAs identify relatively homogeneous groups of patients with IIM. The significance of this classification is diminished by the fact that MSAs occur only in about 35% of patients.10
Table 1 gives the clinical classification currently favoured. Another classification, based on myositis-specific autoantibodies (MSAs) is given in Table 2. MSAs identify relatively homogeneous groups of patients with IIM. The significance of this classification is diminished by the fact that MSAs occur only in about 35% of patients.10
Table 1 : Clinical classification
of the idiopathic inflammatory myopathies |
|
| Group I Group II Group III Group IV Group V Group VI |
Idiopathic polymyositis in adults (PM) Idiopathic dermatomyositis in adults (DM)* DM/PM associated with malignancy Childhood associated DM/PM DM/PM associated with CTD Inclusion body myositis (IBM) |
*Also includes amyopathic dermatomyositis’
Clinical Features
Typically, patients present with a recent-onset (a
few weeks to months) difficulty in getting up from chair, climbing stairs,
lifting objects and combing hair. The ocular muscles are never involved.
The facial and distal muscles are spared in the majority. Neck-drop (weakness
of neck-flexors) and dysphagia (weakness of pharyngeal muscles) are frequent
features. Advanced cases may develop weakness of respiratory muscles.
Myalgia and muscle tenderness is quite uncommon. In the author’s
series (76 cases), dermatomyositis was the commonest subset (47%), followed
by CTD-associated group (29%) and idiopathic PM (17%). IBM is exceedingly
rare in India. Juvenile dermatomyositis is not as rare but under-reported
from India.11,12 Table 3 gives a comparative account of demographic and
clinical features. Two Indian series are also included for comparison.13-16
Clinical features of dermatomyositis and polymyositis are compared in
Table 4. Table 5 gives the serological profile of IIMs, including MSAs.14-17
MSA-based subsets have not been identified in Indian population. The data
are grossly inadequate and more work is needed in this area. Significant
HLA associations were found in the author’s series, with DR3 and
B8.
Laboratory Investigations
Despite their limitations, muscle biopsy, electromyography and muscle enzyme levels (particularly, CPK) are useful in establishing the diagnosis of an inflammatory myopathy. In order to assess the response to treatment, one needs to reliably test the activity of disease. For this purpose, numerous clinical instruments have been described but all suffer from drawbacks.18-22 Laboratory plays a supplementary role in discriminating between active and chronic disease. ESR and other acute-phase reactants are not useful in the evaluation of IIM.23 Similarly, limitations of muscle enzymes such as CPK when used alone to measure disease activity are well known.24-26 Serum CPK levels are also influenced by exercise.27 Although muscle histology can provide useful information on the disease activity, the currently used technique of open muscle biopsy can not be recommended for monitoring purposes. In the research setting this problem has been overcome with the use of a conchotome. This semi-open technique can be used with little discomfort to the patient for performing repeated biopsies.28
Despite their limitations, muscle biopsy, electromyography and muscle enzyme levels (particularly, CPK) are useful in establishing the diagnosis of an inflammatory myopathy. In order to assess the response to treatment, one needs to reliably test the activity of disease. For this purpose, numerous clinical instruments have been described but all suffer from drawbacks.18-22 Laboratory plays a supplementary role in discriminating between active and chronic disease. ESR and other acute-phase reactants are not useful in the evaluation of IIM.23 Similarly, limitations of muscle enzymes such as CPK when used alone to measure disease activity are well known.24-26 Serum CPK levels are also influenced by exercise.27 Although muscle histology can provide useful information on the disease activity, the currently used technique of open muscle biopsy can not be recommended for monitoring purposes. In the research setting this problem has been overcome with the use of a conchotome. This semi-open technique can be used with little discomfort to the patient for performing repeated biopsies.28
Magnetic Resonance Imaging
MRI provides a non-invasive but expensive modality of diagnosis and assessment of disease activity. However, it can not replace muscle biopsy for the diagnosis of IIM. In follow-up studies, a strong correlation was observed between increased T2 and STIR signal intensity and disease activity.29-31
MRI provides a non-invasive but expensive modality of diagnosis and assessment of disease activity. However, it can not replace muscle biopsy for the diagnosis of IIM. In follow-up studies, a strong correlation was observed between increased T2 and STIR signal intensity and disease activity.29-31
Magnetic Resonance Spectroscopy (MRS) And
Ultrasound
Phosphorus MRS, assesses muscle bioenergetic metabolites such as phosphocreatine (PCr) and ATP. In active dermatomyositis, levels of these metabolites are reduced, while the ratio of inorganic phosphate (Pi) to PCr (Pi/PCr) is increased relative to controls. Exercise accentuates these abnormalities further.31,32 MRS abnormalities underscore the significance of metabolic disturbances in the pathogenesis of the muscle weakness and point to the need for therapies other than immunosuppressants. Muscle bioenergetic defects have been shown to precede other changes and even persist after resolution of inflammation.32,34 Proton MRS determines lipid-to-water ratio in the muscle. In the active stage of dermatomyositis, the ratio was found abnormally low and it rose markedly at 3 months of treatment.35 Urinary proton MRS metabolic profiles may also have the potential to be a non-invasive method for assessment of disease activity in IIM patients. Ultrasound does not seem to be helpful because muscle echogenicity bears no correlation with muscle strength.
Phosphorus MRS, assesses muscle bioenergetic metabolites such as phosphocreatine (PCr) and ATP. In active dermatomyositis, levels of these metabolites are reduced, while the ratio of inorganic phosphate (Pi) to PCr (Pi/PCr) is increased relative to controls. Exercise accentuates these abnormalities further.31,32 MRS abnormalities underscore the significance of metabolic disturbances in the pathogenesis of the muscle weakness and point to the need for therapies other than immunosuppressants. Muscle bioenergetic defects have been shown to precede other changes and even persist after resolution of inflammation.32,34 Proton MRS determines lipid-to-water ratio in the muscle. In the active stage of dermatomyositis, the ratio was found abnormally low and it rose markedly at 3 months of treatment.35 Urinary proton MRS metabolic profiles may also have the potential to be a non-invasive method for assessment of disease activity in IIM patients. Ultrasound does not seem to be helpful because muscle echogenicity bears no correlation with muscle strength.
Management
Corticosteroids are the mainstay of treatment of this disease even though their use is not based on rigorous scientific evidence. A starting dose of prednisone of 0.75 mg/kg/day (which corresponds to 40-60 mg/day) is recommended.36 There are no data to show that higher doses are associated with superior outcome. Tapering could be started when a normal or close to normal muscle function has been achieved (usually, after 4-12 weeks), irrespective of
Corticosteroids are the mainstay of treatment of this disease even though their use is not based on rigorous scientific evidence. A starting dose of prednisone of 0.75 mg/kg/day (which corresponds to 40-60 mg/day) is recommended.36 There are no data to show that higher doses are associated with superior outcome. Tapering could be started when a normal or close to normal muscle function has been achieved (usually, after 4-12 weeks), irrespective of
CPK levels. Tapering of corticosteroids should be
begun at the rate of 10 mg reduction/month, initially. When a dose of
20 mg/day is reached, the reduction should be more gradual. Maintenance
dosage of 5-15 mg/day is often required for several years. An attempt
to withdraw should be made after 2-3 years.37 Significant clinical improvement
is noted in 60-80% of the patients.38-40
There are two situations in which other immunosuppressives
are required: steroid-resistant cases (about 30%) and steroid-responsive
patients who develop major adverse effects.41 In both situations azathioprine
(2.5 mg/kg/day) has been found to be useful.42 A combination of oral methotrexate
with azathioprine may prove beneficial in refractory cases.43 IVIG was
found beneficial in treatment-resistant dermatomyositis patients but its
role in polymyositis remains controversial.44 Plasmapheresis had no positive
effect compared to corticosteroids alone in a controlled trial.45 Open
studies and case reports indicate a beneficial effect of methotrexate
(7.5 -25 mg/week administered orally, i.m., or up to 100 mg/week i.v.)
in steroid-resistant cases.45,47 The effect of cyclophosphamide in IIM
is more controversial. There are scant data on the beneficial effects
of cyclosporin A in adults with refractory IIM. The effect is often seen
within a few weeks of treatment. In IBM, it is still controversial whether
immunosuppressive drugs have a beneficial effect. Some authorities advocate
a combination of steroids and other immunosuppressants from the start
of therapy.36,48
Physical Exercise And Rehabilitation
For a long time, there have been few advocates of
physical exercise in the management of IIMs because of fear of causing
disease flare-ups. Recent studies however, have demonstrated the safety
and usefulness of active exercise in stable IIM.49,50 Active physical
exercises such as mild aerobic programme on a bicycle or in the pool can
be introduced when disease activity begins to subside.51
Prognosis
The IIM are serious disorders with as many as two-thirds of patients developing residual functional impairment in the long-term.52,53
The IIM are serious disorders with as many as two-thirds of patients developing residual functional impairment in the long-term.52,53
Conclusions
IIMs are a challenging group of muscle disorders both from the pathogenetic and therapeutic standpoint. Recent work from NIH, USA has shed some light on their immunopathogenesis. A new classification based on myositis-specific autoantibodies has been proposed which represents a substantial advance in this area. However, MSAs are found only in 35-40% of patients. Thus, large lacunae remain in our current understanding of these disorders. The use of MRS to assess metabolic abnormalities may throw some light in this regard and also serve as a means of disease activity assessment. On the therapeutic front, there is paucity of hard scientific evidence with regard to the best treatment. Considering the high frequency of sequelae of disease and substantial mortality, some authorities have recommended combinations of steroids and immunosuppressive drugs from the start. Active physical exercises have an important role in the management of IIM once the activity of disease is brought under reasonable control. The present treatment protocols for IIM are based on experience gained from uncontrolled clinical trials. Many patients suffer from serious side effects of steroid therapy. There is an urgent need for developing a validated disease activity measure and performing controlled trials to develop better treatment strategies. There is also a need to develop molecular approaches to the treatment of IIM similar to those developed for rheumatoid arthritis. Another important area, which needs to be explored, is the possible metabolic disturbance in IIM as a cause of the persisting muscle weakness
IIMs are a challenging group of muscle disorders both from the pathogenetic and therapeutic standpoint. Recent work from NIH, USA has shed some light on their immunopathogenesis. A new classification based on myositis-specific autoantibodies has been proposed which represents a substantial advance in this area. However, MSAs are found only in 35-40% of patients. Thus, large lacunae remain in our current understanding of these disorders. The use of MRS to assess metabolic abnormalities may throw some light in this regard and also serve as a means of disease activity assessment. On the therapeutic front, there is paucity of hard scientific evidence with regard to the best treatment. Considering the high frequency of sequelae of disease and substantial mortality, some authorities have recommended combinations of steroids and immunosuppressive drugs from the start. Active physical exercises have an important role in the management of IIM once the activity of disease is brought under reasonable control. The present treatment protocols for IIM are based on experience gained from uncontrolled clinical trials. Many patients suffer from serious side effects of steroid therapy. There is an urgent need for developing a validated disease activity measure and performing controlled trials to develop better treatment strategies. There is also a need to develop molecular approaches to the treatment of IIM similar to those developed for rheumatoid arthritis. Another important area, which needs to be explored, is the possible metabolic disturbance in IIM as a cause of the persisting muscle weakness
References
1. Dalakas MC. Polymyositis. dermatomyositis, and inclusion-body myositis. N Engl J Med 1991;325:1487-98.
2. Bunch TW. Worthington JW. Combs JJ. IIstrup DM. Engel AG. Azathioprine with prednisone for polymyositis. Ann Intern Med 1980:92:365-9.
3. Kroll M, Otis J, Kagen L. Serum enzyme myoglobin and muscle strength relationships in polymyositis and dermatomyositis. J Rheumatol 1986:13:349-55.
4. Lundberg I, Kartz A-K, Nennesmo I, Andersson U, Klareskog L. Effects of corticosteroid treatment on IL-1 and ILß expression in muscle tissue in patients with inflammatory myopathies. Arthritis Rheum 1997;40S180.
5. Newman ED, Kurland RJ. P-31 magnetic resonance spectroscopy in polymyositis and dermatomyositis. Arthritis Rheum 1992;35:199-203.
6. Park JH, Vital TL, Ryder NM, Hernanz-Schulman M, Partain CL. Price RR, et al. Magnetic resonance imaging and P-31 magnetic resonance spectroscopy provide unique quantitative data useful in the longitudinal
management of patients with dermatomyositis. Arthritis Rheum 1994;37:736-46.
7. Chung YL, Smith EC, Williams SCR, et al. In vivo proton magnetic resonance spectroscopy in polymyositis and dermatomyositis: A preliminary study. Eur J Med Res 1997:2:483-7.
8. Bohan A, Peter JB, Polymyositis and dermatomyositis: First of two parts. N Engl J Med 1975;292:344-47.
9. Wortmann RL. Inflammatory diseases of the muscle and other myopathies. In : Kelley WN. Harris ED Jr. Ruddy S. Sledgc CB (Eds): Textbook of Rheumatology. 5th Edition. Philadelphia. WB Saunders 1996.
10. Targoff IN. Immune manifestations of inflammatory muscle disease. Rheum Dis Clin North Am 1994;20:857-80.
11. Seth V, Kabra SK, Semwal OP, Jain Y. Juvenile dermatomyositis. Indian J Pediatr 1996;63:375-9.
12. Singh S, Kumar L, Shankar KR. Juvenile dermatomyositis in north India.Indian Pediatr 1997;34:193-8.
13. Prasad ML, Sarkar C, Roy S, et al. Idiopathic inflammatory myopathy: clinico-pathological observations in the Indian population. Brit J Rheumatol 1992;31:835-39.
14. Chowdhary V, Aggarwal A, Misra R. Prevalence and clinical association of myositis-specific autoantibodies in North Indian patients with idiopathic inflammatory myopathy. APLAR J Rheumatol 2001.
15. Love LA. LefTRL, Frascr DD, et al. A new approach to classification of idiopathic inflammation myopathies: Myositis-specific autoantibodies define useful homogeneous patients groups. Medicine (Baltimore) 1991;70:360-74.
16. Hausmanowa-Petrusewicz I, Kowalska-Oledzka E, Miller FW, et al Clinical, serologic and immunogenetic features in Polish patients with idiopathic inflammatory myopathies. Arthritis Rheum 1997;40:1257-66.
17. Brouwer R, Hengstman GJ, Vree Egberts W, et al. Autoantibody profiles in the sera of European patients with myositis. Ann Rheum Dis 2001;60:116-23.
18. Daniels L, Worthingham C. Muscle testing. 4th edn. Philadelphia: WB Saunders. 1972. Helewa A. Goldsmith CH. Smythe HA. The modified sphygmomanometer—An instrument to measure muscle strength: A validation study. J Chron Dis 1981;34:353-61.
19. Stroll T, Brühlmann P, Stucki G, Seifert B, Michel BA. Muscle strength assessment in polymyositis and dermatomyositis: evaluation of the reliability and clinical use of a new, quantitative, easily applicable method. J
Rheumatol 1995;22:473-7.
20. Csuka M. McCarty DJ. Simple method for measurement of lower extremity muscle strength. Am J Med 1985;78:77-81.
21. Josefson A, Romanus E, Carlsson J. A functional index in myositis. J Rheumatol 1996;23:1380-4.
22. Barwick DD, Walton JN. Polymyositis Am J Med 1963;35:646-60.
23. Fudman EJ, Schnitzer TJ. Dermatomyositis without creatine kinase elevation. Am J Med 1986;80:329-32.
24. Adams EM. Plotz PH. The treatment of myositis. Rheum Dis Clin North Am 1995;21:179-97.
25. Rose AL, Walton JN, Polymyositis: A survey of 89 cases with particular reference to treatment and prognosis. Brain 1966;89:747-68.
26. Bohan A, Peter JB, Bowman RL, Pearson CM. A computer-assisted analysis of 153 patients with polymyositis and dermatomyositis. Medicine 1977;86:255-86.
27. Noakes TD. Effect of exercise in serum enzymes activities in humans. Sports Med 1987;4:245-67.
28. Lundberg IE, Dorph C, Nennesmol. Percutaneous conchotome technique—A valuable and safe procedure for muscle biopsies. Arthritis Rheum 1998;1024:S203.
29. Fraser DD, Frank JA, Dalakas Miller FW, Ricks JE, Plotz P. Magnetic resonance imaging in the idiopathic inflammatory myopathies. J Rheumatol 1991;18:1693-700.
30. Reimers CD, Schedel H, Fleckenstein JL, et al. Magnetic resonance imaging of skeletal muscles in idiopathic inflammatory myopathies of adults. J Neurol 1994;241:306-14.
31. Kaufman LD, Gruber BL, Gerstman DP, Kaell AT. Preliminary observation on the role of magnetic resonance imaging for polymyositis and dermatomyositis. Ann Rheumatol Dis 1987;46:569-72.
32. Park JH, Vital TL, Ryder NM, Hernanz-Schulman M, Partain CL. Price RR, et al. Magnetic resonance imaging and P-
31 magnetic resonance spectroscopy provide unique quantitative data useful in the longitudinal
management of patients with dermatomyositis. Arthritis Rheum 1994;37:736-46.
33. Kaufman LD, Gruber BL, Gerstman DP, Kaell AT. Preliminary observation on the role of magnetic resonance imaging for polymyositis and dermatomyositis. Ann Rheumatol Dis 1987;46:569-72.
34. Kari S, Olsen NJ, Park JH. Evaluation of muscle diseases using artificial neural network analysis of 31P MR spectroscopy data. Magn Reson Med 1995;34:664-72.
35. Chung YL. Wassif WS. Bell D, et al. Urinary assessment of disease activity in polymyositis by in vitro NMR Proceedings of the International Society for Magnetic Resonance in Medicine 1996;2:1091.
36. Lundberg I, Chung YL. Treatment and investigation of idiopathic inflammatory myopathies. Rheumatology 2000;39:7-17.
37. Rose AL, Walton JN. Polymyositis: A survey of 89 cases with particular reference to treatment and prognosis. Brain 1966;89:747-68.
38. Vignos PJ, Bowling GF, Watkins MP. Polymyositis Arch Intern Med 1964;114:263-77.
39. Bohan A, Peter JB, Bowman RL, Pearson CM. A computer-assisted analysis of 153 patients with polymyositis and dermatomyositis. Medicine 1977;86:255-86.
40. Henriksson KG, Lindvall B. Polymyositis and dermatomyositis 1990—diagnosis, treatment and prognosis. Prog Neurobiol 1990;35:181-93.
41. Henriksson KG, Sandstedt P. Polymyositis—treatment and prognosis. Acta Ncurol Scand 1982;65:280-300.
42. Bunch TW. Prednisone and azathioprine for polymyositis. Arthritis Rheum 1981:24:45-8.
43. Villalba L, Hicks JE, Adams EM et al. Treatment of refractory myositis. Arthritis Rheum 1998:41:392-9.
44. Dalakas MC, Illa I, Dambrosia JM et al. A controlled trial of high-dose intravenous immune globulin infusions as treatment for dermatomyositis. N Engl J Med 1993;329:1993-2000.
45. Miller FW, Leitman SF, Cronia ME. Controlled trial of plasma exchange and leucapheresis in polymyositis and dermatomyositis. N Engl J Med 1992;326:1380-4.
46. Malaviya AN, Many R, Schunong RS. Treatment of dermatomyositis with methotrexate. Lancet 1968;2:485-8.
47. Metzgcr AL, Bohan A, Goldberg LS, Bluestonc R, Pearson CM. Polymyositis and dermatomyositis: Combined methotrexate and corticosteroid therapy. Ann Intern Med 1974;81:182-9.
48. Adams EM, Plotz PH. The treatment of myositis. Rheum Dis Clin North Am 1995;21:179-97.
49. Alexanderson H, Stenstrom C, Lundberg I. Safety of a home exercise programme in patients with polymyositis and dermatomyositis: a pilot study. Rheumatology 1999;38:608-11.
50. Wiesinger GF, Quittan M, Aringer M, et al. Improvement of physical fitness and muscle strength in polymyositis/dermatomyositis patients by a training programme. Br J Rheumatol 1998;37:196-200.
51. Hicks JE. Role of rehabilitation in the management of myopathies. Curr Opin Rheumatol 1998;10:548-55.
52. Henriksson KG, Sandstedt P. Polymyositis—treatment and prognosis. Acta Neurol Scand 1982;65:280-300.
53. Thymms KE, Webb J. Dermatomyositis and other connective tissue diseases. A review of 105 cases. J Rheumatol 1985;12:1140-8.
1. Dalakas MC. Polymyositis. dermatomyositis, and inclusion-body myositis. N Engl J Med 1991;325:1487-98.
2. Bunch TW. Worthington JW. Combs JJ. IIstrup DM. Engel AG. Azathioprine with prednisone for polymyositis. Ann Intern Med 1980:92:365-9.
3. Kroll M, Otis J, Kagen L. Serum enzyme myoglobin and muscle strength relationships in polymyositis and dermatomyositis. J Rheumatol 1986:13:349-55.
4. Lundberg I, Kartz A-K, Nennesmo I, Andersson U, Klareskog L. Effects of corticosteroid treatment on IL-1 and ILß expression in muscle tissue in patients with inflammatory myopathies. Arthritis Rheum 1997;40S180.
5. Newman ED, Kurland RJ. P-31 magnetic resonance spectroscopy in polymyositis and dermatomyositis. Arthritis Rheum 1992;35:199-203.
6. Park JH, Vital TL, Ryder NM, Hernanz-Schulman M, Partain CL. Price RR, et al. Magnetic resonance imaging and P-31 magnetic resonance spectroscopy provide unique quantitative data useful in the longitudinal
management of patients with dermatomyositis. Arthritis Rheum 1994;37:736-46.
7. Chung YL, Smith EC, Williams SCR, et al. In vivo proton magnetic resonance spectroscopy in polymyositis and dermatomyositis: A preliminary study. Eur J Med Res 1997:2:483-7.
8. Bohan A, Peter JB, Polymyositis and dermatomyositis: First of two parts. N Engl J Med 1975;292:344-47.
9. Wortmann RL. Inflammatory diseases of the muscle and other myopathies. In : Kelley WN. Harris ED Jr. Ruddy S. Sledgc CB (Eds): Textbook of Rheumatology. 5th Edition. Philadelphia. WB Saunders 1996.
10. Targoff IN. Immune manifestations of inflammatory muscle disease. Rheum Dis Clin North Am 1994;20:857-80.
11. Seth V, Kabra SK, Semwal OP, Jain Y. Juvenile dermatomyositis. Indian J Pediatr 1996;63:375-9.
12. Singh S, Kumar L, Shankar KR. Juvenile dermatomyositis in north India.Indian Pediatr 1997;34:193-8.
13. Prasad ML, Sarkar C, Roy S, et al. Idiopathic inflammatory myopathy: clinico-pathological observations in the Indian population. Brit J Rheumatol 1992;31:835-39.
14. Chowdhary V, Aggarwal A, Misra R. Prevalence and clinical association of myositis-specific autoantibodies in North Indian patients with idiopathic inflammatory myopathy. APLAR J Rheumatol 2001.
15. Love LA. LefTRL, Frascr DD, et al. A new approach to classification of idiopathic inflammation myopathies: Myositis-specific autoantibodies define useful homogeneous patients groups. Medicine (Baltimore) 1991;70:360-74.
16. Hausmanowa-Petrusewicz I, Kowalska-Oledzka E, Miller FW, et al Clinical, serologic and immunogenetic features in Polish patients with idiopathic inflammatory myopathies. Arthritis Rheum 1997;40:1257-66.
17. Brouwer R, Hengstman GJ, Vree Egberts W, et al. Autoantibody profiles in the sera of European patients with myositis. Ann Rheum Dis 2001;60:116-23.
18. Daniels L, Worthingham C. Muscle testing. 4th edn. Philadelphia: WB Saunders. 1972. Helewa A. Goldsmith CH. Smythe HA. The modified sphygmomanometer—An instrument to measure muscle strength: A validation study. J Chron Dis 1981;34:353-61.
19. Stroll T, Brühlmann P, Stucki G, Seifert B, Michel BA. Muscle strength assessment in polymyositis and dermatomyositis: evaluation of the reliability and clinical use of a new, quantitative, easily applicable method. J
Rheumatol 1995;22:473-7.
20. Csuka M. McCarty DJ. Simple method for measurement of lower extremity muscle strength. Am J Med 1985;78:77-81.
21. Josefson A, Romanus E, Carlsson J. A functional index in myositis. J Rheumatol 1996;23:1380-4.
22. Barwick DD, Walton JN. Polymyositis Am J Med 1963;35:646-60.
23. Fudman EJ, Schnitzer TJ. Dermatomyositis without creatine kinase elevation. Am J Med 1986;80:329-32.
24. Adams EM. Plotz PH. The treatment of myositis. Rheum Dis Clin North Am 1995;21:179-97.
25. Rose AL, Walton JN, Polymyositis: A survey of 89 cases with particular reference to treatment and prognosis. Brain 1966;89:747-68.
26. Bohan A, Peter JB, Bowman RL, Pearson CM. A computer-assisted analysis of 153 patients with polymyositis and dermatomyositis. Medicine 1977;86:255-86.
27. Noakes TD. Effect of exercise in serum enzymes activities in humans. Sports Med 1987;4:245-67.
28. Lundberg IE, Dorph C, Nennesmol. Percutaneous conchotome technique—A valuable and safe procedure for muscle biopsies. Arthritis Rheum 1998;1024:S203.
29. Fraser DD, Frank JA, Dalakas Miller FW, Ricks JE, Plotz P. Magnetic resonance imaging in the idiopathic inflammatory myopathies. J Rheumatol 1991;18:1693-700.
30. Reimers CD, Schedel H, Fleckenstein JL, et al. Magnetic resonance imaging of skeletal muscles in idiopathic inflammatory myopathies of adults. J Neurol 1994;241:306-14.
31. Kaufman LD, Gruber BL, Gerstman DP, Kaell AT. Preliminary observation on the role of magnetic resonance imaging for polymyositis and dermatomyositis. Ann Rheumatol Dis 1987;46:569-72.
32. Park JH, Vital TL, Ryder NM, Hernanz-Schulman M, Partain CL. Price RR, et al. Magnetic resonance imaging and P-
31 magnetic resonance spectroscopy provide unique quantitative data useful in the longitudinal
management of patients with dermatomyositis. Arthritis Rheum 1994;37:736-46.
33. Kaufman LD, Gruber BL, Gerstman DP, Kaell AT. Preliminary observation on the role of magnetic resonance imaging for polymyositis and dermatomyositis. Ann Rheumatol Dis 1987;46:569-72.
34. Kari S, Olsen NJ, Park JH. Evaluation of muscle diseases using artificial neural network analysis of 31P MR spectroscopy data. Magn Reson Med 1995;34:664-72.
35. Chung YL. Wassif WS. Bell D, et al. Urinary assessment of disease activity in polymyositis by in vitro NMR Proceedings of the International Society for Magnetic Resonance in Medicine 1996;2:1091.
36. Lundberg I, Chung YL. Treatment and investigation of idiopathic inflammatory myopathies. Rheumatology 2000;39:7-17.
37. Rose AL, Walton JN. Polymyositis: A survey of 89 cases with particular reference to treatment and prognosis. Brain 1966;89:747-68.
38. Vignos PJ, Bowling GF, Watkins MP. Polymyositis Arch Intern Med 1964;114:263-77.
39. Bohan A, Peter JB, Bowman RL, Pearson CM. A computer-assisted analysis of 153 patients with polymyositis and dermatomyositis. Medicine 1977;86:255-86.
40. Henriksson KG, Lindvall B. Polymyositis and dermatomyositis 1990—diagnosis, treatment and prognosis. Prog Neurobiol 1990;35:181-93.
41. Henriksson KG, Sandstedt P. Polymyositis—treatment and prognosis. Acta Ncurol Scand 1982;65:280-300.
42. Bunch TW. Prednisone and azathioprine for polymyositis. Arthritis Rheum 1981:24:45-8.
43. Villalba L, Hicks JE, Adams EM et al. Treatment of refractory myositis. Arthritis Rheum 1998:41:392-9.
44. Dalakas MC, Illa I, Dambrosia JM et al. A controlled trial of high-dose intravenous immune globulin infusions as treatment for dermatomyositis. N Engl J Med 1993;329:1993-2000.
45. Miller FW, Leitman SF, Cronia ME. Controlled trial of plasma exchange and leucapheresis in polymyositis and dermatomyositis. N Engl J Med 1992;326:1380-4.
46. Malaviya AN, Many R, Schunong RS. Treatment of dermatomyositis with methotrexate. Lancet 1968;2:485-8.
47. Metzgcr AL, Bohan A, Goldberg LS, Bluestonc R, Pearson CM. Polymyositis and dermatomyositis: Combined methotrexate and corticosteroid therapy. Ann Intern Med 1974;81:182-9.
48. Adams EM, Plotz PH. The treatment of myositis. Rheum Dis Clin North Am 1995;21:179-97.
49. Alexanderson H, Stenstrom C, Lundberg I. Safety of a home exercise programme in patients with polymyositis and dermatomyositis: a pilot study. Rheumatology 1999;38:608-11.
50. Wiesinger GF, Quittan M, Aringer M, et al. Improvement of physical fitness and muscle strength in polymyositis/dermatomyositis patients by a training programme. Br J Rheumatol 1998;37:196-200.
51. Hicks JE. Role of rehabilitation in the management of myopathies. Curr Opin Rheumatol 1998;10:548-55.
52. Henriksson KG, Sandstedt P. Polymyositis—treatment and prognosis. Acta Neurol Scand 1982;65:280-300.
53. Thymms KE, Webb J. Dermatomyositis and other connective tissue diseases. A review of 105 cases. J Rheumatol 1985;12:1140-8.