IDIOPATHIC INFLAMMATORY MYOPATHY: CLINICOPATHOLOGICAL OBSERVATIONS IN THE INDIAN POPULATION
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1 British Journal of Rheumatology ;3:83-83 IDIOPATHIC INFLAMMATORY MYOPATHY: CLINICOPATHOLOGICAL OBSERVATIONS IN THE INDIAN POPULATION BY M. L. PRASAD*t, C. SARKAR*, S. ROY*, U. BAGCHI*, R. R. SINGHf Y. N. SINGHfH, S. SHARMA'U AND A. N. MALAVIYAf * Department of Pathology and tclinical Immunology Section, Department of Medicine, All India Institute of Medical Sciences, New Delhi, India SUMMARY The present study attempts to investigate the pathological basis of the two clinically different forms of idiopathic inflammatory myopathy (IIM) rlamely, polymyositis (PM) and dermatomyositis (DM). Clinicopathological analysis of 3 cases showed that muscle fibre necrosis and regeneration were more frequent in PM than in DM, the latter being significantly so (P<0.0). On the other hand, vasculitis was more often associated with DM while perifascicular atrophy of the muscle fibres was confined to it. Vasculitis was present in eight cases. Its incidence in patients with myositis with systemic connective tissue disease (4/) was significantly more than in other PM and DM patients (P<0.Ql). An equally significant higher frequency of perimysial inflammatory infiltrate was also seen in the former as compared to the latter. Interestingly, idiopathic DM affected men as often as women and juvenile IIM affected boys more frequently than girls. A female predilection was noted in the remaining groups of IIM. These observations indicate that there may be some basic immunopathogenetic differences between polymyositis and dermatomyositis as well as between idiopathic PM/DM and that associated with systemic connective tissue diseases. Though the number of patients studied is small, the absence of female predilection in idiopathic DM and juvenile IIM may be peculiar to the IIM in the tropics. KEY WORDS: Dermatomyositis, Myositis, Polymyositis. IDIOPATHIC inflammatory myopathy is a group of rare diseases with an incidence of / in the western population []. Although no epidemiological studies are available from India, the disease is not uncommon in tertiary referral centres []. Small clusters of cases of myositis have been observed from time to time in several hospitals in the northern and central parts of India [3 ]. Clinical observations on IIM have revealed that the two distinct non-overlapping subsets namely, PM and DM do not show conversion of one into another during the course of disease. While both the variants of IIM may be idiopathic or associated with systemic connective tissue diseases (SCTD), IIM associated with underlying malignancy was always in the form of DM []. Immunological studies support a central role of disordered cellular and humoral immunity in the pathogenesisof IIM [-]. The present study was aimed at finding out histological features if any, distinctive of the different subsets of Submitted 0 June ; revised version accepted January. Correspondence to Dr M. L. Prasad, Assistant Professor, Department of Pathology, G. B. Pant Hospital, New Delhi 0 00, India. ^Present address: Department of Pathology, G. B. Pant Hospital, New Delhi, India. Present address: Department of Immunology, Sanjay Gandhi Post-Graduate Institute of Medical Sciences, Lucknow, India. Present address: Hunter Immunology Unit, Royal Newcastle Hospital, Newcastle, New South Wales, Australia. ^Present address: Department of Pathology, Rush Presbyterian Hospital, Chicago, Illinois. IIM or which may have a bearing on the clinical presentation and course of the disease and to highlight the differences in the clinicopathological characteristics of IIM in the western and the Indian population. METHODS Eighty-six muscle biopsies belonging to as many patients of IIM were identified from through 8 from the histopathology records of the Department of Pathology, All India Institute of Medical Sciences. Muscle biopsies were routinely done in all patients suspected of suffering from myopathy. IIM in these patients was diagnosed using the widely accepted clinical and laboratory criteria of Bohan and Peter [0]. These criteria were: () symmetrical weakness of the proximal muscles of the extremities and trunk; () raised serum levels of muscle enzymes, e.g. creatinine phosphokinase (CPK), aldolase, lactate dehydrogenase and transaminase; (3) electromyographic abnormalities which included short, small polyphasic motor units, insertional irritability with numerous fibrillation potentials and bizarre, high frequency, repetitive discharges; (4) evidence of myositis on muscle biopsy; and () in dermatomyositis, involvement of the skin. Involvement of other muscles such as those of deglutition, mastication, respiration and neck movement, presence of myalgia, arthritis and arthralgia were noted. Serum CPK levels were available in all but two patients. Other muscle related enzymes were also raised in most patients. Antinuclear antibody, anti- DNA antibody and rheumatoid factor tests were done in patients with underlying connective tissue diseases // $08.00/0 83 British Society for Rheumatology
2 83 BRITISH JOURNAL OF RHEUMATOLOGY VOL. XXXI NO. Clinical features Median age (years) Sex ratio (M:F) Symmetrical weakness Dysphagia Joint pain Raised serum CPK levels EMG suggestive of IIM Myositis on muscle biopsy 'Definite' cases F, female; M, male; n, number of patients. *PM and DM. TABLE SALIENT CLINICAL FEATURES IN THE Group I ("=33) 3 : /3 8/30 3 I DIFFERENT GROUPS OF IIM Group II ("=) : 0 8/ /0 0 Group III («=) 3 0: / / Group IV {niy : 0 / / Group V (n=) 30 0: / /8 The presence of four criteria was considered definite and three as probable evidence of IIM. Patients having fewer than three criteria were excluded from the present study as were those with neurological diseases, evidence of infection or parasitic infestation, history of intake of alcohol or drugs causing myositis. Thus, 3 patients were excluded. The remaining 3 patients were classified into: group I, idiopathic PM; group II, idiopathic DM; group III, DM with underlying malignancy; group IV, juvenile PM/DM; and group V, PM/DM associated with SCTD [0]. Group V comprised of four patients of DM and two of PM associated with systemic sclerosis, and three of PM associated with rheumatoid arthritis. Muscle biopsies were obtained under local anaesthesia from the vastus lateralis muscle of the side opposite to that on which EMG was done (if the latter was done prior to the biopsy). Histological features such as presence of inflammatory infiltrate, vasculitis, necrosis, regeneration and atrophy of myofibre were noted and their relative frequency in different categories of PM and DM compared. Vasculitis was diagnosed when the wall of the small blood vessels, especially arterioles and venules, were infiltrated by inflammatory cells which were predominantly lymphocytes with few plasma cells and occasional neutrophils and eosinophils. The infiltrate was moderate to severe and associated with endothelial cell swelling and nuclear prominence. Fibrinoid necrosis of the vessel wall, though characteristic, was not considered essential for diagnosing vasculitis. Neutrophilic infiltration of the capillary wall in the absence of necrosis was not taken as vasculitis as it may be seen in acute inflammations even in the absence of vasculitis. All the patients were treated with corticosteroids and in the non-responsive ones cytotoxic drugs were added, namely methotrexate, cyclophosphamide or occasionally, azathioprine. The follow-up period varied from 3 months to 3 years. Chi-square and Fisher's test were used for the statistical analysis. RESULTS The distribution of patients in different groups is given in Table I. Of the 3 patients included in the present study, 40 had PM and 33 had DM. The proportion of patients with definite DM (/33) was slightly more than those with definite PM (30/40). The salient clinical and investigative features are given in Table I. The widest age range (- years) was seen in the patients of DM who otherwise tended to be younger than those of PM. A female preponderance was noted in all groups except in idiopathic DM and juvenile IIM. IIM associated with connective tissue diseases was seen exclusively in young women between and 3 years of age. Of the DM patients,.% sought medical advice within months of the onset of symptoms as compared to 0% of the PM cases. Symmetrical weakness of the proximal and distal muscles of the limbs was the most frequent complaint followed by dysphagia and joint TABLE II FREQUENCY OF VARIOUS HISTOLOGICAL FEATURES IN THE DIFFERENT GROUPS OF IIM Histological features Group I («=33) Group II ("=) Group III («=) Group IV ( ) Group V ("=) Myofibre necrosis Regeneration Atrophy Perifascicular atrophy Perimysial inflammatory infiltrate Vasculitis ) 4
3 PRASAD ETAL.: IDIOPATHIC INFLAMMATORY MYOPATHY _ 83 A FIG. 3. Photomicrograph showing perifascicular-atrophy in a case of DM (H & E x ). pain. Joint pain with or without polyarthritis was seen most frequently in IIM patients with associated SCTD. Creatinine phosphokinase (CPK) levels in the serum were raised in 88.% (3/) of the cases. In 84.4% (/ 4) of the patients electromyography (EMG) showed changes suggestive of myositis as mentioned earlier. Histopathology showed evidence of myositis in muscle biopsies (Table II). Inflammatory infiltrate consisting predominantly of lymphocytes, few macrophages and plasma cells in the endomysial location accompanied by myofibre necrosis and regeneration was seen in the majority of biopsies (Figs and ). These features tended to be more frequent in PM than in DM, regeneration being significantly so (P<0.0). Perivascular and perimysial inflammation was variably present in all the groups. The latter was more frequently observed in IIM with SCTD than without it (P<0.0). Small and atrophic fibres were generally intermixed with normal fibres, but almost one-fourth of the muscle biopsies in DM showed a perifascicular distribution of the atrophic fibres (Fig. 3). Vasculitis was seen in eight patients (0.%), four of whom had associated SCTD (PM with rheumatoid arthritis, one; PM with systemic sclerosis, one; DM with systemic sclerosis, two). Only one case of juvenile dermatomyositis showed acute necrotizing vasculitis. The remaining seven showed predominantly lymphocytic vasculitis. Endothelial cell swelling and nuclear prominence was seen in all eight cases and in one, it led to occlusion of the vessel lumen. On the whole, vasculitis was present in three cases of PM and five of DM (Fig. 4). The incidence of vasculitis in DM was double (.%) that in PM (.%). It affected women three times more commonly than men. During the course of treatment seven patients died while still in the hospital. Myositis was the apparent cause of death in all except two patients with advanced malignancy. All had DM with an acute onset. Lymphocytic vasculitis of the small vessels was seen in two cases (one each in groups III and V). In addition, the second patient of malignancy had deep vein thrombosis on clinical examination and in another patient leucoclastic vasculitis was detected on skin biopsy. FIG.. Photomicrograph showing necrotic myofibres in a case of DM (H & E x ). FIG. 4. Photomicrograph showing lymphocytic vasculitis () in a case of DM (H & E x ). DISCUSSION Muscle biopsy in DM has been described to have features suggestive of a vasculopathy such as reduction in the capillary density within the muscle, perifascicular atrophy, perimysial and perivascular inflammation and vasculitis [, 3]. In the present series, perifascicular atrophy was confined to the muscle biopsies from DM patients. Vasculitis and perimysial inflammatory FIG.. Photomicrograph showing endomysial inflammatory infiltrate in a case of PM (H & E x ).
4 838 BRITISH JOURNAL OF RHEUMATOLOGY VOL. XXXI NO. infiltrate, too, were more frequently seen in DM than in PM. It is difficult to explain the significantly higher incidence of regenerating fibres in PM as compared to DM. Perhaps the higher frequency of muscle fibre necrosis and endomysial inflammatory infiltrate in the former stimulated a greater regenerating response. On the other hand, the underlying vasculopathy in DM might have curbed myofibre regeneration. PM/DM associated with SCTD and malignancy was seen exclusively in females. Women were also more prone to the development of vasculitis. The possibility of an immune complex mechanism has been suggested by the demonstration of vascular deposition of immunoglobulins, complement and membrane attack complexes more commonly in DM and in overlap syndrome than in PM [4-]. In the present series, the high association of vasculitis in patients of PM/DM with SCTD, all of whom were women, also favours its immunoinflammatory nature. The authors feel that a young woman with PM/DM showing vasculitis in muscle biopsy must be investigated for an associated connective tissue disease. In the present study, IIM associated with SCTD distinguished itself from idiopathic PM/DM by showing a significantly higher frequency of vasculitis and perimysial inflammatory infiltrate in the muscle biopsy (P<0.0). Normal biopsies in IIM are reported in % []. The higher incidence in the present study is possibly because of: () sampling error; () the multifocal nature of the disease; and (3) partial treatment received by some patients before attending the outpatient services of the All India Institute of Medical Sciences, a tertiary referral hospital. The latter may be partly responsible for the normal serum CPK and EMG. Interestingly, the female preponderance seen in IIM in the western population was not so prominent among our patients. In the idiopathic DM and juvenile group the male to female ratio was equal and.: respectively. The mean age of idiopathic PM/DM in our series was almost 0 years less than their western counterpart [,, 8], another fact that remains unexplained. Although the number of cases with underlying malignancy was too small to draw any conclusions, these patients were almost 0 years older than other patients with adult myositis. The frequency of muscle weakness, skin involvement, dysphagia and joint symptoms in the present series compares well with that reported by others [-]. Patients of DM tended to present earlier than those of PM perhaps due to the visible nature of the skin lesions. The mortality in IIM varies from 3.% to 40% [0, 3, 4]. Causes of death in most series have included sepsis, malignancy, cardiac involvement, gastrointestinal perforation, cerebrovascular accidents, etc. In the present series, although no autopsies were done, the acute presentation of the disease among the dead and the involvement of skin in all of them bring to light the more severe nature and course of DM. On muscle biopsy vasculitis was seen in two of the seven patients dying of IIM. In addition, deep vein thrombosis and leucoclastic vasculitis in the skin biopsy was seen in one case each. Thus vasculitis, especially when associated with DM, is likely to have a more severe and non-remitting course []. REFERENCES. Rose AL, Walton JN. Polymyositis: a survey of 8 cases with particular reference to treatment and prognosis. Brain ;8:4-8.. Malaviya AN, Kumar A, Singh RR et al. The spectrum of rheumatic diseases as seen by a tertiary referral center in northern India. SEAPAL Bull 8;:-. 3. Malaviya AN. Profile of collagen vascular diseases in India. In: Ahuja MMS, ed. Progress in clinical medicine. Series 3. New Delhi: Arnold-Heinemann, : Malaviya AN, Ahuja GK, Narayanan et al. Connective tissue diseases in India IV. Clinical and immunological profile in polymyositis and dermatomyositis. J Assoc Phys India 8 ;: Singh RR, Malaviya AN. Dermato-polymyositis: a recent outbreak. J Assoc Phys India 88;3:8-.. Hochberg MC, Feldman D, Stevens MB. Adult onset polymyositis/dermatomyositis: analysis of clinical and laboratory features and survival in patients with a review of the literature. Semin Arthritis Rheum 8;:8-8.. Arahata K, Engel AG. Monoclonal antibody analysis of mononuclear cells in myopathies. V. Ann Neurol 88;: Iyer V, Lawron AR, Fenichel GM. T-cell subsets in polymyositis. Ann Neurol 83;3:4-3.. Plotz PH, Dalakas M, Leff RL, Love LA, Miller FW, Cronin ME. Current concepts in the idiopathic inflammatory myopathies: polymyositis, dermatomyositis and related disorders. Ann Intern Med 8;lll: Bohan A, Peter JB. Polymyositis and dermatomyositis (I). N Engl J Med ;: Banker QB. Dermatomyositis in childhood. / Neuropathol Exp Neurol ;34:4-.. Carpenter S, Karpati G, Rothman S et al. The childhood type of dermatomyositis. Neurology ;: RingelSP, Carry MR, AguileraAJ etal. Quantitative histopathology of the inflammatory myopathies. Arch Neurol 8;43: Kissel JT, Mendell JR, Rammohan KW. Microvascular deposition of complement membrane attack complex in dermatomyositis. A' Engl J Med 8;34: Oxenhandler R, Adelstein EH, Hart MN. Immunopathology of skeletal muscle. Human Pathol ; 8:3-8.. Sufit RL, Barden MT, Ringel SP et al. Antibodies in inflammatory myopathies. Trans Am Neurol Ass 8 ;0:3-8.. TymmsKE, Webb J. Dermatomyositis and other connective tissue diseases: a review of 0 cases. J Rheumatol 8;: Henriksson KG, Sandstedt P. Polymyositis treatment and prognosis: a study of 0 patients. Acta Neurol Scand 8;: BenbassatJ, Gefel D, Larholt K, SukenikS, Morgenstern V, Zlotnick A. Prognostic factors in polymyositis/dermatomyositis: A computer assisted analysis of cases. Arthritis Rheum 8;8: Bohan A, Peter JB, Bowman RL, Pearson CM. A
5 PRASAD ETAL.: IDIOPATHIC INFLAMMATORY MYOPATHY 83 computer assisted analysis of 3 patients with polymyositis and dermatomyositis. Medicine ;: -8.. Hoffman GS, Franck WA, Raddatz DA, Stallones L. Presentation, treatment and prognosis of idiopathic muscle disease in a rural hospital. Am J Med 83;: Holden DJ, Brownell AKW, Fritzler MJ. Clinical and serologic features of patients with polymyositis or dermatomyositis. Can Med Ass J 8;3: DeVere R, Bradley WJ. Polymyositis: its presentation, laboratory features and survival in patients with a review of the literature. Semin Arthritis Rheum 8;: Riddoch D, Morgan-Hughes JA. Prognosis of adult polymyositis. J Neurol Sci ;:-80.. Crowe WE, Bove KE, Levinson JE, Hilton PK. Clinical and pathogenetic implications of histopathology in childhood polydermatomyositis. Arthritis Rheum 8;:-3. What are the long terra follow-up results of silastic metacarpophalangeal and proximal interphalangeal joint replacements? THE principles of lower limb total joint replacement such as hip and knee replacement do not lend themselves to the small joints of the upper limb. Most hand and wrist joints are too small to accommodate metal and cement devices. As the several attempts at adapting this principle to the area of the hand have proved, they have so far all met with failure, although research along these lines continues. Flexible silicone rubber (Silastic) is the mainstay of arthroplasty of the MCP and PIP joints. It is important to realize that the Silastic implant does not become a joint in its own right but helps tofillthe gap left after excisional arthroplasty: the 'joint' is the complex of Silastic plus encapsulating fibrous tissue. The Silastic implant is designed to act merely as a 'spacer' around which fibrous tissue condenses: there is no real long term 'implant' as one understands in the hip, for example. Correct balancing of the soft tissues around the implant is an essential part of this type of surgery as there is little inherent strength in the silicone implant. Soft-tissue imbalance produces excessive torque and eccentric strain during flexion-extension cycling of the joints, leading to premature fatigue failure of the implant, fragmentation and mechanical problems. Thus, in the MCP joint, ulnar drift must be controlled; in the PIP joint, lateral instability as well as swan-neck and boutonniere deformities must be remedied. Small particle granulomata have been reported in a small number of patients, our own experience with more than 3000 silicone implants have so far shown only three instances of this event each of whom have been successfully treated. Silastic replacement of the MCP joints is a 'best buy' for the rheumatoid hand in which the disease process has caused significant joint damage, providing, however correct soft tissue care is undertaken. There are some long-term studies of Silastic implants. Both of the available large studies have a mean follow-up of only two and a half years. Interestingly, CLINICAL CONUNDRUM both studies report that, despite implant fracture, only a quarter of patients with implant fracture experienced any untoward symptoms suggesting that the soft tissue correction alone in many of these patients was the real success factor. Mannerfelt and Andersson [] reported 44 MCP joints with a mean follow-up of. years. Four of the implants were fractured, but this was symptomatic in only one. Beckenbaugh etal. [] from the Mayo Clinic found 3 fractures in 8 Swanson implants. Despite a general reluctance to perform arthroplasty of the PIP joint, Silastic arthroplasty has been a valuable procedure in our patients. Work from this unit has shown that there were few failures in terms of pain relief and hand function [3]. Poor results did occur when swan-neck or boutonniere deformities remained uncorrected. Swanson silicone implant arthroplasty remains the mainstay of replacement surgery of the small joints of the hand. However, great care is necessary in correcting the soft tissue deformity, and we suggest that this type of surgery is best undertaken by surgeons with experience in this area. Increasing awareness of the technical exactness necessary to achieve a good functional result and the importance of correct patient selection is bound to provide satisfaction to the patient, rheumatologist, therapist and to the surgeon. J. K. STANLEY, R. A. EVANS Department of Hand Surgery, Wrightington Hospital, Appley Bridge, Wigan, Lanes REFERENCES. Mannerfelt L, Andersson K. Silastic arthroplasty of the metacarpophalangeal joints in rheumatoid arthritis. J Bone Jt Surg ;-A: Beckenbaugh RD, Dobyns JH, Linscheid RL, Bryan RS. Review and analysis of silicone-rubber metacarpophalangeal implants. J Bone Jt Surg ;8-A: Pena M, Joshi A, Stanley JK. A long term study of Swanson arthroplasty of the proximal interphalangeal joint. / Hand Surg submitted.
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