Case report Polymyositis in Chagas's disease · Polymyositis in Chagas'sdisease 279 Fig. 5 IgMsegmentaldeposition in vascular wall (fluorescence micropsy. x 400). Onemonthafter admission

Annals ofthe Rheumatic Diseases, 1978, 37, 277-280

Case report

Polymyositis in Chagas's diseaseW. COSSERMELLI, H. FRIEDMAN, E. H. PASTOR, M. R. NOBRE,A. MANZIONE, M. E. CAMARGO, AND M. SHIROMAFrom the Rheumatology Research Unit and Department of Pathology, Faculty of Medicine, University ofSao Paulo, Brazil

suMMARY Polymyositis marked the clinical onset of Chagas's disease in a patient with rheumatoidarthritis. This is unusual, although clinically unimportant muscle involvement in trypanosomiasishas been described. The plasma cell infiltrate and vascular deposition of IgM and C3 suggest thatthe humoral immune system may play a role in the pathogenesis of chagasic polymyositis. It is notknown whether the rheumatoid diseases predisposed to the polymyositis.

There are few reports of myositis in Chagas'sdisease, although this is commonly seen in experi-mental models (Wolf et al., 1952; Andrade andAndrade, 1968). Myositis associated with thepresence of parasites was demonstrated by Ponce(1972) in sequential biopsies of the gastrocnemiusmuscle in patients with chronic and acute Chagas'sdisease and cardiopathy. Cenget and Rojas (1959)observed deltoid myositis in 96-3% of 27 chagasicpatients, but did not mention parasites in the musclelesions.

Cossio et al. (1974a, b) described a circulatingautoantibody that reacts against endocardium, aswell as vessels and interstitium of skeletal muscleand myocardium and interacts with complement(EVI antibody). It was found in 95% of patients withChagas's heart disease and in 45% of asymptomaticindividuals infected with Trypanosoma cruzi. In theearly stage of acute heart disease EVI antibody is ofIgM class but one month later both IgM and IgGantibodies are found. We report a patient withdefinite rheumatoid arthritis who developed chagasicpolymyositis.

Case report

A 43-year-old white female had suffered fromrheumathoid arthritis from age 17 years. Early inthe course of the disease she received gold salts withremarkable improvement. After a 15-year periodwithout symptoms, she then started to complain of

Accepted for publication September 5, 1977Correspondence to Dr W. Cossermelli, Faculdade deMedicina, Universidade de Sao Paulo, SP 2921, Sao Paulo-SP Brazil.

joint pain in both hands, shoulders, and knees, withmorning stiffness and fever of 38°C. Nonsteroidalanti-inflammatory drugs provided some relief. Atthis time she had her tonsils removed. Postoperativelyshe received 500 ml of fresh blood. 10 days aftersurgery her joint pains increased and were accom-panied by muscle weakness and pain in the shoulders,thighs, and legs, fever of 40°C ,and tachycardia. Shewas wholly incapacitated by the muscle weakness.Raised values of transaminases and LDH isoenzymesand positive antinuclear factor were recorded. Pred-nisone 80 mg bd was started, but 20 days later shewas no better and was admitted to the Hospital dasClinicas da Universidade de Sao Paulo.Her general condition was fair, blood pressure

110/70 mmHg, pulse rate 100/min, respiratory rate30/min, and temperature 38°C. No cardiac murmursor changes in heart sounds or rhythm disturbanceswere found. The lungs were normal on examination.The spleen was not palpable, but the liver wasenlarged about 3 cm. There was pain on joint move-ment in both hands, shoulders, knees, and ankles.The left ankle was swollen without limited movement.Muscle weakness in a symmetrical, proximaldistribution was the prominent feature, and theaffected muscles were tender to pressure. Tendonreflexes were well preserved.The erythrocyte sedimentation rate was 49 mm/h,

RA latex fixation test 1:80, negative LE-cell test,antinuclear antibodies (ANA) positive at a 1:5000dilution (rat liver preparation), total haemolyticcomplement 15 U (normal: 166-333), C3 0-6 g/l(normal 0 8-1 * 2 g/l). Total protein measured 102 g/l,gammaglobulin 44 g/l. Serum muscle enzymes weremarkedly raised: creatine phosphokinase (CPK)

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278 Cossermelli, Friedman, Pastor, Nobre, Manzione, Camargo, Shiroma

176 IU/I (normal 0-50 IU/I), latic dehydrogenase(LDH) 746 IU/I (normal 80-240 IU/I), and SGOT207 Frankel U/ml (normal 8-40 U/ml). Electro-myography suggested primary myopathy withsome signs of denervation. X-ray showed erosionsand joint-space loss in metacarpophalangeal andproximal interphalangeal joints in both hands.The diagnosis of American trypanosomiasis was

suggested by specific serological reactions and con-firmed by the histopathological findings. The formerincluded the complement fixation test, positive at1:64; the immunofluorescent indirect reaction forT. cruzi showed IgM and IgG antibodies at 1:160and 1:320 respectively, and haemagglutination testwith red cells coated with protein and polysac-charide extracts of T. cruzi were both positive at1:320.Rectal biopsy showed leishmania parasites within

smooth muscle fibres and ganglion cells (Fig. 1).Two skeletal muscle biopsies were performed, onebefore and one after the introduction of specifictherapy for acute Chagas's disease. Both showedmyositis with hyalin focal necrosis in muscle fibres(Figs. 2, 3), but parasites were found only in theformer. Lymphocytes, plasma cells, and macro-phages were present, predominantly arranged inlarge perivascular collections (Fig. 4).

In the chagasic muscle, direct immunofluorescentreactions showed granular deposits of IgM and C3in the walls of small arteries (Fig. 5), while thereaction for IgG had a linear sarcolemmal pattern.IgA and fibrinogen were not found. In the normalcontrol muscle all reactions were negative, includingthe indirect immunofluorescent reaction for EVIantibody, using the patient's serum.

40

- .1, /Fig. 1 Rectal biopsy showing a pseudocyst ofleishmanias within a smooth muscle fibre of muscularismucosae. Haematoxylin and eosin. x 230.

Fig. 2 Segmental necrosis of skeletal muscle fibre.Haematoxylin and eosin. x 275.

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Fig. 3 Diffuse infiltrate ofplasma cells in musclebiopsy. Note incipient and segmental hyalindegeneration offibre. Haematoxylin and eosin. x 260.

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Fig. 4 Muscle biopsy showing perivascular collectionof mononuclear inflammatory cells. Haematoxylin andeosin. x 260.

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Polymyositis in Chagas's disease 279

Fig. 5 IgM segmental deposition in vascular wall(fluorescence micropsy. x 400).

One month after admission she developed cardiacfailure which was difficult to control. She was dis-charged during specific therapy for acute Chagas'sdisease, without corticosteroids. Her general con-dition and the muscle weakness were moderatelyimproved.

Discussion

The earlier diagnosis of rheumatoid arthritis wasaccepted when the patient was admitted to thishospital, despite her symptomatology and thelaboratory findings at admission. At this stage it wasthought that she was starting to develop an overlapsyndrome ofconnective tissue disease with prominentfeatures of polymyositis, besides her underlyingrheumatoid arthritis. The typical clinical features ofpolymyositis were confirmed by the raised serumLDH, CPK, and SGOT and by the characteristicfindings in the electromyography.

It is difficult to explain the presence of antinuclearantibody in such high titres since this is uncommonin disease other than systemic lupus erythematosus.However, she had no other evidence to supportthis diagnosis. 'Corticosteroid myopathy' wasruled out since we observed clinical impairmentand further rises in serum enzyme concentrationsafter corticosteroids were withdrawn. Further-more, the myopathy induced by corticosteroidsis not inflammatory, but is an atrophic process(Adams, 1975).

The clinical and laboratory evidence of poly-myositis was out ofproportion to that which has beenrecorded as occasionally accompanying rheumatoidarthritis. The finding of parasites in the musclelesions suggests a chagasic aetiology for the poly-myositis. The parasite presumably gained access tothe body through the blood transfused one monthbefore. No other mode of transmission can beinvoked since she had not been in an endemic zonefor several years. These data, together with theresults of the haemagglutination and immuno-fluorescent reactions, strongly suggest acute Chagas'sdisease and rule out the possibility of a chronicsubclinical form of Chagas's disease reactivated bythe corticosteroid therapy.

In the acute stage of Chagas's disease, the clinicalpicture is generally unimpressive but there may begeneral and cardiac manifestations. Polymyositis hasnot been reported as a clinical manifestation of anystage of Chagas's disease although histopathologicalstudies of skeletal muscle have often shown conspic-uous myositis (Cenget and Rojas, 1959; Ponce, 1972).It seems likely that minor degrees of clinical skeletalmuscle involvement may pass unnoticed in thepresence of more dramatic cardiac or other features.The occurrence of synovitis in association with

dermatomyositis and the presence of myositisin rheumatoid arthritis raises the possibilitythat the skeletal muscles in a patient withrheumatoid arthritis may be more vulnerable todamage from other causes. As far as the pathogenesisof polymyositis is concerned, there is evidence thatcell-mediated reaction to skeletal muscle and con-comitant humoral immunodeficiency are involved(Dawkins, 1975). The vascular deposition of IgMand C3 seen in this case suggest that humoral immunefactors may have played a pathological role here.Whitaker and Engel (1972) noted granular deposistof IgG, IgM, and C3 in skeletal muscle blood vesselwalls and suggested that the vasculitis may be oneof the mechanisms of muscle injury, particularly indermatomyositis of children.

In our case, the significant findings were thedeposition of IgM and C3 in arterial wall and theperivascular mononuclear infiltrate. Necrotisingvasculitis, which was frequently found in Ponce'sseries, was not observed and the EVI factor des-cribed by Cossio was not found. We believe that theclinical polymyositis resulted from vascular involve-ment besides the myositis itself. Our observationsalso suggest that in Chagas's disease the humoralimmune system must play an important role in thepathogenesis of polymyositis.

We are very grateful to Professor H. L. F. Curreyfor help and advice in completing this paper.

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References

Adams, R. (1975). Diseases of Muscle, 3rd ed., pp. 335-337.Harper and Row, Maryland.

Andrade, S. G., and Andrade, Z. (1968). Patologia dadoenqa de Chagas experimental de larga duraqao. Revistado Instituto de Medicina Tropical de Sao Paulo, 10, 180-187.

Cenget, D. D., and Rojas, R. (1959). La biopsia de musculodelt6ides en la enfermedad de Chagas. Revista da Faculdadde Medicina de Tucuman, 2, 27-37.

Cossio. P. M., Diez, C., Szarfman, A., Kreutzer, E., Candiolo,B., and Arana, R. M. (1974a). Chagasic cardiopathy.Demonstration of a serum gammaglobulin factor whichreacts with endocardium and vascular structures.Circulation, 49, 13-21.

Cossio, P. M., Languens, R. P., Diez, C., Szarfman, A.,Segal, A., and Arana, R. M. (1974b). Chagasic cardiopathy.

Antibodies reacting with plasma membrane of striatedmuscle and endothelial cells. Circulation, 50, 1252-1259.

Dawkins, R. L. (1975). Experimental autoallergic myositis,polymyositis and myasthenia gravis. Autoimmune muscledisease associated with immunodeficiency and neoplasia.Clinical and Experimental Immunology, 21, 185-201.

Ponce, L. A. F. Z. (1972). Miopatia chagisica esquel6tica.Thesis, Universidad Nacional Mayor de San Marcos, Lima.Peru.

Whitaker, J. N., and Engel, W. K. (1972). Vascular depositsof immunoglobulin and complement in idiopathic inflam-matory myopathy. New England Journal of Medicine, 286,333-338.

Wolf, A., Kabat, E. A., Bezer, A. E., and Fonseca, J. R. C.(1952). The effect of cortisone in activating trypanosomalencephalitis and myocarditis in rhesus monkeys. Journal ofNeuropathology and Experimental Neurology, 11, 84-85.

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