Henry Ford Hospital Medical Journal

Volume 33 Number 4 Article 13

12-1985

Dermatomyositis Complicated by Thrombotic Thrombocytopenic Purpura

Maria A. Sawdyk

Jeffrey Jundt

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Recommended Citation Sawdyk, Maria A. and Jundt, Jeffrey (1985) "Dermatomyositis Complicated by Thrombotic Thrombocytopenic Purpura," Henry Ford Hospital Medical Journal : Vol. 33 : No. 4 , 214-218. Available at: https://scholarlycommons.henryford.com/hfhmedjournal/vol33/iss4/13

This Article is brought to you for free and open access by Henry Ford Health System Scholarly Commons. It has been accepted for inclusion in Henry Ford Hospital Medical Journal by an authorized editor of Henry Ford Health System Scholarly Commons. Henry Ford Hosp Med Vol 33, No 4, 1985 Case Report

Dermatomyositis Complicated by Thrombotic Thrombocytopenic Purpura

Maria A. Sawdyk, MD,* and Jeffrey Jundt, MDt

A 65-year-old woman who had a documented history of endothelium with demonstration of IgM and complement dermatomyositis was hospitalized for evaluation of a synco­ deposits as the origin of the condition. Further, there are pal attack. During the course of her stay, she experienced reported cases of TTP associated with collagen disorders progressive neurologic dysfunction, hemolytic anemia, and such as systemic lupus erythematosus, rheumatoid arthritis, thrombocytopenia. A clinical diagnosis of thrombotic polyarteritis nodosa, and Sjogren's syndrome. To our knowl­ thrombocytopenia purpura (TTP) was made, and therapy edge, this represents the first known case of an association was initiated with glucocorticoids, plasmapheresis, plasma of TTP with dermatomyositis. Because of the implication of infusion, and antiplatelet medication. The pathogenesis of an immunologic pathogenesis for these disorders, this TTP has not been cleady elucidated. However, reports in association is worth noting. the literature have postulated immune damage of the

Thrombotic thrombocytopenic purpura (TTP) was origi­ changes of the face, upper arms and back. Creatine phosphokinase nally described by Moschowitz in 1925 (1). Since that time (CPK) and aldolase levels were elevated, and an electromyogram (EMC) showed myopathic changes in the right and left quadriceps. more than 300 cases have been reported, but the etiology Findings of biopsy of muscle from the left quadriceps were remains unclear. Recent studies show that extensive micro- consistent with a diagnosis of myositis, and results of biopsies of thrombi formation involving many internal organs is respon­ skin from the right midback and right outer arm were consistent sible for the clinical symptomatology of hemolytic anemia, with the diagnosis of dermatomyositis (Figs 1,2). Findings of repeat thrombocytopenia, fever, neurologic symptoms, and renal biopsies of skin in 1980 and 1982 were also consistent with this diagnosis, CPK and aldolase values were elevated in early 1982, abnormalities. These microthrombi are believed to form as and findings of repeat EMC were consistent with the ongoing a result of vascular damage (2,3), but their actual pathogene­ inflammatory features of myopathy. Corticosteroid therapy of sis is still debated. Many mechanisms for vascular damage various doses produced subjective clinical improvement. have been postulated including toxins (4), viruses (4), At admission, medications included hydrochlorothiazide (25 mg immune complexes (5-8), platelet aggregating factor (9), every morning), lente insulin (30 units every morning), and mechanical damage (10), and abnormalities of endothelial prednisone (20 mg every day). function (11,12). The patient was moderately obese and had hyperpigmented scaling patches on the extensor surfaces of the arms and shoulders. No The association of TTP with recognized immunologic Gottron's papules or heliotrope rash were noted, and no petechial disorders has great significance if one postulates an immuno­ or ecchymotic lesions were seen on initial examination. Proximal logic mechanism for TTP. Thus far, the disorder has been muscle strength was minimally decreased. described in association with Sjogren's syndrome (13), The day after admission the patient became confused, her systemic lupus erythematosus (14-17), rheumatoid arthritis temperature rose to 38°C, and her hemoglobin level was dropping. (18), and polyarteritis nodosa (19), Heretofore there have Schistocytes and thrombocytopenia were seen on the peripheral been no reports of TTP associated with dermatomyositis, but blood smear (Fig 3). Based on the triad of hemolytic anemia with microangiopathic changes in erythrocytes, thrombocytopenia, and we present such a case. Because of the implication of an fluctuating neurologic abnormalities described by Moskowitz (1), immunologic pathogenesis for these disorders, their associa­ we made the clinical diagnosis of TTP, tion in this patient is worth noting.

Case Report Submitted for publication: june 5, 1984 A 65-year-old woman was admitted for evaluation of a syncopal Accepted for publication: lune 10, 1985 episode. Her past medical history was significant for dermato­ •Department of Internal Medicine, Division of Hematology, Henry Ford Hospital myositis, hypertension, and type II diabetes mellitus. 'Department of Internal Medicine, Henry Ford Hospital The dermatomyositis diagnosis was established in 1975 at which Address rephnl requests to Dr Sawdyk, Department of Internal Medicine, 2799 W time the patient presented with proximal muscle weakness and skin Grand Blvd, Detroit, Ml 48202.

214 Dermatomyositis Complicated by TTP

Fig 1 Fig 2 Biopsy of skin in 1980. Findings were histologically compatible with Muscle biopsy from quadriceps 1980. infiltrative accumulation of dermatomyositis. inflammatory cells is seen.

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215 Sawdyk and Jundt

Table l-lospital Course

Platelets Blood Prothrombin Time/ Fibnn Hemoglobin (thousand/ Products Partial Thromboplastin Fibrinogen Degradation Blood Urea Nitrogen/ Date Ciinical (g/dL) mm^) Transfused Time (seconds) (mg/dL) (/xg/mL) Creatinine (mg/dL) 7/26 Syncopal episode 9.5 7 15/30 315 <10 31/1.1 7/28 Delirious 7.5 12 10 units 30/110 236 <10 14/0,9 platelets; 4 units fresh frozen plasma; 2 units packed red blood cells 7/30 Seizures; 10,0 16 10 units 17/110 76 80 23/2.6 2° disseminated platelets; 5 intravascular units fresh coagulation frozen plasma 7/31 Opens eyes; moves 6.9 124 10 units 19.5/110 188 80 16/1.7 extremities platelets; 2 units fresh frozen plasma 8/2 Moves all 9.9 115 4 units fresh 15/36 218 <10 20/1.3 extremities; frozen plasma responds to commands 8/4 Alert; responding; 11.4 49 4 units fresh 15/30 263 20 20/1.0 2° pneumonia frozen plasma 8/5 Alert; responding; 10.6 12 10 units 17/36 221 20 60/2.5 pneumonia platelets; 4 progressing units fresh frozen plasma 8/6 Hypotension; 6.8 15 27/110 198 20 85/4,1 seizures; cardiac arrest

Therapy included high doses of corticosteroids (2 g methylpredni­ has been suggested because of the apparent association of solone sodium succinate every four hours), plasmapheresis with TTP with disorders of autoimmune origin (13-19). plasma replacement (Table), and antiplatelet agents (100 mg dipyridamole every six hours). The clinical course consisted initially Because our patient experienced TTP several years after she of progressive neurologic deterioration leading to coma and had been treated for dermatomyositis, we would like to seizures. Likewise, the thrombocytopenia and hemolytic anemia pursue the possible association of the disorders by an persisted. Indeed, with the intense hemolysis, a secondary dissemi­ nated coagulopathy was triggered. However, by the sixth day the immunologic pathogenesis. patient exhibited significant neurologic improvement as well as In 1972, Mant and his associates (5) described immuno­ signs of stabilization of her hematologic parameters with concur­ fluorescent studies done on autopsy specimens from a rent correction of the disseminated coagulopathy. Unfortunately, secondary pneumonia disrupted this course, leading to the patient's patient who died of TTP. IgM and complement and fibrin final demise. Specific details are listed in the Table. Autopsy findings were demonstrated in the vicinity of the endothelium and revealed multiple microcirculatory hyaline thrombi, most pro­ in small-blood-vessel thrombi in multiple organs. Subse­ nounced in portions ofthe brain, heart, and kidney (Figs 4,5), These quently, Weisenburger and associates (6) demonstrated a histologic changes have been described previously in cases of TTP case of TTP with deposition of IgM and C3 in small vessels (20), using immunofluorescent studies. Meister and colleagues (7) This form of therapy in TTP has led to remissions in 60% to 80% reported circulating immune complexes in a patient who had of cases. Improvement is achieved consistently when glucocorti­ coids, platelet inhibitors, and plasma exchange transfusions are TTP. These complexes cleared with plasma-exchange ther­ used in combination (21). apy, and the patient's condition returned to normal. Garvey and Freedman (8) demonstrated complement activation that Discussion induced complement coating of both platelets and red blood A variety of etiologies of TTP have been postulated and cells in their patient who had TTP. Following plasma investigated. These include: the presence of a platelet exchange, results of the direct antiglobulin test became aggregating factor (9), deficiency of a naturally occurring negative, and CH50, serum C3 and C4, and red-blood-cell inhibitor of a platelet aggregating factor (12), abnormalities bound C3d levels became normal. Cameron and Vick (22) of endothelial function (11), and an immune etiology, which reported low plasma levels of C3 in five of ten patients who

216 Dermatomyositis Complicated by TTP

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Fig 4 Autopsy specimen of heart showing smaller arterioles thrombosed.

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Fig 5 Autopsy specimen of kidneys demonstrating the presence of small thrombi within glomerular tufts. Mild degree of nephrosclerosis is seen.

217 Sawdyk and Jundt

had hemolytic uremic syndrome and TTP. These reports all implies that (at least) childhood dermatomyositis may be supported the concept of a possible primary immunologic associated with an abnormal immune response. etiology for the vascular damage that occurs in patients who During this patient's illness, laboratory evidence also dem­ had TTP. onstrated disseminated intravascular coagulation (DIC). This Immunoglobulin concentrations and complement staining of secondary phenomenon has been studied previously in muscle tissue have been evaluated in patients who had other patients who had TTP, Jaffe and associates (24) studied dermatomyositis. Whitaker and Engel (23) studied biopsy the coagulation parameters in 12 patients who had TTP and specimens of muscle tissue from 36 patients who had found coagulation abnormalities consistent with dissemi­ inflammatory myopathies and described deposits of IgG, nated intravascular coagulation in three. IgM, and/or C3 within morphologically abnormal muscle fibers in 21 of the patients. These findings were most An evaluation of the clinical course and coagulation data in frequently associated with cases of childhood dermato­ Jaffe's series does not support the concept that DIC played myositis. The deposits were noted in small vein walls and, a primary pathogenetic role in TTP. When present, DIC less frequently, in small artery walls in agreement with appeared to be a secondary phenomenon related to previously noted morphologic vascular alterations. exacerbation of the hemolytic process with subsequent The deposits of immunoglobulin IgM and C3, alone or in release of red-blood-cell fragments. Additional evidence combination, were detected in the walls of blood vessels not against DIC as a primary mechanism for TTP was suggested just in the endomysium. This observation suggests that these by the failure of heparin administration to influence the findings are not simply a nonspecific change but represent course of the disease. Our patient also received heparin a primary vascular abnormality. Consequently, the study therapy with no apparent effect on the outcome.

References 1. Moskowitz E. An acute febrile pokiochiomic anemia with hyaline 13. Steinberg AD, Green WT, Talal N. Thrombotic thrombocytopenic thrombosis of terminal arterioles and capillaries; an undescribed purpura complicating Sjogren's syndrome. JAMA 1971;215:757-61. disease. Arch Intern Med 1925;36:89. 14. Dekker A, O'Brien ME, Cammarata RJ, The association of thrombotic 2. Nalbandian RM, Henry RL. A proposed comprehensive pathophysiol­ thrombocytopenic purpura with systemic lupus erythematosus. Am J ogy of thrombotic thrombocytopenic purpura with implicit novel tests Med Sci 1974;267:243. and therapies. Semin Thromb Hemost 1980;6:356-90. 15. Beigelman PM. Variants of the platelet thrombosis syndrome and their 3. Kwaan HC. The pathogenesis of thrombotic thrombocytopenic pur­ relationship to disseminated lupus. Arch Pathol Lab Med 1951 ;51:21 3. pura. Semin Thromb Hemost 1979;5:184-98. 16. Laszio MH, Alvarez A, Feldman F. The association of thrombotic 4. Watson CC, Cooper W. Thrombotic thrombocytopenic purpura: thrombocytopenic purpura and disseminated lupus erythematosus. Concomitant occurrence in husband and wife. JAMA 1971;215:1821- Ann Intern Med 1955;42:1308. 2. 17. Levine S, Shearn MA. Thrombotic thrombocytopenic purpura and 5. Mant MJ, Cauchi MN, Medley G. Thrombotic thrombocytopenic systemic lupus erythematosus. Arch Intern Med 1964;1 1 3:826. purpura: Report of a case with possible immune etiology. Blood 1972;40:416-21. 18. Blackman NS, Cohen BM, Watson J. Thrombotic thrombocytopenic purpura: Report of a case. JAMA 1952;148:456. 6. Weisenburger DD, O'Conner ML, Hart MN. Thrombotic thrombocy­ topenic purpura with C'3 vascular deposits. Am J Clin Pathol 19. Benitz L, Mathew M, Mallory GK. Platelet thrombosis with polyarteritis 1977;67:61-3. nodosa: Report of a case. Arch Pathol Lab Med 1964;77:116. 7. Meister RJ, Sacher RA, Phillips T. Immune complexes in thrombotic 20. Feldman JD, Mardiney MR, Unanue ER, Cutting H. The vascular thrombocytopenic purpura. Ann Intern Med 1979;90;717. pathology of thrombotic thrombocytopenic purpura. An immunohisto­ chemical ultrastructural study. Lab Invest 1966;15:927. 8. Garvey MB, Freedman J. Complement in thrombotic thrombocytope­ nic purpura. Am J Hematol 1983;15:397-8, 21. Myers TJ, Wakem CJ, Ball ED, Tremont SJ. Thrombotic thrombocytope­ 9. Lian EC. The role of increased platelet aggregation in TTP. Semin nic purpura. Combined treatment with plasmapheresis and antiplatelet Thromb Hemost 1980;6;401-15. agents. Ann Intern Med 1980;92:149-55. 10. Brain MD, Dacie JC, Hourehane DO. Microangiopathic hemolytic 22. Cameron JS, Vick R. Plasma C'3 in hemolytic uremic syndrome and anemia: The possible role of vascular lesions in pathogenesis. Br J thrombotic thrombocytopenic purpura. Lancet 1973;2:975. Haematol 1962;8:358. 23. Whitaker JN, Engel WK. Vascular deposits of immunoglobulin and 11. Remuzzi G, Rossi EC, Misiani R, et al. Prostacyclin and thrombotic complement in idiopathic inflammatory myopathy. N Engl J Med microangiopathy. Semin Thromb Hemost 1980;6:391-4. 1972;286:333-8. 12. Hensby CN, Lewis PJ, Hilgard P, Mufti GJ, Howe J, Webster J, 24. Jaffe EA, Nachman RL, Merskey C. Thrombotic thrombocytopenic Prostacyclin deficiency in thrombotic thrombocytopenic purpura. purpura—coagulation parameters in twelve patients. Blood Lancet 1979;2:748. 1973;42:499-507.

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