□ CASE REPORT □ Thrombotic Thrombocytopenic Purpura with Severe Hypertension in a Patient with Systemic Sclerosis Sine Scleroderma and Polymyositis Masao Iwagami, Kanae Kubo, Ryoichi Tanaka, Kimito Kawahata, Akiko Okamoto, Noboru Hagino and Kazuhiko Yamamoto Abstract We present the first documented case of thrombotic thrombocytopenic purpura (TTP) with severe hyperten- sion complicated by polymyositis and systemic sclerosis sine scleroderma. TTP developed in the progressive phase of visceral fibrosis in the absence of skin thickening. ADAMTS13 activity was not useful for the diag- nosis of TTP. Although TTP and scleroderma renal crisis (SRC) share similar findings of thrombotic mi- croangiopathy, severe thrombocytopenia with multiple organ injuries and hemorrhagic manifestations sug- gested TTP rather than SRC. The patient’s condition improved dramatically with plasmapheresis. Key words: Polymyositis, Systemic sclerosis sine scleroderma, Thrombotic microangiopathy, Thrombotic thrombocytopenic purpura (Intern Med 50: 2413-2416, 2011) (DOI: 10.2169/internalmedicine.50.5653) ferential diagnosis between TTP and SRC. Introduction Case Report Thrombotic thrombocytopenic purpura (TTP) is character- ized by microangiopathic hemolytic anemia (MAHA), A 70-year-old Japanese woman was admitted to our hos- thrombocytopenia and functional impairment of multiple or- pital in August 2008 with headache and epigastric pain. She gans, especially the brain and kidneys. Thrombocytopenia had a 6-year history of polymyositis with anti-aminoacyl- and MAHA are shared by many disorders, including hemo- tRNA synthetase antibody and anti-signal recognition parti- lytic uremic syndrome (HUS), malignant hypertension, dis- cle antibody, which was under control with tapering of pred- seminated intravascular coagulation, drug-induced disorders, nisolone from the initial dose of 60 mg. She also had a his- antiphospholipid syndrome and scleroderma renal crisis tory of insulin-controlled diabetes with HbA1c of 6-7% and (SRC). TTP and HUS are often described as TTP-HUS syn- hypertension treated with candesartan for at least 6 years. In drome because of the similar clinical features and the diffi- addition, she had been diagnosed as having scleroderma culty in distinguishing between the two conditions. The spectrum disorder, considered as ssSSc (1), with Raynaud’s pathological findings are endothelial cell injury, and mi- phenomenon, contraction of lingual frenulum, bleeding of crovascular aggregation of platelets leading to ischemia, nailfold, telangiectasia, reflux esophagitis and interstitial called thrombotic microangiopathy (TMA). pneumonia, in the absence of anti-centromere antibody, anti- TTP is a rare complication of systemic sclerosis (SSc) topoisomerase I antibody and anti-U1-RNP antibody. No ob- and polymyositis, and has not been reported in association vious skin thickening was observed on physical examination with SSc sine scleroderma (ssSSc). We present a case of except for temporarily suspected sclerodactyly of one finger. TTP with severe hypertension, ssSSc and polymyositis, and Three months before admission, she presented with chest discuss the clinical features of the present case and the dif- pain and pericardial effusion on echocardiography sugges- Department of Allergy and Rheumatology, The University of Tokyo Hospital, Japan Received for publication April 14, 2011; Accepted for publication July 6, 2011 Correspondence to Dr. Kanae Kubo, [email protected] 2413 Intern Med 50: 2413-2416, 2011 DOI: 10.2169/internalmedicine.50.5653 Figure 1. Clinical course: laboratory data and treatment. LDH: lactate dehydrogenase, ACE: an- giotensin-converting enzyme, ARB: angiotensin II receptor blocker, FFP: fresh frozen plasma tive of pericarditis associated with polymyositis and ssSSc, tivity was high after diuretics use (47.5 ng/mL/h; reference which persisted during her hospital stay. Candesartan was range 0.2-2.7 ng/mL/h). Urinary findings included protein- once discontinued because of a drop in blood pressure to uria of 1 g/day without hematuria, granular and red blood around 90/60 mmHg. Her blood pressure then became ele- cell casts. vated to 144/98 mmHg one month before admission. Ileus Upon a provisional diagnosis of TTP, plasmapheresis was without mechanical obstruction, which was diagnosed as in- initiated on hospital day 1 along with prednisolone 40 mg/ testinal pseudo-obstruction associated with ssSSc, occurred day and intravenous nicardipin for hypertension in the state in the following month. of disturbed consciousness, which did not permit oral ad- Physical examination revealed a normal temperature, an ministration of antihypertensive drugs. After plasmapheresis elevated blood pressure of 204/122 mmHg, fluctuating levels for two consecutive days, her consciousness level and of drowsiness and disorientation, and ecchymosis on her ex- thrombocytopenia were dramatically improved. Captopril, tremities, but no skin sclerosis over her extremities. A com- valsartan and nifedipine were added for uncontrolled hyper- puted tomography (CT) showed wall thickening of jejunum tension. Abdominal pain was resolved within a week. Renal and ascending colon. Platelet count was significantly de- function was gradually improved (Fig. 1). Thrombocy- creased from a pre-admission level of around 18×104/μL to topenia and hemolytic anemia repeatedly relapsed during 3.2×104/μL. A decrease in hemoglobin from 11.8 g/dL one plasmapheresis tapering but they responded well to daily month before to 8.5 g/dL, a reticulocyte count of 7.2%, in- plasmapheresis. Infusion of fresh frozen plasma was not ef- creased levels of bilirubin (2.7 mg/dL) and lactate dehydro- fective. Renal function remained stable. She underwent plas- genase (1,099 IU/L; reference range 125-237 IU/L) with mapheresis for two and a half months to sustain a remission. normal ranges of aspartate aminotransferase (47 IU/L) and Follow-up CT showed improvement of intestinal wall thick- alanine aminotransferase (26 IU/L), undetectable haptoglo- ening after withdrawal of plasmapheresis. Activity of bin, and fragmented erythrocytes indicated microangiopathic ADAMTS13 (a disintegrin and metalloprotease domain, hemolytic anemia. Coombs’ test was negative. Serum cre- with thrombospondin type 1 motif 13) on admission was atinine was elevated from 0.64 mg/dL one month before to within the normal range (86%), and anti-ADAMTS13 inacti- 1.62 mg/dL. Normal ranges of prothrombin time (10.5 s), vating antibodies were negative. She was readmitted for activated partial thromboplastin time (30.7 s), and fibrinogen pseudo-obstruction and malnutrition associated with (368 mg/dL) with small elevation of D-dimer (3.4 μg/mL; scleroderma and died of miliary tuberculosis 8 months later. reference range 0-0.9 μg/mL), thrombin antithrombin com- Autopsy revealed fibrotic changes in the gastrointestinal plex (4.4 ng/mL; reference range 0-2.9 ng/mL), and no an- tract, myocardium and skeletal muscles, and diabetic neph- tiphospholipid antibodies ruled out coagulation disorders ropathy with nodular lesions of the glomerular extracellular such as disseminated intravascular coagulation and antiphos- matrix, glomerulosclerosis, interstitial fibrosis and mild re- pholipid syndrome. Serum complement levels were C3 59 duplication of the internal elastic lamina in small arteries of mg/dL, C4 8 mg/dL, and CH50 33.9 IU/mL. Plasma renin ac- the kidney. There was no evidence of persistent TMA. 2414 Intern Med 50: 2413-2416, 2011 DOI: 10.2169/internalmedicine.50.5653 oles, organization and recanalization of luminal thrombi, in- Discussion terstitial fibrosis, and glomerulosclerosis as a result of chronic ischemic damages. Marked intimal thickening leads ssSSc is characterized by visceral involvement typical of to severe luminal narrowing in renal arteries after SRC (9). SSc including esophageal hypomotility, small bowel hypo- However, it is difficult to determine the cause of intimal fi- motility, pulmonary interstitial fibrosis, pulmonary arterial brosis without severe luminal narrowing, interstitial fibrosis hypertension and scleroderma renal crisis, and peripheral and glomerulosclerosis, as in the present case, because this vascular involvement such as Raynaud’s phenomenon, digi- pattern of chronic changes may be seen in the chronic stage tal pitting scars, digital-tip ulcers and abnormal nailfold cap- of TTP, longstanding essential hypertension, and SSc with- illaries, without skin sclerosis. It is thought to be in the out SRC (9). spectrum of SSc (1). Cases of SRC sine scleroderma were Patients with idiopathic TTP do not typically have severe reported previously and have been shown to have poor renal hypertension, though SSc-associated TTP is often accompa- prognosis even with the use of angiotensin-converting en- nied by mild to severe hypertension (7). In the present case, zyme inhibitors (2). TMA with acute renal dysfunction and antihypertensive drug withdrawal before admission may hypertension may be primarily regarded as hypertensive have resulted in exacerbation of essential hypertension. It is SRC in the course of scleroderma, as well as in ssSSc (3). It difficult, however, to associate the high plasma renin activity is often difficult to distinguish TTP from SRC because of during hospitalization with SRC on the grounds of the clini- similar clinical and pathological features of TMA. However, cal response to plasmapheresis and histological findings the differentiation of TTP from SRC is indispensable, since from autopsy. High plasma