Case report Scleroderma renal crisis as an initial presentation of systemic sclerosis: a case report and review of the literature K.M. Logee, S. Lakshminarayanan Division of Rheumatology, University ABSTRACT precipitously. An evaluation for hae- of Connecticut Health Center, Farmington, Scleroderma renal crisis (SRC) is a life- molysis revealed an elevated serum lac- Connecticut, USA. threatening complication of systemic tate dehydrogenase which rose to 1155 Kristin M. Logee, DO sclerosis (SSc) that is characterised U/L and an undetectably low hapto- Santhanam Lakshminarayanan, MD by new-onset malignant hypertension globin. Peripheral smear showed schis- Please address correspondence and progressive acute renal failure, of- tocytes with evidence of microangio- and reprint requests to: ten with associated microangiopathic pathic haemolytic anaemia (MAHA). Dr Kristin M. Logee, haemolytic anaemia and thrombocy- Division of Rheumatology, The patient was thought to have throm- University of Connecticut Health Center, topenia. SRC was at one time almost botic thrombocytopenic purpura (TTP) 263 Farmington Avenue, uniformly fatal, with death often occur- with MAHA and treated with methyl- Farmington, ring within a few weeks. With the de- prednisolone 1g IV daily for 3 days and Connecticut 06030, USA. velopment of angiotensin-converting- plasmapheresis. ADAMTS13 level was E-mail: [email protected] enzyme inhibitors (ACE-I), survival ordered. Received on March 21, 2014; accepted in has improved dramatically, but death Over the next several days, despite revised form on November 24, 2014. rates still remain unacceptably high. treatment for TTP, the patient’s condi- Clin Exp Rheumatol 2015; 33 (Suppl. 91): About 20% of SRC cases occur prior to tion continued to worsen. Her platelet S171-S174. making a diagnosis of SSc and, in some count fell to 43 k/uL and her haemo- © Copyright CLINICAL AND cases, there is no evidence of skin scle- globin dropped to 6.2 g/dL, her creati- EXPERIMENTAL RHEUMATOLOGY 2015. rosis at the time that SRC develops. In nine rose to 4.1 mg/dL and she devel- this report, we present a case in which oped pulmonary oedema. At that point Key words: systemic sclerosis, a patient developed SRC prior to being she was started on haemodialysis. Her renal crisis, literature review diagnosed with scleroderma. Addition- ADAMTS13 activity level was 43%, ally, we review the pathogenesis, pre- which, in combination with her intact senting signs and symptoms, manage- mental status and lack of improvement ment and prognosis of SRC. with treatment, brought the diagnosis of TTP into question. Given her history of Case report Sjögren’s syndrome and cutaneous vas- A 60-year-old Hispanic female with a culitis, as well as her clinical picture of long-standing history of Sjögren’s syn- hypertension, acute renal failure, throm- drome and cutaneous vasculitis, charac- bocytopenia and MAHA, the diagnosis terised by tender, erythematous, ulcerat- of scleroderma renal crisis (SRC) was ing nodules involving the extremities, considered and a rheumatology con- initially presented to the Emergency sultation was requested. The patient Room with a 3-week history of epigas- was noted to have 3+ sclerodactyly and tric pain, nausea, vomiting and diar- loss of digital pulp. Serologic studies rhoea. As an outpatient, she had been revealed a positive ANA (speckled pat- taking 15 mg of prednisone daily for her tern, titer 1:5120) and a positive scl-70 vasculitis and lisinopril 2.5 mg daily. antibody at 90 U/mL. Anti-glomerular Upon presentation, her blood pressure basement membrane, anti-neutrophil was 178/85 mmHg, her creatinine was cytoplasmic and anti-RNA III polymer- 1.4 mg/dL (increased from her baseline ase antibodies were negative. of 0.7 mg/dL) and her platelet count was Based on these findings, the patient 143K/ul. She was admitted for further was started on treatment for SRC with evaluation. captopril. After 3 days of treatment, her Over the next two days, the patient re- blood pressure remained uncontrolled mained persistently hypertensive and and valsartan was added. Over the next her creatinine continued to rise. Her week, her blood pressure, anaemia and Competing interests: none declared. platelet count and haemoglobin dropped thrombocytopenia gradually improved. S-171 CASE REPORT Scleroderma renal crisis: a literature review / K.M. Logee & S. Lakshminarayanan Her platelet count increased to 105 k/ Risk factors arteries of SRC patients. In the future, uL and she was able to safely undergo Certain risk factors for SRC have been ET-1 receptor blockade may serve as an a renal biopsy to clarify her diagno- identified. Patients with early, diffuse alternative therapy for SRC (17, 18). sis. Light microscopy showed marked SSc (disease duration <4 years) have Corticosteroid use has been associated edematous intimal expansion of the been found to be at greatest risk of de- with SRC in multiple studies (8, 10, interlobular arteries with skeins of fi- veloping SRC (11). A retrospective case 19-21). One retrospective study of 50 brinoid material and interstitial fibro- series of 110 patients with SRC showed SRC patients demonstrated that 60% sis. The glomeruli were normocellular that only 2% with lcSSc versus 12% had been exposed to corticosteroids but appeared ischaemic and markedly with dcSSc developed SRC. Also, 66% prior to SRC onset, with an odds ratio congested. The diagnosis reported was developed renal crisis within the first of 24.1 for developing SRC associated “thrombotic microangiopathy consist- year of SSc diagnosis. In fact, in 22% of with corticosteroid exposure in the pre- ent with scleroderma renal crisis.” the patients¸ renal crisis was the initial ceding 3-month period (19). Steen et al. The patient’s hypertension remained presenting feature, occurring before the report a case-controlled study of 110 controlled with captopril and valsartan diagnosis of SSc was made (5). Addi- SSc patients in which 36% of SSc pa- and her thrombocytopenia and MAHA tional risk factors include: rapidly pro- tients receiving steroids (at least 15 mg resolved. She was then discharged from gressive skin thickening, new cardiac of prednisone/day) developed SRC ver- the hospital but has remained dialysis- events such as pericardial effusions and sus 12% not receiving steroids (10). A dependent over the following 3 years. congestive heart failure, new anaemia recent systematic review also supported (9), presence of anti-RNA polymerase the association between the use of me- Literature review antibodies and use of corticosteroid dium and high dose corticosteroids and Introduction therapy (>15 mg prednisone/day) (10). the development of SRC (21). Howev- Systemic sclerosis (SSc) is a multisys- er, this relationship was not found in the tem connective tissue disease charac- Pathogenesis review of 110 SRC patients by Penn et terised by immune system activation, Although incompletely understood, the al. (5). A systematic review by Iudici et microvascular injury and widespread pathogenesis of SRC appears to result al. found that a beneficial role of low to fibrosis of skin and internal organs from an initial trigger of vascular en- medium dose corticosteroids in SSc is (1). It primarily affects the skin, heart, dothelial injury resulting in increased limited, although they could be used in lungs, kidneys and gastrointestinal permeability and intimal oedema. This certain situations (i.e. for treatment of tract and exists in both diffuse (dcSSc) results in a cascade of events as the sub- interstitial lung disease, diffuse cutane- and limited forms (lcSSc). endothelial connective tissue is exposed ous disease or myositis) (22). Immuno- Scleroderma renal crisis (SRC) is a life- to circulating elements in the blood, suppressive agents such as methotrex- threatening complication of SSc that causing activation of the coagulation ate, azathioprine or cyclophosphamide was first characterised by Moore and cascade and thrombosis. Additionally, may be used to minimise corticosteroid Sheehan in 1952 as malignant hyperten- the connective tissue reacts to the in- exposure (10). When corticosteroids are sion and acute renal failure (2), often jury, resulting in fibroblastic and nonfi- needed, the lowest possible dose should with associated thrombotic microangi- broblastic stromal proliferation. These be used and patients should be closely opathy. While SRC remains a very seri- events (oedema, thrombosis and stromal monitored with regular blood pressure ous complication of SSc, it was at one proliferation) result in narrowing of re- checks and serum creatinine levels to time almost uniformly fatal, with death nal arterial vessels and decreased renal allow for early detection of SRC (23). often occurring within a few weeks. perfusion with subsequent hyperplasia With the development and usage of an- of the juxtaglomerular apparatus and Presentation giotensin-converting-enzyme inhibitors increased renin release. The increase in SRC typically presents as a new onset (ACE-I) in the late 1970s, 1-year sur- renin causes accelerated hypertension of significant systemic hypertension vival from SRC improved dramatically, and further renal injury (12-16). SRC and acute renal failure. Approximately from 18% to 76% (3). However, early patients often have markedly elevated 10% of patients may be normotensive diagnosis and treatment remain critical renin levels, and hypertension has been but almost invariable have an increase to improving outcome. shown to improve dramatically after ne- in blood