Scleroderma is a rare, chronic autoimmune disease that causes fibrosis in multiple body systems. It affects more than half a million people in the United States. As is typical of autoimmune disorders, it is more common in women than men. It usually affects young adults but can also occur in children and the elderly. The etiology is unknown. Scleroderma can be broadly divided into two types; systemic sclerosis and a less severe form, localized scleroderma. Systemic sclerosis has the highest mortality of all connective tissue diseases.1
Systemic sclerosis can affect both the central nervous system (CNS) and the peripheral nervous system (PNS). According to one comprehensive review, the most common CNS complications were headache, seizures, cognitive impairment, and stroke or transient ischemic attack (TIA).2 Peripheral nervous system involvement included myopathy, trigeminal neuropathy, sensorimotor polyneuropathy, and carpal tunnel syndrome. Autonomic neuropathy was common. Depression and anxiety were also frequent.
The name scleroderma comes from its scarring effect on skin, but scleroderma also affects circulatory, digestive, and immune systems as well as joints, kidneys, lungs, and muscles. Cutaneous and parenchymal fibrosis, microvascular occlusive disease with vasospasm and intimal proliferation occurs, as well as increased susceptibility to atherosclerosis.3
An epidemiologic study of 1238 patients with systemic sclerosis compared with 12,380 controls revealed that systemic sclerosis was associated with an 43% increased risk of new onset ischemic stroke and constitutes an independent risk factor for ischemic stroke.3 In another large population study, patients with systemic sclerosis had increased relative risk (RR) of myocardial infarction (RR 1.80), stroke (RR 2.61) and peripheral vascular disease (RR 4.35).1
Pathophysiology includes damaged vascular endothelial cells, perivascular inflammatory cell infiltrates, intimal thickening and vessel narrowing. Small arteries become fibrotic, less elastic, and prone to thrombosis. Dysregulated angiogenesis also occurs.2
This patient’s uncontrolled hypertension was the most likely etiology for both his current intracerebral hemorrhage (Figure 1) and prior ischemic stroke (Figure 2). The prior ischemic stroke had not produced clinical symptoms. Such “silent strokes” are not uncommon.4 Concentric left ventricular hypertrophy on the echocardiogram suggests longstanding hypertension. Accelerated atherosclerosis due to systemic sclerosis may have contributed to the ischemic stroke. Poor adherence with antihypertensive therapy likely triggered the hypertensive crisis associated with his acute hemorrhagic stroke.
Systemic sclerosis is a rare and challenging disorder to manage. Many neurologic complications can occur, including cerebral hemorrhage and ischemic stroke. In addition to improved medication adherence, this patient requires close follow up for hypertension management and secondary stroke prevention. Immune therapy for systemic sclerosis may need to be considered.
Take home messages
1. Systemic sclerosis is an independent stroke risk factor
2. Central and peripheral nervous system complications commonly occur in systemic sclerosis
3. Uncontrolled hypertension is a major risk factor for ischemic and hemorrhagic stroke
4. Ischemic and hemorrhagic stroke may co-occur
For more information, see: SIF (Scleroderma International Foundation).
*Details of this case were significantly changed to protect patient confidentiality.
1. Man A, Zhu Y, Zhang Y, et al. The risk of cardiovascular disease in systemic sclerosis: a population-based study. Ann Rheum Dis. 2013;72:1188-1193.
2. Amaral TN, Peres FA, Lapa AT et al. Neurologic involvement in scleroderma: A systemic review. Semin Arthritis Rheum. 2013;43:335-347.
3. Chiang CH, Liu CJ, Huang CC et al. Systemic sclerosis and risk of ischaemic stroke: a nationwide cohort study. Rheumatology. 2013;52:161-165.
4. Seshadri S, Wolf PA. Modifiable risk factors and determinants of stroke. In: Grotta JC, Albers GW, Kasner E, et al. Stroke, Pathophysiology, Diagnosis, and Management, 6th Edition. 2016; Elsevier, Inc.