|Year : 2015 | Volume
| Issue : 1 | Page : 37-39
Systemic sclerosis presenting with severe digital ischemia: A rare case report
Sourya Acharya1, Samarth Shukla2, SN Mahajan1
1 Department of Medicine, JN Medical College, DMIMS University, Sawangi (Meghe), Wardha, Maharashtra, India
2 Department of Pathology, JN Medical College, DMIMS University, Sawangi (Meghe), Wardha, Maharashtra, India
|Date of Submission||11-May-2014|
|Date of Decision||14-Oct-2014|
|Date of Acceptance||23-Dec-2015|
|Date of Web Publication||12-Feb-2015|
Department of Medicine, JN Medical College, DMIMS University, Sawangi (Meghe), Wardha - 442 004, Maharashtra
Source of Support: None, Conflict of Interest: None
Digital ischemic loss is a cause of significant morbidity in patients with systemic sclerosis (SSc). Both small and large digital arteries are involved causing perfusion defects leading to ischemia. Microvascular disease causes intimal proliferation and luminal narrowing of small digital arteries, macrovascular disease causes narrowing or occlusion of larger digital arteries. Immediate clinical evaluation and treatment are mandatory at the onset of critical digital ischemia to prevent digital loss. We present a case of 38-year-old female suffering from SSc who presented with acute onset severe digital ischemia of all four limbs.
Keywords: Systemic sclerosis, ischemia, microvascular, macrovascular
|How to cite this article:|
Acharya S, Shukla S, Mahajan S N. Systemic sclerosis presenting with severe digital ischemia: A rare case report. J Med Sci 2015;35:37-9
| Introduction|| |
Systemic sclerosis (SSc) is a disease of unknown etiology characterized by immune activation, tissue fibrosis, and vasculopathy. Peripheral vascular involvement manifesting as Raynaud's phenomenon (RP) affects almost all patients. Episodes of progressive digital ischemia can result in a digital ulcer and sustained reduction in digital perfusion with impaired tissue viability can lead to critical ischemia, in some cases resulting in gangrene necessitating amputation. Neuroendothelial imbalance of vasoconstriction and vasodilatation, structural abnormalities of the vasculature, and intravascular factors such as platelet activation, procoagulants, and oxidative stress are the predominant factors that affect the microvasculature and cause critical ischemia. Recent studies on macrovascular disease in SSc suggest that ischemic demarcation and loss of digits occur secondary to narrowing or occlusion of larger digital arteries (vessels of the palmar arch, radial, or ulnar artery) or medium-sized and large arteries in the lower extremities.
| Case Report|| |
A 38-year-old female, housewife, diagnosed as limited SSc 2 years back presented with gradually progressive painful discoloration of digits of the upper and lower extremities since 7 days duration. There was a history of presence of RP since 3 years.
Her treatment history included a tablet prednisolone 10 mg alternate days, tablet nicardipine 10 mg once daily, and tablet pentoxifylline 400 mg 8 hourly.
On examination, there was obvious bluish black discoloration of all the digits of the upper limbs including the hands and lower limbs up to the ankle joint bilaterally with a visible line of demarcation suggesting ischemic gangrene [Figure 1] and [Figure 2]. Skin of the extremities (sclerodactyly) and face were thickened. Bilateral hands and feet were cold. Bilateral radial arteries were palpable, but in the lower limbs bilateral dorsalis pedis and posterior tibial arteries were not palpable. Allen's test was abnormal with poor refill bilaterally. Capillaroscopic examination of the periungal regions revealed dilated capillary loops. No peripheral bruits were audible.
An angiogram revealed evidence of a bilateral obliterative vasculopathic process in the superficial and deep palmar arches in the upper limbs and thrombotic occlusion of bilateral popliteal arteries of the lower limbs. Radiographs of the hands did not reveal any bony abnormality. Further investigations revealed a positive antinuclear antibody with titer >1260 and anti-centromere specificity. Anti-centromere antibodies (ACA) were confirmed by enzyme-linked immunosorbent assay at >110 U/mL. Anti-double stranded DNA, antineutrophil cytoplasmic antibodies, anticardiolipin antibodies, C-reactive protein, complete blood count, and urinalysis were all normal or negative. Chest radiograph, echocardiogram were normal.
She was treated with intravenous (IV) heparin, IV methyl prednisolone, clopidogrel, pentoxifylline, intravascular thrombolysis with urokinase for the lower limb thrombotic disease. But there was no clinical improvement and the pain and necrosis increased further. The patient was referred to a higher center.
| Discussion|| |
Systemic sclerosis has a prevalence of 1-50 cases per 100,000 people worldwide.  A retrospective review of the clinical status of 98 patients with SSc, seen between 1985 and 1990, showed that amputation of one or more digits due to ischemia occurred in 20.4% of the patients while 9.2% had multiple digit loss as in our case.  Of two prospective cohort studies in UK, one study found that 28 (16%) of 171 SSc patients had at least one digital amputation and 73 (43%) had experienced at least one episode of severe digital ischemia,  and in another study, 17.4% were found to have complications related to severe digital vasculopathy including digital ulcers, critical digital ischemia, gangrene, or the need for digital sympathectomy. Furthermore, 1.6% of the total cohort developed critical digital ischemia, 1.4% developed digital gangrene, and 0.9% required amputation. 
Observational studies have shown that limited cutaneous SSc is associated with more prominent vasculopathy than its diffuse counterpart.
Several studies have demonstrated that the severity of the vasculopathy requiring amputation is associated with the presence of specific antibodies such as anti-cardiolipin, anti-centromere, anti-beta2-glycoprotein I, and anti-topoisomerase antibodies. ,
Smoking is also independently associated with severe digital gangrene. 
Evaluation should ideally start with meticulous clinical examination, palpation of peripheral pulses, and assessing for persistent discoloration (cyanosis or pallor), digital ulceration, extreme tenderness, or frank gangrene. Nailfold capillaroscopic changes may be predictive of the development of digital ischemia.  Arterial Doppler and Ankle brachial pressure index estimation is also helpful.
Laboratory analysis for prothrombotic states including the antiphospholipid antibodies (lupus anticoagulant, anti-cardiolipin, and anti-beta2-glycoprotein I antibodies), ACA should be performed in all patients. Prompt clinical evaluation and referral for treatment are critical to the prevention of progression to digital loss.
Angiographic evaluation for digital occlusions includes conventional angiography, magnetic resonance angiography, or computed tomography angiography. Conventional angiography is extremely sensitive for identifying the stenosis, occlusion, aneurysm, or other vascular irregularities and is still considered gold standard.
Digit-threatening ischemia is a medical emergency. It warrants prompt and aggressive treatment to control symptoms and prevent digital loss.
Nonpharmacologic treatments aim toward keeping the limb warm and giving rest to the part with decreased activity. Xeroform dressing with an antibiotic ointment can be used to prevent a superinfection and allow wound healing. IV antibiotics should be used to overlying infection or osteomyelitis. Surgical debridement is generally reserved for patients with purulent drainage, necrotic/late stage ischemic tissue, or severe structural arterial disease who do not respond to medical therapies.
Analgesia with opioids is of utmost importance. Local anesthetic blocks with lidocaine or bupivacaine without epinephrine may be helpful for pain control.
Anticoagulation with IV heparin is recommended.
Aggressive vasodilatation in form oral calcium channel blocker, IV prostacyclins is considered the mainstay of management for acute digital ischemia. IV epoprostenol or iloprost (0.5-2 ng/kg/min) daily infusions for 1-3 days, each infusion lasting 6 h, is the recommended regimen.  If symptoms are persistent and medical therapy fails, proximal or digital sympathectomy, microsurgical revascularization of the hand, and digital arterial reconstruction have been reported to improve digital vascular perfusion, heal digital ulcers, and substantially relieve or eliminate pain. 
If there is larger vessel occlusive disease, especially at the level of the ulnar or radial artery, successful reconstruction can be performed with vein grafts.  Peripheral artery bypass is a good alternative in the vasoocclusive disease of the superficial palmar arch and tarsal arch, and also in relieving symptoms in lower limb larger arterial occlusive disease.
| References|| |
Chifflot H, Fautrel B, Sordet C, Chatelus E, Sibilia J. Incidence and prevalence of systemic sclerosis: A systematic literature review. Semin Arthritis Rheum 2008;37:223-35.
Wigley FM, Wise RA, Miller R, Needleman BW, Spence RJ. Anticentromere antibody as a predictor of digital ischemic loss in patients with systemic sclerosis. Arthritis Rheum 1992;35:688-93.
Hider S, Lunt M, Herrick AL. Amputations in systemic sclerosis: The influence of disease subtype, anti-centromere antibody and smoking status. Rheumatology 2001;40 Suppl 1.
Nihtyanova SI, Brough GM, Black CM, Denton CP. Clinical burden of digital vasculopathy in limited and diffuse cutaneous systemic sclerosis. Ann Rheum Dis 2008;67:120-3.
Herrick AL, Heaney M, Hollis S, Jayson MI. Anticardiolipin, anticentromere and anti-Scl-70 antibodies in patients with systemic sclerosis and severe digital ischaemia. Ann Rheum Dis 1994;53:540-2.
Boin F, Franchini S, Colantuoni E, Rosen A, Wigley FM, Casciola-Rosen L. Independent association of anti-beta(2)-glycoprotein I antibodies with macrovascular disease and mortality in scleroderma patients. Arthritis Rheum 2009;60:2480-9.
Harrison BJ, Silman AJ, Hider SL, Herrick AL. Cigarette smoking as a significant risk factor for digital vascular disease in patients with systemic sclerosis. Arthritis Rheum 2002;46:3312-6.
Sebastiani M, Manfredi A, Colaci M, D'amico R, Malagoli V, Giuggioli D, et al.
Capillaroscopic skin ulcer risk index: A new prognostic tool for digital skin ulcer development in systemic sclerosis patients. Arthritis Rheum 2009;61:688-94.
Pope J, Fenlon D, Thompson A, Shea B, Furst D, Wells G, et al.
Iloprost and cisaprost for Raynaud's phenomenon in progressive systemic sclerosis. Cochrane Database Syst Rev 2000;CD000953.
Bogoch ER, Gross DK. Surgery of the hand in patients with systemic sclerosis: Outcomes and considerations. J Rheumatol 2005;32:642-8.
Kwon ST, Eun SC, Baek RM, Minn KW. Peripheral arterial-bypass grafts in the hand or foot in systemic sclerosis. J Plast Reconstr Aesthet Surg 2009;62:e216-21.
[Figure 1], [Figure 2]