Digital gangrene associated with anticentromere antibodies.

Anticentromere antibodies have been associated with peripheral vascular occlusive disease, but then it is mostly accompanied by sclerodactyly in the context of a connective tissue disorder. We report a case of digital gangrene in a 75 year old lady with no other associations except positive anticentromere antibodies.

What was known?

Anticentromere antibodies are known to be associated with peripheral vascular occlusive disease, mostly in the context of a connective tissue disorder.

Introduction

The presence of anticentromere antibodies (ACA) is most commonly associated with limited scleroderma. To a lesser extent, ACA have been reported in other disorders including: Raynaud's syndrome, Raynaud's phenomenon associated with sclerodactyly, primary biliary cirrhosis (PBC), and Sjogren's syndrome.[1] Patients with circulating ACA associated with limited scleroderma or sclerodactyly have been reported to be at increased risk of significant peripheral vascular occlusive disease.[2] There is only scanty evidence in literature, of digital ischemia associated with ACA without associated Raynaud's phenomenon, sclerodactyly or other connective tissue disease. The only previous case report was in 53 year old lady who had digital gangrene and positive ACA. We report the case of a 75-year-old woman presenting with digital gangrene and a positive ACA without other features of connective tissue disease.

Case Report

A 75 year old lady presented with sudden onset of severe pain and blackish discoloration of the index finger of her left hand. She did not give any history suggestive of Raynaud's phenomenon, or arthritis. In fact she did not have any significant illness in the past, including diabetes, hypertension, or coronary artery disease. She did not have any addictions and she was not on any regular medications. On examination, there was digital necrosis of the distal finger Figure 1 with an adjacent area of pale swollen tissue with ulceration. No sclerodactyly was evident. There was no evidence of peripheral vascular disease. All her peripheral pulses were felt equally on both sides. There was no audible bruit. Her BP was 130/80 mm of Hg. All system examinations were within normal limits. Investigations revealed normal hemoglobin, total leukocyte count, platelet count and ESR. Her blood sugar, renal and liver function tests were within normal limits. ECG, X-ray chest and USG abdomen were also normal. Her ANA titre was elevated and ANA profile showed a strongly positive anticentromere antibody. Anti-double stranded DNA, anti-Sjogren's Syndrome A, anti-Sjogren's Syndrome B and anti-ribonucleoprotein antibodies (anti-SSA, anti-SSB, anti-RNP), anti-Sm, anti-Scl-70 were negative.

Figure 1

Digital gangrene

Discussion

The common causes of digital gangrene are atherosclerosis, diabetes, connective tissue diseases, vasculitis, infectious causes like infective endocarditis and HIV. Connective tissue diseases are the commonest cause of digital ischemia in young and middle aged especially females. Presence of a positive ANA need not signify an underlying disease. A high titre of ACA is reported in association with thrombotic vascular disease.[3] Hence the presence of a positive ACA should alert one to the presence of an underlying connective tissue disorder. However, ACA has been detected incidentally in patients without other features of connective tissue disease.[4] ACA antibodies are commonly associated with CREST syndrome, diffuse systemic sclerosis, PBC and other connective tissue diseases. There is also a strong correlation between ACA and Raynaud's phenomenon. Other associations of ACA include rheumatoid arthritis, systemic lupus erythematosus systemic lupus erythematosus (SLE), erythema nodosum, polyarthritis and relatives of patients with scleroderma. There have been case reports of patients with digital ischemia associated with ACA, but they also had other risk factors like smoking, Raynaud's phenomenon.[3]

Can there be a situation where a patient develops digital ischemia without other commonly associated risk factors but has ACA positivity? There has been one case report (and to our knowledge the only one in world literature), where a 53 year old lady presented with digital ischemia in association with a positive antinuclear antibody ANA and ACA without features of sclerodactyly, Raynaud's phenomenon or any other connective tissue disease or other risk factors like smoking, diabetes.[5] It has been postulated that ACA, rather than being a marker antibody may have a direct pathogenic role in vascular endothelial injury.[6]

It has been observed that human dermal endothelial cells (HDEC) exposed to sera containing ACA demonstrate increased apoptosis and altered gene expression. These include increased expression of genes linked to apoptosis and development of fibrosis, as well as diminished expression of angiogenesis promoting genes.[7]

Conclusions

Our patient's case illustrates the need to consider an autoimmune contribution to pathogenesis of digital ischemia even in the absence of a recognizable connective tissue disease and as this particular case demonstrates even in the elderly. Furthermore, digital ischemia may be the presenting feature or initial manifestation of an underlying evolving connective tissue disease.

What is new?

The possibility of an autoimmune basis to the pathogenesis of digital ischemia should be considered even in the elderly.