Digital dry gangrene as a primary manifestation of systemic lupus erythematosus

Abstract

Digital dry gangrene is commonly seen in cases of connective tissue disease such as systemic sclerosis. In systemic lupus erythematosus (SLE) digital gangrene is rare. As initial manifestation, it is again a rare phenomenon because it occurs late in the course of disease. Here we are reporting the case of a woman who was having extensive cutaneous gangrene of her fingers and toes, as a first and foremost presentation without any other typical signs and symptoms of SLE. Her serology was positive for SLE. The patient was treated conservatively and responded well.

Background

Systemic lupus erythematosus (SLE) is a chronic inflammatory, autoimmune disease involving multiple organs and systems with varied clinical features. Digital gangrene, a form of vascular injury in SLE, is a rare and severe complication that may cause amputation of digits.¹ Atherosclerosis, vasculitis, hypercoagulability and vasospasm are responsible for the development of such a complication.

Here a middle-aged woman presented first time as a case of digital gangrene of all limbs due to SLE. SLE with digital gangrene was first reported by Dubois and Arteberry² and Alarcon-Segovia and Osmundson.³ It is found only in 1.3% of cases of SLE.^{2 4} Gangrene of digits as an initial presentation is very rare and is often found in the late stage of the disease. Till now only a few cases are reported for the primary manifestation of SLE as digital gangrene.

Case presentation

A 40-year-old woman presented to medicine outdoor with the chief complaint of 1.5-month history of rapidly developing, painful digital gangrene of the bilateral fingers and toes. The patient had no previous history of joint pain, hair loss, photosensitivity, oral ulcers, malar rash or butterfly rash. No history was suggestive of Raynaud’s phenomenon. There was no history of diabetes mellitus and hypertension. No history of tobacco smoking or medication in the past. History of trauma, infection, or exposure to chemical substance was also not there. On general examination, she was afebrile, conscious and oriented. Her pulse rate was 70/min, regular, normovolemic and all peripheral pulses were palpable while blood pressure was 130/84 mm Hg. Ankle-brachial index was normal. All other systemic examinations were normal. There was dry gangrene involving the fingers and toes (figure 1).

Figure 1.

Dry gangrene in finger tips of all four limbs.

Investigations

Biochemical tests showed haemoglobin of 127 g/L, total leucocyte count 10.23×10⁹/L, platelets 170×10⁹/L. Red blood cells count was 3.08×10¹²/L and haematocrit 38.3%. Fasting lipid profile was normal. Erythrocyte sedimentation rate (ESR) was raised to 75 mm/hour (normal 0–29 mm/hour for women). Higher C reactive protein (CRP) of 31.5 mg/L (normal 0–8 mg/L) found. Echocardiography (2D-echo), ultrasonography abdomen and bilateral lower limb Doppler study were normal.

Immunologic studies like antinuclear antibody (ANA) was positive with homogeneous staining pattern of titre 1: 100 (low titres are in the range of 1:40 to 1:60), Antidouble-stranded (ds) DNA was positive at 56 IU/L (normal <50 IU/L) hence also the extractable nuclear antigen screen. Anti-β2 glycoprotein (GPI) (immunoglobulin (Ig) G) was normal with a titre of 3 AU/mL (normal 0–12). Lupus anticoagulant, anticardiolipin antibodies and antineutrophil cytoplasmic antibody were also negative. Fibrin degradation product and D-Dimer tests were found negative to explain any intravascular coagulation. Further tests of serum cryoglobulin and cryofibrinogen were done and both found negative. Urine dipstick and microscopy were normal. Kidney and liver profiles were normal along with negative viral markers like hepatitis B and C. Diabetes mellitus and any possibility of atherosclerosis was negative. Random blood sugar was 120 g/dL and HbA1C was 5.5%. Rheumatoid arthritis factor was also negative.

Based on history, examination and investigations diagnosis of lupus digital gangrene without antiphospholipid syndrome (APS) was made.

Differential diagnosis

Patient presented with digital gangrene suggestive of microvascular occlusion. On the basis of history and investigations infections, drugs and addiction, trauma, diabetes or emboli were ruled out. Hyperviscosity syndrome like cryoglobulinaemia and polycythaemia vera was not found. Hypercoagulable states both hereditary and acquired were also not present. Among small vessel vasculitis, scleroderma, antiphospholipid antibody syndrome, lupus (SLE) and rheumatoid, were the differential diagnosis. SLE was confirmed in this patient due to the presence of high titre of ANA and anti-ds-DNA.

Treatment

Treatment was started using antibiotics, corticosteroids, immunosuppressives and anticoagulants. Glucocorticoid (1 mg/kg/day) and aspirin (81 mg/day) were started. Two infusions, of 1000 mg rituximab at a 14-day interval were given with significant reduction in ESR and CRP and elevation of complements. After completion of two infusions we added 100 mg/day azathioprine and 200 mg/day hydroxychloroquine in therapy. Glucocorticoid was tapered up to 5 mg/day in 3 months.

Outcome and follow-up

During treatment, there was auto amputation of distal phalanx of four fingers of right hand except for the thumb, within 2–3 weeks, which gradually healed up. However, there was a marked improvement in all other fingers and toes, within 3–4 months of treatment. After 1 year of treatment and follow-up patient improved significantly. There was reduction in ESR to 28 mm/hour and CRP to 7 mg/L.

Discussion

SLE with primary symptoms of digital gangrene is a very rare entity and literature are more about SLE with antiphospholipid antibodies.⁵ It was further asserted by Rosato et al ⁶ that digital ulcers and gangrene are never found as the first presentation in SLE. Kurnia et al,⁷ Omair et al ⁸ also reported such a rare presentation, where the patient had SLE with secondary antiphospholipid antibody syndrome and overlap syndrome respectively. To date, the exact aetiology behind digital gangrene in SLE remains unclear. The probable mechanism and pathophysiology of digital gangrene in SLE is thromboembolism, premature atherosclerosis, vasospasm, hypercoagulability and vasculitis.⁹ A study was done by Liu et al in 2684 SLE patients, where 18 patients had digital gangrene and their average age at complication was 33.1±11.8 years and the average disease duration was 99.1±60.1 months. It was also observed that longer disease duration (≥4 years), Raynaud's phenomenon and elevated serum CRP were highly prone for digital gangrene. Here it was found that early and aggressive high dose corticosteroid treatment prevented gangrene from progression and improved prognosis.⁹ In a case report of a 12-year-old girl by Zieaa et al steroids and mycophenolate mofetil were given for her digital gangrene and good results were found.¹⁰ Jeffery et al found critical peripheral ischaemia as one of the causes along with positive antiphospholipid antibody syndrome. Treatment with rituximab responded by one.¹¹ Orhan et al also reported a similar case report of SLE with digital ischaemia and managed by rituximab.¹²

APS (in 3.3%–7.5% of cases), and β2GPI are an important risk factor for digital gangrene in SLE. Raynaud's phenomenon also associated with digital gangrene in SLE.³

Serological markers define management options such as vasodilator drugs would be required in patients of mixed connective tissue disorder/overlap syndrome. Early diagnosis and treatment including corticosteroid, immunosuppressives and lipid-lowering agents and anticoagulation are streamlined management strategies of digital gangrene in SLE. Risk of digital amputation gets decreased after the use of corticosteroids.⁹

Learning points.

• Systemic lupus erythematosus having digital gangrene as the initial symptom is rare.

• Serological markers define management options.

• Steroids, rituximab, cyclophosphamide and mycophenolate mofetil are the treatment available.