Digital Gangrene in Early Systemic Lupus Erythematosus: An Uncommon Presentation

INTRODUCTION

The clinical presentations of systemic lupus erythematosus (SLE) are variable and can affect multiple organs including the skin. The cutaneous involvement may be seen in 57–85% of affected patients with SLE.¹ However, digital gangrene despite being sporadically reported in various populations is a rare presentation, especially in relatively early disease.^1–4 The etiopathogenesis of digital gangrene in SLE is complex involving several factors including antiphospholipid syndrome (APS), vasculitis, premature atherosclerosis, vasospasm, and thromboembolism. Prompt evaluation and management may prevent the need for amputation thus reducing the morbidity of SLE.

CASE DESCRIPTION

A 45-year-old female presented to our outpatient department with painful digital gangrene for the past 1.5 months involving the thumb and index finger of both hands associated with pus discharge from the right thumb for a few days. There was no history of diabetes mellitus, cardiovascular or other systemic disorders, sensorineural deficit, trauma, smoking, substance abuse, or similar episodes in the past. On further inquiry, the patient gave a history suggestive of episodes of Raynaud’s phenomenon and polyarthralgia for 1.5 years. She had low-grade undocumented fever with the appearance of pinhead-sized itchy papular lesions predominantly over extremities for 2–3 months. The patient took tablet paracetamol 500 mg or diclofenac 50 mg occasionally for symptomatic relief and applied topical creams procured over the counter along with tablet cetirizine 10 mg for itching. There was a partial response in symptoms and apparent improvement in skin lesions. No other drug history was present. There was no history of tightening of skin, swelling or ulceration of digits, oral ulceration, photosensitivity, muscular weakness, hair loss, or other skin lesions suggestive of connective tissue disorders.

General physical examination was unremarkable. All peripheral pulses were palpable and systemic examination except the musculoskeletal system was normal. There was gangrene of the thumb and index finger of both hands with minimal slough on the right thumb. Residual healed post-inflammatory hyperpigmented lesions were appreciable predominantly over lower limbs (Figs 1 and 2).

Baseline investigations including complete hemogram, ESR, renal function tests, liver function tests, lipid profile, HbA1C, serum C-reactive protein, coagulogram, viral markers, chest X-ray, ECG, and ultrasonography abdomen were normal. Arterial Doppler of upper limbs was non-suggestive for any atherosclerotic plaques, thrombus or calcification. Pus culture from slough in right thumb showed growth of methicillin-sensitive Staphylococcus aureus sensitive to linezolid. Additionally, a slit skin smear examination was negative for lepra bacilli.

The patient tested positive for antinuclear antibody (ANA) with a homogeneous staining pattern (4+, titer 1:640), following which detailed immunological serology was done. The dsDNA was 1+ (titer 1:10), and C3 was low. Perinuclear Anti-neutrophil Cytoplasmic antibodies (P-ANCA) was +ve (titer 1:160) by immunofluorescence technique. Antiphospholipid antibodies (APLA) profile and protein C and S levels were normal. Rheumatoid (RA) factor, Anti-CCP, anticentromere and U1 Small nuclear ribonucleoproteins (SNRP) antibodies were negative. The amount of urinary protein excreted over a 24-hour period was 630 mg/dL, and a subsequent renal biopsy was suggestive of lupus nephritis (class II). High-resolution computed tomography (HRCT) chest showed subpleural reticulations in bilateral basal segments of lungs suggestive of early interstitial lung disease. Echocardiography (2D-echo) was suggestive of Libman-Sacks vegetation.

The patient was diagnosed with SLE-associated digital gangrene with secondary infection, grade II lupus nephritis, and Libman-Sacks endocarditis. The residual healed post-inflammatory hyperpigmented lesions on the legs were suggestive of healed lesions of cutaneous vasculitis. She was started on injections of dexamethasone 8 mg IV OD, injection of tramadol 50 mg IV OD, Tablet linezolid 600 mg bid, and vasodilators (tab nifedipine 20 mg bid, losartan 25 mg od, cilostazol 100 mg bid,) aspirin 75 mg od and Injection enoxaparin 0.6 mL subcutaneously od thus halting the progression of gangrene and healing of the secondary infection appreciable over the next ten days. The surgical team advised against surgical amputation at this stage of her disease (Fig. 3). She was subsequently put under the multidisciplinary care of a rheumatologist, surgeon, and nephrologist for further multidisciplinary management.

DISCUSSION

The involvement of skin in SLE can have a wide spectrum of presentations.

Classically malar rash, photosensitivity, Raynaud’s phenomenon, alopecia, and features of vasculitic skin involvement like palpable purpura, papulonodular lesions, livedo reticularis, and cutaneous infarcts may be seen in SLE.⁵

Digital gangrene in SLE patients is a relatively uncommon presentation. A cohort study from South India noted gangrene in only 20 (5.81%) out of 344 SLE patients over about 10 years.⁶ It has been reported in only 18 (0.67%) out of 2,684 in a Chinese cohort and frank gangrene has been reported in 5 (1.03%) out of 485 Caucasian patients by Isenberg et al. with an average duration of onset 99.1 ± 0.1 months and 9.4 years respectively.^7,8 Development of gangrene early in the disease is also rare although few such cases have been reported.^9,10 Digital gangrene is more common in systemic sclerosis noted in 16% of patients of scleroderma by Giuggioli et al.¹¹ Gangrene is relatively much more commonly associated with the presence of accompanying Antiphospholipid Syndrome in SLE patients.¹² The role of Anti-neutrophil cytoplasmic antibodies (ANCA) in SLE is unclear and in absence of enzyme-linked immunosorbent assay (ELISA)-based testing for subcellular antigens, routine testing for ANCA in SLE patients lacks diagnostic and prognostic implications.^13,14 Factors such as disease duration, Raynaud’s phenomenon, elevated C-reactive protein (CRP), and dyslipidemia further contribute to the complex etiopathogenesis of gangrene.⁷ Other causes like diabetes mellitus, infections, drugs, cardiovascular and thromboembolic phenomenon, Buerger’s disease, malignancies, deficiency of protein C or protein S, other connective tissue disorders, and leprosy must be ruled out with good clinical history, examination, imaging, and relevant investigations.¹⁵ Besides specific internal organ-based interventions early treatment with glucocorticoids, immune suppressants, vasodilators, and anticoagulants can help terminate the progression of this rare but challenging complication of SLE, requiring minimal surgical interventions as observed in this case.

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