Peripheral gangrene secondary to vasculitis: A rare extra-articular manifestation of rheumatoid arthritisMB Indu, DS Meena, P Jain, B Sharma
Department of General Medicine, ABVIMS and Dr. Ram Manohar Lohia Hospital, New Delhi, India
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/jpgm.jpgm_1126_21
Source of Support: None, Conflict of Interest: None
A 45-year-old male, reformed smoker presented to us with gangrenous changes on the fingertips of left hand for 2 weeks [Figure 1]a. There was no history of fever, arthralgia, rash or pain. On examination, his pulse, blood pressure, and oxygen saturation were normal. He had multiple punched out ulcers on extensor aspects of left upper and lower limbs [Figure 1]b. There were synovial thickening over left second and third proximal interphalangeal joints and ulnar deviation of both wrists [Figure 1]a. There were no swelling, redness, or tenderness over any of the joints. On respiratory system examination, reduced intensity of breath sounds over all lung areas and bilateral wheeze were found. Cardiovascular, abdomen, and nervous system examination were normal.
He had a history of inflammatory small joint pain with early morning stiffness for 8 months; two years back for which he took methotrexate, sulfasalazine, and hydroxychloroquine for about 6 months. His symptoms improved and he stopped medications.
On investigations, erythrocyte sedimentation rate (ESR)-65 mm/1sth, C-reactive protein (CRP)->15 mg/dL, hemogram, renal and liver function tests, and lipid profile were normal. Rheumatoid factor and anticyclic citrullinated peptide (CCP) titers were 75 IU/mL and 320 IU/mL, respectively. X-ray bilateral hands showed periarticular osteopenia, erosions, and ulnar deviation [Figure 2]a. X-ray bilateral foot also showed periarticular osteopenia and erosions [Figure 2]b. USG arterial Doppler showed triphasic flow across all arteries in all four limbs. 2D Echo showed normal chamber dimensions and valves with an ejection fraction of 50%. There were no vegetations, thrombus, or pulmonary artery hypertension.
Antinuclear antibody (ANA), extractable nuclear autoantibody (ENA) profile, and antineutrophil cytoplasmic antibodies (ANCA), HIV, and Hepatitis B and C serology were negative. Skin biopsy from ulcer edge showed disruption of vessel wall by neutrophils, fibrinoid necrosis of vessel wall, endothelial swelling, and red blood cell extravasation suggestive of small vessel vasculitis [Figure 2]c.
A diagnosis of rheumatoid arthritis-associated vasculitis was made. He was started on immunosuppressive therapy with steroids followed by cyclophosphamide pulse; his symptoms improved, gangrene receded [Figure 1]c, and cutaneous ulcers resolved. He is on regular follow-up without any fresh complaints.
Rheumatoid vasculitis is a rare extra-articular manifestation of rheumatoid arthritis (prevalence of 1%–5%). It occurs exclusively in seropositive patients and hence an immune complex-mediated pathology is suggested. The mean duration between the diagnosis of rheumatoid arthritis and the onset of vasculitis is 10–14 years. The onset of rheumatoid vasculitis within first 5 years of the onset of arthritis is rare. Long standing rheumatoid arthritis with deformities, male gender, smoking, and high titers of rheumatoid factor are the other risk factors associated with it. The present patient had no active joint complaints at the onset of vasculitis and vasculitis developed early in the disease course (within 2 years of the onset of rheumatoid arthritis symptoms).
Small to medium vessels are most commonly involved. However, any organ of the body can be affected in rheumatoid vasculitis. The most common among the vasculitic manifestations are cutaneous and peripheral nerve involvement (>80% cases of rheumatoid vasculitis). Cutaneous involvement may be in the form of palpable purpura, ulcers, nodules, digital gangrene, or livedo reticularis. Involvement of peripheral nervous system may manifest as mononeuritis multiplex, distal symmetric sensory or motor neuropathy. However, it can also involve internal organs, central nervous system, acute renal failure, mesenteric vasculitis and acute myocardial infarction - which can be difficult to diagnose and therefore life threatening.
A good history and a relevant clinical examination in all cases of suspected vasculitis are a must. If any one or more of the following occurs in the presence of rheumatoid arthritis: (1) mononeuritis multiplex or peripheral neuropathy, (2) peripheral gangrene, (3) biopsy evidence of acute necrotizing arteritis in the presence of systemic illness (fever and weight loss), (4) deep cutaneous ulcers, or other extraarticular diseases (e.g., pleurisy, pericarditis, and scleritis), a diagnosis of rheumatoid vasculitis can be made.
Definitive diagnosis is by tissue biopsy. Mononuclear or neutrophilic infiltration of vessel wall with fibrinoid necrosis, leukocytoclasis, and disruption of internal elastic lamina are seen in histology.
Treatment is aimed to reduce systemic inflammation. Mild cases with skin and peripheral nerve involvement may respond to steroids, methotrexate, and azathioprine. However, internal organ involvement can be life threatening and hence need aggressive treatment with intravenous steroid pulse followed by cyclophosphamide pulse therapy or other biologicals. We had opted for cyclophosphamide therapy despite the lack of internal organ involvement once the clinical diagnosis was made and infections and other differential diagnoses were ruled out. This was because gangrene had a rapid progression and the action of oral disease-modifying antirheumatoid drugs takes 3–12 weeks to establish. Aggressive treatment of risk factors like smoking cessation and other modifiable atherosclerotic risk factors is also recommended.
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[Figure 1], [Figure 2]