CASE STUDIES Rheumatoid arthritis with ANCA associated vasculitis

Recent reported the development of AAV in patients with rheumatoid The present study discusses an uncommon case of AAV in a 50-year old patient with RA. Antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) are rarely associated with autoimmune diseases. The present report describes an uncommon case of a 50-year old women with the co-occurrence of antineutrophil cytoplasmic antibody associated vasculitis with rheumatoid arthritis. The patient was treated with steroids and cyclophosamide and achieved complete recovery of the lesions, following 4-weeks of treatment.


Introduction
Antineutrophil cytoplasmic antibody associated vasculitis are rare autoimmune diseases, characterized by inflammation of small and medium sized blood vessels. 1 AAV is rarely associated with immune mediated diseases such as systemic lupus erythematosus, scleroderma, membranous glomerulonephritis and anti-glomerular basement membrane disease. 2 Recent studies have reported the development of AAV in patients with rheumatoid arthritis. 2 The present study discusses an uncommon case of AAV in a 50-year old patient with RA.

Case report
A 50-year-old female presented to the outpatient department with sudden onset blackening of ring, index and middle finger of the left-hand (Fig. 1). The symptom was progressive with associated severe paresthesia throughout the hand. She was diagnosed with seropositive rheumatoid arthritis from two-years and was on methyl prednisolone (5 mg/day) and methotrexate (10 mg/ week), for 6-months. The subject fulfilled the 2010 ACR EULAR criteria for RA. History of fever, chest pain, skin rashes, reduced urine output, trauma, sinusitis, cough and hemoptysis were absent in the patient.
The blood pressure, pulse and SpO2 of the patient was160/90,100 and 99% respectively. Reduced pulse was noted in the radial and ulnar arteries of the left hand. Tenderness was noted in few joints of the hand with minimal swelling. The patient had normal cardiovascular function.
ANA and APLA workup of the patient was negative with highly positive C-ANCA (Table 1). Her chest X-ray was normal. The ultrasound scan of the abdomen showed

Discussion
Active vasculitis associated with RA is a rare complication, affecting only about 1% of the patient population, and occurs in patients with longstanding RA and with severe joint deformities. 3 Apart from classic presentation of rheumatic vasculitis, mononeuritis multiplex, other manifestations include weight loss, hepatomegaly, splenomegaly, ocular inflammation, pleuritis, pericarditis, and Felty's syndrome. 4 The involvement of kidney is less common in rheumatic vasculitis. 5 ANCA associated vasculitis constitutes: microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA) or Wegener's granulomatosis and eosinophilic granulomatosis with polyangiitis (EGPA) or Churg-Strauss syndrome, and occurs from the antineutrophil cytoplasmic antibody, directed towards myeloperoxidase (MPO) or proteinase 3 (PR3).6 Clinically, MPA mostly involves MPO-ANCA and GPA involves PR3-ANCA. 6 The disease effects organs such as kidney, stomach, intestine, and lungs, and include clinical features such as fever, anemia, malaise, weight loss, synovitis and rash. 7,8 In the present patient, RA activity was less severe with minimal joint tenderness and swelling, and was of short duration. The ultrasound of the abdomen revealed only mild fatty liver and normal kidneys. Additionally, the cardiovascular function was normal. Hence the possibility Renal involvement is a common manifestation in AAV. The highest frequency of renal involvement has been reported in MPA (upto 100%), followed by GPA (upto 70%) and EGPA. 9, 10 Draibe and Salama (2015), based on a retrospective analysis concluded that renal involvement is a common manifestation among rheumatoid arthritis patients developing AAV. 2 However, in the present patient renal involvement was absent. 11 ANCA associated vasculitis typically involves capillaries, arterioles, venules and small vessels. 12 Literature evidence suggests that the involvement of large and medium sized vessels in ANCA associated vasculitis has a lower prevalence. 12 However, in the present patient, narrow lumen was noted in medium vessels such as the left hand radial and ulnar artery. There was no involvement of other small vessels for the patient, which is a classical presentation of the disease.
Over 35 cases of overlap between RA and AAV has been reported so far. 2 The cohort study conducted by Draibe and Salama (2015) reported six cases of RA patients developing ANCA associated vasculitis in an average 10.5 years, following the diagnosis of RA. 2 The study reported that the patients frequently presented with vasculitis renal manifestations and RF positivity, during AAV diagnosis. Similarly, previous studies have also reported function deformity in renal and RF positivity in majority of the cases. However, cases of overlapping RA and AAV with negative ANCA was also reported. 2 The overlap of RA with AAV has been attributed to the presence of common genes, such as the PTPN22, found in both RA and AAV. 13,14 The study by Menegatti et al. (2009)   AAV is treated with induction therapy, which uses a combination of cyclophosphamide and steroids, at high doses. 16 Methotrexate and mycophenolate mofetil are considered for induction therapy in patients with no evidence of major organ disease. 17 Maintenance therapy mostly involves the use of azathioprine. However, recent studies have demonstrated the superiority of rituximab over azathioprine. 18 The commonly used drugs for the treatment of RA includes methotrexate, prednisolone, anti-TNFs and hydroxychloroquine. ANCA associated vasculitis are treated with drugs such as cyclophosphamide, glucocorticoids and rituximab. 8

Conclusion
Although ANCA associated vasculitis is rare, they should be considered in RA patients without active disease.