Case discussion
The 39-year-old female patient presented with inflammatory backache, symmetrical small and large joint pain, and limitation in knee movement. She had hair loss and disturbed sleep for 3 months. An ophthalmic examination revealed that she had a mild vascular leak in the right eye and neovascularisation in the left eye suggestive of retinal inflammatory disease and vasculitis. Her hand and pelvis X-rays were normal, and the knee joint showed grade I osteoarthritis changes.
Evidence of retinal vasculitis and musculoskeletal features of inflammatory back pain and symmetric non-destructive arthritis suggests the following diagnostic possibilities: vasculitis of systemic nature/ autoimmune origin (medium to small vessel disease), vasculitis of retina overlapping with unrelated SpA, SpA presenting with retinal and uveal inflammation, infective etiology like syphilis, other chronic infections like TB, and a rare possibility of sarcoidosis.
Retinal vasculitis is seen in 4% of the patients with polyarteritis nodosa.1 Inflammatory eye disease is present in 50% to 60% of the patients with ANCA-positive vasculitis, and in 8% to 16% at the beginning of the disease.2 Scleritis and episcleritis are the most common manifestations; whereas the present patient had vasculitis with iridocyclitis and had features suggestive of scleritis in the form of redness and eye pain. Arthritis is seen in 50 to 70% of the patients with ANCA-related vasculitis. All the symptoms noted in the present case are suggestive of ANCA-related vasculitis, except inflammatory back pain.
Overlap of SpA with vasculitis could be suspected, but the chance is rare when considering the normal pelvis X-ray and the age/gender of the patient. The patient does not fulfill ESSG criteria for diagnosing SpA. Among the infections, syphilis can have similar manifestations, whereas the disease is rare in the current decades and was excluded by the treponema pallidum hemagglutination (TPHA) test. The other possibility to be considered is TB and it cannot be ruled out in patients with extrapulmonary or classical lesions of Wegener's granulomatosis (WG) or vasculitis. In a Mexican study, 44.4% of the 45 TB patients were positive for ANCA by indirect immunofluorescence (IF) and 40% of patients by ELISA, which was higher than the control groups. Thus, in a country with a high prevalence of TB, the direct interpretation of an ANCA‐positive result as indicative of primary systemic vasculitides, especially WG, is not advocated.3 This is more important in patients with no classical features of the disease. The combined reactivity of IF and anti-PR3 would seem to be more suggestive of WG and is recommended in a clinical setting to distinguish between ANCA-associated vasculitis (Wegener's granulomatosis) and TB mimicry.4 Tb quantiferon and/or Mantoux should be performed to exclude the possibility of tuberculosis. The challenges are the difficulty to interpret these tests in an endemic area of TB and the necessity to perform anti-PR3 and anti-MPO by ELISA/blot method to confirm the diagnosis.
Another probable diagnosis is sarcoidosis. But the absence of mediastinal lymph nodes and typical clinical and ophthalmic features suggests that sarcoidosis is less likely. However, serum ACE level assessment excluded the possibility in the current case.
As per the 2012 Revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides, the present case cannot be classified as any of the specific vasculitis groups.5 The criteria for the classification of ANCA-associated vasculitis is the presence of necrotizing vasculitis with a few or no immune deposits, predominantly affecting small vessels (i.e., capillaries, venules, arterioles, and small arteries), and associated with myeloperoxidase (MPO) ANCA or proteinase 3 (PR3) ANCA. Not all patients with ANCA vasculitis should be positive for ANCA. Hence it is important to add a prefix indicating ANCA reactivity in the diagnosis, e.g., MPO-ANCA, PR3-ANCA, and ANCA negative. A biopsy assessment was necessary to evaluate the fulfillment of the aforementioned criteria, but it was not accessible. Hence, it is difficult to categorize the current case as ANCA-associated vasculitis and can be grouped as unclassifiable ANCA-positive vasculitis.
Final Diagnosis
ANCA-positive, unclassified vasculitis
Follow-up
The patient is managed with a small dose of steroids and azathioprine. The patient showed significant improvement in musculoskeletal and eye symptoms.
Learning points
- Vasculitis may present with isolated eye manifestations and need a detailed clinical and laboratory workup.
- It is paramount to distinguish TB mimicry from ANCA-associated vasculitis.
- It is preferable to perform ANCA by both IF and blot to confirm the specificity.
References
- Pagnoux C, Seror R, Henegar C, Mahr A, Cohen P, Le Guern V, et al. Clinical features and outcomes in 348 patients with polyarteritisnodosa: a systematic retrospective study of patients diagnosed between 1963 and 2005 and entered into the French Vasculitis Study Group Database. Arthritis Rheum. 2010 Feb;62(2):616–26.
- Pakrou N, Selva D, Leibovitch I. Wegener's granulomatosis: ophthalmic manifestations and management. Semin Arthritis Rheum. 2006 Apr;35(5):284–92.
- Flores‐Suárez LF, Cabiedes J, Villa AR, Woude FJ van der, Alcocer‐Varela J. Prevalence of antineutrophil cytoplasmic autoantibodies in patients with tuberculosis. Rheumatology. 2003 Feb 1;42(2):223–9.
- Teixeira L, Mahr A, Jaureguy F, Noël L-H, Nunes H, Lefort A, et al. Low seroprevalence and poor specificity of antineutrophil cytoplasmic antibodies in tuberculosis. Rheumatology (Oxford). 2005 Feb;44(2):247–50.
Jennette JC, Falk RJ, Bacon PA, Basu N, Cid MC, Ferrario F, et al. 2012 Revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis & Rheumatism. 2013 Jan 1;65(1):1–11.
