Polyarteritis Research Articles

An Atypical Case of Hepatitis B-Associated Vasculitis

One of the many extra-hepatic manifestations of hepatitis B virus (HBV) infections is vasculitis. While the classic HBV-associated vasculitis is polyarteritis nodosa, other vasculitides have been reported. The authors present an atypical case of acute HBV-associated vasculitis in a 57-year-old male with tobacco use disorder, characterised by extremity ischaemia, gangrene, splenic infarction, and positive proteinase-3 antibodies without sinopulmonary, gastrointestinal, or renal disease. The aggressiveness of the patient’s disease necessitated pulse-dose corticosteroids, cyclophosphamide, and two courses of plasmapheresis, and ultimately required multiple amputations of fingers and toes.

P19 Our experience diagnosing and treating deficiency of adenine deaminase 2 (DADA2) vasculitis

Abstract Introduction Deficiency of adenine deaminase 2 (DADA2) is caused by biallelic pathogenic variants in the gene on chromosome 22q11. It is autosomal recessive with incomplete penetrance, and a variable presentation. It typically manifests as a systemic vasculopathy with early onset strokes, cutaneous manifestations, immunodeficiency and cytopenia. Traditional immunosuppressants have limited efficacy, but vasculitic manifestations have been reported to respond to biologic TNF-inhibitors. We report a patient with confirmed ADA2 deficiency whose cutaneous manifestations were previously classified as Sneddon syndrome. After a period of stability on adalimumab she developed marked cutaneous ulceration that healed following a therapy switch to intravenous infliximab. Case description We report a 39-year-old female with a long clinical history that started in childhood when she developed Diamond-Blackfan anaemia that went into remission following corticosteroid treatment and transfusions. In 2006, she suddenly had two thalamic infarcts and was thoroughly investigated but was found to have unremarkable vascular imaging, a negative antiphospholipid syndrome and autoantibody testing, a modestly elevated CRP (5-15 mg/L) and a notably persistent low serum IgM. She continued to experience frequent migraines associated with transient sensorimotor symptoms. Subsequently, she developed recurrent botchy, polymorphic macular eruptions on the lower limbs. A deep cutaneous biopsy demonstrated lymphocytic predominant perivascular inflammation of deep dermal vessels associated with thrombus formation and endothelial proliferation. A putative diagnosis of Sneddon’s syndrome was made. However, after the subsequent identification of ADA2-deficiency vasculitis, the patient underwent genetic screening which identified a compound heterozygosity for two novel ADA2 mutations (c6634_636, delTTC (p.Phe212del) and c.1225C>T (p.Pro409Ser)). Her mother was as a carrier. She was started on adalimumab injections to which she had a good clinical response with improved cutaneous disease and no further neurological symptoms. However, after two years of disease stability, she then developed a significant ‘punched out’ ulcer on the mid-calf which was painful and increasing in size to a maximum of 2 x 3 cm. Dermatology colleagues were reluctant to re-biopsy due to a high likelihood of non-specific appearances and increased risk of poor healing leading to worsening ulceration. Drawing on experience from rheumatoid arthritis that a switch in anti-TNF biological will often restore efficacy following secondary non-response to adalimumab; we empirically switched treatment to intravenous infliximab, with a reducing course of prednisolone (40mg per day tapering to 5mg after 12 weeks). This was associated with a notable improvement within one month and a complete healing of the ulcer within 4 months. Discussion DADA2 remains a rare condition with a carrier frequency estimated at 1 in 236 persons worldwide and a predicted disease prevalence of approximately 1 in 222,000 persons. Patients with DADA2 who have haematological manifestations tend to present during early infancy, whereas delayed presentation is common in patients with vasculitis and systemic inflammation. It should be suspected in patients with early onset strokes, livedo and other haematological and immunological features. Additionally, many previously diagnosed cases of Sneddon syndrome may in fact have DADA2, with a low IgM level favouring the later. Diagnosis can be confirmed by genetic studies or by a biochemical assay that demonstrates near-absent levels of ADA2 activity in the plasma or serum. Interestingly, on screening of adult patients with polyarteritis nodosa (PAN) 3.4% possessed biallelic pathogenic ADA2 variants and similarly, in genomic survey of patients with Diamond-Blackfan anaemia 2% possessed biallelic pathogenic ADA2 variants in the absence of the ribosomal protein gene mutations associated with it. Treatment is phenotype based with a preference for lifelong TNF inhibitor and biosimilar use in those with vasculitis and/or systemic inflammation, though not currently commissioned for this indication. Glucocorticoids, disease-modifying antirheumatic drugs, and other biologic agents may partially ameliorate systemic inflammation. Unfortunately, they are all ineffective for severe hematologic manifestations and hematopoietic cell transplantation (HCT) is currently the only treatment option. Treating asymptomatic patients and mildly symptomatic patients picked up on screening remains senior clinician led on a risk benefit basis. Disease activity is clinically monitored with an overall mortality rate estimated at 8%. Key learning points The main learning points for me included an increased awareness of this syndrome, its variable presentation, association with other autoimmune illnesses, diagnosis, and treatment initiation. In addition, I learnt about screening of family members, weighing the benefits versus risks when considering treating mildly symptomatic and asymptomatic patients, clinical monitoring for response, and when to switch to other anti-TNFs and biosimilars. From this conference, I would like to explore the experience of our rheumatology colleagues with similar cases.

Cerebral Aneurysms and Recurrent TIAs in a 42-Year-Old Patient With DADA2 Mutation: A Case Report.

Deficiency of adenosine deaminase 2 (DADA2) is a rare, recessively inherited autoinflammatory disease with a wide clinical spectrum of manifestations, including strokes and vasculitis. We report a case of a patient with DADA2 who presented with neurologic manifestations. A 42-year-old woman with a known diagnosis of polyarteritis nodosa experienced several episodes of TIAs. Neuroimaging revealed 2 aneurysms in unusual locations. Her young age, ethnic origin, absent of cardiovascular risk factors, and skin involvement raised the suspicion of DADA2. Genetic testing confirmed the diagnosis, and a directed treatment with anti-TNF was initiated. DADA2, although thought to be rare, needs to be borne in mind when evaluating patients with a combination of neurologic and systemic symptoms, as early diagnosis and treatment are imperative in preventing permanent disability.

Polyarteritis Nodosa is a Medium-Sized Negative ANCA Vasculitis which is Frequent in Patients who Suffer Hepatitis B

Polyarteritis Nodosa is a Medium-Sized Negative ANCA Vasculitis which is Frequent in Patients who Suffer Hepatitis B

E37 Clinical and demographic criteria of Juvenile primary systemic vasculitis in Libyan Children

Abstract Introduction Primary vasculitis syndromes are rare in childhood. The clinical manifestations depend on the vessels involved and can lead to significant mortality and morbidity. Aim To study demographic and clinical characteristics of patients with diagnosed with vasculitis other than Kawazaki disease and Henoch-Schonlein purpora (HSP) and to report the outcome of the patients. Materials and methods This is a case series conducted by reviewing the files of patients diagnosed with vasculitis and followed up at the pediatric rheumatology unit of the Tripoli Children Hospital, Libya from year 2000–2022. Data regarding patients’ demography, time of diagnosis, clinical features, laboratory results, treatment and complications were retrieved. Results A total of 37 cases included in the study. 17 (45.9%) were males and 20 (54%) were females followed up for a mean period of 4.48 ± 4.21. Mean age at diagnosis was 8.39 ± 3.84 years. Regarding the diagnosis, there were 3 (8.1%) patients with Takayasu arteritis, 5 (13.5%) patients with polyarteritis nodosa, 2 (5.4%) patients with cutaneous polyarthritis nodosa, 1 (2.7%) patients with granulomatosis with polyahgitis, 1 (2.7%) patient with microscopic polyangiitis, 3 (8.1%) patients with Chrug-Strauss disease, 16 (43.2%) patients with Behcet disease, 1 (2.7%) patients with cogan syndrome, 3(8.1%) patients with urticarial vasculitis, 1 (2.7%) patient with hypocomplementaemic vasculitis, and 1 (2.7%) patient with DADA2. Mean period between the start of symptoms and diagnosis was 1.4 ± 2.8 years. In 6 (16.2%) of the patients there was family history of vasculitis and in 11 (29.7%) the parents are consanguineous. Angiography revealed abnormalities in 5 (13.5%) of the patients. Skin biopsy was done in 4 (10.8%) patients [2 patients with polyarthritis nodosa and 2 patients with urticarial vasculitis] and renal biopsy was done in 1 (2.7%) patient. Steroid was used in 24 (64.9%), Azathioprine in 4 (10.8%) patients. Cellcept was used in 10 (27%) of the patients. Ciclosporin was used 1(2.7%) patient, cyclophosphamide in 3 (8.1%) patients and Immunoglobulin in 6 (16.2%) of patients. Biologics were used in six patients, adalimumab in one patient which was discontinued because of recurrent abscess. In the two patients who used infliximab, treatment was effective. Three patients were treated with tocilizumab, it was ineffective in two, therefore discontinued. However, tocilizumab was effective in one patient with Takayasu arteritis. Complications developed in 23 (62.2%). Muscle atrophy in 1, deforming arthritis in 1, osteoporosis in 1, mouth ulcers in 2, hypertension in 2, hearing loss in 1, chronic sinusitis in 1, cardiovascular accident in 1, cataract in 1, visual impairment in 3, proteinuria in 2, pulmonary fibrosis in 1, chronic asthma in 3, impaired renal function in 1. Conclusion This is the first report of pediatric vasculitis cases in Libya. It showed a heterogeneous spectrum of vasculitis with high rate of consanguinity and low rate of reported family history of vasculitis. Hopefully this report will increase awareness among clinicians of vasculitis and more cases will be diagnosed.

Clinical features and long-term outcomes of patients with systemic polyarteritis nodosa diagnosed since 2005: Data from 196 patients

BackgroundThe landscape of polyarteritis nodosa (PAN) has substantially changed during the last decades. Recent data regarding causes, characteristics, and prognosis of systemic PAN in the modern era are lacking. MethodsThis retrospective study included patients with systemic PAN referred to the French Vasculitis Study Group between 2005 and 2019. Characteristics, associated conditions and outcomes were collected, and predictors of relapse and death were analyzed. Results196 patients were included. Main clinical symptoms were constitutional (84%), neurological (59%), skin (58%) and musculoskeletal (58%) manifestations. Secondary PAN accounted for 55 (28%) patients, including myelodysplastic syndrome (9%), solid cancer (7%), lymphoma (4%) and autoinflammatory diseases (4%). No patient had active HBV infection. All treated patients (98.5%) received glucocorticoids (GCs), alone (41%) or in combination with immunosuppressants (59%), with remission achieved in 90%. Relapses were independently associated with age >65 years (HR 1.85; 95% CI1.12–3.08), gastrointestinal involvement (1.95; 95% CI1.09–3.52) and skin necrotic lesions (HR 1.95; 95%CI 1.24–3.05). One-, 5- and 10-year overall survival rates were 93%, 87% and 81%, respectively. In multivariate analyses, age >65 years (HR 2.80; 95%CI 1.23–6.37), necrotic purpura (HR 4.16; 95%CI 1.62–10.70), acute kidney injury (HR 4.89; 95% 1.71–13.99) and secondary PAN (HR 2.98; 95%CI 1.29–6.85) were independently associated with mortality. ConclusionLandscape of PAN has changed during the last decades, with the disappearance of HBV-PAN and the emergence of secondary PAN. Relapse rate remains high, especially in aged patients with gastrointestinal and cutaneous necrosis, as well as mortality.

Kawasaki disease or polyarteritis nodosa: coronary involvement, a diagnostic conundrum.

Polyarteritis nodosa (PAN) is a medium-vessel vasculitis presenting with cutaneous and multisystem involvement with considerable morbidity. The necrotizing vasculitis in PAN typically involves renal, celiac, and mesenteric vascular beds. Coronary artery involvement is a characteristic feature of Kawasaki disease, another medium-vessel vasculitis; however, it has been rarely reported with PAN. Here, we present 2 cases with PAN involving coronaries mimicking Kawasaki disease. A 3.5-year-old boy with classical features of Kawasaki disease with giant coronary aneurysm refractory to IVIg, methylprednisolone, infliximab presented with persistent rise in inflammatory markers and gastrointestinal bleeding. Digital subtraction angiography (DSA) revealed celiac artery branches stenosis and beading suggestive of PAN. Another 2-year-old girl presented with persistent fever, abdominal pain, and distension. She had hypertension, hepatomegaly, and splenomegaly on examination. Echocardiography revealed multiple coronary aneurysms and DSA revealed numerous renal artery aneurysms. Coronary aneurysm although is a rare presentation of childhood PAN, and can mimic Kawasaki disease. Although both are medium-vessel vasculitis differentiation between these two entities is pivotal, as there are differences in treatment modalities, duration of immunomodulatory therapy, and the outcome. This manuscript describes the salient differences which can help differentiate PAN masquerading as Kawasaki disease at initial presentation.

Polyarteritis Nodosa: Gangrene in a Rheumatoid Arthritis Patient.

A 67-year-old Japanese woman with rheumatoid arthritis of 30 years duration presented with digital gangrene (Fig. 1) and diarrhea. The conventional angiography showed a left medial plantar artery aneurysm (an arrow, Fig. 2A), a left renal artery aneurysm (an arrow, Fig. 2B), and an ileocolic artery aneurysm (an arrow, Fig. 2C). Based on her symptoms and the results of the conventional angiography, she was diagnosed with polyarteritis nodosa. Gangrene of the lower limb in a patient with rheumatoid arthritis might suggest rheumatoid vasculitis or arterial occlusive disease, but both were unlikely due to the negative rheumatoid factor and the absence of atherosclerosis on computed tomography. Polyarteritis nodosa is typically a medium-sized vasculitis with visceral artery aneurysms, but microaneurysms may not be detectable on computed tomography or magnetic resonance imaging. In such cases, it may be advisable to perform conventional angiography to diagnose before organ damage occurs.FIGURE 1: Digital gangrene.FIGURE 2: The conventional angiography: (A) a left medial plantar artery aneurysm, (B) a left renal artery aneurysm, and (C) an ileocolic artery aneurysm.DIFFERENTIAL DIAGNOSIS Rheumatoid vasculitis, arterial occlusive disease, granulomatosis with polyangiitis, Behçet syndrome

#2663 KIDNEY INVOLVEMENT IN MYELODYSPLASTIC SYNDROMES

Abstract Background and Aims Myelodysplastic syndromes (MDS) are hematologic disorders characterized by ineffective and dysplastic hematopoiesis that can be associated with systemic inflammatory and autoimmune diseases. The objective of this study was to describe kidney involvement in MDS patients, their treatments, and outcomes. Method We conducted a French and American multicenter retrospective observational study in nine centers, identifying MDS patients with acute kidney injury (AKI), chronic kidney disease (CKD), and urine abnormalities. Results Seventeen patients (males n = 11, median age 76 [70-79]) developed a kidney disease 6 months [0-31] after the diagnosis of MDS. Median urinary protein to creatinine ratio was 1.9g/g [0.8-3.3], and median serum creatinine was 3.5mg/dL [1.5-4.7]. Twelve patients (70%) had AKI at presentation, and 14 (82%) extra-renal symptoms, which consisted mostly in cutaneous and pneumological manifestations. The renal diagnoses included antineutrophilic cytoplasmic antibody (ANCA) associated vasculitis (AAV) (n = 8, 47%), ANCA negative vasculitis (n = 4, 24%), C3 glomerulonephritis (n = 2), immune complex-mediated glomerulonephritis (n = 1), polyarteritis nodosa (n = 1), and IgA vasculitis (n = 1). Kidney biopsies were performed in 10 of the cases. All patients, except one, received a treatment following the MDS-associated kidney injury (n = 16, 94% with steroids). The effect of MDS treatment on kidney injury could be assessed in 8 patients treated with azacitidine, and renal function evolution was heterogenous. After a median follow-up of 9 months [4.1-14.2], 4 patients had CKD stage 3, 4 CKD stage 4, 5 an end stage kidney disease. Three patients evolved to an acute myeloid leukemia (AML), and 3 died. Compared to 84 MDS controls, patients who had a kidney involvement were younger (p = 0.03), had a higher number of dysplasia lineages (3 lineages, p = 0.001), and were more eligible to receive hypomethylating agents (p = 0.031), but no survival difference was seen between the two groups (p = 0.5227). Compared to 265 AAV without MDS, MDS-associated AAV were older (p = 0.019), ANCA serology was more frequently negative (p = 0.014), and more cutaneous lesions were seen (p = 0.003). Conclusion The spectrum of kidney injuries associated with MDS is mostly represented by vasculitis, and especially AAV. A diagnosis of ANCA vasculitis in an elderly patient, or with a cutaneous manifestation, or without ANCA positivity, should lead to the search for a possible MDS.

Intraperitoneal hemorrhage secondary to ruptured omental artery aneurysm associated with polyarteritis nodosa: a case report

BackgroundPolyarteritis nodsa (PAN) is a rare disease characterized by acute focal inflammatory damage to small and medium arteries. PAN complicated by ruptured aneurysm is an infrequent presentation with the most affected arteries being the renal and mesenteric arteries.Case presentationA 76-year-old female presented with a low-grade fever, generalized body aches, and abdominal pain. Investigation revealed intraperitoneal bleeding secondary to a ruptured and actively bleeding right omental artery aneurysm. Clinical manifestation, angiography and histology were consistent with PAN. Laparotomy was performed for stabilization and resection of the bleeding aneurysm followed by post operative steroids and cyclophosphamide. Patient was discharged in a stable condition. We reviewed seven cases found in the literature of omental artery aneurysm and rupture. Four cases were proceeded with laparotomy and aneurysm resection while three cases were proceeded with a less invasive approach of arterial embolization.ConclusionsOmental artery aneurysm is a rare occurrence with even fewer reported cases associated with PAN. Of the seven reported cases, all patients were treated with a surgical intervention. In addition, PAN patients should be treated post-operatively with a course of steroids and cyclophosphamide.

Autoimmune disease and new-onset atrial fibrillation: A UK Biobank study

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Senior Scientist Grant from the Dutch Heart Foundation. Background and Aims The underlying mechanisms of atrial fibrillation (AF) are largely unknown. Inflammation may underlie atrial remodeling. Autoimmune diseases, and their accompanying increased (systemic) inflammation, may therefore be associated with new-onset AF. Purpose To assess the association of various autoimmune diseases with new-onset AF in the general population. Additionally, we aimed to investigate the causal relationship between the aforementioned conditions. Methods Participants from the population-based UK Biobank were screened for rheumatic fever, gastrointestinal autoimmune diseases, autoimmune diseases targeting the musculoskeletal system and connective tissues, and neurological autoimmune diseases. Between 2006 and 2022, participants were followed for incident AF. Cox proportional hazards analyses were conducted to calculate hazard ratios (HR) and 95% confidence intervals (CI) to quantify the associations. Moreover, using large publicly available summary data of genome-wide association studies, two-sample Mendelian randomization (MR) analyses, inverse variance weighted method, were performed to assess the potential causality between the genetic predisposition to various autoimmune diseases and AF. Further sensitivity analyses in the form of weighted median estimator, MR-Egger, and MR-PRESSO were performed. Results 494,072 participants free from AF at baseline were included (median age 58.0 years, 54.8% women). After a median of 12.8 years, 27,194 (5.5%) participants were diagnosed with new-onset AF. Rheumatic fever without heart involvement (HR, 95%CI: 1.47, 1.26-1.72), Crohn’s disease (1.23, 1.05-1.45), ulcerative colitis (1.17, 1.06-1.31), rheumatoid arthritis (1.39, 1.28-1.51), polyarteritis nodosa (1.82, 1.04-3.09), systemic lupus erythematosus (1.82, 1.41-2.35), and systemic sclerosis (2.32, 1.57-3.44) were associated with a larger AF risk. In sex-stratified analyses, rheumatic fever without heart involvement, multiple sclerosis, Crohn’s disease, seropositive rheumatoid arthritis, psoriatic and enteropathic arthropathies, systemic sclerosis and ankylosing spondylitis were associated with larger AF risk in women, whereas only men showed a larger AF risk associated with ulcerative colitis. Two-sample MR analyses showed no significant associations between any of the included autoimmune diseases and AF. Conclusions Various autoimmune diseases are associated with new-onset AF, more distinct in women. Lack of causal associations between autoimmune diseases and AF could suggest that inflammation itself, rather than the autoimmune disease, is the major risk marker for incident AF. Our findings further elaborate on the pathophysiological differences in autoimmunity and AF risk between men and women.

Childhood rheumatic diseases: bites not only the joint, but also the heart.

Cardiovascular involvement in juvenile rheumatic diseases is the primary manifestation in paediatric vasculitis and a major organ manifestation in paediatric connective tissue diseases. Though coronary vasculitis is the prototypical manifestation of Kawasaki disease, it can also be seen in patients with polyarteritis nodosa. Pericarditis is the most common manifestation seen in juvenile rheumatic diseases like systemic onset JIA, and lupus. Cardiac tamponade, valvular insufficiency, aortic root dilatation and arrhythmias are seen rarely. Cardiac involvement is often recognized late in children. The development of cardiac disease in juvenile systemic sclerosis is associated with a poor outcome. In long term, childhood onset of rheumatic diseases predisposes to diastolic dysfunction and premature atherosclerosis during adulthood. Key Points • Pericarditis is the most common cardiac manifestation in SLE and can lead to tamponade. • Conduction defects are common in juvenile mixed connective tissue disease and systemic sclerosis. • Pulmonary hypertension is a significant contributor to mortality in juvenile systemic sclerosis. • In Kawasaki disease, early treatment can reduce risk of coronary artery aneurysms.

Cutaneous arteritis: Clinicopathological study of 21 cases

AbstractObjectivesWe conducted this study to clarify the progress of cutaneous arteritis.MethodsWe examined 21 cases of cutaneous arteritis that were diagnosed at our hospital between 2005 and 2020. The male‐to‐female ratio was 1:6 with a mean age of 52.2 years.ResultsThe lower legs were involved in all cases, and the upper extremities or trunk was also involved in some cases. Cutaneous manifestations presented as indurated erythema (n = 15), subcutaneous induration (11), edema (7), livedo (6), and ulcer (3). In addition, extracutaneous conditions including numbness (10), arthritis (8), fever (2), and myalgia (1) were observed. Laboratory tests showed an increase of inflammatory markers in most cases (14). Histopathological features showed necrotizing vasculitis of small‐sized arteries at the dermo‐subcutaneous junction, and the inflammatory stages of arteritis were histopathologically divided into acute stage (5), subacute stage (5), reparative stage (7), and healed stage (1). The therapies administered were oral prednisolone (11), antiplatelet drug (14), warfarin (1), non‐steroidal anti‐inflammatory drugs (6), biological drug (1), and other drugs (14). There were no cases showing progression to systemic polyarteritis nodosa during follow‐up period. All three patients with ulceration complained of numbness, and one was revealed to have mononeuropathy multiplex. They were treated with low‐dose oral prednisolone. Three ulceration cases were histopathologically classified into the acute and subacute stages.ConclusionsIn conclusion, all 21 patients followed a chronic course with recurrent skin lesions without systemic complications. Cases with ulceration seem to reveal neurological symptoms and need systemic steroid treatment.

E017 ANCA-associated but not vasculitis

Abstract Background/Aims A 72-year-old lady presented in primary care with complaints of generalised body aches, bilateral leg weakness and constitutional symptoms following a first dose of COVID-19 vaccine. Blood tests showed slightly raised inflammatory markers. She was initially diagnosed with polymyalgia rheumatica and was started on 40 mg prednisolone with minimal improvement. Methods The examination in the rheumatology clinic was unremarkable. Investigations revealed raised white cell count, consistent with high dose steroid treatment, and elevated monocytes. There was mild improvement in inflammatory markers. The working diagnosis was of self-limiting viral illness. Further testing discovered strongly positive MPO ANCA (115 IU/ml), and the patient received three pulses of 500 mg methylprednisolone for suspected vasculitis arranged by the medical team. There was no evidence of renal involvement. The diagnosis made at this point was autoimmune inflammatory disorder with unclear aetiology. At the subsequent clinic visit she reported mild shortness of breath, but no other symptoms suggestive of either vasculitis or connective tissue disease. Repeat ANCA showed significant reduction in MPO titre following pulse steroid treatment. CT of chest, abdomen and pelvis demonstrated a localised lobular/nodular deformity of the liver. Viral hepatitis screen was negative. CA19-9 was raised at 100 U/ml. Liver biopsy was reported as poorly differentiated carcinoma without specific localising immunohistochemical features. Results The patient underwent hemi-hepatectomy for histologically confirmed pT2pNXM0R0 liver cholangiocarcinoma in a tertiary centre followed by adjuvant chemotherapy with capecitabine. With treatment, her MPO ANCA and CA19-9 levels declined. An interval CT scan of chest, abdomen and pelvis performed ten months after the surgery, showed no recurrence of malignancy. Given the fact that the patient’s MPO ANCA fell following the treatment of cholangiocarcinoma, it is likely that positive MPO ANCA is associated with underlying malignancy rather than an active vasculitis. Conclusion This unusual case describes an evolution of the diagnostic process guided by non-specific symptoms and ANCA positivity, arriving at an unexpected diagnosis of malignancy. Although ANCA is a sensitive and specific marker of vasculitides, it can be positive in other conditions particularly hepatitis B, inflammatory bowel disease and autoimmune liver disorders. Malignancy can also be associated with ANCA in the absence of vasculitis. In one study, of 118 ANCA positive patients without ANCA-associated vasculitis, four were found to have malignancy. In a study of 1024 patients who had ANCA tested, 61 patients were found to have malignancy, predominantly haematological and lung cancers. However, after adjustment for sex, age and time of blood draw, no association was found between ANCA status and incidence of cancer. Interestingly, paraneoplastic vasculitis such as polyarteritis nodosa (PAN) has been described in the context of underlying cholangiocarcinoma, and is associated with ANCA rise. Moreover, patients with raised ANCA and PAN also have raised CA 19-9. Disclosure V. Saulite: None. S. Dahiya: None.

E032 Deficiency of Adenosine Deaminase 2: a rare diagnosis in a case of suspected vasculitis

Abstract Background/Aims Deficiency of adenosine deaminase 2 (DADA2) is a rare autosomal recessive condition first described in 2014 which is characterised by vasculitis, systemic inflammation, immunodeficiency and cytopenias. The vasculitis is difficult to differentiate from polyarteritis nodosa and typically presents with recurrent strokes. It can also affect the skin and present with livedo racemosa. Clinical presentation varies widely; from vasculitic manifestations which tend to present later in life to severe haematological abnormalities such as bone marrow failure which tend to present earlier in life. Treatment with TNF inhibitors reduces the risk of additional strokes and controls inflammation in the presence of vasculitis but is not very effective against bone marrow failure. Methods We present the case of a 44-year-old gentleman who was being investigated for possible vasculitis by the rheumatology team in view of a history of Raynaud’s, 20-year history of recurrent leg ulcers and a previous pontine infarct. He presented acutely to the emergency department with numbness below the midthoracic level, weakness of his lower limbs and hands and urinary retention. His symptoms had progressed over a period of a few hours. On examination power was 4/5 on the MRC power scale for shoulder abduction and elbow flexion, 2/5 for elbow extension, 3/5 for wrist extension and 1/5 for finger extension. Power was 1/5 on his lower limbs. Sensation to pain was reduced with a T6 sensory level. Proprioception and vibration sense were intact. Upper limb reflexes were brisk. Knee jerks and left ankle jerk were difficult to elicit. Plantars were downgoing. Cranial nerves were normal. Results Bloods showed a white cell count of 6.7x109/l, haemoglobin of 96g/l (microcytic), platelets of 243x109/l, creatinine 119μmol/l (baseline 85μmol/l) and CRP of 42.9mg/l. Vitamin B12 was 200ng/l and folate levels were 2.2μg/L. ANA, ANCA, cryoglobulins and hepatitis serology were negative. MRI brain showed a 4mm area of hyper-density in the left pons. MRI whole spine was unremarkable. CSF showed normal protein, white cell count and glucose level. The patient was transferred to a tertiary neurology centre and a diagnosis of anterior spinal cord infarction was made. A nerve biopsy was performed which showed evidence of vasculitis and he was pulsed with methylprednisolone and commenced on high dose oral steroids. Genetic testing showed a pathogenic mutation in the adenosine deaminase 2 gene. He is currently awaiting to commence treatment with TNF inhibitors. Conclusion We conclude that DADA2 is an important differential in a young patient with suspected vasculitis especially in the presence of infarction. Identification of DADA2 allows initiation of treatment with TNF inhibitors which reduces the risk of additional strokes. Disclosure M. Xenophontos: None. J. Gan: None. A.C. Seneviratne: None.

P024 Vasculitis of the female genital tract: is it a single organ or systemic disease?

Abstract Background/Aims Vasculitis of the female genital tract is rare. At one institution, incidence among all gynaecological surgeries was 0.15%. It is usually an incidental finding on histopathological examination after surgery done for another reason. Most commonly, it presents with vaginal bleeding, but can also present with pelvic pain, uterine prolapse, asymptomatic abdominal mass or atypical cervical smear. Constitutional and musculoskeletal symptoms are reported in about a quarter of cases. It can be localised to the female genital tract, most commonly the uterus and cervix. Less commonly, it can be part of a systemic vasculitis, including giant cell arteritis, polyarteritis nodosa, granulomatosis with polyangiitis, microscopic polyangiitis, cryoglobulinaemic vasculitis, lupus and rheumatoid vasculitis. Although data is limited, one review found 31.3% of cases to have systemic involvement. Approximately 60% of patients with vasculitis of the female genital tract and systemic vasculitis had GCA. In this group, about one third do not present with classical cranial, systemic or polymyalgia rheumatica symptoms. In localised disease, anaemia or raised inflammatory markers are unlikely. Histopathology mostly shows non-granulomatous inflammation. With systemic involvement, anaemia, raised inflammatory markers and granulomatous inflammation are more likely to be present. Localised vasculitis of the female genital tract tends not to require treatment. However, it can predate symptoms and signs of systemic disease. Therefore, follow-up for at least 12 months is recommended. Methods Written consent was obtained from the patient. Data was obtained from the patient's case notes, electronic records and histopathology results. Results We describe a 63-year-old lady with no past medical history and on no medications who presented with post-menopausal bleeding and abdominal cramping. Hysteroscopy showed two endometrial polyps. Biopsy showed grade 1A endometrial carcinoma. Total hysterectomy and bilateral salpingo-oophorectomy was performed. Histopathological analysis confirmed endometrial cancer but also showed some foci of granulomatous inflammation with multi-nucleating giant cells surrounding both small and medium calibre vessels. The vessels showed fibrinoid necrosis and disruption of the internal elastic lamina, suspicious for vasculitis. On review by the rheumatology team this lady was found to be well with no history of Raynaud’s; rashes; arthritis; ocular; ear, nose and throat; gastroenterological; respiratory; neurological; or constitutional symptoms. Examination was normal. C-reactive protein and immunoglobulins were normal. Anti-nuclear antibody, anti-neutrophil cytoplasmic antibody, rheumatoid factor and anti-CCP antibody were negative. Urine protein was raised at 0.29 (0-0.1) but protein/creatinine ratio was normal at 11 mg/mmol. Chest x-ray was clear. Conclusion In conclusion, female genital tract vasculitis is rare and is usually an incidental finding on histopathology. In this case, it appeared to be an isolated vasculitis of the female genital tract. It is important to recognise that uncommonly this condition can be associated with systemic involvement and therefore follow up in rheumatology clinic is recommended. Disclosure T. Nadin: None. N. Goadby: None. R. Smith: None.

Tofacitinib as monotherapy in cutaneous polyarteritis nodosa: a case series.

Cutaneous polyarteritis nodosa (CPAN) is a distinct clinical entity represented by a chronic, relapsing, benign course, with rare systemic involvement. Treatment is with CSs, CYC or other conventional synthetic DMARDs (csDMARDs). In this case series, we aimed to share our varied clinical experience of successfully treating patients with CPAN, with tofacitinib in a refractory/relapsing course or as upfront monotherapy without CSs/csDMARDs. We report this retrospective case series managed at our rheumatology centre in Bangalore from 2019 to 2022. Four patients identified as CPAN on biopsy were able to achieve disease-free remission with tofacitinib as part of their treatment, with no relapse on further follow-up. Our patients presented with subcutaneous nodules and cutaneous ulcers. After systemic evaluation, all the patients underwent skin biopsy, which showed fibrinoid necrosis in the vessel walls of the dermis, with a histopathological impression of CPAN. They were initially treated with a conventional approach of CSs with/without csDMARDs. On experiencing a refractory/relapsing course, tofacitinib was tried in all the patients as either CS sparing or upfront monotherapy without concomitant csDMARDs. Use of tofacitinib resulted in improvement of ulcers and paraesthesia and in gradual healing of skin lesions, albeit with scarring, with no further recurrence or relapse over a follow-up period of 6 months for all the patients. The therapeutic effect of tofacitinib was consistent when used either as CS sparing or as upfront monotherapy, thereby proving the drug to be a promising option that warrants larger trials in future to treat the subset of patients with established CPAN. Tofacitinib could be used for disease-free remission as monotherapy for CPAN either upfront or as CS sparing, even without concomitant csDMARDs, in those patients who are dependent on CSs or multiple DMARDs.

Analysis of the clinical course, complications and causes of mortality at the onset of the primary necrotizing systemic vasculitis

BACKGROUND: Primary necrotizing systemic vasculitis is a significant problem of practical healthcare due to a severe progressive clinical course and a high risk of complications, including life-threatening damage.
 AIM: To evaluate the features of the clinical course of primary necrotizing systemic vasculitis during the first 3 years of the disease.
 MATERIALS AND METHODS: The study included 232 patients with primary necrotizing systemic vasculitis, who were hospitalized in Saint Petersburg clinics from 2010 to 2018. The features of the clinical course, complications, causes of mortality during the first 3 years of the disease were assessed.
 RESULTS: The cohort of patients with рrimary necrotizing systemic vasculitis consisted of patients with granulomatosis with polyangiitis (n = 94), microscopic polyangiitis (n = 46), eosinophilic granulomatosis with polyangiitis (n = 69), polyarteritis nodosa (n = 23). The highest values of the Birmingham Vasculitis Activity Score index were noted among patients with granulomatosis with polyangiitis and microscopic polyangiitis (21.4 and 21.5 points, respectively). Patients with microscopic polyangiitis were significantly more likely to develop chronic kidney disease (C3aC5 stages) compared to other primary necrotizing systemic vasculitis (p 0.001). We established that the average value of the Vasculitis Damage Index after 36 months of the disease was highest in the group of patients with granulomatosis with polyangiitis (4.7 points) and significantly exceeded the corresponding indicator at the same period of the disease in the group of patients with microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis, polyarteritis nodosa (3.8, 2.7 and 3.1 points, respectively).
 CONCLUSIONS: The most unfavorable prognosis among primary necrotizing systemic vasculitis during the first 3 years of the disease was noted in patients with granulomatosis with polyangiitis, which is reflected in the high level of the Vasculitis Damage Index that shows the number of irreversible organ lesions.

Immunopathological features of myopathy associated with small-to-medium-sized vessel vasculitis and differences from autoimmune myositis.

Patients with systemic vasculitis may develop myalgia as an initial symptom. However, the immunopathology of vasculitic myopathy remains unclear. We investigated the immunopathological features of skeletal muscle in small-to-medium-sized vessel vasculitis. We analysed muscle tissue biopsies from 15 patients with vasculitis, including antineutrophil cytoplasmic antibodyassociated vasculitis and polyarteritis nodosa, and 15 patients with autoimmune myositis (AIM), including polymyositis and immune-mediated necrotising myopathy, as comparison disease controls. Immunohistochemical staining for CD56/neural cell adhesion molecule (NCAM), major histocompatibility complex class I, C5b-9/membrane attack complex (MAC), and CD31 was performed. The vascularity score was defined as the total number of CD31-expressing blood vessels. The association between CD56/NCAM-expressing myofibers and clinical findings was evaluated in patients with vasculitis. Patients with vasculitis had a significantly lower frequency of CD56/NCAM-expressing myofibers than those with AIM and a positive correlation between the frequency of CD56/NCAM-expressing myofibers and serum aldolase levels. Patients with vasculitis had significantly fewer major histocompatibility complex class I-expressing myofibers and C5b-9/MAC deposits on the sarcolemma than those with AIM. C5b-9/MAC deposits in blood vessels were observed in >70% of patients with vasculitis. Patients with vasculitis had significantly higher vascularity scores in the endomysium than those with AIM. Patients with vasculitis demonstrated mild myofiber damage based on the lower involvement of CD56/NCAM-expressing myofibers compared to those with AIM. Complement component deposits on the vessel walls and hypervascularity in the endomysium areas may be immunopathological features of vasculitic myopathy.

Autoimmune Diseases and Retina

Autoimmune diseases are a group of diseases that can result in organ-specific and/or systemic (systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis,...) anatomical deformation and loss of function as a result of the body's immune system attacking its own antigens under the influence of genetic and environmental factors. The eye is a potential target for complications related to autoimmunity, and depending on the severity of the immune response, vision-threatening problems can be observed. Immune complexes accumulate in and around the vessel walls as a result of humoral immunity, in which the autoantibody-related complement system is activated, and cellular immune response can lead to retinal vasculitis, vaso-occlusion, retinal hemorrhage, retinal ischemia, ischemic optic neuropathy, and inflammation of periorbital tissues. Therefore, the role of ophthalmologists in disease management is important in diagnosing, investigating, and treating ocular symptoms in a timely manner. Early diagnosis and treatment can play a critical role to decrease the risk of irreversible immunological damage to the retinal tissue. A multi-disciplinary approach for complete management and evaluation is needed in this disease group. This study aimed to provide a detailed review of the current clinical perspective for the diagnosis, workup, and treatment of autoimmune diseases with retinal manifestations. Systemic lupus erythematosus, Polyarteritis Nodosa, Dermatomyositis, Scleroderma, Wegener's Granulomatosis, Churg-Strauss Syndrome, Takayasu Arteritis, Susac Syndrome, and Nodular Panniculitis are discussed under this heading.