Query: EULAR/PRINTO/PRES criteria for Henoch-Schönlein purpura,childhood polyarteritis nodosa

title: EULAR/PRINTO/PRES criteria for Henoch Schonlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part II: Final classification criteria
abstract: To validate the previously proposed classification criteria for Henoch Schonlein purpura (HSP) childhood polyarteritis nodosa (c PAN) c Wegener granulomatosis (c WG) and c Takayasu arteritis (c TA) Methods Step 1: retrospective/prospective web data collection for children with HSP, c PAN, c WG and c TA with age at diagnosis =18 years. Step 2: blinded classification by consensus panel of a representative sample of 280 cases. Step 3: statistical (sensitivity, specificity, area under the curve and k agreement) and nominal group technique consensus evaluations.  827 patients with HSP, 150 with c PAN, 60 with c WG, 87 with c TA and 52 with c other were compared with each other. A patient was classified as HSP in the presence of purpura or petechiae (mandatory) with lower limb predominance plus one of four criteria: (1) abdominal pain; (2) histopathology (IgA) (3) arthritis or arthralgia; (4) renal involvement. Classification of c PAN required a systemic inflammatory disease with evidence of necrotising vasculitis OR angiographic abnormalities of medium /small sized arteries (mandatory criterion) plus one of five criteria: (1) skin involvement; (2) myalgia/muscle tenderness; (3) hypertension; (4) peripheral neuropathy; (5) renal involvement. Classification of c WG required three of six criteria: (1) histopathological evidence of granulomatous inflammation; (2) upper airway involvement; (3) laryngo tracheo bronchial involvement; (4) pulmonary involvement (x ray/CT) (5) antineutrophilic cytoplasmic antibody positivity; (6) renal involvement. Classification of c TA required typical angiographic abnormalities of the aorta or its main branches and pulmonary arteries (mandatory criterion) plus one of five criteria: (1) pulse deficit or claudication; (2) blood pressure discrepancy in any limb; (3) bruits; (4) hypertension; (5) elevated acute phase reactant.  European League Against Rheumatism/Paediatric Rheumatology International Trials Organisation/Paediatric Rheumatology European Society propose validated classification criteria for HSP, c PAN, c WG and c TA with high sensitivity/specificity.

title: EULAR/PRINTO/PRES criteria for Henoch Schonlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part I: Overall methodology and clinical characterisation
abstract: To report methodology and overall clinical, laboratory and radiographic characteristics for Henoch Schonlein purpura (HSP) childhood polyarteritis nodosa (c PAN) c Wegener granulomatosis (c WG) and c Takayasu arteritis (c TA) classification criteria.  The preliminary Vienna 2005 consensus conference, which proposed preliminary criteria for paediatric vasculitides, was followed by a EULAR/PRINTO/PRES supported validation project divided into three main steps. Step 1: retrospective/prospective web data collection for HSP, c PAN, c WG and c TA, with age at diagnosis =18 years. Step 2: blinded classification by consensus panel of a subgroup of 280 cases (128 difficult cases, 152 randomly selected) enabling expert diagnostic verification. Step 3: Ankara 2008 Consensus Conference and statistical evaluation (sensitivity, specificity, area under the curve, k agreement) using as 'gold standard' the final consensus classification or original treating physician diagnosis.  A total of 1183/1398 (85% samples collected were available for analysis: 827 HSP, 150 c PAN, 60 c WG, 87 c TA and 59 c other. Prevalence, signs/symptoms, laboratory, biopsy and imaging reports were consistent with the clinical picture of the four c vasculitides. A representative subgroup of 280 patients was blinded to the treating physician diagnosis and classified by a consensus panel, with a k agreement of 0.96 for HSP (95% CI 0.84 to 1) 0.88 for c WG (95% CI 0.76 to 0.99) 0.84 for c TA (95% CI 0.73 to 0.96) and 0.73 for c PAN (95% CI 0.62 to 0.84) with an overall k of 0.79 (95% CI 0.73 to 0.84) Conclusion EULAR/PRINTO/PRES propose validated classification criteria for HSP, c PAN, c WG and c TA, with substantial/almost perfect agreement with the final consensus classification or original treating physician diagnosis.

title: EULAR/PRINTO/PRES criteria for Henoch Schonlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part I: Overall methodology and clinical characterisation (Annals of the Rheumatic Diseases (2010) 69, (790 797)

title: Part II: Final classification criteria and childhood Takayasu arteritis: Ankara 2008. nodosa, childhood Wegener granulomatosis Schonlein purpura, childhood polyarteritis EULAR/PRINTO/PRES criteria for Henoch

title: AB1012 HENOCH SCHoNLEIN PURPURA AND UVEITIS, AN UNUSUAL ASSOCIATION
abstract: Henoch Schonlein purpura (HSP) is the most common childhood vasculitis characterized by cutaneous palpable purpura predominantly located in the lower limbs, arthralgia/arthritis, renal and bowel involvement. To our knowledge only 4 cases of HSP with ocular involvement have been reported so far.  We describe a 6 year old female patient who presented HSP and panuveitis.  Describe a case report.  A 6 year old female, previously in good health, received the diagnosis of HSP for cutaneous palpable purpura on her lower limbs, bilateral ankle arthritis and haematuria. Two weeks later the girl was admitted to our Emergency Department due to monolateral ocular pain with red eye. At ophthalmological assessment there was evidence of anterior uveitis with and edema of the optic disc. Blood tests showed increased values of CRP (1.92 mg/dl) and ESR (69 mm/h) with normal values of complement levels and complete blood count. Urinalysis displayed mild hematuria and proteinuria. Immunoglobulin levels were slightly increased: IgG (1850 mg/dl, n.v. 540 1330 mg/dl) IgA 244 mg/dl (n.v. 50 240 mg/dl) and IgM 72 mg/dl (n. v. 50 180 mg/dl) An extensive infectious work up for viral, bacterial and parasitic infections was negative. ANA, ANCA, ASCA, LAC, HLA B27 and B51 were all negative. Chest X ray, abdominal ultrasound and echocardiography were negative. A brain MRI with contrast revealed an iris inflammation and excluded CNS involvement. Systemic therapy was started with i.v. methylprednisolone (30mg/kg/d for three consecutive days) and continued with oral prednisone (2 mg/kg/day) with a progressive improvement of the ocular, skin, nephrological and articular involvement. Prednisone was then gradually tapered over 2 months without disease recurrence.  In our literature search we were able to find an association between HSP and uveitis only in two adults and in an 11 year old child. All these patients showed cutaneous and articular involvement and 3/4 nephrological involvement. Uveitis was observed in the first week of vasculitis onset. Although rare, the presence of ocular involvement can occur during HSP.

title: FRI0483 Sulfasalazine as a potential treatment for iga vasculitis (HENOCH SCHONLEIN PURPURA) in adults
abstract: Primary IgA vasculitis and inflammatory bowel diseases (IBD) share many clinical, endoscopic, and radiological signs. It may suggest a common pathogenetic background for both pathological conditions. While sulfasalazine (SASP) is one of the well known potential agents able to improve symptoms in IBD, the usefulness of SASP in treatment of the primary IgA vasculitis remains unclear.  Retrospective study to assess a therapeutic value of the SASP in primary IgA vasculitis.  Totally 78 adult patients with primary IgA vasculitis were enrolled in this study. Diagnosis was made on the basis of EULAR/PRES criteria1 after thorough screening to exclude a secondary nature of the disease, including colonoscopy. Purpura/petechia was present in all patients being mandatory diagnostic criterion. Arthritis/arthralgia was seen in 48 patients (61,5% There were no patients with abdominal syndrome just before enrollment, although 46 (59% patients had transient abdominal pains in the history. Mild to moderate signs of renal involvement (hematuria and/or proteinuria) was seen in 35 (45% patients without renal impairment. There were 20 (25% drug naive patients, 40 (51% patients after unsuccessful immunosuppressive treatment and 18 (23% patients failed to respond to anticoagulants or antiplatelet agents. Initially SASP was prescribed in a daily dose 1 g followed with gradual titrating up to the 2 g/day depending on tolerability and clinical response. Most patients (96% have been taking SASP longer than 6 month and about a half of the patients (56% longer than year. The longest treatment was 5 years.  Complete clinical remission of the skin rash was achieved in 48 patients (58,9% In 27 patients (35% there was partial improvement of the skin eruptions, characterised with less quantity of the skin purpura or longer periods free of symptoms (see table 1) Four patients failed to improve at all. Persistent remission of the arthritis/arthralgia was found in 41 patients (85% One patient did not improve. Complete resolution of the urinary abnormalities were registered in 14 patients (40% improvement in 17 cases (48,5% further deterioration in 4 patients (11,5% There were side effects in 13 patients (16% In 4 (5,1% cases there were headache and nausea, respectively. In 2 (2,5% cases treatment was accompanied with skin itching and urticarial rash. Most severe complication presented with reversible cytolysis, characterised with increase of AST and ALT up to the 2 5 normal limits in 3 cases (2,5%.Abstract FRI0483 Table 1 Clinical response to SASP treatment in primary IgA vasculitis (n=78) Clinical features Complete remission Partial remission No response Worsening n n n n Skin purpura (n=78) 46 58,9 27 35 4 5,1 arthritis or arthralgia (n=48) 41 85 6 13 1 1,2 hematuria and/or proteinuria) (n=35) 14 40 17 48,5 4 11,5  To our knowledge, this is the first experience of SASP in treatment of primary IgA vasculitis not reported before. Preliminary results look promising and worthy of further evaluation. Reference  Ozen S, et al. EULAR/PRINTO/PRES criteria for Henoch Schonlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part II: Final classification criteria.  Disclosure of Interest None declared

title: SAT0264 A Single Centre Experience of Childhood Polyarteritis Nodosa from North India
abstract: Polyarteritis nodosa (PAN) is a necrotizing vasculitis involving medium or small sized vessels. It is characterized by a variable clinical presentation, ranging from a benign cutaneous involvement to a more severe systemic disease with multisystem involvement  We describe clinical and laboratory features, treatment and outcome of pediatric PAN patients  A retrospective case review of all children diagnosed as PAN at a single tertiary care hospital in north India between 1990 to 2014 was done. Diagnosis of PAN was based on European League against Rheumatism (EULAR)/Paediatric Rheumatology European Society (PRES)/Paediatric Rheumatology International Trials Organisation (PRINTO) classification criteria.  A total of 16 children (12 boys and 4 girls) with PAN were identified. Median age of symptom onset and diagnosis was 8 years (range 1 11 years) and 9 years, respectively. The presenting symptoms were fever (68% CNS complaints [headache, seizures, altered sensorium, stroke or vision loss] (50% fatigue (44% myalgia (44% gangrene (31% weight loss (31% gastrointestinal complaints [pain abdomen, bleed] (31% and bluish black patches over body (19% Hypertension was present in 88% patients at admission. Various neurological manifestations were seen in 62.5% patients. Skin involvement (digital gangrene, livedo reticularis, bluish black patches, erythema nodosum or necrotic ulcer) was seen in 50% patients. Renal and gastrointestinal involvements were seen in 38% patients each. CT angiography was done in 13 patients. Aneurysmal dilatation of vessels was seen in 6 patients, while 3 patients showed features of renal infarcts. CT angiography was normal in 4 patients. In 2 such patients, digital subtraction angiography (DSA) showed aneurysmal dilatation of vessels. ANCA was positive in 4 patients (c ANCA in 3 and p ANCA in 1) HBsAg was positive in 3 patients (not treated as liver function remained normal) ASO was positive in 4 patients (2 patients were given penicillin; one patient had a relapse with high ASO titres on stopping penicillin) Two patients had only a single visit to the clinic; hence their treatment details were not available. Treatment regimen included cyclophosphamide (78% methylprednisolone pulses (43% oral prednisolone (93% maintenance azathioprine (36% and IVIg and methotrexate (14% each) Mean follow up was for 4.8 years (range 0 25 years) Five patients experienced relapses with more than 1 relapses seen in 2 patients. Relapses were noted as early as 6 months and as late as 22 years after diagnosis  We found a significant male preponderance in our cohort. Streptococcal infection can have a pathogenic role in the disease progression and relapse, and penicillin prophylaxis can prevent disease relapse in susceptible patients References Ozen S, Pistorio A, Iusan SM, Bakkaloglu A, Herlin T, Brik R, et al. EULAR/PRINTO/PRES criteria for Henoch Schonlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part II: Final classification criteria.

title: FRI0468 SYSTEMIC AND CUTANEOUS POLYARTERITIS NODOSA IN COLOMBIAN PEDIATRIC PATIENTS: CUTANEOUS POLYARTERITIS IS NOT SO BENIGN
abstract: Polyarteritis nodosa (PAN) is the third most frequent vasculitis in pediatrics, Cutaneous PAN (CPAN) being more common that Systemic PAN (SPAN) CPAN is frequently described as a benign disease. In children, PAN onset is frequent between 9 and 11 years of age, with no sex differences, and its clinical features may be nonspecific.  To characterize pediatric patients who were diagnosed with CPAN and SPAN and to compare their clinical features, treatments, and outcome.  A descriptive study was conducted in two centers from Medellin Colombia, using retrospective data from January 2010 to December 2019. Patients under 18 years of age classified as PAN according to EULAR/PRINTO/PRES(1) criteria were included. CPAN patients were defined according to EULAR/PRES definition (2) Data from medical records were registered, and were expressed in median and ranges and mean and standard deviation (SD) according to their distribution. A univariate analysis was carried out by comparing signs, symptoms, and treatment between CPAN and SPAN, and a p value  Twenty patients were included. The median age at diagnosis was ten years. 60% were boys. The median follow up period was 27 months. CPAN was diagnosed in 11 (55% and SPAN in 9 patients (45% The most frequent symptoms were cutaneous manifestations (95% fever (60% and Calf Pain (55% Mucosal ulcers were described in four patients; 3 of them were defined as CPAN. Lingual necrosis was present in two CPAN, and peripheral nervous system involvement was found in one SPAN and two CPAN patients in skin affected with lesions; even though, no significant statistical differences between CPAN and SPAN were found in constitutional, cutaneous, muscle skeletal symptoms, and acute phase reactants. Arteriographic anomalies as hepatic and renal microaneurysms, carotidal aneurysms without aortic involvement, and renal infarction were found in one patient each. Skin Biopsy was performed in 18 patients, being compatible with PAN in 16. All PAN patients (CPAN and SPAN) required treatment with glucocorticoids. None of the patients died during the follow up period.  In this Colombian pediatric cohort of PAN patients, the disease was more common in boys than girls, and CPAN was more frequent than SPAN, as already been described. As is evident in this cohort, although CPAN has been considered a benign disease, these patients may be severely ill, requiring glucocorticoid treatment. Pediatric CPAN patients should be strictly followed with particular attention to identify systemic involvement, considering that constitutional, cutaneous, and muscle skeletal features may be very similar between CPAN and SPAN.

title: AB0082 New insights to the pathogenesis of two orphan anca[ vasculitides: childhood polyarteritis nodosa and behCet disease
abstract: Vasculitides are characterized by inflammation of the vessel wall. However, we still do not know the pathogenesis of the inflammation and why they affect the target organs that they do.  The aim of this study was to study the role of TNF a, MMP9 and the balance between Th17 and Tregs in two vasculitides, polyarteritis nodosa and Behcet disease.  The study group included four patients with childhood PAN who met the classification criteria suggested by Ankara 2008, PReS/Pr into/EULAR endorsed criteria  the four BD vasculitis patients met the Lancet criteria  Blood was drawn while all patients had active disease. The control group consisted of 3 healthy individuals with a median age of 20 who were bled for routine pre operative work. The expression levels of FOXP3, IL 17, MMP9, TNF a in PBLs were analyzed using qRT PCR in patients and normal controls.  IL 17, MMP9, TNF a expressions were significantly increased compared to normal controls (p=0.0308, p=0.0022, and p=0.0127 respectively) There was no difference in the expression for FoxP3.  TNF a, a cytokine with immunomodulatory effect, has been implicated in the pathogenesis of many vasculitides. Our results implicating both TNF a and MMP9 in the pathogenesis of PAN and BD, may provide support for the use of anti TNF a. Increased levels of MMPs have been reported in other common vasculitides such as Kawasaki disease [3] and HSP  The increased expression of MMP9 among our patients highlights its role in both PAN and BD. Th17 cells, a distinct subtype of T helpers, are considered to take a major role in the pathogenesis of autoimmune and chronic inflammatory disorders  In a recent GWAS, IL 23/IL 17 axis has been identified as a disease susceptibility locus in BD [6] Our study supports that Th17 cells seem to be operative in both of BD and PAN. Understanding the inflammatory pathway may lead us to design more specific treatment. These results suggest that TNF a, MMP9, and IL 17 may indeed be potential targets for therapy in these troublesome diseases.

title: THU0210 The comparison of childhood polyarteritis nodosa and cutaneous polyarteritis NODOSA
abstract: Polyarteritis nodosa (PAN) is a predominantly medium size vasculitis characterized by non granulomatous necrotizing vasculitis. In children (c the disease may be confined to the skin only (cutaneous involvement PAN) or may present with systemic involvement (systemic c PAN) as in adult polyarteritis nodosa.  We aimed to evaluate clinical, laboratory and imaging features of cutaneous c PAN and the systemic c PAN form in a large international pediatric vasculitis registry available on the PRINTO database.  We extracted from the PRINTO database all the patients who fulfilled the Ankara 2008 EULAR/PRES/PRINTO criteria for systemic c PAN. The cutaneous c PAN patients as per the treating physician diagnosis were also extracted. To define clinical and laboratory characteristics who could help to differentiate cutaneous PAN from cPAN and univariate logistic regression analysis was performed.  There were 109 and 45 patients classified as systemic c PAN, and cutaneous c PAN respectively with a mean age at diagnosis of 9.47+ 3.59 years; and 9.12+ 3.83 years; respectively. The female/male ratio and ethnicity did not differ in the 2 subtypes. The cutaneous group had significantly less constitutional features and less acute phase reactant levels, as expected. The median values (IQR 25 75% for the ESR and CRP for cPAN were 78 (48 108) mm/h and 7.36 (2.76 15.03) mg/dL. Musculoskeletal features such as myalgia was present in 82 (75.2% patients with c PAN and 18 (40.9% patients with cutaneous PAN (p<0.001) both groups. As differentiating features skin infarcts were observed in c PAN only and constitutional features, angiographic abnormalities, and organ involvement was not seen in any of the cutaneous PAN patients. Malaise, fever, severe headache, motor mononeuritis multiplex, sensory peripheral neuropathy, abdominal pain, and hematuria were the most statistically significant clinical characteristics able to differentiate these two entities.  This is the first study comparing the features of childhood PAN and cutaneous PAN in a large group of pediatric patients. Further biological studies are needed to effectively differentiate the two entities.