Patients with low penetrance mutations for Autoinflammatory syndromes (AID) can have severe clinical manifestations, which require to be treated with biological drugs anti-IL-1. Objectives: To evaluate the response of AID to treatment with the recombinant human IL-1 receptor antagonist anakinra or with the anti-IL-1b

Giovanni Corsello

Luca Cantarini

Maria Cristina Maggio

Rolando Cimaz

Umberto Corpora

English

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heterozygotes, 1 homozygous patient); I591T (3 heterozygotes).Some of them had 2 or more mutations in association. All the pa-tients were treated with colchicine with a complete (95%) or partialresponse to the treatment. None of the patients developed amyloid-osis. Three patients from unrelated families, had a vasculitis (2 Kawa-saki Disease; 1 Schoenlein-Hoenoch Purpura) and all presented thesame association: P369S and R408Q.Conclusion: This finding verifies the importance of molecular diagnosisand detailed sequencing which is recommended to perform in particu-lar for the countries with a high risk of FMF.In several instances, family studies provided the prevalence of a singlemutation in patients experiencing a pathogenic effect, with molecularevidence for pseudodominant transmission. We evidenced a variable clin-ical and serological pattern between patients in the same family; the gen-etic study was in fact extended to parents and brothers of the indexcase, with the recommendation to dose Serum amyloid A (SAA), bloodpressure and evaluate an urine analysis to exclude proteinuria.The M694V homozygous and heterozygous genotype was found to be as-sociated with a higher prevalence of amyloidosis and arthritis and higherlevels of SAA. The parents of our patients with M694V mutation have moresevere clinical manifestations and a lower response to colchicine.Further studies are needed to highlight generational differences ofclinical spectrum and SAA levels in FMF patients of the same family,carrying the same mutations.Disclosure of InterestNone Declared.P188Anti-IL1 in patients with low penetrance mutations forautoinflammatory diseases: tuscany and sicilian case series frompaediatric to adult ageMaria Cristina Maggio1, Luca Cantarini2, Giovanni Corsello1,Umberto Corpora3, Rolando Cimaz41University Department Pro.Sa.M.I. “G. D’Alessandro”, University ofPalermo, Palermo, Italy; 2Research Center of Systemic AutoinflammatoryDiseases and Behçet’s Disease Clinic, Department of Medical Sciences,Surgery and Neurosciences, University of Siena, Siena, Italy; 3UniversitaryDepartment Pro.Sa.M.I. “G. D’Alessandro”, University of Palermo, Palermo,Italy; 4Pediatric Rheumatology Unit, Neurofarba Department, AOU Meyer,University of Florence, Florence, ItalyCorrespondence: Maria Cristina MaggioPediatric Rheumatology 2017, 15(Suppl 2):P188Introduction: Patients with low penetrance mutations for Autoinflam-matory syndromes (AID) can have severe clinical manifestations, whichrequire to be treated with biological drugs anti-IL-1.Objectives: To evaluate the response of AID to treatment with the re-combinant human IL-1 receptor antagonist anakinra or with the anti-IL-1b.Methods: We enrolled from 3 centers (U.O. of Rheumatology, Univer-sitary Hospital “S. Maria Le Scotte”, Siena; S.O.D.C. of PaediatricRheumatology, “A. Meyer” Hospital, Florence and U.O. of PaediatricClinic, Children Hospital “G. Di Cristina”, Palermo) 26 patients withSAI and low penetrance mutations, with age: 0.8-58 years (11 M, 15F; age:4-62 years; medium age of paediatric patients: 11.2 years). Thesymptoms started in paediatric age in all the patients; however adultpatients received the diagnosis in adult age.Results: All the patients (9 CAPS, 10 TRAPS, 2 HIDS, 2 FMF, 3 sJIA) re-ceived anti-IL-1b drugs (anakinra or canakinumab). The subjects kept adiary of symptoms at the diagnosis and at the outset, and underwentclinical and laboratory assessments, including measurement of the SAA,ESR, CRP, blood count, urinalysis.At the outset, the 84.6% showed recurrent episodes of fever, variously as-sociated with: rash (61.5%), abdominal pain (50%), arthralgia and/or myal-gia (88%), arthritis (46%). All the patients, before starting anti-IL-1b drugs,were treated with NSAIDs, steroids, DMARDs, colchicine with a poor con-trol of the disease. The 30.7% associate the anti-IL-1b to one or more ofother drugs. The 57.7% (38.5% between children, 19.2% between adults)showed a complete remission; the 19.2% incomplete, the 23.1% did notrespond. SAA was increased in 88.5% (M: 155,86; n.v. < 6,4 mg/l), reducedin 58%. CRP was increased before anti-IL-1b drug in the 50%, with a nor-mal value in the 92% after the drug was started. ESR was increased inthe 69.2%, with a normal value in the 42.3%.Proteinuria was detected in the 8% before the anti-IL-1b drug wasstarted and was in the normal range after they was treated with thebiological drug.In children, prevalent clinical manifestations were abdominal pain andarthritis; in adults thorax pain and pericarditis were more frequent.Conclusion: The clinical features of the AID were correlated with age,also in patients with low penetrance mutations: some manifestationswere more frequent in adults, others in childhood. The remarkable re-sponse on clinical and haematological parameters (76.9% of all thepatients) to anakinra or canakinumab suggests that IL-1β has a funda-mental role in the pathogenesis of inflammation associated with lowpenetrance mutations as well. In paediatric age, IL-1 blockade higher ef-ficacy was probably linked to a more severe clinical phenotype.Disclosure of InterestNone Declared.P189Genetic and clinical profile of a sicilian population with R92QmutationMaria Cristina Maggio1, Carmelo Fabiano2, Giuliana Vitaliti1,Giovanni Corsello11University Department Pro.Sa.M.I. “G. D’Alessandro”, University ofPalermo, Palermo, Italy; 2Molecular Genetic Laboratory, Haematologyand Rare Diseases of blood and haematopoietic organs, Ospedali RiunitiVilla Sofia-Cervello, Palermo, ItalyCorrespondence: Maria Cristina MaggioPediatric Rheumatology 2017, 15(Suppl 2):P189Introduction: Gene TNFRSF1A mutation is linked to TRAPS, autosomaldominant Autoinflammatory Disease (AID) with recurrent attacks offever (2-3 weeks long), abdominal pain, vomiting, serositis, arthralgiaand/or arthritis, myalgia, fasciitis, rash. The disease starts precociouslyand amyloidosis is reported in the 25% of the patients. Patients carry-ing the mutation R92Q usually show a mild clinical phenotype, with anextreme interindividual variability. Arthralgia and serositis are frequentlyless severe, however oral ulcers and pharyngitis are recurrent.Objectives: We studied the clinical and biochemical impact of themutation R92Q in our population and the treatment outcome in allthe patients with clinical relevant symptoms.Methods: We followed 15 patients (6 M and 9 F), 11 children and 4adults, carrying the R92Q heterozygous mutation of the geneTNFRSF1A. The diagnosis of children were done at the age of 4-14years, o the adults was performed following the sons diagnosis. SAAlevels were significantly high in 8/11 children and in 2/4 adults.Results: All the symptomatic patients were treated with NSAIDs, ste-roids, colchicine with a variable control of the disease. The colchicinewas not sufficient in 4/5 patients and 2 of them were treated withthe anti-IL-1 β biological drug canakinumab.Conclusion: Functional studies performed on R92Q evidenced achanged conformational structure vs. the wild type.Our patients showed polymorphic clinical features: some of them areasymptomatic, other record different symptoms with an intrafamilialvariability. In paediatric age, the clinical phenotype is more severealso in correlation with the symptoms of parents carrying the samemutation. We stress the data that all our patients underwent thegenetic study because they recorded symptoms linked to AID.Disclosure of InterestNone Declared.P190A paediatric FMF patient with recurrent priapism during attacksBalahan Makay, Nesrin GülezBehçet Uz Children s Hospital, Izmir, TurkeyCorrespondence: Balahan MakayPediatric Rheumatology 2017, 15(Suppl 2):P190Pediatric Rheumatology 2017, 15(Suppl 2):65 Page 104 of 191Introduction: Priapism, a prolonged penile erection lasting >4 hours, isa rare condition in childhood. The commonest causes of priapism inchildren are sickle cell disease, leukaemia, trauma, idiopathic, andpharmacologically induced. To date, the association of familial Mediter-ranean fever (FMF) and priapism has not been reported.Objectives: To report an FMF patient experiencing priapism during attacks.Methods: To report an FMF patient experiencing priapism during attacks.Results: A 20-months-old boy was referred to our pediatric rheumatologydepartment with the episodes of fever, monoarthritis, and pustules onthe face recurring every month since 10-months of age. Because MEFVanalysis revealed M694V homozygote mutation, he was started 0.25 mg/day colchicine by his pediatrician when he was 14-months-old. Despitethe adjustment of colchicine to 0.5 mg/day, he continued to have recur-rent fever and pustules. In his immunologic evaluation, white blood cellnumber, immunogobuline G,M,A levels, lymphocyte subgroup disturba-tion, phagoburst test was normal.He was given a short-course of cortic-steroid because of fever and a painful erythema nodosum-like lesionwhen he was 26-months old. PSTPIP1 mutation was negative for PAPA.When he was 2.5 years-old, he had penile erection during an attack. Col-chicine dose was increased to 1 mg/day. He experienced two more at-tacks of priapism with fever and pustules of the face. He was started ananti-interleukine 1 treatment, anakinra 1 mg/kg/day. He never hadpriapism, pustules, arthritis and fever attacks after the initiation of ana-kinra. After one year, anakinra was stopped. He is currently taking onlycolchicine since one year and doing well.Conclusion: To the best of our knowledge, this is the first case show-ing an association of priapism with FMF attacks.Disclosure of InterestNone Declared.P191Severe arthritis as clinical presentation in a a novel case of COPAsyndromeStefano Volpi1, Marcello Mariani1, Claudia Pastorino1, Anthony K. Shum2,Angelo Ravelli1, Marco Gattorno1, Paolo Picco11Pediatria 2, Istituto Giannina Gaslini, Genova, Italy; 2Division ofPulmonary and Critical Care, University of California San Francisco, SanFrancisco, CA, USACorrespondence: Marcello MarianiPediatric Rheumatology 2017, 15(Suppl 2):P191Introduction: Heterozygous mutations of COPA gene have been re-cently linked to an autoimmune syndrome characterised by polyarthri-tis and lung disease with interstitial fibrosis or alveolar haemorrhagesas complication (1). The gene encodes for a regulator of vesicular retro-grade transport between Golgi and the endoplasmic reticulum (ER). Inmost cases the presenting symptoms are cough and tachypnea, thatappear in the early childhood with articular manifestations appearinglately before di age of 10. At laboratory tests, autoimmunity is charac-terised by the presence of autoantibodies, with the majority of patientsshowing a frankly positive ANA titer (80%). Rheumatoid factor is re-ported to be raised in 43% of cases; a few patients showed alsopositivity for cANCA and pANCA (2).Objectives: We report one case referring to our centre of a younggirl that presented at 3 year of age with polyarticular arthritis.Methods: The patient was clinically evaluated by the pediatricrheumatology unit of Istituto Giannina Gaslini. The family gave per-mission for publication of clinical and laboratory data and photo-graphic images as well as molecular analysis.Results: The patient firstly referred to our centre at 3 year of age fora polyarticular arthritis involving metacarpophalangeal joints, hip andcervical spine. Lab results were performed showing raised ESR andCRP, high titer rheumatoid factor and antinuclear antibodies positivity.For a newly-onset of a persistent cough with no evidence of infectiousprocess a chest X-ray and then a lung CT scan was performed showingan interstitial lung disease with tree-in-a-bud appearance and air-filledcysts. In order to treat the arthritic process oral and intra-articularsteroids were administered with good response. Methotrexate and aba-tacept used as steroid-sparing drugs failed to control diseaseprogression. The molecular analysis of COPA gene showed the reportedc.698G > A mutation. Patient intentionally discontinued therapy for 3years as well as clinical follow-up. After that time with patient referringagain at our centre, a very severe osteoarthritis with joint damage anddeformities of multiple joints was found.Conclusion: COPA syndrome could be more common than thoughtdue the autosomal dominant inheritance. When molecular diagnosisis confirmed a therapeutic aggressive approach is required to pre-vent permanent joint deformities and reduce the risk of life threaten-ing complications such as pulmonary haemorrhages.1. Vece TJ, Watkin LB, Nicholas SK, Canter D, Braun MC, GuillermanRP, et al. Copa Syndrome: a Novel Autosomal Dominant ImmuneDysregulatory Disease. J Clin Immunol. 2016;36(4):377–87.2. Watkin LB, Jessen B, Wiszniewski W, Vece TJ, Jan M, Sha Y, et al.COPA mutations impair ER-Golgi transport and cause hereditaryautoimmune-mediated lung disease and arthritis. Nat Genet. NaturePublishing Group; 2015;47(6):654–60.Disclosure of InterestNone Declared.P192Paediatric autoinflammatory diseases in cyprus: insights from thenational registryDespoina Maritsi1, Avraam Elia2, Maria Kolliou2, Maria Kousparou2,Margarita Onoufriou11Rheumatology Unit, Department of Paediatrics, ‘Archbishop Makarios III”Children’s Hospital, Nicosia, Cyprus; 2Department of Paedatrics,“Archbishop Makarios III” Children’s Hospital, Nicosia, CyprusCorrespondence: Despoina MaritsiPediatric Rheumatology 2017, 15(Suppl 2):P192Introduction: Autoinflammatory diseases (AID) are rare in theory;however with raising awareness their incidence seems to be increas-ing. Early recognition and appropriate management prevents long-term sequelae and establishes an improved quality of life.Objectives: To describe the epidemiology, demographic, clinicaland disease characteristics as well as treatment options in patients withAID followed up in a national referral center for PediatricRheumatology.Methods: Cross sectional observational study including thirty-fivechildren with an AID regularly followed up at “Archbishop MakariosIII” Paediatric Hospital of Nicosia, Cyprus from January 2012 todate. Children with PFAPA, SJIA and Behcet’s disease were excludedfrom this cohort.Results: Of those 35 children (55% boys), 62% were diagnosed withmutation proven FMF, 3.5% with TRAPS, 3.5% with HIDS, while theremaining were classified as a multisystem autoinflammatory disease.69% of patients were Cypriots, 8% were of Eastern Mediterraneanorigin, 8% were Eastern European while the remaining were of mixedethnic origin. Mean age at disease onset was 8.4 years (range 0.4 to17 years). Mean time from disease onset to diagnosis was 1.5 years(range 0.6 to 3.5 years). Positive family history was evident in 25% ofcases. All patients presented with fever of unknown origin. Othermajor symptoms included abdominal pain 65%, diarrhoea 18%, thor-acic pain 7%, asthenia 27%, weight loss 14%, headache 42%, arthral-gia and myalgia 23%. Skin manifestations were evident at 21% ofpatients; arthritis was present in 27% of patients, 25% of patients de-veloped serositis (primarily pericarditis) at some point throughoutthe course of their disease. Lymph node enlargement was noted in11%, parotid enlargement in 7%, while 14% had splenomegaly. Uve-itis was present in 3.4%. Renal involvement was observed in 12% ofour cohort (proteinuria). Renal biopsy was performed on two occa-sions proving secondary amyloidosis. Oral apthous ulcers were no-ticed in 15% of patients while hidradenitis suppurativa in 3.5%. Themajority of our patients had received NSAIDS prior to referral; 22%reported temporal alleviation of their constitutional symptoms. Col-chicine remained the mainstay of treatment for the majority of thesepatients (79%). 67% of these children had received steroids duringthe course of their disease. Eight 23% of the patients receivedPediatric Rheumatology 2017, 15(Suppl 2):65 Page 105 of 191

Anti-IL1 in patients with low penetrance mutations for autoinflammatory diseases: tuscany and sicilian case series from paediatric to adult age

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Anti-IL1 in patients with low penetrance mutations for autoinflammatory diseases: tuscany and sicilian case series from paediatric to adult age

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