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BD is rarely encountered in children where the disease is very difficult to recognize. The outcome ofpatients with few symptoms is currently unknown

Osteolytic lesions are the hallmark of a number of inherited (DIRA and Majeed syndrome) and multifactorial (CRMO and SAPHO) autoinflammatory diseases.

The Q703K is a variant of NLRP3 gene has an unknown pathogenetic significance. It, has been considered to be a clinically unremarkable polymorphism, due to its presence in 12-20% of general population. However, a recent study has shown that carriers of the Q703K display an higher secretion of IL-1b, thus suggesting a possible pathogenic role of this variant.

One of the main features, in the follow-up of a patient with a chronic disorder is severity. Definition in severity is quite difficult since the disease manifests with various clinical and laboratory features. On the other hand, there have been many articles reported in literature about the lack of consistency between currently used severity scores such as Mor, Pras and Tel Hashomer criteria.

Recurrent pericarditis represents an important complication of acute pericarditis. Therapeutic approach during recurrences consists of NSAID (non-steroidal anti-inflammatory drugs) administration. However steroid is often necessary to control disease flares. IL-1 inhibitors efficacy has been anecdotally described as effective in the control of the disease in steroid-dependent and colchicine-resistant patients.

Results Monocytes isolated from PAPA patients tent to secrete higher levels of IL-1b but this was not consistent in all the patients (p = 0.144). Variability in IL-1b release occurred even in the presence of the same PSTPIP1 variant and it did not parallel disease activity when the whole cohort was taken in consideration. However, IL-1b levels varied according to the clinical picture (p = 0.0197), and it was significantly higher (P < 0.05) in patients displaying articular manifestations (N = 3) compared to those affected by cutaneous (N =6 ) or combined (N = 2) lesions. In the former, IL-1b secretion was increased in the presence of acute phase reactants elevation and active joint lesions, and treatment with Anakinra resulted in acute phase reactans normalization and symptom-free period. Silencing of of NLRP3 activity consistently inhibited LPS-induced IL-1b release in both PAPA and HD monocytes. Conclusion IL-1b secretion is higher in PAPA patients displaying prevalent articular manifestations. In these patients, IL-1b release correlates with disease activity and it is mediated by NLRP3.

Recurrent pericarditis represents an important complication of acute pericarditis. Therapeutic approach during recurrences consists of NSAID administration. However steroid is often necessary to control disease flares. IL-1 inhibitors efficacy has been anecdotally described as effective in the control of the disease in steroid-dependent and Colchicine-resistant patients.

The autoinflammatory diseases (AID) include monogenic and polygenic disorders characterized by primary dysfunction of the innate immune system.

Patients showed recurrent flares of pericarditis with malaise, precordial pain, tachyorthopnoea, sometimes fever. 2/3 developed a life-threatening cardiac tamponade needing pericardiotomy. None of them presented signs or symptoms consistent with a chronic rheumatic disease: antinuclear, anti-coxsackie and anti adenovirus antibodies were negative. Genetic analysis ruled out Familial Mediterranean Fever. Mean disease duration was 2 years and mean rate of recurrences was 4 yearly. Pericarditis seemed steroid dependent and poorly responsive to colchicine.

Osteolytic lesions are the hallmark of a number of inherited (DIRA and Majeed syndrome) and multifactorial (CRMO and SAPHO) autoinflammatory diseases. We report a clinical case in which bone lesions are part of the clinical picture of an additional inherited AID.

Pyogenic sterile Arthritis Pyoderma gangrenosum and Acne (PAPA) syndrome is a rare autosomal dominant inherited autoinflammatory disease caused by mutations in Proline-serine-threonine phosphatase-interacting protein 1 (PSTPIP1). In childhood, the syndrome is featured by recurrent sterile, erosive arthritis, potentially leading to joint destruction. By puberty, cutaneous symptoms become predominant, with recurrent onset of pathergy, abscesses, severe cystic acne, and pyoderma gangrenosum. Typically, both articular and cutaneous outcomes occur following a minor trauma. PSTPIP1 may interact with NLRP3 and caspase-1 but a clear involvement of IL-1β is still controversial. While anti-IL1 treatment seems to be effective on joint manifestations, IL inhibition does not display the same effectiveness in the management of skin lesions.

The syndrome of periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) is the most common periodic fever disease in young children. The etiology of this disorder is still unknown. Palatine tonsils are sites where innate immunity leads to onset of the adaptive immunity, mediated by B and T lymphocytes. Three families of pathogen sensors mediate the recognition of microbes: Toll-like receptors (TLRs), NOD-like receptors (NLRs) and RIG-I-like receptors (RLRs). The interplay of these receptors ensures the efficient coordination of innate immune responses.

Familial Mediterranean Fever (FMF) is the most common of the hereditary autoinflammatory disorders. FMF is caused by mutations of MEFV gene which encodes for pyrin. It has been recently reported that frequency of FMF-like symptoms decreases from patients carrying two high penetrance mutations towards patients with a single low penetrance mutation. The effectiveness of interleukin (IL)-1b blockers has suggested that IL-1b may play a role in the pathophysiology of the disease. However, evidence of dysregulated IL-1b secretion in FMF patients is so far missing. Moreover, the role of NLRP3 has never been directly examined in FMF patients.

Results Both case #1 (M.T) and #2 (V.C) displayed a mild clinical phenotype (episodes of urticarial rash and arthralgia associated with elevation of acute phase reactants), compatible with FCAS and Muckle-Wells syndrome, respectively. Both patients displayed good response to NSAID and/or steroid on demand. Compared to HD controls, patients displayed enhanced and delayed IL1b secretion. This was accompanied by higher levels of lL1Ra and IL-6 without any significant differences in IL-8. Interestingly, parents carrying the mutation also displayed higher levels of secreted IL-1b compared to HD control group. Conclusion The I313V mutation is associated with a mild CAPS phenotype and with an increased IL-1b secretion.

ADA2 deficiency, a recently described disease, is characterized by systemic vasculopathy and episodes of strokes. The defect is due to a loss of function mutation of CECR1 gene, codifying for Adenosine Deaminase 2 protein. This protein regulates the catabolism of extracellular adenosine, which we have recently shown is an important regulator of Class Switch Recombination in B lymphocytes. Accordingly DADA2 patients can present hypogammaglobulinemia.

Mevalonate kinase deficiency (MKD) is a rare autoinflammatory disease, caused by mutations in the isoprenoid pathway that lead to fever episodes. Approximately 300 MKD patients are known.

Mevalonate kinase deficiency (MKD) is a rare autoinflammatory syndrome, characterized by febrile episodes and generalized inflammation.

FMF diagnosis is made clinically and may be supported by identifying mutations in the MEFV gene. The most commonly used diagnostic criteria for FMF are those of Tel Hashomer and the Livneh criteria, which have been established in the Jewish adult population. Recently, a Turkish group (Yalcinkaya-Ozen) proposed new criteria for diagnosis of FMF in children.

The Eurofever Registry for autoinflammatory diseases: results of the first 15 months of enrolment N Toplak, J Frenkel, S Ozen, F De Benedetti, M Hofer, I Kone-Paut, H Girschick, B Neven, H Ozdogan, J Kummerle-Deschner, J Arostegui, A Simon, S Stojanov, R Vesely, C Wouters, V Hentgen, C Rose, P Dolezalova, H Lachmann, P Woo, I Touitou, A Martini, N Ruperto, M Gattorno, PRINTO, Eurofever and Eurotraps Projects

PAPA syndrome is a very rare autoinflammatory condition. Few data are nowadays available about the clinical characteristic, the response to treatment and the outcome of this disease.