Case Report: Crossing a rugged road in a primary immune regulatory disorder

over the last decades, Inborn errors of immunity (IEI) characterized by an immune dysregulatory picture, isolated or combined with infections, have been increasingly identified and referred as primary immune regulatory disorders (PIRD). PIRD diagnosis may be difficult due to heterogeneity of time onset, sequence of clinical manifestations and laboratory abnormalities. moreover, the dissection of a PIRD vs. a secondary immunodeficiency (SID) might be a real challenge since the same indications for immunosuppressant treatments might represent per se a PIRD clinical expression. here we report a female patient with a history of recurrent respiratory and urinary tract infections since early infancy and a diagnosis of rheumatoid arthritis in adulthood. after poor response to several biologicals she was treated with rituximab and sent to immunology referral for a severe hypogammaglobulinemia. clinical and immunological features matched a diagnosis of common variable immunodeficiency and when IgG replacement therapy and antibiotic prophylaxis were added a good infectious control was obtained. hh next generation sequencing analysis has revealed a novel heterozygous VUS in the IKBKB gene (c.1465A > G; p.Ser489Gly). functional analysis has shown a reduced capacity of B lymphocytes and CD4 positive T cells in inducing I kappa B alpha degradation, with negative impact on NF-kB pathway. due to recurrent infections attributed to a common condition in childhood and to an exclusive autoimmunity-centered approach in adulthood, both diagnosis and suitable treatment strategies have suffered a significant delay. to reduce the diagnostic delay, pediatricians, general practitioners and specialists should be aware of IEI and the challenges to differentiate them from SID. furthermore, genetic characterization and functional analysis may contribute to a personalized approach, in a perspective of targeted or semi-targeted therapy

The steroid-sparing effect of JAK inhibitors across multiple patient populations

IntroductionJAK-inhibitors (JAK-i) represent an effective treatment in Rheumatoid Arthritis (RA) and Psoriatic Arthritis (PsA). Oral glucocorticoids (OGC) are commonly used in combination with JAK-i to reach therapeutic target. We aimed to assess, in a real-life setting, the reduction of OGC dose during JAK-i treatment in active RA and PsA patients. MethodsWe prospectively enrolled 103 patients (88 RA, 15 PsA) treated with JAK-i: 24% bio-naïve (b-naïve), 76% bDMARD-insufficient responders (bDMARD-IR) and 40% difficult to treat (D2T), defined as failure of ≥2 bDMARDs with different mechanism of action. Disease activity (DAS28 and DAPSA, VAS-pain, GH) and OGC dose was collected at baseline and after 3, 6 and 12 months (T3, T6, T12) of treatment.ResultsIn all the cohort and in b-naïve patients we reported a reduction of OGC dose at all time-points; bDMARD-IR patients were able to reduce OGC dose at T3 and T12; D2T ones only at T3. We reported an improvement of disease activity and withdrawal of OGC as early as three months of therapy, at all time-points, regardless of line of bDMARD treatment. ConclusionChronic OGC may cause detrimental bone, metabolic, cardiovascular side effects and infections; therefore JAK-i steroid-sparing effect may be beneficial for patients in long-term treatment

A rare but fatal behçet variant: the hughes–stovin syndrome—successful case report and new evidence from literature review

hughes-stovin syndrome (HSS) is a rare potentially fatal vasculitis supposedly belonging to the spectrum of behçet disease without ocular involvement. HSS tends to play by a temporal pattern, starting with thrombosis and followed by formation of pulmonary aneurysms. wince its mortality can reach 25% of cases, early recognition and appropriate therapy represent the major clinical challenges. we describe a rare case of HSS successfully treated via multidisciplinary management by an endovascular approach and immunosuppressive therapy

Table_1_The steroid-sparing effect of JAK inhibitors across multiple patient populations.docx

IntroductionJAK-inhibitors (JAK-i) represent an effective treatment in Rheumatoid Arthritis (RA) and Psoriatic Arthritis (PsA). Oral glucocorticoids (OGC) are commonly used in combination with JAK-i to reach therapeutic target. We aimed to assess, in a real-life setting, the reduction of OGC dose during JAK-i treatment in active RA and PsA patients. MethodsWe prospectively enrolled 103 patients (88 RA, 15 PsA) treated with JAK-i: 24% bio-naïve (b-naïve), 76% bDMARD-insufficient responders (bDMARD-IR) and 40% difficult to treat (D2T), defined as failure of ≥2 bDMARDs with different mechanism of action. Disease activity (DAS28 and DAPSA, VAS-pain, GH) and OGC dose was collected at baseline and after 3, 6 and 12 months (T3, T6, T12) of treatment.ResultsIn all the cohort and in b-naïve patients we reported a reduction of OGC dose at all time-points; bDMARD-IR patients were able to reduce OGC dose at T3 and T12; D2T ones only at T3. We reported an improvement of disease activity and withdrawal of OGC as early as three months of therapy, at all time-points, regardless of line of bDMARD treatment. ConclusionChronic OGC may cause detrimental bone, metabolic, cardiovascular side effects and infections; therefore JAK-i steroid-sparing effect may be beneficial for patients in long-term treatment.</p

Demographic and clinical data of 171 patients with Rheumatoid Arthritis included in the study.

<p>Demographic and clinical data of 171 patients with Rheumatoid Arthritis included in the study.</p

Association analysis between TRAF3IP2, STAT4, PSORS1C1 and PTPN2 polymorphisms and response to TNF-inhibitors treatment in RA patients.

<p>Association analysis between TRAF3IP2, STAT4, PSORS1C1 and PTPN2 polymorphisms and response to TNF-inhibitors treatment in RA patients.</p

Association between analyzed polymorphisms and response to Etanercept treatment in RA patients.

<p>Association between analyzed polymorphisms and response to Etanercept treatment in RA patients.</p