Henoch-Schönlein Purpura (HSP) is an acute small vessel vasculitis. It is the most common vasculitis in children. In majority of the cases, the disease is self-limited. Relapses can occur, in ...particular during the first year of the disease. There is no consensus on a specific treatment. The efficacy and safety of steroidal treatment in treating HSP is still controversial. Immunosuppressive treatment of HSP nephritis is used in patients with severe renal involvement (nephrotic range proteinuria and/or progressive renal impairment). The literature on immunosuppressive treatment of severe HSP without kidney involvement is scanty.
We report 2 case reports of 2 adolescents affected from Henoch-Schönlein Purpura and severe gastrointestinal involvement. Both patients presented a poor response to steroids treatment.
The diagnosis of HSP was made according to the diagnostic criteria published by European League against Rheumatism and Pediatric Rheumatology European Society in 2006.
In consideration of the recurrence of the Henoch Schönlein Purpura and the gastrointestinal involvement, we decided to start Mycophenolate Mofetil treatment.
In both patients all clinical manifestations resolved in few days.
In our cases of HSP with gastrointestinal involvement Mycophenolate Mofetil treatment has been very effective. This experience teaches us that immunosuppressive agents may be very useful to induce and maintain remission not only in renal involvement, but in all cases of persistent, recurrent, or complicated Henoch Schönlein Purpura in children.
We evaluated chronic kidney disease (CKD) (proteinuria or estimated glomerular filtration rate < 60 mL/min/1.73 m
2
) or hypertension prevalence in 110 children with juvenile idiopathic arthritis ...(JIA). CKD and hypertension were clustered under the umbrella term of “renal injury”. Median age at the last visit was 14 years. Nine out of 110 (8.1%) patients showed renal injury (8 hypertension, 1 proteinuria). Patients with renal injury presented higher age at last visit, longer duration of active JIA, shorter intervals free from JIA relapses, longer duration of non-steroidal anti-inflammatory drugs (NSAIDs) treatment but with similar cumulative NSAIDs dose and higher rate of methotrexate (MTX) prescription, longer time of MTX administration, and higher cumulative MTX dose compared to patients without renal injury. At the last visit, patients with and without renal injury presented similar prevalence of active disease. The cumulative proportion of patients free from renal injury at 240 months since JIA onset was 40.72% for all population; while the cumulative proportion was 23.7% for patients undergoing NSAIDs+MTX treatment and 100% for those undergoing NSAIDs (
p
= 0.039) treatment.
Conclusion
:About 8% of the children with JIA develop hypertension or CKD. The main risk factor was longer exposure to both NSAIDs and MTX due to a more severe form of the disease.
What is Known
•Anecdotal reports showed that rarely juvenile idiopathic arthritis (JIA) could present renal involvement due to prolonged and uncontrolled inflammation (renal amyloidosis) or to long exposure to anti-rheumatic drugs.
•No cohort studies investigated renal health in children with JIA.
What is new
•About 8% of the children with JIA developed hypertension or chronic kidney disease.
•The main risk factor was long exposure to non-steroidal anti-inflammatory drugs and methotrexate for patients suffering from a more severe form of the disease.
•In JIA patients, periodic evaluation of renal function, blood pressure and proteinuria should be warranted.
Abstract
Objective
The objective of this study was to use real-world data to evaluate the effectiveness and safety of canakinumab in Italian patients with systemic JIA (sJIA).
Methods
A retrospective ...multicentre study of children with sJIA was performed. Clinical features, laboratory parameters and adverse events were collected at baseline, and 6 and 12 months after starting canakinumab. The primary outcome measure of effectiveness was clinically inactive disease (CID) off glucocorticoids (GCs) treatment at 6 months.
Results
A total of 80 children from 15 Italian centres were analysed. Of the 12 patients who started canakinumab in CID while receiving anakinra, all maintained CID. Of the 68 with active disease at baseline, 57.4% achieved CID off GCs at 6 months and 63.8% at 12 months. In univariate analysis, the variables significantly related to non-response were number of active joints (NAJs) ≥5, history of macrophage activation syndrome (MAS) and disease duration. Multivariate analysis confirmed the association between non-response and NAJs ≥5 odds ratio (OR) 6.37 (95% CI: 1.69, 24.02), P = 0.006 and between non-response and history of MAS OR 3.53 (95% CI: 1.06, 11.70), P = 0.039. No serious adverse events were recorded in this series. There were two cases of MAS during canakinumab, leading to a rate of 2.9 episodes per 100 patient years.
Conclusion
We have confirmed, using real-world data, the efficacy of canakinumab in sJIA in a multicentric cohort. History of MAS and higher NAJ were associated with lower probability of achieving CID.
Objective
We aimed to evaluate the clinical usefulness of the systemic score in the prediction of life‐threatening evolution in Still disease. We also aimed to assess the clinical relevance of each ...component of the systemic score in predicting life‐threatening evolution and to derive patient subsets accordingly.
Methods
A multicenter, observational, prospective study was designed including patients included in the Gruppo Italiano Di Ricerca in Reumatologia Clinica e Sperimentale Adult‐Onset Still Disease Study Group and the Autoinflammatory Disease Alliance Network Still Disease Registry. Patients were assessed to see if the variables to derive the systemic score were available. The life‐threatening evolution was defined as mortality, whatever the clinical course, and/or macrophage activation syndrome, a secondary hemophagocytic lymphohistiocytosis associated with a poor prognosis.
Results
A total of 597 patients with Still disease were assessed (mean ± SD age 36.6 ± 17.3 years; male 44.4%). The systemic score, assessed as a continuous variable, significantly predicted the life‐threatening evolution (odds ratio OR 1.24; 95% confidence interval CI 1.07–1.42; P = 0.004). A systemic score ≥7 also significantly predicted the likelihood of a patient experiencing life‐threatening evolution (OR 3.36; 95% CI 1.81–6.25; P < 0.001). Assessing the clinical relevance of each component of the systemic score, liver involvement (OR 1.68; 95% CI 1.48–2.67; P = 0.031) and lung disease (OR 2.12; 95% CI 1.14–4.49; P = 0.042) both significantly predicted life‐threatening evolution. The clinical characteristics of patients with liver involvement and lung disease were derived, highlighting their relevance in multiorgan disease manifestations.
Conclusion
The clinical utility of the systemic score was shown in identifying Still disease at a higher risk of life‐threatening evolution in a large cohort. Furthermore, the clinical relevance of liver involvement and lung disease was highlighted.
A few studies have reported the safety profile of interleukin (IL)-1 blockers from real life. The aim of this study is to describe anakinra (ANA) and canakinumab (CAN) safety profile in children and ...adults, based on data from a real-life setting. Demographic, clinical, and therapeutic data from patients treated with ANA and CAN were retrospectively collected and analyzed. Four hundred and seventy five patients were enrolled; ANA and CAN were prescribed in 421 and 105 treatment courses, respectively. During a mean follow-up of 24.39 ± 27.04 months, 89 adverse events (AE) were recorded; 13 (14.61%) were classified as serious AE (sAE). The overall estimated rate of AE and sAE was 8.4 per 100 patients/year. Safety concerns were more frequent among patients aged ≥ 65 years compared with patients < 16 years (
p
= 0.002). No differences were detected in the frequency of safety concerns between monotherapy and combination therapy with immunosuppressants (
p
= 0.055), but a significant difference was observed when injection site reactions were excluded from AE (
p
= 0.01). No differences were identified in relation to gender (
p
= 0.462), different lines of biologic therapy (
p
= 0.775), and different dosages (
p
= 0.70 ANA;
p
= 0.39 CAN). The overall drug retention rate was significantly different according to the occurrence of safety concerns (
p
value < 0.0001); distinguishing between ANA and CAN, significance was maintained only for ANA (
p
< 0.0001 ANA;
p >
0.05 CAN). Treatment duration was the only variable associated with onset of AE (OR = 0.399 C.I. 0.250–0.638,
p
= 0.0001). ANA and CAN have shown an excellent safety profile; the risk for AE and sAE tends to decrease over time from the start of IL-1 inhibition.
To derive a list of opportunistic infections (OI) through the analysis of the juvenile idiopathic arthritis (JIA) patients in the Pharmachild registry by an independent Safety Adjudication Committee ...(SAC).
The SAC (3 pediatric rheumatologists and 2 pediatric infectious disease specialists) elaborated and approved by consensus a provisional list of OI for use in JIA. Through a 5 step-procedure, all the severe and serious infections, classified as per MedDRA dictionary and retrieved in the Pharmachild registry, were evaluated by the SAC by answering six questions and adjudicated with the agreement of 3/5 specialists. A final evidence-based list of OI resulted by matching the adjudicated infections with the provisional list of OI.
A total of 772 infectious events in 572 eligible patients, of which 335 serious/severe/very severe non-OI and 437 OI (any intensity/severity), according to the provisional list, were retrieved. Six hundred eighty-two of 772 (88.3%) were adjudicated as infections, of them 603/682 (88.4%) as common and 119/682 (17.4%) as OI by the SAC. Matching these 119 opportunistic events with the provisional list, 106 were confirmed by the SAC as OI, and among them infections by herpes viruses were the most frequent (68%), followed by tuberculosis (27.4%). The remaining events were divided in the groups of non-OI and possible/patient and/or pathogen-related OI.
We found a significant number of OI in JIA patients on immunosuppressive therapy. The proposed list of OI, created by consensus and validated in the Pharmachild cohort, could facilitate comparison among future pharmacovigilance studies.
Clinicaltrials.gov NCT01399281; ENCePP seal: awarded on 25 November 2011.
Long-term efficacy and safety of tocilizumab (TCZ) in adult-onset Still's disease (AOSD) mostly derive from small case series. Herein we report a registry-based study investigating TCZ efficacy and ...safety in a cohort of patients with AOSD evaluated by clinical and serum inflammatory markers as well as drug retention rate analysis.
This is an international multicentre study analyzing data from patients with AOSD regularly enrolled in the AIDA registry. TCZ efficacy was evaluated between baseline and last follow-up assessment in terms of changes in the Pouchot score and laboratory findings. Drug-retention rate was estimated by the Kaplan-Meier method, while Cox-regression analysis was employed to detect potential predictive factors of treatment withdrawal.
Data from 31 patients (15 men, 16 women) refractory to the conventional therapies and treated with TCZ were extracted from the AIDA registry. Mean ± SD time of treatment duration with TCZ was 24.32 ± 20.57 months. Median (IRQ) Pouchot score significantly decreased throughout the study period (p=0.001) with a significant difference between baseline 2.00 (4.00) and 6 month-follow-up 0.00 (0.00) (p=0.003) and between baseline and last follow-up assessment 0.00 (0.00) (p=0.032), while no differences were observed between 6 month-evaluation and last follow-up assessment (p=0.823). Similarly, laboratory parameters significantly decreased from baseline to the last follow-up visit. With regard to drug survival, cumulative TCZ retention rate at 12-, 24-, and 36-month follow-up visit were 83.1%, 71.7% and 63.7%, respectively, without significant differences between biologic naïve patients and those previously treated with other biologics (p=0.329). Likewise, no significant differences were observed between chronic articular course of AOSD and other types of disease course (p=0.938) or between patients co-administered with conventional immunosuppressants and patients receiving TCZ as monotherapy (p=0.778). Cox-regression analysis identified no variable associated with a higher hazard of treatment withdrawal. Treatment was discontinued in 9 patients due to long-term remission (n=4), adverse events (n=2), loss of efficacy (n=1), non-medical reason (n=1) and unspecified cause (n=1). Mean glucocorticosteroids daily dose significantly decreased from baseline (18.36 ± 24.72 mg) to the last follow-up assessment (4.02 ± 4.99 mg, p=0.003).
TCZ allows control of disease activity as well as normalization of serum inflammatory markers in both systemic and chronic articular form of AOSD. Additionally, TCZ displays an excellent drug retention rate while minimizing the risk of long-term exposure to corticosteroids.
A 17-year-old female patient affected by systemic lupus erythematosus (SLE) (who had been taking 300 mg/die of hydroxychloroquine for 3 years), Graves’ disease (treated with 10 mg/die of tapazole), ...and celiac disease came to our attention for urticarial vasculitis. She had been taking prednisone (25 mg/die) for 3 days, and her blood tests showed high levels of
Mycoplasma pneumoniae
IgM and IgG antibodies. The association between urticaria and
M. pneumoniae
infections can be present in up to 7% of the cases and, to the best of our knowledge, only two reports of urticarial vasculitis and
M. pneumoniae
in adults are available in the literature. Urticarial vasculitis can also be a rare cutaneous manifestation of SLE (affecting 2% of the patients), and our case is the first in the literature describing the coexistence of
M. pneumoniae
infection, SLE, and urticarial vasculitis in a pediatric patient, a case that rises an important differential diagnosis issue about the origin of urticarial vasculitis: SLE reactivation or urticarial vasculitis due to
M. pneumoniae
infection?
•Clinical characteristics of still's disease patients treated with MTX were described in a large cohort.•MTX effectiveness was confirmed in reducing the disease activity and decreasing the ...inflammatory markers.•The GC-sparing effect of MTX was shown as additional relevant clinical benefit in these patients.
To describe clinical characteristics of patients with Still's disease treated with methotrexate (MTX) and to assess drug effectiveness evaluating change in disease activity, reduction of inflammatory markers, and glucocorticoid (GC)-sparing effect.
Patients with Still's disease treated with MTX were assessed among those included in AIDA Network Still Disease Registry.
In this registry, 171 patients with Still's disease were treated with MTX (males 43.3%, age 37.1 ± 16.0 years). They were mainly characterised by joint features and fever without a prominent multiorgan involvement. MTX was administered with GCs in 68.4% of patients, with other conventional synthetic DMARDs in 6.4%, and with biologic DMARDs in 25.1%. A significant reduction of the modified systemic score was observed, and 38.6% patients were codified as being in clinical remission at the end of follow-up. The concomitant administration of a biologic DMARD resulted a predictor of the clinical remission. Furthermore, a reduction of inflammatory markers and ferritin levels was observed following the administration of MTX. Additionally, a marked reduction of the dosage of concomitant GCs was identified, while 36.7% discontinued such drugs. Male gender appeared as a predictor of GC discontinuation. MTX was discontinued in 12.3% of patients because of adverse effects, and in 12.3% for lack of efficacy.
Clinical characteristics of patients with Still's disease treated with MTX were described, mainly joint features and fever without a prominent multiorgan involvement. The clinical usefulness of MTX was reported in reducing the disease activity, decreasing the inflammatory markers, and as GC-sparing agent.
Inflammation has been associated with an increased risk for cancer development, while innate immune system activation could counteract the risk for malignancies. Familial Mediterranean fever (FMF) is ...a severe systemic inflammatory condition and also represents the archetype of innate immunity deregulation. Therefore, the aim of this study is to investigate the risk for cancer development in FMF.
The risk ratio (RR) for malignancies was separately compared between FMF patients and fibromyalgia subjects, Still's disease patients and Behçet's disease patients. Clinical variables associated with cancer development in FMF patients were searched through binary logistic regression.
580 FMF patients and 102 fibromyalgia subjects, 1012 Behçet's disease patients and 497 Still's disease patients were enrolled. The RR for the occurrence of malignant neoplasms was 0.26 (95% Confidence Interval CI. 0.10-0.73, p=0.006) in patients with FMF compared to fibromyalgia subjects; the RR for the occurrence of malignant cancer was 0.51 (95% CI. 0.23-1.16,
=0.10) in FMF compared to Still's disease and 0.60 (95% CI. 0.29-1.28,
=0.18) in FMF compared to Behçet's disease. At logistic regression, the risk of occurrence of malignant neoplasms in FMF patients was associated with the age at disease onset (β1 = 0.039, 95% CI. 0.001-0.071,
=0.02), the age at the diagnosis (β1 = 0.048, 95% CI. 0.039-0.085,
=0.006), the age at the enrolment (β1 = 0.05, 95% CI. 0.007-0.068,
=0.01), the number of attacks per year (β1 = 0.011, 95% CI. 0.001- 0.019,
=0.008), the use of biotechnological agents (β1 = 1.77, 95% CI. 0.43-3.19,
=0.009), the use of anti-IL-1 agents (β1 = 2.089, 95% CI. 0.7-3.5,
=0.002).
The risk for cancer is reduced in Caucasic FMF patients; however, when malignant neoplasms occur, this is more frequent in FMF cases suffering from a severe disease phenotype and presenting a colchicine-resistant disease.
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