Systemic lupus erythematosus (SLE) is a genetically predisposed, female-predominant disease, characterized by multiple organ damage, that in its most severe forms can be life-threatening. The ...pathogenesis of SLE is complex and involves cells of both innate and adaptive immunity. The distinguishing feature of SLE is the production of autoantibodies, with the formation of immune complexes that precipitate at the vascular level, causing organ damage. Although progress in understanding the pathogenesis of SLE has been slower than in other rheumatic diseases, new knowledge has recently led to the development of effective targeted therapies, that hold out hope for personalized therapy. However, the new drugs available to date are still an adjunct to conventional therapy, which is known to be toxic in the short and long term. The purpose of this review is to summarize recent advances in understanding the pathogenesis of the disease and discuss the results obtained from the use of new targeted drugs, with a look at future therapies that may be used in the absence of the current standard of care or may even cure this serious systemic autoimmune disease.
Axial spondyloarthritis (axSpA) is a chronic inflammatory disease involving the spine, peripheral joints, and entheses. This condition causes stiffness, pain, and significant limitation of movement. ...In recent years, several effective therapies have become available based on the use of biologics that selectively block cytokines involved in the pathogenesis of the disease, such as tumor necrosis factor-α (TNFα), interleukin (IL)-17, and IL-23. However, a significant number of patients show an inadequate response to treatment. Over 10 years ago, small synthetic molecules capable of blocking the activity of Janus kinases (JAK) were introduced in the therapy of rheumatoid arthritis. Subsequently, their indication extended to the treatment of other inflammatory rheumatic diseases. The purpose of this review is to discuss the efficacy and safety of these molecules in axSpA therapy.
Background and Objectives: Interleukin-17 (IL-17) is a cytokine family consisting of six members and five specific receptors. IL-17A was the first member to be identified in 1993. Since then, several ...studies have elucidated that IL-17 has predominantly pro-inflammatory activity and that its production is involved in both the defense against pathogens and the genesis of autoimmune processes. Materials and Methods: In this review, we provide an overview of the role of interleukin-17 in the pathogenesis of juvenile idiopathic arthritis (JIA) and its relationship with IL-23, the so-called IL-23–IL-17 axis, by reporting updated findings from the scientific literature. Results: Strong evidence supports the role of interleukin-17A in the pathogenesis of JIA after the deregulated production of this interleukin by both T helper 17 (Th17) cells and cells of innate immunity. The blocking of IL-17A was found to improve the course of JIA, leading to the approval of the use of the human anti-IL17A monoclonal antibody secukinumab in the treatment of the JIA subtypes juvenile psoriatic arthritis (JPsA) and enthesitis-related arthritis (ERA). Conclusions: IL-17A plays a central role in the pathogenesis of JIA. Blocking its production with specific biologic drugs enables the effective treatment of this disabling childhood rheumatic disease.
Background and Objectives: To investigate the etiology, clinical features, ocular complications, and visual outcomes in children with infectious uveitis referred to a tertiary uveitis hospital-based ...service. Materials and Methods: Children with infectious uveitis were included in a retrospective cohort study. The data set was obtained after reviewing the medical records of pediatric patients with uveitis of different causes referred to our center during the period from 2009 to 2019. Clinical evaluations were performed at the time of diagnosis and the end of follow-up. Results: Uveitis of infectious origin was present in 57 (72 eyes) of 314 (18.1%) patients examined. The median age at presentation was 10.9 years (6.1–15.8), 52.6% of patients were female, and 47.4% were male. The main cause of infectious uveitis was viral (56.1% of cases), followed by Toxoplasma gondii infection (24.5%). The anatomical location of uveitis was posterior in 40.3%, anterior in 36.8%, panuveitis in 15.7%, and intermediate in 7% of cases. Ocular involvement was unilateral in 42 children (73.7%) and bilateral in 15 (26.3%) cases. The main causes of reduced visual acuity were cataract and maculopathy in 57.1% and 28.5% of cases, respectively. During the follow-up period, 75% of patients showed significant improvements in visual acuity. Conclusions: Specialist management in a tertiary referral eye care center facilitates early diagnosis and effective treatment of this serious cause of morbidity and vision loss in children.
T-helper 17 (Th17) cells represent a subpopulation of CD4+ T lymphocytes that play an essential role in defense against pathogens. Th17 cells are distinguished from Th1 and Th2 cells by their ability ...to produce members of the interleukin-17 (IL-17) family, namely IL-17A and IL-17F. IL-17 in turn induces several target cells to synthesize and release cytokines, chemokines, and metalloproteinases, thereby amplifying the inflammatory cascade. Th17 cells reside predominantly in the lamina propria of the mucosa. Their main physiological function is to maintain the integrity of the mucosal barrier against the aggression of infectious agents. However, in an appropriate inflammatory microenvironment, Th17 cells can transform into immunopathogenic cells, giving rise to inflammatory and autoimmune diseases. This review aims to analyze the complex mechanisms through which the interaction between Th17 and pathogens can be on the one hand favorable to the host by protecting it from infectious agents, and on the other hand harmful, potentially generating autoimmune reactions and tissue damage.
We describe the unusual case of a young woman with tubulointerstitial nephritis and uveitis (TINU) with bilateral diffuse uveitis and optic nerve inflammatory involvement since she was a child in the ...1990s. Imaging diagnostic tools such as fluorescein angiography, indocyanine green angiography, optical coherence tomography (OCT), and OCT angiography revealed inactive juxtapapillary choroidal neovascularization (CNV) after 25 years of follow-up. After treatment, uveitis went into remission with BCVA 20/20 in both eyes and CNV lesions became inactive. Although anterior uveitis is more frequently reported in TINU, posterior uveitis with inflammatory involvement of the optic nerve should be accurately investigated to rule out juxtapapillary CNV, both at the time of active uveitis and during follow-up, since TINU may be complicated by CNV even at the later stages of the inflammatory process.
Background: Tubulointerstitial nephritis and uveitis syndrome (TINU) is a rare disorder typically characterized by sudden-onset non-granulomatous anterior uveitis associated with tubulointerstitial ...nephritis (TIN). However, the prevalence and clinical features of TINU are still a matter of debate. To add information about TINU, we describe here the clinical features of a series of patients affected by TINU in a retrospective study. Methods: A total of 9358 clinical records of both adult and pediatric patients up to 21 years of age, referred to the Uveitis Center of the Sapienza University of Rome, were examined. The medical records covered a period from 1990 to 2020. Various demographic and clinical features were analyzed in patients who met the criteria for TINU. Results: Twenty-one patients with TINU were identified. TINU was classified as definite, possible, or probable by the currently recognized international criteria. The median age at diagnosis was 14 years (interquartile range 12–35). Females were predominant (15/21, 71.4%). In most cases (14/21, 66.6%), patients developed ocular disease concurrently with renal disease. The most frequent type of ocular involvement was bilateral anterior uveitis (9/21, 42.8%). In two cases, patients presented with bilateral intermediate uveitis; in three cases, they presented with bilateral or unilateral alternating posterior uveitis; and in four cases, they presented with bilateral panuveitis. In one case, the uveitis was anterior in the right eye (OD) and posterior in the left eye (OS), and two cases presented with bilateral asynchronous or unilateral alternating anterior uveitis. All patients received treatment with systemic corticosteroids and topical ocular therapy. At the end of the follow-up, a significant improvement in ocular signs and symptoms with a return to normal visual acuity was generally observed. In all patients, acute kidney injury (AKI) reverted completely and none progressed to chronic kidney disease (CKD). Conclusions: Patients with TINU may often present with atypical uveitis. We suggest that patients with sudden-onset uveitis, even if not bilateral anterior, should be referred to a nephologist for an assessment of the possible presence of renal disease.
Background: Juvenile idiopathic arthritis (JIA) is a rheumatic condition of childhood that is frequently associated with anterior chronic uveitis. Evidence suggests that uveitis may persist up to ...adulthood in some cases, possibly causing severe visual impairment. Methods: We conducted a retrospective study on a series of patients aged 16 years or older with JIA-related active uveitis who were referred to the Uveitis Service of Sapienza University of Rome from 1990 to 2019 to evaluate the characteristics of ocular disease in patients with JIA-associated uveitis (JIA-U) who still exhibit uveitis in adulthood. Data on clinical features, treatment, complications and visual outcomes were collected. Results: Twenty adults (85% female; median age 23.4 ± 6.6 years, range 16−38 years) with ongoing uveitis (35 eyes) were identified. The median age at JIA onset was 6.15 ± 2.9 years (range 2−10), and uveitis onset was 8.7 ± 4.7 years (range 3−20). The patients were observed in a median follow-up of 16 ± 7.7 years (range 4−35). Fifty-seven percent of affected eyes (20 eyes) had good visual acuity (>0.4 logMAR), while eleven percent of affected eyes (4 eyes) were blind (≤20/200). Uveitis required topical steroids and mydriatic/cycloplegic in all cases. Orbital steroid injection was performed in 13 eyes. Systemic corticosteroids and biologic drugs were used in 14 patients. Conclusions: Although the visual prognosis of JIA-U has improved in recent years, persistent uveitis up to adulthood is still observed. Therefore, protracted follow-up of JIA-U patients is warranted because of the high burden of delayed visual complications.
To assess the efficacy and safety of infliximab in the treatment of sight-threatening uveitis and extraocular manifestations in patients with Behçet's disease.
Twelve patients with Behçet's disease ...and uveitis were treated with infliximab after unsuccessful therapy with other immunosuppressive drugs. The main outcome measures were as follows: the number of uveitis relapses, the number of Behçet's disease-related extraocular lesions, and the amount of corticosteroids administered during the treatment as well as during an equal prior period of time while the patients were on other immunosuppressive agents. Visual acuity was recorded at the beginning of infliximab therapy and at the end of follow-up, and was defined as stable if it did not change from baseline, increased if it showed at least one line of improvement from baseline, and decreased if it showed at least a one line decrease from baseline.
During an average follow-up of 16.67 +/- 7.63 months (median, 15 months), 11 patients (91.6%) showed a reduction in the number of ocular relapses (relapse/month, from 0.35 +/- 0.17 to 0.12 +/- 0.17, P < 0.001). All of the patients (n = 11) who were taking corticosteroids before infliximab were able to reduce the amount of corticosteroids taken daily during infliximab treatment (from 24.33 +/- 10.84 mg/prednisone per day to 8.97 +/- 6.81 mg/prednisone per day, P < 0.001), and all presented with a reduced onset of extraocular manifestations of Behçet's disease (mean total number, from 2.83 +/- 3.61 to 1.51 +/- 2.35, P = 0.039). One patient, who had to stop treatment 2 months after starting because of the onset of pulmonary tuberculosis, showed the same number of relapses during infliximab treatment but was able to reduce the mean daily corticosteroid dose. Visual acuity increased by one or more lines in three eyes (12.5%) and remained unchanged in 87.5% of the eyes. Infliximab-related side effects appeared in four patients (33.3%).
Infliximab was effective in the treatment of uveitis in these Behçet's disease patients, significantly reducing the number of ocular relapses and making possible a significant reduction in the daily dose of corticosteroids administered. Extraocular manifestations of Behçet's disease were also controlled by infliximab. Nevertheless, side effects were not uncommon, and an extensive study of systemic conditions before infliximab administration had to be carried out to exclude systemic infection, particularly prior tuberculosis.
To evaluate the changes in corneal sensitivity after corneal collagen crosslinking (CXL) with the epithelium off (epi-off) and with the epithelium on (epi-on) in eyes with keratoconus.
Prospective ...interventional case series.
Eye Clinic, A. Fiorini Hospital, Terracina (Latina), Rome, Italy.
On the basis of the corneal pachymetry at the area of topographic steepening, eyes treated with CXL were divided in 2 groups: those with a corneal thickness of 400 μm or more (epi-off) and those with a corneal thickness of less than 400 μm (epi-on). Corneal sensitivity was measured using a contact esthesiometer (Cochet-Bonnet) before treatment and 1 and 7 days and 1, 3, 6, 9, and 12 months after treatment.
The study evaluated 50 CXL-treated eyes in 50 patients (25 epi-on and 25 epi-off) from January 7, 2012, to December 15, 2012. In the epi-off group, corneal sensitivity was statistically significantly reduced for up to 3 months after CXL and gradually returned to normal levels. In the epi-on group, corneal sensitivity was statistically significantly reduced for up to 7 days but was not statistically significantly different from preoperative values at other measurement times. At 7 days, the corneal sensitivity was statistically significantly lower in the epi-off eyes than in the epi-on eyes.
Epi-off and epi-on CXL both caused hypoesthesia, but corneal sensitivity subsequently recovered completely. The corneal hypoesthesia was more pronounced in eyes in which the epi-off technique was used, and the recovery time was shorter for eyes treated using epi-on CXL.
No author has a financial or proprietary interest in any material or method mentioned.
