RESUMO
PURPOSE: To retrospectively analyze long-term outcomes of pediatric pars planitis (PP). METHODS: PP was defined as vitreal inflammation with snowbank or snowball formation in the absence of a related disease. Eighty-five eyes of 44 patients were included in this study. Demographic and clinical characteristics were obtained from medical records. RESULTS: Approximately 70% of the patients were males; the mean patient age was 10.4 ± 3.6 years at presentation, and the mean follow-up time was 42.8 ± 27.9 months. At presentation, the mean best corrected visual acuity (BCVA, logMAR) was 0.17 ± 0.27 in the right eyes and 0.27 ± 0.33 in the left eyes. Common symptoms included blurry vision (29 eyes, 65%), redness (17, 38%), pain (8, 18%), and floaters (5, 11%). Sight-threatening complications included optic disc edema/hyperemia (26, 30%), cataracts (16, 18%), macular edema (16, 18%), and glaucoma (15, 17%). All 38 patients who initially required systemic treatment received corticosteroids. During the follow-up, 24 patients were treated with azathioprine, 20 with methotrexate, 11 with cyclosporine, 20 with adalimumab, and 8 with infliximab. At the final examination, the mean BCVA of the right and left eyes improved significantly (0.08 ± 0.23 and 0.06 ± 0.17, p = 0.006 and p < 0.001, respectively). The severities of vitritis, anterior chamber inflammation, snowbank/snowball formation, and endotheliitis decreased (all p < 0.001). Thirty-one patients remained on systemic treatment, with only four patients still receiving corticosteroids. No life-threatening adverse effects were reported. CONCLUSION: Despite pediatric PP's mild course, severe vision-threatening complications can occur. Immunomodulatory or biologic agents are important for controlling inflammation and tapering corticosteroids. Further research could enhance understanding of optimal treatments.
RESUMO
PURPOSE: To present a presumed case of non-paraneoplastic autoimmune retinopathy (nPAIR) following COVID-19 in a healthy woman. METHODS: A single case was evaluated and followed for 32 months. RESULTS: A healthy 32-year-old woman presented with photopsia and paracentral scotoma (OU) after a recent COVID-19 infection. Past medical history and family history were unremarkable. Her visual acuity was normal (OU). Retinal atrophy, mild disc pallor, and foveal reflex attenuation were observed (OU). Optical coherence tomography (OCT) scans showed outer nuclear layer thinning and ellipsoid zone disruption (OU). The visual field test showed blind spot enlargement and arcuate scotomas (OU). Uveitis workup and underlying malignancy investigations were negative. A diagnosis of nPAIR was presumed. At the time, she refused therapy, and 20 months later, her visual acuity was stable, but there were progressive retinal atrophic changes and visual field constriction. After initiation of glucocorticoids and immunosuppressive therapy, flashing lights completely disappeared, her visual field was stabilized without progression, and OCT scans showed partial recovery of ellipsoid zone. CONCLUSION: SARS-CoV-2 infection may be a trigger for nPAIR in susceptible individuals, but further research is needed to determine this association.
RESUMO
PURPOSE: Patients with Crohn's disease (CD) and subsequent ocular manifestations may have worse outcomes when compared to matched patients with CD without ocular disease. METHODS: In this retrospective cohort study, an aggregated electronic health records research network, TriNetX (Cambridge, MA, USA), was used to identify patients diagnosed with CD stratified by the presence or absence of ocular involvement with at least 1 year of follow-up. Propensity score matching (PSM) was performed to control for baseline demographics and medical comorbidities. RESULTS: Patients with CD with ocular disease showed a greater risk of undergoing bowel resections (RR: 2.06, 95% CI: 1.48-2.85, p < 0.001), developing other CD-related gastrointestinal complications (RR: 1.31, CI: 1.15-1.49, p < 0.001), or acquiring Clostridioides difficile infections (RR: 2.19, CI: 1.89-2.54, p < 0.001). Further, patients with CD with ocular sequelae had a greater risk of developing NASH (RR: 1.43, CI: 1.31-1.56, p < 0.001), CD-related nutrient deficiencies (RR: 1.38, CI: 1.29-1.49, p < 0.001), iron deficiency anemia (RR: 1.41, CI: 1.33-1.50, p < 0.001), CD-related dermatological disease (RR: 1.84, CI: 1.65-2.05, p < 0.001), osteoporosis (RR: 1.49, CI: 1.37-1.64, p < 0.001) and primary sclerosing cholangitis (RR: 1.63, CI: 1.11-2.38, p = 0.011). Among patients with CD with ocular involvement, there was an elevated risk of MI (RR: 1.36, CI: 1.14-1.63, p < 0.001), stroke (RR: 1.42, CI: 1.18-1.70, p < 0.001), VTE (RR: 1.37, CI: 1.22-1.54, p < 0.001), and sepsis (RR: 1.53, CI: 1.37-1.71, p < 0.001). CONCLUSIONS: Patients who have CD and subsequent ocular involvement have an increased risk of local intestinal complications, extraintestinal morbidity, and cardiovascular complications when compared to patients with CD without ocular involvement.
RESUMO
BACKGROUND: Dupilumab, a novel therapy targeting the T helper (Th) 2-mediated inflammation, is showing clinical benefits in treating bullous pemphigoid (BP). However, limited research investigated the serum biomarkers that reflect the inflammation alterations throughout the disease course. OBJECTIVES: To explore the changes of the serum inflammatory biomarkers under dupilumab therapy in BP and establish their correlations with disease severity and clinical outcomes. METHODS: This exploratory study evaluated serum samples from 40 patients with BP at baseline, 30 of these patients following 16-week dupilumab therapy, and 20 senior healthy controls. Serum levels of 29 cytokines and chemokines were quantified using the Magnetic Luminex Assay. RESULTS: Two distinct clusters based on serum inflammatory profiles were identified. The first cluster, characterized by elevated levels of inflammatory activation, exhibited worse disease severity and poorer remission outcomes. Following the 16-week dupilumab therapy regimen, a significant suppression of Th2-mediated inflammation in the serum was observed, alongside a relative upregulation of Th1 responses. Patients treated with adjuvant systemic steroids exhibited an enhanced suppression of B cell activating factor compared to those receiving dupilumab alone. Significant correlations were unveiled between Th2 biomarkers and clinical scores, eosinophil counts, and anti-BP180 immunoglobulin G levels. Baseline levels of CCL18, Periostin, interleukin (IL)-6, and IL-16 constitute an optimal combination to distinguish between inflammatory clusters. CONCLUSIONS: Cluster analysis of serum inflammatory biomarkers provided novel insights into the heterogeneity of the inflammation profiles in BP. Baseline levels of CCL18, Periostin, IL-6, IL-16 emerged as effective predictors for disease severity and therapy response to dupilumab.
Assuntos
Anticorpos Monoclonais Humanizados , Biomarcadores , Citocinas , Penfigoide Bolhoso , Índice de Gravidade de Doença , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Feminino , Masculino , Biomarcadores/sangue , Idoso , Penfigoide Bolhoso/tratamento farmacológico , Penfigoide Bolhoso/sangue , Penfigoide Bolhoso/imunologia , Penfigoide Bolhoso/diagnóstico , Citocinas/sangue , Análise por Conglomerados , Pessoa de Meia-Idade , Resultado do Tratamento , Células Th2/imunologia , Células Th2/efeitos dos fármacos , Idoso de 80 Anos ou mais , Estudos de Casos e ControlesRESUMO
Cutaneous immune-related adverse events (irAEs) of immunotherapies, such as anti-programmed cell death protein-1 (PD-1), suggest that immune checkpoint factors may contribute to the pathobiology of lichenoid interface dermatitis in immunotherapy-naïve patients. Our study aimed to describe innate and adaptive immune markers via immunohistochemical (IHC) staining of lichenoid interface dermatoses. We studied the staining patterns of PD-L1, STING, IL-36 gamma, CD8, PD-1, and LAG-3 in five interface dermatoses: oral lichen planus (LP) (n = 10), cutaneous LP (n = 10), chronic cutaneous lupus erythematosus (CLE) (n = 11), erythema multiforme (EM) (n = 11), and toxic epidermal necrolysis (TEN) (n = 13), by immunohistochemistry (IHC) analysis. Expression was evaluated semi-quantitively according to the percentage of keratinocytes and dermal lymphocytes stained compared to keratinocytes and resident pericapillary lymphocytes in normal human skin. All interface dermatoses evaluated showed increased expression of PD-L1 on keratinocytes and LAG-3 in lymphocytes. STING was increased on the keratinocytes of most specimens. Expression of IL-36 gamma, in basal layer keratinocytes was more extensive in oral LP and cutaneous LP and varied in CLE, EM, and TEN. Lymphocytic infiltration expressing PD-1 was elevated in oral LP, cutaneous LP, and CLE. Current thinking is that interface dermatitis is the result of a cell-mediated immune reaction involving cytotoxic CD8+ T-cell-mediated apoptosis of keratinocytes. The findings of this study suggest that in addition to cell-mediated immunity, innate immune factors may contribute to pathobiology.
RESUMO
Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by the presence of antiphospholipid antibodies (aPLs) that predispose individuals to thrombotic events and pregnancy-related complications. APS can occur as a primary condition or in association with other autoimmune diseases, most commonly systemic lupus erythematosus (SLE). Catastrophic APS (CAPS) is a rare, severe variant of APS, marked by rapid-onset, widespread thrombosis leading to multi-organ failure, often triggered by infections, surgical procedures, or cessation of anticoagulation therapy. Both APS and CAPS present significant clinical challenges due to their potential for severe morbidity and mortality. This comprehensive review aims to provide a detailed overview of the pathogenesis, clinical features, diagnostic criteria, and management strategies for APS and CAPS. The review highlights the immunological mechanisms underlying APS, including the role of aPLs, complement system activation, and endothelial cell dysfunction in developing thrombosis. It also outlines the clinical manifestations of APS, such as venous and arterial thrombosis, pregnancy morbidity, and neurological symptoms, along with the diagnostic criteria based on clinical and laboratory findings. The review delves into its pathogenesis, clinical presentation, and diagnostic challenges in the context of CAPS, emphasizing the need for immediate and intensive therapy to manage this life-threatening condition. Current management strategies for APS, including anticoagulant therapy, immunomodulatory treatments, and specific interventions for pregnancy-related complications, are discussed. The review highlights the importance of a multidisciplinary approach for CAPS, combining anticoagulation, high-dose corticosteroids, plasma exchange, and intravenous immunoglobulin. The review also addresses the prognosis and long-term outcomes for patients with APS and CAPS, underlining the necessity for ongoing monitoring and follow-up to prevent recurrent thrombotic events and manage chronic complications. Finally, future directions in research are explored, focusing on emerging therapies, biomarkers for early diagnosis, and the need for clinical trials to advance the understanding and treatment of these complex syndromes. By enhancing the understanding of APS and CAPS, this review aims to improve diagnosis, treatment, and patient care, ultimately leading to better health outcomes for those affected by these conditions.
RESUMO
Nivolumab, an investigational monoclonal antibody targeting a specific immune pathway, has shown promise in treating various autoimmune diseases. However, like other immunomodulatory agents, it has potential side effects. This case report describes a rare adverse event of nivolumab-induced diabetic ketoacidosis (DKA) in a patient with a history of adrenal insufficiency secondary to nivolumab. The patient presented with symptoms of hyperglycemia, metabolic acidosis, and ketosis after receiving nivolumab therapy for 12 cycles. Prompt recognition and management of nivolumab-induced DKA are crucial to prevent complications and ensure patient safety.
RESUMO
Approximately 5%-10% of fractures go on to delayed healing and nonunion, posing significant clinical, economic, and social challenges. Current treatment methods involving open bone harvesting and grafting are associated with considerable pain and potential morbidity at the donor site. Hence, there is growing interest in minimally invasive approaches such as bone marrow aspirate concentrate (BMAC), which contains mesenchymal stromal cells (MSCs), macrophages (Mφ), and T cells. However, the use of cultured or activated cells for treatment is not yet FDA-approved in the United States, necessitating further exploration of optimal cell types and proportions for effective bone formation. As our understanding of osteoimmunology advances, it has become apparent that factors from anti-inflammatory Mφ (M2) promote bone formation by MSCs. Additionally, M2 Mφ promote T helper 2 (Th2) cells and Treg cells, both of which enhance bone formation. In this study, we investigated the interactions among MSCs, Mφ, and T cells in bone formation and explored the potential of subsets of BMAC. Coculture experiments were conducted using primary MSCs, Mφ, and CD4+ T cells at specific ratios. Our results indicate that nonactivated T cells had no direct influence on osteogenesis by MSCs, while coculturing MSCs with Mφ and T cells at a ratio of 1:5:10 positively impacted bone formation. Furthermore, higher numbers of T cells led to increased M2 polarization and a higher proportion of Th2 cells in the early stages of coculture. These findings suggest the potential for enhancing bone formation by adjusting immune and mesenchymal cell ratios in BMAC. By understanding the interactions and effects of immune cells on bone formation, we can develop more effective strategies and protocols for treating bone defects and nonunions. Further studies are needed to investigate these interactions in vivo and explore additional factors influencing MSC-based therapies.
Assuntos
Macrófagos , Células-Tronco Mesenquimais , Osteogênese , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Osteogênese/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/citologia , Humanos , Técnicas de Cocultura , Animais , Células Cultivadas , Linfócitos T/citologia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Diferenciação CelularRESUMO
Prurigo nodularis (PN) is a chronic inflammatory skin disease characterized by intense pruritus and skin nodules. Beyond the skin, PN involves circulating blood inflammation that may contribute to systemic disease comorbidities. Dupilumab was recently approved for treatment of PN, but its effects on systemic inflammation are unknown. Thus, we aimed to characterize changes in plasma concentrations of inflammatory proteins after dupilumab treatment. In this exploratory study, plasma samples were collected from 3 patients with moderate-to-severe PN before and after ≥6 months of dupilumab treatment. All patients exhibited clinically significant improvements after treatment. Of the 2569 proteins tested, 186 were differentially expressed after treatment (q < 0.1, fold change > 1.3). Downregulated proteins included cytokines associated with T helper (Th) 1 (IFN-γ, TNF-α), Th2 (IL-4, IL-13), and Th17/Th22 (IL-6, IL-22) signaling. Markers of innate immunity (IL-19, toll-like receptor 1, nitric oxide synthase 2), immune cell migration (CCL20, CD177), and fibrosis (IL-11, IL-22) were also decreased (q < 0.1). Gene set variation analysis of Th2, Th17, and epithelial-mesenchymal transition gene sets showed reduced pathway expression in the post-treatment cohort (P < .05). Plasma cytokine levels of IL-11, nitric oxide synthase 2, IL-13, IL-4, and IFNG (R2 > 0.75, q < 0.10) showed the strongest correlations with pruritus severity. Dupilumab may reduce systemic inflammatory proteins associated with multiple immune and fibrosis pathways in patients with PN, potentially modulating the development of systemic disease comorbidities.
RESUMO
OBEJECTIVE: To compare the effectiveness of endometrial receptivity and pregnancy outcomes of four common immunomodulatory therapies for patients with thin endometrium. METHOD: This systematic review and network meta-analysis using a literature search up to January 2024, to identify relevant trials comparing endometrial receptivity and pregnancy outcomes of human chorionic gonadotropin (hCG), platelet-rich plasma (PRP), infusion of granulocyte colony-stimulating factor (IG-CSF), and peripheral blood mononuclear cell (PBMC) for patients with thin endometrium. We used surface under the cumulative ranking (SUCRA) to ranked four common immunomodulatory therapies on endometrium thickness, implantation rate (IR), clinical pregnancy rate (CPR), and live birth rate (LBR). RoB2 and ROBINS-I were used to assess the certainty of evidence. RESULTS: The pooled results of 22 studies showed that hCG (mean difference [MD]: 3.05, 95% confidence interval [CI]: 1.46-4.64) and PRP (MD: 0.98, 95% CI: 0.20-1.76) significantly increase endometrium thickness. The hCG was the best among the IG-CSF (MD = -2.56, 95% CI = -4.30 to -0.82), PBMC (MD = -2.75, 95% CI = -5.49 to -0.01), and PRP (MD = -2.07, 95% CI = -3.84 to -0.30) in increasing endometrium thickness. However, IG-CSF and PRP significantly improved IR (IG-CSF: risk ratio (RR; IG-CSF: RR = 1.33, 95% CI = 1.06-1.67; PRP: RR = 1.63, 95% CI = 1.19-2.23), and LBR (IG-CSF: RR = 1.53, 95% CI = 1.16-2.02; PRP: RR = 1.59, 95% CI = 1.08-2.36). CONCLUSIONS: Available evidence reveals that hCG and subcutaneous or intrauterine CSF (SG-CSF) may be the best treatment options for current thin endometrium patients. However, future high-quality and large-scale studies are necessary to validate our findings.
Assuntos
Gonadotropina Coriônica , Endométrio , Metanálise em Rede , Humanos , Feminino , Endométrio/patologia , Endométrio/efeitos dos fármacos , Gravidez , Gonadotropina Coriônica/uso terapêutico , Gonadotropina Coriônica/administração & dosagem , Plasma Rico em Plaquetas , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Taxa de Gravidez , Leucócitos Mononucleares , Implantação do EmbriãoRESUMO
Rapidly progressive dementia (RPD) presenting initially as schizophrenia spectrum disorder poses significant diagnostic challenges. We present the case of a 55-year-old woman initially diagnosed with schizophrenia spectrum disorder due to symptoms including social withdrawal, disorganized behavior, and psychosis. However, the rapid progression of cognitive decline and motor dysfunction prompted further investigation, leading to the diagnosis of anti-N-methyl-d-aspartate (NMDA) receptor antibody-mediated encephalitis. Cerebrospinal fluid analysis revealed the presence of anti-NMDA receptor antibodies, guiding targeted immunomodulatory therapy with intravenous immunoglobulin and corticosteroids. This resulted in significant clinical improvement, highlighting the importance of comprehensive diagnostic evaluation and timely initiation of immunomodulatory therapy in autoimmune-mediated RPD. This case underscores the complexities of overlapping psychiatric and neurological conditions and emphasizes the need for a multidisciplinary approach to diagnosis and management.
RESUMO
At the beginning of the coronavirus disease 2019 (COVID-19) pandemic in December 2019 there was no available evidence regarding the management of immunosuppressive or immunomodulatory treatment and the potential outcomes of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infections in inflammatory rheumatic diseases (IRD). As a result, the Justus Liebig University of Giessen, Germany, in collaboration with the German Society for Rheumatology, established the German COVID-19 register ( www.covid19-rheuma.de ). The COVID-19 register enabled for the first time a systematic documentation and evaluation of viral infections in patients with IRD. The data collection started as early as March 2020. Currently, the register is one of the largest global registers in the field of COVID-19 and IRD. As of 18 December 2023 the register has recorded more than 7100 cases. The first scientific findings on SARS-CoV2 infections in IRD patients were generated from the register in 2020, showing an association between disease activity of IRD, certain comorbidities, such as cardiovascular diseases and treatment with rituximab, with an unfavorable course. The contents and construction of the database of the register were designed at the conception to allow collaboration and data exchange with other national and international registers (e.g., EULAR COVID-19 register, COVID-19 global rheumatology alliance and the Lean European open survey on SARS-CoV2 infected patients). In addition, other registers and surveys were initiated. A vaccination register documents the tolerability and possible adverse reactions to COVID-19 vaccination in IRD patients. The data resulted in numerous publications and formed the basis for national and international recommendations for action in the care and vaccination of IRD patients during the COVID-19 pandemic. In summary, the German COVID-19 register has made a significant contribution to the understanding of the course of COVID-19 in IRD patients and has facilitated international collaboration for a better understanding of COVID-19 and IRD.
Assuntos
COVID-19 , Sistema de Registros , Doenças Reumáticas , Humanos , Antirreumáticos/uso terapêutico , Comorbidade , COVID-19/epidemiologia , COVID-19/imunologia , Alemanha/epidemiologia , Sistema de Registros/estatística & dados numéricos , Doenças Reumáticas/tratamento farmacológico , Doenças Reumáticas/epidemiologia , Doenças Reumáticas/imunologia , Reumatologia/métodos , Reumatologia/estatística & dados numéricos , Reumatologia/tendências , SARS-CoV-2RESUMO
Increasing evidence of brain-immune crosstalk raises expectations for the efficacy of novel immunotherapies in Alzheimer's disease (AD), but the lack of methods to examine brain tissues makes it difficult to evaluate therapeutics. Here, we investigated the changes in spatial transcriptomic signatures and brain cell types using the 10x Genomics Visium platform in immune-modulated AD models after various treatments. To proceed with an analysis suitable for barcode-based spatial transcriptomics, we first organized a workflow for segmentation of neuroanatomical regions, establishment of appropriate gene combinations, and comprehensive review of altered brain cell signatures. Ultimately, we investigated spatial transcriptomic changes following administration of immunomodulators, NK cell supplements and an anti-CD4 antibody, which ameliorated behavior impairment, and designated brain cells and regions showing probable associations with behavior changes. We provided the customized analytic pipeline into an application named STquantool. Thus, we anticipate that our approach can help researchers interpret the real action of drug candidates by simultaneously investigating the dynamics of all transcripts for the development of novel AD therapeutics.
Assuntos
Encéfalo , Modelos Animais de Doenças , Transcriptoma , Animais , Camundongos , Encéfalo/metabolismo , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Imunomodulação/efeitos dos fármacos , Demência/genética , Demência/terapia , Doença de Alzheimer/genética , Doença de Alzheimer/terapia , Perfilação da Expressão Gênica , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismoRESUMO
Sepsis remains a critical healthcare challenge, characterized by dysregulated immune responses to infection, leading to organ dysfunction and high mortality rates. Traditional treatment strategies often fail to address the underlying immune dysregulation, necessitating exploring novel therapeutic approaches. Immunomodulatory therapy holds promise in sepsis management by restoring immune balance and mitigating excessive inflammation. This comprehensive review examines the pathophysiology of sepsis, current challenges in treatment, and recent advancements in immunomodulatory agents, including biologics, immunotherapy, and cellular therapies. Clinical trial outcomes, safety profiles, and future research and clinical practice implications are discussed. While immunomodulatory therapies show considerable potential in improving sepsis outcomes, their successful implementation requires further research, collaboration, and integration into standard clinical protocols.
RESUMO
PURPOSE: We report a rare and challenging case of bilateral necrotizing scleritis in primary Sjögren's syndrome (pSS). METHODS: Retrospective case report. RESULTS: A 72-year-old diabetic, hypertensive female patient presented with sudden onset of painful red left eye and was noted to have a corneal ulcer with severe thinning. She was managed with topical fortified antibiotics and tissue glue and bandage contact lens. During subsequent follow-ups, she developed necrotizing scleral melts in both eyes. On investigations, antinuclear antibodies were positive in a dilution of 1:160 with 2+ speckled pattern, with antinuclear antibody line immunoassay showing anti SS-A/ Ro52 positive. In view of rapidly developing scleral thinning and impending perforation, she was started on intravenous methylprednisolone 1 g/day for 3 days, along with steroid-sparing immunomodulatory therapy (mycophenolate mofetil 500 mg twice a day). She showed a rapid response to therapy and is currently stable on tapering oral steroids and mycophenolate mofetil. CONCLUSION: This case underscores the unique presentation of pSS, characterized by bilateral necrotizing scleritis. The favorable outcome was attained through prompt immunosuppressive intervention and a collaborative, multidisciplinary approach. Further, this case report addresses a gap in the existing literature concerning pSS-related scleritis. It also emphasizes the crucial role of a rheumatologist in the comprehensive management of this condition.
RESUMO
BACKGROUND: Ocular inflammatory diseases, including scleritis and uveitis, have been widely treated with immunomodulatory therapies (IMTs) as a steroid-sparing approach. Such strategy includes conventional therapies (antimetabolites, alkylating agents, and calcineurin inhibitors) as well as biologic agents like adalimumab, infliximab, rituximab, and tocilizumab. Cyclophosphamide (CP) is an alkylating agent and mainly inhibits the functioning of both T and B cells. Though known to have potential adverse events, including bone marrow suppression, hemorrhagic cystitis, and sterility, CP has been shown to be efficacious, especially in recalcitrant cases and when used intravenous (IV) for a limited period. MAIN FINDINGS: We conducted a retrospective case-series to assess the safety and efficacy of CP therapy for patients with severe ocular inflammatory diseases who failed other IMTs. Medical records of 1295 patients who presented to the Uveitis Clinic at the Byers Eye Institute at Stanford between 2017 and 2022 were reviewed. Seven patients (10 eyes) who received CP therapy for ocular inflammatory diseases with at least one year of follow-up were included. The mean age of the patients (4 males, 3 females) was 61.6 ± 14.9 (43.0-89.0) years. Clinical diagnoses included necrotizing scleritis (5 eyes), peripheral ulcerative keratitis (2 eyes), orbital pseudotumor (1 eye), HLA-B27 associated panuveitis and retinal vasculitis (2 eyes). Ocular disease was idiopathic in 3 patients, and was associated with rheumatoid arthritis, IgG-4 sclerosing disease, dermatomyositis, and ankylosing spondylitis in 1 patient each. All the patients had history of previous IMT use including methotrexate (5), mycophenolate mofetil (3), azathioprine (1), tacrolimus (1), adalimumab (2), infliximab (4), and rituximab (1). The mean follow-up time was 34.4 ± 11.0 (13-45) months, and mean duration of CP therapy was 11.9 ± 8.8 (5-28) months. Remission was achieved in 5 patients (71.4%). Four patients (57.1%) experienced transient leukopenia (white blood cell count < 4000/mL). SHORT CONCLUSION: CP therapy can be considered a potentially effective and relatively safe therapeutic option for patients with severe ocular inflammatory diseases who failed other IMTs including biologics (TNFa and CD20 inhibitors).
RESUMO
Patients who undergo restorative proctocolectomy and ileoanal anastomosis can develop pouchitis as a common chronic complication. A rare subset of patients fails to respond to multiple antibiotic therapies and develop chronic antibiotic-refractory pouchitis (CARP). We present a case of a 45-year-old male with pouchitis refractory to chronic antibiotic therapy and histology demonstrating chronic inflammatory changes. Management involved mesalamine and probiotics, resulting in a positive clinical response and symptom absence on follow-up. This case highlights the intricacies of treating chronic pouchitis post ileoanal anastomosis, showcasing the efficacy of a personalized approach using mesalamine and probiotics. CARP is emerging as an entity associated with poor quality of life and increased healthcare costs. CARP fails to respond to multiple courses of antibiotic therapy. Therefore, the management of CARP is difficult and limited. Current literature on the management of CARP is scarce and mainly involves immunomodulatory therapy and probiotics. It is essential to keep this differential diagnosis in mind in patients with recurrent pouchitis episodes and start them on immunomodulator treatment and probiotics rather than repeated courses of antibiotics.