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International Urogynecology Journal May 2016Bladder pain syndrome/interstitial cystitis (BPS/IC) has various treatments; however, no standardized treatment has been established. The aim was to analyze different... (Review)
Review
INTRODUCTION AND HYPOTHESIS
Bladder pain syndrome/interstitial cystitis (BPS/IC) has various treatments; however, no standardized treatment has been established. The aim was to analyze different types of treatment of BPS/IC and their effectiveness.
METHODS
A literature review with a search strategy for articles related to BPS/IC published between 1990 and 2014 was conducted on MEDLINE, PUBMED, and SCOPUS. Only randomized controlled trials in women were included in the meta-analysis, while other experimental studies were used as bases for a systematic review of the topic. Clinical trial quality was defined according to the Jadad scale.
RESULTS
Of 356 articles, 13 were included in the analysis. The intervention methods were as follows: instillation of hyaluronic acid, botulinum toxin A, intravesical lidocaine, hyperbaric chamber, massage, physiotherapy, phosphate-buffered saline, piroxicam in combination with doxepin, and others. We did not find any treatment with at least two randomized controlled trials for meta-analysis. Among the assessment tools for symptoms of BPS/IC, the most frequently used were the visual analogue scale, voiding record, and the O'Leary-Sant questionnaire.
CONCLUSION
Existing studies were not able to define the best approach for the treatment of BPS/IC. The lack of standardized treatment may be related to the diversity of interventions used; therefore, further studies with better methodological quality are needed.
Topics: Acetylcholine Release Inhibitors; Adjuvants, Immunologic; Administration, Intravesical; Anesthetics, Local; Anti-Inflammatory Agents, Non-Steroidal; Antidepressive Agents; Botulinum Toxins, Type A; Cystitis, Interstitial; Drug Therapy, Combination; Female; Humans; Hyaluronic Acid; Hyperbaric Oxygenation; Lidocaine; Pentosan Sulfuric Polyester; Physical Therapy Modalities; Sodium Chloride
PubMed: 26272202
DOI: 10.1007/s00192-015-2815-5 -
American Journal of Ophthalmology Jul 2021To describe the prevalence and spectrum of disease of pentosan polysulfate (PPS) maculopathy in a large multimodal retinal imaging study and to report the results of...
PURPOSE
To describe the prevalence and spectrum of disease of pentosan polysulfate (PPS) maculopathy in a large multimodal retinal imaging study and to report the results of choroidal vascularity index (CVI) analysis.
DESIGN
Prospective cohort study Methods: Of 741 patients prescribed PPS within a large university database, 100 (13.4%) with any consumption agreed to participate in a prospective screening investigation. Multimodal retinal imaging including near-infrared reflectance (NIR), fundus autofluorescence (FAF), and spectral domain optical coherence tomography (SD-OCT) was performed in all patients. Characteristic findings of affected patients were identified, and affected and unaffected cohorts were compared. CVI, defined as stromal choroidal area (SCA) divided by the total choroidal area, was analyzed.
RESULTS
The prevalence of PPS maculopathy was 16%. NIR illustrated punctate hyperreflective lesions with early presentation. FAF illustrated a speckled macular network of hypo- and hyperautofluorescence colocalized with multifocal hyperreflective retinal pigment epithelial lesions on SD-OCT. Advanced cases demonstrated varying degrees of atrophy. The affected cohort exhibited significantly greater mean PPS therapy duration, mean daily dosage, and mean cumulative dosage (19.5±5.5 years, 433.9±137.6 mg, 3,103.1±1,402.2 g) compared with the unaffected cohort (7.1±6.6 years, 291.6±177.6 mg, 768.4±754.8 g). SCA was significantly lower and CVI was significantly greater in the affected vs the unaffected group.
CONCLUSIONS
This prospective cohort study identified a prevalence of PPS maculopathy of 15%-20% among PPS users who agreed to participate. A spectrum of findings may be observed with multimodal retinal imaging. Significant choroidal abnormalities associated with this characteristic maculopathy may provide surrogate markers of macular toxicity.
Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Body Mass Index; Choroid; Female; Fluorescein Angiography; Humans; Male; Middle Aged; Multimodal Imaging; Optical Imaging; Pentosan Sulfuric Polyester; Perfusion Index; Prevalence; Prospective Studies; Retina; Retinal Diseases; Retinal Pigment Epithelium; Tomography, Optical Coherence; Visual Acuity; Young Adult
PubMed: 33651989
DOI: 10.1016/j.ajo.2021.02.025 -
Retinal Cases & Brief Reports Nov 2023The purpose of this study was to describe the characteristic pattern of progression of pentosan polysulfate (PPS) maculopathy with multimodal retinal imaging in two...
BACKGROUND/PURPOSE
The purpose of this study was to describe the characteristic pattern of progression of pentosan polysulfate (PPS) maculopathy with multimodal retinal imaging in two patients, including one with over 9 years of follow-up.
METHODS
Two patients with PPS maculopathy were sequentially evaluated with near-infrared reflectance (NIR) and optical coherence tomography.
RESULTS
Near-infrared reflectance showed characteristic centrifugal progression of the parafoveal hyperreflective lesions toward the vascular arcades with the development of hyporeflective areas in both cases. Optical coherence tomography demonstrated focal retinal pigment epithelium (RPE) thickening that corresponded to the hyperreflective lesions on NIR. On subsequent optical coherence tomography scans, the hyperreflective areas resolved with the development of ellipsoid zone attenuation, RPE disruption, and atrophy, which colocalized with hyporeflectivity on NIR.
CONCLUSION
This report describes the progression of pentosan polysulfate maculopathy over almost 10 years of PPS treatment and highlights the importance of NIR as a tool for the diagnosis and monitoring of PPS maculopathy. Pentosan polysulfate lesions present as areas of focal RPE thickening with ensuing development of ellipsoid zone loss and RPE drop-out. The pathophysiology of PPS toxicity is unknown and may either result from primary RPE or choroidal toxicity.
Topics: Humans; Pentosan Sulfuric Polyester; Retina; Retinal Diseases; Macular Degeneration; Retinal Pigment Epithelium; Tomography, Optical Coherence; Fluorescein Angiography
PubMed: 35344532
DOI: 10.1097/ICB.0000000000001276 -
Mayo Clinic Proceedings Jun 2021
Topics: Adult; Cystitis, Interstitial; Humans; Macular Degeneration; Middle Aged; Pentosan Sulfuric Polyester
PubMed: 34088428
DOI: 10.1016/j.mayocp.2021.04.002 -
Obstetrics and Gynecology May 2020Recent studies have implicated long-term pentosan polysulfate use with vision loss from a newly described macular condition. Affected patients report difficulty with...
Recent studies have implicated long-term pentosan polysulfate use with vision loss from a newly described macular condition. Affected patients report difficulty with reading and adjusting to dim lighting, and they occasionally develop severe visual disability. Macular changes resemble those seen in age-related macular degeneration, potentially leading to misdiagnosis. The objectives of this Current Commentary are to summarize studies evaluating the association between pentosan polysulfate use and macular disease, to educate pentosan polysulfate prescribers about the clinical manifestations of this condition, and to provide recommendations for screening at-risk patients.
Topics: Adult; Aged; Cystitis, Interstitial; Female; Humans; Macular Degeneration; Middle Aged; Pentosan Sulfuric Polyester
PubMed: 32282604
DOI: 10.1097/AOG.0000000000003794 -
International Urogynecology Journal May 2021Oral pentosan polysulphate (PPS) has been used in the treatment of bladder pain syndrome/interstitial cystitis (BPS/IC) for almost 35 years. However, in some recent... (Review)
Review
INTRODUCTION AND HYPOTHESIS
Oral pentosan polysulphate (PPS) has been used in the treatment of bladder pain syndrome/interstitial cystitis (BPS/IC) for almost 35 years. However, in some recent studies, questions have been raised about its efficacy in treating this condition. We aimed to evaluate the published medical literature and discuss the clinical utility of oral PPS in the treatment of BPS/IC.
METHODS
PUBMED was searched for BPS/IC, treatment and PPS. Of the initial 398 articles screened, 7 randomized controlled trials, 3 systematic reviews and 3 meta-analyses were finally included in this study (Fig. 1). Other relevant literature such as observational studies and various clinical guidelines was also reviewed. The inclusion criteria, intervention methodology and end points of the studies were examined.
RESULTS
Of the seven RCTs, five found a clear beneficial role of oral PPS in IC/BPS. The only study which did not have cystoscopy as a diagnostic and inclusion criterion failed to show any benefit of oral PPS compared to placebo. Two out of three meta-analyses clearly concluded that oral PPS had a positive role to play in the treatment of BPS/IC. Various open-label studies did conclude in favour of oral PPS as a treatment modality for these patients.
CONCLUSION
Oral PPS remains a useful pharmacological agent for treatment of BPS/IC, even though it may be effective only in a subgroup of patients.
Topics: Cystitis, Interstitial; Cystoscopy; Humans; Pentosan Sulfuric Polyester; Randomized Controlled Trials as Topic
PubMed: 32894327
DOI: 10.1007/s00192-020-04517-9 -
Biochemical Pharmacology May 2020Hepcidin peptide is crucial in the regulation of systemic iron availability controlling its uptake from the diet and its release from the body storage tissues. Hepcidin...
Hepcidin peptide is crucial in the regulation of systemic iron availability controlling its uptake from the diet and its release from the body storage tissues. Hepcidin dysregulation causes different human disorders ranging from iron overload (e.g. hemochromatosis) to iron deficiency (e.g. anemia). Hepcidin excess is common in the Anemia of Chronic Diseases or Anemia of Inflammation and in the genetic form of anemia named IRIDA; the pharmacological downregulation of hepcidin in these disorders could improve the anemia. Commercial heparins were shown to be strong inhibitors of hepcidin expression, by interfering with BMP6/SMAD pathway. The non-anti-coagulant heparins, modified to abolish the anti-thrombin binding site, were equally potent and could be used to improve iron status. To perform its anti-hepcidin activity heparin needs 2O- and 6O-sulfation and an average molecular weight (MW) up to 4000-8000 Dalton, depending on the sulfation level. The pentosane polysulfate (PPS), which shares with heparin a high degree of sulfation, is a compound with low anti-coagulant activity that is already in use for pharmaceutical treatment. In the present work we analyzed the anti-hepcidin activity of PPS in vitro and in vivo. We found that it acts as a strong inhibitor of hepcidin expression in HepG2 cells with an effect already visible after 2-3 h of treatment. It also suppressed hepcidin in mice in a dose dependent manner after 3 h and with a significant redistribution of systemic iron without evident side effects. PPS is also able to abolish the LPS dependent hepcidin upregulation similarly to that showed for heparin derivatives. These results suggest PPS as an interesting compound to control hepcidin in vivo.
Topics: Administration, Oral; Animals; Gene Expression; Hep G2 Cells; Hepcidins; Humans; Injections, Subcutaneous; Liver; Male; Mice; Mice, Inbred C57BL; Pentosan Sulfuric Polyester
PubMed: 32088260
DOI: 10.1016/j.bcp.2020.113867 -
Canadian Journal of Ophthalmology.... Apr 2024Pentosan polysulfate (PPS; ELMIRON, Janssen Pharmaceuticals, Titusville, NJ) is a U.S. Food and Drug Administration-approved oral medication for interstitial cystitis....
OBJECTIVE
Pentosan polysulfate (PPS; ELMIRON, Janssen Pharmaceuticals, Titusville, NJ) is a U.S. Food and Drug Administration-approved oral medication for interstitial cystitis. Numerous reports have been published detailing retinal toxicity with the use of PPS. Studies characterizing this condition are primarily retrospective, and consequently, alert and screening systems need to be developed to actively screen for this disease. The goal of this study was to characterize ophthalmic monitoring trends of a PPS-using patient sample to construct an alert and screening system for monitoring this condition.
METHODS
A single-institution retrospective chart review was conducted between January 2005 and November 2020 to characterize PPS use. An electronic medical record (EMR) alert was constructed to trigger based on new PPS prescriptions and renewals offering ophthalmology referral.
RESULTS
A total of 1407 PPS users over 15 years was available for characterization, with 1220 (86.7%) being female, the average duration of exposure being 71.2 ± 62.6 months, and the average medication cumulative exposure being 669.7 ± 569.2 g. A total of 151 patients (10.7%) had a recorded visit with an ophthalmologist, with 71 patients (5.0%) having optical coherence tomography imaging. The EMR alert fired for 88 patients over 1 year, with 34 patients (38.6%) either already being screened by an ophthalmologist or having been referred for screening.
CONCLUSIONS
An EMR support tool can improve referral rates of PPS maculopathy screening with an ophthalmologist and may serve as an efficient method for longitudinal screening of this condition with the added benefit of informing pentosan polysulfate prescribers about this condition. Effective screening and detection may help determine which patients are at high risk for this condition.
Topics: Humans; Female; Male; Pentosan Sulfuric Polyester; Retrospective Studies; Eye; Retinal Diseases; Face
PubMed: 36878265
DOI: 10.1016/j.jcjo.2023.01.019 -
Journal of Virology Aug 2015Arthritogenic alphaviruses such as Ross River virus (RRV) and chikungunya virus (CHIKV) cause large-scale epidemics of severe musculoskeletal disease and have been...
UNLABELLED
Arthritogenic alphaviruses such as Ross River virus (RRV) and chikungunya virus (CHIKV) cause large-scale epidemics of severe musculoskeletal disease and have been progressively expanding their global distribution. Since its introduction in July 2014, CHIKV now circulates in the United States. The hallmark of alphavirus disease is crippling pain and inflammation of the joints, a similar immunopathology to rheumatoid arthritis. The use of glycans as novel therapeutics is an area of research that has increased in recent years. Here, we describe the promising therapeutic potential of the glycosaminoglycan (GAG)-like molecule pentosan polysulfate (PPS) to alleviate virus-induced arthritis. Mouse models of RRV and CHIKV disease were used to characterize the extent of cartilage damage in infection and investigate the potential of PPS to treat disease. This was assessed using histological analysis, real-time PCR, and fluorescence-activated cell sorting (FACS). Alphaviral infection resulted in cartilage destruction, the severity of which was alleviated by PPS therapy during RRV and CHIKV clinical disease. The reduction in cartilage damage corresponded with a significant reduction in immune infiltrates. Using multiplex bead arrays, PPS treatment was found to have significantly increased the anti-inflammatory cytokine interleukin-10 and reduced proinflammatory cytokines, typically correlated with disease severity. Furthermore, we reveal that the severe RRV-induced joint pathology, including thinning of articular cartilage and loss of proteoglycans in the cartilage matrix, was diminished with treatment. PPS is a promising new therapy for alphavirus-induced arthritis, acting to preserve the cartilage matrix, which is damaged during alphavirus infection. Overall, the data demonstrate the potential of glycotherapeutics as a new class of treatment for infectious arthritis.
IMPORTANCE
The hallmark of alphavirus disease is crippling pain and joint arthritis, which often has an extended duration. In the past year, CHIKV has expanded into the Americas, with approximately 1 million cases reported to date, whereas RRV continues to circulate in the South Pacific. Currently, there is no licensed specific treatment for alphavirus disease, and the increasing spread of infection highlights an urgent need for therapeutic intervention strategies. Pentosan polysulfate (PPS) is a glycan derivative that is orally bioavailable, has few toxic side effects, and is currently licensed under the name Elmiron for the treatment of cystitis in the United States. Our findings show that RRV infection damages the articular cartilage, including a loss of proteoglycans within the joint. Furthermore, treatment with PPS reduced the severity of both RRV- and CHIKV-induced musculoskeletal disease, including a reduction in inflammation and joint swelling, suggesting that PPS is a promising candidate for drug repurposing for the treatment of alphavirus-induced arthritis.
Topics: Animals; Cartilage; Chikungunya Fever; Chikungunya virus; Disease Models, Animal; Glycosaminoglycans; Humans; Joint Diseases; Mice; Mice, Inbred C57BL; Pentosan Sulfuric Polyester
PubMed: 26018160
DOI: 10.1128/JVI.00224-15 -
Clinical Ophthalmology (Auckland, N.Z.) 2021To investigate the prevalence of retinal pathology in patients with a history of exposure to pentosan polysulfate sodium (PPS).
AIM
To investigate the prevalence of retinal pathology in patients with a history of exposure to pentosan polysulfate sodium (PPS).
METHODS
Patients exposed to PPS and seen in the ophthalmology clinic at Northwestern University during 1/1/2002 to 1/1/2019 were identified from electronic health records (EHR) by an electronic data warehouse (EDW) search. Visual acuity (VA), reasons for clinic visit, ocular conditions, and duration of exposure to PPS were noted. Chart review was performed for fundus exam findings and ophthalmologic imaging, specifically fundus photography, fundus autofluorescence, and ocular coherence tomography (OCT) images. When OCT or fundus photography was available, studies were evaluated by two independent graders.
RESULTS
A total of 131 patients who were exposed to PPS and seen at the Northwestern Ophthalmology clinic were identified in the EHR. Forty patients of 131 had imaging. Patients with imaging or fundus examination suspicious for PPS maculopathy were placed into the suspect group. Of the 40 patients that had imaging, 5 (12.5%) had features suspicious for PPS maculopathy. Of the remaining 91, 5 (5.4%) had macular pigmentary changes described on fundus exam. Among the 10 patients in the suspect group, the average duration of PPS use was 4.2 years (range 0.3-11.6 years, interquartile range 5.5 years) and the average cumulative dose was 380g (range 29-1092g, interquartile range 132g).
CONCLUSION
A novel drug-induced maculopathy has been associated with PPS use with a distinct clinical constellation that can be accurately identified with multimodal imaging.
PubMed: 33603329
DOI: 10.2147/OPTH.S285013