Oral lichen planus: comparative efficacy and treatment costs-a systematic review.

OBJECTIVE: To compare the reported efficacy and costs of available interventions used for the management of oral lichen planus (OLP). MATERIALS AND METHODS: A systematic literature search was performed from database inception until March 2021 in MEDLINE via PubMed and the Cochrane library following PRISMA guidelines. Only randomized controlled trials (RCT) comparing an active intervention with placebo or different active interventions for OLP management were considered. RESULTS: Seventy (70) RCTs were included. The majority of evidence suggested efficacy of topical steroids (dexamethasone, clobetasol, fluocinonide, triamcinolone), topical calcineurin inhibitors (tacrolimus, pimecrolimus, cyclosporine), topical retinoids, intra-lesional triamcinolone, aloe-vera gel, photodynamic therapy, and low-level laser therapies for OLP management. Based on the estimated cost per month and evidence for efficacy and side-effects, topical steroids (fluocinonide > dexamethasone > clobetasol > triamcinolone) appear to be more cost-effective than topical calcineurin inhibitors (tacrolimus > pimecrolimus > cyclosporine) followed by intra-lesional triamcinolone. CONCLUSION: Of common treatment regimens for OLP, topical steroids appear to be the most economical and efficacious option followed by topical calcineurin inhibitors. Large-scale multi-modality, prospective trials in which head-to-head comparisons interventions are compared are required to definitely assess the cost-effectiveness of OLP treatments.

Onset of Pyoderma Gangrenosum in Patients on Biologic Therapies: A Systematic Review.

OBJECTIVE: To summarize clinical outcomes of paradoxical pyoderma gangrenosum (PG) onset in patients on biologic therapy. METHODS: The authors conducted MEDLINE and EMBASE searches using PRISMA guidelines to include 57 patients (23 reports). RESULTS: Of the included patients, 71.9% (n = 41/57) noted PG onset after initiating rituximab, 21.1% (n = 12/57) noted tumor necrosis factor α (TNF-α) inhibitors, 5.3% (n = 3/57) reported interleukin 17A inhibitors, and 1.8% (n = 1/57) reported cytotoxic T-lymphocyte-associated protein 4 antibodies. The majority of patients (94.3%) discontinued biologic use. The most common medications used to resolve rituximab-associated PG were intravenous immunoglobulins, oral corticosteroids, and antibiotics, with an average resolution time of 3.3 months. Complete resolution of PG in TNF-α-associated cases occurred within an average of 2.2 months after switching to another TNF-α inhibitor (n = 1), an interleukin 12/23 inhibitor (n = 2), or treatment with systemic corticosteroids and cyclosporine (n = 3), systemic corticosteroids alone (n = 1), or cyclosporine alone (n = 1). CONCLUSIONS: Further investigations are warranted to determine whether PG onset is associated with underlying comorbidities, the use of biologic agents, or a synergistic effect. Nevertheless, PG may develop in patients on rituximab or TNF-α inhibitors, suggesting the need to monitor and treat such adverse effects.

Interventions for treating oral lichen planus.

BACKGROUND: Oral lichen planus (OLP) is a common chronic autoimmune disease associated with cell-mediated immunological dysfunction. Symptomatic OLP is painful and complete healing is rare. OBJECTIVES: To assess the effectiveness and safety of any form of therapy for symptomatic OLP. SEARCH STRATEGY: The following electronic databases were searched: the Cochrane Oral Health Group Trials Register (to 26 January 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 1), MEDLINE via OVID (1950 to 26 January 2011) and EMBASE via OVID (1980 to 26 January 2011). There were no restrictions regarding language or date of publication. SELECTION CRITERIA: All randomised controlled clinical trials (RCTs) of therapy for symptomatic OLP which compared treatment with a placebo or between treatments or no intervention were considered in this review. DATA COLLECTION AND ANALYSIS: The titles and abstracts of all reports identified were scanned independently by two review authors. All studies meeting the inclusion criteria were assessed for risk of bias and data were extracted. For dichotomous outcomes, the estimates of effects of an intervention were expressed as risk ratios (RR) together with 95% confidence intervals. For continuous outcomes, mean differences (MD) and 95% confidence intervals were used to summarise the data for each group. The statistical unit was the patient. Meta-analyses were done only with studies of similar comparisons reporting the same outcome measures. MAIN RESULTS: 28 trials were included in this review. Pain is the primary outcome of this review because it is the indication for treatment of OLP, and therefore this review indicates as effective, only those treatments which significantly reduce pain. Although topical steroids are considered first line treatment for symptomatic OLP, we identified no RCTs that compared steroids with placebo. There is no evidence from the three trials of pimecrolimus that this treatment is better than placebo in reducing pain from OLP. There is weak evidence from two trials, at unclear and high risk of bias respectively, that aloe vera may be associated with a reduction in pain compared to placebo, but it was not possible to pool the pain data from these trials. There is weak and unreliable evidence from two small trials, at high risk of bias, that cyclosporin may reduce pain and clinical signs of OLP, but meta-analysis of these trials was not possible.There were five trials that compared steroids with calcineurin inhibitors, each evaluating a different pair of interventions. There is no evidence from these trials that there is a difference between treatment with steroids compared to calcineurin inhibitors with regard to reducing pain associated with OLP. From six trials there is no evidence that any specific steroid therapy is more or less effective at reducing pain compared to another type or dose of steroid. AUTHORS' CONCLUSIONS: Although topical steroids are considered to be first line treatment, we identified no RCTs that compared steroids with placebo in patients with symptomatic OLP. From the trials in this review there is no evidence that one steroid is any more effective than another. There is weak evidence that aloe vera may reduce the pain of OLP and improve the clinical signs of disease compared to placebo. There is weak and unreliable evidence that cyclosporin may reduce pain and clinical signs of OLP. There is no evidence that other calcineurin inhibitors reduce pain compared to either steroids or placebo. From the 28 trials included in this systematic review, the wide range of interventions compared means there is insufficient evidence to support the effectiveness of any specific treatment as being superior.

Evaluation and management of steroid-unresponsive nephrotic syndrome.

PURPOSE OF REVIEW: Idiopathic nephrotic syndrome in children is commonly associated with minimal change disease and response to steroid therapy. Steroid-unresponsive nephrotic syndrome is often characterized by persistent proteinuria and progression to chronic kidney disease. Focal segmental glomerulosclerosis is the leading cause of steroid-unresponsive nephrotic syndrome in childhood. There is no uniformed consensus as to the treatment of steroid-unresponsive nephrotic syndrome. Advances in the pathogenesis, genetics and biomarkers or surrogate markers may be useful for the diagnosis and identification of patients with steroid-unresponsive nephrotic syndrome, severity of disease, progression and response to therapy. RECENT FINDINGS: This review is intended to describe some of the recent changes in the epidemiology of steroid-unresponsive nephrotic syndrome, in particular focal segmental glomerulosclerosis, its pathogenesis and alternative therapies. SUMMARY: Recent studies in both children and adults have shown an increase in the incidence of focal segmental sclerosis as a cause of steroid-unresponsive nephrotic syndrome. Advances in the pathogenesis and noninvasive methods of diagnosis may allow for the identification of steroid-responsive patients.

Erupción vesiculosa asociada a inyección conjuntival / Vesicular eruption associated with conjunctival injection

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Tratamiento del liquen plano oral: una revisión / Treatment of oral lichen planus: a review

El objetivo del presente estudio fue realizar una revisión sobre los actuales tratamientos del liquen plano oral(LPO). Antes de iniciar el tratamiento al paciente, debe de realizarse una biopsia para establecer el correcto diagnóstico. Dado que para el LPO no hay tratamiento curativo, el primer objetivo en los pacientes sintomáticos es el efecto paliativo. Entre las alternativas terapéuticas se incluyen: corticosteroides tópicos, sistémicos e intralesionales; retinoides tópicos o sistémicos; ciclosporina tópica, tacrolimus tópico, azatioprina, fototerapia y tratamiento quirúrgico (AU)

The aim of the present study was to review about the current treatment of oral lichen planus (OLP). Before a patients is started on therapy a biopsy must be done to establish an accurate diagnosis. Because there is no curative therapy for OLP, the primary goal for symtomatic patients is palliative. Treatment modalities include the use of: topical, systemic and intralesional corticosteroids; topical and systemic retinoids, topical cyclosoporine; topical tacrolimus; azathioprine; phototherapy and surgical procedures (AU)

Estrategias para optimizar el tratamiento con efalizumab / Strategies to improve treatment with efalizumab

Con el objetivo de optimizar los resultados clínicos de efalizumab y garantizar su empleo bajo criterios de seguridad resulta fundamental adquirir una cierta sistemática en su manejo. De forma previa a proponer y prescribir el tratamiento, el dermatólogo deberá cerciorarse de que el paciente cumple los requisitos para poder iniciarlo y de que, por otro lado, no presenta ninguna contraindicación grave que pueda comprometer su seguridad a corto o largo plazo. Durante el curso del tratamiento deberán establecerse unas pautas de seguimiento que permitan tanto contrastarla evolución del paciente con respecto a las perspectivas generales de efalizumab como monitorizar y manejarlos efectos adversos más habituales asociados a su empleo. Finalmente, será adecuado familiarizarse con la evolución natural de la enfermedad una vez suspendido el tratamiento en aquellos casos en los que esta actuación decida o deba tomarse (AU)

It is essential to improve the clinical results of efalizumab and to assure that it is used under safety criteria in order to obtain a systemic management of the treatment. Prior to proposing and prescribing the treatment, the dermatologist should make sure that the patient fulfills pills the requirements to be able to initiate it and that, on the other hand, there is no serious contraindication that may affect its short-to-long term safety. During the course of the treatment, some follow-up guidelines should be established that will make it possible to compare the evolution of the patient with the general perspectives of efalizumab as well as to monitor and manage the most common adverse effects associated to its use. Finally, it would be convenient to become familiar with the natural course of the disease once the treatment is discontinued in those cases in which this action is decided or should be carried out (AU)

Un caso con excelente respuesta a efalizumab. Experiencia en el Hospital Universitario de Salamanca / A case of excellent response of efalizumab. Experience in the University Hospital of Salamanca

Antes de iniciar el tratamiento con efalizumab, o con cualquier tratamiento biológico, es necesario utilizar técnicas de valoración objetiva que nos permitan evaluar la actividad y la evolución de la psoriasis, para así poder justificar la indicación de la terapia biológica, así como valorar el porcentaje de respuesta al tratamiento, la pérdida de respuesta o su posible ineficacia. A pesar de sus limitaciones, el índice de intensidad y gravedad de la psoriasis (PASI) es la mejor opción disponible. La definición de psoriasis moderada se ha propuesto a partir de un PASI basal = 7 mientras que para la psoriasis grave es, según los distintos autores, 10 o 121. En la práctica clínica habitual, en la definición de la gravedad de la psoriasis y en la indicación de establecer un tratamiento sistémico es preciso valorar también otros parámetros, ya que algunas formas de psoriasis tienen un curso más agresivo (psoriasis eritrodérmica, pustulosa) y existen localizaciones (cabeza, genitales, manos, etc.) que interfieren más intensamente en la calidad de vida de los pacientes, con aumento de la disfunción social, de la discapacidad física y del deterioro psicológico 2,3. Todos los pacientes tratados con terapia biológica en nuestro centro hospitalario cumplen los criterios establecidos por la European Medicines Evaluation Agency (EMEA): pacientes adultos con psoriasis en placas crónica moderada grave que no han respondido o tienen contraindicada o no toleran otra terapia sistémica incluyendo ciclosporina, metotrexato o fototerapia (AU)

Before initiating treatment with efalizumab, or with any other biological treatment, it is necessary to use objective assessment techniques that allow us to evaluate the activity on course of psoriasis, thus being able to justify the indication of biological therapy and to evaluate the percentage of response to treatment, loss of response or its possible inefficacy. In spite of its limitations, Psoriasis Area and Severity Index (PASI) is the best available option. The definition of moderate psoriasis has been proposed as beginning with a baseline PASI =7 while serious psoriasis has a score of, according to the different authors, 10 or 121 In the usual clinical practice, other parameters must also be evaluated in the definition of the seriousness of psoriasis and in the indication of establishing a systemic treatment since some forms of psoriasis have a more aggressive course (erythrodermicpsoriasis, pustulous psoriasis) and there are locations (head, genitals, hands, etc.) that interfere more intensely with the quality of life of the patients, with increase of social dysfunction, physical incapacity and psychological deterioration 2,3. All of the patients treated with biological therapy in our hospital site fulfill the criteria established by the European Medicines Evaluation Agency (EMEA): adult patients with psoriasis in chronic moderate-to-serious ones who have not responded or in its use is contraindicated or who do not tolerate another systemic therapy, including, cyclosporine, methotrexate or phototherapy (AU)

[Follow up of Crohn's disease under therapy with hydro-MRI]. / Hydro-MRT in der Verlaufsbeobachtung des Morbus Crohn unter Therapie.

PURPOSE: Evaluation of typical MRI-findings in patients with Crohn's disease receiving therapy. Correlation with the course of disease. PATIENTS AND METHODS: 81 follow-up MRI-studies in 25 patients conducted within a period of 3 weeks to 4 years were evaluated retrospectively. Therapy consisted in various combinations of antibiotics and immunosuppressive agents and if necessary operation. The findings of the MRI-studies were correlated with clinical data (e.g.operation of Crohn's complications) and the subjective perception during therapy. RESULTS: The morphological substrate of Crohn's disease in the Hydro-MRI images is reliably detected. Especially in a delineation of extraluminal changes MRI is superior to endoscopy and enteroclysis. Independent from clinical symptoms short- and mid-term follow-up showed inflammatory changes of the intestinal wall in all 25 patients. In 24/81 studies there was persistence or even progression of Crohn's disease in the MRI-studies, although patients were free of symptoms by the time of image acquisition. CONCLUSION: Hydro-MRI is a modality for the evaluation of inflammatory changes in patients with Crohn's disease. Independent from clinical symptoms persistence of Crohn's disease is detectable.

Advances in the treatment of lupus nephritis.

Systemic lupus erythematosus (SLE) is an autoimmune disease that leads to the formation and deposition of immune complexes throughout the body, which are pathogenic for the disease. Different forms of glomerulonephritis can occur in patients with SLE and can contribute significantly to the associated morbidity and, ultimately, mortality from the disease. Over the past two decades, there have been significant strides in our understanding of the disease and in treatments that attempt to control the formation and deposition of anti-DNA auto-antibodies and immune complexes, as well as the subsequent inflammatory cascade mediated through various cellular and humoral pathways leading to progressive renal damage and end-stage renal disease. In this chapter, we review the current understanding of the pathogenesis and treatment of lupus nephritis in its various stages and discuss the experimental and human data regarding some of the potential newer forms of therapy. We discuss data regarding the use of steroids, azathioprine, cyclophosphamide, cyclosporine A, mycophenolate mofetil, gammaglobulin, plasmapheresis, LJP 394, flaxseed oil, bindarit, anti-CD40 ligand, and CTLA4Ig.

Alopecia areata / Alopecia Areata

La alopecia areata es una enfermedad de base autoinmune crónica de etiología incierta. La información recolectada en el presente artículo se presenta de forma clara y concisa, enfatizando los aspectos más relevantes de la etiopatogenia, epidemiología, clasificación, características clínicas, histopatología, diagnóstico diferencial y tratamiento. Además, se incluye un test de autoevaluación como parte de la actividad de aprendizaje de la sección Formación Médica Continuada (AU)

Interventions for treating oral lichen planus.

BACKGROUND: Oral lichen planus is a chronic autoimmune disease of unknown aetiology that affects the inner surface of the mouth. The symptomatic forms are painful,tend to worsen with age and with remissions being rare. Current treatment is palliative and not curative, many topical and systemic agents have been tried with little hard evidence for efficacy. OBJECTIVES: To assess the effectiveness and safety of any form of palliative therapy against placebo for the treatment of symptomatic oral lichen planus. SEARCH STRATEGY: Electronic databases, handsearching of conference proceedings and specific journals, researchers in the field, drug manufacturers. SELECTION CRITERIA: Any placebo-controlled trial of palliative therapy for symptomatic oral lichen planus, using a randomised or quasi-randomised design that measured changes in symptoms and/or clinical signs. DATA COLLECTION AND ANALYSIS: Change in symptoms (pain, discomfort) and clinical signs (visual impression, lesion measurements) at the end of therapy. Odds ratio of improvement vs no improvement for each trial outcome and pooling where appropriate. MAIN RESULTS: A total of nine RCTs were identified. The nine interventions were grouped into four separate classes (cyclosporines, retinoids, steroids and phototherapy) for comparison. No therapy was replicated exactly, the closest replication involved two trials using high and low dose cyclosporine mouthwash. Only trials recording the same outcomes in each therapeutic class were pooled. The largest number of pooled trials was three. Large odds ratios with very wide confidence intervals indicating a statistically significant treatment benefit were seen in all trials. However this has to be tempered by considerations of the small study sizes, the lack of replication, the difficulty in measuring outcome changes and the very high likelihood of publication bias. Only systemic agents were associated with treatment toxicities, all other side-effects were mild and mainly limited to local mucosal reactions. REVIEWER'S CONCLUSIONS: The review provides only weak evidence for the superiority of the assessed interventions over placebo for palliation of symptomatic OLP. The results highlight the need for larger placebo-controlled RCTs with more carefully selected and standardised outcome measures before between-treatment comparisons can be properly interpreted.

[Immunosuppression--a tightrope walk between iatrogenic harm and therapy]. / Immunsuppression--Gratwanderung zwischen latrogenie und Therapie.

The therapeutic effect of most immunosuppressive agents is unspecific and therefore often limited by an increased risk of infection by viral, bacterial or fungal organisms as well as by an increased incidence of malignant neoplasms. This short review includes the most commonly used immunosuppressants such as corticosteroids, azathioprine, methotrexate, cyclophosphamide and cyclosporine. The most common risks of long-term corticosteroid treatment are Cushing-like changes, decreased glucose tolerance and the usually benign steroid diabetes. Also clinically important is osteoporosis, since it can be prevented by physical training, calcium supplementation and treatment with vitamin D if necessary. Although there is still no proof of a significantly increased risk of peptic ulcer during steroid therapy, patients may develop gastrointestinal hemorrhage and even perforation without producing pain while being treated with corticosteroids. Mineralocorticoid effects, such as salt and water retention, are seen only with hydrocortisone and prednisone, whereas with synthetic steroids such as dexamethasone, sodium retention is absent despite their strong antiphlogistic activity. The most important side effect of the cytotoxic agents azathioprine, methotrexate and cyclophosphamide is marrow suppression. Due to the high turnover of neutrophils, patients most frequently suffer neutropenia rather than thrombocytopenia or anemia. Neutropenia, as well as impaired humoral and cellular immune mechanisms, are responsible for increased susceptibility to bacterial, viral or parasitic diseases during immunosuppressive therapy. Hepatotoxicity has been reported among patients receiving azathioprine (cholestatic hepatitis) and methotrexate (elevated AST levels and, rarely, liver fibrosis or cirrhosis). Cyclophosphamide causes hemorrhagic cystitis in a substantial proportion of patients, as well as an increased incidence of urothelial neoplasms. Both these side effects may be prevented by Mesna. The most important side effects of cyclosporine are acute and chronic nephrotoxicity usually associated with significantly elevated plasma levels of the drug. It must be borne in mind that severe nephrotoxicity may occur in patients receiving cyclosporine and ketoconazole together, since the latter may inappropriately increase the plasma cyclosporine level.

Antimalarial activity of cyclosporins A, C and D.

Cyclosporin A (CsA) is an immunosuppressive drug widely used in organ transplants. It is also accumulated by the erythrocyte, a site that accommodates one of the stages of malaria parasite. We observe that CsA and its less potent immunosuppressive analogues CsC and CsD were as effective as chloroquine in inhibiting P. berghei malaria parasite development in vivo (when administered orally) and P. falciparum parasite in vitro. They were, however, not inhibitory to the liver stages and the gametocytes. In vivo the minimum effective dose was 10 mg/Kg administered on two consecutive days whereas, in vitro CsA and its analogues inhibited parasite development at concentrations of 10 micrograms/ml and above.