RESUMEN
BACKGROUND: With approximately 500 people affected in Austria, epidermolysis bullosa (EB) is a rare genetic skin disease reducing the quality of life of those affected and their relatives. The intensive efforts of the patient organisation DEBRA Austria during the last decades have led to a unique situation of those affected and their relatives, with increased support and broader knowledge about the disease in the general population. The aim of the study is to evaluate the current situation of patients and their relatives living in Austria, with a focus on burdens and helpful practices. RESULTS: The mixed-methods study consisted of two parts: a qualitative interview study to identify psychosocial aspects of EB in those affected and their relatives, and a subsequent online survey to further assess those aspects in a larger sample, resulting in a total of n=78 Austrian participants. The impact of EB on the quality of life of EB patients and their relatives in Austria is related to the current health status, psychological burden, mobility, visibility, financial situation as well as job prospects. Personal and social resources and external support have a significant influence on the individual situation. CONCLUSIONS: The outcome is mapped to concrete implications regarding targeted support for EB patients and their relatives on an individual level and their needs in regard to the Austrian health care system.
Asunto(s)
Epidermólisis Ampollosa , Calidad de Vida , Humanos , Austria/epidemiología , Masculino , Femenino , Adulto , Persona de Mediana Edad , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Epidermolysis bullosa (EB) is a rare disease characterised by skin fragility and a wide variety of symptoms. The Quality of Life in Epidermolysis Bullosa (QOLEB) score is an English 17-item EB-specific validated measurement tool with two dimensions: functioning and emotions. The aim of this cross-sectional study was to develop and validate a culturally adapted German QOLEB. The following steps were carried out: translation, expert evaluation, back translation, linguistic and cultural adaptation, sample-based psychometric testing and evaluation. Data analysis was performed with n = 46 patients across all EB types. The reliability and internal consistency of the translated German QOLEB were excellent (α = 0.901). Regarding convergent validity, the QOLEB correlated highly with the iscorEB (r = 0.879; p < 0.001). Structural similarity with the English original version was confirmed through exploratory factor analysis. In conclusion, the German QOLEB demonstrates internal reliability and construct validity and is suitable to assess the quality of life in German-speaking EB patients.
RESUMEN
BACKGROUND: In contrast to clinical diagnosis via external examination, patient-related outcome measures (PROMs) allow access to patients' internal perceptions. In the case of epidermolysis bullosa (EB) - a rare disease characterized by a wide variety of symptoms and individual disease courses - it is important to integrate the patient's perspective into diagnostic processes. The Instrument for Scoring Clinical Outcomes of Research for EB (iscorEB) is an EB-specific measurement tool, combining a clinician score (iscorEB-c) and a patient questionnaire (iscorEB-p). OBJECTIVES: The aim of this study is to establish the iscorEB-p as an independent PROM tool by exploring its psychometric properties. METHODS: Sample-based psychometric testing and evaluation were performed on data collected via a multinational online cross-sectional study. RESULTS: Data analysis was performed with n = 95 participants across all EB types. The reliability and internal consistency of the iscorEB-p was excellent (α = 0.90). Principal component analysis with a varimax rotation resulted in a two-factor solution, explaining 55.6% of the total variance, with the distinct factors 'everyday life functioning' and 'specific EB symptoms'. Convergent validity was shown by high correlations to the Satisfaction With Life Scale (r = -0.52, P < 0.001), the Quality of Life in Epidermolysis Bullosa questionnaire (r = 0.72, P < 0.001) and the Epidermolysis Bullosa Family Burden of Disease questionnaire (r = -0.73, P < 0.001). CONCLUSIONS: The iscorEB-p is a reliable and valid instrument to assess patient-reported health status of people with EB.
Epidermolysis bullosa (EB) is a rare chronic condition characterized by fragility of the skin. Even minimal friction leads to the formation of blisters and wounds. People with EB are often called 'butterfly children' because their skin is as fragile as a butterfly's wings. EB affects about 500,000 people worldwide and there is currently no cure. As EB is a chronic disease, it is associated with constantly changing periods of better and worse health. To monitor the impact of EB on patients, it is important to record a range of relevant possible symptoms using a valid questionnaire. The Instrument for Scoring Clinical Outcomes of Research for EB (iscorEB) is such a measurement tool, combining a clinician score (iscorEB-c) and a patient questionnaire (iscorEB-p). However, until now, the patient questionnaire could only be used in addition to the clinician score. In this study, we aimed to emphasize patients' perspectives and strengthen the patient questionnaire so that it can be used independently. The questionnaire can support patients to assess even minimal changes over a period of the last 4 weeks. We collected data from 95 patients with EB from all over the world. Through statistical analysis, we found that the questionnaire is a useful new standalone instrument to obtain a patient-based view of their health status. Overall, our study findings suggest that the iscorEB-p is a reliable and valid tool and could be usefully applied in clinical practice, as an addition to quality-of-service monitoring and in future research studies.
Asunto(s)
Epidermólisis Ampollosa , Medición de Resultados Informados por el Paciente , Psicometría , Calidad de Vida , Humanos , Epidermólisis Ampollosa/diagnóstico , Epidermólisis Ampollosa/psicología , Epidermólisis Ampollosa/terapia , Psicometría/normas , Masculino , Femenino , Adulto , Estudios Transversales , Reproducibilidad de los Resultados , Persona de Mediana Edad , Adolescente , Adulto Joven , Niño , Encuestas y Cuestionarios/normas , Anciano , Índice de Severidad de la Enfermedad , PreescolarRESUMEN
BACKGROUND: Inherited epidermolysis bullosa (EB) is a cluster of rare, genetic skin and mucosal fragility disorders with multi-system and secondary effects, in which blistering and erosions occur in response to friction/mechanical trauma. Considering the incurable and potentially life-limiting nature of the condition and the challenges posed by its symptoms, a palliative approach to EB-related care is necessary. However, knowledge and experience related to the provision of EB palliative care is minimal. Evidence-based, best care guidelines are needed to establish a base of knowledge for practitioners to prevent or ease suffering while improving comfort at all stages of the illness, not just the end of life. METHODS: This consensus guideline (CG) was begun at the request of DEBRA International, an international organization dedicated to improvement of care, research, and dissemination of knowledge for EB patients, and represents the work of an international panel of medical experts in palliative care and EB, people living with EB, and people who provide care for individuals living with EB. Following a rigorous, evidence-based guideline development process, the author panel identified six clinical outcomes based on the results of a survey of people living with EB, carers, and medical experts in the field, as well as an exhaustive and systematic evaluation of literature. Recommendations for the best clinical provision of palliative care for people living with EB for each of the outcomes were reached through panel consensus of the available literature. RESULTS: This article presents evidence-based recommendations for the provision of palliative healthcare services that establishes a base of knowledge and practice for an interdisciplinary team approach to ease suffering and improve the quality of life for all people living with EB. Any specific differences in the provision of care between EB subtypes are noted. CONCLUSIONS: Because there is yet no cure for EB, this evidence-based CG is a means of optimizing and standardizing the IDT care needed to reduce suffering while improving comfort and overall quality of life for people living with this rare and often devastating condition.
Asunto(s)
Epidermólisis Ampollosa , Cuidados Paliativos , Cuidado Terminal , Epidermólisis Ampollosa/terapia , HumanosRESUMEN
Background: Dystrophic Epidermolysis bullosa (DEB) is a rare inherited mechanobullous disease characterised by the hyperfragility of the skin and mucous membranes. It is (typically) caused by (loss-of-function) mutations in the COL7A1 gene that impair the formation of collagen type VII, which represents the major constituent of anchoring fibrils within the basement membrane zone of epithelialised tissues. In a 4-year-old patient diagnosed with the clinical features of recessive DEB, genotyping via Next-Generation EB Panel Sequencing initially revealed the homozygosity of the maternal c.425A>G mutation, while the paternal heterozygosity in exon 3 was lacking. This genetic profile suggested incongruent gene transmission due to uniparental isodisomy (UPD) or the occurrence of a hemizygous deletion of unknown size. Methods: Thus, the EB panel sequencing of genomic DNA, followed by a paternity test and analysis of microsatellite markers, as well as multiplex ligation-dependent probe amplification (MLPA) copy number analysis using patient and parental DNA, were performed. Results: This approach revealed a paternally derived hemizygous deletion spanning from exon 3 to exon 118. Linear amplification-mediated PCR (LAM-PCR) determined the breaking points within intron 2 of the COL7A1 gene, comprising a 40kb segment within intron 1 of the adjacent PFKFB4 gene. Conclusion: This report highlights the relevance of advanced molecular profiling to determine new/exceptional/unusual genotypes and the accurate mode of genetic transmission in DEB.
RESUMEN
BACKGROUND: Cold atmospheric pressure plasma (CAP) has antimicrobial and wound-healing properties. Patients affected by severe autosomal recessive dystrophic epidermolysis bullosa (RDEB) suffer from widespread, difficult-to-treat wounds, which require complex wound management. OBJECTIVE: In a pilot project, we investigated over a period of 5 months the response and tolerability of a CAP wound therapy in a 21-year-old and a 28-year-old female patient with severe generalized RDEB and following cutaneous squamous cell cancer (cSSC) in the older patient. MATERIALS AND METHODS: In both patients, diagnosis of RDEB was confirmed by molecular genetics. Individual- and patient-specific wound therapy was continued during the study period, and additionally CAP therapy with a dielectric barrier discharge (DBE) device was initiated. CAP treatment was performed for 90â¯s per wound and could be applied every day or every other day. Clinical evaluation included photographic documentation and regular interviews of patients and parents. RESULTS: CAP-treated wounds largely demonstrated improved wound healing and signs of a reduced bacterial contamination. Furthermore, CAP proved to prevent wound chronification. When applied on a polyester mesh, it was well-tolerated on most body sites. CONCLUSION: The introduction of CAP could improve the wound management of EB patients and should be evaluated in clinical studies. The effect of CAP on cSSC development should be particularly studied.
Asunto(s)
Carcinoma de Células Escamosas , Epidermólisis Ampollosa Distrófica , Epidermólisis Ampollosa , Gases em Plasma , Adulto , Epidermólisis Ampollosa Distrófica/diagnóstico , Epidermólisis Ampollosa Distrófica/genética , Epidermólisis Ampollosa Distrófica/terapia , Femenino , Humanos , Proyectos Piloto , Gases em Plasma/uso terapéutico , Cicatrización de HeridasRESUMEN
BACKGROUND: Wound management is a critical factor when treating patients with the inherited skin fragility disease dystrophic epidermolysis bullosa (DEB). Due to genetic defects in structural proteins, skin and mucous epithelia are prone to blistering and chronic wounding upon minor trauma. Furthermore, these wounds are commonly associated with excessive pruritus and predispose to the development of life-threatening squamous cell carcinomas, underscoring the unmet need for new therapeutic options to improve wound healing in this patient cohort. Vitamin D3 is acknowledged to play an important role in wound healing by modulating different cellular processes that impact epidermal homeostasis and immune responses. In this study, we evaluate the safety and efficacy of low-dose calcipotriol, a vitamin D3 analogue, in promoting wound healing and reducing itch and pain in patients with DEB. METHODS: Eligible DEB patients, aged ≥ 6 years and with a known mutation in the COL7A1 gene, were recruited to a placebo-controlled, randomized, double blind, cross-over phase II monocentric clinical trial. Patients were required to have at least two wounds with a minimum size of 6 cm2 per wound. The primary objective was to evaluate efficacy of daily topical application of a 0.05 µg/g calcipotriol ointment in reducing wound size within a 4-week treatment regimen. Secondary objectives were to assess safety, as well as the impact of treatment on pruritus, pain, and bacterial wound colonization in these patients. RESULTS: Six patients completed the clinical trial and were included into the final analysis. Topical low-dose calcipotriol treatment led to a significant reduction in wound area at day 14 compared to placebo (88.4% vs. 65.5%, P < 0.05). Patients also reported a significant reduction of pruritus with calcipotriol ointment compared to placebo over the entire course of the treatment as shown by itch scores of 3.16 vs 4.83 (P < 0.05) and 1.83 vs 5.52 (P < 0.0001) at days 14 and 28, respectively. Treatment with low-dose calcipotriol did not affect serum calcium levels and improved the species richness of the wound microbiome, albeit with no statistical significance. CONCLUSIONS: Our results show that topical treatment with low-dose calcipotriol can accelerate wound closure and significantly reduces itch, and can be considered a safe and readily-available option to improve local wound care in DEB patients. Trial Registration EudraCT: 2016-001,967-35. Registered 28 June 2016, https://www.clinicaltrialsregister.eu/ctr-search/trial/2016-001967-35/AT.
Asunto(s)
Epidermólisis Ampollosa Distrófica , Calcitriol/análogos & derivados , Colágeno Tipo VII , Método Doble Ciego , Humanos , Pomadas , Dolor/tratamiento farmacológico , Dolor/etiología , Prurito/tratamiento farmacológico , Prurito/etiología , Cicatrización de HeridasRESUMEN
Impaired wound healing complicates a wide range of diseases and represents a major cost to healthcare systems. Here we describe the use of discarded wound dressings as a novel, cost effective, accessible, and non-invasive method of isolating viable human cells present at the site of skin wounds. By analyzing 133 discarded wound dressings from 51 patients with the inherited skin-blistering disease epidermolysis bullosa (EB), we show that large numbers of cells, often in excess of 100 million per day, continually infiltrate wound dressings. We show, that the method is able to differentiate chronic from acute wounds, identifying significant increases in granulocytes in chronic wounds, and we show that patients with the junctional form of EB have significantly more cells infiltrating their wounds compared with patients with recessive dystrophic EB. Finally, we identify subsets of granulocytes and T lymphocytes present in all wounds paving the way for single cell profiling of innate and adaptive immune cells with relevance to wound pathologies. In summary, our study delineates findings in EB that have potential relevance for all chronic wounds, and presents a method of cellular isolation that has wide reaching clinical application.
Asunto(s)
Vendajes , Separación Celular , Epidermólisis Ampollosa , Granulocitos , Linfocitos T , Cicatrización de Heridas , Enfermedad Aguda , Adulto , Enfermedad Crónica , Epidermólisis Ampollosa/metabolismo , Epidermólisis Ampollosa/patología , Epidermólisis Ampollosa/terapia , Granulocitos/metabolismo , Granulocitos/patología , Humanos , Masculino , Linfocitos T/metabolismo , Linfocitos T/patologíaRESUMEN
BACKGROUND: Epidermolysis bullosa (EB) comprises inherited mechanobullous dermatoses with considerable morbidity and mortality. While current treatments are symptomatic, a growing number of innovative therapeutic compounds are evaluated in clinical trials. Clinical research in rare diseases like EB, however, faces many challenges, including sample size requirements and recruitment failures. The objective of this study was to determine attitudes of EB patients towards clinical research and trial participation as well as the assessment of contextual motivating and discouraging factors in an effort to support patient-centered RD trial designing. METHODS: A 53-items questionnaire was handed over to EB patients (of all types and ages) in contact with the EB House Austria, a designated national center of expertise for EB care. Main categories included level of interest in and personal knowledge about clinical studies, pros/cons for participation and extent of individual expenses considered acceptable for participation in a clinical study. Descriptive subgroup analysis was calculated with SPSS 20.0 and Microsoft Excel. RESULTS: Thirty-six individuals (mean age 25.7 years), diagnosed for recessive dystrophic EB (36.1%), EB simplex (33.4%), junctional EB (8.3%), dominant dystrophic EB (2.8%) and acral peeling syndrome (2.8%) participated. Motivation for participation in and the desire to increase personal knowledge about clinical trials were (outmost) high in 57.2 and 66.7%, respectively. Altruism was the major motivating factor, followed by hope that alleviation of the own symptoms can be achieved. The greatest hurdle was travel distance, followed by concerns about possible adverse reactions. Patients diagnosed for severe subgroups (RDEB, JEB) were more impaired by the extent of scheduled invasive investigations and possible adverse reactions of the study medication. Patients with generally milder EB forms and older patients were accepting more frequent outpatient study visits, blood takes, skin biopsies and inpatient admissions in association with trial participation. CONCLUSIONS: This study provides additional indications to better determine and address attitudes towards clinical research among EB patients as well as guidance to improve clinical trial protocols for patient centricity.
Asunto(s)
Epidermólisis Ampollosa Distrófica , Epidermólisis Ampollosa , Adulto , Actitud , Austria , Humanos , PielAsunto(s)
Carcinoma de Células Escamosas/complicaciones , Cetuximab/administración & dosificación , Epidermólisis Ampollosa Distrófica/complicaciones , Neoplasias Cutáneas/complicaciones , Cicatrización de Heridas , Adulto , Antineoplásicos Inmunológicos/administración & dosificación , Carcinoma de Células Escamosas/patología , Epidermólisis Ampollosa Distrófica/patología , Femenino , Humanos , Neoplasias Cutáneas/patologíaRESUMEN
Generalized severe epidermolysis bullosa simplex (EBS-gen sev) is caused by mutations within either the KRT5 or KRT14 gene, phenotypically resulting in blistering and wounding of the skin and mucous membranes after minor mechanical friction. In a clinical phase 2/3 trial, diacerein has recently been shown to significantly reduce blister numbers upon topical application. In this study we addressed basic pharmacokinetic parameters of locally applied diacerein in vitro and in vivo. Ex vivo experiments using a Franz diffusion cell confirmed the uptake and bio-transformation of diacerein to rhein in a porcine skin model. Rhein, the active metabolite of diacerein, was also detected in both urine and serum samples of two EBS-gen sev patients who topically applied a 1% diacerein ointment over a period of 4 weeks. The accumulated systemic levels of rhein in EBS-gen sev patients were lower than reported levels after oral application. These preliminary findings point towards the uptake and prolonged persistance of diacerein / rhein within the intended target organ - the skin. Further, they imply an acceptable safety profile at the systemic level. TRIAL REGISTRATION: DRKS. DRKS00005412 . Registered 6 November 2013.
Asunto(s)
Antraquinonas/farmacocinética , Antraquinonas/uso terapéutico , Antiinflamatorios/farmacocinética , Antiinflamatorios/uso terapéutico , Epidermólisis Ampollosa Simple/tratamiento farmacológico , Administración Tópica , Antraquinonas/administración & dosificación , Antraquinonas/química , Antiinflamatorios/administración & dosificación , Antiinflamatorios/química , Humanos , Masculino , Estructura MolecularRESUMEN
Recessive dystrophic epidermolysis bullosa (RDEB) patients suffer from chronic and repeatedly infected wounds predisposing them to the development of aggressive and life-threatening skin cancer in these areas. Vitamin D3 is an often neglected but critical factor for wound healing. Intact skin possesses the entire enzymatic machinery required to produce active 1-alpha,25-dihydroxyvitamin D3 (calcitriol), underscoring its significance to proper skin function. Injury enhances calcitriol production, inducing the expression of calcitriol target genes including the antimicrobial peptide cathelicidin (hCAP18), an essential component of the innate immune system and an important wound healing factor. We found significantly reduced hCAP18 expression in a subset of RDEB keratinocytes which could be restored by calcipotriol treatment. Reduced scratch closure in RDEB cell monolayers was enhanced up to 2-fold by calcipotriol treatment, and the secretome of calcipotriol-treated cells additionally showed increased antimicrobial activity. Calcipotriol exhibited anti-neoplastic effects, suppressing the clonogenicity and proliferation of RDEB tumor cells. The combined wound healing, anti-microbial, and anti-neoplastic effects indicate that calcipotriol may represent a vital therapeutic option for RDEB patients which we could demonstrate in a single-patient observation study.
Asunto(s)
Antibacterianos/farmacología , Antineoplásicos/farmacología , Calcitriol/análogos & derivados , Fármacos Dermatológicos/farmacología , Epidermólisis Ampollosa/metabolismo , Queratinocitos/efectos de los fármacos , Cicatrización de Heridas , Anciano , Péptidos Catiónicos Antimicrobianos/genética , Péptidos Catiónicos Antimicrobianos/metabolismo , Calcitriol/farmacología , Línea Celular , Células Cultivadas , Epidermólisis Ampollosa/patología , Humanos , Queratinocitos/metabolismo , Masculino , CatelicidinasRESUMEN
BACKGROUND: Epidermolysis bullosa simplex (EBS) is a rare genetic, blistering skin disease for which there is no cure. Treatments that address the pathophysiology of EBS are needed. OBJECTIVE: Compare the impact of 1% diacerein cream with placebo in reducing the number of blisters in EBS. METHODS: In a randomized, placebo-controlled, phase 2/3 trial we used a 1% diacerein topical formulation to treat defined skin areas in 17 patients. In a 2-period crossover trial, patients were randomized to either placebo or diacerein for a 4-week treatment and a 3-month follow-up in period 1. After a washout, patients were crossed over during period 2. The prespecified primary end point was the proportion of patients with a reduction of number of blisters by more than 40% from baseline in selected areas over the treatment episode. RESULTS: Of the patients receiving diacerein, 86% in episode 1 and 37.5% in episode 2 met the primary end point (vs 14% and 17% with placebo, respectively). This effect was still significant after the follow-up. Changes in absolute blister numbers were significant for the diacerein group only. No adverse effects were observed. LIMITATIONS: Low patient numbers and no invasive data acquisition because of clinical burden in children. CONCLUSION: This trial provides evidence of the impact of 1% diacerein cream in the treatment of EBS.
Asunto(s)
Antraquinonas/uso terapéutico , Epidermólisis Ampollosa Simple/diagnóstico , Epidermólisis Ampollosa Simple/tratamiento farmacológico , Producción de Medicamentos sin Interés Comercial , Administración Tópica , Antiinflamatorios , Niño , Preescolar , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Esquema de Medicación , Femenino , Estudios de Seguimiento , Humanos , Masculino , Cooperación del Paciente , Medición de Riesgo , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
Ichthyoses are a group of rare genetic skin disorders that pose numerous clinical challenges, in particular with respect to the correct diagnosis and appropriate management. The present update of the German ichthyosis guidelines addresses recent diagnostic advances that have resulted in the Sorèze consensus classification. In this context, we provide an updated diagnostic algorithm, taking into account clinical features as well as the molecular genetic basis of these disorders. Moreover, we highlight current therapeutic approaches such as psychosocial support, balneotherapy, mechanical scale removal, topical therapy, and systemic retinoid therapy. General aspects such as the indication for physical therapy, ergotherapy, or genetic counseling are also discussed. The present update was consented by an interdisciplinary consensus conference that included dermatologists, pediatricians, human geneticists, and natural scientists as well as representatives of the German patient support organization Selbsthilfe Ichthyose e. V.
Asunto(s)
Adhesión a Directriz , Ictiosis/diagnóstico , Ictiosis/terapia , Adolescente , Adulto , Niño , Preescolar , Diagnóstico Diferencial , Femenino , Predisposición Genética a la Enfermedad/genética , Alemania , Humanos , Ictiosis/clasificación , Ictiosis/genética , Lactante , Recién Nacido , Masculino , Embarazo , Pronóstico , Adulto JovenRESUMEN
Accurately addressing the diverse and complex issues of rare diseases (RD) in terms of prevention, recognition, diagnosis, treatment, care and research along key RD specificities, such as great heterogeneity, a limited number of patients, scarcity of relevant knowledge and expertise as well as enormous costs for patient care is a challenging task for healthcare providers and authorities that makes a supranational approach particularly feasible. The European Union has acknowledged RD matters by several initiatives, including efforts to implement national centres of expertise and European reference networks as well as a cross-border referral mechanism to foster access to expert services and to boost dissemination of clinical expertise and research activities. Exemplified by the EB House Austria, a centre of expertise for epidermolysis bullosa cross-linked with international reference partner institutions, this strategy proves its potential to be translated into optimized patient care and to meet the major medical, scientific, social and health-economic impact of RD.
Asunto(s)
Epidermólisis Ampollosa/diagnóstico , Epidermólisis Ampollosa/terapia , Unión Europea/organización & administración , Hospitales Generales/organización & administración , Modelos Organizacionales , Grupo de Atención al Paciente/organización & administración , Austria , Medicina Basada en la Evidencia , Humanos , Relaciones Interinstitucionales , Manejo de Atención al Paciente/organización & administración , Enfermedades Raras/diagnóstico , Enfermedades Raras/terapiaRESUMEN
Blistering in epidermolysis bullosa simplex type Dowling-Meara (EBS-DM) is associated with an inflammatory phenotype, which can be disrupted by diacerein in vitro. In this pilot study we hypothesized, that a topical formulation of diacerein 1% reduces blistering. Five patients initially applied diacerein underneath both armpits. Then, each participant received 1% diacerein-cream for one armpit, and placebo for the other (randomized withdrawal). The number of blisters was reduced significantly (left: -78%; right: -66% of baseline) within two weeks and remained significantly below the initial level even during withdrawal in four patients. These findings point to a relevant effect of diacerein and provide important information for a confirmative study.