Thio, H.B.

Perigranuloma localization and abnormal maturation of B cells emerging key players in sarcoidosis? (Article)

2013-02-15T00:00:00Z

Rationale: Recent observations of abnormal immunoglobulin responses and case reports describing successful B-cell ablative therapy suggest involvement ofBcells in the pathogenesis of sarcoidosis. Objectives: To investigate how abnormal B-cell maturation and function in patients with sarcoidosis contribute to disease. Methods: Patients with sarcoidosis (n = 32) were included for detailed analysis by immunohistochemistry of tissue, flow cytometry of blood B-cell subsets, andserumimmunoglobulin levels.Vaccinationresponses in patients with sarcoidosis to influenza virus and encapsulated bacteria andmolecular analysis ofimmunoglobulin heavy chain transcriptswere studied for functional analysis of immunoglobulin responses. Measurements and Main Results: Perigranuloma localization of IgAproducing plasma cells and numerous B cells were found in affected tissues. Total blood B-cell numbers were normal, CD271 memory B cells were significantly reduced, and CD272IgA1 B cells were significantly increased; the results are normalized in patients treated with TNF-ablockers.Despitethis,patientshadnormal serumimmunoglobulin levels and normal antigen-specific immunoglobulin responses. IgAand IgGtranscripts, however, showed highfrequencies of somatic hypermutations and increased usage of downstream IgG subclasses, suggestive for prolonged or repetitive responses. Conclusions: The large B-cell infiltrates in granulomatous tissue and increased molecular signs of antibody maturation are indicative of direct involvement of B cells in local inflammatory processes in patients with sarcoidosis. Moreover, CD272IgA1 B cells could be a marker for treatment with TNF-a blockers. These findings of B cells as emerging key players provide a rationale for a systematic study on B-cell ablative therapy in patients with sarcoidosis. Copyright

The influence of the location of the lesion on the absolute risk of the development of skin cancer in a patient with actinic keratosis (Article)

2012-10-16T00:00:00Z

The objective of this paper is to answer the clinical question whether the location of the lesion in an individual patient with actinic keratosis (AK) influences the absolute risk of the development of skin cancer. Between 0.025% and 16% of AK lesions advance towards squamous cell carcinoma per year. It is not well known whether this risk differs between locations on the body. A systematic search of available literature resulted in seven articles of which the two highest scoring on relevance and validity were selected. These two studies indicate that the absolute risk on the development of skin cancer in patients with AK differs between locations of the lesion and that time to progression from AK to squamous cell carcinoma is not different among the locations of the lesions. However, both studies have very limited sample sizes. © 2012 The Authors. Journal of the European Academy of Dermatology and Venereology

The skin-blanching assay (Article)

2012-10-01T00:00:00Z

The skin-blanching assay is used for the determination and bioequivalence of dermatologic glucocorticoids (GCs). The exact mechanism of the production of blanching is not fully understood, but it is considered that local vasoconstriction of the skin microvasculature and the consequent blood-flow reduction cause this phenomenon. Several factors influence skin blanching, including drug concentration, duration of application, nature of vehicle, occlusion, posture and location. The intensity of vasoconstriction can be measured in several ways: visual or quantitative methods, such as reflectance spectroscopy, thermography, laser Doppler velocimetry and chromametry. In literature, contradicting results in the correlation of the skin-blanching assay with different tests to determine GC sensitivity have been reported, limiting its clinical usefulness. © 2012 The Authors. Journal of the European Academy of Dermatology and Venereology

Fumarates vs. methotrexate in moderate to severe chronic plaque psoriasis: a multicentre prospective randomized controlled clinical trial (Article)

2011-04-01T00:00:00Z

Background Methotrexate and fumarates are effective systemic therapies for moderate to severe psoriasis according to the European S3 guidelines. Objectives We conducted a randomized controlled trial comparing the effectiveness and the adverse events of methotrexate and fumarates. Methods Sixty patients with moderate to severe psoriasis vulgaris were randomly assigned to treatment for 16 weeks with either methotrexate (30 patients; 15 mg per week) or fumarates (30 patients; 30 mg, followed by 120 mg according to a standard progressive dosage regimen) and were followed up for 4 weeks. The primary endpoint with respect to the efficacy was the difference in mean change from baseline in Psoriasis Area and Severity Index (PASI) after 12 weeks of treatment. The study was powered to detect a difference of five points. Analyses were by intention to treat. Results Six patients were excluded because five were not eligible and one withdrew consent. Two patients in the methotrexate group and one in the fumarate group dropped out during the 12 weeks of treatment because of nonappearance at the outpatient clinic. In total, 25 patients in the methotrexate group and 26 in the fumarate group were evaluated in the primary analysis. After 12 weeks of treatment, the mean ± SD PASI decreased from 14·5 ± 3·0 at baseline to 6·7 ± 4·5 in the 25 patients treated with methotrexate, whereas it decreased from 18·1 ± 7·0 to 10·5 ± 6·7 in the 26 patients treated with fumarates. After adjustment for baseline values, the absolute difference (fumarates minus methotrexate) in the mean values at 12 weeks was 1·4 (95% confidence interval −2·0 to 4·7; P = 0·417). Conclusions In this randomized trial methotrexate and fumarates were found to be equally effective in the treatment of patients with moderate to severe psoriasis. No serious or irreversible adverse events were observed in any of the patients.

European S3-guidelines on the systemic treatment of psoriasis vulgaris (Article)

2009-10-01T00:00:00Z

Neoplasms of the Facial Skin (Article)

2009-07-01T00:00:00Z

Neoplasms of the skin are found most often on the face. Malignant tumors of the facial skin pose a challenge in treatment, prohibiting compromises between oncologically responsible surgery and functional plus cosmetic outcome. The incidence of melanoma and nonmelanoma skin cancers is rising. Not all malignancies of the skin need to be treated by surgery. For in situ variants there are other options, such as photodynamic therapy and medical treatment. Knowledge of the clinical manifestation, behavior, and prognosis and histopathologic analysis lead to correct diagnosis and choice of suitable treatment. This article presents a synopsis of nonmelanoma, melanoma, and other cancers of the skin.

Skin manifestations of diabetes (Article)

2008-12-01T00:00:00Z

Diabetes mellitus can be complicated by a variety of cutaneous manifestations. Good metabolic control may prevent some of these manifestations and may support cure. Unfortunately, most glucose-lowering drugs also have cutaneous side effects. It is important to be able to recognize these signs and symptoms and to either treat them appropriately or refer the patient to a dermatologist or diabetologist.

Knowledge, attitudes and use of the guidelines for the treatment of moderate to severe plaque psoriasis among Dutch dermatologists (Article)

2008-08-01T00:00:00Z

Background: In 2003, the Dutch psoriasis guidelines were among the first evidence-based medicine guidelines in dermatology. Although pivotal, the implementation of dermatological guidelines has not been assessed. Objectives: To evaluate various aspects that affect implementation of clinical guidelines such as knowledge, attitudes and practices among dermatologists. Methods: A cross-sectional anonymous postal survey was conducted among all Dutch dermatologists. In addition to questions about knowledge and practices, 24 items assessed guidelines attitudes. Factor analysis was applied to merge these items into attitudinal scales and multiple linear regression was used to identify predictors for these scales. Results: Of the 353 dermatologists, 161 (46%) completed the questionnaire. Almost all respondents were aware of the guidelines and 60% reported to have a decent knowledge of their content. Factor analysis retained 22 items divided into three scales: usefulness and content, barriers, and reliability. Apart from some disagreement on the user-friendliness and communication facilitating properties, the dermatologists' attitudes were generally positive. A larger volume of patients with psoriasis was associated with more frequent use of the guidelines [adjusted odds ratio (OR) = 2.42; 95% confidence interval (CI) 1.02-5.72]. Good familiarity predicted a more positive attitude towards the guidelines' usefulness and content (P < 0.001), perceived barriers (P < 0.001), and more frequent use in practice (adjusted OR = 8.38; 95% CI 3.08-22.81). Conclusions: Dutch dermatologists seem to know and appreciate their psoriasis guidelines and use them more often when they have a larger psoriasis population. Enhancing the familiarity of the guidelines among users may result in a more positive attitude towards them and a higher frequency of use.

Is imatinib mesylate a promising drug in systemic sclerosis? (Article)

2008-08-01T00:00:00Z

A patient with therapy-resistant and progressive systemic sclerosis (SSc) with pulmonary involvement who was treated with imatinib mesylate is described herein. Prior to treatment, pulmonary fibroblasts obtained from the patient were cultured and incubated with imatinib mesylate. Preincubation of the fibroblasts for 16 hours with 2.5 μg/ml imatinib mesylate efficiently abrogated platelet-derived growth factor BB-induced fibroblast proliferation. Furthermore, transforming growth factor β1-induced type I collagen gene transcription was blocked. During treatment, the patient's pulmonary involvement stabilized and her skin tightness improved. To our knowledge, this is the first report of a patient with therapy-refractory SSc responding to treatment with imatinib mesylate.

Loss-of-function mutations in the filaggrin gene lead to reduced level of natural moisturizing factor in the stratum corneum (Article)

2008-08-01T00:00:00Z

Repigmentation of vitiligo during efalizumab (Article)

2008-08-01T00:00:00Z

Evaluation of the reimbursement criteria for biological therapies for psoriasis in the Netherlands (Article)

2008-05-01T00:00:00Z

Authors' reply [2] (Article)

2008-02-01T00:00:00Z

The use of serological titres of IgA and IgG in (early) discrimination between rectal infection with non-lymphogranuloma venereum and lymphogranuloma venereum serovars of Chlamydia trochomotis (Article)

2007-07-01T00:00:00Z

Objectives: To investigate whether serological titres of species-specific IgA and IgG antibodies in patients with rectal chlamydial infection could discriminate between infection with serovar L2 lymphogranuloma venereum (LGV) and infection with non-LGV serovars. Methods: A total of 39 male patients with chlamydial infection of the rectum were tested for titres of IgA and IgG antibodies within 14 days after detection of the infection and 6 and 12 months after adequate treatment. Data were collected regarding demographics, sexual orientation, HIV serostatus, history of chlamydial infection, concomitant sexually transmitted infection (STI) or HIV infection, hepatitis C virus antibodies and new STIs during follow-up. Results: Between May 2003 and November 2005, 24 men with confirmed L2 proctitis and 15 men with non-LGV rectal chlamydial infection were recruited. In multivariable analyses, both high titre of IgA within 14 days after detection of the infection and older age of the individual were found significantly associated with L2 proctitis (p<0.001 and p = 0.001, respectively). A total sum score of seven times IgA titre and individual's age ≥50 years resulted in an overall sensitivity of 92% and specificity of 100%. This total sum score was highly accurate for detection of LGV proctitis, with an area under the curve in a receiver operating characteristic curve of 0.989. Conclusions: An increased IgA antibody response and the age of the infected individual are of possible diagnostic value for (early) detection of LGV proctitis.

Unfavorable cardiovascular risk profiles in untreated and treated psoriasis patients (Article)

2007-01-01T00:00:00Z

Psoriasis is a chronic inflammatory skin disease that is associated with an increased cardiovascular risk profile. The systemic inflammation present in psoriasis, various systemic treatments for psoriasis and an increased prevalence of unhealthy life style factors may all contribute to this unfavorable risk profile. The purpose of this article is to provide an overview of what is known about these risk factors in psoriasis, the way they influence the cardiovascular risk of psoriasis patients, and what can be done to reduce this risk. Genetic studies demonstrate that psoriasis and cardiovascular disease share common pathogenic features in which, for example inflammatory cytokines like TNF-α and IL-1 play an important role. The chronic inflammation in psoriasis has an unfavorable effect on the cardiovascular risk profile. Multiple cardiovascular risk factors seem to be influenced; the blood pressure, oxidative stress, dyslipidemia, endothelial cell dysfunction, homocysteine levels and blood platelet adhesion. Moreover, classic cardiovascular risk factors like smoking and obesity that have an increased prevalence among patients with psoriasis, indirectly also worsen the cardiovascular risk profile by stimulating the psoriasis activity. Systemic treatments in psoriasis reduce the cardiovascular risk by diminishing the inflammation, but it should be taken into account that most therapies also have adverse cardiovascular effects like dyslipidemia, hyperhomocysteinemia and hypertension. As a consequence preventive measures may be indicated at least during long-term treatments. Prospective research is warranted to accurately estimate the increased cardiovascular risk in psoriasis, to determine the underlying processes and to consider preventive measures according to the absolute risk of cardiovascular disease. The present overview provides data to advice health care providers to pay more attention to the cardiovascular risk profile in psoriasis patients.

Rescue of progeria in trichothiodystrophy by homozygous lethal Xpd alleles. (Article)

2006-10-30T00:00:00Z

Although compound heterozygosity, or the presence of two different mutant alleles of the same gene, is common in human recessive disease, its potential to impact disease outcome has not been well documented. This is most likely because of the inherent difficulty in distinguishing specific biallelic effects from differences in environment or genetic background. We addressed the potential of different recessive alleles to contribute to the enigmatic pleiotropy associated with XPD recessive disorders in compound heterozygous mouse models. Alterations in this essential helicase, with functions in both DNA repair and basal transcription, result in diverse pathologies ranging from elevated UV sensitivity and cancer predisposition to accelerated segmental progeria. We report a variety of biallelic effects on organismal phenotype attributable to combinations of recessive Xpd alleles, including the following: (i) the ability of homozygous lethal Xpd alleles to ameliorate a variety of disease symptoms when their essential basal transcription function is supplied by a different disease-causing allele, (ii) differential developmental and tissue-specific functions of distinct Xpd allele products, and (iii) interallelic complementation, a phenomenon rarely reported at clinically relevant loci in mammals. Our data suggest a re-evaluation of the contribution of "null" alleles to XPD disorders and highlight the potential of combinations of recessive alleles to affect both normal and pathological phenotypic plasticity in mammals.