Reinhart Speeckaert

Ghent University | UGhent · Department of Dermatology

Vitamin D-binding protein (DBP), also known as Gc-globulin, is a protein that affects several physiological processes, including the transport and regulation of vitamin D metabolites. Genetic polymorphisms in the DBP gene have a significant impact on vitamin D levels and may have implications for disease risk. DBP polymorphisms are linked to differ...

The early detection of gynecological cancers, which is critical for improving patient survival rates, is challenging because of the vague early symptoms and the diagnostic limitations of current approaches. This comprehensive review delves into the game-changing potential of infrared (IR) spectroscopy, a noninvasive technology used to transform the...

Renal amyloidosis is a set of complex disorders characterized by the deposition of amyloid proteins in the kidneys, which causes gradual organ damage and potential kidney failure. Recent developments in diagnostic methods, particularly mass spectrometry and proteome profiling, have greatly improved the accuracy of amyloid typing, which is critical...

Background/Objectives: There is currently no guidance on how to interpret the global degrees of activity (worsening) and repigmentation (improvement) in vitiligo. Stratification into global degrees can be completed for static evaluations (e.g., visible disease activity signs) and dynamic assessments (e.g., evolution over time). For the latter, the...

Skin pigmentation by melanocytes is regulated by complex mechanisms including melanoblast migration, melanosome transport, melanosome transfer and melanogenesis. Melanogenesis is influenced by UV light, and endocrine, paracrine and autocrine factors. This leads to a large differential diagnosis of pigmentary disorders. Additionally, melanocytes are...

Although warmth is a key sign of inflammatory skin lesions, an objective assessment and follow‐up of the temperature changes are rarely done in dermatology. The recent availability of accurate, sensitive and cost‐effective thermography devices has made the implementation of thermography in clinical settings feasible. The aim of this scoping review...

Chronic kidney disease (CKD) is a growing health concern with a complex etiological landscape. Among the numerous factors implicated, vitamin D binding protein (VDBP) has emerged as a focal point of scientific studies because of its critical role in vitamin D metabolism and immune modulation. The relationship between VDBP and CKD reveals a complex...

Reactive oxygen species (ROS) generated during melanogenesis make melanocytes particularly vulnerable to oxidative stress, influencing their survival and melanin synthesis. Oxidative stress, significantly present in vitiligo and recently also detected in melasma, triggers inflammatory cascades and melanogenesis, making antioxidants a promising ther...

Hematological diseases, due to their complex nature and diverse manifestations, pose significant diagnostic challenges in healthcare. The pressing need for early and accurate diagnosis has driven the exploration of novel diagnostic techniques. Infrared (IR) spectroscopy, renowned for its noninvasive, rapid, and cost-effective characteristics, has e...

Raman spectroscopy, a non-invasive diagnostic technique capturing molecular vibrations, offers significant advancements in skin cancer diagnostics. This review delineates the ascent of Raman spectroscopy from classical methodologies to the forefront of modern technology, emphasizing its precision in differentiating between malignant and benign skin...

Haptoglobin (Hp) is a polymorphic protein that was initially described as a hemoglobin (Hb)-binding protein. The major functions of Hp are to scavenge Hb, prevent iron loss, and prevent heme-based oxidation. Hp regulates angiogenesis, nitric oxide homeostasis, immune responses, and prostaglandin synthesis. Genetic polymorphisms in the Hp gene give...

There is evidence of a link between disease activity in vitiligo and clinical visible signs such as confetti‐like depigmentation, Koebner phenomenon and hypochromic areas/borders. Despite its established value, dermatologists and researchers continue to have a limited understanding of the vitiligo disease activity signs. The primary goal of this st...

Uromodulin, also known as Tamm-Horsfall protein, represents the predominant urinary protein in healthy individuals. Over the years, studies have revealed compelling associations between urinary and serum concentrations of uromodulin and various parameters, encompassing kidney function, graft survival, cardiovascular disease, glucose metabolism, and...

The current understanding of the placebo response in vitiligo is limited. Nonetheless, it is difficult to compare the outcomes of vitiligo trials if the repigmentation rates in placebo patients vary significantly. We conducted a meta‐analysis of the placebo response in vitiligo trials. Overall, repigmentation rates in patients receiving placebo wer...

Background The treatment of vitiligo can be challenging and depends on several factors such as the subtype, disease activity, vitiligo extent, and treatment goals. Vitiligo usually requires a long‐term approach. To improve the management of vitiligo worldwide, a clear and up‐to‐date guide based on international consensus with uniform stepwise recom...

Background The treatment of vitiligo can be challenging. Up‐to‐date agreed consensus recommendations on the use of topical and systemic therapies to facilitate the clinical management of vitiligo are currently lacking. Objectives To develop internationally agreed‐upon expert‐based recommendations for the treatment of vitiligo. Methods In this con...

Clinician-reported outcome measures (ClinROMs) are essential for assessment of vitiligo in clinical trials and daily practice. Several instruments have been developed and tested to measure e.g., vitiligo extent, repigmentation and activity. The goal of this review was to identify all introductory publications of ClinROMs for vitiligo that include a...

Growth differentiation factor-15 (GDF-15) is a GDF subfamily member with potential kidney protective functions. Its nephroprotective activity is associated with both inflammation downregulation and upregulation of nephroprotective factors with anti-inflammatory activity, such as Klotho in tubular cells. However, GDF-15 has diverse and partially opp...

Chemokine research offers insightful information on the pathogenesis of cutaneous immune disorders, such as vitiligo. Compared to cytokines, the higher detectable levels of chemokines display promising potential as future disease biomarkers. Nonetheless, some published study results are contradictory, which can be attributed to patient characterist...

Advanced glycation end products (AGEs) are a class of compounds formed by nonenzymatic interactions between reducing sugars and proteins, lipids, or nucleic acids. AGEs can alter the protein structure and activate one of their receptors, specifically the receptor for advanced glycation end products (RAGE). These phenomena impair the functions of ce...

Vitamin D is an important immune modulator that is linked to infection susceptibility. It has been suggested that vitamin D deficiency plays a role in sepsis and septic shock because vitamin-D-related pathways are associated with various immunological, endocrine, and endothelial functions. Previous research has yielded inconclusive results regardin...

Extracellular vesicles are a diverse group of particles that include exosomes, microvesicles, and apoptotic bodies and are defined by size, composition, site of origin, and density. They incorporate various bioactive molecules from their cell of origin during formation, such as soluble proteins, membrane receptors, nucleic acids (mRNAs and miRNAs),...

Background : The management of vitiligo is guided by the assessment of disease activity. However, this assessment is hampered by the absence of a highly feasible and reliable single marker to evaluate activity. Furthermore, the need for an objective, easy, preferably noninvasive marker is further stressed by the increased amount of research perform...

Members of the European Academy of Dermatology and Venereology (EADV) Task Force on Quality of Life (QoL) and Patient Oriented Outcomes reviewed the instruments available for health-related (HR) QoL assessment in vitiligo and together with external vitiligo experts (including representatives of the EADV Vitiligo Task Force) have made practical reco...

Importance: The minimally important difference (MID) represents the point at which a difference in an outcome measure (eg, Dermatology Life Quality Index) is important enough that it warrants a change in treatment, and, to the authors' knowledge, the robustness and limitations of MIDs have not been thoroughly evaluated in skin diseases. The MID is...

Background There is a lack of consensus related to the collection of standardized data for individuals with vitiligo enrolled in clinical trials and registries as well as those seen in clinical practice which causes difficulty in accurately interpreting, comparing, and pooling of data. Several years ago, efforts to initiate work on developing core...

Background: Clinician-reported outcome measures (ClinROMs) are frequently used in clinical trials and daily practice to evaluate the disease status and evolution of skin disorders. The minimal important difference (MID) represents the smallest difference that decreases the disease impact enough to make a treatment change worthwhile for patients. A...

Several digital image analysis systems have been developed for surface calculation of vitiligo lesions. Critical assessment of their measurement properties is crucial to support evidence‐based recommendations on the most suitable instruments and will reveal the need for future research. A systematic review was performed to systematically summarize,...

The targeted inhibition of effector cytokines such as interleukin 17 (IL-17) in psoriasis and IL-13 in atopic dermatitis offers impressive efficacy with a favorable side effect profile. In contrast, the downregulation of interferon gamma (IFN-γ) in T helper (Th) 1-dominant skin disorders may lead to more adverse events, given the crucial role of IF...

Background: The epidermal growth factor (EGF) is a globular protein that is generated in the kidney, especially in the loop of Henle and the distal convoluted tubule. While EGF is nonexistent or hardly detectable in plasma, it is present in normal people's urine. Until now, risk stratification and chronic kidney disease (CKD) diagnosis have relied...

Background: The assessment of the individual evolution of vitiligo is important for therapeutic decision-making in daily practice. A fast, simple and validated physician reported score to assess clinical changes in depigmentation over time in separate parts (activity and improvement) is currently missing. Objective: To develop and validate the V...

Melanocytes exhibit a complex and intriguing relationship with the skin immune response, leading to several clinical conditions. In some disorders, inappropriate melanocyte destruction (e.g. vitiligo, halo naevi) is problematic, while in others immune tolerance should be broken (melanoma). Important parts of the dysregulated pathways have been unra...

According to several animal and human studies, vitamin D appears to play a significant role in the development of diabetic nephropathy. However, the possible renoprotective effect of vitamin D and its influence on the reversal of already existing renal damage remains doubtful. At this moment, there are a few hypotheses concerning the underlying mol...

Large-scale vaccination strategies are currently being deployed against severe acute respiratory syndrome coronavirus-2 (SARS-Cov-2). Whether systemic medication for skin diseases affects the efficacy of vaccination and whether temporary interruption or extension of the dosing interval is necessary is under debate. Most immunomodulating/immunosuppr...

Disappearance of melanocytes is the pathogenic hallmark of vitiligo. Progressive depigmentation of the skin has a high negative impact on patients’ quality of life. To date, vitiligo remains a therapeutic challenge. Several theories have been proposed to explain disease pathogenesis, considering the roles of increased inflammatory and cytotoxic imm...

Identifying which factors contribute to vitiligo severity and determining their individual weight are important in the management of vitiligo. The aim of this study is to investigate the predictive variables concerning vitiligo severity as perceived by the patients. Based on a questionnaire, several factors that may contribute to the Patient Global...

The biologic era has greatly improved the treatment of Crohn's disease and ulcerative colitis. Biologics can however induce a wide variety of skin eruptions, especially those targeting the TNF-α and Th17 pathway. These include infusion reactions, eczema, psoriasis, lupus, alopecia areata, vitiligo, lichenoid reactions, granulomatous disorders, vasc...

The autoimmune basis of segmental vitiligo (SV) has only recently been recognized. Systemic autoimmune diseases are less frequently associated compared to non-segmental vitiligo (NSV), but localized skin disorders – in particular linear morphea – have been repeatedly observed in patients with SV. The inflammatory response is documented on a clinica...

Isoforms of the receptor for advanced glycation end-product (RAGE) protein, which lack the transmembrane and the signaling (soluble RAGE or sRAGE) domains are hypothesized to counteract the detrimental action of the full-length receptor by acting as a decoy, and they provide a potential tool to treat RAGE-associated diseases. Multiple studies have...

It is largely unknown how reliable patients with psoriasis and eczema can estimate their involved body surface area (BSA). Nonetheless, this calculation is important for the development of patient‐reported outcome measures (PROMs). The current standards remain the rule of hands (= 1 hand palm surface area equals 1% BSA) and the rule of nines (= cha...

Background The Self Assessment Vitiligo Extent Score (SA‐VES) is a validated, patient reported outcome measure to assess the body surface area affected with vitiligo. Information on how to translate the obtained score into extent, severity and impact strata (mild‐moderate‐severe) is still lacking. Stratification is helpful to define inclusion crite...

Vitiligo is a common chronic depigmenting skin disease. We explored the utility of near‐infrared (NIR) spectroscopy in the identification of spectral changes associated with disease activity in vitiligo patients. In vivo spectral measurements were performed directly on the perilesional skin of 70 vitiligo patients. Relative intensities (second deri...

Background: The association between disease activity and several clinical signs in vitiligo has been described, but a widely accepted and validated scoring system is lacking. Objective: To validate the Vitiligo Signs of Activity Score (VSAS) for physicians. Methods: Three visible clinical signs were scored on 15 body locations: Confetti-like d...

Background: Clinical photography is an important component of the initial assessment and follow up of vitiligo patients in clinical practice and research settings. Standardization of this photographic process is essential to achieve useful, high quality and comparable photographs over time. Objective: The aim is to develop an international conse...

The impressive potential of biologics has been demonstrated in psoriasis, hidradenitis suppurativa, and urticaria. Numerous biologicals are entering the field for a restricted number of skin disorders. Off-label use of biologics in other recalcitrant skin diseases has increased. Mounting data point to the potential of already existing biologics act...

Koebner phenomenon (KP) is a well-known entity in dermatology. It was first described in 1876 by Heinrich Koebner, a German dermatologist, as “the development of lesions at sites of specifically traumatized uninvolved skin of patients with cutaneous diseases”. Since then, this isomorphic response has been reported in a several skin diseases, such a...

Segmental vitiligo is characterized by its early onset, rapid stabilization and unilateral distribution (Chap. 6). Prevalences between 3.5% and 20.5% of all patients with vitiligo have been reported [1]. Many studies across decades and all over the world have attempted to clarify the pathogenesis behind it, but the exact pathophysiology of segmenta...

Background The accurate determination of the dosage of topical treatments is important given its repercussions on patient adherence and therapeutic efficacy. Up till now, the fingertip unit calculated by the rule of hands is considered the gold standard, although its use is associated with several drawbacks. Objective To compare different methods...

Vitiligo is an unpredictable depigmenting disorder for which a static method to assess disease activity is lacking. Presence of certain skin manifestations may be indicative of disease activity. Here, we evaluated the current evidence for an association between clinical signs and reported disease activity in vitiligo. A systematic review and meta‐a...

Initially considered as a macrophage inhibitor (macrophage inhibitory cytokine-1), growth differentiation factor 15 (GDF-15) has been identified as a pleiotropic protein that plays key roles in prenatal development, in inflammation, in the regulation of cellular responses to stress signals, and in tissue repair after acute injuries in adult life. M...

Multiple reports confirm elevated circulating IL‐17 levels and increased numbers of Th17 lymphocytes in patients with non‐segmental vitiligo. Additionally, melanocyte damaging characteristics have been ascribed to IL‐17. A single‐arm pilot study using secukinumab in active non‐segmental vitiligo was conducted. The large majority of patients develop...

Currently, vitiligo lacks a validated Physician Global Assessment (PGA) for disease extent. This PGA can be used to stratify and interpret the numeric scores obtained by the Vitiligo Extent Score (VES). We investigated the interrater reliability of a 5‐point PGA scale during an international vitiligo workshop. Vitiligo experts from 5 different cont...

甲真菌病是甲的真菌感染。在近几十年中,相对于重要风险因素(例如,糖尿病)的增多和生活方式的改变,甲真菌病的发病率总体增高,最常用于诊断甲真菌病的检测(例如氢氧化钾溶液、过碘酸‐希夫染色组织病理学检查和培养)耗时或需要经过特殊训练的人员。相对于肉眼,红外光谱能让医生们更细致地观察皮肤。近期,由于所用仪器的显著进步和新技术的开发,红外光谱领域已扩展出了令人激动的新应用。这种技术表现出了吸引人的特征,如迅速、简单、无创,甚至便携。此外,只需要极低水平的专业技能,准备成本低,即光谱仪的固定成本是一次性的。这项研究的目的是确定“衰减全反射傅里叶转化红外” (ATR‐FTI)光谱能否在实验室和患者中检测和辨别甲真菌病的原因。这项研究得出了以下结论,即可通过 ATR ‐FTIR 光谱以一种简单快速的方式检...

Onychomycosis is a fungal infection of the nail. During recent decades, the rate of onychomycosis has been rising globally in relation to increases in important risk factors (e.g. diabetes mellitus) and lifestyle changes (e.g. occlusive footwear). Tests commonly used in the diagnosis of onychomycosis (such as potassium hydroxide preparation, histop...

BACKGROUND: The determination of causative organisms of onychomycosis is still not optimal. There remains a need for a cheap, fast and easy-to-perform diagnostic tool with a high capacity to distinguish between organisms. OBJECTIVES: To determine whether attenuated total-reflectance Fourier transform infrared (ATR-FTIR) spectroscopy can detect and...

Background Objective measurement of target lesions in vitiligo is important for clinical practice and trials, yet no a preferred tool has been defined. Reported digital tools have shortcomings related to feasibility aspects and often lack information on validity, reliability and responsiveness. Moreover, studies are not yet based on UV photography....

New promising treatments have been developed for psoriasis that target different parts of the interleukin (IL)-23/IL-17 pathway. This approach is believed to be more disease specific, and sparing the T helper 1 pathway might prevent serious long-term adverse events. Moreover, superior Psoriasis Area and Severity Index improvements are observed, whi...

Melanocytes are situated in the basal layer of the epidermis and are surrounded by keratinocytes. By a complex interacting signaling process, they form epidermal melanin units consisting of one melanocyte with 30-40 associated keratinocytes. In lighter-skin types, the melanosomes are retained to an area above the nuclei of the keratinocytes and res...

The bulge area of the human hair follicle has now been identified as a niche for follicular epidermal as well as melanocyte stem cells. The potential of these cells to repigment depigmented patches of vitiligo has been explored recently. This is possible by the technique of non-cultured extracted follicle outer root sheath cell suspension transplan...

What role do antibiotics have in the treatment of uncomplicated skin abscesses after incision and drainage? A recent study suggested that, for small uncomplicated skin abscesses, antibiotics after incision and drainage improve the chance of short term cure compared with placebo. Triggered by this trial, the Rapid Recommendation team produced a new...

BACKGROUND: The pathogenesis of vitiligo remains a topic of extensive debate. This is partly due to the moderate efficacy of current treatments. The role of the oxidative stress pathway in vitiligo is a popular although controversial research topic. METHODS AND FINDINGS: We conducted a systematic search of the existing literature on the aberrancie...

Purpose Ipilimumab can induce durable responses in patients with metastatic melanoma. Unfortunately the majority of patients do not respond to ipilimumab in monotherapy. Preclinical data and early clinical data suggest synergistic antitumor activity between ipilimumab and high-dose radiotherapy. Here, we report the results of our phase I trial, eva...

Linked Article: Jacquemin et al. Br J Dermatol 2017; 177: 1367–1375.

Protein carbamoylation is a non-enzymatic post-translational modification that binds isocyanic acid, which can be derived from the dissociation of urea or from the myeloperoxidase-mediated catabolism of thiocyanate, to the free amino groups of a multitude of proteins. Although the term 'carbamoylation' is usually replaced by the term “carbamylation...

The pathophysiology of vitiligo is becoming increasingly clarified. In non-segmental vitiligo, early factors include activation of innate immunity, inflammasome activation, oxidative stress, and loss of melanocyte adhesion. Nonetheless, the main mechanism leading to non-segmental vitiligo involves an immune-mediated destruction of melanocytes. Anti...

The pathophysiology of vitiligo is complex although recent research has discovered several markers which are linked to vitiligo and associated with disease activity. Besides providing insights into the driving mechanisms of vitiligo, these findings could reveal potential biomarkers. Activity markers can be used to monitor disease activity in clinic...

The international vitiligo community had last December its first "vitiligo only" research meeting in the Eternal City. Vitiligo is a well-recognized but poorly addressed public health concern worldwide. The Vitiligo International Symposium (VIS) is a strong signal for the medical world of the coming of age of vitiligo as a major research field. Bec...

Segmental vitiligo is characterized by its early onset, rapid stabilization, and unilateral distribution. Recent evidence suggests that segmental and nonsegmental vitiligo could represent variants of the same disease spectrum. Observational studies with respect to its distribution pattern point to a possible role of cutaneous mosaicism, whereas the...

Being a member of the IL-17 family, comprising six structurally related ligands, IL-17A is a cytokine, produced by multiple cell types, such as CD4+αβ T cells, γδ T cells, natural killer cells and neutrophils. IL-17A participates in tissue inflammation by inducing the expression of chemokines, proinflammatory cytokines and matrix metalloproteases....

Vitiligo is a chronic skin condition characterized by progressive depigmentation of the skin. S100B is a damage-associated molecular pattern (DAMP) protein expressed in melanocytes, which has been proposed as a marker of melanocyte cytotoxicity. While the use of S100B as a biomarker in melanoma is well established, its association with vitiligo act...

Background Antibodies blocking programmed cell death 1 (PD-1) have encouraging responses in patients with metastatic melanoma. Response to anti-PD-1 treatment requires pre-existing CD8+ T cells that are negatively regulated by PD-1-mediated adaptive immune resistance. Unfortunately, less than half of melanoma tumours have these characteristics. Com...

Protein carbamoylation is a non-enzymatic post-translational modification that binds isocyanic acid, which can be derived from the dissociation of urea or from the myeloperoxidase-mediated catabolism of thiocyanate, to the free amino groups of a multitude of proteins. Although the term 'carbamoylation' is usually replaced by the term "carbamylation...

Inflammation is a key player in the development of an increasing amount of diseases. The soluble urokinase plasminogen activator receptor (suPAR) is a highly flexible molecule with intrinsic chemotactic properties. This glycoprotein has been evaluated as a biomarker of inflammation, immune activation, organ damage and clinical outcome in several pa...

Interleukin-17A is an important cytokine in the pathogenesis of psoriatic arthritis. Secukinumab is a recombinant, high-affinity, fully human immunoglobulin G1κ monoclonal antibody with a selective binding and neutralization of interleukin-17A. By providing an alternative mechanism of action to current treatments, secukinumab has shown efficacy in...

Background: The Vitiligo Extent Score (VES) has recently been introduced as a physicians' score for the clinical assessment of the extent of vitiligo, but a good patient self-assessment score is lacking. Objective: The objective is to develop and validate a simplified version of the VES as a patient-reported outcome measure (PROM). Methods: Af...

Abnormal skin pigmentation represents a common skin problem which may be congenitally determined or acquired during life. The former are discussed in Chapter [70]. Acquired pigmentary disorders encompass a broad range of diseases resulting not only in abnormal melanin pigmentation of the skin but also in skin colour change produced by a variety of...

The recent interest and elucidation of the JAK/STAT signaling pathway created new targets for the treatment of inflammatory skin diseases (ISDs). JAK inhibitors in oral and topical formulations have shown beneficial results in psoriasis and alopecia areata. Patients suffering from other ISDs might also benefit from JAK inhibition. Given the develop...

Importance It is difficult to determine disease activity in vitiligo owing to the absence of inflammatory signs, such as erythema or scaling. A biomarker that could confirm active disease and indicate likely future disease progression would therefore be of considerable value. Objective To investigate whether soluble CD27 (sCD27), sCD25, or sCD40L...

Background: Galectin-3 is a member of a closely related lectin family, which is detected in several vertebrate epithelial and myeloid cell types. This beta-galactoside-binding soluble protein plays an important role in multiple biological processes. Depending on its location, type of injury or site of damage, the effects by galectin-3 can be vario...

For decades an extensive debate is continued on the pathophysiology of vitiligo. Numerous hypotheses have been put forward, many supported by well documented arguments. Regardless of the initiating steps, most experts agree that an immune based melanocyte destruction is responsible for the final steps leading to epidermal depigmentation. It is rema...