Scleroderma: skin stiffness assessment using the stress-strain relationship under progressive suction.

in Expert Opinion on Medical Diagnostics (2013), 7(2), 119-25

Introduction: A few non-invasive biometrological methods are available for monitoring skin stiffening in systemic scleroderma. Among them, the Cutometer(R) is used for years by several clinical teams ... [more ▼]

Introduction: A few non-invasive biometrological methods are available for monitoring skin stiffening in systemic scleroderma. Among them, the Cutometer(R) is used for years by several clinical teams. Objectives: To revisit the microscopic structure of the dermal fibrous networks in scleroderma and the relationship with changes in viscoelasticity. Methods: The suction method delivered by the Cutometer(R) was applied following the progressive stress-vs-strain modality. Results: The test procedure was sensitive enough to document the initial progression steps of acroscleroderma. Four stages were thus identified including i) the incipient, ii) the progressive, iii) the overt, and iv) the regressive acroscleroderma. Conclusion: The non-invasive determination of skin biomechanical functions is relevant both in routine clinical practice and in antisclerotic drug development. It is complementary although not a substitute for the determination of selected serum biomarkers. [less ▲]

Fibromyalgie: un syndrome d'Ehlers-Danlos de type hypermobile qui s'ignore?

in Revue Médicale de Liège (2013), 68(1), 22-4

Some patients suffering from fibromyalgia present with clinical signs and alterations in the histopathology, immunohistochemistry and ultrastructure of the dermis similar to the Ehlers-Danlos syndrome ... [more ▼]

Some patients suffering from fibromyalgia present with clinical signs and alterations in the histopathology, immunohistochemistry and ultrastructure of the dermis similar to the Ehlers-Danlos syndrome, hypermobile type (EDSH). Some types of fibromyalgia possibly represent an undiagnosed EDSH. [less ▲]

Comprehensive clinical and molecular analysis of 12 families with type 1 recessive cutis laxa.

in Human Mutation (2013), 34(1), 111-21

Autosomal recessive cutis laxa type I (ARCL type I) is characterized by generalized cutis laxa with pulmonary emphysema and/or vascular complications. Rarely, mutations can be identified in FBLN4 or FBLN5 ... [more ▼]

Autosomal recessive cutis laxa type I (ARCL type I) is characterized by generalized cutis laxa with pulmonary emphysema and/or vascular complications. Rarely, mutations can be identified in FBLN4 or FBLN5. Recently, LTBP4 mutations have been implicated in a similar phenotype. Studying FBLN4, FBLN5, and LTBP4 in 12 families with ARCL type I, we found bi-allelic FBLN5 mutations in two probands, whereas nine probands harbored biallelic mutations in LTBP4. FBLN5 and LTBP4 mutations cause a very similar phenotype associated with severe pulmonary emphysema, in the absence of vascular tortuosity or aneurysms. Gastrointestinal and genitourinary tract involvement seems to be more severe in patients with LTBP4 mutations. Functional studies showed that most premature termination mutations in LTBP4 result in severely reduced mRNA and protein levels. This correlated with increased transforming growth factor-beta (TGFbeta) activity. However, one mutation, c.4127dupC, escaped nonsense-mediated decay. The corresponding mutant protein (p.Arg1377Alafs(*) 27) showed reduced colocalization with fibronectin, leading to an abnormal morphology of microfibrils in fibroblast cultures, while retaining normal TGFbeta activity. We conclude that LTBP4 mutations cause disease through both loss of function and gain of function mechanisms. [less ▲]

Proteomic kinetic analysis of blister fluid and serum in a patient with drug-induced toxic epidermal necrolysis. A comparison with skin immunohistochemistry.

in Current Drug Safety (2012), 7(5), 339-51

Drug-induced toxic epidermal necrolysis (TEN) is a rare but potentially lethal bullous disease whose complex pathomechanisms remain uncertain. The aim of the study was an exploratory attempt to assess TEN ... [more ▼]

Drug-induced toxic epidermal necrolysis (TEN) is a rare but potentially lethal bullous disease whose complex pathomechanisms remain uncertain. The aim of the study was an exploratory attempt to assess TEN pathobiology using a combination of immunohistochemistry and proteomics. Skin blister fluid (BF) and serum were collected in a patient in the early TEN stage at day (D) +4 of evolution and three days later (D +7). Intravenous cyclosporine A (CsA) treatment was initiated since D +4. Immunohistochemistry was performed on skin blister biopsies. In addition, proteomic analyses compared the BF protein content before and at the issue of the 3-day CsA treatment. Proteins were selected according to their prominent differential abundance in BF between D+4 and D+7, when influenced by lesional skin cells, but not in serum. Among 300 proteins, four were considered. Glutathione transferase pi was related to oxidative stress in TEN epidermis. The monocyte differentiation antigen CD14 and myeloperoxidase indicated macrophage activation. The proinflammatory S100-A8 protein probably originated from activated keratinocytes and/or macrophages. These proteomic findings were in line with immunohistochemistry and supported the prominent involvement of keratinocytes and macrophages in TEN pathomechanism. As opposed to CD14, other proteins were mainly present in BF at D+7, confirming that CsA expressed little effect, if any, on the activity of keratinocytes and macrophages in the present TEN patient. Of note, the present exploratory study using proteomic analyses in a single TEN case supports a pathogenic hypothesis without establishing any firm conclusion. [less ▲]

Deciphering supportive treatment strategies for toxic epidermal necrolysis.

in Current Drug Safety (2012), 7(5), 361-6

Toxic epidermal necrolysis (TEN) is a dreadful life-threatening syndrome typically induced by an adverse drug reaction. This condition is characterized by the sudden and extensive destruction of the ... [more ▼]

Toxic epidermal necrolysis (TEN) is a dreadful life-threatening syndrome typically induced by an adverse drug reaction. This condition is characterized by the sudden and extensive destruction of the epidermis. The patient should be promptly addressed to a burn unit where three types of treatment should be administered, namely, (a) specific topical care of the bullous/eroded skin areas, (b) systemic anti-apoptotic/necrotic treatments, and (c) supportive care preventing secondary internal organ failures. This latter aspect is covered by the present review and focuses on (a) early withdrawal of the causative drug, (b) airway management, (c) hydro-electrolytic control, (d) nutritional support, (e) antibiotherapy, (f) prevention of venous thrombosis and gastroduodenal ulcers, and (g) analgesia and anesthesia. [less ▲]

Toxic epidermal necrolysis and antifolate drugs in cancer chemotherapy.

in Current Drug Safety (2012), 7(5), 357-60

Folates are one-carbon donors essential for synthesizing purines, pyrimidines, serine, and methionine. They correspond to anionic hydrophilic molecules essential for DNA synthesis in mammalian cells. The ... [more ▼]

Folates are one-carbon donors essential for synthesizing purines, pyrimidines, serine, and methionine. They correspond to anionic hydrophilic molecules essential for DNA synthesis in mammalian cells. The latter cells lack the capacity to synthesize folates. In some patients, high dosages of antifolate drugs (eg: methotrexate, pemetrexed) used in cancer chemotherapy alter the keratinocytes, endothelial cells and Factor XIIIa+ dermal dendrocytes in a range of various severities. Such conditions clinically designed under the heading antifolate cytotoxic skin reaction (ACSR) occasionally resemble the toxic epidermal necrolysis (TEN) / Stevens-Johnson syndrome (SJS) spectrum. Whether or not the TEN/SJS presentation of ACSR is a regular condition similar to that induced by other drugs or a variant condition supported by a unique pathomechanism is unsettled. [less ▲]

How to manage hair changes in cancer patients.

in Vereecken, P.; Awada, A. (Eds.) Handbook of skin care in cancer patients. (2012)

Impact climatique sur les ulcères veineux de jambe.

in Revue Médicale de Liège (2012), 67

Le melanome cutane: une seule maladie?

in Revue Médicale de Liège (2012), 67(9), 458-60

For the media and the public at large, malignant melanoma is the most dreadful cancer of the skin. This statement is obvious. However, some nuances merit to be considered. The clinical presentations ... [more ▼]

For the media and the public at large, malignant melanoma is the most dreadful cancer of the skin. This statement is obvious. However, some nuances merit to be considered. The clinical presentations, histopathology and molecular genetics point to the fact that malignant melanoma is not a single monolithic pathological condition. Different types of melanomas are distinguished based on distinct origins and contrasted prognoses. The management and information for the patient should be handled individually. [less ▲]

Le melanome metastatique: un vent d'espoir porte par l'ipilimumab et le vemurafenib.

in Revue Médicale de Liège (2012), 67(2), 64-8

Treating a patient with cutaneous malignant melanoma relies on the recognition of a clever stratification of the distinct stages of the disease. The histoprognostic criteria were recently revisited. In ... [more ▼]

Treating a patient with cutaneous malignant melanoma relies on the recognition of a clever stratification of the distinct stages of the disease. The histoprognostic criteria were recently revisited. In addition, translational research fueled the development of new treatments with at last increased efficacy in the metastatic stage. Such therapeutic advance improves the median overall survival for a few months. Some combined treatments could possibly boost the beneficial effects. [less ▲]