Pascale Quatresooz

Novel Treatments for Drug-Induced Toxic Epidermal Necrolysis (Lyell’s Syndrome)

Drug-induced toxic epidermal necrolysis (TEN) is a life-threatening disease characterized by extensive destruction of the epidermis. It apparently results from the formation of specific toxic drug metabolites by the keratinocytes. The mortality rate which averages 25–30% is mainly due to secondary septicemia, and to ionic and metabolic disturbances following loss of epidermal integrity. Apoptosis is the likely mechanism leading to massive keratinocyte death in TEN. Dysregulations in the tumor necrosis factor-α (TNF-α) pathway, CD95 system (Fas ligand, CD95L; Fas receptor, CD95R) and calcium homeostasis in the epidermis are involved in this apoptotic process. An active role has also been ascribed to T lymphocytes, macrophages and factor XIIIa-positive dermal dendrocytes. Despite progress, treatment of TEN remains controversial. In the past, systemic glucocorticoids were used in order to target the inflammatory reaction in TEN. However, there was no evidence for improvement of the healing process, while corticosteroids worsened the prognosis by increasing the risk of septicemia. Only a few cases have been treated with other drugs including cyclophosphamide, pentoxyfilline, thalidomide, anti-TNF-α antibodies and cyclosporin A. In the recent past, some TEN patients were treated with intravenous human immunoglobulins (IVIG). The rationale for such a treatment was to block the CD95 system on keratinocytes. The early promising clinical results of IVIG treatment in TEN were subsequently challenged. This review compares the effectiveness and drawbacks of the major drugs presently used in TEN treatment. Some future prospects in TEN management are also discussed.

Blood vessel changes during pregnancy: a review.

The profound endocrine upheaval of pregnancy is frequently associated with changes in the function and structure of the blood and lymph microvasculature of the skin and mucosae. Palmar erythema is frequent but rarely severe and is associated with burning sensations. Spider telangiectasias develop in the majority of pregnant White women but are less often identified in women with darker skin. Hemangiomas and glomus tumors occur in one-third of women. A firm edema may develop on the face and extremities in the final months of pregnancy. Venous hypertension and varicosities of the lower limbs are common. Gingivitis, gum hypertrophy, and pyogenic granuloma are common in the oral cavity. The vaginal mucosa is also affected, showing a violaceous aspect, at times accompanied by varicosities of the vulva. Many gestational vascular changes regress spontaneously in the postpartum phase. Some vascular tumors may need to be treated with a vascular laser or intense pulsed light.

Distribution of varicella zoster virus and herpes simplex virus in disseminated fatal infections.

AIMS: To study the cutaneous and visceral distribution of herpes simplex virus (HSV) and varicella zoster virus (VZV) in fatal infections. METHODS: Standard histology, immunohistochemistry (monoclonal antibodies VL8 and VL2 and polyclonal antibody IE63 directed against VZV; monoclonal antibodies IBD4 and HH2 and polyclonal antibodies directed against HSVI and HSVII) and in situ hybridisation (anti-HSV and anti-VZV probes) were applied to formalin fixed, paraffin wax sections. RESULTS: On histological examination, Herpesviridae infection was evident in various organs including the lungs, liver and skin. In addition, immunohistochemistry and in situ hybridisation revealed the presence of HSV and VZV antigens and nucleic acids in several cell types and tissues showing no cytopathological alterations suggestive of Herpesviridae infection. The organs with histological evidence of infection also contained VZV or HSV antigens and their genes. CONCLUSIONS: These findings suggest that organ failure in disseminated VZV and HSV infections is primarily caused by HSV or VZV induced cell damage and lysis. They also indicate that immunohistochemistry and in situ hybridisation can provide an accurate, type-specific diagnosis on formalin fixed, paraffin wax embedded tissue even when classic histological and cytological characteristics are lacking.

Skin climacteric aging and hormone replacement therapy

A gender perspective is indispensable for a full understanding of aging. Menopause is a turning point in womens lives. In addition to the effects of chronological aging, sunlight exposure, and other environmental and endogenous stimuli, the climacteric appears to exert some dramatic consequences on skin biology and aspect. The epidermis may become xerotic and exhibit altered functions. The dermis thins out and its elasticity decreases in concert with the decline in bone mass. The skin microcirculation is impaired. These aspects are some of the better worked‐out changes of the climacteric, which in turn seem to be stabilized or in part reversible with hormone replacement therapy (HRT). The HRT effect on menopause consequences on hair growth and sebum production is less impressive. This review summarizes some important impacts of the climacteric on skin, and highlights the benefits of HRT that may influence cosmetic dermatology.

Ehlers-Danlos-like dermal abnormalities in women with recurrent preterm premature rupture of fetal membranes.

Preterm premature rupture of membranes (PPROM) likely results from weakening of the constituent connective tissue. It is uncertain if the alterations are limited to the fetal membranes or are also present in other sites such as the skin. The aim of the study was to compare the dermal structure of women suffering from recurrent PPROM with the dermis of both non-pregnant women and women with uneventful gestation. Skin biopsies were taken from 42 women who recently underwent PPROM, 33 women with uneventful gestation and 33 non-pregnant women. Histochemistry, immunohistochemistry, and electron microscopy were performed on these specimens and analyzed blindly. Morphologic changes were found in the dermis of most (33 of 42 at optical microscopy and 40 of 42 at ultrastructure) of the women suffering from PPROM. They were reminiscent of those found in some types of Ehlers-Danlos Syndrome (EDS). However, there was no clinical evidence suggesting a recognized form of EDS. We conclude that some cases of PPROM are a systemic connective tissue disorder representing a yet unidentified type of EDS.

Sweaty skin, background and assessments

Overproduction of sweat, sweaty skin, and body malodors are felt unpleasant by many people in diverse social groups. This review summarizes the functional aspects of the eccrine, apocrine, and apoeccrine sweat glands as encountered in health and disease. A series of measuring methods are conveniently used to explore any trouble in sweat production. These include the gravimetric method, water evaporation quantification, skin staining procedures, dye injections, casting replicas, average electrometric assessments, and skin capacitance mapping / imaging (SCM). Qualitative assessment is provided by collection of sweat and volatile compounds followed by chromatographic analysis. At present, SCM appears to be the most valuable method for assessing the number of active glands and their individual sweat production by the eccrine and apoeccrine glands.

Immunohistochemical clues at aging of the skin microvascular unit

Background:  Skin aging is a multifaceted process influenced by various factors affecting at variable degree at different body sites. This study focused on the aging process affecting dermal dendrocytes and the microvasculature. We also explored the effect of substance P released by capsaicin because this neuropeptide is known to affect the microvasculature environment.

The therapeutic potential of TNF-alpha antagonists for skin psoriasis comorbidities.

Importance of the field: Alopecia, psoriatic arthritis, the metabolic syndrome, inflammatory bowel diseases and cardiovascular diseases may occur as skin psoriatic comorbidities. TNF-α antagonists are used to treat psoriasis. Adalimumab is one of the recognized active agents for this indication. Areas covered in this review: The current peer-reviewed publications and presentation of original findings. What the reader will gain: Adalimumab is active on recalcitrant psoriasis and some of its comorbidities, particularly arthropathies and Crohns disease. However, the progression of the radiological alterations is limited with regression of the bony erosions. Psoriatic enthesopathy also regresses. Mortality associated with psoriasis arthropathy is on the decline. Crohns disease, the most frequent inflammatory bowel comorbidity of psoriasis, is responsive to adalimumab. The effect of adalimumab on the metabolic syndrome and cardiovascular involvement is more erratic. The spectacular effects of adalimumab may be associated with some adverse effects. In particular, despite a marked reduction in the psoriasis area-and-severity index (PASI) score some new acute lesions of cutaneous psoriasis may develop corresponding to paradoxical psoriasis. Other potential adverse effects include infections, granulomas, rapid growth of cancers and occurrence of lymphomas. Take home message: Adalimumab frequently controls moderate-to-severe forms of cutaneous psoriasis and some of its comorbidities.

Weathering of the hairless scalp: a study using skin capacitance imaging and ultraviolet light-enhanced visualization

The balding scalp is particularly exposed to sunlight, hence, the overall ageing process modulated by ultraviolet and near‐infrared light may be increased at this location. The induced changes are better revealed under ultraviolet light examination. Any alteration in the epidermal maturation is potentially reflected by stratum corneum changes observed as disturbances on skin‐capacitance imaging.

Skin homing of Treponema pallidum in early syphilis: an immunohistochemical study.

The incidence of syphilis is increasing in most parts of the world including some major European cities. The lesions developing during secondary syphilis may be difficult to diagnose clinically. Similarly, the histopathologic changes do not always fulfill the typical diagnostic criteria. The objective of this study was to assess the contribution of immunohistochemistry for the identification and localization of Treponema pallidum on the skin. We retrieved from our files 12 paraffin-embedded biopsies of skin lesions, which had posed diagnostic problems in the past. Only a serologic test had proven that the patients had syphilis. Controls consisted of lichenoid dermatoses unrelated to syphilis and borreliosis. Immunohistochemistry using an antispirochete (T. pallidum and Borrelia) antibody was performed retrospectively. In all samples from primary and secondary syphilis, T. pallidum was highlighted, but none of the control lesions unrelated to syphilis showed positivity. Interestingly enough, T. pallidum present in the lower mid-part of the epidermis often outnumbered that in the dermis. This difference was more striking in secondary syphilis compared with primary syphilis. Immunohistochemistry for T. pallidum considerably increased the sensitivity and the specificity of the histologic diagnosis. The strong epidermal homing of T. pallidum is highlighted in early syphilis.