[Treatment of actinic keratosis with topical imiquimod (Aldara): the cutaneous erosion appears beneficial].
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Biomedical subjects
Publications and source records attributed to J-H Saurat.
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INTRODUCTION: Cidofovir (Vistide) is an antiviral marketed for the treatment of cytomegalovirus retinitis. Clinical efficacy has been reported with its broad antiviral spectrum that includes poxvirus, human papilloma virus and Herpes simplex. In immunodepressed patients, these infectious dermatoses are often recurrent and resistant. In an open study, we assessed the efficacy and clinical tolerance of cidofovir gel at 1 p. 100. PATIENTS AND METHODS: Twelve HIV-infected adults were included. Cidofovir gel at 1 p. 100 was applied directly on the lesions, once a day, for two weeks on the molluscum and condylomas, four weeks on the warts and one week on the chronic herpes. RESULTS: Four patients presented with warts and 3 of them with verruca plana. In 2 of the verruca plana patients, regression was complete although relapse was observed. Two failures were noted. Local application of the gel was not tolerated by one patient suffering from condylomas of the penis. Four patients presented with molluscum contagiosum. Two complete regressions with strong local reaction and two partial regressions were observed. The latter two patients exhibited severe immunodepression, one of them subsequently received infusions of cidofovir. Two women suffering from vulvar and perianal herpes resistant to acyclovir were treated for one week with cidofovir gel at 1 p. 100: no response was obtained. One of the patients stopped treatment because of local intolerance. A third, less immunodepressed, woman responded partially. COMMENTS: In HIV-positive patients, cidofovir in topical form appears to be indicated in extensive and confluent molluscum contagiosum. However, the effect occurs at the cost of local inflammation. The results are disappointing in papillomavirus lesions and in chronic acyclovir-resistant herpes ulcerations, efficacy is debatable.
Psoriasis is a chronic, immune-mediated disorder that usually requires long-term treatment for control. Approximately 25% of patients have moderate to severe disease and require phototherapy, systemic therapy or both. Despite the availability of numerous therapeutic options, the long-term management of psoriasis can be complicated by treatment-related limitations. With advances in molecular research and technology, several biological therapies are in various stages of development and approval for psoriasis. Biological therapies are designed to modulate key steps in the pathogenesis of psoriasis. Collectively, biologicals have been evaluated in thousands of patients with psoriasis and have demonstrated significant benefit with favourable safety and tolerability profiles. The limitations of current psoriasis therapies, the value of biological therapies for psoriasis, and guidance regarding the incorporation of biological therapies into clinical practice are discussed.
We report the case of an 80-year-old patient who had intense pruritus which did not respond to a 3-month treatment with topical corticosteroids. On dermoscopy examination of the excoriations, we found the typical dermoscopic aspect of the scabies mite at a distance. Dermoscopy allows identifying a triangular structure which corresponds to the anterior section of the mite including the mouth part and the 2 pairs of front legs. This aspect has been described as resembling a jetliner with its trail, a delta glider or a spermatozoid. Traditional diagnostic methods for scabies failed in this case because the mites were at a distance from the burrows. This was due to the fact that the reaction to the mite was less pronounced and the diagnosis is frequently missed. Dermoscopy is a useful tool for the diagnosis of scabies either as a diagnostic test or to guide the traditional diagnostic tests.
BACKGROUND: Localized vulval childhood pemphigoid is a rare variant within the pemphigoid group. Although its prognosis seems favorable, the best therapeutic strategy remains unclear. OBSERVATION: We here describe the case of an 8-year-old girl presenting with a 5-year history of relapsing vulval pain and lesions suggestive of lichen sclerosus. Clinical features, light microscopy and direct immunofluorescence microscopy were consistent with vulval cicatricial pemphigoid, although the autoantigen(s) involved could not be characterized. Her disease responded to treatment with topical tacrolimus ointment 0.1% within 3 months without any evidence for disease activity, except for slight residual scarring. After 12 months, her treatment was stopped without relapse. CONCLUSION: This observation suggests that in this rare immune-mediated blistering disease topical tacrolimus is an interesting therapeutic option without the adverse effects associated with topical steroids.
Fulminant herpetic sycosis is a rare but well-known manifestation of herpes simplex virus (HSV) infection occurring in the context of viral recurrence in immunodepressed patients. We present here the case of a 32-year-old male patient, without notable medical history, who developed papulovesicular lesions of the beard accompanied by fever, painful cervical lymphadenopathy and odynophagia, with a clinical evolution that was initially unfavourable under antibiotic treatment. The diagnosis of herpetic sycosis was established by means of direct immunofluorescence and culture which confirmed positivity for HSV-1 and serologies compatible with a primary viral infection. No sign for a latent immune deficit was found at the time of investigations. The clinical evolution was rapidly favourable with administration of intravenous aciclovir for 1 week. To our knowledge, herpetic sycosis as a presentation of primary viral infection has not been reported previously. The possibility of a herpetic sycosis of the beard must be considered in the case of non-response to antibiotic or antifungal treatment.
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Amyloid elastosis is a rare variant of primary systemic amyloidosis characterized by amyloid deposited around elastic fibres. Only two cases, with pseudoxanthoma elasticum-like features and fatal outcome, have been reported. A 56-year-old woman presented with polyneuropathy and a diffuse plane xanthoma-like eruption. Light and electron microscopy studies revealed deposits of amyloid L encasing either normal-looking or short, fragmented elastic fibres in the dermis in a pattern characteristic of amyloid elastosis. The patient had medullary plasmocytosis with lambda light chain restricted expression and underwent autologous stem cell transplantation, which resulted in progressive regression of mucocutaneous signs and stabilization of the polyneuropathy. Our case extends the spectrum of clinical and histopathological presentations of amyloid elastosis. Haematopoietic cell transplantation might improve outcome in patients with multisystem disease.
BACKGROUND: Dermoscopy, a noninvasive technique used to help physicians better visualize pigmented skin lesions, is becoming widely used by dermatologists. Yet despite its popularity, to our knowledge basic aspects such as the best immersion fluid (IF) to use and proper procedures for applying the IF and dermatoscope have never been the subject of a systematic investigation. OBJECTIVES: To determine the best techniques for application of IF and the dermatoscope; to discover which IF results in the least amount of air inclusions; to determine which IF provides the best image quality. MATERIALS AND METHODS: This study was divided into three phases. Phase I examined several techniques of taking digital dermoscopic photographs in an attempt to eliminate air bubbles. Phase II tested seven IFs to analyse quantitatively the number of air inclusions for each IF. Phase III investigated these same IFs to judge the image quality for each. RESULTS: Phase I: in our hands, the best technique to apply an IF is to use an eyedropper and place the IF directly onto the skin in combination with a 'roll-on technique': the dermatoscope's edge is placed on the skin first and is then rotated until the glass plate lies flat against the skin. Phase II: the alcoholic IF resulted in the least amount of air bubble inclusions (70% ethanol, 90% isopropanol and alcoholic disinfectant), while liquid paraffin (a mineral oil) resulted in the most air bubbles. Phase III: dermoscopic structures were equally clear with alcohols and liquid paraffin, but slightly blurry with ultrasound gel and water. CONCLUSIONS: Although 90% isopropanol performed slightly better in terms of air inclusions, we prefer to use 70% ethanol in most circumstances because it has the advantage of being odourless, unlike its counterpart. Additionally, ethanol will not stain clothing, does not crystallize on the dermatoscope, disinfects and evaporates immediately (does not need to be wiped off). For certain local considerations, such as dermoscopy on mucosa or the nail, we prefer to use ultrasound gel because it will not flow.
Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that regulate the expression of target genes involved in many cellular functions including cell proliferation, differentiation and immune/inflammation response. The PPAR subfamily consists of three isotypes: PPAR alpha, PPAR beta/delta and PPAR gamma, which have all been identified in keratinocytes. PPAR beta/delta is the predominant subtype in human keratinocytes, whereas PPAR alpha and PPAR gamma are expressed at much lower levels and increase significantly upon keratinocyte differentiation. PPAR beta/delta is not linked to differentiation, but is significantly upregulated upon various conditions that result in keratinocyte proliferation, and during skin wound healing. In vitro and in vivo evidence suggests that PPARs appear to play an important role in skin barrier permeability, inhibiting epidermal cell growth, promoting epidermal terminal differentiation and regulating skin inflammatory response by diverse mechanisms. These proprieties are pointing in the direction of PPARs being key regulators of skin conditions characterized by hyperproliferation, inflammatory infiltrates and aberrant differentiation such as psoriasis, but may also have clinical implications in inflammatory skin disease (e.g. atopic dermatitis), proliferative skin disease, wound healing, acne and protease inhibitor associated lipodystrophia.
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Erosive pustular dermatosis of the leg is a distinct form of spongiform amicrobial pustulosis. The disorder typically affects the lower limbs of elderly patients presenting with chronic venous insufficiency and stasis dermatitis, and has a chronic course. Three elderly patients with chronic venous ulcers are described, who developed pustules and moist eroded lesions on the leg. The clinical and histological features were typical for erosive pustular dermatosis. The lesions rapidly responded to topical treatment with either tacrolimus or corticosteroids. Of note, this condition was associated with a diverticular disease in two patients, while in another patient an epidermoid carcinoma of the tongue was present. Erosive pustular dermatosis of the leg is an uncommon but distinct skin disorder typically associated with trophic changes of the lower limbs. Our observations raise the question of the relation of erosive pustular dermatosis of the leg with the group of neutrophilic dermatoses. Topical immunotherapy with tacrolimus may constitute a novel therapeutic option for this frequently recalcitrant condition.
Membrane-bound Fas ligand (FasL, Apo-1L, CD95L) induces rapid apoptosis of Fas (CD95)-sensitive cells on interaction with Fas, and is an important effector molecule of cytolytic T lymphocytes (CTLs). Melanomas are immunogenic and induce the production of specific CTLs, but are usually able to escape immune destruction. We investigated Fas expression and function in 53 cutaneous melanocytic lesions and 13 melanoma cell lines grown in vitro. Immunohistochemical analysis of Fas expression in cutaneous melanocytic lesions showed moderate to high levels of Fas in common benign melanocytic naevi, but low to undetectable levels in atypical naevi, primary (superficial spreading melanoma, nodular melanoma) and cutaneous melanoma metastases. Fluorescence-activated cell sorting (FACS) analysis of Fas expression in melanoma cell lines revealed undetectable or low levels of cell surface Fas expression in five of the 13 melanoma cell lines. Analysis of Fas signalling by quantification of cell death following exposure to recombinant FasL showed that a reduction in Fas expression results in resistance to FasL-mediated cell death. Furthermore, two of the 13 melanoma cell lines were found to be resistant to FasL-mediated cell death despite conserved Fas expression. Thus seven of the 13 melanoma cell lines were found to have impaired Fas signalling. Taken together, our results indicate that downregulation of Fas expression and resistance to Fas-mediated apoptosis are frequent in melanoma.
Epidermal-type fatty acid-binding protein (E-FABP), a protein related to the intracellular trafficking of fatty acids, is expressed in melanocytic tumours but not in normal human melanocytes. E-FABP interacts with S100A7. The presence of these two proteins was investigated in the urine of patients with cutaneous melanoma or other types of cancer, and healthy controls. The first voided morning urine samples of 31 patients with melanoma, 73 patients with other types of cancer and 17 healthy controls were concentrated and submitted to sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) immunoblotting for protein detection. In the healthy controls, the incidences of urinary detection of these proteins were higher in females than in males, being 50% (five out of 10) versus 0% (zero out of seven) for E-FABP ( < 0.05), and 70% (seven out of 10) versus 0% (zero out of seven) for S100A7 ( < 0.05). Both proteins were detected in the urine of patients with melanoma. The incidence of S100A7 was higher in the urine of patients with melanoma (77%, 24 out of 31) compared with healthy controls (41%, seven out of 17) and patients with other types of cancer (53%, 39 out of 73) ( < 0.03). In contrast, the incidence of E-FABP was the same among the melanoma group (39%, 12 out of 31), healthy controls (29%, five out of 17) and patients with other types of cancer (23%, 17 out of 73). Surprisingly, E-FABP was always detected in the urine of females with stage I/II or III melanoma, but was no longer detectable in the urine of patients with stage IV melanoma. Urinary S100A7 may have some specificity to the host response to melanoma since its incidence was not increased in other cancers. The lack of E-FABP detection in the urine of patients with distant metastases suggests an inverse relationship between E-FABP release and the spread of melanoma.
BACKGROUND: The stratum corneum (SC), as the skin layer most exposed to various environmental factors, is particularly susceptible to oxidative stress. Due to the high lipid content of the SC, lipophilic antioxidants such as alpha-tocopherol are expected to play a major role in scavenging reactive oxidant intermediates produced during oxidative stress. OBJECTIVES: Since the skin of atopic dermatitis patients has an impaired barrier function, we wondered if they were more susceptible to environmental oxidative stress than healthy subjects. METHODS: SC was collected by scraping the forearm of 14 healthy volunteers and 14 patients with atopic dermatitis; then, alpha-tocopherol and lipid peroxide concentrations were assessed by high-performance liquid chromatography and ferrous oxidation, respectively. RESULTS: The SC from atopic patients showed a higher concentration of alpha-tocopherol (16.1 +/- 2.2 nmol/g) as compared to healthy controls (7.7 +/- 0.9 nmol/g; p < 0.01), as well as a slightly but significantly lower concentration of lipid peroxides (1,353 +/- 128 and 1,818 +/- 154 nmol/g for atopic dermatitis patients and healthy controls, respectively; p < 0.05). CONCLUSIONS: These results show that the SC of atopic dermatitis patients exhibits a significantly less pronounced oxidative state. This may be the consequence of an increase in cutaneous antioxidant defences due to chronic inflammation.
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