Non-dermatophyte Dermatoses Mimicking Dermatophytoses in Humans.

Human dermatophytic cutaneous infections usually present as single or multiple slowly progressing annular erythemato-squamous lesions with a tendency to central healing on the hairless skin. In the intertriginous regions (feet, inguinal, axillar, submammary), dermatophytic colonisations and infections manifest as whitish, slightly hyperkeratotic, pruritic and sometimes fissurated lesions. On the scalp, dermatophytic infections commonly lead to single or multiple more or less inflammatory and alopecic lesions. On the plantar and palmar aspects of the feet and hand, dermatophytosis presents as an eczema-like chronic dermatosis. Abscess-like lesions may occur due to zoophilic dermatomycosis. Dermatophytic infections of the nails reveal ill-defined whitish-yellowish colorations of the distal end or the lateral aspects of the nails, sometimes combined with partial nail embrittlement or even complete destruction. Despite the ubiquity of dermatophytic skin infections and their usually highly typical clinical features, a differential diagnosis has to be considered, in particular when treatment is not efficient or when treatment resistance occurs. This review presents the differential diagnosis in terms of frequency as well as the diagnostic methods permitting the distinction of annular, intertriginous, alopecic, palmoplantar, abscess-like and onychodystrophic lesions.

Satellite lesions accompanying herpes zoster: a new prognostic sign for high-risk zoster.

BACKGROUND: The incidence, clinical relevance and pathogenesis of single, isolated, varicella-like skin lesions occurring far beyond the primary herpes zoster (HZ)-affected dermatome remain unclear. OBJECTIVES: To search prospectively for these satellite lesions in 120 patients with HZ and to correlate their presence with a series of clinical, histological and virological data. METHODS: Relevant clinical data were recorded from 109 patients with proven HZ using immunohistochemistry on Tzanck smears. Furthermore, skin biopsies and blood samples were obtained from a subgroup of patients presenting with primary HZ with and without satellite lesions for histology, immunohistology, serology and real-time polymerase chain reaction. RESULTS: This study identified satellite lesions in 21·1% of the patients with HZ. Their presence conveyed a statistically significant relative risk (RR) for severe (RR 3·27, P < 0·001), multidermatomal (RR 10·6, P < 0·001) and multistage HZ (RR 3·30, P < 0·001); systemic signs (RR 2·08, P = 0·0031); immunosuppression (RR 2·38, P = 0·0014) and hospitalization (RR 2·94, P < 0·001). Varicella zoster virus (VZV) viraemia was higher (mean 4075 copies mL(-1) ) in patients with HZ with satellite lesions than in those without (mean 1466 copies mL(-1) ). In contrast to HZ lesions, satellite lesions often presented positive VZV immunostaining in endothelial cells, suggesting a similar pathogenesis to varicella. A limitation of this study is the centre-linked overrepresentation of immunocompromised patients. CONCLUSIONS: Total-body examination searching for satellite lesions is a rapid, simple and reliable tool for identifying patients with high-risk HZ.

Ipilimumab induces simultaneous regression of melanocytic naevi and melanoma metastases.

Ipilimumab blocks cytotoxic T-lymphocyte-associated antigen (CTLA)-4, potentiating the antimelanoma T-cell host response. Ipilimumab has been shown to improve overall survival in patients with previously treated metastatic melanoma. CTLA-4 antibodies generate immune responses to the melanoma-associated antigens Melan-A, NY-ESO-1 and glycoprotein (gp)100 in metastatic melanoma. Digital epiluminescence microscopy (DELM) is a noninvasive method permitting the monitoring of the morphology of melanocytic lesions over time. A 50-year-old man with metastatic melanoma received four ipilimumab injections after failure of dacarbazine chemotherapy. Positron emission tomography revealed regression of pulmonary metastases, and simultaneously, DELM showed regression of several melanocytic naevi. On histological examination of the regressing naevi, prominent CD8+, CD4+ and CD45R0 lichenoid lymphohistiocytic infiltrates were seen, whereas nonregressing naevi were almost free of inflammatory infiltrate. Expression of melanoma-associated antigens in benign melanocytic naevi may explain the induction of naevus regression by ipilimumab. DELM could represent a valuable noninvasive method to monitor ipilimumab efficacy.

Clinicopathologic presentations of dermatomycoses in cancer patients.

Many of the skin fungal infections in cancer patients may look similar to those infections in non-cancer patients. However, in some cases, they become more extensive and even life threatening. Prolonged and severe neutropenia is the main risk factor for the dramatic issue of fungal infections. The dermatomycoses in cancer patients can be classified in four broad groups: primary superficial dermatophytoses, primary superficial yeast infections, opportunistic mold infections with distinct potential for dissemination and secondary cutaneous manifestations of fungaemia. Occasionally, more than one fungus are found inside a given skin lesion. A special condition is represented by the mycotic colonization of mucosal squamous cell carcinomas. Angio-invasion by fungi accounts for the frequency of disseminated infections prevailing in immunocompromised cancer patients. In case of skin involvement, the dermatologist may assist by recognizing subtle semiological signs and performing biopsies for swift histological examination, molecular biology and/or culture.

[Clinicopathological confrontation. Was the skin cancer eradicated?]. / Confrontation anatomo-clinique. Le cancer cutané a-t-il été éradiqué?

Distinguishing complete removal of a skin cancer and its partial destruction is frequently requested by the clinicians and their patients. The information is awaited from the laboratory, but it is not always correctly interpreted by the information-seekers. The factors influencing this assessment include the combination of the nature of the antineoplastic therapy, the sampling modality of the area to be examined, and the quality of the dermatopathology procedure. In addition, the possibility of neoplastic regression linked to scarring or, conversely, the existence of a possible field cancerisation should be taken into consideration.

[Pedunculated and pigmented basal cell carcinoma: an unusual presentation]. / Le cas clinique du mois. Carcinome basocellulaire pédiculé et pigmenté: une présentation inhabituelle.

Basal cell carcinomas (BCC) are the most common malignant neoplasms in humans. Clinical misdiagnoses are not uncommon. These cancers are classified according to their histological and clinical characteristics which exhibit distinct malignant behaviours. It is important to be aware of the different clinical presentations both for the accurate diagnosis and tumour management. We report the case of a 78-year-old man, who presented an unusual pedunculated and pigmented BCC. This combined aspect is rarely encountered.

[The skin and menopause]. / La peau et le temps de la ménopause.

The estrogen deficit occurring at menopause manifests itself under various modalities in the diverse organs and their functions. Skin does not escape this global involutive process. In addition to the effects of chronological ageing, sunlight exposure and other environmental and endogenous stimuli, the climacteric appears to exert some dramatic consequences on skin biology and aspect. The epidermis, its adnexae and the dermis are altered by this process. The epidermis may become xerotic and exhibits 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 skin climacteric changes of which in turn seem to be stabilized or in part reversible with hormone replacement therapy (HRT).

[Hic et Nunc. Naevus or melanoma?]. / Hic et Nunc. Naevus ou mélanome?

In Wallonia, the incidence of cutaneous melanoma has steadily increased over the past decades. Hopefully, the early diagnosis made at the premetastatic stage has benefited from great advances both in the clinical and laboratory fields. Thanks to the "Groupement Oncologique Universitaire Wallonie-Liège" (GOUWL) organization, some efforts are currently made in order to better frame and normalize the management of cancer patients. Some medical staffs involved in prospective clinical research bring by their own experience further practical insights for the benefit to the patients. In this field, Belgium is not destituted. We report a brief review of the contribution of the Mosan Study Group of Pigmentary Tumors (GMETP) at the University Hospital of Liège.

A one-year survey of Microsporum audouinii infections in Belgium: epidemiological and genotypic characterization.

During recent years the proportion of tinea capitis infections due to Microsporum audouinii has increased in both Belgium and other European countries. To better understand the emergence of this species, the Belgian National Reference Centre for dermatophytes launched an epidemiological survey on the main anthropophilic dermatophytes causing tinea capitis in Belgium and included the genomic characterization of M. audouinii isolates. In total, 116 strains of M. audouinii were confirmed and characterized by the DiversiLab(®) system (bioMérieux). Six genotypic variants were identified, among which one major group included 90 isolates and the reference strain. Another variant group (11 strains) was exclusively confined to a geographical region in south Belgium. Analysis of epidemiological characteristics of the infected population showed that the main age category was 5- to 9-year-old children with a sex ratio (male/female) of 1.97. Data concerning the geographic origin of the family revealed a majority of Belgian nationality (44.7%), suggesting that the infection originated in Belgium. Other nationalities were primarily African. At this time, no clear correlation has been established between one particular strain and a specific country of origin.

[Genophotodermatoses]. / Génophotodermatoses.

Genophotodermatoses can result from a defect in melanin synthesis, a defect in DNA repair or a congenital photosensibility.

Treatment and prophylaxis of tinea infections.

Superficial fungal infections affect millions of people throughout the world. Among them, tinea represents cutaneous infections by dermatophytes. Therapeutic strategies depend upon the affected body site. Hence, clinicians distinguish several types of tinea including the corporis, faciei, cruris, pedis, manuum, capitis, barbae and unguium variants. There are several ways of tackling the tinea problem. Numerous topical and oral antifungals are available today. Topical antifungals remain the most commonly recommended treatment for many superficial dermatophytoses. Active compounds include imidazoles, morpholines and allylamines, with a few other miscellaneous drugs. The recent development of new generation oral agents (fluconazole, itraconazole, terbinafine) has enhanced the armamentarium against difficult-to-treat tineas. The antifungal efficacy and pharmacokinetic profiles of these drugs allow shorter durations of treatment and the innovative use of intermittent pulse regimens. The modern formulations fully meet the requirements of being well tolerated, involving little risk and acting specifically against relevant pathogens. However, the response rates to date do not always come up to the high expectations offered by in vitro studies.

Detection of cytomegalovirus, Pneumocystis carinii, and aspergillus species in bronchoalveolar lavage fluid. A comparison of techniques.

Cytomegalovirus (CMV), Pneumocystis carinii, and Aspergillus species are common causes of fatal pulmonary infections in immunocompromised hosts. Therefore, rapid and reliable methods of establishing the diagnosis of these types of pneumonia are essential. Bronchoalveolar lavage (BAL) has proved to be a rapid and safe procedure for procuring large numbers of bronchial and alveolar cells from the lung. To assess various methods of detecting CMV, P. carinii, and aspergillosis in lavage specimens, 47 BAL samples from adults at high risk for these infections were evaluated. The visualization of these agents was performed by cytologic examination and in situ hybridization for CMV; cytologic examination, Gomori's methenamine silver (GMS) stain, and immunofluorescence for P. carinii; and cytologic examination, GMS stain, and immunocytologic studies for Aspergillus species. Cytomegalovirus was detected in 2 of 47 specimens (4%) by cytologic examination and 7 of 47 (15%) by in situ hybridization. Cells with nuclear and/or cytoplasmic inclusions invariably were labeled with the CMV DNA probe. The weak diagnostic value of the cytologic examination resulted from the absence of characteristic inclusions in many specimens with positive results by in situ hybridization. P. carinii was the most frequent pathogen isolated from BAL fluid (9 of 47 cases; 19%). It was found in 1 of 47 specimens (2%) by the cytologic examination of Papanicolaou-stained smears, 4 of 47 (8.5%) by the GMS stain, and 8 of 47 (17%) by immunofluorescence. Most P. carinii-positive cases (five of nine cases) were detected by immunofluorescence only. Aspergillus species was diagnosed in 2 of 47 specimens (4%) by cytologic examination and GMS staining. Immunocytologic studies had positive results in these specimens and detected one additional case of Aspergillus infection (3 of 47 cases; 6%). These data show that techniques using CMV DNA probes and anti-P. carinii or anti-Aspergillus antibodies are rapid and more sensitive than conventional diagnostic procedures.

Inverse modulation of intraepithelial Langerhans' cells and stromal macrophage/dendrocyte populations in human papillomavirus-associated squamous intraepithelial lesions of the cervix.

Ninety-four cervical biopsies from normal tissue to high-grade squamous intraepithelial lesion (SILs) were examined for the presence of intraepithelial Langerhans' cells and subpopulations of stromal macrophages/dendrocytes by immunohistochemistry using anti-S100, -L1, -CD68 and -factor XIIIa antibodies. Human papillomavirus (HPV) detection was performed in all cases by using first a mixture of DNA probes for 14 HPV types commonly found in anogenital biopsies at low stringency conditions (Tm -40 degrees C) and by reanalyzing the tissues at high stringency (Tm -10 degrees C) with HPV 6/11, 16/18 and 31/33/35 biotinylated probe cocktails and individual digoxigenin-labelled probes. SILs and metaplastic tissues were significantly associated with a depletion of S100-positive intraepithelial Langerhans' cells when compared with normal epithelium. In contrast, there was a significant increase in L1-positive stromal macrophages in SIL biopsies compared with normal or metaplastic cervix. A significantly higher density of CD68-positive macrophages was also observed in high-grade SILs compared with normal or metaplastic biopsies and with low-grade SILs. The density of factor XIIIa-positive dendrocytes was found to be higher in SILs compared with metaplastic tissues and in high-grade SILs when compared with normal cervical biopsies. No specific relationship was found between the densities of these cells and the HPV type detected in SILs separated into low grade and high grade. The significance of this inverse modulation of intraepithelial Langerhans' cells and stromal macrophages/dendrocytes in normal and SIL biopsies is discussed in relation to HPV infection and malignant transformation.

Factor XIIIa-positive dendrocytes and proliferative activity of cutaneous cancers.

Factor XIIIa-positive dendrocytes present at the periphery and inside epithelial neoplasms are an heterogeneous group of cells. They are subsets of mesenchymal cells, cancer-associated macrophages and antigen-presenting cells. Factor XIIIa, other tissue transglutaminases, alpha 2-macroglobulin and tumour necrosis factor-alpha represent a complex network of mediators influencing tumour progression in the skin. In the present study we searched for the presence of dendrocytes and alpha 2-macroglobulin deposits inside and in the vicinity of cutaneous carcinomas (90 basal cell carcinomas and 46 squamous cell carcinomas) and malignant melanomas (69 primary and 28 metastatic tumours). We also studied the proliferation of the same neoplasms by Ki-67 immunohistochemistry. Dendrocytes were numerous, abutting on and infiltrating most basal cell carcinomas and thin malignant melanomas. In contrast, they were present in only low numbers or even absent in thick primary malignant melanomas and in their metastases. They appeared unmodified around squamous cell carcinomas compared with the surrounding skin. Extracellular deposits of alpha 2-macroglobulin were often found in locations where dermal dendrocytes were numerous. No correlation was found between the Ki-67 indices of carcinomas and the density of peritumoral dendrocytes. In contrast, negative relationships were found between the Ki-67 indices and the number of dendrocytes present inside basal cell carcinomas and thin malignant melanomas. This study has yielded circumstantial evidence to link the density of factor XIIIa-positive dendritic cells and a low proliferative rate of neoplastic cells in basal cell carcinomas and malignant melanomas.

Macrophages and tumor necrosis factor alpha in toxic epidermal necrolysis.

BACKGROUND: We studied the immunopathologic characteristics of five cases of toxic epidermal necrolysis by using a large panel of antibodies. OBSERVATIONS: The pattern and amount of the inflammatory cell infiltrate varied according to the stage of the disease. The main constant feature was the prominent involvement of the monocyte-macrophage lineage, including factor XIIIa+HLA-DR+ dendrocytes and CD68+ Mac 387+ macrophages, before and during the epidermal necrosis. The number of CD4+ and CD8+ lymphocytes was comparatively small. This was associated with a dense labeling of the epidermis for tumor necrosis factor alpha. CONCLUSIONS: Cells of the monocyte-macrophage lineage largely outnumber lymphocytes in the lesions of toxic epidermal necrolysis. Tumor necrosis factor alpha is likely a major cytokine that is responsible for necrosis.

A plea to bridge the gap between antifungals and the management of onychomycosis.

Onychomycosis represents a stubborn problem for the clinician facing up to the realities of antifungal treatments. There are obvious discrepancies between data given by in vitro antifungal testings, pharmacodynamics and pharmacokinetics, and those gathered from clinical experience. This critical review is an attempt at bridging the gap between in vitro and in vivo information about oral antifungals that aim to treat onychomycoses. Common sense shows that the in vitro concept of fungicidy cannot be simply extrapolated into clinical practice. Indeed, chlamidoconidia and arthroconidia present in vivo are much more resistant to antifungals than hyphae. Corneofungimetry may be a realistic bioassay in predicting antifungal activity in human infections. Boosting hyphae growth from conidia while taking antifungals is a new and appealing treatment modality that deserves controlled study.

Experimental dermatophyte infection abated by povidone-iodine: assessment by computerized-assisted corneofungimetry.

The effect of antiseptics upon fungal growth inside human stratum corneum is poorly documented. Therefore the present study was undertaken to assess the anti-dermatophyte activity of a diluted povidone-iodine wash solution using the corneofungimetry bioassay. When compared to a non-medicated cleansing product, regular applications of the antimicrobial for two weeks significantly abated the fungal invasiveness inside human stratum corneum. The present findings are most likely relevant for the clinical practice.

Itraconazole.

Itraconazole is a broad spectrum triazole antifungal agent. It has favourable pharmacodynamic and pharmacokinetic profiles and is available as both oral and i.v. formulations. Over the last two decades, clinical and animal infection studies have demonstrated the efficacy of itraconazole in a wide range of superficial fungal infections including difficult-to-treat dermatophytoses and onychomycoses. Furthermore, shortened treatment regimens have proven to be effective, ranging from 1-day treatment for vaginal candidosis to 1-week pulse therapy per month, for 2-4 months, in onychomycosis and follicular dermatophytosis. Clinical experience with itraconazole in the treatment of deep mycoses is less comprehensive. However, results in systemic candidosis, sporotrichosis, blastomycosis, paracoccidioiodomycosis, certain types of histoplasmosis and aspergillosis are extremely encouraging. Itraconazole is less effective in the treatment of chromomycosis and coccidioidomycosis. Nevertheless, considering the refractory nature of these diseases, itraconazole has proven to be a valuable addition to the antifungal drugs currently available for treatment. Itraconazole has been well-tolerated with doses of up to 400 mg/day being generally free of serious adverse effects. However, a potential for drug interactions exists, mediated through the cytochrome P450 enzyme 3A4 system, which should be considered when itraconazole is used as part of a multi-drug regimen.

Breast cancer metastatic to the eyelids.

Metastases to the eyelids are rare. They may appear as diffuse swellings, nodules or ulcerations. Most often they correspond to the dissemination of a breast adenocarcinoma. An 83 year old woman is reported with mammary adenocarcinoma metastasizing to the eyelids.

Effect of ketoconazole-medicated shampoos on squamometry and Malassezia ovalis load in pityriasis capitis.

Pityriasis capitis is improved by the use of antifungal shampoos. A double-blind randomized, placebo-controlled study was conducted to compare the efficacy of ketoconazole 0.5 percent and 1 percent formulation shampoos. Evaluations were made in seventy-eight volunteers before and after a two-week duration of daily shampooing. Grading the Malassezia ovalis load in dandruff and values of squamometry were used as noninvasive methods to evaluate efficacy.