Homoeopathic remedies in dermatology: a systematic review of controlled clinical trials.

BACKGROUND: Homoeopathic therapies are routinely used for the management of skin diseases. However, there is a lack of evidence-based data on their effectiveness. OBJECTIVES: To assess the evidence for the efficacy of homoeopathic treatments in dermatology. METHODS: We designed a systematic review of the controlled clinical trials (January 1962-April 2011) investigating homoeopathic therapies for the treatment of cutaneous diseases. We collected data from MEDLINE, PubMed, Current Contents, HomInform (Glasgow), reference lists, specialist textbooks and contacts with homoeopathic manufacturers. There was no restriction on language. Subsets were defined according to treated skin disease/condition. For each subset, two reviewers extracted data for information on study quality, type of remedy, population and outcomes. RESULTS: After an extensive search, we isolated a very limited number of trials investigating homoeopathic treatments for cutaneous diseases. Overall, of the 12 trials with interpretable results, nine trials indicated no positive effects of homoeopathy. The three trials showing a positive effect were of low methodological quality. CONCLUSIONS: Reviewed trials of homoeopathic treatments for cutaneous diseases were highly variable in methods and quality. We did not find sufficient evidence from these studies that homoeopathy is clearly efficacious for any single dermatological condition.

Curettage treatment for molluscum contagiosum: a follow-up survey study.

BACKGROUND: Although curettage is commonly used to treat molluscum contagiosum, prospective studies on its effectiveness are lacking. OBJECTIVES: To evaluate prospectively the efficacy of curettage in the treatment of molluscum contagiosum and to identify the risk factors associated with treatment failure. METHODS: A systematic 2-month follow-up survey study was carried out on 73 patients treated by curettage for molluscum contagiosum. RESULTS: Treatment of molluscum contagiosum by curettage was associated with a high risk of treatment failure at week 4 (42/64, 66%) and at week 8 (25/55, 45%). Risk factors for treatment failure at week 4 and 8 were the number of lesions at day 0 (P < 0.001), the number of involved anatomical sites (P < 0.001) and concomitant atopic dermatitis (P = 0.038 and P < 0.001, at weeks 4 and 8, respectively). CONCLUSIONS: The main risk factor for treatment failure is lesion number, underlining the importance of the early detection of the lesions or, alternatively, emphasizing the need for therapeutic options other than curettage in patients with numerous lesions.

Origin of threshold behaviour in psoriatic skin.

The mechanisms that lead to the psoriatic morphology are not fully elucidated. Several lines of evidence suggest that the positive feedback between keratinocytes and immunocytes plays a key role in the development of the lesions. On the other hand, little information is available on the negative regulatory controls that maintain a new homoeostasis level in psoriatic skin. We suggest here that the interplay of these two contrary feedbacks is likely to entail a hysteresis effect and that psoriasis is likely to be interpreted as a critical phenomenon characterized by a catastrophic shift of the skin from a normal to a hyperplastic state.

Black Skin Dermatology Online, from the project to the website: a needed collaboration between North and South.

BACKGROUND: Whereas teledermatology is an emerging discipline, to date, no teledermatology service has been developed, which is specifically dedicated to black skins. OBJECTIVES: To create and develop a teledermatology service that provides a complete range of communication, information, telediagnosis and teaching services. METHODS: A multilingual clinical description of the lesion was provided for each photograph using a five-level disease classification from the 10th revised International Classification of Diseases. In parallel, a usability study to assess and improve the functionality of the platform was also conducted. RESULTS: A web prototype has been developed which integrates image acquisition, submission, clinical description, translation as well as validation, security and data protection aspects and almost 2000 images were obtained from which 600 have been integrated in the 'store and forward' telemedicine system (http://www.black-skin.org). Initial usability tests with native French medical students show good perceived usefulness, perceived usability and internal consistency (Cronbach's alpha = 0.80 and 0.84). CONCLUSION: The Black Skin project (North and South collaboration project) offers possibilities for continuous medical education (pedagogical cases), teleteaching (educational quiz) or asking for a second opinion ('Ask a specialist' item).

Iron chelators inhibit the growth and induce the apoptosis of Kaposi's sarcoma cells and of their putative endothelial precursors.

Iron is suspected to be involved in the induction and/or progression of various human tumors. More particularly, iron may be involved in the pathogenesis of Kaposi's sarcoma, a tumor of probable vascular origin. This study was designed to investigate the effect of iron deprivation on Kaposi's sarcoma. The effects of iron chelators and iron deprivation associated with serum withdrawal were investigated on Kaposi's sarcoma-derived spindle cells, on a transformed Kaposi's sarcoma cell line (Kaposi's sarcoma Y-1) and on endothelial cells, which are the probable progenitors of Kaposi's sarcoma cells. Desferrioxamine and deferiprone, two chemically unrelated iron chelators, induced a time- and concentration-dependent inhibition of endothelial and Kaposi's sarcoma cell growth. The inhibition of cell growth was associated with a decrease in Ki-67 and in both stable and total proliferating cell nuclear antigen expression. Inhibition of the progression through the G1-phase of the cell cycle was further evidenced by decreased expression of cyclin D1 and of p34 cyclin-dependent kinase 4. Terminal deoxynucleotidyl transferase-mediated desoxyuridinetriphosphate nick end labeling assay, flow cytometry with annexin-V-fluorescein and morphologic analysis indicated that iron chelation also induced a time- and concentration-dependent apoptosis. This apoptotic effect was prevented by the addition of exogenous iron. Induction of iron deprivation in the culture medium by serum withdrawal led to similar cell cycle effects, which, however, could only be partly reverted by the addition of exogenous iron. In conclusion, these results show that iron deprivation inhibits the growth and induces the apoptosis of Kaposi's sarcoma cells and of their putative endothelial precursors. This suggests that iron chelators may represent a potential therapeutic approach for the treatment of Kaposi's sarcoma.

Early- and late-stage Kaposi's sarcoma-derived cells but not activated endothelial cells can invade de-epidermized dermis.

Whether Kaposi's sarcoma is a true neoplasm or a reactive endothelial cell outgrowth triggered by inflammatory cytokines remains unclear. In this study, we investigated the differential invasive properties of activated endothelial cells and Kaposi's sarcoma cells in a model of de-epidermized dermis, supplying the cells with matrix barriers similar to those found in vivo. Cells derived from early "patch-stage" and from late "nodular-stage" Kaposi's sarcoma lesions exhibited similar invasive properties, which indicates that cells with an invasive potential are present in the early stages of tumor development. Slow accumulation of the cells into the extracellular matrix, together with a low proliferation index and with expression of anti-apoptotic proteins, suggest that the progression of Kaposi's sarcoma may be related to escape from cell death rather than to increased proliferation. The Kaposi's sarcoma-Y1 cell line, which is tumorigenic in nude mice, also exhibited invasive properties. By contrast to the Kaposi's sarcoma-derived spindle cells, however, which were scattered between the collagen bundles, the Kaposi's sarcoma-Y1 cell population had a higher proliferation index and displayed a multilayer arrangement. Inflammatory cytokines and Kaposi's sarcoma cell supernatant could activate and stimulate the growth of human dermal microvascular endothelial cell, but could not induce their invasion in this model, showing that activated endothelial cells do not fit all the requirements to traverse the various barriers found in the dermal extracellular matrix. These results confer to Kaposi's sarcoma cells a tumor phenotype and suggest that the in vivo dominant endothelial cell population represents a reactive hyperplasia rather than the true tumor process.

Overexpression of Bcl-2 in Kaposi's sarcoma-derived cells.

The pathogenesis of Kaposi's sarcoma (KS), a tumor of probable vascular origin, remains an enigma. It is still unclear whether KS is a true malignancy or whether it represents a reactive polyclonal process. Using both an immunohistochemical and an immunoblot approach, we found that cells derived from KS lesions express significant levels of Bcl-2, a protein known to prolong cellular viability and to antagonize apoptosis. Bcl-2 expression was found in AIDS-related KS-derived cells, as well as in cells derived from iatrogenic and sporadic KS, indicating that Bcl-2 upregulation may be important in the pathogenesis of KS regardless of its epidemiologic form. By contrast, fibroblasts and dermal microvascular endothelial, cells which are the probable vascular progenitors of KS cells, expressed low levels of Bcl-2. The expression of Bcl-2 in KS-derived cells was associated with a long-term survival in serum-deprived conditions, a situation that has been shown to induce apoptosis in various cell types. Incubation of fibroblasts or of dermal microvascular endothelial cells with KS cell-free supernatants did not enhance Bcl-2 expression, suggesting that Bcl-2 expression is not mediated by an agent released by KS cells. Analogously, KS supernatants failed to promote the viability of fibroblasts and of dermal microvascular endothelial cells cultured in serum-free conditions. Our findings suggest that the spindle cells derived from KS have a survival advantage and may adequately represent the tumor cells of KS.

Kaposi's sarcoma, oncogenic viruses, and iron.

INTRODUCTION: Iron is required for many cellular processes, but it is also toxic in excess quantities. Therefore, iron homeostasis and utilization must be strictly maintained, and defects in iron absorption or transport result in iron depletion or accumulation. Most research has been directed to enteral and placental transfer of iron, but little is known about iron entry through the skin. We present evidence that exposure to wet clay soils in Africa is an important risk factor for Kaposi's sarcoma (KS) and speculate that iron may be responsible for soil toxicity contributing to the pathogenesis of KS. STUDY DESIGN: Evidence gathered from case control studies and related investigations in Uganda between 1995 and 1998 are summarized. RESULTS: A large case control study of KS in HIV-infected adults disclosed affluence and mobility that suggest enhanced sexual exposure to human herpesvirus-8, the putative aetiologic agent of KS. Another study in endemic KS (HIV-negative) also showed affluence and mobility as risk factors. In addition, barefoot exposure to wet soil was an important risk factor for men with endemic KS. Other studies point to diminish delayed hypersensitivity in the lower limbs of KS patients. Geographic similarities of KS to podoconiosis (non-filarial elephantiasis) in Africa implicate soil absorbtion through the skin in the pathogenesis of KS and podoconiosis. CONCLUSION: The hypothesis of soil exposure as a risk for endemic KS has been strengthened by recent investigation. Particulate soil exposure may cause localized microtrauma and inflammation, predisposing to KS on the extremities in HHV-8 infected men. A role for iron toxicity is yet to be determined.

A unique clonal chromosome 2 deletion in endomyometriosis.

The cytogenetic analysis of a short-term culture from a so-called endomyometriosis revealed a unique clonal del(2)(p21). The embryologic origin of this uterine-like mass is controversial. The finding of a clonal chromosome aberration favors the proliferation hypothesis and suggests that endomyometriosis is a true neoplasm and that a somatic mutation might be involved in the etiology of this lesion.

PCR assay fails to detect molluscum contagiosum virus-related sequences in AIDS-related Kaposi's sarcoma.

Previous PCR-based studies have demonstrated the presence of various viral DNA or RNA sequences in Kaposi's sarcoma (KS) tissues. To date, only human herpesvirus 8 (HHV-8) DNA sequences are found consistently in KS. The putative role of this agent in KS pathogenesis remains, however, to be determined; HHV-8 could infect populations endemically and could be reactivated in patients with KS. A close association between AIDS-related KS and molluscum contagiosum occurrence was found and this study was conducted primarily to search for the presence of molluscum contagiosum virus DNA sequences in KS. Frozen KS samples were examined for the presence of both HHV-8 and molluscum contagiosum virus DNA sequences by PCR. Despite a high rate of co-infection, no molluscum contagiosum virus (MCV) DNA sequence could be found in the KS samples whereas HHV-8 was uniformly detected. These results suggest that the high prevalence of MCV in AIDS patients with KS relies on a mode of transmission common for HHV-8 and molluscum contagiosum virus rather than on a multiviral etiology of KS. They may also indicate a particular susceptibility of the host to viral reactivation. If this is so, the failure to detect MCV DNA sequences in KS tissues by PCR indicates that locally produced or released cyotokines are not involved in the latter process.

Iron induces Bcl-2 expression in human dermal microvascular endothelial cells.

Iron is suspected to be involved in the induction and/or progression of various human tumors. The present study was designed to investigate the effects of iron on endothelial cells, keeping in mind that the homeostasis of microvessels plays a critical role in neo-angiogenesis. Applying a model of human dermal microvascular endothelial cell terminal differentiation and death induced by serum deprivation, we found that iron salts (iron chloride and ferric nitrilotriacetate) provided a survival advantage to endothelial cells. Using immunohistochemistry and Western Blot analysis, we found that the extended cellular life span induced by iron was paralleled by an increase of Bcl-2 protein expression. Taken together, these observations suggest that iron may give a survival advantage to endothelial cells and represent a novel mechanism through which iron may contribute to tumorigenesis.

In vitro sensitivity of Kaposi's sarcoma cells to various chemotherapeutic agents including acyclic nucleoside phosphonates.

The involvement of a viral agent in the pathogenesis of Kaposi's sarcoma (KS) points to antiviral agents as possible therapeutic and/or prophylactic options in the management of the disease. In the present study we investigated the antiproliferative effects of various chemotherapeutic agents, including acyclic nucleoside phosphonates, on the growth of KS-derived cells. Nested PCR amplification demonstrated that these cells do not contain human herpesvirus 8 (HHV-8) DNA sequences. The cytotoxicity of the chemotherapeutic compounds was less pronounced in KS cells than in human dermal microvascular endothelial cells, which are considered to be the normal counterpart of KS cells. Stimulation of KS cells with basic fibroblast growth factor (bFGF) and correction of the IC50 values by the doubling times revealed that the apparent chemotherapeutic resistance of KS cells could mainly be attributed to the long doubling times of these cells. bFGF-stimulated KS cells still exhibited no particular sensitivity to the acyclic nucleoside phosphonates whose activity extends to HHV-8, which is consistent with the absence of linear HHV-8 DNA synthesis in these cells. Our data suggest that neither anti-cancer agents nor antiviral agents such as the acyclic nucleoside phosphonates can discriminate efficiently between KS cells and normal endothelial cells.

Pre-Kaposi's sarcoma: an expansion of the spectrum of Kaposi's sarcoma lesions.

We report on a lymphoedematous form of classic Kaposi's sarcoma (KS) in which characteristic purplish lesions were surrounded by atypical oedematous, flesh-coloured papules. Histological examination of these papular lesions revealed a proliferation of grouped, rather thick-walled capillaries with inflammatory infiltrates. Hot-start PCR amplification with KS 330-233 primer sequences demonstrated the presence of human herpesvirus 8 (HHV-8) sequences. In addition, cells isolated from these oedematous papules showed morphological and immunohistochemical features similar to those reported for KS-derived spindle cells. As a whole, these results suggest that these oedematous papular lesions represent pre-KS lesions and may expand the clinico-pathological spectrum of KS. The role of oedema in their induction is discussed.

Cutaneous necrotizing vasculitis after low dose methotrexate therapy for rheumatoid arthritis: a possible manifestation of methotrexate hypersensitivity.

Large haemorrhagic and necrotic cutaneous lesions developed after two low dose (5 mg) methotrexate injections in a patient suffering from long standing rheumatoid arthritis. Differential clinical diagnosis included factitia dermatitis, infectious processes, pyoderma gangrenosum, rheumatoid neutrophilic dermatitis, necrotizing arteritis and vasculitis. Histological and direct immunofluorescent examinations of skin biopsies supported the diagnosis of leucocytoclastic vasculitis. We discuss the respective roles of methotrexate and rheumatoid arthritis in the outbreak of leucocytoclastic vasculitis. Hypersensitivity is strongly suspected.

Cultured Kaposi's sarcoma tumor cells exhibit a chemokine receptor repertoire that does not allow infection by HIV-1.

BACKGROUND: HIV-1 is known to play a critical role in the pathogenesis of AIDS-associated Kaposi's sarcoma (KS). However, it remains controversial whether KS cells are target cells for HIV infection. The aim of this study was to investigate the expression of chemokine receptors in KS cell cultures and to determine whether these cells can be infected by HIV-1. MATERIAL AND METHODS: KS-derived cells and KS-Y1 cells were investigated using RT-PCR for the expression of CD4, CCR3, CCR5, CCR8 and CXCR4 mRNA. HIV infectivity of these cells was determined by p24 antigen and HIV-1 RNA production, as well as by HIV-1 DNA integration. RESULTS AND DISCUSSION: With the exception of CCR8 which is expressed by KS-derived spindle cell cultures but not by KS-Y1 cells, unstimulated KS cells express no significant levels of CD4, CCR3, CCR5 or CXCR4 mRNA. HIV infectivity assays showed that KS cells were unpermissive to HTLVIIIB and JRFL strains. Although the expression of CXCR4 mRNA could be upregulated by interleukin-1beta, stimulation of KS cells by this cytokine did not allow infection by HIV-1. CONCLUSIONS: This shows that KS cells exhibit a chemokine receptor repertoire that does not allow infection by HIV-1. Other cell types making up KS lesions, such as inflammatory cells, are likely to represent the source of HIV-1 products cooperating to promote KS development and progression.