Cutaneous lichenoid graft-versus-host disease mimicking lupus erythematosus.

Graft-versus-host disease (GVHD) is the main complication of allogeneic bone marrow transplantation and the skin is the most commonly involved organ. The clinical presentation is varied and may resemble autoimmune diseases, such as scleroderma, lichen planus or lichen sclerosus. Chronic GVHD presenting with a butterfly malar rash mimicking lupus erythematosus is uncommon. We report a series of five patients with cutaneous lichenoid GVHD that presented with a butterfly malar rash. Two of our patients had positive antinuclear antibody titres. The evolution was poor with development of sclerodermatous GVHD lesions in three patients and relapse of their haematological disease in two.

Quality of life in mild to moderate acne: relationship to clinical severity and factors influencing change with treatment.

BACKGROUND: Because of its effects on quality of life, acne vulgaris is more than a merely physiological or cosmetic entity. OBJECTIVES: To describe the influence of mild to moderate acne on patients' quality of life, measured using Skindex-29, and to correlate changes in Skindex-29 scores with changes in objective and subjective indices in clinical severity after treatment with topical 4% erythromycin 0.2% zinc. Also, to evaluate efficacy and side-effects of the treatment. METHODS: Observational, prospective study of 1878 patients cared for by 252 clinicians in Spain. Data included epidemiological information and responses to Skindex-29, a subjective change and objective severity index. RESULTS: Baseline Skindex scale scores were worse in women, older patients, and those with more severe clinical disease. Skindex was sensitive to changes in objective severity but changes in Skindex scale scores were also related to other factors. Patients who reported their skin condition to be 'the same' or 'worse' at the end of the study had significantly worse baseline scores on the 'symptoms' and 'emotions' scales but 'functioning' scores were not worse than for those who reported their condition had improved. CONCLUSION: The effects of acne vulgaris on quality of life and changes in quality of life after treatment are not only explainable by objective severity of acne. Patients' and clinicians' judgements about acne severity are different.

Implication of MT1-MMP in the maturation steps of benign melanocytic nevi.

BACKGROUND: Metalloproteinases (MMPs) are proteins involved in extracellular matrix breakdown and have been implicated in stages of migration and metastasis. MT1-MMP is an MMP anchored to the cell membrane. During maturation, melanocytic nevi penetrate the extracellular matrix and express MMPs. METHODS: We studied 10 junctional, 10 compound, and 10 intradermal nevi diagnosed by clinical and histological studies and by performing immunohistochemical study to assess MT1-MMP activity. RESULTS: We found evidence of MT1-MMP expression in melanocytic nevus cells, particularly around the entire border of cell nests. Expression was more intense in junctional nevi and gradually decreased with acquisition of intradermal component and became nonexistent in nevi in the deep dermis. CONCLUSIONS: MT1-MMP is expressed in the membrane of nevus cells, with expression greater in nest cells in contact with the extracellular matrix. The intensity of expression correlated inversely with the maturation phase of the nevus, being very high in junctional nevi and low in intradermal nevi.

Maculopapular eruption with enlarged macrophages in eight patients receiving G-CSF or GM-CSF.

In the last years, granulocyte and granulocyte-macrophage colony-stimulating factors (G-CSF and GM-CSF) are being increasingly used and several cutaneous eruptions have been reported in relation to these treatments. In 1991 Horn et al. described three patients with maculopapular eruption that paralleled the time of infusion of GM-CSF. Two of the cases showed an increase in the number and size of macrophages in the biopsy specimen. Since then, several cases have been reported showing this histopathological alteration that has been considered characteristic of reaction to G-CSF or GM-CSF. Although maculopapular eruption with enlarged macrophages can appear after chemotherapy treatment, we have found that the presentation of this eruption after the beginning of cytokine treatment is suggestive of the involvement of G-CSF and GM-CSF in the eruption. We described eight cases of patients treated with G-CSF or GM-CSF that developed maculopapular eruptions with enlarged macrophages.

Diagnostic and neural analysis of skin cancer (DANAOS). A multicentre study for collection and computer-aided analysis of data from pigmented skin lesions using digital dermoscopy.

BACKGROUND: Early detection of melanomas by means of diverse screening campaigns is an important step towards a reduction in mortality. Computer-aided analysis of digital images obtained by dermoscopy has been reported to be an accurate, practical and time-saving tool for the evaluation of pigmented skin lesions (PSLs). A prototype for the computer-aided diagnosis of PSLs using artificial neural networks (NNs) has recently been developed: diagnostic and neural analysis of skin cancer (DANAOS). OBJECTIVES: To demonstrate the accuracy of PSL diagnosis by the DANAOS expert system, a multicentre study on a diverse multinational population was conducted. METHODS: A calibrated camera system was developed and used to collect images of PSLs in a multicentre study in 13 dermatology centres in nine European countries. The dataset was used to train an NN expert system for the computer-aided diagnosis of melanoma. We analysed different aspects of the data collection and its influence on the performance of the expert system. The NN expert system was trained with a dataset of 2218 dermoscopic images of PSLs. RESULTS: The resulting expert system showed a performance similar to that of dermatologists as published in the literature. The performance depended on the size and quality of the database and its selection. CONCLUSIONS: The need for a large database, the usefulness of multicentre data collection, as well as the benefit of a representative collection of cases from clinical practice, were demonstrated in this trial. Images that were difficult to classify using the NN expert system were not identical to those found difficult to classify by clinicians. We suggest therefore that the combination of clinician and computer may potentially increase the accuracy of PSL diagnosis. This may result in improved detection of melanoma and a reduction in unnecessary excisions.

Pustular acral erythema in a patient with acute graft-versus-host disease.

Acral erythema is a well-known side-effect of chemotherapy treatment but it is not common in patients undergoing bone marrow transplant. We report a post-transplant patient with clinical and histological acute graft-versus-host disease (GVHD) who concurrently developed acral erythema presenting as painful, well-defined and self-limiting palmar erythema with pustules. A skin biopsy from the palm showed abnormal keratinocyte maturation and eccrine squamous syringometaplasia. This case illustrates the difficulties in establishing the differential diagnosis of cutaneous eruptions in patients undergoing bone marrow transplant.

Tetraspanins are localized at motility-related structures and involved in normal human keratinocyte wound healing migration.

We have described previously that beta1 integrins, which mediate keratinocyte cell adhesion and migration, are in ligand-occupied conformation at the basal surface but not at the lateral and apical surfaces of keratinocytes. This led us to study the cellular localization and function of tetraspanin molecules, which have been postulated to modulate integrin activity. We found that CD9 and CD81 are highly expressed by keratinocytes clearly delineating filopodia at lateral and apical surfaces. CD63 and CD151 are largely expressed in the intracellular compartment, although some membrane expression is observed. We found accumulation of CD9, CD81, and CD151 together with alpha3 and beta1 integrins at intercellular junctions. In low calcium medium, this intercellular space is crossed by a zipper of filopodia enriched in alpha3beta1 and tetraspanin proteins. Interestingly, the expression of CD9, CD81, and beta1 and alpha3 integrins was detected in the footprints and rippings of motile keratinocytes, suggesting their role in both adhesion to extracellular matrix and keratinocyte motility. beta1 integrins were only partially activated in the rips, whereas cytoskeleton-linking proteins such as talin were completely absent. On the other hand, antitetraspanin antibodies did not stain focal adhesions, which contain talin. The involvement of tetraspanins in keratinocyte motility was assessed in a wound healing migration assay. Inhibition of cell migration was observed with antibodies to CD9, CD81, beta1, and alpha3, and, to a lesser extent, to CD151. Together these results indicate that tetraspanin-integrin complexes might be involved in transient adhesion and integrin recycling during keratinocyte migration, as well as in intercellular recognition.

The Spanish version of Skindex-29.

BACKGROUND: Most currently available dermatologic quality-of-life measures were originally created in English, and must be translated and adapted for use in other cultures. Our purpose was to translate and adapt culturally into Spanish a skin-related quality-of-life measure, Skindex-29, and to begin preliminary assessments of its reliability and validity. METHODS: Transcultural adaptation and cross-sectional questionnaire studies were performed. One hundred and fourteen adult persons (patients and healthy people) responded to the Spanish version of Skindex-29. Evaluations of the semantic equivalence of back-translated items, reliability, construct validity, and content validity of the Spanish version were the main outcome measures. Comparison between Spanish and American responses was also performed. RESULTS: Six problematic items required a second translation and back-translation to achieve satisfactory agreement with the original instrument. The final Spanish version of Skindex-29 was internally reliable (range of Cronbach alpha for the scales, 0.70-0.87). The instrument demonstrated both construct and content validity. As hypothesized, scores for dermatologic patients were higher than those for healthy persons (mean global scores 21 vs. 5, P < 0.01) and scores for patients with inflammatory diseases were higher than those for persons with isolated skin lesions (mean global scores 32 vs. 11, P < 0.01), indicating a poorer quality of life. In addition, most patients' responses to an open-ended question about their skin disease were addressed by items in the instrument. Skindex scale scores of American and Spanish respondents were similar. CONCLUSIONS: We have developed a semantically equivalent translation of Skindex-29 into Spanish. Our preliminary evaluation of its measurement properties suggests that it is a reliable and valid measure of the effects of skin disease on the quality of life in Spanish patients.

Differential expression of activation epitopes of beta1 integrins in psoriasis and normal skin.

In the epidermis, beta1 integrin expression is normally confined to the basal layer; however, suprabasal expression of beta1 integrins in keratinocytes has been found in psoriasis, and it has been suggested that it could be a pathogenic factor of the disease. We have investigated herein the functional state of beta1 integrins of human keratinocytes in normal skin and psoriasis. The expression of beta1-activation-reporter epitopes was monitored with two monoclonal antibodies, HUTS-21 and MG5A7, that recognize epitopes whose expression parallels functional activity of beta1 integrins and correlates with the ligand binding activity of these heterodimeric glycoproteins. We have found that keratinocytes express activation epitopes of beta1 integrins, and that these epitopes can be modulated by manganese. The expression of activation epitopes of beta1 integrins was related to an enhanced adhesion to fibronectin and collagen. Immunohistochemical studies of normal and psoriatic skin with HUTS-21 and other monoclonal antibodies indicate that, although there is suprabasal expression of beta1 integrins in psoriasis, these molecules seem to be in an inactive state. Moreover, most beta1 integrins in lateral and apical surfaces of basal keratinocytes of psoriasis are also in a nonactive conformation, implying a decrease of activity compared with normal skin, in which active beta1 integrins are distributed all over the basal keratinocytes.

Perforating granuloma annulare.

BACKGROUND: Perforating granuloma annulare (PGA) is considered an histologic subtype of granuloma annulare (GA) and it is described as a very rare disease, usually of children, affecting the dorsum of the hands. Mechanisms leading to perforation are unknown. Our experience suggested a different clinical presentation, so we decided to review our patients and the cases published. METHODS: We present six cases of PGA and review 52 PGA cases reported in the literature. Data regarding sex, age, time of evolution of disease, clinical features, laboratory findings, treatment, and follow-up were collected. The significance level was determined by the chi 2 or Student t test when appropriate. RESULTS: The prevalence of PGA could be up to 5% of GA. Pustular-like lesions can be found in 26% of cases, and scars in 37%; papular, umbilicated, and crusted lesions being the most common finding. While PGA appears as a single lesion in only 9% of cases, and half of the patients are older than 30 years. In GA 50% of cases present as a single lesion and 80% of patients are younger than 30 years. CONCLUSIONS: PGA is different to GA not only histologically but also clinically. It is a disseminated disease, affecting both children and adults, which is characterized by the presence of multiple papules, most of them umbilicated and/or crusted, and characteristically pustular lesions and scars. Histology suggests that the superficial localization of the necrobiotic granuloma leads to the epidermal perforation. Treatment is disappointing.