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.

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.

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.

Mechanism of mannose toxicity.

Mannose toxicity in honeybees is due to a marked shortage of mannosephosphate isomerase that leads to a large accumulation of mannose-6-P and a marked depletion of ATP. Drosophila melanogaster and Ceratitis capitata are insensitive to mannose and have excess of mannosephosphate isomerase over hexokinase. 2-Deoxyglucose is as toxic as mannose for honeybees and is toxic also for the other insects studied, which supports the conclusion that the mechanism of mannose toxicity involves large accumulation of a hexosephosphate.

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.

Reticular erythematous mucinosis associated with human immunodeficiency virus infection.

We report the case of a 56-year-old woman with reticular erythematous mucinosis (REM). During her workup infection with the human immunodeficiency virus (HIV) was detected. She developed a cerebral toxoplasmosis, salmonella sp. bacteremia and oral ulcerations with the presence of type I herpes simplex virus and cytomegalovirus. The relation of REM with the deposition of mucin in AIDS patients' bone marrow and HIV infection is discussed. To our knowledge, this is the first report where REM is associated with HIV disease.

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.

Microscopic polyangiitis. A systemic vasculitis with a positive P-ANCA.

A young girl presented with a purpuric rash on lower limbs, fever, eosinophilia, peripheral neuropathy and progressive renal insufficiency. She developed vesicles, purpuric macules and papules on the head, several nodules on the palmar sides of hands and fingers, splinter haemorrhages, and a disfiguring, facial oedema. A renal biopsy specimen disclosed a focal and segmental necrotizing glomerulonephritis with crescents. Peripheral ANCA with antimyeloperoxidase specificity [P-ANCA (MPO)] was positive and cytoplasmic ANCA with PR3 specificity was negative. Treatment with prednisone and cyclophosphamide was started with a good clinical response, stabilization of renal insufficiency and disappearance of P-ANCA (MPO). Our case fulfils the diagnostic criteria for microscopic polyangiitis (microscopic polyarteritis, MPA), namely a segmental necrotizing and crescentic glomerulonephritis associated with extrarenal vasculitis involving small-sized vessels, without granulomas or asthma. This is a rare disease, which has a poor prognosis in the absence of aggressive therapy, and is infrequently reported in dermatological journals.

Cutaneous meningioma underlying congenital localized hypertrichosis.

A 28-year-old man had a circumscribed hypertrichotic area on the left lumbar region since birth. A biopsy specimen showed numerous normal-appearing hair follicles and arrector pili muscles. In the subcutaneous layer a mass of dense collagenous connective tissue formed the background in which ill-defined foci of meningothelial cells in nests and pseudovascular spaces were seen. Collagenous structures (pseudopsammoma bodies), some of which showed calcification (psammoma bodies), were also seen. A diagnosis of cutaneous meningioma was made.

Pseudoxanthoma elasticum-like papillary dermal elastolysis. A report of two cases and review of the literature.

Pseudoxanthoma elasticum-like papillary dermal elastolysis is a peculiar idiopathic elastolytic disorder with cutaneous lesions clinically resembling pseudoxanthoma elasticum with partial or total band-like elastolysis of the papillary dermis histopathologically, and without systemic complications. We here report 2 new cases and review the clinicopathological features of patients with this diagnosis in the literature. The possible pathogenesis of this recently described entity is discussed.

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.

Recall phenomenon with the unusual presence of eccrine squamous syringometaplasia.

The recall phenomenon is an inflammatory reaction limited to a previously X-irradiated field when the patient is treated months or years later with certain drugs. Only a few cases have been reported in dermatological journals. We report a patient with lymphoma who was treated with low-dose abdominal irradiation and high-dose irradiation to the knees and who, 2 months later, when chemotherapy was started, developed a pronounced inflammatory reaction limited to the areas treated with high-dose irradiation. A skin biopsy specimen showed features of radiation damage, marked epidermal changes and extensive eccrine squamous syringometaplasia. This case of the recall phenomenon is of interest because we have found that there is apparently a radiation dose threshold for this event, and because this is the first report of its association with eccrine squamous syringometaplasia.

Keratosis punctata of the palmar creases: case report and prevalence study in Caucasians.

Keratosis punctata of the palmar creases (KPPC) is a variant of keratosis punctata of palms and soles in which lesions are confined to palmar creases. We present a patient with KPPC and study the prevalence of the disease in Caucasians. The survey included 1,001 white patients, that were examined for palmar lesions. We could not find any case that fulfilled the diagnostic criteria for KPPC. We conclude that KPPC is a rare disease among Caucasians but rather common in the black race.

Lichen amyloidosus and human immunodeficiency virus infection.

A case of lichen amyloidosus in an HIV-infected patient is presented. To our knowledge, the association between lichen amyloidosus and HIV infection has not been described previously. The possible relationship between both entities is discussed.