Chronic idiopathic acrocyanosis and methylenetetrahydrofolate reductase C677T (p.Ala222Val) and A1298C (p.Glu429Ala) polymorphisms.

BACKGROUND: Chronic idiopathic acrocyanosis is a common acrosyndrome. Methylenetetrahydrofolate reductase (MTHFR) is an enzyme involved in the metabolism of folate. Two functional polymorphisms of MTHFR have been identified, C677T and A1298C. OBJECTIVE: To compare the prevalence of these two MTHFR polymorphisms in patients with chronic idiopathic acrocyanosis to a control group. MATERIALS AND METHODS: The study was conducted on 43 consecutive patients with acrocyanosis and on 100 controls. RESULTS: The risk of acrocyanosis was significantly higher in patients homozygous for the mutation c.677C>T compared to those with no mutation (OR = 4.8 (95%CI 1.5-14.9)). The homozygosity TT was associated with an increased homocysteine level. CONCLUSION: On the basis of our findings, acrocyanosis could be considered as a cutaneous sign of a "latent" cardiovascular risk. This should be taken into account particularly when acrocyanosis is associated either to other medical conditions that determine vessel wall damage or to conditions that predispose to the risk of thromboembolism.

Therapy with rituximab for autoimmune pemphigus: results from a single-center observational study on 42 cases with long-term follow-up.

BACKGROUND: Rituximab induces depletion of B cells and has shown efficacy in antibody-mediated autoimmune disorders. In studies on small series of patients with pemphigus, rituximab administration results in significant improvement. However, differences in inclusion criteria, treatment protocols, and follow-up make it difficult to derive uniform conclusions. OBJECTIVES: We sought to test the efficacy and tolerability of rituximab as adjuvant therapy to corticosteroids in the treatment of pemphigus. METHODS: In all, 42 patients with pemphigus were treated with rituximab and followed up for up to 5 years. No additional immunosuppressive agents were used. Steroids were rapidly tapered. Outcomes were the proportion of patients who achieved a complete response on or off therapy, the rate of discontinuation of corticosteroid within 6 months, length of remission, time to relapses, and occurrence of adverse events. RESULTS: In all, 36 of 42 patients (86%; 95% confidence interval 75%-96%) achieved a complete response on or off therapy and discontinued steroids within 6 months from induction therapy. Six patients had a complete response off therapy with an additional infusion of rituximab 6 months after initial treatment. Twenty patients experienced a total of 34 relapses; the time to relapse was 8 to 64 months. Every relapse was treated with rituximab (500 mg) without corticosteroids, which induced a new complete response. No serious adverse events were observed. LIMITATIONS: Lack of a control group is a limitation. CONCLUSIONS: Rituximab therapy induces prolonged clinical remission in patients with pemphigus. Coadministration of other immunosuppressive agents is not necessary. Relapses can be managed with additional infusions administered on demand.

Treatment of severe pemphigus with rituximab: report of 12 cases and a review of the literature.

BACKGROUND: Treatment of pemphigus vulgaris can be challenging. Systemic steroids associated with other immunosuppressant agents are the mainstay of therapy and have dramatically reduced morbidity and mortality from pemphigus vulgaris. In some patients, however, these agents are not able to control the disease or have severe adverse effects. Rituximab (MabThera; Roche, Basel, Switzerland), a chimeric monoclonal anti-CD20 antibody, induces depletion of B cells in vivo and has shown efficacy in patients with refractory antibody-mediated autoimmune disorders. We report 10 cases of pemphigus vulgaris and 2 cases of pemphigus foliaceous treated with rituximab--to our knowledge the largest series of patients so far--and review the existing literature on the topic. OBSERVATION: The 12 patients were selected for treatment with the anti-CD20 antibody. Rituximab was administered intravenously at a dosage of 375 mg/m(2) once weekly for 4 weeks. The treatment was well tolerated, and all 12 patients showed a good clinical response during an 18-month follow-up period, along with a consensual decline of the serum antidesmoglein titers. No infectious complications were observed. CONCLUSIONS: Rituximab is able to induce a prolonged clinical remission in patients with both pemphigus vulgaris and pemphigus foliaceous after a single course of 4 treatments. The preliminary experiences worldwide make rituximab a promising therapeutic option for patients with autoimmune diseases. The high costs and the limited knowledge of long-term adverse effects, however, limit its use to selected patients with treatment-resistant or life-threatening disease.

Nevus type in dermoscopy is related to skin type in white persons.

BACKGROUND: Dermoscopic classification of acquired melanocytic nevi (AMN) is based on the evaluation of 3 main criteria-global pattern, pigment distribution, and color. OBJECTIVE: To determine whether these features are different in AMN in white people with different skin types (STs) according to the Fitzpatrick classification. DESIGN: Digital dermoscopic images of AMN were evaluated, and the correlation of the 3 main dermoscopic criteria with patient ST was analyzed. SETTING: Consecutive patients were recruited from 7 pigmented lesion clinics between June 1, 2004, and June 30, 2005. Patients For each patient, the ST (I [always burns, never tans] to IV [rarely burns, tans with ease]) was scored, and 1 representative AMN (defined as the AMN showing a dermoscopic typology that is repeatedly seen in the same patient) was selected and photographed. MAIN OUTCOME MEASURES: The distribution of the dermoscopic criteria of AMN in patients with different STs was calculated by univariate analysis. Differences in prevalence were tested using the chi(2) test. The correlation between dermoscopic criteria and ST, adjusted for age, sex, and enrolling center, was evaluated by calculating odds ratios and 95% confidence intervals by logistic regression analysis. RESULTS: Of 680 included patients, dermoscopic analysis revealed significant differences in the prevalent nevus pattern in the 4 ST groups. Light brown AMN with central hypopigmentation were associated with ST I, and ST IV was associated with the so-called black nevus (P<.001), typified by reticular pattern, central hyperpigmentation, and dark brown coloration. A significant association was also found between multifocal pattern and ST II and ST III. CONCLUSIONS: The dermoscopic nevus type varies according to different ST in white people. This knowledge may have an effect on obtaining for biopsy lesions that exhibit unusual dermoscopic patterns when patient ST is considered.

Dermoscopy improves accuracy of primary care physicians to triage lesions suggestive of skin cancer.

PURPOSE: Primary care physicians (PCPs) constitute an appropriate target for new interventions and educational campaigns designed to increase skin cancer screening and prevention. The aim of this randomized study was to determine whether the adjunct of dermoscopy to the standard clinical examination improves the accuracy of PCPs to triage lesions suggestive of skin cancer. PATIENTS AND METHODS: PCPs in Barcelona, Spain, and Naples, Italy, were given a 1-day training course in skin cancer detection and dermoscopic evaluation, and were randomly assigned to the dermoscopy evaluation arm or naked-eye evaluation arm. During a 16-month period, 73 physicians evaluated 2,522 patients with skin lesions who attended their clinics and scored individual lesions as benign or suggestive of skin cancer. All patients were re-evaluated by expert dermatologists at clinics for pigmented lesions. Referral accuracy of both PCP groups was calculated by their scores, which were compared to those tabulated for dermatologists. RESULTS: Referral sensitivity, specificity, and positive and negative predictive values were 54.1%, 71.3%, 11.3%, and 95.8%, respectively, in the naked-eye arm, and 79.2%, 71.8%, 16.1%, and 98.1%, respectively, in the dermoscopy arm. Significant differences were found in terms of sensitivity and negative predictive value (P = .002 and P = .004, respectively). Histopathologic examination of equivocal lesions revealed 23 malignant skin tumors missed by PCPs performing naked-eye observation and only six by PCPs using dermoscopy (P = .002). CONCLUSION: The use of dermoscopy improves the ability of PCPs to triage lesions suggestive of skin cancer without increasing the number of unnecessary expert consultations.

Vascular structures in skin tumors: a dermoscopy study.

OBJECTIVES: To describe the different vascular structures seen by dermoscopy and to evaluate their association with various melanocytic and nonmelanocytic skin tumors in a large series of cases. DESIGN: Digital dermoscopic images of the lesions were evaluated for the presence of various morphologic types of vessels. SETTING: Specialized university clinic. PATIENTS: From a larger database, 531 excised lesions (from 517 patients) dermoscopically showing any type of vascular structures were included. MAIN OUTCOME MEASURES: The frequency and positive predictive value of the different vascular structures seen in various tumors were calculated, and the differences were evaluated by the chi2 or Fisher exact test. RESULTS: Arborizing vessels were seen in 82.1% of basal cell carcinomas, with a 94.1% positive predictive value (P<.001). Dotted vessels were generally predictive for a melanocytic lesion (90.0%, P<.001), and were especially seen in Spitz nevi (77.8% of lesions). In melanoma, linear-irregular, dotted, and polymorphous/atypical vessels were the most frequent vascular structures, whereas milky-red globules/areas were the most predictive ones (77.8%, P = .003). The presence of erythema was most predictive for Clark nevus, whereas comma, glomerular, crown, and hairpin vessels were significantly associated with dermal/congenital nevi, Bowen disease, sebaceous hyperplasia, and seborrheic keratosis, respectively (P<.001 for all). CONCLUSIONS: Different morphologic types of vessels are associated with different melanocytic or nonmelanocytic skin tumors. Therefore, the recognition of distinctive vascular structures may be helpful for diagnostic purposes, especially when the classic pigmented dermoscopic structures are lacking.

Inter- and intra-variability of pigmented skin lesions: could the ABCD rule be influenced by host characteristics?

BACKGROUND/PURPOSE: Many differences in color, shape and dimension exist between different moles even in the same individual. Major differences might be accounted for anatomical location, genetic factors and by environmental factors, mainly sunlight exposure. Therefore, it would be of great value, when evaluating skin lesions, to take into account the degree of intra- and inter-variability of several diagnostic parameters. In order to assess the morphologic and chromatic differences between lesions belonging to different patients and between lesions belonging to the same individual, we examined objective digital parameters obtained with dermatoscopic analysis, using the DBDermo MIPS system (BIO MIPS Engineering, S.R.L, siena, Italy). METHODS: The automatic classifier inside the software is based on a 'match by similarity' algorithm, based on the measurement of the Euclidean distances of all variables considered from the reference image. Two-hundred and four clinically benign pigmented lesion, belonging to 18 patients were examined, stored and automatically processed. For each lesion objective parameters related to geometry, color and texture were automatically evaluated. RESULTS: We found skin color (healthy skin) is objectively different from subject to subject and the lesion color is more similar among different lesions of the same patient than among lesions belonging to different individuals both in their darkest and slightly dark component. We also observed that lesion dimensions are individual correlates, i.e. the probability for a lesion to be large is higher when the other, in the same patient, is large. CONCLUSION: Many parameters of pigmented skin lesions evaluated by digital dermoscopy analysis are similar in the same patient and different from those belonging to different individuals. This indicates that, when considering a lesion, we should take into account the peculiar patient's characteristics.

Melanoma computer-aided diagnosis: reliability and feasibility study.

BACKGROUND: Differential diagnosis of melanoma from melanocytic nevi is often not straightforward. Thus, a growing interest has developed in the last decade in the automated analysis of digitized images obtained by epiluminescence microscopy techniques to assist clinicians in differentiating early melanoma from benign skin lesions. PURPOSE: The aim of this study was to evaluate diagnostic accuracy provided by different statistical classifiers on a large set of pigmented skin lesions grabbed by four digital analyzers located in two different dermatological units. EXPERIMENTAL DESIGN: Images of 391 melanomas and 449 melanocytic nevi were included in the study. A linear classifier was built by using the method of receiver operating characteristic curves to identify a threshold value for a fixed sensitivity of 95%. A K-nearest-neighbor classifier, a nonparametric method of pattern recognition, was constructed using all available image features and trained for a sensitivity of 98% on a large exemplar set of lesions. RESULTS: On independent test sets of lesions, the linear classifier and the K-nearest-neighbor classifier produced a mean sensitivity of 95% and 98% and a mean specificity of 78% and of 79%, respectively. CONCLUSIONS: In conclusion, our study suggests that computer-aided differentiation of melanoma from benign pigmented lesions obtained with DB-Mips is feasible and, above all, reliable. In fact, the same instrumentations used in different units provided similar diagnostic accuracy. Whether this would improve early diagnosis of melanoma and/or reducing unnecessary surgery needs to be demonstrated by a randomized clinical trial.

Three-point checklist of dermoscopy. A new screening method for early detection of melanoma.

BACKGROUND: Dermoscopy used by experts has been demonstrated to improve the diagnostic accuracy for melanoma. However, little is known about the diagnostic validity of dermoscopy when used by nonexperts. OBJECTIVE: To evaluate the diagnostic performance of nonexperts using a new 3-point checklist based on a simplified dermoscopic pattern analysis. METHODS: Clinical and dermoscopic images of 231 clinically equivocal and histopathologically proven pigmented skin lesions were examined by 6 nonexperts and 1 expert in dermoscopy. For each lesion the nonexperts assessed 3 dermoscopic criteria (asymmetry, atypical network and blue-white structures) constituting the 3-point method. In addition, all examiners made an overall diagnosis by using standard pattern analysis of dermoscopy. RESULTS: Asymmetry, atypical network and blue-white structures were shown to be reproducible dermoscopic criteria, with a kappa value ranging from 0.52 to 0.55. When making the overall diagnosis, the expert had 89.6% sensitivity for malignant lesions (tested on 68 melanomas and 9 pigmented basal cell carcinomas), compared to 69.7% sensitivity achieved by the nonexperts. Remarkably, the sensitivity of the nonexperts using the 3-point checklist reached 96.3%. The specificity of the expert using overall diagnosis was 94.2% compared to 82.8 and 32.8% achieved by the nonexperts using overall diagnosis and 3-point checklist, respectively. CONCLUSION: The 3-point checklist is a valid and reproducible dermoscopic algorithm with high sensitivity for the diagnosis of melanoma in the hands of non-experts. Thus it may be applied as a screening procedure for the early detection of melanoma.

Dermoscopy of pigmented skin lesions: results of a consensus meeting via the Internet.

BACKGROUND: There is a need for better standardization of the dermoscopic terminology in assessing pigmented skin lesions. OBJECTIVE: The virtual Consensus Net Meeting on Dermoscopy was organized to investigate reproducibility and validity of the various features and diagnostic algorithms. METHODS: Dermoscopic images of 108 lesions were evaluated via the Internet by 40 experienced dermoscopists using a 2-step diagnostic procedure. The first-step algorithm distinguished melanocytic versus nonmelanocytic lesions. The second step in the diagnostic procedure used 4 algorithms (pattern analysis, ABCD rule, Menzies method, and 7-point checklist) to distinguish melanoma versus benign melanocytic lesions. kappa Values, log odds ratios, sensitivity, specificity, and positive likelihood ratios were estimated for all diagnostic algorithms and dermoscopic features. RESULTS: Interobserver agreement was fair to good for all diagnostic methods, but it was poor for the majority of dermoscopic criteria. Intraobserver agreement was good to excellent for all algorithms and features considered. Pattern analysis allowed the best diagnostic performance (positive likelihood ratio: 5.1), whereas alternative algorithms revealed comparable sensitivity but less specificity. Interobserver agreement on management decisions made by dermoscopy was fairly good (mean kappa value: 0.53). CONCLUSION: The virtual Consensus Net Meeting on Dermoscopy represents a valid tool for better standardization of the dermoscopic terminology and, moreover, opens up a new territory for diagnosing and managing pigmented skin lesions.

Dermoscopic and histopathologic diagnosis of equivocal melanocytic skin lesions: an interdisciplinary study on 107 cases.

BACKGROUND: Dermoscopy (dermatoscopy, epiluminescence microscopy) is increasingly employed for the preoperative detection of cutaneous melanoma; dermoscopic features of pigmented skin lesions have been previously defined using histopathology as the key to the code. In a preliminary study on 10 cases evaluated by nine dermoscopists and nine histopathologists, the authors experienced that when at least two dermoscopists disagree in evaluating a melanocytic lesion, even histopathologic consultations may give equivocal results. METHODS: One hundred seven melanocytic skin lesions, consecutively excised because of equivocal clinical and/or dermoscopic features, were retrospectively examined by eight dermoscopists and eight histopathologists; the diagnostic interobserver agreement was calculated by means of the Schouten k statistics. After histopathologic consultations, all 107 lesions underwent unblinded dermoscopic re-evaluation in order to find which dermoscopic features had given rise to histopathologic diagnostic difficulties. RESULTS: The interobserver ageement was good for both dermoscopy (k = 0.53) and histopathology (k = 0.74). Out of 48 cases evaluated by the dermoscopists in complete accordance, only 8 (16.7%) received at least one conflicting histopathologic diagnosis. Instead, among the remaining 59 cases with at least one disagreeing dermoscopic diagnosis, 21 (35.6%) received at least one disagreeing histopathologic diagnosis. The unblinded dermoscopic re-evaluation showed that five out of seven lesions with clear-cut regression structures were histopathologically controversial. CONCLUSIONS: At least for selected and reasonably difficult lesions, a diagnostic discrepancy among formally trained dermoscopists seems to be predictive for a diagnostic disagreement among histopathologists. Lesions showing clear-cut regression structures are prone to give some histopathologic disagreement.