Background: Limited data report thalidomide improves cutaneous sarcoidosis; no benefit has been reported for pulmonary localization.Objectives: To evaluate feasibility and efficacy of prolonged treatment with thalidomide for cutaneous sarcoidosis associated to pulmonary involvement in patients with resistance or contraindications to steroids.Methods: Nineteen patients were treated with thalidomide for 24 months starting with 200 mg/d for first 2 weeks, followed by 100 mg/d for 11 weeks and a maintenance dose of 100 mg on alternate days for 35 weeks, and a gradual scaling down until therapy interruption. Criteria of efficacy were: skin score, serum ACE levels (s-ACE), chest X-ray (CXR), lung function tests (LFTs), and diffusing lung capacity for CO (DLCO). The skin score was computed as arithmetic sum of seven score parameters (min: 0, max: 28).Results: Skin score significantly decreased (P < 0.001). Lower skin scores occurred after 3 and 6 months (P < 0.05). s-ACE levels decreased over time at the third month (P < 0.001). CXR assessed by radiological stage significantly improved during the first 6 months (P < 0.001). DLCO showed a continuous trend of improvement. Minor side effects that have forced the suspension of the drug were drowsiness/sedation (74%), constipation (68%), and weight gain (53%). Deep vein thrombosis of the lower limbs occurred in one patient (who did not drop out the study). Eight patients (42%) abandoned thalidomide for axonal sensitive peripheral neuropathy (PN) between the ninth and the 24th month of treatment.Conclusions: Thalidomide, long-term at mid-low doses, can be considered as an effective therapeutic alternative in chronic sarcoidosis with resistance or contraindications to steroids. (C) 2012 Elsevier Masson SAS. All rights reserved.
AIM We aimed to test a new teledermatologic method that permits to match a high level of diagnostic accuracy, comparable with or higher to that of the Store and Forward method, with the highest handiness, comparable to that achievable with a video call, without suffering from the limitations of the two methods. METHODS We used latest-generation cell phones with a HSDPA network broad-band internet access system for video calling and for sending via e-mail high-definition images, chosen by the specialist-at-a-distance during the video call, in times comparable to those achievable with fixed-wired access systems. We tested the diagnostic reliability, the compliance and the efficacy of the method. RESULTS We found a significant concordance both between direct and via video call description of the objective signs and between direct and on high definition image description. The Spearman Rank showed a higher correlation between direct observation and high definition image observation than between direct and via video call observation: this last finding matched the experimenters' subjective experience. The compliance was positive and the efficacy comparable with the ambulatorial follow-up. CONCLUSION In conclusion, the Phone and Mail method can be seen as being capable of joining together the necessary diagnostic precision and effectiveness with a high degree of practicality and simplicity, thanks to the ease of use of the cell phone, within the reach of everybody, to the ubiquity of its utilization, to the allowed rapidity of diagnosis, practically in real time, and to the low cost of the system.
AIM:The aim of this study was to analyze the involvement of the retinal pigment epithelium (RPE) and optic nerve in patients with vitiligo (N.=40, 12 males and 28 females, age 12-82 years; average 45.8). METHODS:The dermatological and ophthalmological examinations have been followed by electro-oculography (EOG) and pattern visual evoked potential (VEP) tests. RESULTS:The results of the fundus examination were normal, showing no characteristics that might be considered typical of vitiligo. Sixteen patients had an altered VEP (9 with amplitude reduction, 7 with amplitude reduction and increased latency); 4 patients showed only an Arden Index (AI) > or =180; and 4 patients showed both an altered VEP and AI < or =180. EOG detected 1 pathological case (AI < or =160); 7 subnormal patients (AI 160-180); and 32 normal patients (AI > or =180). The mean AI was 249 in the vitiligo patients compared to 277.2 in the normal controls. Patients with both an altered VEP and an abnormal EOG had higher than average skin involvement and a longer disease duration, and the alterations in VEP (amplitude and latency) were much more marked than in the other patients. CONCLUSION:These results confirm that the simultaneous presence of abnormal VEP and EOG is characteristic of severe disease. Patients with only a pathological VEP (N.=12) had a noticeably longer mean disease duration, while those only with AI < or =180 showed a slightly higher degree of skin involvement. It may be concluded that patients with more extensive skin involvement and a longer disease duration will also exhibit more markedly negative ocular electro-physiologic findings. Pattern VEP and EOG offer useful tools to evaluate the evolution of vitiligo, because they can detect subclinical involvement of the optic nerve and RPE. The results of these two tests are correlated with the disease duration and extent of cutaneous involvement.
We describe the case of a 30-year-old female with no family history of psoriasis and suffering from Crohn's disease successfully treated with infliximab at the dosage of 5 mg/kg. On the 15th week from the start of therapy, the patient developed a palmoplantar pustular psoriasis, which spread to the arms, trunk and scalp with erythematosquamous plaques. Deeming the dermatitis onset due to the anti-TNF-alpha, we decided to discontinue infliximab, while starting with a topical therapy with emollients and corticosteroids and a systemic therapy with cyclosporine. These treatments achieved a clear improvement of psoriasis after 2 months and a complete regression of skin lesions after 4 months. Several cases have been reported of psoriasis induced by anti-TNF-alpha, which have shown to exert an effective therapeutic action on this disease. The pathogenic mechanism of such a paradoxical effect has not yet been explained, though a number of hypotheses were proposed, among which one of the most intriguing is that the rapid and strong blockade of TNF-alpha could result in an enhancement of INF-alpha activity with consequent induction of psoriasis.
We examined 44 subject (Group A) of both sexes (27 males and 17 females) aging between 16 and 80 (average: 45±16.6), divided into age bands, affected by mild-medium psoriasis with PASI (psoriasis area and severity index) between 1.2 and 48.6 (average: 11.2±9.7) without any other disease and we performed pattern transient VEP (Visual Evoked Potential) at the frequencies usually used in clinical experience (73′, 36', 18' check size). For a good statistic comparison we choose 55 healthy subjects (group B) divided into age bands on which we performed the same test. Comparison of VEP parameters between psoriatic and healthy subjects, showed in group A 10 normal (22.7%) and 34 pathological (77.3%). In the latter group there are 16 subjects who show only a P100 reduced amplitude (36.3%), 3 with only increased latency (6.8%), 15 with alterations of both values (34%). The achieved data show that more than 3/4 of group A subjects have VEP alterations as index of the presence of a sub clinic optic neuritis with a probably toxic autoimmune origin due to the action of TNFα, of IgG, of ECP or of other cytokines (IL6, IL7, etc) that are increased in the blood of this patients. The electro physiologic monitoring of optic nerve seems to represent a good routine test to evaluate the global conditions of psoriatic patients.
The evaluation of burn depth is mainly performed by clinical assessment. Although rapid and useful, this approach is sometimes inaccurate and subjective. In this study, the reliability of subjective clinical assessment of burn depth by clinicians is compared to the reliability of a colorimetric measurement technique. Using clinical scoring and objective assessment with a tri-stimulus colorimeter, the authors evaluated 123 patients with superficial and deep partial-thickness burns. Healing time was correlated to the clinical scoring and instrumental data on burn depth. Superficial wounds had a significantly higher luminance (L*, p < 0.05) and redness (a*, p < 0.05) when compared to deep wounds. The overall accuracy of deep burn depth estimation was significantly more accurate with the colorimeter than with clinical scoring. This study shows that an overall evaluation of partial-thickness burns with a colorimeter is more reliable than clinical evaluation by observers.
Functional microcirculatory aspects of burned sites were examined including areas of self-healed burns, and grafted areas. Donor areas were also examined.In 10 patients with burns in the lower limbs, both self-healed and with grafts, the microcirculatory response was evaluated by Laser Doppler flowmetry (LDF) measuring for each site the resting flux at 36degrees, the postural venular-arteriolar reflex (VAR) and the flux at 41degrees (heating). The first evaluation was carried out on discharge, and subsequently at approximately 45 day intervals during uniform therapy follow-up (elastocompression).The burn-affected area (self-healed, graft) and those donor areas present should increase resting flux by comparison with control areas. This was particularly so in the self-healed burn, which does however tend to converge in time towards control values. Response to stress tests (VAR and heating) presents percentage variations similar to normal skin in the various areas, with the exception of the grafted areas which present a reduced response in the 1st weeks following engraftment. No significant differences in response to heating were detected.It can be suggested that these differences are due to anatomic variations in revascularization and healing in the different areas as well as to alterations in microvascular innervation and local response to vasoactive substances. (C) 2004 Published by Elsevier Ltd and ISBI.
Telomerase, a ribonucleoprotein, is capable of adding telomeric sequences (TTAGGG hexameric repeats) to the ends of chromosomes and, thereby, halting the erosion of chromosome at each cell division. Whereas most normal somatic cells contain minimal or no detectable telomerase activity, most immortal and tumour cells exhibit significant levels of telomerase activity and show no net loss of telomere length during proliferation. The evaluation of telomerase has been proposed for diagnostic and therapeutic purposes in human cancer. Skin cancer is the most common cancer in humans; the precise molecular events in skin carcinogenesis are numerous and complicated and not yet completely clarified. In this study, we evaluated telomerase in 35 basal cell carcinomas and in 14 squamous cell carcinomas in order to determine if activation of the telomerase enzyme was a pivotal step in the development of skin cancer and whether telomerase activity levels were different between the two histotypes. A higher enzymatic level was shown to be associated with squamous cell carcinomas, while low levels were mainly detected in the basal cell histotype (chi2 test; p=0.02). Telomerase complex activity is dependent on its catalytic subunit, telomerase reverse transcriptase hTERT. By reverse transcription-PCR, using primers within the reverse transcriptase domain of hTERT, we observed a significant correlation between hTERT expression and telomerase activity in our skin tumour samples (p=0.0003). We detected the presence of multiple, alternately spliced transcripts, corresponding to full-length messages as well as spliced messages with critical reverse transcriptase motifs deleted. A higher telomerase messenger level was shown to be associated with squamous cell carcinomas (chi2 test; p<0.0001), as for telomerase activity. Our results provide arguments supporting the role of telomerase in skin cancer and suggest RT-PCR of telomerase RNA as a tool easier and faster than TRAP assay to identify more aggressive malignancies among non-melanoma skin specimens.
Angiogenesis is a central process in the growth of solid tumors. The purpose of our study was to analyze the angiogenic pattern in squamous and basal cell carcinomas and to point out differences in microvessel density that could explain their different biological behaviour. Thirty-nine skin tumors (26 basal and 13 squamous cell carcinomas) were analyzed. In all samples, the microvessels density (MVD) and the levels of vascular endothelial growth factor mRNA (VEGFmRNA) were analyzed, together with the inter-relationship between these two variables. Using the median value of the entire series (33 vessels per 2.22 mm2), tumors with low and high MVD were identified. The majority of cancers with high vascularization belonged to the squamous histotype (12 of 39), while 19 of the 26 basal cell carcinomas showed a lower number of microvessels than the median value (p = 0.0001). The median value of VEGFcDNA quantitation allowed us to distinguish tumors with high VEGF expression (> 470 molecules cDNA) from those with low (< or = 470 molecules) VEGF expression: 20 of the 26 basal cell carcinomas showed low VEGF expression, while 11 of the 13 squamous cell carcinomas showed high VEGFcDNA levels (p = 0.0003). Moreover, a significant association between a high microvessel density and high VEGFmRNA levels (p = 0.006) was found. Furthermore, when studying VEGF expression by immunohistochemistry, we obtained similar results and noted a correlation with VEGFmRNA expression (p < 0.0001). The association between high vascularization, high VEGF levels, and squamous cell histotype suggests the possible role of neoangiogenesis in determining the more aggressive biological behaviour of this type of cancer.
Aims and Background Thickness and level of invasion are the main morphological elements for an approximate but not sufficiently sensitive prognostic evaluation of cutaneous melanomas. By using immunohistochemical methods it is possible to detect biological markers related to prognosis. We have studied p53, PCNA, Bcl-2 and P-gp expression in 49 primary cutaneous melanomas. Materials We used the immunophosphatase APAAP immunohistochemical method. The percentage of labeled cells (according to four classes of positivity: <5%; 5-25%; 25-50%; >50%) and the localization of immunoreactivity were expressed for each marker. Statistical analysis was performed to determine the correlations between markers and level or thickness of melanomas. Results We found a good correlation between p53 expression and melanoma thickness (P <0.005), PCNA and P-gp expression. No relationship was observed between Bcl-2 expression and the different variables considered or other markers. Conclusions Our data seem to indicate an unfavorable prognostic role of higher nuclear p53 expression. However, we believe that our results need to be integrated with patients’ clinical follow-up and with the study of the expression of these markers in benign melanocytic lesions to gain more accurate information about their prognostic significance.
Lichen myxedematosus is a rare disease that is characterized by the formation of lichenoid papules and plaques. Histologic examination shows deposition of mucinous material in the dermis. We report the case of a patient with cutaneous and systemic involvement and examine the clinical and postmortem data.