Thalidomide for improving cutaneous and pulmonary sarcoidosis in patients resistant or with contraindications to corticosteroids.

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 100mg 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.

The "phone and mail" system in a teledermatology service for chronic psychiatric patients.

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.

Vitiligo: ocular and electrophysiological findings.

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.

Psoriasis induced by infliximab in a patient suffering from Crohn's disease.

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.

Pattern VEP alterations in psoriatic patients may indicate a sub clinic optic neuritis.

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 TNFalpha, 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.

Molecular staging of the sentinel lymph node in melanoma patients: correlation with clinical outcome.

BACKGROUND: This study was designed to determine the debated prognostic significance of reverse transcriptase-polymerase chain reaction (RT-PCR) positivity in melanoma patients' sentinel lymph node (SLN) negative by conventional histopathology (PATH). PATIENTS AND METHODS: Patients with primary stage I-II cutaneous melanoma underwent radioguided sentinel lymphadenectomy. Their SLNs were assessed for tyrosinase (Tyr) and melanoma antigens recognized by T-cells (MART-1) mRNA expression using RT-PCR, in parallel with hematoxylin and eosin staining and immunohistochemistry. Tyr and MART-1 expression in the SLNs were correlated with PATH assay results, standard prognostic factors, time to progression and overall survival. RESULTS: Twenty-three of the 124 patients (18.5%) had positive SLNs by both PATH and RT-PCR (PATH+/PCR+). Sixteen patients (13%) were negative by PATH and positive by RT-PCR (PATH-/PCR+). Eighty-five patients (68.5%) had SLNs that were negative by both PATH and RT-PCR (PATH-/PCR-). At a median follow-up of 30 months, recurrence rates among the three cohorts were statistically different (PATH+/PCR+, 60%; PATH-/PCR+, 31%; PATH-/PCR-, 9.4%). Seven of 23 (30%) and two of 16 (12.5%) patients died in the PATH+/PCR+ and PATH-/PCR+ SLN groups, respectively, whereas no patient died in the PATH-/PCR- SLN group. CONCLUSIONS: RT-PCR is more sensitive than PATH to detect SLN metastases and it is a reliable predictor of disease relapse in stage I-II melanoma patients.

Skin blood flow pattern in burns outcomes.

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 36 degrees, the postural venular-arteriolar reflex (VAR) and the flux at 41 degrees (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.

Evaluation of telomerase in non-melanoma skin cancer.

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.

Lichen myxedematosus with systemic involvement: clinical and autopsy findings.

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.

Immunohistochemical study of 49 cutaneous melanomas: p53, PCNA, Bcl-2 expression and multidrug resistance.

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.

Increased burn patient survival with once-a-day high dose teicoplanin and netilmicin. An Italian multicenter study.

This is the final report of a large, controlled, multicenter Italian study on immuno- and chemotherapy in adult patients with burns affecting 20 to 95% of total body surface area (mean 35%). The antibiotic treatment of burn patients consisted of topical silver sulfadiazine, short-term antimicrobial chemoprophylaxis with pefloxacin (800 mg i.v. qd) for the first 4 days and polychemotherapy with teicoplanin (800 mg i.v. qd) together with netilmicin (300 mg i.m. qd) in one or more cycles of 5-12 days. At random, half of the patients received thymostimulin, 70 mg i.m. qd for the first month and every other day thereafter. The analysis at completion of 634 valid cases showed that when the results are stratified by means of the Roi risk index, 396 of the 530 patients who contracted wound infection (84%) after chemoprophylaxis were in the first three categories and a mean of 95% survived. Of the remaining 134 patients (Roi index 4-5) only 50% survived. There was no difference in survival of the immunotherapy group in comparison with the parallel group without thymostimulin. The short-term antimicrobial prophylaxis prevented wound infection in only 104 of 634 patients (16%) and they were at low risk (84% Roi index 1). Of the bacterial pathogens involved in septic complications Staphylococcus aureus and Pseudomonas aeruginosa were prevalent (86%): eradication was achieved in 43% of patients and clinical cure or improvement were seen with combination chemotherapy in 64% of all patients, mainly with only one treatment cycle. This value increased to 79% for the 395 protocol-complying patients and went down to 20% in the 135 non-compliers. The total survival of complier and non-complier patients was 447 of the 530 valid patients (84%). The overall mortality of the 634 evaluable patients was 13.1%, ranging from less than 2% to 68%. Burn mortality was directly proportional to the percentage of burned body surface area, to increasing age and other variables of the Roi index, a 50% mortality being associated with a 72.5% total body surface area burned. Normoergic burn patients had a mortality rate of 9.1% versus 35.7% in anergic patients.

[Therapy of atopic dermatitis in children. Study on the use of a desensitizing preparation]. / Sulla terapia della dermatite atopica nel bambino. Studio sull'impiego di un preparato iposensibilizzante.

Children with Atopic Dermatitis have been treated with Histaglobin (gamma globulin + histamine) applied by hypodermic injections. The patients (42) were divided into three groups: the first one (ten cases) aged between 9 and 5 years; the second one (eight cases) between 5 and 2 years and the third one (twenty four cases) aged less than two years. The trial has been carried out in two phases: the first one consisted of nine injections with increasing doses ranging from 1/3 to 1 ampoule with 4-6 day intervals; the second one, "the maintenance period", was made by nine injections of 1 ampoule with increasing intervals from two up to four weeks. The following four parameters were checked along all the therapy period: prurigo, erythema, exudation, scratching lesions. All the listed symptoms have been observed to decrease of intensity mainly during the first phase, until the complete disappearance of some of them; the residual symptoms continued to have a further improvement during the second phase; in most case disappeared completely. Absolutely no troubles of any kind have been noticed. Consequently the Authors consider the desensitization therapy by Histaglobin on the whole satisfying.

The suppressive activity of T-lymphocytes and serum factors in burned patients.

This study was performed to investigate the cell-mediated immune response in burned patients with no septic episodes. The results show that burned patients with percentage body burn higher than 20 had an impaired lymphocyte reactivity to phytohaemagglutinin and conconavalin A. This hyporesponsiveness appeared on day 3-4 and in all cases reached its maximum on day 7-8 post burn, while recovery occurred between day 11 and 29 depending on the severity of the injury. The serum from immunodepressed patients was able to inhibit the response to phytohaemagglutinin and conconavalin A of normal lymphocytes. This immunosuppressive activity was present very early after injury (on day 1-2) and before the onset of lymphocyte hyporesponsiveness to mitogens and was no longer detectable on day 7-8 post burn, when patient lymphocytes showed the greatest hyporesponsiveness to mitogens. This late depression was due to T suppressor cells.