A randomized clinical trial in psoriasis: synchronous balneophototherapy with bathing in Dead Sea salt solution plus narrowband UVB vs. narrowband UVB alone (TOMESA-study group).

BACKGROUND: Synchronous balneophototherapy (sBPT) simulates treatment conditions at the Dead Sea for outpatient use. In the past, sBPT proved to be an effective treatment for psoriasis. However, there is a lack of sufficiently large randomized controlled clinical trials evaluating the additional benefit of sBPT compared with ultraviolet B (UVB) monotherapy. OBJECTIVES: The purpose of this study was to compare the effectiveness and safety of sBPT with UVB phototherapy (PT) alone in a randomized controlled effectiveness study. METHODS: In this phase III, multicentre effectiveness study, 367 patients with moderate to severe psoriasis were randomly allocated in a 1 : 1 ratio to receive either sBPT consisting of narrowband UVB PT with 311 nm and synchronous bathing in 10% Dead Sea salt solution or PT with 311 nm alone. Primary endpoint, analysed on an intention-to-treat basis (n = 356), was the relative improvement of the Psoriasis Area and Severity Index (PASI) from baseline to end of treatment (35 sessions or clearance). Sample size calculation aimed at the detection of superiority of at least 10%. RESULTS: Median PASI values were comparable at baseline (sBPT: 15.1, interquartile range: 10.9-24.3; PT: 15.3, interquartile range: 10.0-23.7). A clinically relevant and statistically significant difference of 49.5% between sBPT and PT could be proven at the end of the therapy phase (P < 0.001; Wilcoxon-Mann-Whitney test). Exploratory testing showed a statistically significant superiority of sBPT after 6 months. CONCLUSIONS: In routine clinical practice, sBPT is superior to PT alone after 35 treatment sessions and a follow-up of 6 months. Both treatments demonstrated to be safe.

A first prospective randomized controlled trial on the efficacy and safety of synchronous balneophototherapy vs. narrow-band UVB monotherapy for atopic dermatitis.

BACKGROUND: Data from an uncontrolled trial suggest synchronous balneophototherapy (sBPT), which simulates treatment conditions at the Dead Sea, to be effective in the management of atopic dermatitis (AD). OBJECTIVES: The purpose of this prospective randomized controlled study was to compare the efficacy and safety of sBPT with narrow-band (NB) UVB monotherapy (PT) for AD. METHODS: In this phase III multicentre trial, 180 patients with moderate-to-severe AD were allocated to two groups in a 1:1 ratio; group 1 received sBPT consisting of NB UVB treatment and synchronous bathing in 10% Dead Sea salt solution, group 2 monotherapy with UVB 311 nm. The confirmatory study design consisted of up to 35 treatment sessions. Primary endpoint, analysed on an intention-to-treat-basis (n=169), was the relative improvement of the severity SCORing of the Atopic Dermatitis Index (SCORAD) from baseline to the end of treatment (35 sessions or early cure). Sample-size calculation aimed at establishing at least 15% superiority. RESULTS: SCORing of the Atopic Dermatitis Index at baseline was comparable between sBPT (61.8±14.1) and PT (61.5±12.4) group. At the end of therapy, a clinically relevant and statistically significant difference of 26.2% could be shown (P<0.001). Exploratory testing showed statistically significant superiority of sBPT after 6 months. Mild adverse events more frequently occurred in the sBPT group (n=46, PT: n=31), whereas more patients withdrew early because of adverse events in the PT group (n=6, sBPT: n=2). CONCLUSIONS: A clear advantage of sBPT in comparison to PT was proven. Tolerability was comparable; both treatments showed to be safe.

Prognostic significance of DNA cytometry in comparison with histologic measurements in malignant melanomas.

In the present study we evaluated the prognostic impact of both DNA cytometry and quantitative histology in patients with malignant melanoma (MM). In contrast to previous investigations on sections, rapid image analysis (IA) of imprint specimens was performed to measure DNA cytometric features; 34 cases of stage I MM with low (< 1.5 mm, n = 20) and higher tumor thickness (TTH) (> 1.5 mm, n = 14) were analyzed. We found significant correlations between cytometric features and TTH, which is accepted as the most important prognostic criterion in MM. Higher TTH was closely correlated with the rate of markedly aneuploid nuclei, which is indicated by the 5c exceeding rate (5cER; r, 0.89; p < 0.001). The gain of chromatin in thicker tumors was accompanied by higher mean nuclear area (MAREA; r, 0.60; p < 0.001) and mean DNA content (MDNA; r, 0.58; p < 0.001). Additional evidence for prognostic significance of cytometry was obtained by preliminary survival analysis of 16 cases (four patients died within 2 1/2 years and 12 patients survived for at least 4 1/2 years). Applying multivariate stepwise discriminant analysis, a combination of TTH, level of invasion (LEV), 2c deviation index (2cDI), and modified standard deviation of the DNA values (SDNAM) proved to be most effective. One hundred percent of the cases were correctly classified as survivors or nonsurvivors. TTH and the 5cER were found to be the best univariate criteria for prognosis. In the U test according to Mann and Whitney, a significant discrimination of survivors and nonsurvivors was possible using either TTH or the 5cER, respectively (p < 0.02). Thus, we would like to conclude that IA of imprint specimens can be recommended as a rapid and simple additional method for grading.

Teledermatology--the requirements of dermatologists in private practice.

Eighty-four dermatologists in private practice in Bavaria were surveyed by postal questionnaire. Of the 45 who responded (a 54% response rate), 96% used a computer in their private practice. Fifty-seven per cent of respondents owned systems with Pentium processors, while 23% were still using 386 or 486 processors. Most of them used the Windows 95, UNIX or Apple operating system. Of the respondents who had a modem, 74% used ISDN. There were few modems connected to the ordinary telephone network. Of all respondents, 56% used email regularly. Several possible teledermatology applications were proposed in the survey (i.e. teleconsultation, on-line/off-line videoconferencing, email attachments). Fifty-six per cent of respondents said that they would perform teleconsultations with dermatology clinics, 40% preferred a teleconsultation via telephone and computer, and 42% sending files via email. The survey demonstrated that a high proportion of dermatologists in private practice would use a teledermatology service.

Are dermatologists in private practice interested in teledermatological services?

Diagnosing dermatologic skin conditions can be difficult, especially in pigmented skin lesions. Therefore, the consultation of an expert via teledermatology could prove vital. For this purpose, a rapid transfer of medical data including high resolution images is essential. This transfer can be performed with a variety of modern telecommunication technologies, including ISDN, highspeed-ISDN, Internet, and Intranet. As the levels of both communication software and camera-systems can be quite different, our survey investigated the equipment of 84 dermatologists in private practice. A questionnaire was distributed on computer equipment, operating system software, and any image documentation systems used, as well as required telecommunications equipment and possible applications of tele-dermatology. This survey showed a response rate of 54% and proves that dermatologists in private practice are interested in telemedicine services. Most dermatologists surveyed use Windows 95 operating software and 74% have access to modern ISDN modems or PC-cards. Dermatologists currently prefer applications with low-tech communication hardware and software requirements. Consultation of dermatological centers was the favored application with 59%. Our survey clearly demonstrates that a high percentage of dermatologists in private practice would use tele-dermatology. In our experience, for the excellence of this service an image documentation system is essential to provide the tele-dermatological expert with standardized images with constant illumination.

Improving early recognition of malignant melanomas by digital image analysis in dermatoscopy.

The malignant melanoma (MM) is the most dangerous human skin disease. The incidence increased dramatically during the last years. The only chance for the patient is an early recognition and excision of the MM. The best diagnostic method for this is skin surface microscopy or dermatoscopy. Its use, however, requires much expertise. In order to support learning and using the method, a computer-based dermatoscopy workstation is being developed. Among others, new complexity measures are used for the image analysis.

One-year follow-up of a lentigo maligna: first dermoscopic signs of growth.

We report a 64-year-old man with a pigmented lesion on his forehead, initially thought to be actinic lentigo. At follow-up 1 year later the lesion had increased in size and showed new areas of pigmentation. Dermoscopic observation and biopsy led to a diagnosis of lentigo maligna and the lesion was excised. The dermoscopic features indicative of early growth of lentigo maligna are identified and discussed.

Long-term dermoscopic follow-up of melanocytic naevi: clinical outcome and patient compliance.

BACKGROUND: Digital dermoscopy for the follow-up of melanocytic naevi (MN) is becoming more common in dermatological private practice. OBJECTIVES: To evaluate the clinical outcome, including the patient's compliance, in a long-term follow-up of single MN. METHODS: Criteria for the selection of MN for follow-up: clinically suspicious without dermoscopically atypical features, or typical for the patient. Clinical outcome measures: number of detected malignant melanomas (MM) and/or atypical MN; quantity, quality, and differences in morphological changes between 'low-risk' patients (no MM in history and < 50 MN) and 'high-risk' patients (MM in history and/or > 50 MN). Compliance: the number of patients who joined a recommended follow-up scheme. RESULTS: No MM was found in 145 consecutive patients (mean age 28 years, 54% female) during a 4-year period (median follow-up per patient: 24 months; ranging 4-45; at least three visits). In five patients (3%), seven histologically proven atypical MN were shown on whole body examination at sites other than those documented. A total of 1968 images in 177 'low-risk' and 95 'high-risk' MN were analysed: 37% (n = 65) of 'low-risk' and 32% (n = 30) of 'high-risk' MN showed dermoscopic changes (difference not statistically significant), none were suspicious for MM. Compliance, evaluated within a separate database of 303 consecutive patients (mean age 32 years, 52% female) over a 6-month period, was only 46%, although recall letters were used. CONCLUSIONS: (i) In our setting of daily routines in dermatological private practices long-term follow-up of a single MN seems not to be helpful for the detection of MM. (ii) A whole body examination must be done at each visit. (iii) The clinician's experience of the type and number of possible morphological changes in MN is crucial in order to avoid unnecessary excisions. (iv) The patient's compliance might be an important problem. (v) Cost-effectiveness has yet to be analysed.

[How large is the loss of effectiveness of a treatment procedure between "theory" and "practice"? Evaluating health economics basic data within the scope of a trial model of ambulatory synchronous balenophototherapy of atopic eczema]. / Wie gross ist der Effektivitätsverlust eines Behandlungsverfahrens zwischen "Theorie" und "Praxis"? Evaluierung gesundheitsökonomischer Basisdaten im Rahmen des Erprobungsmodells ambulante synchrone Balneophototherapie bei atopischem Ekzem.

BACKGROUND AND OBJECTIVE: Before introducing new treatment modalities, efficacy has to be proven in clinical trials. Furthermore, it is of special interest to what extent results of clinical trials can be transferred to daily routine. PATIENTS/METHODS: In the framework of a trial on out-patient synchronous balneophototherapy, a possible loss in treatment efficacy from "clinical trial" to "daily routine" was examined. Therefore all patients without protocol deviations (representing treatment success available in a "clinical trial") and all patients with at least one treatment session regardless of protocol deviations (model for "daily routine") were analyzed. RESULTS: 257 "daily routine" and 1281 "clinical trial" patients with atopic dermatitis were analyzed. Relative SCORAD-improvements provided a clear loss in treatment efficacy in the "daily routine" group of 14.2%: 55% of patients received less than the planned 3 treatments per week and 48% left the study early because of noncompliance, good improvement, lack of time or lack of efficacy. CONCLUSIONS: For the first time a loss of efficacy of a treatment modality between "theory" and "practice" can be demonstrated in a representative number of patients suffering from atopic dermatitis. For the optimal use of rare financial resources, the comparison of different treatment modalities under "daily routine" conditions is also necessary in future.

[Type I pachyonychia congenita (Jadarssohn-Lewandowsky)]. / Pachyonychia congenita Typ-I (Jadassohn-Lewandowsky).

BACKGROUND: Pachyonychia congenita is considered to be a genodermatosis of autosomal inheritance. It is characterized by nail hypertrophy, shortly present after birth. Later on follicular keratosis of the extremities and hyperkeratosis of palms and soles can be found. HISTORY AND CLINICAL FINDINGS: We report a child with pachyonychia congenita type-I (Jadassohn-Lewandowsky). Shortly after birth nail hypertrophy of all finger- and toenails and leukoplakia of the palate and tongue were found. At the age of 3 years follicular keratosis of the extremities and plantar bullae could be found additionally. CONCLUSION: The underlying disturbance is a mutation within genes for keratin 6, 16 and 17 which leads to formation of abnormal tonofilaments. In adult patients retinoids can be used for symptomatic treatment especially of the palmoplantar keratosis.

Evaluation of different image acquisition techniques for a computer vision system in the diagnosis of malignant melanoma.

BACKGROUND: Digital image analysis was found to be a useful technique for improved accuracy of preoperative diagnosis of melanocytic lesions. In previous studies digitized color slides were used as input for digital image analysis. New technologies and smaller video cameras made it possible to develop a camera system that allows the digitization of skin lesions directly from the patient. OBJECTIVE: We investigated whether conventional color slides or directly digitized images should be used for a reliable recognition of malignant melanoma. METHODS: Computer features describing characteristics of the lesions were computed for 404 digitized color slides and for 309 directly acquired lesions. Statistical analysis and classifier construction was performed by the commercial statistical classification program CART. RESULTS: With the data set derived either from the color slides or from the directly digitized lesions a sensitivity of about 90% for the recognition of malignant melanoma could be obtained. CONCLUSION: Both image acquisition techniques allow a reliable detection of malignant melanoma and both are appropriate as input for an image analysis system regarding its efficiency as a diagnostic tool. However, none of the classifiers can be applied with reasonable significance to both techniques.

Willingness to pay and time trade-off: sensitive to changes of quality of life in psoriasis patients?

BACKGROUND: Willingness to pay (WTP) and time trade-off (TTO) have been used successfully as quality of life (QOL) measurements in dermatology. However, until now there have been no studies available individually comparing these measures pre- and post-treatment. OBJECTIVES: To check sensitivity to changes for WTP and TTO (i). pre- to post-treatment, and (ii). to a 6-month follow-up period. METHODS: We performed a prospective multicentre study in outpatients with psoriasis vulgaris treated with synchronous balneo-phototherapy (simultaneous application of narrowband ultraviolet B and bathing in 10% Dead Sea salt solution). Besides WTP and TTO, the Psoriasis Disability Index (PDI) and the Psoriasis Area and Severity Index (PASI) were monitored. RESULTS: One hundred and ninety-four patients participated in the pretreatment survey, of whom 138 (71%; 84 men, 54 women; mean age 43.9 years) also returned the post-treatment questionnaire. WTP (percentage of monthly income) was shown to be independent of patients' income. During treatment, mean +/- SD WTP fell from 13.8 +/- 19.2% to 11.5 +/- 15.9% (relative improvement 16.7%; P < 0.05), TTO (h per day) from 2.7 +/- 3.8 to 2.3 +/- 3.6 (relative improvement 15%; P < 0.001), PDI improved from 29.8 +/- 18.6 to 23.5 +/- 18.9 (relative improvement 21.1%; P < 0.001) and PASI (available for 113 patients) from 14.9 +/- 7.7 to 5.6 +/- 5.0 (relative improvement 62.4%; P < 0.001). Changes in WTP, PDI and PASI were statistically significantly correlated. Ninety-one of 138 patients (66%) also completed a third survey after a follow-up period: no further changes in PDI, WTP and TTO were found, indicating a stable QOL post-treatment. CONCLUSIONS: Correlation analysis indicated that WTP, assessed as percentage of monthly income, seems to be an appropriate way to measure QOL, unbiased by income of patients. WTP, TTO and PDI were correlated and were sensitive to changes during treatment. WTP and TTO therefore also seem to be appropriate tools for assessment of QOL in interventional studies, especially for pharmacoeconomic analyses.

Differences in efficacy between intention-to-treat and per-protocol analyses for patients with psoriasis vulgaris and atopic dermatitis: clinical and pharmacoeconomic implications.

BACKGROUND: Pharmacoeconomic outcome research is based on three criteria: (i) evaluation of objective therapeutic effects; (ii) quality of life; and (iii) treatment costs. Evaluation of therapeutic effect is mainly based on the results of clinical trials using objective clinical measures, e.g: Psoriasis Area and Severity Index (PASI) (score for psoriasis vulgaris) and the Severity Scoring of Atopic Dermatitis (SCORAD) (score for atopic dermatitis). In most studies, only results for a treatment-optimized subpopulation (patients treated according to the protocol) are presented in publications. The relevance of such data for daily routine therapy is doubtful. OBJECTIVES: Our purpose was to investigate the expected loss of effectiveness of switching from a clinical trial to daily routine therapy for the synchronous application of narrow-band ultraviolet (UV) B phototherapy (311 nm) and bathing in 10% Dead Sea salt solution (synchronous balneophototherapy) for patients with psoriasis vulgaris and atopic dermatitis. METHODS: We conducted a multicentre, uncontrolled observational study of outpatients. To achieve data for 'clinical trial' and 'daily routine' situations, two populations were compared: (i) all patients strictly treated according to the protocol (ATP) with no protocol deviations (data published in clinical trials), and (ii) all patients participating in the study who received active treatment at least once, despite treatment irregularities, non-compliance, early withdrawal or other protocol violations [intention-to-treat-population (ITT), model for 'daily routine']. RESULTS: A total of 2526 patients were included in the ITT analysis for psoriasis vulgaris (n = 487 for atopic dermatitis), of which 818 patients could be analysed according to protocol (n = 104 for atopic dermatitis). Striking differences in the therapeutic effect between both groups (ITT and ATP) were found using relative PASI and SCORAD score improvement: 11% (57% 'daily routine' vs. 68% in 'clinical trial') for psoriasis vulgaris and 16% (39% 'daily routine' vs. 55% 'clinical trial') for atopic dermatitis. The main reasons for excluding patients from the 'clinical trial' group were early study withdrawal in 29% (atopic dermatitis, 47%) of patients and fewer treatments per week than planned in the protocol in 24% (atopic dermatitis, 52%). CONCLUSIONS: Our data clearly indicate that for the prediction of the therapeutic effect for daily routine therapy the ITT data appear to be more relevant than the ATP results (i.e. those presented in clinical trials). Although these data are only a first step for evaluating the 'real' therapeutic effect of a treatment modality in daily routine, they seem to support the requirements for ITT analyses in efficacy studies and demonstrate the necessity of ITT data for pharmacoeconomic evaluation.

Willingness to pay and time trade-off: useful utility indicators for the assessment of quality of life and patient satisfaction in patients with port wine stains.

BACKGROUND: For cost utility analyses in health economic research it is necessary to assess quality of life for content validation. Previously, both quality of life questionnaires and utility indicators such as willingness to pay and time trade-off have been used successfully in patients with chronic skin diseases, such as psoriasis vulgaris or atopic eczema. OBJECTIVE: For the first time to assess willingness to pay and time trade-off in patients with port wine stains, and to study possible correlations between these indicators, patient income, quality of life questionnaires and subjective or objective outcome measures. METHODS: The results of a survey on 36 patients with facial lesions who had completed laser treatment were used for assessments. The 'Chronic Skin Disease Questionnaire' (CSDQ) and the 'Short Form-36 Health Survey' (SF-36) were used as quality of life questionnaires. Special questions were used as a basis for calculating the utility indicators, willingness to pay and time trade-off. RESULTS: Completed questionnaires were sent back by 25 patients (69%). Willingness to pay and time trade-off were used as instruments for the assessment of quality of life [questions answered by 23 (92% of respondents)]; patients were willing to pay 11.8% of their monthly income and would offer a mean value of 1.2 h per day for an imaginary therapy leading to complete cure of the skin problem. Statistical correlation analyses were not performed because this pilot study included only a small number of patients. Frequency distributions show no apparent correlation between willingness to pay and patients' profession (used as a surrogate for income). Possible correlations were seen between willingness to pay, time trade-off, the scales 'anxiety/avoidance' and 'helplessness' of the CSDQ as well as 'social function' of SF-36 and subjective or objective efficacy. Twenty-nine patients (80%) were willing to pay for the treatment, a surrogate measure for patients' satisfaction with treatment modality. Overall, patients would pay an average of 16.0 euros per single treatment and 192.0 euros for the whole course of treatments. In contrast with patients who evaluated treatment modality as excellent or very good (willingness to pay for single treatment, euro 22.0; for whole treatment, 270.0 euros), patients who judged treatment good (8.0 euros, 145.0 euros), moderate or bad (12.0 euros, 146 .0 euros) were willing to pay markedly less. CONCLUSIONS: (i) The questions for willingness to pay and time trade-off were understood by most patients and produced meaningful answers. (ii) There were apparent correlations between the utility indicators, subjective or objective outcome and the scales of the quality of life questionnaires. (iii) The results show that these indicators have a high potential for use in this dermatological condition, especially as a basis for health economic evaluations.

Improvement of monitoring of melanocytic skin lesions with the use of a computerized acquisition and surveillance unit with a skin surface microscopic television camera.

BACKGROUND: Photographic documentation of melanocytic skin lesions is important. Storage and retrieval of slides, however, take much time and space. OBJECTIVE: Our purpose was to develop and clinically test a computerized acquisition and surveillance (CAS) unit with a television camera for monitoring including measurements of lesional areas. METHODS: A CAS unit connected with a skin surface microscopic television camera was used for monitoring of melanocytic nevi (MN). The lesional area and the skin surface microscopic appearance (SMA) were analyzed after 10 to 21 months in 54 of 1355 MN. RESULTS: In 19 MN (35.2%), changes were found. In eight cases, changes in size of more or less than 15% were detected; in five cases only the SMA changed. In six cases both characteristics changed. CONCLUSION: In approximately 25% of MN, changes were only detectable in the SMA but not with area measurements. This favors the use of systems such as CAS because only they allow a time-saving comparison of actual and previous images.

Evaluation of a multicentre study of synchronous application of narrowband ultraviolet B phototherapy (TL-01) and bathing in Dead Sea salt solution for psoriasis vulgaris.

The synchronous application of narrowband UVB phototherapy with 311 nm lamps (Philips TL-01) and bathing in Dead Sea salt solution was evaluated in a multicentre trial (n = 60) in outpatients suffering from psoriasis vulgaris. The study design consisted of an initial therapy phase of up to 35 treatments (three to five times a week) followed by maintenance therapy with up to 35 further applications (once or twice a week). Evaluation was performed separately for patients in according-to-protocol (ATP) (n = 280) and intention-to-treat (ITT) (n = 692) groups. An overall significant improvement of the Psoriasis Area and Severity Index (PASI) score (P < 0.05) could be shown for both groups during initial therapy with 71.4% improvement for ATP and 61% for ITT patients. The mean PASI for ATP (values for ITT in parentheses) was 17.7 (18.6) at baseline, 9.5 (10.7) after 20 applications and 5.2 (7.4) at the end of initial therapy. On average, ATP patients received 3.9 (3.5) applications per week with a cumulative irradiation dose of 19.5 J cm-2 (16.2 J cm-2). The most frequent side-effect was erythema, observed in 8.7% of the patients. Subjective evaluation of the therapy by the patients (n = 168) was excellent. Seventy-nine per cent of patients preferred the new treatment strategy in comparison with other previous therapies and 88% regarded this therapy as pleasant and comfortable. In conclusion, we could demonstrate a significant effect of therapy in both the ATP and the ITT groups for this new treatment system which imitates, as far as possible, the Dead Sea climatic conditions, with no severe side-effects and a high acceptance by the patients.

Improvement of early recognition of lentigo maligna using dermatoscopy.

BACKGROUND: The clinical differentiation between lentigo senilis/initial seborrheic keratosis and lentigo maligna on the face can be difficult. OBJECTIVE: Our purpose was to determine whether dermatoscopy (eg, skin surface microscopy at 10x magnification) can reliably differentiate between these entities. METHODS: Dermatoscopic slides of 87 consecutive patients presenting 37 malignant and 50 benign pigmented skin lesions on the face were analyzed with the use of 27 dermatoscopic criteria. RESULTS: Univariate analysis selected two criteria specific for lentigo maligna: asymmetric pigmented follicular openings and dark (brown or black) rhomboidal structures. Location-specific importance in relation to facial location was attributed to the color "slate-gray, " especially in combination with structures such as dots, globules, streaks, and homogeneous areas. Multivariate analysis (logistic regression model) revealed the 4 most important features to be asymmetric pigmented follicular openings, dark rhomboidal structures, slate-gray globules, and slate-gray dots with a sensitivity of 89% and a specificity of 96%. CONCLUSION: Three conclusions can be drawn from our study: With a set of 4 dermatoscopic features, early lentigo maligna can be detected with high accuracy; dermatoscopic features on the face differ from criteria used in other locations; and our progression growth model for lentigo maligna delineates the different steps of malignant growth in lentigo maligna.

Wells' syndrome associated with idiopathic hypereosinophilic syndrome.

Wells' syndrome, or eosinophilic cellulitis, is characterized by recurrent cutaneous swellings which resemble acute bacterial cellulitis, and by distinctive histopathological changes. Skin lesions show dermal eosinophilic infiltration and the characteristic 'flame figures', which are composed of eosinophil major protein deposited on collagen bundles. The idiopathic hypereosinophilic syndrome is a multisystem disease with a high mortality rate. It is characterized by peripheral blood eosinophilia and eosinophilic infiltration of many organs, including the skin. The most common skin lesions are pruritic maculopapules and nodules over the trunk and limbs, with urticaria and angio-oedema. In contrast to Wells' syndrome, the pathology of these skin lesions is non-specific with variable eosinophil infiltration. We report overlapping clinical and histopathological findings characteristic of both syndromes in one patient. Our data favour the hypothesis that both syndromes represent an abnormal eosinophilic, response to a variety of underlying diseases or causative agents and thus are different expressions of one disease entity linked to the immunobiology of eosinophils.

Multivariate DNA cytometry discriminates between Spitz nevi and malignant melanomas because large polymorphic nuclei in Spitz nevi are not aneuploid.

To elucidate the reasons for the malignant histologic appearance of melanocytic nuclei within benign Spitz nevi (SN), we evaluated nuclear DNA distribution and nuclear size using a computerized image analysis system. In each case of 28 SN and 34 malignant melanomas (MM), about 100 randomly sampled nuclei were analyzed, prepared as monolayers from paraffin-embedded tissues. Large nuclei in MM (nuclear area > mean nuclear area of normal melanocytes + 4 delta) were significantly more likely to be aneuploid (DNA content > or = 5c) than large nuclei in SN chi2 test, p < 0.0001). Only two of 990 large SN nuclei exhibited DNA values higher than 5c, whereas 236 of 2,024 large MM nuclei were aneuploid or polyploid. Accordingly, in multivariate analysis, five features of DNA distribution proved to be most important for objective discrimination between MM and SN: 2c deviation index, 5c exceeding rate, standard deviation of the nuclear DNA content, and both the 85th and the 95th percentiles of DNA distributions. On the basis of these features, we could define a linear discriminant function that allowed a correct diagnosis in 94% of the cases. Our data demonstrate that diagnostically misleading large nuclei in SN are euploid, in contrast to MM. It is thus possible to discriminate SN and MM with high accuracy using DNA cytometry. Because paraffin-embedded tissue can be used, this technique could be a valuable complement to routine histology in equivocal cases.