Normal-appearing Skin Research Articles

Early Inflammatory Changes in the “Perilesional Skin” of Psoriatic Plaques: Is there Interaction between Dendritic Cells and Keratinocytes?

Early inflammatory changes in psoriatic plaques were investigated immunohistochemically by studying the normal-appearing skin adjacent to the plaques (perilesional skin), lesional skin, and distant uninvolved skin from psoriasis patients. Perilesional epidermis contained numerous CD1a-positive Langerhans cells, some of which expressed HLA-DR, CD83, CD80, and CD86, at the same time expressing Langerin. There were also numerous CD83-positive, CD11c-positive, Langerin-negative dendritic cells (DCs) in the epidermal-dermal junction of perilesional skin. CD3-positive T lymphocytes were sparse in the perilesional skin. Perilesional epidermis expressed keratin K6 and K16, inflammatory keratins, and C/EBPbeta, a transcription factor related to inflammatory cytokines. Our results demonstrated the abundant distribution of activated DCs in the perilesional skin of psoriatic plaques, where early inflammatory changes occur in the epidermal keratinocytes, which suggests their involvement in the provocation of epidermal inflammation in the perilesional epidermis and further pathogenic roles in the formation of psoriatic plaques.

Placebo Response in Two Long-Term Randomized Psoriasis Studies that were Negative for Rosiglitazone

Previous research has suggested that the thiazolidinedione rosiglitazone may possess anti-psoriatic activity. To compare the efficacy and safety of rosiglitazone with that of placebo in the treatment of chronic plaque psoriasis. Two large-scale, randomized, double-blind, multicenter studies (study A, n = 1563; study B, n = 1032) were conducted over 52 weeks (plus optional 44 weeks safety extension) in an outpatient setting. The subjects (aged 18-75 years) had moderate-to-severe chronic plaque psoriasis affecting >or=10% body surface area (BSA) with plaques of any elevation above normal-appearing skin (or >or=6% BSA involvement with marked elevation) and had not used phototherapy during the previous month or thiazolidinediones within the previous 3 months. Rosiglitazone was administered as 2, 4, or 8 mg tablets once daily. The main outcome measure was the proportion of subjects achieving >or=75% improvement from baseline in the Psoriasis Area and Severity Index (PASI 75) at week 26. Rosiglitazone was well tolerated but no more effective than placebo for moderate-to-severe chronic plaque psoriasis. However, there was a large placebo response unrelated to concomitant rescue medication. Interestingly, subjects had been advised to expect a long period before onset of action. At week 26 and across both studies for subjects receiving placebo, the PASI 75 was 9% (48/506) and the PASI 50 (proportion of subjects who achieved at least 50% improvement from baseline) was 27% (135/506). In addition, few subjects withdrew from placebo or rosiglitazone treatment because of 'lack of efficacy' and the majority persisted in the year-long study. While these large-scale, robust studies demonstrated that rosiglitazone is not active in psoriasis, they also showed that for a large proportion of subjects receiving placebo, the expectation of a successful treatment, the favorable adverse effect profile of the drug, and the supportive environment of a clinical study conferred beneficial effects. These results may have implications for the design of future placebo-controlled studies in patients with psoriasis.

Fabry disease: an ultrastructural comparative study of skin in hemizygous and heterozygous patients

Fabry disease is a rare X-linked lysosomal storage disorder due to alpha galactosidase A deficiency, better known after the advent of a promising treatment, a periodical enzyme replacement. As other hereditary X-linked disorders, females have historically been considered non-affected carriers, although they are, actually, clinically and pathologically affected to a variable degree. Some women are asymptomatic, but the majority present milder forms of the disease and later onset. This wide range of disease expression is supposed to be related to the levels of enzymatic activity, probably in accordance with a skewing of X inactivation. Lysosomal deposits of ceramide trihexoside have been repeatedly documented in a wide range of tissues, including those found in angiokeratoma, the characteristic cutaneous lesion which allowed the definition of Fabry disease. The aim of this study was to investigate whether there was any difference in the amount of dermal lysosomal storage in males and females, thus accounting for the difference in clinical severity of both groups. For that purpose, with electron microscopy and quantitative methods, we studied the extent of lysosomal deposits in dermal fibroblasts of normal-appearing skin in six females and nine men, enzymatically and genetically proven as to have Fabry disease, and results were compared. Our results indicate a statistically significant difference between the two groups regarding both the percentage of dermal fibroblasts bearing stored material, and the storage surface occupied in 100 fibroblasts per case. We suggest that periodical ultrastructural examination of normal-appearing skin could be an indicator of the efficacy of enzyme replacement therapy and could help to evaluate results.

Absence of Intraepidermal Glycosyltransferase ppGalNac-T3 Expression in Familial Tumoral Calcinosis

Hyperphosphatemic familial tumoral calcinosis (HFTC) is a rare autosomal recessive disorder characterized by progressive, tumor-like calcifications in the dermis and subcutaneous tissues. The disease is associated with primary hyperphosphatemia due to increased renal tubular reabsorption of phosphate. We recently identified mutations in GALNT3 as the proximal cause of this metabolic disorder. GALNT3 encodes the glycosyltransferase UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyl-transferase 3 (ppGalNAc-T3), which initiates mucin-type O-glycosylation and thus takes part in posttranslational modification and formation of mucin-type glycoproteins. A number of studies have previously described the histopathological and ultrastructural features of lesional skin in HFTC, but little is currently known about the morphology of the normal-appearing non-lesional skin. We obtained biopsies of uninvolved skin from two HFTC patients carrying a known splice site mutation in GALNT3. Light and electron microscopic examination of a biopsy of one of the two patients did not reveal abnormal findings in the epidermis or dermis. However, immunohistochemical studies of frozen skin sections of biopsies of the two patients using monoclonal antibodies directed against three ppGalNac isoforms revealed the complete absence of immunostaining for ppGalNAc-T3 while the staining pattern for ppGalNAc-T2 and -T6 was identical in skin biopsies obtained from HFTC patients and healthy control individuals. Our data provide for the first time evidence for ppGalNAc-T3 deficiency in the skin of HFTC patients and suggest that immunostaining of skin biopsy samples for ppGal-Nac-T3 might be a useful tool for the diagnosis of HFTC.

Ceramide profiles of the uninvolved skin in atopic dermatitis and psoriasis are comparable to those of healthy skin

Ceramides are sphingolipids consisting of sphingoidbases, which are amide-linked to fatty acids. In the stratum corneum, they represent the major constituent of the free extractable intercellular lipids and play a significant role in maintaining and structuring the water permeability barrier of the skin. Using thin layer chromatography, which represents the method of the first choice in analyzing the stratum corneum ceramides, at least seven classes can be distinguished. Each ceramide class contains various species, which have the same head group and different chain lengths. As in many other skin disorders, atopic dermatitis and psoriasis show derangements in content and profile of the ceramides. Such derangements were reported for both the lesional involved as well as for the normal-appearing uninvolved skin. In this study, we focused on investigating the stratum corneum ceramides of the uninvolved skin in atopic dermatitis and psoriasis patients compared to healthy skin. The aim of the investigations was to explore possible significant and specific differences which can be accomplished for purposes of early diagnostics. The skin lipids were collected by means of an in vivo topical extraction procedure using an extraction mixture consisting of n-hexane and ethanol, (2:1). An automated multiple development-high performance thin layer chromatography (AMD-HPTLC) method with photodensitometric detection were applied to separate the ceramides and to estimate their contents. For studying their molecular profile within each ceramide class, a new method of normal phase HPLC with atmospheric pressure chemical ionization mass spectrometry were used. The results obtained by AMD-HPTLC exposed no significant alterations regarding the relative composition of the major stratum corneum lipids and primarily the ceramides. In addition, the mass spectrometric profiles within each ceramide class were similar in the patients and the healthy control subjects. In conclusion, this study revealed that the normal-appearing uninvolved skin of atopic dermatitis and psoriasis patients does not prove significant or specific deficiencies with respect to the free extractable major stratum corneum lipids and mainly the ceramides, when compared to healthy skin. Thus, they cannot be used for diagnostic purposes. Furthermore, our data are not consistent with the concept that impairments in the ceramide composition represent an obligate etiologic factor for both diseases.

Cellular immunophenotyping of exfoliative dermatitis in canine leishmaniosis (Leishmania infantum)

Lymphocyte subsets, major histocompatibility complex (MHC)-II expressing cells and number of amastigotes in the epidermis and dermis were investigated immunohistochemically in 48 dogs with patent leishmaniosis, with or without exfoliative dermatitis (ED) to study the immunopathogenesis of this common cutaneous form of the disease. Skin biopsies were obtained and compared for ED sites (group A, n = 26), normal-appearing skin from the same animals (group B, n = 24), and leishmanial dogs not exhibiting ED (group C, n = 22), and normal controls (group D, n = 22). The CD3+, CD45RA+, CD4+, CD8+ (CD8a+), CD21+, and MHC-II+ cells and leishmania amastigotes were identified immunohistochemically and counted with the aid of an image analysis system. Pyogranulomatous to granulomatous dermatitis, expressed in various histopathological patterns, was noticed in all groups A and B and in half of group C dogs. In the epidermis, the low number of T-cells and their subsets did not differ significantly between groups A and B, but CD8+ outnumbered CD4+ lymphocytes in both groups. MHC-II+ expression on epidermal keratinocytes was intense in the skin with and without lesions from dogs with ED but not in group C dogs. CD3+, CD8+ and MHC-II+ cells were fewer in group C compared to group A and B dogs. In the dermis, CD3+ cells in group A animals were mainly represented by the CD8+. CD45RA+ and CD21+ cells were also seen in high numbers. MHC-II expression, potentially in lymphocytes, fibroblasts, dendritic cells, and macrophages was intense. The numbers of all cellular subpopulations in the dermis were significantly different between the groups, being highest in group A and lowest in group D. In sebaceous adenitis sites, CD4+ outnumbered CD8+ cells in contrast to the neighbouring dermis and the epidermis. The number of CD21+ and CD45RA+ cells was much lower in the inflamed sebaceous glands compared to the dermis. Finally, the number of amastigotes in the normal-appearing skin was significantly higher in the ED dogs (group B) than in those not exhibiting this cutaneous form of the disease (group C).

Multiple Subclinical Syringomatous Proliferations Encountered during Mohs Surgery for Basal Cell Carcinoma

Examination of Mohs surgery frozen sections may lead to discovery of incidental benign neoplasms such as syringomas. An unusual occurrence of numerous subclinical syringomatous proliferations discovered during Mohs surgery for a basal cell carcinoma that posed a diagnostic and management dilemma is reported. Clinical records and histologic sections are examined. Multiple syringomatous proliferations were noted around a basal cell carcinoma during Mohs surgery. A few foci were atypical appearing and focally extending into the deep dermis causing a diagnostic dilemma. All atypical syringomatous proliferations were excised. Evaluation of final Mohs margins by permanent sections and biopsies of normal-appearing facial skin showed multiple benign syringomas. Although solitary subclinical syringomas have been described in association with basal cell carcinomas, the occurrence of multiple syringomas and syringomatous proliferations has not been previously reported. Dermatologists should be aware of the existence of this phenomenon and consider permanent section evaluation to better determine nature of unusual incidental tumors identified in frozen sections during Mohs surgery.

Multiple Subclinical Syringomatous Proliferations Encountered during Mohs Surgery for Basal Cell Carcinoma

BACKGROUND Examination of Mohs surgery frozen sections may lead to discovery of incidental benign neoplasms such as syringomas. OBJECTIVE An unusual occurrence of numerous subclinical syringomatous proliferations discovered during Mohs surgery for a basal cell carcinoma that posed a diagnostic and management dilemma is reported. METHODS Clinical records and histologic sections are examined. RESULT Multiple syringomatous proliferations were noted around a basal cell carcinoma during Mohs surgery. A few foci were atypical appearing and focally extending into the deep dermis causing a diagnostic dilemma. All atypical syringomatous proliferations were excised. Evaluation of final Mohs margins by permanent sections and biopsies of normal-appearing facial skin showed multiple benign syringomas. CONCLUSION Although solitary subclinical syringomas have been described in association with basal cell carcinomas, the occurrence of multiple syringomas and syringomatous proliferations has not been previously reported. Dermatologists should be aware of the existence of this phenomenon and consider permanent section evaluation to better determine nature of unusual incidental tumors identified in frozen sections during Mohs surgery.

Study of the Incidence and Nature of “Very Subtle Epidermal Melasma” in Relation to Intense Pulsed Light Treatment

BACKGROUND Skin rejuvenation with intense pulsed light (IPL) is effective for clearing epidermal pigment disorders. Complications are mild and limited to epidermal burns caused by excessive settings. Some patients, however, experience IPL-induced melasma-like hyperpigmentation despite the appearance of normal skin. These patients seem to have very subtle epidermal melasma not visible to the naked eye. Ultraviolet photography has been useful in identifying these patients and preventing complications. OBJECTIVE The study investigated the incidence of very subtle melasma in patients using UV photography, and assessed this tool in identifying high-risk patients. SUBJECTS AND METHODS 223 Japanese women, 30–69 years old, participated in the study. Very subtle melasma invisible to the naked eye under normal light was diagnosed by UV photography by two physicians, and any relationship among the disease incidence, age, and regular sunscreen use was examined. RESULTS Sixty-three cases of very subtle melasma (28.3%) were identified among the 223 subjects, with a significantly lower incidence in sunscreen users. CONCLUSIONS Patients diagnosed with subtle epidermal melasma and treated with mild IPL parameters did not suffer induced secondary hyperpigmentaion. To help avoid complications after treatment, IPL users should be aware of the age and sunscreen-related incidence of this phenomenon in Asian patients.

Oral Mucous Membrane Pemphigoid Associated with Lichen Planus: a Subtype of Lichen Planus Pemphigoides?

Lichen planus pemphigoides is a rare bullous disorder with bullae arising from papules of lichen planus and from normal-appearing skin. Oral cavity-limited lichen planus pemphigoides has never been reported. This report presents a 47-year-old woman who had oral mucous membrane pemphigoid with lichen planus. This lesion is not known among existing clinical diagnoses. When considering the heterogeneous nature of lichen planus pemphigoides, this case may be classified as a variant of lichen planus pemphigoides.

Study of the incidence and nature of "very subtle epidermal melasma" in relation to intense pulsed light treatment.

Skin rejuvenation with intense pulsed light (IPL) is effective for clearing epidermal pigment disorders. Complications are mild and limited to epidermal burns caused by excessive settings. Some patients, however, experience IPL-induced melasma-like hyperpigmentation despite the appearance of normal skin. These patients seem to have very subtle epidermal melasma not visible to the naked eye. Ultraviolet photography has been useful in identifying these patients and preventing complications. The study investigated the incidence of very subtle melasma in patients using UV photography, and assessed this tool in identifying high-risk patients. 223 Japanese women, 30-69 years old, participated in the study. Very subtle melasma invisible to the naked eye under normal light was diagnosed by UV photography by two physicians, and any relationship among the disease incidence, age, and regular sunscreen use was examined. Sixty-three cases of very subtle melasma (28.3%) were identified among the 223 subjects, with a significantly lower incidence in sunscreen users. Patients diagnosed with subtle epidermal melasma and treated with mild IPL parameters did not suffer induced secondary hyperpigmentaion. To help avoid complications after treatment, IPL users should be aware of the age and sunscreen-related incidence of this phenomenon in Asian patients.

Relative importance of IL-4 and IL-13 in lesional skin of atopic dermatitis.

Although both interleukin-4 (IL-4) and IL-13 induce immunoglobulin E (IgE) production in vitro, the relative contribution of the two cytokines in various skin lesions of atopic dermatitis remains unclear. We examined the relative importance of IL-4 and IL-13 in lesional skin of atopic dermatitis for IgE production. The study group comprised 28 atopic dermatitis patients with serum IgE levels more than 2000 IU/ml. The expression levels of IL-4 mRNA and IL-13 mRNA versus that of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were determined using a semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) method in samples of normal-appearing skin from seven patients, very mild lesions from eight patients, subacute lesions from ten patients and lichenified lesions from ten patients with atopic dermatitis, and in samples of normal skin from six healthy control subjects. IL-4 mRNA expression was identified in only two of the eight very mild lesions, one of the ten subacute lesions, and none of the ten lichenified lesions, whereas IL-13 mRNA expression was identified in 27 of the 28 skin lesions of atopic dermatitis. The IL-13 mRNA/GAPDH mRNA ratios (x100) in the subacute lesions (94.4+/-20.6) and lichenified lesions (71.4+/-40.4) were significantly greater than in the skin of healthy controls (13.1+/-17.7; P<0.01, P<0.05, respectively). Upregulation of IL-13 mRNA in subacute and chronic lesions of atopic dermatitis along with scant expression of IL-4 mRNA suggest that IL-13 is a crucial cytokine in lesional skin.

Characteristics of skin surface morphology and transepidermal water loss in clinically normal-appearing skin of patients with atopic dermatitis: a video-microscopy study.

In patients with atopic dermatitis (AD), it is debatable whether clinically normal-appearing skin is equal to non-atopic normal skin. The aim of this study was to quantitatively evaluate the characteristics of normal-appearing skin of AD. We examined the value of skin surface morphological changes using a new, simple, computer-assisted method with a video microscope. We also investigated the physiological function as represented by transepidermal water loss (TEWL) levels in 44 patients with AD and 15 normal controls. The morphological changes were represented by a variation coefficient score that reflected the irregularity of skin ridges, named the surface irregularity index (SII). There were significant differences between the normal-appearing skin of AD and non-atopic normal skin in both SII (P<0.001) and in TEWL (P<0.01). Especially for the SII, there were significant differences between AD subgroups subdivided by peripheral blood eosinophil count (Eo), serum lactate dehydrogenase level, and clinical score. TEWL values were significantly higher in the high-Eo AD group (n=15) than in the low-Eo AD group (n=29) (P<0.05). These findings indicate that clinically normal-appearing skin of AD patients with high disease activity differs from non-atopic normal skin in both surface morphology and physiology and that these changes reflect the current disease activity.

023 Development of Tissue Engineering Skin Based on Acellular Dermal Matrix

Aim: In tissue engineering of the skin, the selection of a scaffold or a matrix in which a cultured cells grow is quite important. We have developed a tissue engineering skin composed of human keratinocytes and fibroblasts on an acellular allogenic dermal matrix (ADM), derived from cryopreserved human skin. Methods: ADM was prepared from cryopreserved split‐thickness human skin by treating with Dispase and Triton X‐100. The tissue engineering skin were produced by seeding human keratinocytes and fibroblasts on ADM. Several days after seeding, the tissue engineering skin was exposed to an air‐liquid interface for another 7 days. Then, the histological structure of the skin and the production of growth factors by the skin were investigated. Results: The produced ADM was found to be completely acellular with remaining structure of the basement membrane components, such as type IV collagen and laminin. The developed tissue engineering skin had stratified keratinocytes on the surface of the ADM migrating fibroblasts in the dermal collagen structure, resembling to the normal skin appearance. It was found that several important growth factors in wound healing process, such as TGF‐α, TGF‐β and VEGF, were produced by the tissue engineering skin. Conclusions: It was suggested that ADM is suitable for a scaffold in tissue engineering of the skin.

Multiple Pigmented Basal Cell Carcinomas Arising in the Normal-Appearing Skin After Radiotherapy for Carcinoma of the Cervix

BACKGROUND The most frequent radiation-induced skin cancers are basal cell carcinomas (BCCs), and in many cases, they may occur subsequent to tinea capitis, hypertrophic tonsillitis, acne vulgaris, atopic dermatitis, and hyperthyroidosis. BCCs occurring after radiotherapy for carcinoma of the cervix are extremely rare. OBJECTIVE To describe a case of multiple pigmented BCCs caused by radiotherapy for carcinoma of the cervix. RESULTS A 76-year-old female presented with four tumoral lesions within a previously irradiated area. The patient had undergone radiation therapy for cervical cancer 38 years before. All of the lesions were totally excised and histopathologically diagnosed as BCCs. There was no apparent gross chronic radiodermatitis around the lesions, but characteristic histopathologic alterations of radiodermatitis were observed. No new tumors were observed to date. CONCLUSION The latent period for radiation-induced skin cancer is generally very long; secondary skin cancers can develop very late in life. Patients previously treated with radiation therapy require careful follow-up for life.

Selective up-regulation of matrix metalloproteinase-9 expression in human erythema migrans skin lesions of acute lyme disease.

Despite the absence of enzymes that digest extracellular matrix, Borrelia burgdorferi spreads in the skin to form erythema migrans (EM) lesions and then disseminates to other organs. We studied the induction by bacteria of host matrix metalloproteinases (MMPs) in EM skin lesions of patients with acute Lyme disease. In blister fluid from the EM lesions, the expression of MMP-9 was selectively increased by 1900%+/-1037%, compared with blister fluid from the surrounding normal-appearing skin. The expression of all other MMP messenger RNAs was similar in the EM lesions and normal-appearing skin. Selective up-regulation of MMP-9 in the EM lesions was found. Fibroblasts and, to a lesser degree, mononuclear cells were the sources of local MMP-9 production. These results demonstrate specific up-regulation of MMP-9 in the EM skin lesions of patients with acute Lyme disease. Bacterial induction of host proteases may play a role in the dissemination of B. burgdorferi.

Demarcation of nonmelanoma skin cancer margins in thick excisions using multispectral polarized light imaging.

More than a million cases of nonmelanoma skin cancers are diagnosed every year. Treatment of cancer patients could benefit greatly if a real-time, noninvasive, reliable, and cost-effective technique for delineating tumor margins were available. A novel multispectral dye-enhanced polarized light imaging technique that enables rapid imaging of large tumor fields is described. A tunable monochromatic light source and a CCD camera were employed as the imaging device. Linear polarizers were introduced into both the incident and collected light pathways in order to limit the measurement volume to the superficial tissue layers. To enhance the tumor contrast in the image, aqueous solutions of toluidine blue or methylene blue were topically applied to fresh thick skin excisions for several minutes. Then the specimens were rinsed in saline solution. Images were acquired before and after staining at the selected wavelengths. The two sets of wavelengths corresponding to the hemoglobin Soret absorption band and to the absorption bands of the dyes were used to demarcate the areas of enhanced hemoglobin and dye absorption, respectively. The resulting images demonstrate that staining significantly enhances contrast of the tumor in the image and enables reliable delineation of cancer. Locations and shapes of tumor lobules revealed by polarized light images closely correspond to those found in Mohs frozen sections for 41 specimens out of 45. The study demonstrates that the suggested technique has significant potential as a guidance tool in tumor excision surgery.

Management of Spitz nevi: A survey of dermatologists in the United States

Background: There is no consensus concerning management of Spitz nevi. Objective: This study was carried out to ascertain how dermatologists manage Spitz nevi. Methods: A questionnaire was sent to 997 fellows of the American Academy of Dermatology, 284 pediatric dermatologists, and 27 directors of pigmented-lesion clinics. The results are based on the 381 questionnaires returned. Results: The vast majority of responding dermatologists (93%) recommend biopsies of suspected Spitz nevi. Of this group, 43% recommend total biopsies and 55% recommend partial biopsies; 2% would recommend either total or partial biopsies, depending on the clinical situation. Sixty-nine percent of physicians would completely excise a lesion that was histologically diagnosed as an incompletely removed Spitz nevus. Seventy percent of general dermatologists and 80% of pediatric dermatologists would recommend excision with a 1- to 2-mm margin of normal-appearing skin around a Spitz nevus. Nine percent of general dermatologists would recommend margins of 4 mm or more; however, all pediatric dermatologists surveyed would recommend margins less than 4 mm. Physicians were less likely to monitor patients whose Spitz nevi were completely removed. Three fourths (74%) of respondents believe Spitz nevi are entirely benign, 4% believe they are precursors to melanoma, and 22% are not sure. Seven percent of general dermatologists and 4% of pediatric dermatologists have seen metastatic melanomas arise at sites of lesions initially diagnosed histologically as Spitz nevi; 40% of pigmented-lesion clinic directors have seen such lesions. Conclusions: We believe that the lack of consensus, both in our survey and in the medical literature, reflects to some extent the lack of certainty in the histologic differentiation of Spitz nevi from melanomas and that concern about melanoma influences management. At the pigmented-lesion clinic of the New York University Skin and Cancer Unit, because of this concern about melanoma, it is usually recommended that Spitz nevi be completely excised. (J Am Acad Dermatol 2002;47:224-30.)

Management of Spitz nevi: A survey of dermatologists in the United States

<h2>Abstract</h2> <b>Background:</b> There is no consensus concerning management of Spitz nevi. <b>Objective:</b> This study was carried out to ascertain how dermatologists manage Spitz nevi. <b>Methods:</b> A questionnaire was sent to 997 fellows of the American Academy of Dermatology, 284 pediatric dermatologists, and 27 directors of pigmented-lesion clinics. The results are based on the 381 questionnaires returned. <b>Results:</b> The vast majority of responding dermatologists (93%) recommend biopsies of suspected Spitz nevi. Of this group, 43% recommend total biopsies and 55% recommend partial biopsies; 2% would recommend either total or partial biopsies, depending on the clinical situation. Sixty-nine percent of physicians would completely excise a lesion that was histologically diagnosed as an incompletely removed Spitz nevus. Seventy percent of general dermatologists and 80% of pediatric dermatologists would recommend excision with a 1- to 2-mm margin of normal-appearing skin around a Spitz nevus. Nine percent of general dermatologists would recommend margins of 4 mm or more; however, all pediatric dermatologists surveyed would recommend margins less than 4 mm. Physicians were less likely to monitor patients whose Spitz nevi were completely removed. Three fourths (74%) of respondents believe Spitz nevi are entirely benign, 4% believe they are precursors to melanoma, and 22% are not sure. Seven percent of general dermatologists and 4% of pediatric dermatologists have seen metastatic melanomas arise at sites of lesions initially diagnosed histologically as Spitz nevi; 40% of pigmented-lesion clinic directors have seen such lesions. <b>Conclusions:</b> We believe that the lack of consensus, both in our survey and in the medical literature, reflects to some extent the lack of certainty in the histologic differentiation of Spitz nevi from melanomas and that concern about melanoma influences management. At the pigmented-lesion clinic of the New York University Skin and Cancer Unit, because of this concern about melanoma, it is usually recommended that Spitz nevi be completely excised. (J Am Acad Dermatol 2002;47:224-30.)

Occurrence of patchy parakeratosis in normal-appearing skin in patients with active atopic dermatitis and in patients with healed atopic dermatitis: a cause of impaired barrier function of the atopic skin

It remains unclear whether an impaired barrier function often seen in areas of normal-appearing skin in patients with active atopic dermatitis (AD) is primary event in nature or secondary to subclinical eczematous change. We then attempted to evaluate the barrier function of normal-appearing skin in both active and healed AD patients, and as well as see whether a subclinical eczematous change exists or not in the normal-appearing skin using a non-invasive method. Transepidermal water loss (TEWL) measurement and exfoliative cytology method for corneal layer were applied in 153 AD patients who have active skin lesions and 29 individuals with completely healed AD for at least 5 years and 40 normal individuals. The TEWL of normal-appearing skin in severe, moderate and mild AD cases was 10.5±2.9, 8.3±2.4 and 7.3±2.1 g/m 2 per h, respectively. The TEWL values in severe and moderate cases were significantly higher than the normal controls (6.2±1.6 g/m 2 per h). However, the TEWL was not deranged in patients with completely healed AD. An exfoliative cytology examination of corneal layer disclosed that patchy parakeratosis appeared in normal-appearing skin in severe, moderate and mild AD cases at a rate of 42, 29 and 19%, respectively. However, no patchy parakeratosis was recognized in patients with completely healed AD. The occurrence of patchy parakeratosis in normal-appearing skin in patients with active AD suggests that an impaired barrier function often seen in normal-appearing skin in AD patients is secondary to subclinical eczematous change in the area.