Non-involved Skin Research Articles

Thermosensory abnormalities and blood flow dysfunction in psoriatic skin.

Accumulating data have shown evidence of involvement of cutaneous nerve fibres and neuropeptides in psoriasis. Although ample evidence of structural and biochemical data exist no studies have been done on assessing the function of small nerve fibres in this disease. To investigate the function of small nerve fibres in patients with psoriasis between psoriatic plaques and non-involved skin and in comparison with healthy controls. We performed computerized psychophysical thermal sensory testing of warmth, cold and heat pain thresholds and skin blood flow using laser Doppler imaging in psoriatic lesions vs. non-involved skin and healthy skin. We evaluated these parameters before and immediately after barrier perturbation, and 1 week after as a measure of barrier repair. There is a significantly elevated warm and decreased cold sensation threshold in psoriatic skin compared with non-involved skin and skin of healthy controls in the same sites. These differences were particularly abnormal 1 week poststripping. The warm sensation threshold was significantly elevated in non-involved skin in psoriatics vs. skin of healthy controls after tape stripping. These findings suggest there is an abnormal function of cutaneous nerve fibres in response to trauma to the stratum corneum, which is not limited to the visible plaque but could be generalized and aggravated by stressful events. Skin blood flow was significantly elevated in psoriatic plaques and inversely correlated to warm sensation thresholds while in healthy controls a direct correlation was noted. Our data demonstrate an abnormal thermosensory response in psoriasis.

Application of a Novel and Noninvasive Skin Sampling Technique for Analyzing Cytokine-Mediated Inflammation in Rosacea

A novel Sebutape™ skin sampling technique was recently developed and has been applied to the noninvasive study of skin inflammation. Using a simple procedure of Sebutape application and removal from the skin, we have previously detected changes in the profiles of cytokine adsorption from various forms of compromised skin and scalp, including, diaper dermatitis, UV exposed skin, surfactant-treated skin, dandruff, and seborrheic dermatitis. In the current study, we applied this method to the analysis of the chronic skin disorder, rosacea, a condition characterized by inflammation, but for which little is know about the inflammatory process, including the role of cytokines. Sebutape samples were collected from involved and noninvolved (control) facial skin sites of subjects with active rosacea of varying severity. These samples were compared with other samples obtained from the facial skin of normal subjects. The rosacea skin sites were characterized by significantly elevated recoveries of the cytokine, inte...

Distinct TCR delta repertoires are present in the cutaneous lesions and inflamed duodenum of patients with dermatitis herpetiformis.

Intraepithelial gammadelta T cells are increased in the inflamed small bowel and are also found in increased numbers in cutaneous lesions from patients with dermatitis herpetiformis (DH). Thus, these cells might play an important role in the pathogenesis of the disease. We investigated the T-cell receptor (TCR) delta repertoire in involved and non-involved skin and compared it with the TCR delta repertoire of the inflamed duodenum and peripheral blood of the same patients. An identical TCR delta repertoire in the small bowel and in the cutaneous lesions would suggest a migration of antigen-specific gammadelta T cells from the intestine to the skin which cross-react with cutaneous antigens. T-cell receptor DV1-DV3 transcripts were amplified by reverse transcriptase (RT)-PCR and analyzed by complementarity determining region 3 (CDR3) size spectratyping and nucleotide sequencing. Our results indicate that the cutaneous TCR delta repertoires were oligoclonal and identical dominant gammadelta T-cell clones were present in the involved and non-involved skin. Furthermore, the TCR delta repertoire of the skin was distinct from that in the small bowel. The peripheral blood exhibited a restricted TCR delta repertoire, which differed from that in the intestine and skin. Thus, cutaneous gammadelta T cells are not specifically expanded within the involved skin and are unlikely to be derived from the inflamed duodenum.

Circumscribed palmar or plantar hypokeratosis: A distinctive epidermal malformation of the palms or soles

Background: Epidermal malformations of the skin include a group of heterogeneous developmental defects that result from errors in morphogenesis of the epidermis during intrauterine life. Objective: The purpose of this study was to report the clinical and histopathologic features of a distinctive epidermal malformation involving the skin of the palms or soles. Methods: Ten patients were included in this study. All of them showed the same clinical features that consisted of a solitary circumscribed and circular area of erythematous depressed skin on the palm or on the sole. Diagnosis was confirmed by histopathologic study. Results: All patients were middle aged or elderly. Nine patients were women and one was a man. The lesions showed predilection for the skin of the thenar and hypothenar regions of the palm or the medial side of the sole. Histopathologic study demonstrated a depression of the epidermis, with a sharp stair between normal and involved skin. The epidermis covering the depression showed markedly thinner horny layer and a slightly diminished granular cell layer when compared with adjacent noninvolved skin. Keratinocytes of the squamous cell layer, granular cells, and corneocytes showed, otherwise, a normal appearance. Serial sections failed to demonstrate cornoid lamellation. Conclusion: On the basis of the clinical and histopathologic findings in these 10 patients, we have named this malformation circumscribed palmar or plantar hypokeratosis. This lesion seems to be a distinctive entity that has not been previously described. (J Am Acad Dermatol 2002;47:21-7.)

Papulosis fibroelastolítica del cuello. ¿Es la elastólisis de la dermis papilar un hallazgo histopatológico característico?

Abstract—Two patients, a 69-year-old and a 70-year-old women, presented multiple symmetrical, confluent, whiteyellowish papules on the lateral and dorsal aspects of the neck. The lesions were symptomless and had appeared several years before consultation. Histopathological features disclosed a reduced amount or a complete loss of elastic fibers in the papillary dermis in both involved and non-involved perilesional skin and a non-constant thickening of collagen fibers in the papillary and reticular dermis in involved skin.Morphological similarities and a possible relationship between reports of white fibrous papulosis of the neck (WFPN) and pseudoxanthoma-elaticum-like papillary dermal elastolysis (PEL-PDE) are discussed. Both entities share similar clinical features and under both concepts identical lesions have been reported. The observation of papillary dermal elastolysis in both non-involved and involved skin seems to suggest that this finding should not be considered a diagnostic characteristic feature.Probably both entities should be considered as a unified disorder (fibroelastolytic papulosis of the neck). These entities probably correspond, as has been previously proposed, to morphological variants that reflect cutaneous intrinsic aging (fibroelastolytic patterns of intrinsic skin aging).

TNFalpha and IL-6 are mediators in the blistering process of pemphigus.

Pemphigus is an autoimmune disease characterized by intraepidermal blisters induced by pemphigus IgG. In addition to autoantibodies, molecular mechanisms involved in acantholysis remain largely unknown. For this reason, we address a possible role of the inflammatory cytokines IL-6 and TNFalpha in pemphigus lesions. Sixteen biopsies from patients with different types of pemphigus were studied by in situ hybridization using DNA fluorescent probes for IL-6 and TNFalpha mRNA. Fifty-six percent of lesional biopsies exhibited cytokine gene expression, which was poorly expressed in noninvolved skin. Deposits of TNFalpha and IL-6 were products of in situ transcription at the epidermal level. Inflammatory cytokine expression around the blister could play a mediator role in pemphigus lesions by increasing epithelial damage.

Clinical and immunologic variables in skin of patients with atopic eczema and either positive or negative atopy patch test reactions

Background: Epicutaneous application of aeroallergens induces a positive atopy patch test (APT) response in about 50% of patients with atopic eczema (AE) and sensitization for these allergens. Objective: To elucidate the mechanisms determining the outcome of the APT, the following questions were addressed. Are there differences in clinical features between patients with AE who have positive versus negative APT responses? Is a macroscopically negative APT response also histologically negative, and if so, are there differences in clinically noninvolved skin between the two groups regarding (1) the sensitivity toward an irritant, (2) the composition of cellular infiltrate, (3) the presence of aeroallergen-specific T cells, and (4) the number of IgE+ cells? Methods: Punch biopsy specimens from both house dust mite patch tested and the clinically noninvolved skin of patients with AE who have positive APT responses (n = 10) and negative APT responses (n = 10) and those from the normal skin of atopic individuals without AE (n = 10) and nonatopic volunteers (n = 10) were analyzed by using immunohistochemistry with mAbs against eosinophil cationic protein, IgE, the high-affinity receptor for IgE, and CD3 and CD25 mAbs. Furthermore, T-cell lines were propagated from noninvolved skin of all patient and control groups. The T-cell lines were tested for house dust mite specificity. Results: Negative APT sites were immunohistochemically similar to clinically noninvolved AE skin. There were no significant differences between patients with AE who had positive and negative APT results regarding either clinical features, the composition of cellular infiltrate, or the presence of allergen-specific T cells in clinically noninvolved skin. However, differences were observed regarding the presence of IgE on epidermal CD1a+ cells. Conclusion: Our results indicate that a positive APT reaction requires the presence of epidermal IgE+ CD1a+ cells in clinically noninvolved skin, but that also other, as yet unknown, discriminatory factors are involved. (J Allergy Clin Immunol 2000;105:1008-16.)

Expression of RANTES in biopsies of skin and upper gastrointestinal tract from patients with systemic sclerosis

Inflammatory infiltrates and upregulated collagen production are hallmarks of systemic sclerosis (SSc). There are indications that chemokines are involved in accumulation of inflammatory and matrix-synthesizing cells in SSc skin lesions. Therefore, we searched for the expression and localization of the chemokine RANTES ("regulated upon activation and normal T cells expressed and secreted") in skin and esophageal biopsies from patients with SSc. Using immunohistochemistry and in situ hybridization, skin biopsies derived from clinically involved and noninvolved skin of 18 patients with early and long-term SSc were examined for RANTES expression and compared with nondiseased skin sections of seven patients without SSc. In addition, esophageal snap biopsies were taken in a subgroup of six SSc patients. Strong expression of RANTES could be detected in the epidermis in keratinocytes of patients with short-term and long-term disease, both on the mRNA and protein level. The percentage of RANTES-expressing cells were significantly higher in clinically noninvolved skin sections than in involved skin areas. In contrast, no RANTES expression was found in esophageal biopsies or in the control group. The results indicate that RANTES is present in human sclerodermatous skin. RANTES may be involved in early pathogenesis of SSc as well as in fibrosis pathways, either by chemoattraction of immunocompetent cells and/or by modulation of collagen production.

Two Ceramide Subfractions Detectable in Cer(AS) Position by HPTLC in Skin Surface Lipids of Non-Lesional Skin of Atopic Eczema

The non-involved skin of atopic eczema (NEAE) is characterized by severe dryness and an impaired barrier function of the stratum corneum as indicated by an increased transepidermal water loss. Previous studies have demonstrated that this barrier impairment coincides with marked alterations in the amount and composition of stratum corneum ceramides. The aim of this study was to identify specific alterations in NEAE that may be used in the diagnosis of the atopic eczema. Using a classical procedure for high performance thin layer chromatography we could confirm earlier results: apart from Cer(EOH), which contains omega-hydroxy fatty acid (O) ester-linked to linoleic acid (E) and amide-linked to 6-hydroxy-4-sphingenine (H), the quantities of all ceramide fractions were significantly decreased. Furthermore, Cer(EOH)/Certotal was significantly increased, whereas the percentage of Cer(EOS), which contains sphingosine (S), and Cer(NP), which contains non-hydroxy fatty acid (N) amide-linked to phytosphingosine (P), were significantly decreased. Using a modified procedure for high performance thin layer chromatography we could demonstrate the formation of a double peak in the position of Cer(AS), which contains alpha-hydroxy fatty acid (A), in lipids of NEAE. The subfractions of the double peak comprised 15% and 12% of Certotal. MALDITOF mass spectrometry suggested that the double peak was formed by a homologous series of mono-hydroxylated and mono-unsaturated ceramides of different chain length, e.g., Cer(AS) subfractions containing either (C16,18) or (C22,24,26) alpha-hydroxy fatty acids. In contrast, in normal skin a single peak in Cer(AS) position, which comprised 22% of Certotal, was mainly formed by the long chain subfraction. In some cases this single peak displayed a small shoulder at its right flank, but never showed a clear peak separation when developed with NEAE samples. Furthermore, even in senile xerosis, or in either non-involved skin of psoriasis or seborrhoic eczema, only a single peak occurred in Cer(AS) position. Accordingly, the double peak might be specific for NEAE and turn out to be a marker for atopic eczema.

Mast cells in developing subepidermal bullous diseases: emphasis on tryptase, chymase and protease inhibitors.

The possible involvement of mast cell tryptase and chymase in subepidermal bullous diseases was studied enzyme-histochemically in specimens from erythematous and vesicular skin and from non-involved skin of patients with dermatitis herpetiformis, bullous pemphigoid, erythema multiforme, infective bullous eruption and linear IgA dermatosis. Patients with pemphigus were biopsied for comparison. The immunoreactivity of chymase inhibitors, alpha1-proteinase inhibitor (alpha1-PI) and alpha1-antichymotrypsin (alpha1-AC), in mast cells was demonstrated using the sequential double staining method. Tryptase-positive mast cells were unchanged or only slightly increased in number in erythematous lesions and slightly decreased in blistering skin compared with healthy-looking skin. Only occasionally were mast cells seen in apparent contact with the basement membrane zone. Chymase-positive mast cells and the chymase/tryptase ratio steadily decreased during the development of the lesions in each subepidermal bullous disease. The percentage of alpha1-PI+ and/or alpha1-AC+ mast cells increased simultaneously, which could explain the disappearance of chymase activity. Similar results were obtained regardless of the bullous disease. The results were also similar in pemphigus, which is an intraepidermal bullous disease. In conclusion, these results show significant alterations in mast cell chymase and protease inhibitors in a range of different bullous diseases, suggesting mast cell involvement. The apparent inactivation of chymase could be due to the action of chymase inhibitors detected in numerous mast cells. However, these alterations probably reflect general inflammation rather than a specific reaction in a certain bullous disease.

Epidermal calprotectin in drug-induced toxic epidermal necrolysis.

Calcium ions (Ca++) in excess alter cell viability. Their potential role in drug-induced toxic epidermal necrolysis (TEN) was investigated. Thirteen TEN patients were biopsied at the site of early bullous lesions and on clinically normal-looking skin at least 2 cm distant from blisters. Immunohistochemistry was applied using the mouse monoclonal antibody Mac 387 recognizing the cytosolic protein complex L1 (calprotectin). The L1 antigen is a calcium-binding protein expressed by human granulocytes, monocytes-macrophages and injured epidermis, but not by normal epidermis and other cells harboured in the skin. The majority (8/13) of TEN samples from apparently non-involved skin expressed the L1 antigen in a patch-like pattern inside the epidermis where inflammatory cells were scant or absent. As assessed by computerized image analysis of TEN bullous skin, the intensity of the L1 expression in the epidermis was not statistically correlated with the amount of the infiltrating inflammatory cells (Mac 387+ macrophages, UCLH1 + T lymphocytes and Factor XIIIa+ dendrocytes) present in the dermis and in the epidermis. Such findings suggest a key role for keratinocytes in the production of the L1 calcium-binding complex. As the L1 complex formation is a calcium-dependent process, one of the first biological events in TEN could be a dramatic increase in keratinocytes intracellular Ca++ concentration following damage by the involved drug metabolites. The ultimate toxic cell dysregulation would result from the disturbance in the intracellular Ca++ homeostasis.

The Repertoire of T Cell Antigen Receptor β-Chain Variable Regions Associated with Psoriasis Vulgaris

We investigated whether the pattern of T-cell receptors expressed by T cells in inflamed psoriatic skin differed substantially from the pattern seen in T cells from the peripheral blood. A bias or restriction in the repertoire of T-cell receptors found in the lesional skin of different patients might imply that specific subsets of T cells were causally associated with initiating or maintaining the lesions. By using a polymerase chain reaction-based assay of T-cell receptor beta-chain variable region mRNA, we found that the patterns of beta-chain mRNAs displayed in 14 samples of lesional skin or six samples of noninvolved skin were not significantly less diverse than the patterns found in matched peripheral blood samples. There was no evidence that the active lesions of multiple patients showed overexpression of T cells expressing one or a few T-cell receptor forms. The pattern of T-cell receptors displayed in clinically normal skin from normal control individuals showed about the same diversity as normal blood. While these results may not exclude either classical antigen or superantigen-based T-cell activation mechanisms in active plaques, the absence of a simple pattern of Vbeta usage in different patients suggests than other aspects of T-cell biology including trafficking, proliferation, co-stimulation, or responses to cytokines must also be considered.

Emollient therapy in atopic dermatitis

Atopic dermatitis (atopic eczema) has shown a marked increase in the last decade, affecting 10-15% of children. The clinical presentation is that of an itchy, dermatitic, dry skin which results from immunological dysfunction and includes changes in the noninvolved skin. These alterations include increased itchiness, morphological change, low sebum production, disturbance in water exchange correlated with impaired barrier function, loss of vascular regulation, and secondary staphylococcal colonization. The management of the disease includes both general and topical measures: moisturizers or emollients, antibacterial treatment and cortico-teroids. Humectants are widely used in emollients to increase or maintain the water content in the stratum corneum. The efficacy of emollients may be assessed by clinical and noninvasive methods which determine their effect on skin hydration or barrier function. It is clear that emollients have an important role in improving skin dryness, particularly in atopic dermatitis, often reducing the need for topical corticosteroids. In conclusion, emollients should be used prophylactically, as well as therapeutically, provided they are cosmetically acceptable to the patient and are used frequently.

Patients with psoriasis have elevated levels of serum eosinophil cationic protein and increased numbers of EG2 positive eosinophils in the duodenal stroma

The occurrence of EG2-positive (EG2+) eosinophils and IgE in biopsy specimens of duodenal mucosa and skin from 39 psoriasis patients was studied, with emphasis on the relation to serum eosinophil cationic protein (ECP), serum IgE and the presence or absence of serum IgA and IgG antigliadin antibodies. Psoriasis patients had significantly elevated serum levels of ECP even after exclusion of five of 37 sera which were Phadiatop positive. The elevated serum ECP was not associated with the presence of IgA or IgG antibodies to gliadin. After exclusion of Phadiatop positive sera the serum IgE values did not differ from those of a group of healthy blood donors. Patients with psoriasis had a pronounced increase of EG2+ cells in their duodenal stroma. Patients without antibodies to gliadin tended to have even more EG2+ cells than those with such antibodies and those with increased duodenal intraepithelial lymphocytes. IgE+ cells were present in most duodenal specimens, and in some specimens there were > 100 IgE+ cells/section. The number of EG2+ cells was increased in lesional skin and, in some patients, also in non-involved skin, but there was a more pronounced increase in EG2 reactivity in the duodenal than in the skin specimens. IgE reactivity was increased both in non-involved and involved skin and was significantly related to the number of IgE-positive cells in the duodenal stroma. The results of this study indicate that the gastrointestinal tract and the eosinophil granulocyte might be involved in psoriasis in a hitherto unknown way.

Oncogenesis in HIV-infection

The presence of human Kaposi's sarcoma associated herpesvirus-like sequences (KSHV) was examined in different epidemiological variants of Kaposi's sarcoma (KS) and in KS-derived cell cultures by polymerase chain reaction (PCR). KSHV DNA was present in all tumor biopsies of AIDS-associated KS (59 biopsies), endemic KS (26 biopsies; 21 African endemic KS, 5 Greek endemic KS), sporadic/classical KS (28 biopsies) and post-transplant/iatrogenic KS (6 of 7 biopsies). On the contrary, these sequences were only detected rarely in non-involved skin of KS patients (3 positive specimens of 12), in the peripheral blood mononuclear cells of HIV-infected patients (3 positive specimens of 54) and in lymphoma-biopsies (3 positive specimens of 47). Cell cultures derived from KS skin lesions were positive for KSHV DNA only in the first two passages. However, two longer-term positive cultures from a biopsy of a patient affected with sporadic KS and a biopsy of a patient affected with epidemic KS was identified. A strong association of KSHV with KS tissue was observed in all the different epidemiological variants of KS. Long-term positive KS-derived cell cultures will be an important tool to study the herpesvirus-like agent and to investigate its functional role in the initiation and progression of KS.

Examination of non-involved skin, previously involved skin, and peripheral blood for herpes simplex virus DNA in patients with recurrent herpes-associated erythema multiforme: Brice SL, Leahy MA, Ong L, et al. J Cutan Pathol 1994;21:408–412

Examination of non-involved skin, previously involved skin, and peripheral blood for herpes simplex virus DNA in patients with recurrent herpes-associated erythema multiforme: Brice SL, Leahy MA, Ong L, et al. J Cutan Pathol 1994;21:408–412

The Type I Interferon System Is Locally Activated in Psoriatic Lesions

The expression of mRNAs encoding interferons (IFNs) and IFN-inducible proteins has been studied in psoriatic lesions and in noninvolved skin. The specific mRNAs have been detected by in situ hybridization using antisense RNAs. Signals for the expression of IFN-gamma mRNA have been found exclusively in cells of psoriatic lesions, and most likely represent a subpopulation of infiltrating leukocytes. Weak signals of IFN-alpha mRNA have been detected throughout the hyperkeratotic epidermis, although specific signals for IFN-beta mRNA expression were not detectable. The expression of two IFN-alpha-inducible gene products, namely the MxA protein and the 2'-5' oligoadenylate (2-5A) synthetase, have been studied as markers for the local activation of the IFN-alpha system. Expression of MxA mRNA and protein was observed in psoriatic keratinocytes, but not in normal appearing keratinocytes adjacent to the lesions. Similarly, 2-5A synthetase expression was markedly elevated in psoriatic keratinocytes. The results of the present study indicate that the IFN-alpha system is selectively activated in psoriatic lesions, although it remains silent in noninvolved skin. The implications of this finding are discussed within the boundaries of current understanding of the cytokine network.

Examination of non-involved skin, previously involved skin, and peripheral blood for herpes simplex virus DNA in patients with recurrent herpes-associated erythema multiforme.

The association between infection with HSV and the subsequent development of erythema multiforme is well established, although the role that the virus plays in the pathogenesis of this disorder is not known. HSV DNA has been detected in cutaneous lesions of herpes-associated erythema multiforme (HAEM), and it has been suggested that the tissue damage seen in these lesions is virus-specific. In the current, prospective study, we examined biopsies of lesional, non-involved, and previously involved but healed skin, in addition to specimens of peripheral blood, from patients with HAEM, for HSV DNA by using the polymerase chain reaction. HSV DNA was detected in lesional skin of 10 of 11 patients compared to 2 of 11 non-involved skin biopsies obtained at the same time. HSV was present in 4 of 6 blood specimens obtained during the acute episode. Five patients returned 3 months after the acute episode resolved for biopsies of previously involved skin. HSV was detected in 4 of these 5 biopsies. Thus, the presence of HSV DNA in the skin of patients with HAEM appears to be predominantly in areas of clinical involvement; the virus remains in those cutaneous sites for up to 3 months without evidence of clinical disease; and HSV DNA may be detected in the peripheral blood cells during acute HAEM. Based on these findings, we suggest that the virus plays a role in lesion development, that the skin may function as a site of viral persistence, and that hematogenous spread of viral DNA may be an important factor in the development of HAEM.

Warts and the Atopic

Williams et al 1 in the June 1993 issue of theArchivesseem to favor a negative response to their question: ''Are viral warts seen more commonly in children with eczema?'' While this may refute the widely held notion, they do recognize several variable factors (ie, disease activity and involved or noninvolved skin) that introduce biases that blur the complete phenomenon. During a period from 1989 through 1990, an expert faculty (six allergists and 12 dermatologists) was polled about this issue. 2 On a scale of 1 (most negative) to 5 (most positive), an average score of 3.5 was recorded in response to the following question: ''Do atopics get more warts than nonatopics?'' Responses varied widely. The score was identical by specialty. There was no unanimity of opinion among the experts (four felt very strongly that there was a positive incidence, and three felt strongly that there was not). Patients

Pretibial epidermolysis bullosa: A clinicopathologic study

Pretibial epidermolysis bullosa (PEB) is a rare variant of dystrophic epidermolysis bullosa (DEB) that predominantly involves the pretibial skin. We report 19 cases of DEB with pretibial predilection and our findings on anchoring fibrils. Patients with blisters and scars that primarily involved the pretibial were selected. Blisters and noninvolved skin were studied by light and electron microscopy. Anchoring fibrils were quantified by morphometry. There were 19 patients from 13 families. The inheritance was autosomal dominant in 10 families and sporadic in one family, and sibling involvement was present in two families. Nail dystrophy was noted in all patients. Pruritus was a common feature. Extensive prurigo occurred in four patients. Eight patients had skin lesions that exclusively affected the legs and were diagnosed as PEB. The remaining patients also showed some albopapuloid or hypertrophic scars at sites other than the leg, features seen in the albopapuloid or Cockayne-Touraine types. These were labeled as albopapuloid PEB or Cockayne-Touraine PEB. Common ancestry and various combinations of PEB, with albopapuloid or Cockayne-Touraine type of EB, were noted in some families. Compared with normal controls, the anchoring fibrils were rudimentary and sparser in both lesional and nonpredilected normal skin, although in the latter the changes were less marked in PEB than in the albopapuloid or Cockayne-Touraine types. Common ancestry may contribute to the higher incidence of DEB, especially PEB, in Tainan, Taiwan. The abnormalities of anchoring fibrils were not restricted to the predilected site in PEB and did not distinguish PEB from other types of DEB.