Julia Yu Yun Lee

Histopathological differential diagnosis of keloid and hypertrophic scar

Distinguishing hypertrophic scar (HS) from keloid histopathologically is sometimes difficult because thickened hyalinized collagen (keloidal collagen), the hallmark of keloid, is not always detectable and &agr;-smooth muscle actin (&agr;-SMA), a differentiating marker of HS, is variably expressed in both forms of scar. The aim of this study was to investigate additional distinguishing features to facilitate differentiation between keloid and HS. We compared various histologic features and the expression of &agr;-SMA in 40 specimens of keloid and 10 specimens of HS. The features more commonly seen in keloids were: (a) no flattening of the overlying epidermis, (b) no scarring of the papillary dermis, (c) presence of keloidal collagen, (d) absence of prominent vertically oriented blood vessels, (e) presence of prominent disarray of fibrous fascicles/nodules, (f) presence of a tongue-like advancing edge underneath normal-appearing epidermis and papillary dermis, (g) horizontal cellular fibrous band in the upper reticular dermis, and (h) prominent fascia-like fibrous band. The last three features were found in keloid specimens only, including the ones lacking detectable keloidal collagen. Our study confirmed the diagnostic value of keloidal collagen, but it was only found in 55% of keloid specimens. &agr;-SMA expression was found in both HS (70%) and keloid (45%), thus it would not be a differentiating marker. In scars with no detectable keloidal collagen, the presence of the following feature(s) favors the diagnosis of keloid: non-flattened epidermis, non-fibrotic papillary dermis, a tongue-like advancing edge, horizontal cellular fibrous band in the upper reticular dermis, and prominent fascia-like band.

Demodicosis: A clinicopathological study

BACKGROUND Demodex mites are common commensal organisms of the pilosebaceous unit in human beings and have been implicated in pityriasis folliculorum, rosacea-like demodicosis, and demodicosis gravis. OBJECTIVE We sought to describe the spectrum of clinicopathological findings and therapeutic responses of demodicosis in Taiwanese patients. METHODS We conducted a retrospective study to review clinicopathologic findings and therapeutic responses of 34 cases of diagnosed demodicosis. RESULTS Fifteen cases with positive results of potassium hydroxide examination, standardized skin surface biopsy specimen, and/or skin biopsy specimen, and resolution of skin lesions after anti-Demodex treatment were included for final analysis. Nineteen cases were excluded because of insufficient positive data to make a definite diagnosis. There were 4 male and 11 female patients (age 1-64 years, mean age 38.7 years). The disease was recurrent or chronic with a duration ranging from 2 months to 5 years (mean 15.7 months). The skin lesions were acne rosacea-like (n = 8), perioral dermatitis-like (n = 5), granulomatous rosacea-like (n = 1), and pityriasis folliculorum (n = 1). Skin biopsy was performed in 7 patients. Overall, the histopathology was characterized by: (1) dense perivascular and perifollicular lymphohistiocytic infiltrates, often with abundant neutrophils and occasionally with multinucleated histiocytes; (2) excessive Demodex mites in follicular infundibula; and (3) infundibular pustules containing mites or mites in perifollicular inflammatory infiltrate. The skin lesions resolved after treatment including systemic metronidazole, topical metronidazole, crotamiton, or gamma benzene hexachloride. LIMITATIONS Small sample size and a fraction of patients without long-term follow-up are limitations. CONCLUSION Demodicosis should be considered in the differential diagnosis of recurrent or recalcitrant rosacea-like, granulomatous rosacea-like, and perioral dermatitis-like eruptions of the face. Potassium hydroxide examination, standardized skin surface biopsy, skin biopsy, or a combination of these are essential to establish the diagnosis.

Depletion of stratum corneum intercellular lipid lamellae and barrier function abnormalities after long-term topical corticosteroids

The intercellular lipid lamellae of the stratum corneum (SC) is believed to provide the permeability barrier of the epidermis. Previous functional studies have demonstrated an increase in the transepidermal water loss (TEWL) after long‐term use of topical corticosteroids (TCS); however, direct morphological confirmation of this barrier abnormality is still lacking. The aim of this study was to determine whether any abnormality could be detected in the structure of the SC intercellular lipid lamellae in patients after long‐term TCS. Atrophic skin and untreated normal skin of 10 patients after long‐term TCS were examined by transmission electron microscopy using ruthenium tetroxide‐ fixed tissue for the multilamellar lipid sheets of SC, and oil red O stain for neutral lipids of the SC. Layers of the SC were evaluated by 0·1% methylene blue stain after alkaline expansion, and TEWL was measured by Evaporimeter EPI. The TCS‐treated atrophic skin had fewer layers of horny cells, mean 9–4 layers, than the normal control skin, 18 layers (P<0·001) and increased TEWL of 21·3g/m2 compared with the control skin TEWL of 6·7 g/m2(P<0·01). The mean neutral lipid content of the SC was also significantly lower (P<0·001). Moreover, ultrastructural studies revealed a marked decrease in both the numbers of intercellular lipid lamellae of SC and membrane‐coating granules of stratum granulosum in the atrophic skin. These results suggest that the diminution in the SC intercellular lipid lamellae and SC cell layers play an important part in the pathogenesis of barrier dysfunction after long‐term use of TCS.

Interleukin-19 upregulates keratinocyte growth factor and is associated with psoriasis

Background  Interleukin (IL)‐19, a member of the IL‐10 family, signals through the IL‐20R1/IL‐20R2 heterodimer, which is shown to be involved in abnormal keratinocyte differentiation and proliferation. Little is known about its in vitro biological functions or its role in psoriasis.

Paper-based ELISA for the detection of autoimmune antibodies in body fluid-the case of bullous pemphigoid

Bullous pemphigoid (BP), a common autoimmune blistering disease, is increasing in incidence and conveys a high mortality. Detection of autoantibodies targeting the noncollagenous 16A (NC16A) domain of type XVII collagen using enzyme-linked immunosorbent assay (ELISA) has demonstrated high sensitivity and specificity for diagnosing BP. We have developed a rapid, low-cost, and widely applicable ELISA-based system to detect the NC16A autoimmune antibody and then diagnose and monitor BP disease activity using a piece of filter paper, a wax-printer, and NC16A antigens. Both sera and/or blister fluids from 14 untreated BP patients were analyzed. The control group included healthy volunteers and patients with other blistering disorders such as pemphigus vulgaris. In our established paper-based ELISA (P-ELISA) system, only 2 μL of serum or blister fluid and 70 min were required to detect anti-NC16A autoimmune antibodies. The relative color intensity was significantly higher in the BP group than in the control groups when using either serum (P < 0.05) or blister fluid (P < 0.001) specimens from BP patients. The results of P- ELISA were moderately correlated with the titer of the commercial ELISA kit (MBL, Japan) (rho = 0.5680, P = 0.0011). This newly developed system allows for rapid and convenient diagnosis and/or monitoring of BP disease activity.

Clear cell papulosis of the skin

Clear cell papulosis is a new entity first described in 1987. To date, six patients have been reported: all were young Taiwanese children. The disease is characterized clinically by multiple small, whitish maculopapules distributed along the milk line and by the presence of large, benign pagetoid cells in the epidermis resembling the clear cell of the nipple. The significance of this entity lies in its potential histogenetic link with Pagets disease of the skin. We report four new Taiwanese patients, three girls and one boy, aged between 21 months and 4 years. Two were sisters. Small hypopigmented macules first appeared on the pubis. They were eventually distributed bilaterally along the milk line but were most numerous in the pubic area. The disease may easily be overlooked when the macules are tiny or few in number and thus display no clear milk‐line distribution, or when they occur in white‐skinned individuals. Histologically, solitary large clear cells with large, round pale nuclei were detected in the basal layer of the hypomelaninized epidermis. The numbers of clear cells varied on haematoxylin and eosin staining and were only small in two patients. The cytoplasm of the clear cells was decorated by antikeratin AE1 and anticarcinoembryonic antigen antibodies. AE1 was the best marker of the clear cell. Some of the AE1‐positive cells were tadpole‐like in shape and were situated well above the basal layer. Ultrastructurally, large clumps of disintegrated or vacuolated mucin granules were present in the cytoplasm of the clear cells. The melanocytes appeared normal; the suprabasal keratinocytes were essentially devoid of melanosomes. The pathological findings in the present study support the hypothesis that these clear cells are an aberrant derivative of sweat gland cells in the epidermis and are potentially the precursor cells giving rise to mammary and extramammary Pagets disease. The differential diagnosis includes chicken pox scars, idiopathic guttate hypomelanosis, hypomelanotic tinea versicolor, anetoderma and early, hypopigmented lesions of Pagets disease.

Evanescent and Persistent Pruritic Eruptions of Adult-Onset Still Disease: A Clinical and Pathologic Study of 36 Patients

OBJECTIVE Persistent pruritic eruptions (PPE) are common among our patients with adult-onset Still disease (AOSD). We aimed to characterize the clinicopathologic features of the AOSD-associated evanescent and persistent rashes. METHODS We reviewed the clinicopathologic features of the skin lesions from all AOSD cases diagnosed in our hospital during 1988 to 2009. The diagnoses were based on Yamaguchi criteria for AOSD. RESULTS Altogether, there were 36 patients (6 men and 30 women) with age of onset ranging from 17 to 67 years (average 35.7 years). Evanescent rash was recorded in 31 patients (86%) and PPEs in 28 (78%). PPEs usually appeared at the disease onset and manifested as widespread, pruritic, erythematous urticarial or violaceous to brownish flat-topped (lichenoid) papules and plaques over the trunk, neck, face, and extensor sides of the extremities. PPEs were classified clinically as urticarial papules (n = 21), lichenoid papules (n = 18), prominent linear and dermographism-like (n = 11), dermatomyositis-like (n = 7), prurigo pigmentosa-like (n = 4), and lichen amyloidosis-like (n = 2). The clinical activity score was 5.78 ± 1.11 (range 4 to 8) for the series and 6.57 ± 0.98 and 5.57 ± 1.07, respectively, for the groups with and without dermatomyositis-like PPE (P = 0.0314). Five patients died, 3 of them with dermatomyositis-like PPE. Histopathologically, the evanescent rash (8 specimens) showed a superficial perivascular infiltrate of lymphocytes and neutrophils, whereas the PPEs (32 specimens) revealed solitary or cluster necrotic keratinocytes in the superficial epidermis with infiltration of lymphocytes and neutrophils in the upper and mid dermis. CONCLUSIONS PPEs were very common among our patients with AOSD. Recognition of the characteristic clinical and pathologic features of PPE can facilitate diagnosis of AOSD. Therefore, biopsy of atypical eruptions in AOSD patients is recommended because it is likely that the highly distinctive histopathologic features will allow these eruptions to be readily classified.

Analysis of Taiwanese ichthyosis vulgaris families further demonstrates differences in FLG mutations between European and Asian populations

Background  Mutations in the gene encoding filaggrin (FLG) were identified to underlie ichthyosis vulgaris (IV) and also shown to predispose to atopic eczema. Until now, no FLG mutations have been described in the Taiwanese population.

Pronounced facial flushing and persistent erythema of rosacea effectively treated by carvedilol, a nonselective β-adrenergic blocker

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Treatment of Hereditary Epidermolysis Bullosa: Updates and Future Prospects

Epidermolysis bullosa (EB) represents a group of inherited blistering skin diseases, some forms of which are associated with considerable morbidity and increased mortality. Notably, in recessive dystrophic EB there can be extensive muco-cutaneous fragility and disease complications such as scars, contractures, anemia, malnutrition, and malignancy. Currently, there is no effective therapy or cure for EB. Over the last decade, however, a number of important advances have been made that are bringing new treatments closer to the clinic, including gene therapy, protein replacement therapy, cell therapies [allogeneic fibroblasts, mesenchymal stromal cells (MSCs), bone marrow stem cell transplantation, culturing/grafting revertant mosaic keratinocytes], gene editing/engineering, and clinical application of inducible pluripotent stem cells. Although a cure for EB still remains elusive, recent data on animal models and initial human clinical trials have raised the expectations of patients, clinicians, and researchers that disease modification and improved quality of life are feasible goals. Furthermore, the lessons learned in treating EB are likely to have significant implications for improving the management of other genetic diseases.