Hyun Jung Lim

Potential Immunoinflammatory Role of Staphylococcal Enterotoxin A in Atopic Dermatitis: Immunohistopathological Analysis and in vitro Assay

Background The underlying mechanism of atopic dermatitis (AD) exacerbated by Staphylococcus aureus has not been established. However, we demonstrated recently that the majority of S. aureus strains colonized in the skin of Korean AD patients carried genes encoding staphylococcal enterotoxin A (SEA) and/or toxic shock syndrome toxin-1 (TSST-1). Objective To clarify the role of staphylococcal superantigen, SEA in AD. Methods With the lesional skin of 9 AD patients and normal looking skin of one healthy adult, we examined first the expression of SEA, staphylococcal enterotoxin B (SEB), and TSST-1 using immunohistochemical analysis. In addition, we investigated the effects of SEA on the expression of inflammation-related adhesion molecules and cytokines in human HaCaT keratinocytes and Human Umbilical Vein Endothelial Cells (HUVECs) by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis and enzyme-linked immunosorbent assay. Results Staphylococcal protein A (SPA) and SEA were detected with increased immunoreactivity in AD patients. However, TSST-1 showed mild-to-moderate immunoreactivity in AD patients, whereas SEB was minimally detected. In the double immunofluorescence investigation, SEA and SPA were well co-localized. SEA induced upregulation of adhesion molecules and elicited inflammatory responses in HaCaT keratinocytes and HUVECs. Conclusion This study demonstrates the importance of SEA as an immunoinflammatory triggering factor of AD in Koreans.

Repeated Paradoxical Aggravation of Preexisting Psoriasis during Infliximab Treatment for Crohn's Disease

As more rheumatologists and dermatologists have begun to use biological agents such as TNF-alpha blocker, they have confronted an unexpected complication: psoriasis was paradoxically aggravated or induced by the TNF-alpha blocker. Although it is not a common complication of TNF-alpha blocker, this aggravation may be more common than previously thought. To our knowledge, most reports about TNF-alpha blocker-induced psoriasis have been limited to western countries while only a few cases have been reported in Korea and Japan. In addition, new onset of pustular psoriasis by TNF-alpha blocker has been reported more commonly than worsening of preexisting psoriasis. Now we report a patient whose preexisting psoriasis vulgaris was aggravated repeatedly after using the TNF-alpha blocker, infliximab, to control Crohns disease, which is a rare rheumatologic disease in Korea.

Effects of topical application of a recombinant staphylococcal enterotoxin A on DNCB and dust mite extract-induced atopic dermatitis-like lesions in a murine model

BackgroundAtopic dermatitis (AD) is a chronic inflammatory skin disease with biphasic T cell-mediated abnormalities. Staphylococcal superantigens contribute to the exacerbation of inflammation in AD. The underlying immunopathological mechanisms are not fully understood.ObjectiveTo determine whether epicutaneous application of recombinant staphylococcal enterotoxin A (rSEA) would exacerbate AD-like allergic inflammation induced by 2, 4-dinitrochlorobenzene (DNCB) and house dust mite extract (Dermatophagoides farinae extract, DFE) in a murine model.Materials and MethodsWe first established an AD-like model using BALB/c mice exposed to DNCB/DFE on the ear. Next, Staphylococcus (S.) aureus or rSEA were topically applied to the mice. We evaluated the clinical and histopathological features of the animals. Serum immunoglobulin levels were also measured. In addition, real-time PCR analysis of cytokines produced by T cell subsets in the earswas conducted.ResultsMice treated with S. aureus and rSEA had more severe clinical symptoms, including increased mean dermatitis scores and ear thickness, compared to animals with only AD-like lesions. Total IgE, IgG2a and serum histamine levels were increased in all groups except the normal control group. The S. Aureus- and rSEA-treated groups showed increased levels of cytokines such as IL-4, IL-13, INF-γ, IL-17, and IL-18. In particular, increased cytokine expressionwas more conspicuous in the rSEA-treated group than in mice exposed to S. aureus.ConclusionThe results of this study showed that topical exposure to rSEA as well as SEA-producing S. aureus aggravate atopic skin inflammation. This may be associated with the induction of a mixed Th1/Th2 type dermatitis.

Serial sections of atrophic acne scars help in the interpretation of microscopic findings and the selection of good therapeutic modalities

Background  Acne scar causes problems cosmetically and psychologically. Although microscopic examination of acne scars is a necessity for understanding and treatment of them, and it is not easy to find a paper reporting the microscopic characterization of acne scars.

Efficacy of Piroxicam Patch Compared to Lidocaine Patch for the Treatment of Postherpetic Neuralgia

BACKGROUND The lidocaine patch has been effectively used as a first-line therapy to treat neuropathic pain such as postherpetic neuralgia (PHN). OBJECTIVE To evaluate the safety and efficacy of the topical piroxicam patch as a treatment option for the treatment of PHN. METHODS Eighteen patients completed a 3-session study, applying three different patches (lidocaine, piroxicam and control) in random order. A maximum of three patches were applied to the most painful area for three consecutive days (12 hours on followed by 12 hours off). Each session was conducted at least seven days apart. The changes in visual analog scale (VAS) scores based pain intensity, quality of sleep and adverse effects were recorded. RESULTS When compared to the control, both the lidocaine and piroxicam patches significantly reduced the mean VAS scores of pain intensity of all different types. However, the lidocaine patch was better at reducing allodynia, whereas the piroxicam patch was more effective for dull pain. The lidocaine patch worked faster than the piroxicam patch for the response to overall pain relief. CONCLUSION The results of this study suggest the use of the piroxicam patch for dull pain and in patients where the lidocaine patch is contraindicated.

Case of minocycline-effective confluent and reticulated papillomatosis with unusual location on forehead

Dear Editor, A 19-year-old boy was admitted to our department with erythematous to brownish skin eruptions on his chest and forehead. He reported that the lesions had appeared on his chest and forehead 1 month prior. Topical hydrocortisone prescribed by the local dermatology clinic had been ineffective. Close examination revealed well-demarcated, hyperpigmented, and reticulated papules and patches that were confluent (Fig. 1a,b). The macules had been initially itchyerythematous and later evolved into brownish macules. Family history revealed no similar skin lesions. Both potassium hydroxide examination under direct microscope and Wood’s light showed unremarkable findings. Skin biopsy from the chest and forehead revealed basket-weave hyperkeratosis, papillomatosis, acanthosis, slightly increased pigmentation in the basal layer and perivascular chronic inflammatory infiltrates in the papillary dermis (Fig. 2). Additional periodic acid-Schiff (PAS) and D-PAS staining revealed no evidence of fungal elements. These findings were consistent with confluent and reticulated papillomatosis (CRP). The results of complete blood counts, fasting blood sugar, kidney and thyroid function tests were within normal limits, but the liver function test showed abnormal findings from underlying hepatitis B virus infection. On the basis of numerous reports of the clearance of CRP eruptions after using systemic antibiotics, we initiated oral erythromycin 1000 mg/ day for more than 3 months but the response was minimal. Then, the treatment was switched to minocycline 200 mg/day without any topicals. After 4 weeks, there was complete resolution of the eruption with no relapse for 6 months (Fig. 3a,b). Minocycline was well-tolerated and no significant adverse event has occurred during the therapy. Confluent and reticulated papillomatosis is a rare cutaneous disorder that commonly starts in the intermammary and interscapular areas. Subsequent lesions may develop in the neck, axilla and back. In some patients, the disease can involve shoulders, upper arms and surrounding area of the antecubital and popliteal fossa. It rarely affects the sole, palm or mucous membrane and there was no report of forehead sited CRP in a published work search. The etiology and pathogenesis of CRP remains unclear, but there have been a variety of suggested hypotheses. Proposed pathogenetic factors include genetic predisposition for a disorder of keratinization, or infection of the skin with microorganisms such as Malassezia spp. or yeast. Pointing to the detection of amyloid, some have suggested CRP as a variant of skin amyloidosis, while others have equated CRP with pseudoacanthosis nigricans. The influence of bacterial factors in developing CRP was first described by Katayama from the basis of Staphylococcus aureus being cultured from biopsy specimens and enterotoxin B modulated the production of interleukin (IL)-1α, IL-6 and tumor necrosis factor-α which affect epidermal keratinization. Numerous agents have been used to treat CRP with variable results. Topicals including salicylic acid, hydroquinone or urea usually fail. In patients with no evidence of fungal infection, vitamin D3 analogs and tazarotene have been successful. There are also reports of systemic antibiotics such as erythromycin, tetracycline and minocycline showing excellent response. These data seem to support the hypothesis of a bacterial role in pathogenesis of CRP. Although there was no case of erythromycin resistant CRP in the published work, one consensus regarding the susceptibility of various antibiotics in CRP showed three of four (75%) cases sensitive to erythromycin while seven of eight (88%) cases sensitive to minocycline. Therefore, there might be a possibility that the causative strains for the lesion of our case were erythromycin-resistant and minocyclinesensitive. Besides the antibacterial effect of

Alopecia Areata in the Elderly: A 10-Year Retrospective Study.

Background Alopecia areata (AA) is an organ-specific autoimmune disease that typically occurs in young adults. AA in the elderly is relatively rare, thus little data have been reported. Objective This study aimed to understand the clinical characteristics of AA in the elderly. Methods We performed a 10-year retrospective study of AA in the elderly who visited our dermatologic clinic from January 2002 to December 2011. A clinical review of medical records and telephone interviews were performed by two dermatologists. Results Among 1,761 patients with newly diagnosed AA, 61 (3.5%) were older than 60 years at the first visit. Among those who completed a telephone interview, 74.3% (26/35) had less than 50% of scalp-localized hair loss. There was no association between the extent of AA and hair graying (p=0.679). Favorable therapeutic response was observed in 62.9% (22/35) of cases. Conclusion AA in the elderly shows mild disease severity and favorable treatment response. There is no association between graying and the extent of AA. However, the influence of aging on the pathogenesis of AA in the elderly deserves further investigation.

The Efficacy of Complete Surgical Excision of Keloid and Piercing Sinus Tract on Earlobe Keloid

Dear Editor: The external ear is one of the most common sites for keloid formation. Many different treatment modalities such as surgical excision, intralesional corticosteroids, radiotherapy and pressure earrings have been used for earlobe keloids1. Among them, surgical excision is used either as a monotherapy or as a part of a combination therapy. It is thought that the recurrence rate of earlobe keloids after monotherapy with surgical excision is higher than that after combination therapy. This study evaluated the efficacy of complete surgical excision for earlobe keloids. This study was approved by institutional review boards of Kyungpook National University Hospital. We retrospectively reviewed 20 patients with earlobe keloids treated with complete surgical excision (Fig. 1) regardless of clinical subtypes1 (anterior button, posterior button, dumbbell, wraparound, lobular) from January 2000 to May 2012 in our clinic. In this study, complete surgical excision of earlobe keloids was designed for the total removal of the keloidal mass and piercing sinus tract. Earlobe keloids were diagnosed by clinical and histopathological examination. We also retrospectively evaluated 15 patients with earlobe keloids who were treated with a combination of surgery and post-surgical adjunctive therapy. The recurrence rate of complete surgical excision was compared with that of surgery and adjunctive therapy. In addition, clinical subtypes, age, accompanying keloid and size were assessed for their effect on the recurrence rate after complete surgical excision. Statistical analysis was performed using chi-square and Fishers exact tests. A p<0.05 was considered to be statistically significant. Fig. 1 Complete surgical excision of earlobe keloid. The sinus tract, which is indicated by yellow arrows, should be totally removed. If not, the remaining sinus tract may become a cause of keloid relapse. The age of the 20 patients in the study (the ratio of male to female was 0 : 20) was variable (ages 16 to 52 years; mean age 25.3 years) (Table 1). All patients were treated with complete surgical excision and histopathology confirmed the characteristics of keloids as well as the sinus tract in the keloidal mass were present. Fifteen patients treated with a combination of surgery and postsurgical adjunctive therapy consisted of 12 females and 3 males (ages 20 to 61 years; mean age: 28.2 years) (Table 1). Adjunctive therapy included intralesional injection of corticosteroid, radiotherapy, pressure earrings, intralesional application of 5-fluorouracil and mitomycin C. The recurrence rate of earlobe keloids in patients treated with complete surgical excision was 20% (4 out of 20). The 1-year follow-up recurrence rate of earlobe keloids in patients treated with complete surgical excision was 27% (4 out of 15). The recurrence rate of earlobe keloid after a combination of surgery and postsurgical adjunctive therapy was 40% (6 out 15). The 1-year follow-up recurrence rate of earlobe keloid after a combination of surgery and postsurgical adjunctive therapy was 42% (5 out 12). There was no statistically significant difference in the recurrence rate of earlobe keloids between the two groups (p>0.05). Differences in the recurrence rate of earlobe keloids in patients treated with complete surgical excision according to clinical subtype, age, accompanying keloid and size were not statistically significant (p>0.05). Keloids of the chest and shoulder are relatively resistant to treatment, with high recurrence rates after treatment with a single therapeutic modality. Earlobe keloids need to be considered differently from other keloids. Earlobe keloids show lower tension and have a piercing sinus tract covered with keratinocytes. Many authors have noted a lower rate of keloid recurrence in the earlobe2,3. In the current study, the recurrence rate after complete surgical excision was 20% (27% at the 1-year follow-up). The superior outcome of complete surgical excision of earlobe keloids likely results from the lower skin tension in this region and the removal of the intrakeloidal sinus tract. There have been clinical observations that wounds subjected to increased skin tension are more likely to form keloids. The fleshy tissue of the earlobe makes closure without tension easier to accomplish1. Moreover, discontinuation of the wearing of earrings after complete surgical excision of earlobe keloids reduces the tension from the weight of earrings. Mechanical tension is capable of inducing several cell functions, including stimulation of gene expression, protein synthesis and proliferation4-7. A recent study revealed that there was increased formation of focal adhesion complexes of keloid fibroblasts which had increased expression of transformation growth factor (TGF)-β1, TGF-β2, and collagen I compared with normal fibroblasts8. The sinus tract is thought to be the leading edge and cause of skin irritation in earlobe keloids. The role of keratinocytes is of interest because not only do they secrete autocrine proteins, but they also secrete cytokines in paracrine-like fashion into the extracellular domain to induce local proliferative, metabolic and immunologic activities. One recent study compared the influence of keloid-derived keratinocytes and normal keratinocytes on the growth and proliferation of fibroblasts in an in vitro serum-free coculture system. It revealed that there was a considerable increase in the proliferation of the fibroblasts cocultured with keloid-derived keratinocytes, as compared with the normal keratinocyte controls9. This strongly suggests that keloid-derived keratinocytes might have an important role in keloid pathogenesis by producing signals that stimulate fibroblasts in the underlying dermis to proliferate or produce more extracellular matrix9. Moreover, other data have suggested that the leading edge of the keloid, which is thought to be the sinus tract, is different from the center where the process has already burned out10. This would suggest that removal of the sinus tract may help prevent recurrence of the keloid. Table 1 Patient demographics In this study, all earlobe keloids were removed by complete surgical excision. There was no statistical significance according to clinical subtype. We could not find statistical significance in the recurrence rate of earlobe keloids in patients with complete surgical excision according to age (2 were teenagers, 14 in their 20s, 2 in their 30s, 1 in her 40s and 1 in her 50s), accompanying keloids (5 had an accompanying keloid) and size (8 had a keloid less than 1.0 cm in size and 12 had a keloid over 1.0 cm in size). This study showed the recurrence rate of complete surgical excision was as low as that in combination therapy using surgery and postsurgical adjunctive therapy. We believe these results come from the removal or decrease of keloid-promoting factors, such as removal of the sinus tract and reduction of tension in the tissues. Additional factors including age, clinical subtype, accompanying keloid and size should be further evaluated for their effect on the recurrence rate of earlobe keloids.

The effect of sebocytes cultured from nevus sebaceus on hair growth.

Sebaceous glands are known to affect hair growth. Nevus sebaceus, a sebaceous gland hamartomas, presents as hairless patches. In this study, cultures of nevus sebaceus sebocytes (NSS) and normal scalp hair follicle sebocytes (NS) were used in performance of microarray, RT‐PCR, western blot assay and immunofluorescence staining. NSS‐ and NS‐conditioned media were also added to the culture of outer root sheath cells (ORSCs), dermal papilla cells (DPCs) or normal scalp hair follicle sebocytes. Results of this study showed a decrease in the survival rate of ORSCs and DPCs and hair growth in the NSS‐conditioned medium‐treated group, compared with the control and NS‐conditioned medium‐treated groups. An increase in expression of fibroblast growth factor (FGF)‐5, Dickkopf‐1 and inflammatory cytokines and a decrease in expression of Wnt10b and Lef1 were observed. In conclusion, NSS showed an increase in expression of hair growth‐suppressing bioactive factors, including FGF‐5, and a decrease in expression of hair growth‐stimulating factors.

Clarifying the transmission route of Staphylococcus aureus colonizing the skin in early childhood atopic dermatitis

BACKGROUND We previously found that skin-colonizing Staphylococcus aureus in early childhood atopic dermatitis (AD) originates predominantly from the patients nose, whereas maternal transmission did not contribute substantially to colonization. OBJECTIVE To investigate the transmission route and definitive source of skin-colonizing S aureus in early childhood AD. METHODS A total of 527 children and 32 healthy teachers from 2 kindergartens and 1 elementary school were included in the study. Children were screened for AD and categorized into 3 groups (AD, borderline, and healthy). Samples were collected from 5 to 6 different body sites, including the skin, subungual spaces, and anterior nares. The identity of colonies apparent on mannitol salt agar plates was confirmed by polymerase chain reaction amplification of the nuc gene. The genotypic composition of cultured isolates was examined by pulsed-field gel electrophoresis and analyzed with a dendrogram. RESULTS The total colonization rate was higher in the AD group (34.6%) than in the borderline (21.1%) and healthy groups (25.4%). In the AD group, S aureus was more frequently cultured from the subungual areas (30.8%) than the anterior nares (19.2%). To assess self-contamination or recolonization, dendrogram analysis revealed that most isolate pairs (22/23) had the same pulsed-field gel electrophoresis pattern. CONCLUSION As with the anterior nares, the subungual spaces are important reservoir of skin-colonizing S aureus in early childhood AD. The transmission route for self-contamination or recolonization of S aureus appears to be from childrens anterior nares to the skin through their own fingers. Child-to-child and/or teacher-to-child transmission in a classroom do not seem to be definite routes of S aureus transmission.