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Several studies have determined the correlation between programmed cell death protein-1 (PD-1) and chronic plaque psoriasis (CPP). However, limited studies have assessed the association between PD-1 expression and the clinicoprognostic and distinct clinicopathological characteristics of CPP and guttate psoriasis (GP). Twenty-nine patients with skin biopsy-confirmed CPP were recruited at the Asan Medical Center between January 2018 and June 2020, and 33 patients with biopsy-confirmed GP were enrolled between January 2002 and June 2020. The clinicoprognostic and histopathological characteristics were analyzed according to immunohistochemical PD-1 expression in the epidermal or dermal inflammatory infiltrates. The CPP and GP lesions were divided into PD-1-low and PD-1-high groups. The CPP epidermal PD-1-high group had typical histopathological changes and significantly higher psoriasis area and severity index scores (p = 0.014) and disease duration (p = 0.009) than the epidermal PD-1-low group. In patients with GP, compared with the dermal PD-1-high group, the dermal PD-1-low group exhibited significantly higher disease duration (p = 0.002) and relapse rate of plaque psoriasis (p = 0.005) and significantly lower relapse-free survival (p = 0.016). Upregulated epidermal PD-1 expression was correlated with the chronicity and severity of CPP, while downregulated dermal PD-1 expression was correlated with poor prognosis of GP.

With the increasing incidence of skin cancer, many noninvasive technologies to detect its presence have been developed. This review focuses on reflectance confocal microscopy (RCM), optical coherence tomography (OCT), high-frequency ultrasound (HFUS), electrical impedance spectroscopy (EIS), pigmented lesion assay (PLA), and Raman spectroscopy (RS) and discusses the basic principle, clinical applications, advantages, and disadvantages of each technology. RCM provides high cellular resolution and has high sensitivity and specificity for the diagnosis of skin cancer. OCT provides lower resolution than RCM, although its evaluable depth is deeper than that of RCM. RCM and OCT may be useful in reducing the number of unnecessary biopsies, evaluating the tumor margin, and monitoring treatment response. HFUS can be mainly used to delineate tumor depths or margins and monitor the treatment response. EIS provides high sensitivity but low specificity for the diagnosis of skin malignancies. PLA, which is based on the genetic information of lesions, is applicable for the detection of melanoma with high sensitivity and moderate-to-high specificity. RS showed high accuracy for the diagnosis of skin cancer, although more clinical studies are required. Advances in these technologies for the diagnosis of skin cancer can lead to the realization of optimized and individualized treatments.

Inflammatory skin diseases, such as rosacea and acne, are major causes of facial erythema and accompanying skin barrier dysfunction. Several methods to restore the impaired skin barrier and improve facial erythema, such as medication, radiofrequency, laser, and ultrasound therapy were attempted. This study evaluated the efficacy and safety of dual-frequency ultrasound with impulse mode, for improving skin hydration and erythema in Asian subjects with rosacea and acne. Twenty-six subjects with facial erythema received an ultrasound treatment once per week, for 4 weeks, over both cheeks. The erythema index and transepidermal water loss (TEWL) were measured at each visit. Clinicians assessed the erythema improvement and patients evaluated their satisfaction level. The average decrease in TEWL and erythema index at 6 weeks was 5.37 ± 13.22 g·h−1·m−2 (p = 0.020) and 39.73 ± 44.21 (p = 0.010), respectively. The clinician’s erythema assessment and the subject satisfaction questionnaire score significantly improved at final follow-up (p &lt, 0.001, p = 0.003, respectively). No serious adverse effects were observed during the treatment and follow-up periods. The dual-frequency ultrasound with impulse mode appears to be effective and safe for improving skin hydration and erythema in patients with rosacea and acne.

Importance Large population-based studies investigating the risks of overall and specific cancers among patients with hidradenitis suppurativa (HS) are limited. Objective To assess the overall and specific cancer risks in patients with HS compared with the risks in patients without HS in the Republic of Korea. Design, Setting, and Participants A nationwide population-based cohort study, using the Korean Health Insurance Review and Assessment Service database was conducted over a 2-year period from January 1, 2007, to December 31, 2008. Individuals in the control group who were never diagnosed with HS or cancer during the washout period were randomly extracted and matched by age, sex, index year, and insurance type at a case-control ratio of 1:8, and patients with newly diagnosed HS between January 1, 2009, and December 31, 2017, were included. Follow-up data on incident cancer from January 1, 2009, to December 31, 2018, were included. Main Outcomes and Measures The overall and specific cancer incidence rates were calculated per 100 000 person-years in patients with HS and in the matched control cohort. The risk for cancers was assessed by multivariable Cox regression models in patients with HS compared with the matched control cohort. Results In total, 22 468 patients with HS and 179 734 matched controls were included in the study. The mean (SD) age was 33.63 (17.61) years and 63.7% of the participants in both groups were male. The adjusted hazard ratio (aHR) of overall cancer in patients with HS was 1.28 (95% CI, 1.15-1.42). Patients with HS had significantly higher risk for Hodgkin lymphoma (aHR, 5.08; 95% CI, 1.21-21.36), oral cavity and pharyngeal cancer (aHR, 3.10; 95% CI, 1.60-6.02), central nervous system cancer (aHR, 2.40; 95% CI, 1.22-4.70), nonmelanoma skin cancer (HR, 2.06; 95% CI, 1.12-3.79), prostate cancer (aHR, 2.05; 95% CI, 1.30-3.24), and colorectal cancer (aHR, 1.45; 95% CI, 1.09-1.93). Conclusions and Relevance In this study, HS appeared to be associated with a significantly increased risk of overall cancer as well as several specific cancers.

Extraskeletal osteosarcoma (ESOS) is a rare mesenchymal soft-tissue neoplasm that accounts for approximately 1% of all soft-tissue sarcomas. Over 70% of these malignant tumor progress to local recurrence and metastasis. It commonly metastasizes to the lungs, lymph nodes, bone, and skin and has a poor survival outcome. Cutaneous metastasis is exceedingly rare and known to be a sign of widespread metastases. We present a 57-year-old woman who presented with a rapidly growing protuberant mass on the scalp that was finally diagnosed as metastatic ESOS from a primary pancreatic ESOS. To our knowledge, there has been no reported case of pancreatic ESOS metastasizing to the scalp.

Natural killer/T-cell lymphoma is a rare, Epstein–Barr virus-associated type of cytotoxic lymphoma thatpresents mainly in the nasal cavity and its vicinity. Very few cases of primary cutaneous extranodal natural killer/T-cell lymphoma have been reported till date. All the previously reported cases of primary cutaneous extranodalnatural killer/T-cell lymphoma presented as lesions resembling cellulitis, subcutaneous nodules or ulcers. We report a rare case which presented as erythematous and purpuric round patches on the arms and was finally diagnosed as primary cutaneous extranodalnatural killer/T-cell lymphoma, following a skin biopsy. The atypical patchy lesions presented a diagnostic challenge. We herein describe this clinically novel atypical patch-like presentation of primary cutaneous extranodalnatural killer/T-cell lymphoma together with the key histopathologic features and highlights of the previously reported cases.

Background Anti-programmed cell death-1 (PD-1) immunotherapy using antibodies such as nivolumab or pembrolizumab has shown promise for treating various types of cancer. In this study, we reviewed the frequency and spectrum of cutaneous adverse events (AEs) caused by PD-1 antibodies and their possible correlation with treatment response. Methods We reviewed records of all patients from a single institution treated with either nivolumab or pembrolizumab from August 1, 2014 to April 1, 2017. Results Of 211 patients included in the study, 134 (63.5%) were treated with nivolumab and 77 (36.5%) with pembrolizumab. Thirty-five patients (16.4%) developed cutaneous AEs. Cutaneous AEs were significantly associated with longer treatment cycles (P = 0.001). The prevalence of cutaneous AEs did not differ between nivolumab (17.2%) and pembrolizumab (15.6%). Patient age, gender, baseline Eastern Cooperative Oncology Group scale and underlying malignancy were not associated with development of cutaneous AEs. Median time until onset of cutaneous AEs was 50.0 days (range, 1–378 days). Anti-PD-1 therapy was tolerable in most of patients with grade 1 (65.2%) and grade 2 (23.9%) cutaneous AEs. Pruritus (32.6%) and eczema (21.7%) were the most commonly reported cutaneous AEs. In lung cancer patients, cutaneous AEs were not associated with better treatment outcomes after adjusting for the number of treatment cycles. Conclusion Both pembrolizumab and nivolumab exhibited tolerable cutaneous safety profiles in a variety of cancer patients undergoing anti-PD-1 therapy. Cutaneous AEs of anti-PD-1 therapy were not associated with antibody type, underlying malignancy, patient characteristics, or improved response., Graphical Abstract

It has long been believed that histamine is associated with cutaneous melanogenesis. Specifically, H2-receptor antagonists reportedly inhibit melanogenesis, but H1-receptor antagonists, which are some of the most commonly prescribed medicines in dermatology, have not been studied to determine whether and how they regulate melanogenesis. Therefore, we screened H1-receptor antagonists to determine whether they inhibit melanogenesis and found that loratadine was particularly effective, in this regard without compromising cellular viability. Loratadine downregulated microphthalmia-associated transcription factor (MITF) and tyrosinase in melanocytes. To determine the intracellular signaling pathways, Akt was consistently activated by loratadine. PI3K/Akt pathway inhibitor, LY294002, restored the reduced melanin content that was induced by loratadine. In addition, phospho-GSK-3β also was found to be increased following loratadine treatment. Loratadine reduced the amount of PKC-βII in the membrane fraction, thereby decreasing its activity. Taken together, our data indicate that loratadine regulates melanogenesis via Akt/MITF and PKC-βII signaling, thereby leading to the inhibition of melanogenic proteins. The antimelanogenic effects of loratadine have potentially significant and useful roles in dermatologic practice, although further clinical studies will be required to test this.

Background Psoriasis is characterized by uncontrolled hyperproliferation, aberrant differentiation, and dermal infiltration of immune cells. Recent studies have reported that Wnt5a and Notch1 signaling are altered in psoriatic skin lesions. Objective We aimed to investigate the interaction of Wnt5a with Notch 1 with respect to inflammation-mediated epidermal hyperproliferation in psoriasis. Methods Expression of Wnt5a and Notch1 signaling-related proteins were examined in psoriatic skin biopsies. Wnt5a was upregulated in human keratinocytes by treating the cells with its recombinant form (rWnt5a). Results In psoriatic lesions, expression of Wnt5a increased while that of Notch1 decreased when compared to that in non-lesional and normal skin. Treatment with rWnt5a increased the proliferation of keratinocytes and increased their secretion of interleukin (IL)-23, IL-12, and tumor necrosis factor (TNF)-α. Further, exposure of keratinocytes to IL-1α, TNF-α, transforming growth factor-α, and interferon-γ downregulated Notch1 as well as HES 1, which is downstream to Notch1, but increased the Wnt5a levels. The upregulated Wnt5a in keratinocytes downregulated both Notch1 and HES1. Conclusion Our data suggest that Wnt5a and Notch1 signaling exert counteracting influences on each other and are involved, in part, in the pathomechanism of psoriasis.

Background Reactive oxygen species (ROS) play an important role in the induction of apoptosis under pathological conditions. Recently, a significant increase in ROS production and disrupted apoptosis mechanisms in keloids have been reported. Nuclear factor erythroid 2-related factor 2 (Nrf2) represents one of the most important cellular defense mechanisms against oxidative stress and is implicated in the regulation of apoptosis. Recently, it has been reported that Nrf2 upregulates Bcl-2, an anti-apoptotic protein. Objective To compare Nrf2 protein expression in normal skin tissues to keloid tissues. Methods ROS generation in keloid tissues was evaluated with OxyBlot analysis. Western blotting and/or immunohistochemical staining approaches were used to study expression of Nrf2 or Bcl-2 in keloid and normal skin tissues. Cellular fractionation was performed to examine subcellular distribution of Nrf2. Transfection of fibroblasts with Nrf2-specific small interfering RNA (siRNA) was conducted to understand the relationship between Nrf2 expression and apoptosis induction. Results Protein oxidation, a marker of oxidative stress, is increased in keloid tissues. Western blot analysis clearly showed that Nrf2 and Bcl-2 are downregulated in keloid tissues. Immunohistochemical staining of Nrf2 confirmed the results of the western blot analysis. Transfection of fibroblasts with the Nrf2-specific siRNA results in increased apoptosis and decreased cell viability. Conclusion Collectively, our data indicate that Nrf2 expression is downregulated in keloid tissues, and that Nrf2 is involved in the development of apoptosis in Nrf2 siRNA-transfected fibroblasts. We propose that a defective antioxidant system and apoptotic dysregulation may participate in keloid pathogenesis.

Purpose This study evaluated the incidence of imatinib-associated skin rash, the interventional outcomes of severe rash, and impact of severe rash on the outcomes of imatinib treatment in gastrointestinal stromal tumor (GIST) patients. Materials and methods A total of 620 patients were administered adjuvant or palliative imatinib for GIST at Asan Medical Center between January 2000 and July 2012. This analysis focused on a group of 42 patients who developed a severe rash requiring major interventions, defined as dose interruption or reduction of imatinib or systemic steroid use. Results Of the 620 patients treated with imatinib, 148 patients (23.9%) developed an imatinib-associated skin rash; 42 patients (6.8%) developed a severe rash requiring major intervention. Of these, 28 patients (66.8%) successfully continued imatinib with interventions. Serial blood eosinophil levels during imatinib treatment were associated with skin rash and severity. A significant association was observed between successful intervention and blood eosinophil level at the time of intervention initiation. In metastatic settings, patients with severe rash requiring major interventions tended to show poorer progression-free survival than patients who did not require major intervention and patients with no rash, although this finding was not statistically significant (p=0.326). Conclusion By aggressive treatment of severe rash through modification of imatinib dose or use of systemic steroid, the majority of patients can continue on imatinib. In particular, imatinib dose intensity can be maintained with use of systemic steroid. Measuring the blood eosinophil levels may be helpful in guiding the management plan for skin rash regarding the intensity and duration of interventions.

Epithelioid hemangioma (EH) is an uncommon benign vascular tumor, of controversial etiology that usually presents as a slowly growing nodule on the face or digit of a middle-aged woman. 1 Most lesions have a nonspecific nodular appearance with frequent secondary changes such as excoriation and bleeding. Multiplicity is also a common finding. Histopathologically, EH is characterized by a mixture of vascular proliferation and marked mixed inflammatory cell infiltration, and was first de scribed by Wells and Whimster 2 as angiolymphoid hyperplasia with eosinophilia. The proliferation of vascular structures lined with prominent endothelial cells is a distinguishing feature of EH. The epithelioid endothelial cells that protrude into the vascular lumen create a characteristic “cobble-stone” or “tombstone” appearance. A chronic inflammatory cell infiltration in cluding lymphoplasma cells and eosinophils is a consistent find ing. EH has a diverse range of microscopic features, depending on the composition and distribution of the vascular and inflam matory cellular components. EH has been described in the literature as an inflammatory angiomatous nodule or, an atypical or pseudopyogenic granuloma, 3,4 when infiltration of various inflammatory cells is predominant, and a histiocytoid hemangi oma 5 when cobble stone-like endothelial cells are conspicuous. Some cases of EH consist entirely of solid sheets of epithelioid to spindled cells without fully canalized vascular structures. The solid form of EH can be difficult to diagnose and is occa sionally misdiagnosed as a malignant vascular tumor. EH is a benign neoplasm and surgical excision is sufficient for its treat ment. Recently, we experienced a solid form of EH with no inflammatory component, which showed a dramatic change into the typical morphology on the consecutive biopsy. This is the first reported Korean case of a solid form of EH, which patholo gists should include in the differential diagnosis of epithelioid vascular lesions to avoid overdiagnosis of epithelioid vascular malignancies.

Cutaneous metastasis from gastric adenocarcinoma is uncommon, and the eyelid is a rare metastatic site. Three patterns of clinical presentation of eyelid metastasis have been described: nodular, infiltrative, and ulcerated. The infiltrative pattern, also known as an inflammatory diffuse pattern or mask-like metastasis, can be easily misdiagnosed as cellulitis or contact dermatitis. Here, we report a case of gastric adenocarcinoma in a 75-year-old man who presented with a localized erythematous plaque on his eyelid that developed four months earlier. The patient had been treated with an antimicrobial agent owing to suspicion of preseptal cellulitis. Gastric adenocarcinoma metastasis was diagnosed on the basis of histopathological examination and immunophenotyping (i.e., cytoplasmic epithelial membrane antigen, cytokeratin- 7, cytokeratin-20, and carcinoembryonic antigen). For patients with malignant neoplasms, persistent skin lesions similar to cellulitis or contact dermatitis should be suspected of metastasis derived from an internal malignancy, even for very rare sites of metastasis.

Granular parakeratosis is a recently recognized disorder of keratinization that is usually confined to intertriginous areas. The histopathologic features are distinctive and diagnostic. Rarely, histopathologic variants such as follicular granular parakeratosis and granular parakeratosis of eccrine ostia have been described. In this report, we describe a rare case of granular parakeratosis mostly confined to eccrine ostia.

Dear Editor: Adalimumab is a complete human monoclonal anti-tumor necrosis factor α (anti-TNFα) that is generally well tolerated. With increasing use of adalimumab and other anti-TNFα therapies, several cutaneous adverse events have been reported during the therapy, including immune-mediated skin lesions1. A 39-year-old woman who had an 11-year history of Crohn's disease and was treated with adalimumab (40 mg administered subcutaneously every other week) presented at our clinic with multiple achromic macules and patches on the extremities (Fig. 1). The lesions developed abruptly about 12 months after the initiation of adalimumab therapy. The diagnosis of vitiligo was made after the patient's skin turned blue under a Wood's lamp. Laboratory tests were also performed to check for other autoimmune conditions, including thyroid disorders, and no abnormality was diagnosed. The patient denied any family history of vitiligo. She has been treated with a combination therapy of excimer laser and topical tacrolimus without stopping the adalimumab therapy for about 1 year, and has shown minimal response thus far. Fig. 1 Multiple well-demarcated irregularly shaped depigmented macules and patches (A) on the left proximal thigh, (B) dorsum of the right foot, (C) dorsum of the right hand, and (D) right forearm. The role of anti-TNFα inhibitors in the development of vitiligo is complicated and contradictory. There have been several case reports that showed improvement in vitiligo in patients receiving anti-TNFα therapy for other diseases2. The therapeutic effect of anti-TNFα inhibitors on vitiligo might result from stopping the physiological effect of TNFα on melanogenesis. Concretely, it has been reported that TNFα decreases the level of tyrosinase, a rate-limiting enzyme in melanin biosynthesis in vitro3. The melanocytotoxic effect of TNFα in vitiligo has also been demonstrated2. On the contrary, anti-TNFα inhibitors have been associated with the development of a considerable number of autoimmune diseases such as vitiligo, as well as leukocytoclastic vasculitis, systemic lupus erythematosus, psoriasis-like lesions, and alopecia areata1. Several theories were proposed to explain the mechanisms underlying the development of autoimmunity during treatment with anti-TNFα inhibitors. In vivo, nucleosome numbers (major autoantigens released during apoptosis) increase in patients receiving anti-TNFα therapies. This could lead to the subsequent induction of autoantibodies4. To our knowledge, only two cases of vitiligo have been attributed to adalimumab use. The first case was that of newly developed vitiligo after 8 months of adalimumab therapy for Crohn's disease; this was similar to our case5. In the second case, there was rapid deterioration of vitiligo within 3 months of adalimumab therapy for managing ankylosing spondylitis4. In our case, it could not be determined whether vitiligo was caused by adalimumab therapy or if it developed in association with Crohn's disease because the concomitant occurrence of vitiligo with inflammatory bowel disease has been rarely reported. The long duration of Crohn's disease, and the sudden onset and rapid spreading of cutaneous lesions support the former possibility. Previous reports and our case suggest that anti-TNFα agents, including adalimumab, can induce vitiligo development. Dermatologists should be aware of this possibility for an earlier detection and treatment of vitiligo in patients receiving anti-TNFα therapy.

Dear Editor: Here, we describe a case of acquired dermal melanocytosis involving the dorsum in an Asian woman. A 45-year-old Korean woman presented with a 3-year history of a relatively well-demarcated, pale, blue-grayish, asymptomatic round patch on her interscapular back area (Fig. 1). Hypertrichosis was not observed within the lesion. Physical examination revealed no other similar lesions elsewhere. The patient denied any history of preceding inflammatory changes, trauma, bruises, tattoos, or metal contact on her back. She also denied taking heavy metals or any medicines that may result in hyperpigmentation and had no family history of similar skin lesions. Histopathologic examination revealed multiple spindle-shaped brown pigment-containing cells scattered among collagen fibers in the dermis (Fig. 2A, B). Immunohistochemical staining demonstrated these cells were positive for S100 protein (Fig. 2C) and negative for HMB-45 (data not shown). In addition, the brown pigment stained positive with Fontana-Masson stain, which is indicative of melanin (Fig. 2D), but not with Perls Prussian blue stain for hemosiderin (data not shown). Furthermore, immunohistochemistry revealed CD68-positive cells scattered in the dermis (Fig. 2E). Therefore, the patient was diagnosed with acquired dermal melanocytosis of the back, but no treatment was administered in accordance with the patient's wishes. Fig. 1 A relatively well-demarcated pale blue-grayish round patch on the interscapular area. Fig. 2 Histopathologic examinations and immunohistochemistry. (A, B) Multiple spindle-shaped brown pigment-containing cells scattered among collagen fibers in the dermis (HE A: ×100, B: ×200). (C) Immunohistochemical staining showed ... Dermal melanocytosis is defined by the presence of melanin-containing dendritic melanocytes in the dermis and can be differentiated on the basis of lesion onset and location1. Congenital forms of dermal melanocytosis include Mongolian spot, nevus of Ota, and nevus of Ito. Acquired forms of dermal melanocytosis include nevus of Hori and nevus of Sun, which involve the bilateral and unilateral malar areas, respectively. Acquired dermal melanocytosis located in areas besides the face is very rare; previously reported non-facial sites include the extremities and back1,2. Some of these reported cases were associated with malignancies including melanoma, physical trauma, oral estrogen, and eczema2. Although the pathogenesis of acquired dermal melanocytosis is unclear, one possibility is that dermal melanocytes may pre-exist in an immature state; they subsequently become activated by various stimuli including ultraviolet exposure, sex hormones, and inflammation3,4. This is supported by the observation that dermal melanocytes are also found in the normal-appearing skin neighboring the lesions of acquired dermal melanocytosis5. Nevertheless, the origin of the pre-existing dermal immature melanocytes is not fully understood. They may descend from the basal layer of the epidermis, migrate from hair bulbs, or improperly migrate during the embryonic period4. Acquired dermal melanocytosis does not usually fade; the pigment persists in contrast with Mongolian spots. This persistence may be associated with the extracellular sheath encircling dermal melanocytes, which has been observed in ultrastructural studies4. The extracellular sheaths of Mongolian spots usually fade over time, whereas those of nevus of Ota gradually thicken over time. Extracellular sheaths are also observed in acquired dermal melanocytosis and presumably play a role in protecting dermal melanocytes4. In conclusion, we report a case of acquired dermal melanocytosis with an unusual location that has not been described previously.

Dear Editor: The Harlequin syndrome, first described by Lance et al.1 in 1988, represents an uncommon disorder of the sympathetic nervous system. It is characterized by unilateral diminished sweating and heat- or exercised-induced facial flushing. We present the case of one patient with this remarkable syndrome, including a review of the literature. A 43-year-old woman presented to our clinic with a peculiar pattern of facial flushing. She has been experiencing flushing and sweating on the left side of her face after physical exercise or after taking a hot bath (Fig. 1). The symptoms started about 2 years ago, after she had undergone an endoscopic surgery for the removal of a solitary pulmonary nodule. She has no other medical history besides chronic pancreatitis. She has never been treated for her symptoms before visiting our clinic. On examination at rest, no asymmetric facial flushing or sweating was noted. Neurological examination was normal, and signs of ptosis or miosis were absent. Laboratory tests, including complete blood count, erythrocyte sedimentation rate, glucose, sodium, potassium, and creatinine, revealed no abnormality. As the symptom had appeared only after the endoscopic surgery, we suspected that there might have been an accidental damage to the sympathetic nerve innervating the right facial area during the surgery. The patient was reassured of the benign nature of her complaints and was asked to avoid any aggravating factors. Most cases of Harlequin syndrome are primary in nature. This syndrome is most common in women, and social embarrassment is the main problem of affected persons. In about one-sixth of patients with Harlequin syndrome, the disorder is caused by an underlying disease or a structural lesion (i.e., secondary Harlequin syndrome). The iatrogenic type of Harlequin syndrome, like our case, is recently being reported with a higher frequency. Ten such cases have been reported: one occurring after internal jugular vein catheterization, five after paravertebral thoracic anesthetic blocks, three after surgical resection of a neck mass, and one after thoracic sympathectomy. Physicians should focus on taking the patient's medical history for related factors such as a previous malignancy, as well as recent surgery or anesthesia-related problems. Clinical and neurological examinations are also required, and imaging techniques such as computed tomography or magnetic resonance imaging of the brain, spinal cord, and the carotid arteries and the lung apex should be performed to exclude the presence of a structural lesion. Usually, a patient with a primary or iatrogenic Harlequin syndrome does not need any treatment. If the symptoms are not acceptable, a contralateral sympathectomy may be considered2. Recently, a novel approach to the management of Harlequin syndrome, by using repeated stellate ganglion blocks, was proposed as a less invasive alternative treatment3. To our knowledge, a clinical presentation of Harlequin syndrome has not been previously reported in the Korean dermatological literature. We hope that this report would make dermatologists properly aware of this rare syndrome. Fig. 1 She experienced flushing on the left side of her face following physical exercise.

Precalcaneal congenital fibrolipomatous hamartomas (PCFHs) are characterized clinically by the presence of unilateral or bilateral, asymptomatic nodules in the medial precalcaneal plantar region of the heel. They are skin colored and usually painless nodules. In most patients, the lesions appear within the first few months of life, but they may also be present at birth. Generally PCFHs are benign, but they can grow in proportion to the growth of the infants. Here, we report the case of a 4-month-old boy with a solitary, localized skin-colored nodule on the precalcaneal plantar region of his right heel, diagnosed as a PCFH.

Dear Editor: Grover's disease (GD) is a dermatosis of unknown aetiology that mostly affects men over 40 years-of-age. It is visually characterized by erythematous excoriated papules, which are usually located on the trunk, and is histologically characterized by acantholysis and dyskeratosis. GD has been reported in patients with chronic renal failure, malignancies, and in those with renal and bone marrow transplants1. A 56-year-old man complained of pruritic skin eruptions on his back and on both of his shins, which lasted for 3 months (Fig. 1). He had received a liver transplant 5 months previously for alcoholic liver cirrhosis. He had been taking mycophenolatemofetil, tacrolimus, and methylprednisolone for immunosuppression. Fig. 1 Brownish hyperkeratosis papules on the back (A) and both shins (B). His skin lesions comprised numerous brownish papules, about 2~5 mm in size, which were predominantly located on the backand on both shins. The patient showed no other abnormalities of the skin appendages or mucosa. There was no family history of skin disease. A biopsy of a brownish papule on the back showed epidermal hyperplasia with parakeratotic hyperkeratosis (Fig. 2). The epidermis showed suprabasalacantholysis and dyskeratotic keratinocytes. Corps ronds and grains were also evident along with a slight perivascular lymphohistiocytic infiltration of the dermis. The clinical and histological evidence was compatible with a diagnosis of GD, Darier's disease or Hailey-Hailey disease. The late onset, and the lack of family history and other characteristics consistent with Darier's disease, led to a final diagnosis of GD. The patient was treated with topical calcipotriol, although no clinical improvement was observed. Fig. 2 Histopathology of popular lesions (H&E). (A) Multifocal area of suprabasalclefting and acantholysis (×40). (B) Suprabasalclefting with corps ronds and grain (×200). The aetiology of GD is unknown. This disease is clinically and histologically indistinguishable from Darier's disease and Hailey-Hailey disease, although no mutations in the SERCA2 or SPCA1 genes have been detected in GD2. GD is frequently associated with exposure to heat and sunlight, sweating, and fever. Drugs, ionizing radiation, infection (Malassezia furfur or Demodexfolliculorum) and severe dermatosis (atopic dermatitis, allergic contact dermatitis, and asteatotic eczema) are also associated with GD3. GD has been reported in patients infected with human immunodeficiency virus, and in those with renal failure, haematologic malignancies, and solid carcinomas1. Also, the onset of GD after bone marrow transplantation (eight cases)4,5 and kidney transplantation (one case)1 has been described. To our knowledge, this is the first report of GD developing in a patient after liver transplantation followed by immunosuppressive treatment. Although it is unclear whether the aetiological mechanism underlying GD is immunologic, the immunosuppression may act as a trigger. Our case suggests that GD should be considered as a differential diagnosis in patients presenting with skin eruptions after liver transplantation with immunosuppression. The onset of GD after liver transplantation suggests an immunological mechanism. Further studies will be helpful to identify the relationship between GD and immunological mechanism.

CD4(+)CD25(high+)regulatory T cells (Tregs) are considered to be of vital importance for maintaining immunologic self-tolerance and preventing autoimmune diseases. These cells have been found to be deficient in skin lesions and in the peripheral blood of patients with psoriasis.To investigate the role of Tregs in the pathogenesis of psoriasis and to evaluate the changes in Tregs in relation to the severity and the clinical course of psoriasis.Immunohistochemistry (CD3, 4, 8, 79 and FOXP3) was performed in 22 psoriatic patients compared to 5 normal controls. Flow cytometry (CD3, 4, 8, 25 and FOXP3) was performed in 18 psoriatic patients and 8 normal volunteers and reverse transcriptase polymerase chain reaction (foxp3 mRNA) was performed in 8 psoriasis patients.An increase in the FOXP3(+) cell fraction was detected in the lesional psoriatic skin irrespective of the severity of psoriasis as compared with the normal skin. However, a decrease in FOXP3(+) cells was observed in the samples obtained from psoriasis of 'acute course'. FOXP3(+) Treg populations in the blood of the 'acute course' psoriasis was not different compared to that of 'chronic course' psoriasis and normal controls.The deficiency of FOXP3(+) Tregs in the lesional psoriatic skin might be responsible for the exacerbation of psoriasis.

Matridex® is an injectable skin filler that's composed of a mixture of cross linked hyaluronic acid and dextranomer particles, and it was recently developed for soft tissue augmentation. To the best of our knowledge, there have been few previous reports on complications associated with Matridex. We report here on a delayed inflammatory reaction to an injection of Matridex in the glabellar fold, and this developed five weeks after the injection and it lasted more than a year. The patient was treated with oral doxycycline and intralesional injection of triamcinolone acetonide; this resulted in almost complete resolution of the lesion. The patient should be informed of the potential complications with the use of injectable fillers before treatment, for it could lead to undesirable aesthetic consequences.

Incontinentia pigmenti is a systemic disorder affecting the skin, teeth, eyes, nervous tissue, hair, nails, musculoskeletal system, and heart. We describe an 11-month-old girl with incontinentia pigmenti associated with a ventricular septal defect, left hemiatrophy, hemangiomas, an abnormal labial frenum, and spastic cerebral palsy manifested as left hemiplegia and developmental delay. We believe this patient illustrates that incontinentia pigmenti is a systemic disorder necessitating a multidisciplinary approach to management.

Papulonodular mucinosis (PNM) is a rare variant of lupus erythematosus (LE) eruptions, and PNM is characterized histologically by diffuse dermal mucin without any typical epidermal inflammatory changes. We herein describe a case of papular mucinosis that was characterized by several erythematous papules on the lower back of a 32-year-old man with systemic LE. It is interesting that he didn't display any other skin manifestations of LE such as malar rash, discoid rash and photosensitivity during the previous 2 years. He achieved remission of his PNM without recurrence after 5 months treatment with topical steroids, in addition to receiving systemic antimalarials and steroids.