Jin-Bon Hong

Acne-associated syndromes: models for better understanding of acne pathogenesis.

Acne, one of the most common skin disorders, is also a cardinal component of many systemic diseases or syndromes. Their association illustrates the nature of these diseases and is indicative of the pathogenesis of acne. Congenital adrenal hyperplasia (CAH) and seborrhoea‐acne‐hirsutism‐androgenetic alopecia (SAHA) syndrome highlight the role of androgen steroids, while polycystic ovary (PCO) and hyperandrogenism‐insulin resistance‐acanthosis nigricans (HAIR‐AN) syndromes indicate insulin resistance in acne. Apert syndrome with increased fibroblast growth factor receptor 2 (FGFR2) signalling results in follicular hyperkeratinization and sebaceous gland hypertrophy in acne. Synovitis‐acne‐pustulosis‐hyperostosis‐osteitis (SAPHO) and pyogenic arthritis‐pyoderma gangrenosum‐acne (PAPA) syndromes highlight the attributes of inflammation to acne formation. Advances in the understanding of the manifestation and molecular mechanisms of these syndromes will help to clarify acne pathogenesis and develop novel therapeutic modalities.

Discrimination of collagen in normal and pathological skin dermis through second-order susceptibility microscopy.

Polarization-resolved, second harmonic generation (P-SHG) microscopy at single pixel resolution is utilized for medical diagnosis of pathological skin dermis. In analyzing the large area, pixel by pixel, second-order susceptibility of normal and pathological skin dermis, we found that P-SHG can be used to distinguish normal and dermal pathological conditions of keloid, morphea, and dermal elastolysis. Specifically, we found that the second order susceptibility tensor ratio of d(33)/d(31) for normal skins is 1.27+/-0.20, while the corresponding values for keloid, morphea, and dermal elastolysis are respectively 1.67+/-0.29, 1.79+/-0.30, and 1.75+/-0.31. We also found that the histograms of the d(33)/d(31) ratio for the pathological skins contain two peak values and are 1.5 times wider than that of the normal case, suggesting that the pathological dermal collagen fibers tend to be more structurally heterogeneous. Our work demonstrates that pixel-resolved, second-order susceptibility microscopy is effective for detecting heterogeneity in spatial distribution of collagen fibers and maybe used for future clinical diagnosis and in vivo studies of collagen pathological conditions.

Inducible deletion of the Blimp-1 gene in adult epidermis causes granulocyte-dominated chronic skin inflammation in mice

B lymphocyte-induced maturation protein-1 (Blimp-1) is a transcriptional repressor important for the differentiation and function of several types of immune cells. Because skin serves as a physical barrier and acts as an immune sentinel, we investigated whether Blimp-1 is involved in epidermal immune function. We show that Blimp-1 expression is reduced in skin lesions of some human eczema samples and in stimulated primary keratinocytes. Epidermal-specific deletion of PR domain containing 1, with ZNF domain (Prdm1), the gene encoding Blimp-1, in adult mice caused spontaneously inflamed skin characterized by massive dermal infiltration of neutrophils/macrophages and development of chronic inflammation associated with higher levels of cytokines/chemokines, including granulocyte colony-stimulating factor (G-CSF), and enhanced myelopoiesis in bone marrow. Deletion of Prdm1 in the epidermis of adult mice also led to stronger inflammatory reactions in a tape-stripping test and in a disease model of contact dermatitis. The elevated G-CSF produced by keratinocytes after deletion of Prdm1 in vitro was mediated by the transcriptional activation of FBJ osteosarcoma oncogene (Fos) and fos-like antigen 1 (Fosl1). Systemic increases in G-CSF contributed to the inflammatory responses, because deletion of the G-CSF gene [colony stimulating factor 3, (Csf3)] prevented neutrophilia and partially ameliorated the inflamed skin in Prdm1-deficient mice. Our findings indicate a previously unreported function for Blimp-1 in restraining steady-state epidermal barrier immunity.

Chronic Idiopathic Urticaria in Taiwan: A Clinical Study of Demographics, Aggravating Factors, Laboratory Findings, Serum Autoreactivity and Treatment Response

BACKGROUND/PURPOSE Chronic idiopathic urticaria (CIU) is not uncommon, yet there is little information about the clinical features of CIU patients in Taiwan. The purpose of this study was to investigate the clinical features of CIU in Taiwan. METHODS Patients with CIU were collected consecutively from the Urticaria Special Clinic in a medical center in northern Taiwan from December 2005 to May 2006. Clinical features and laboratory findings were studied. We also evaluated the therapeutic response of CIU patients with second-generation H1 receptor antagonist monotherapy for 6 weeks. RESULTS A total of 62 CIU patients were investigated. The female to male ratio was 2.1:1 with a mean age of 31.8 years. The mean duration of the disease was 25.7 months (1.5-180 months). The most common aggravating factor was weather (79.7%), especially hot weather (50.8%). Fifty percent of the patients had atopy, and 37.3% of patients had positive autologous serum skin test. Besides, 61.3% of patients had at least one serum specific IgE antibody to the 18 common allergens examined. Finally, 60.7% of patients responded well to second-generation H1 receptor antagonist. Non-responders tended to have atopy (p = 0.0471), especially allergic rhinitis (p = 0.0107). CONCLUSIONS This study provided an overview of CIU patients in a medical center in northern Taiwan. We found that atopy did not influence the severity or durtation of CIU. Nevertheless, atopy was associated with a poor therapeutic response of second-generation antihistamine. A survey of personal atopy history, especially allergic rhinitis, is important for management of CIU patients in Taiwan.

A woman with iatrogenic androgenetic alopecia responding to finasteride

1 Kinmonth JB, Taylor GW. Chylous reflux. Br Med J 1964; i:529–32. 2 Chern LC, Lin CS, Wong CK. Cutaneous chylous reflux. Br J Dermatol 1989; 120:695–700. 3 Noel AA, Gloviczki P, Bender CE et al. Treatment of symptomatic primary chylous disorders. J Vasc Surg 2001; 34:785–91. 4 Johnson WT. Cutaneous chylous reflux: the weeping scrotum. Arch Dermatol 1979; 115:464–6. 5 Karg E, Bereczki C, Kovacs J et al. Primary lymphoedema associated with xanthomatosis, vaginal lymphorrhoea and intestinal lymphangiectasia. Br J Dermatol 2002; 146:134–7. 6 Witte CL, Witte MH, Unger EC et al. Advances in imaging of lymph flow disorders. Radiographics 2000; 20:1697–719.

Secondary neoplasms arising from nevus sebaceus: A retrospective study of 450 cases in Taiwan.

Nevus sebaceus is frequently associated with the development of secondary neoplasms. Incidences of malignant transformation vary among different reports and few data is available regarding Asian populations. We aimed to determine the characteristics of secondary tumors developing from nevus sebaceus in a Taiwanese population and to review the published work. Patients with clinically and histologically confirmed nevus sebaceus were identified from 1992 to 2012 in a medical center. Among the 450 cases of nevus sebaceus, 38 secondary neoplasms were noted, accounting for 8.5% of all cases. Benign tumors represented more than 80% of all tumors. Syringocystadenoma papilliferum (2.7%) was the most common benign tumor, followed by trichoblastoma (1.6%) and trichilemmoma (1.6%) whereas basal cell carcinoma (0.9%) was the most frequent malignant tumor on nevus sebaceus and its clinical features were not typical. All the malignant tumors on nevus sebaceus were noted only in adulthood and the mean age of those with basal cell carcinoma was significantly older than that of trichoblastoma (P = 0.028). Our study concludes that malignant transformation is rare in nevus sebaceus and occurs uniquely in adulthood. On the basis of the findings, prophylactic excision of nevus sebaceus can be elective during childhood but is strongly advocated at puberty due to the increased risk of malignant transformation with time.

R26R-GR : A Cre-Activable Dual Fluorescent Protein Reporter Mouse

Green fluorescent protein (GFP) and its derivatives are the most widely used molecular reporters for live cell imagining. The development of organelle-specific fusion fluorescent proteins improves the labeling resolution to a higher level. Here we generate a R26 dual fluorescent protein reporter mouse, activated by Cre-mediated DNA recombination, labeling target cells with a chromatin-specific enhanced green fluorescence protein (EGFP) and a plasma membrane-anchored monomeric cherry fluorescent protein (mCherry). This dual labeling allows the visualization of mitotic events, cell shapes and intracellular vesicle behaviors. We expect this reporter mouse to have a wide application in developmental biology studies, transplantation experiments as well as cancer/stem cell lineage tracing.

Frequent PIK3CA-activating mutations in hidradenoma papilliferums

Hidradenoma papilliferum (HP) is a benign epithelial tumor most commonly seen in the vulva. It is proposed to be derived from the anogenital mammary-like glands and is histologically very similar to the mammary intraductal papilloma (IP). Approximately 60% of mammary IPs have activating mutations in either PIK3CA or AKT1, with each gene accounting for 30% of cases. In this study, we screened the mutation statuses of PIK3CA, AKT1, RAS, and BRAF in 30 HPs. The results showed that activating mutations in either PIK3CA or AKT1 were identified in 20 tumors (67%); 19 tumors had PIK3CA mutations (63%; 13 in exon 20 and 6 in exon 9), and 1 had an AKT1 E17K mutation (3%). BRAF V600E mutation was found in an HP that also had a PIK3CA H1047R mutation. No RAS mutation was found. The mutation status was not correlated with the degree of epithelial cell hyperplasia. We conclude that although there might be site-related variations in the mutation frequencies of PIK3CA and AKT1 genes, HP is histologically and also genetically very similar to the mammary IP, suggesting that HP can be viewed as the extramammary counterpart of mammary IP.

Genetic analysis of CARD14 in non-familial pityriasis rubra pilaris: a case series.

© 2014 The Authors. doi: 10.2340/00015555-1814 Journal Compilation

Scleromyxedema with myopathy was successfully treated by thalidomide

Editor Scleromyxedema is characterized by widespread, closely spaced papules with a predilection on the face, trunk and upper extremities. Histopathologically, deposit of mucin in the upper dermis and marked fibroblast proliferation are found.1 Although myopathy has been reported in association with scleromyxedema, mucinous deposits in muscle was rare.1 We report a case of scleromyxedema with mucin deposition in skeletal muscles. The skin lesions dramatically improved after 10 months of thalidomide use. A 64-year-old man visited our department with numerous pruritic eruptions on his face, trunk and all extremities for 3 years. He also had proximal muscle weakness in lower extremities for 2 years. He did not have constitutional symptoms. Examination showed widespread, firm, 5 to 10 mm, closely spaced, linearly distributed, skin-coloured papules on the neck, chest, upper back, bilateral upper limbs and thighs (Fig. 1a). There were ill-defined diffuse subcutaneous indurations on the face, trunk and especially the distal portion of extremities. Laboratory examinations including complete blood count, thyroid function tests, creatinine kinase and autoimmune profiles were all within normal ranges. Elevated interleukin-6 (IL-6; 28.9 pg/mL, normal < 9.7), serum aspartate aminotransferase (69 IU/L, normal < 37), alanine aminotransferase (48 IU/L, normal < 41) and the presence of antihepatitis C virus antibodies were noted. Serum immunofixation showed no monoclonal gammopathy. Electromyography showed myopathic polyphasic waves in biceps and rectus femoris. Nerve conduction velocity test suggested bilateral median entrapment neuropathy at the wrists. Skin biopsies from the papules on the left forearm and the sclerodermoid indurations on the left 4th finger both revealed dermal fibrosis with fibroblasts proliferation. Mucin deposition in the upper and middle dermis was shown under Alcian blue stain at pH 2.5 (Fig. 1b). Muscle biopsy from right biceps showed scattered degenerated and atrophic fibres without inflammation. Alcian blue stain showed the presence of mucin between muscle fascicles (Fig. 1d). Under the impression of scleromyxedema, the patient received thalidomide 100 mg/day for 2 months. The indurations and pruritus were improved. Thalidomide was increased to 150 mg/day for another 5 months. Due to unstable gait and dizziness, we adjusted the dose to 100 mg/day for 1 month and increased to 200 mg/day after the side effect subsided. After 10 months of treatment, the indurations became softened, and nearly all of the papules became flattened (Fig. 1c). However, the muscle power has not completely recovered. Several systemic manifestations of scleromyxedema have been reported. Paraproteinemia is associated with 83.2% patients of scleromyxedema, and most are associated with IgG-λ light chain.1 Twenty-seven per cent of the patients have skeletal muscle involvement and usually presents as proximal muscle weakness.1 Muscle enzyme may be normal or elevated.2 Muscle biopsy showed non-specific vacuolar myopathy with no or slight muscle atrophy and interstitial inflammation.2 However, mucin deposition has been found in only two patients.1 To our knowledge, our patient is the 3rd case of scleromyxedema showing mucin