Refractory Kasabach–Merritt phenomenon successfully treated with sirolimus,and a mini‐review of the published work

Kasabach–Merritt phenomenon (KMP) is a rare and life‐threatening disease involving a vascular tumor combined with severe consumptive coagulopathy. We present for the first time a case of KMP with the vascular tumor involving two anatomical sites; the patient failed to respond to steroids and vincristine. Following sirolimus therapy at a dose of 0.8 mg/m² twice daily, the lesions shrank and the platelet count improved and remained normal 4 months after initial therapy. Current treatments for KMP are not particularly effective. Sirolimus at 0.8 mg/m² per dose, administrated twice daily, appears to be a safe and effective management option. It appears to be an interesting therapeutic option in refractory KMP, but the time to response is variable.     

Successful combination therapy of propranolol and prednisolone for a case with congenital Kasabach–Merritt syndrome

A male fetus was delivered by cesarean section with a large hemangioma on his right chest and thrombocytopenia. Clinically, Kasabach–Merritt syndrome (KMS) was suspected, and immediately he was treated with daily prednisolone (PSL) 1 mg/kg and recombinant thrombomodulin without response. Additional propranolol (1–3 mg/kg per day) and increased PSL 2 mg/kg per day therapy successfully controlled his disseminated intravascular coagulation and decreased the tumor size without serious side‐effects. No relapse of KMS was observed after cease of PSL and propranolol. Combined use of propranolol and corticosteroid is expected as a candidate therapeutic tool for KMS.     

Ultrasonography and magnetic resonance imaging features of kaposiform hemangioendothelioma and tufted angioma

Kaposiform hemangioendothelioma (KHE) and tufted angioma (TA) primarily occurring in infants are difficult to distinguish. This study evaluated ultrasonography (US) and magnetic resonance imaging (MRI) features of KHE and TA. Pathologically proven TA (n = 21) and KHE (n = 40 [11 KHE + Kasabach–Merritt phenomenon [KMP]]) occurring between January 2015 and December 2017 were reviewed. US (n = 61) and MRI (n = 50) findings were retrospectively evaluated. On US, KHE and TA lesions were subcutaneous, while 40% of KHE exhibited an infiltrative pattern extending into adjacent muscles. Of TA lesions, 42.9% were hyperechoic and 96.15% of KHE lesions exhibited mixed echogenicity. Of TA lesions, 76.2% exhibited well‐defined margins and all KHE lesions exhibited ill‐defined margins. The depth and vascular density of KHE and KHE + KMP were significantly increased compared with TA. The arterial peak systolic blood flow velocity of KHE + KMP was significantly higher than that in TA and KHE. KHE and KHE + KMP were significantly harder than TA on elastography. 3‐D color Doppler revealed branch‐shape blood flow for KHE and KHE + KMP lesions; for TA, it revealed a dot‐like and striped pattern. Considering MRI findings, KHE and KHE + KMP were more likely to exhibit diffuse heterogeneous enhancement after contrast than TA. KHE was infiltrative and more likely to be thick, hypoechoic, ill‐defined, richly vascular and hard than TA on US. KHE lesions were subcutaneous and reticular, with heterogeneous enhancement on MRI. Awareness of these features should prompt radiologists in the differential diagnosis of pediatric masses.     

Fluorofenidone inhibits UV‐A induced senescence in human dermal fibroblasts via the mammalian target of rapamycin‐dependent SIRT1 pathway

The aim of this study was to investigate the protective effect of fluorofenidone (5‐methyl‐1‐[3‐fluorophenyl]‐2‐[1H]‐pyridone, AKF‐PD) on ultraviolet (UV)‐A‐induced senescence in human dermal fibroblasts (HDF) and examine the mechanisms involved. HDF were treated with AKF‐PD. Senescence‐associated (SA)‐β‐galactosidase level, cell viability and expression of p16 were evaluated. In addition, UV‐A‐irradiated HDF were treated with AKF‐PD, rapamycin and MHY1485; SA‐β‐galactosidase staining, 3‐(4 5‐dimethylthiazol‐2‐yl)‐2 5‐diphenyltetrazolium bromide assay and western blot for SIRT1 were performed; and phosphorylated mammalian target of rapamycin (p‐mTOR) expression and reactive oxygen species (ROS) levels were measured. Intracellular ROS was detected by the 2′,7′‐dichlorofluroescein diacetate probe. Our results showed that AKF‐PD substantially attenuated the changes of p16 expression, SA‐β‐galactosidase staining and cellular proliferation induced by UV‐A irradiation in HDF. AKF‐PD rescued the increased mTOR phosphorylation and reduced SIRT1 expression induced by UV‐A irradiation in HDF. AKF‐PD and rapamycin together had a synergistic effect on p‐mTOR reduction and SIRT1 increase. mTOR activator MHY1485 partly blocked the above effects. Moreover, intracellular ROS level induced by UV‐A irradiation could partly decrease by AKF‐PD, and MHY1485 could reduce this effect. Our results indicated that AKF‐PD could alleviate HDF senescence induced by UV‐A‐irradiation by inhibiting the p‐mTOR and increasing SIRT1. Moreover, AKF‐PD may be a potential treatment material for skin.     

Synergism between mTOR pathway and ultraviolet radiation in the pathogenesis of squamous cell carcinoma and its implication for solid‐organ transplant recipients

Nonmelanoma skin cancers (NMSCs) are the most common malignancies in the United States in immunocompetent patients. Among the solid‐organ transplant recipients, NMSCs represent a significant disease burden, and they tend to be multiple and more aggressive. While the precise mechanisms responsible for the higher risk of developing cutaneous squamous cell carcinomas (SCCs) have not been completely elucidated, ultraviolet (UV) light has been established to be critical in initiation and promotion of tumor development. More recently, significant emphasis has been placed on the role of the mammalian target of rapamycin (mTOR) pathway in SCC pathogenesis. Furthermore, some studies have demonstrated the ability of mTOR inhibitors to decrease the incidence of new SCCs in the immunosuppressed transplanted patient population. In this review, we will highlight and examine the most recent available data on the role of UV radiation and its interaction with mTOR pathway signaling in SCC pathogenesis.     

Sparing of the nipple‐areola complex by capillary malformations: Vascular variant of the Bork–Baykal phenomenon

The“Bork‐Baykal phenomenon” refers to the sparing of the nipple‐areola complex in large congenital melanocytic nevi involving the breast. So far, this finding has not been reported in vascular anomalies. We present four patients with an extensive capillary malformation (CM) involving the breast that was found to exhibit a similar sparing of the nipple and areola. All of these capillary nevi were associated with asymmetric overgrowth.     

Consensus guidelines for the management of atopic dermatitis: An Asia–Pacific perspective

Atopic dermatitis (AD) is a relatively common disease in patients in the Asia–Pacific region. It presents a particular clinical challenge and requires careful clinical management. The chronic nature of AD characterized by flares, exacerbations and periods of quiescence requires a multipronged approach aimed at reducing itch, inflammation and the appearance of secondary lesions. In addition, varying levels of maintenance therapy may be required to avoid exacerbations. Survey data from the region indicate that there is significant variation across the Asia–Pacific with regard to current treatment practices. The management of AD may also be influenced by differing health‐care systems, variable climate, access to medical care and cultural diversity. The current consensus guidelines have been developed to provide up‐to‐date and concise evidence‐ and experience‐based recommendations directed towards general practitioners and general dermatologists in the Asia–Pacific region on the management of pediatric and adult AD.     

Successful treatment with narrow‐band UVB therapy for a case of generalized Hailey–Hailey disease with a novel splice‐site mutation in ATP2C1 gene

Hailey–Hailey disease (HHD) is a rare autosomal dominant disorder characterized by development of recurrent blisters, erosions, and crustations in the intertriginous areas. The treatment of HHD is often challenging, and various methods have been tried. We report here a case of a 45‐year‐old woman with a generalized form of HHD that was dramatically improved and well controlled by narrow‐band ultraviolet B phototherapy.     

Characterization of skin blister fluids from children with Epstein–Barr virus‐associated lymphoproliferative disease

Epstein–Barr virus (EBV)‐associated T‐ or natural killer (NK)‐cell lymphoproliferative disease (LPD) is a heterogeneous group of disorders characterized by chronic proliferation of EBV‐infected lymphocytes. Patients may present with severe skin manifestations, including hypersensitivity to mosquito bites (HMB) and hydroa vacciniforme (HV)‐like eruption, which are characterized by blister formation and necrotic ulceration. Skin biopsy specimens show inflammatory reactions comprising EBV‐infected lymphocytes. However, blister fluids have not been fully assessed in patients with this disease. Blister fluids were collected from three patients with EBV‐associated LPD: two with HMB and one with HV. Immunophenotyping of blister lymphocytes and measurement of tumor necrosis factor (TNF)‐α in blister fluids were performed. The patients with HMB and HV exhibited markedly increased percentages of NK and γδ T cells, respectively, in both peripheral blood and blister fluids. These NK and γδ T cells strongly expressed the activation marker human leukocyte antigen‐DR and were considered to be cellular targets of EBV infections. TNF‐α was highly elevated in all blister fluids. Severe local skin reactions of EBV‐associated LPD may be associated with infiltrating EBV‐infected lymphocytes and a high TNF‐α concentration in blister fluids.     

Histological evaluation of dermal tissue remodeling with the 1444‐nm neodymium:yttrium–aluminum–garnet laser in in vivo model

Laser lipolysis has a skin tightening effect by heating the deep dermis, in addition to the removal of fat tissues. The 1444‐nm neodymium:yttrium–aluminum–garnet (Nd:YAG) laser has been expected to be more effective and safe for laser lipolysis, due to higher affinity to fat and water, than 1064‐nm and 1320‐nm wavelengths. The purpose of this study was to evaluate the skin tightening effect of the 1444‐nm Nd:YAG laser through in vivo guinea pig models. The 1444‐nm Nd:YAG laser was used to irradiate shaved dorsal skin of the guinea pigs and compared with controls (no power, only tunneling). Immediately, 1 week, 1 month and 3 months after laser administration, full‐thickness skins were harvested and to evaluate dermal thickness, collagen organization, fibroblast proliferation, and intensity of elastic fibers and mucopolysaccharides, using hematoxylin–eosin, Masson‐trichrome, Verhoeff's stain and Alcian blue stain. Dermal thickness showed an increase with time in all groups. In collagen organization, fibroblast proliferation, and intensity of elastic fibers and mucopolysaccharides, the treatment groups were higher than those of the control group, overall. Our study showed that the 1444‐nm Nd:YAG laser appeared to be effective for the skin tightening effect in in vivo guinea pig models. The 1444‐nm Nd:YAG laser can be used for skin tightening, as well as reduction of fat tissues.     

Epstein–Barr virus involvement in the pathogenesis of hydroa vacciniforme: an assessment of seven adult patients with long‐term follow‐up

Background Hydroa vacciniforme (HV) is a chronic papulovesicular photodermatosis of childhood, with some cases persisting through adulthood. In children, the Epstein–Barr virus (EBV) has been detected in typical HV and in HV evolving into natural killer/T‐cell lymphoma. No exploration of EBV infection has been performed in adult patients with HV with long‐term follow‐up. Objectives To assess EBV infection systematically in blood and in experimentally photoinduced lesions in adult patients with HV. Methods Repeated tests for EBV DNA blood load using real‐time polymerase chain reaction (PCR) and serological EBV tests were performed in seven adult patients with long‐term follow‐up. Skin samples from phototest‐induced lesions and surrounding normal skin were studied using PCR, in situ hybridization and electron microscopy. ZEBRA protein was detected using immunostaining. Thirty‐five patients with other photosensitive disorders were included as controls. Results The EBV DNA blood load was strongly positive in the seven patients with HV and negative in 34 of 35 of the patients with other photosensitive disorders (P < 0·001). The levels were higher in photosensitive patients with HV than in patients with HV in clinical remission. Ultrastructurally, viral particles were detected in lymphocytes and also in keratinocytes in three experimentally phototest‐induced lesions; they were not found in the surrounding normal skin. ZEBRA protein was also detected in phototest‐induced lesions, but not in the surrounding normal skin. Conclusion EBV is involved in HV pathogenesis and persists in adult patients with HV. A positive EBV DNA load, specific to HV in the spectrum of photosensitive disorders, might be a useful biomarker in HV.     

Review of the current medical literature and assessment of current utilization patterns regarding mismatch repair protein immunohistochemistry in cutaneous Muir–Torre syndrome‐associated neoplasms

Muir–Torre syndrome is a clinical variant of Lynch syndrome defined by the synchronous or metachronous occurrence of at least one sebaceous neoplasm and at least one Lynch syndrome‐related internal cancer. Although screening guidelines for patients with colorectal carcinomas have been established, screening guidelines for cutaneous Muir–Torre associated neoplasms are not currently available. As such, we reviewed the current evidence for the use of MLH1, MSH2, MSH6 and PMS2 immunohistochemistry when cutaneous Muir–Torre associated neoplasms are encountered. We identified weak to moderate support overall for the global use of these assays, with some evidence suggesting a tailored approach using clinical parameters as an adjunct. We also assessed the current utilization patterns of attendees of the American Society of Dermatopathology Annual Meeting (Chicago, 2016). We found that 91% of respondents utilize mismatch repair immunohistochemistry, with the majority utilizing these tests only when requested by the submitting clinician.     

Induction of melasma by 1064‐nm Q‐switched neodymium:yttrium–aluminum–garnet laser therapy for acquired bilateral nevus of Ota‐like macules (Hori nevus): A study on related factors in the Chinese population

Laser treatment has emerged as a common treatment modality for acquired bilateral nevus of Ota‐like macules (ABNOM). To identify the ratio of melasma induction and exacerbation before and after laser therapy for ABNOM and to observe the risk factors related to the induction and exacerbation of melasma by laser therapy, we analyzed related factors of 1268 adult Chinese patients who underwent 1064‐nm Q‐switched neodymium:yttrium–aluminum–garnet (Nd:YAG) laser (QNYL) treatment using case series and case–control studies. Overall, 24.0% of the ABNOM patients had mixed melasma. Among the ABNOM patients without melasma, after laser therapy the development of melasma was more frequently noted in patients older than 35 years (P < 0.0001), as well in patients whose ABNOM was less than 10 cm² (P = 0.027), ABNOM were light (similar to yellow‐brown) in color (P = 0.021) and skin types were closer to type IV (P < 0.0001). New melasma lesions also appeared most frequently in the zygomatic region (P < 0.0001). Among the ABNOM patients with melasma, 89.5% experienced worsening of their melasma, irrespective of their related factors above. We concluded that the risk of inducing melasma is great after 1064‐nm QNYL treatment in ABNOM patients, and particularly in the patients with both ABNOM and melasma. ABNOM patients should be treated as early as possible and before the age of 35 years.     

Antimicrobial susceptibility of Staphylococcus aureus isolated from children with impetigo in China from 2003 to 2007 shows community‐associated methicillin‐resistant Staphylococcus aureus to be uncommon and heterogeneous

Background The number of patients with impetigo caused by community‐associated methicillin‐resistant Staphylococcus aureus (CA‐MRSA) has been increasing. Objectives To investigate the antimicrobial susceptibility of S. aureus causing impetigo in children in China from 2003 to 2007 and further characterize isolates of CA‐MRSA. Materials and methods We examined 984 S. aureus isolates for antimicrobial susceptibility to 11 antimicrobials using the agar dilution method. CA‐MRSA isolates were analysed for Panton–Valentine leucocidin (PVL) genes, and staphylococcal cassette chromosome mec (SCCmec) typing was performed. Results The largest proportion (94·5%) of strains were resistant to penicillin, followed by erythromycin (86·2%) and clindamycin (69·6%). In total 772 of 984 (78·5%) S. aureus strains were multiresistant. The incidence of CA‐MRSA was 1·1%, with a high rate of resistance to clindamycin (90·9%) and tetracycline (72·7%), but all were susceptible to ciprofloxacin. The susceptibility profiles of MRSA to other antimicrobial agents were similar to those of methicillin‐sensitive S. aureus (MSSA). None of the S. aureus strains were resistant to vancomycin and fusidic acid; moreover, only one strain was resistant to mupirocin. Typing of the SCCmec showed that 54·5% were type IV, 18·2% were type V and 9·1% were type VI. All the PVL‐positive CA‐MRSA carried SCCmec type IV. Conclusions CA‐MRSA is still relatively uncommon and heterogeneous in children in China. Penicillin and erythromycin are no longer appropriate agents. Effective antibiotic agents for patients with impetigo are mupirocin and fusidic acid.     

Instrumental analysis of the pattern of improvement and that of recurrence of melasma in Thai females treated with Kligman–Willis triple combination therapy: confirmation by using its two different formulae

Background: Melasma is common among females. At present, its most reliable topical treatment is the Kligman–Willis formula. Objectives: To evaluate objectively the pattern of pigmentation improvement and recurrence. Methods: Thirty‐four Thai females with melasma showing similar lesions on both cheeks were randomly assigned to 8‐week daily treatment with either one of two different versions of the formula together with strict sun protection. They were objectively evaluated instrumentally with a Mexameter^® every 2 weeks, and were followed up for the subsequent 40 weeks. Results: Thirty of 34 subjects who completed their 8‐week treatment displayed a similar improvement pattern with either formulae. All expressed satisfaction with the results of the treatment. Instrumental evaluation detected that the pigmentation reached a nadir after 6 weeks, regardless of the formulae. Twenty‐one subjects, who were further followed up, exhibited mild relapse within 2 months after finishing the treatment. Yet, their pigmentation levels remained significantly lower than those before treatment. Both formulae increased transepidermal water loss and skin surface hydration during the treatment period. Conclusion: Melasma in Thai females responded well to the Kligman–Willis formula. A relapse that was detected with the instrumental measurement after treatment discontinuation suggests the necessity to continue even intermittent treatment after attaining therapeutic success.     

A cross‐sectional study using the Children’s Dermatology Life Quality Index (CDLQI) in childhood psoriasis: negative effect on quality of life and moderate correlation of CDLQI with severity scores

Background Juvenile psoriasis is a chronic and incurable skin disease that affects approximately 0·7% of children. Objectives To achieve more insight into the quality of life (QoL) in childhood psoriasis and to investigate whether disease severity scores correlate with QoL scores. Methods All consecutive patients with juvenile plaque psoriasis (≤ 18 years old) who visited our outpatient department were included. At baseline, the Children’s Dermatology Life Quality Index (CDLQI) questionnaire was completed and disease severity was assessed by the Psoriasis Area and Severity Index (PASI) and the Physician Global Assessment (PGA). Results Thirty‐nine patients were included in the study. A median CDLQI of 6 [interquartile range (IQR) 5–9] was reported. Median PASI was 6·3 (IQR 3·3–8·2) and median PGA was 2 (IQR 1–3). The correlation coefficient between PASI and CDLQI was 0·47 (P = 0·003), whereas the correlation coefficient between PGA and CDLQI was 0·51 (P = 0·001). Conclusions The negative effect on QoL in juvenile psoriasis was confirmed in the largest cohort presented up to now. The correlation between disease severity scores and disease‐related QoL in children with psoriasis is only moderate. Therefore, both clinical outcome parameters (PASI, PGA) and measures of QoL (CDLQI) should be included in adequate, patient‐oriented clinical decision making.