Identification of two novel mutations in the PLCD1 gene in Chinese patients with hereditary leukonychia.

Hereditary leukonychia (HL) is a rare nail dystrophy disease, and several different clinical manifestations and mutations in the phospholipase C δ 1 (PLCD1) gene have been reported. The present study reports on one Chinese family and one sporadic case of with HL. The family members exhibited an autosomal dominant pattern of inheritance with the involvement of all the fingers and toenails in all the patients. Of interest, most of the affected members had koilonychia during their childhood. Thus, the present study first used gene mapping with an aim to identify the pathogenic gene underlying koilonychia. Through genome­wide linkage analysis, the pathogenic area of koilonychia was identified on chromosome 3 with multipoint Log of Odds scores >2. A novel pathogenic mutation c.1384G>A (p.E462K) was identified in the PLCD1 gene in all the patients in the family, which confirmed the diagnosis of hereditary leukonychia. A novel mutation c.770G>A (p.R257H) was also detected in one sporadic case of leukonychia. On the basis of these findings and of previous studies, it is suggested that hereditary leukonychia may initially present as koilonychia, whereas hereditary koilonychia does not progress to leukonychia. Moreover, the present study identified two pathogenic variants of the PLCD1 associated with hereditary leukonychia, and highlights the significance of genetic diagnosis.

Photodynamic therapy as an alternative treatment in patients with invasive cutaneous SCC where surgery is not feasible: Single center experience.

The aim of this study was to demonstrate the efficacy of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) as an alternative treatment in cutaneous squamous cell carcinoma (cSCC) patients who are not fit for surgery. Thirty-three invasive cSCC patients who, for some reasons, cannot undergo surgery were enrolled in this study. All patients received plum blossom needle (PBN) pretreated ALA-PDT combined with topical application of 5% imiquimod cream. Two patients dropped the study because of severe pain and two patients discontinue treatment due to lack of response. Of 29 patients, who completed the treatment, 5 patients had complete response after 2-9 sessions of PDT and these patients had no recurrence till 18 months after treatment. Twenty-four patients achieved partial response and are satisfied with treatment outcome in terms of decreased symptoms and improved quality of life. PBN pretreated PDT in combination with topical imiquimod may be a viable treatment option for non resectable cSCC lesions.

Present and future perspectives of photodynamic therapy for cutaneous squamous cell carcinoma.

Cutaneous squamous cell carcinoma (SCC) is the second most common skin cancer. Surgery remains the main stay of treatment, but some patients are not eligible for surgery and, more importantly, lesions at critical sites need nonsurgical approaches for tissue preservation. In this context, photodynamic therapy (PDT) has been extensively studied as noninvasive or minimally invasive treatment, and studies have shown promising results in terms of safety, efficacy, and cosmetic outcome. Also, studies have proposed different mechanism for its efficacy. However, human studies demonstrating its efficacy are limited in terms of sample size and tumor depth of invasion. Good results are mainly seen in case reports of microinvasive SCC, which is defined as SCC limited to papillary dermis. This inadequacy is due to inadequate penetration of topically applied photosensitizers through keratinized tumor surfaces. To overcome these hurdles, pretreatment with lasers or microneedles and encapsulation of photosensitizers into nanoparticles have been tried. Hence, the present article will discuss studies that have demonstrated the efficacy and safety of PDT for cutaneous SCC, studies that have postulated the mechanism of action of PDT, agents that have been used as PDT enhancers, and finally, the recent use of adjuvant therapy in combination with PDT.

Therapeutic effect of Imiquimod enhanced ALA-PDT on cutaneous squamous cell carcinoma.

BACKGROUND: Topical photodynamic therapy (PDT) is approved treatment for actinic keratosis, basal cell carcinoma and Bowen's disease. But currently it is not recommended for invasive squamous cell carcinoma (SCC) of the skin because inadequate penetration of topically applied photosensitizers lead to poor treatment response. Imiquimod (IMQ) as an immune response modifier and Toll-like receptor 7 (TLR7) agonist, is known to exhibit antitumor activity. As an adjunct therapy, it is recently seen to enhance the effect of PDT. METHOD: This is an in vivo experiment performed on 52 SCC implanted mice model. The mice were equally divided into four groups: IMQ group, IMQ + PDT group, PDT group and control group. The mice in IMQ + PDT group were treated with 3 sessions of 5% IMQ cream and ALA-PDT. Mice in IMQ group received only 5% IMQ cream. Similarly, mice in PDT group received only ALA-PDT and control mice received no treatment. The treatment efficacy was compared among these groups via tumor volume and digital photographs. In addition, immunohistochemical (IHC) markers, q PCR and detection of apoptosis were studied on 12 UV induced mice model. After successful result of this animal experiment, we performed human study on two patients with invasive cSCC on lips and foot. The patients were treated with daily application of 5% imiquimod cream and ALA-PDT at 2 weeks interval. Treatment response was assessed via clinical examination, digital photographs and dermoscopy findings. RESULTS: The study demonstrated that combination approach of IMQ + PDT has better effect than IMQ alone or PDT alone. It also showed increased expression of IL-6, IL-8, IFN-α, CXCL9, CXCL10 and TNF-α in IMQ + PDT group but at different time points following treatment (P < 0.05). IHC staining showed that the number of CD4+ cells was similar in IMQ + PDT and PDT groups but CD8+ cells was almost double in IMQ + PDT group when compared to PDT group. In addition, the number of apoptotic cell was maximum in IMQ + PDT group. Human study also delivered excellent results in both the patients with complete clearance of lesion after 3-6 sessions of treatment. CONCLUSION: PDT combined with imiquimod may have enhanced effect for the treatment of invasive cSCC. Maximum number of apoptotic cells in IMQ + PDT group can be attributed to increased number of CD8 + T cells in this group. Additional mechanism of enhanced efficacy in IMQ + PDT group may be due to increased expression of markers tested in this study.

Vertikale Übertragung des Herpes-simplex-Virus: eine Aktualisierung.

Infektionen mit den Herpes-simplex-Viren (HSV)-1 und -2 haben weltweit eine hohe Prävalenz. Eine HSV-Infektion während der Schwangerschaft kann eine neonatale Herpes-Infektion verursachen, die durch eine lebenslange Infektion mit Latenz- und Reaktivierungsperioden gekennzeichnet ist. Ein Säugling kann sich in utero (5 %), peripartal (85 %) oder postnatal (10 %) mit dem HS-Virus infizieren. Herpes neonatorum ist eine seltene aber bedeutsame Infektion, die mit schwerer Morbidität und Mortalität assoziiert sein kann, insbesondere bei Dissemination oder Beteiligung des zentralen Nervensystems. Fortschritte bei Diagnose und Therapie haben zur Verringerung der Mortalität sowie, in geringerem Ausmaß, zu einem verbesserten neurologischen Outcome geführt. Dennoch sind weitere Verbesserungen wünschenswert. Dabei ist es entscheidend, Ärzte in die Lage zu versetzen, diejenigen Säuglinge, die einem erhöhten Risiko einer HSV-Infektion ausgesetzt sind, zu erkennen und die Mutter-Kind-Übertragung effektiver zu verhindern. Ein lohnendes Ziel für die Zukunft ist die Entwicklung neuer antiviraler Wirkstoffe mit höherer Wirksamkeit.

Dermatologic manifestations of inflammatory bowel disease: a review.

Inflammatory bowel disease (IBD) is a chronic relapsing disease of the gastrointestinal tract with unknown etiology and pathogenesis. It includes Crohn's disease (CD) and ulcerative colitis (UC). Approximately one-third of the patients with IBD are seen to develop extraintestinal manifestations, among which cutaneous manifestations are the most common and should be managed in close collaboration with a dermatologist. Depending upon the nature of the association, skin conditions associated with IBD can be listed under 4 categories: specific, reactive, secondary to malnutrition or malabsorption, and secondary to drug therapy. Skin conditions that do not fit into these categories are listed under the fifth category named as miscellaneous by some authors. The aim of the present review is to discuss some of the noteworthy skin disorders associated with IBD and highlight their importance in context to IBD.

Zinc pthalocyanine-loaded chitosan/mPEG-PLA nanoparticles-mediated photodynamic therapy for the treatment of cutaneous squamous cell carcinoma.

Zinc pthalocyanine (ZnPc) is a second-generation photodynamic therapy (PDT) sensitizer with sufficient PDT activity for squamous cell carcinoma (SCC). ZnPc is hydrophobic and insoluble in water, which creates hurdles in systemic administration and hence restricts its use in clinic. Here we have loaded ZnPc on chitosan/methoxy polyethylene glycol-polylactic acid (CPP) nanoparticles to form Z-CPP to enhance PDT efficacy. In vitro and in vivo studies were performed to see dark toxicity of the compounds ZnPc, CPP and Z-CPP. Then PDT was done and its growth inhibitory effect on SCC cells was evaluated. In addition, reactive oxygen species (ROS) formation and apoptosis of cancer cells following PDT were studied. The results showed that the tested compounds exhibit no dark toxicity and the effect of PDT was significantly better with Z-CPP when compared to free ZnPc (P < .05). Photoactivation of Z-CPP led to a dose-dependent growth inhibition of cancer cells of >50% at 1 µM to >80% at 10 µM concentration. Also Z-CPP-treated cells had highest number of apoptotic cells and produced more ROS compared to free ZnPc-treated cells (P < .05). Hence, this study suggests that Z-CPP is a suitable pharmaceutical compound to increase PDT efficacy.

Vertical transmission of herpes simplex virus: an update.

Herpes simplex virus (HSV)-1 and -2 infections are highly prevalent worldwide. HSV infection during pregnancy can result in neonatal herpes infection, which is characterized by lifelong infection with periods of latency and reactivation. HSV can be acquired by an infant during one of three periods: in utero (5 %), peripartum (85 %), or postnatal (10 %). Neonatal HSV is a rare but significant infection that may be associated with severe morbidity and mortality, especially if there is dissemination or central nervous system involvement. Diagnostic and therapeutic advances have led to a reduction in mortality and, to a lesser extent, improvement of neurodevelopmental outcomes, but further developments are still needed. It is essential to improve the clinician's ability to identify infants who are at increased risk of HSV infection and to prevent mother-to-child transmission. The development of novel antiviral agents with higher efficacy is a worthwhile aim for the future.

ALA-PDT as palliative care in a patient with secondary perineum EMPD.

Extramammary Paget's disease (EMPD) is a rare intraepithelial neoplasm arising in apocrine rich area of the skin. It is divided into primary and secondary EMPD based on whether there is an underlying malignancy, either local apocrine cancers or distant neoplasms. Therefore, all patients with EMPD should undergo an extensive and targeted cancer workup, depending on the histological staining pattern and the location. Surgical removal is considered the mainstay of treatment for patients with EMPD. Herein, we present a case of secondary EMPD where photodynamic therapy was effective in terms of improving symptoms and quality of life. Owing to preexisting comorbid conditions, large area of disease and risk of post-surgery mutilation and functional impairment, surgery could not be elected for this patient, necessitating nonsurgical approach.

Application of high frequency ultrasound in dermatology.

High frequency ultrasound (HFUS) refers to the ultrasound probe frequency of more than 10 MHz. HFUS has shorter wavelengths, is absorbed more easily, and is therefore not as penetrating. This explains its use for superficial structures and hence its increasing application in the field of dermatology. HFUS is a simple, reliable, and noninvasive technique that is being used along with the physical examination for the assessment, diagnosis, and management of many dermatologic conditions. In addition, it can also be used for the evaluation of normal skin structure. In the present article, we aim to describe the basic principles of cutaneous ultrasound, imaging findings of normal skin, and current applications of HFUS in the diagnosis, treatment, and follow-up of various dermatologic conditions.

UVA1 a promising approach for scleroderma.

Scleroderma is a complex connective tissue disease characterized by fibrosis, vasculopathy, and immune system dysfunction. The heterogeneity of disease presentation and poorly understood etiology has made the management of scleroderma difficult. The available treatment options like immunosuppressive agents are associated with potentially hazardous side effects and physiotherapy, which to a certain degree helps to minimize the loss of function in digits and limbs, has only limited success. Also, studies investigating antifibrotic therapies have failed to report any significant improvement. Hence, there is currently no effective therapy for scleroderma. Recently, phototherapy has been extensively studied and found to be effective in treating scleroderma. Initially psoralen + ultraviolet A (PUVA) significantly enriched the therapeutic panel, but more recently ultraviolet A1 (UVA1) is seen to replace PUVA therapy. This might be because of UVA1 therapy being free of side effects seen with psoralens such as nausea, vomiting or photokeratitis. In addition, UVA1 is seen to lower risk of phototoxic reactions with deeper penetration of radiation. The present review will put some light on the use of UVA1 for treating cutaneous lesion in scleroderma and we aim to find the most benefitted group of patients and most effective dose of UVA1 for different types of scleroderma.

Pemphigus vulgaris induced by 5-aminolaevulinic acid-based photodynamic therapy.

Pemphigus vulgaris (PV) is an autoimmune disorder resulting from the interaction between autoantibodies and desmoglein. Here, we report a case of PV developed after 5-aminolaevulinic acid-based photodynamic therapy (ALA-PDT). The harmful and deleterious effects of UV radiation on the onset, during course, and perpetuation of PV have been observed for decades. Correlation between reactive oxygen species (ROS) and PV have also been reported. Oxidative proteins, which are modified by ROS, and subsequent production of antibodies by immune system seem to be responsible for PV developed following ALA-PDT. We emphasize that ALA-PDT should be added to the list of possible factors triggering PV and this condition should be considered if blistering arises following ALA-PDT.

Erythema elevatum diutinum involving palms and soles: a case report and literature review.

Erythema elevatum diutinum (EED) is a rare chronic inflammatory dermatosis and a part of the spectrum of cutaneous leukocytoclasticvasculitis. The most common site of involvement is extensor surface of the extremities, with a predilection for the skin overlying joints, particularly hands, feet, elbows and knees, as well as buttocks and Achilles tendons. Here we report a case of EED with atypical presentation involving palms and soles. The patient showed dramatic response to the treatment with prednisolone combined with Tripterygium wilfordii glycoside (TWP). The lesions improved significantly after three months of therapy. We will also review the atypical cases of EED that were previously published in English literature.

Successful treatment of Rosai-Dorfman disease using in situ photoimmunotherapy.

Rosai-Dorfman disease is difficult to cure. In situ photoimmunotherapy combines local photothermal therapy with immunoadjuvant. In the present case report, a 39-year-old Chinese man with Rosai-Dorfman disease lesions below the left nostril and left preauricular region was treated with in situ photoimmunotherapy. The patient was treated with daily application of topical imiquimod (5%) and laser irradiations every 2 weeks for 8 weeks. After three cycles of treatment, the lesions improved markedly without adverse effects. Our results showed that in situ photoimmunotherapy can be used as an effective treatment for Rosai-Dorfman disease.

A review of the mechanism of action of lasers and photodynamic therapy for onychomycosis.

Onychomycosis is one of the most common diseases in the field of dermatology. It refers to the fungal infection of the nail plate or nail bed with high incidence in the general population. The available treatment options for onychomycosis have limited use due to side effects, drug interactions, and contraindications, which necessitates the application of an alternative treatment for onychomycosis. In the recent years, lasers and photodynamic therapy (PDT) have been recognized as alternative treatment options. Most of the previous studies have found them to be safe and effective treatment modalities in this indication; however, the results varied greatly and the in vitro and in vivo outcomes are contradictory. In the present review, studies related to the mechanism of action of lasers and PDT for the treatment of onychomycosis will be discussed, with a focus on to find explanation to the contradictory results.

Antifungal effect of plant extract and essential oil / 中国结合医学杂志

The advancement of phytochemical and phytopharmacological sciences has enabled elucidation of the composition and biological activities of several medicinal plant products including plant extract and essential oils. These products have been widely used around the world since ancient times for the treatment of various disorders such as diabetes, hypertension, peptic ulcer disease, microbial infection, sexual disorder and many more. Its popularity in the modern system of medicine is mainly due to their availability and fewer adverse reactions compared to synthetic drugs. Various scientifific investigations have been conducted to look for the potential of the extract from the plant or isolated compounds for the continued use of these products in the treatment and prevention of various kinds of human diseases. It is evident from the available literature and scientifific investigations that many plant species possess potential for use as a benefificial therapeutic remedy with multiple pharmacological actions such as analgesic, anti-inflflammatory, antipyretic, hypoglycemic, hypotensive, antimicrobial, antiulcer and anticonvulsant activities. The present review aims to provide relevant updated information about certain plant products, its composition, preparation and its fungicidal or fungistatic effects on different species of fungus as evaluated by studies done in the past. It introduces six medicinal plants that have been studied for their antifungal property and are found to be effective. The overall objective is to provide comprehensive information about the use of plant extract and essential oil for treating fungal infections and to explore the evidence supporting its effectiveness in treating fungal diseases without causing any serious adverse reactions.

Photodynamic therapy for onychomycosis: A systematic review.

Other than a cosmetic concern, Onychomycosis is also a prevalent nail disease, which is extremely difficult to treat, and sometimes is refractory to conventional therapy. Moreover, many patients are not eligible to take oral antifungals owing to polypharmacy and comorbidities. Systemic side effects seen with oral antifungals have lead to patient nonadherence and adverse events. Therefore, newer therapies are being investigated for onychomycosis that would be free of systemic complications posed by oral therapy. Photodynamic therapy (PDT) is one of those being currently studied, which involves the use of photosensitizer and a light source to excite the photosensitizer to generate reactive oxygen species. The present review will put some light on PDT as an upcoming treatment modality for onychomycosis. We performed a systematic review of the literature to find the articles relevant to the use of PDT for onychomycosis. From the primary search of 43 articles, 17 papers are included in this review.

Photodynamic therapy for the treatment of different severity of acne: A systematic review.

INTRODUCTION: Acne, a disease of pilosebaceous unit, is a common dermatologic disorder affecting about 80%-95% of people in both genders in adulthood. The available treatment options are conventional topical and/or oral medications, which are associated with adverse effects, partial response only, contraindications and reoccurrences. This necessitates the need for the introduction of novel treatment for improving acne lesions. OBJECTIVE: The aim of writing this review is to provide evidence-based information regarding safety and efficacy of PDT in treating acne lesions. METHOD: The search term 'Acne and PDT' were entered into a search of the National Library of Medicine's PubMed Database. The search returned a total of 143 sources among which 36 studies pertaining to the use of PDT in acne are included in this review article. RESULT: 36 clinical trials were selected among which 24 trials were performed to see the effect of PDT in acne whereas 12 trials compared the effect of PDT with light or laser alone therapy. Among 24 trials that used PDT only, 3 were clinical trials with control, 14 were clinical trials without control, 6 were randomized controlled trials (RCT) and 1 was retrospective study. On the basis of results of these trials, it is seen that PDT is safe and effective method of treatment for acne lesions. Studies have shown that PDT can control both inflammatory and non-inflammatory acne lesions and can improve all severity of lesions from mild to severe. CONCLUSION: Photodynamic therapy (PDT) has been extensively studied and found to be effective treatment modality for acne lesions. However, more RCTs are needed to establish standard guidelines regarding concentrations and incubation period of photosensitizers and optimal parameters of light sources. Further studies are needed to guide future research and help dermatologist to choose PDT as an effective treatment modality for treating acne lesions.