Cancer-associated genodermatoses: a personal history

Cancer-associated genodermatoses are a group of genetic disorders inherited in an autosomal-dominant fashion in which unique cutaneous findings are a reliable marker for the risk of developing internal malignancies. The historical, clinical and dermatopathological aspects of basal cell nevus syndrome, Muir-Torre syndrome, Cowden syndrome, Carney complex and Birt-Hogg-Dubé syndrome are reviewed in a personal and informal fashion. The latest advances in the molecular genetics of the disorders are also summarized.     

microRNA在炎症性皮肤病中作用的研究进展

【摘要】 microRNA（miRNA）是一类转录后调控基因表达的非编码RNA分子,参与皮肤各种病理生理过程。近年来,miRNA表达谱的变化已被报道与部分炎症性皮肤病相关,例如miR-203、miR-146a、miR-21在银屑病皮损中表达上调;miR-155、miR-146a在特应性皮炎皮损中表达上调;miR-21、miR-223、miR-142-3p、miR142-5p在过敏性接触性皮炎皮损表达上调;而miR-146a、miR-155在系统性红斑狼疮患者外周血表达下调;miR-223在皮肌炎皮损中表达下调等。本文综述miRNA与部分炎症性皮肤病发生、发展之间的联系。     

Safety and efficacy of vaccines

For the past two centuries, vaccines have provided a safe and effective means of preventing a number of infectious diseases. Although the safety of some vaccines has been questioned in recent years, the currently available vaccines are more than a millionfold safer than the diseases they are designed to prevent. Vaccines, however, should always be used in conjunction with other public health interventions. One important intervention is education because the general public can be led to believe that vaccines are unsafe and not needed by misinformation readily available electronically and in print. Not only are some vaccines available via injection but other vaccines are also given orally or intranasally. New vaccines are being studied for topical and intravaginal use. In addition, new systems are being developed for more efficient production of vaccines, especially for influenza. Vaccines are currently available for only a limited number of viral and bacterial diseases. In the future, it is anticipated that safe and effective vaccines will be developed against a number of other viral and bacterial infections as well as fungal and protozoan diseases.     

Idiopathic Multiple Eruptive Milia Occurred in Unusual Sites

Milia are small, white, benign keratinous cysts that are frequently encountered. Multiple eruptive milia are rare, and are characterized by the development of milia that are more extensive in number and distribution than would be expected in primary milia. We report a case of a 19-year-old girl with tiny, white papules in her axillae and on her abdomen with a review of the relevant literature.     

Subcutaneous mycoses: chromoblastomycosis,sporotrichosis and mycetoma

Subcutaneous mycoses are common in subtropical and tropical regions of the world. They are rarely observed in Europe. These mycoses are heterogeneous, but all are caused by penetrating trauma of the skin. Most cases in Europe are observed in returning travelers, aid workers, archaeologists and immigrants. Therefore, a careful, thorough history is essential in order to reach a proper diagnosis. We provide up‐to‐date epidemiological, clinical, diagnostic, and therapeutic data on the three most important imported subcutaneous mycoses in Europe: chromoblastomycosis, sporotrichosis and mycetoma.     

Evaluating and treating patients with oral lichen planus

Lichen planus (LP) is a relatively common disorder with a reported incidence approximating that of psoriasis. Unlike cutaneous lesions, which in the majority of instances are self-limiting, oral lesions are chronic and are a potential source of significant morbidity. Furthermore, compared to cutaneous lesions, oral lesions are more difficult to control and are often refractory to therapy. Patients with oral lichen planus (OLP) frequently have concomitant disease in one or more extraoral sites and therefore require a thorough evaluation to uncover all affected sites of involvement. Genital involvement, which develops in approximately 20% of women patients with OLP, and esophageal involvement may result in scarring if undetected and not treated appropriately. Since no therapy for OLP is curative, the primary goal for symptomatic patients is palliation. Relief can be achieved in the majority of patients with topical corticosteroids alone or in combination with other immunomodulatory topical agents. Infrequently patients require the prolonged use of systemic medications to control the disorder. All treatments are nonspecific and directed at eliminating inflammation, and therefore are only partially successful.     

Molecular mechanisms of genetic disorders of keratinization.

An attempt is made to organize our current knowledge about genetically determined disorders of keratinized tissue, which primarily affect the epidermal structural proteins. Type I defects are those involving a change in a single amino acid and are analogous to sickle cell anemia. Type II defects are associated with abnormal retention of a normal structural protein intermediate. Type III defects are related to alterations in the normal post-translational cross-linking seen in keratinized tissues. Type IV defects are associated with altered proportions of fibrous proteins and are analogous to thalassemia. In type V defects, primary genetic disorders of other tissues profoundly affect keratinization in a secondary fashion. Examples from genetic disorders of the hair and epidermis are used to build this conceptual scheme.     

Nail manifestations of some important genetic disorders in children

There are some genetic disorders in which nail changes are the major feature, such as the nail patella syndrome and pachyonychia congenita. Nail abnormalities are a constant feature of other disorders such as hidrotic ectodermal dysplasia, dyskeratosis congenita, some forms of epidermolysis bullosa, and ichthyosis follicularis with alopecia and photophobia. Nail changes often occur in mal de Meleda, Papillon–Lefèvre syndrome, and the keratitis-ichthyosis-deafness (KID) syndrome and are an occasional feature in some other ichthyoses and in incontinentia pigmenti. In Goltz syndrome, nail changes can be supportive of the diagnosis in a case in which the other features are minimal or subtle. In Darier disease, nail changes may be the first sign of the disorder and lead to the diagnosis being made. Nail changes may occur in some conditions such as Apert syndrome and Adams–Oliver syndrome as a result of abnormalities of the distal phalanges.     

Nail beauty

Nail beauty depends firstly upon nail health. It is a truism to say that a beautiful nail is always a healthy nail. In addition, there are subjective and evolving aspects of nail beauty which are related to fashion. The texture of the nail affects its appearance and function. Soft or brittle nails are fragile. This results in unattractive longitudinal and horizontal splitting. Fragility is encouraged by wet work and excessive nail manicuring, especially by the removal of nail cosmetics. Critical to the aesthetic appeal of the nail is its shape. Most pleasing are nails are those that conform to the 'magic' ratio, in which the nail's length is approximately equal to its breadth, especially for the thumbs. The role of nail decoration and nail art in nail beauty is a subjective and evolving question of fashion.     

Embryology of the epidermis: ultrastructural aspects. II. Period of differentiation in the mouse with mammalian comparisons.

A detailed light and electron microscopic study of the cellular morphology of the epidermis in the 13 through 16 day mouse fetus reveals that an occasional intermediate cell is interposed between the basal and peridermal layers on day 13. All layers are mitotically active. Tonofilaments, unassociated with desmosomes, are present within the basal cell cytoplasm and the mitotic axis of the basal cells has changed from a parallel to a perpendicular plane with respect to the epidermal surface. At 14 days, a complete stratum intermedium, composed of one or two cell layers, is present. Rarely, developing hemidesmosomes are observed. Pools of glycogen are present in all cells below the periderm. The periderm is dense and no longer mitotically active. The skein of filaments, present in the inferior cytoplasmic region of the basal cells on days 12 and 13, is now absent. In the 15 day fetus, numerous developing hemidesmosomes are present. The stratum intermedium contains three to four layers of cells, and filaments are located deep within the cytoplasm of these intermediate cells. Rarely, a few developing keratohyalin granules and keratinosomes are present. A stratum intermedium is no longer present in the 16 day fetus. This region is now composed of a stratum spinosum and a stratum granulosum. Numerous keratinosomes are located in the upper stratum spinosum and lower stratum granulosum. The cells in the stratum granulosum are nucleated and the uppermost cells contain large keratohyalin granules. Three heterogeneous and one homogeneous type of keratohyalin granule is described. Dense bodies are present within mitochondria, nuclei, glycogen pools and the peridermal cytoplasm. The periderm is no longer dense and glycogen and keratohyalin granules are not observed in this layer.     

Lichen Striatus: A Model for the Histologic Spectrum of Lichenoid Reactions

Three phases of lichenoid reactions are defined: 1) the primary phase, 2) the established phase; and 3) the senescent phase. Lichen striatus is characterized by a primary pattern that may be apparent in the epidermis, the hair follicles, and rarely the sweat glands and ducts. Focal areas of established lichenoid reaction, that are indistinguishable from lichen planus, are common. They usually are confined to the tips of elongated rete ridges. Established lichenoid patterns are occasionally present in hair follicles and are indistinguishable from those seen in lichen planopilaris. Eccrine hidradenitis, a feature of lichen striatus, is rarely seen in lichen planus. Lichen planus may be an adaptive epidermal response to a clone of aggressive lymphocytes and, as such, may be a manifestation of auto-immunity. In lichen striatus, senescent lichenoid patterns resemble those seen in lichen nitidus.     

Multiple cutaneous granular cell tumors: case report of a 19-year-old African American female

BACKGROUND AND OBJECTIVE: This is a somewhat rare case of a 19-year-old African American female with multiple cutaneous granular cell tumors. Granular cell tumors are of neural origin, except in rare cases, and are considered benign, with a low incidence of malignancy. The clinical presentation varies greatly, but these tumors are most commonly painful and slow growing, with two-thirds occurring on the head and neck. Patients are most commonly in their second to fourth decades of life, two-thirds are black, and two-thirds are women. Granular cell tumors are diagnosed by the characteristic pathologic findings of polygonal cells with eosinophilic granular cytoplasm. CONCLUSION:These tumors are most commonly singular but can be multiple in 10 to 15% of patients. Older patient age, rapid growth or enlargement, and a history of local recurrence should raise concern for malignant behavior. The distribution and family history in this case are suggestive of possible mosaicism.     

Therapie von Keloiden

Keloids are benign fibrous growths that appear after surgery, trauma or “spontaneously” as a consequence of microtrauma in predisposed patients. Keloids are distinguished from hypertrophic scars in that keloids extend beyond the margins of the original wound and do not tend to regress spontaneously. Keloids are often associated with pruritus and pain and can lead to functional and cosmetic deformities. Keloids are a therapeutic challenge for the dermatologist; although multiple treatment options are available, a reliably effective approach with few side effects remains elusive. High quality research in evaluating keloid therapy is also lacking. This article summarizes the methods used for the treatment of keloids showing their advantages and disadvantages.     

Combination therapy in the treatment of psoriasis

In addition to topical monotherapy for mild and systemic monotherapy for moderate to severe psoriasis, combination therapy plays an important role in daily practice. Although clinical trials almost exclusively evaluate monotherapy regimens, in real life psoriasis patients are usually treated with combination therapies. All combinations are used, topical/topical, topical/UV‐light, topical/systemic or UV‐light/systemic. Often not only two but more drugs/therapies are combined. Not every combination provides additive or synergistic effects. Some combinations are not possible and may be regarded as contraindications. Data on a benefit‐risk‐assessment are much more sparse in medical literature as compared to monotherapies. We summarize current knowledge about the use of combination therapies in psoriasis on the basis of published literature in the form of a table to show which combinations are possible, useful or which can not be recommended. This provides a quick overview of available options.     

Update on immunoglobulin a nephropathy. Part II: Clinical,diagnostic and therapeutical aspects

Immunoglobulin A nephropathy (IgAN) is characterized by different clinical manifestations and by long-term different outcomes. Major problem for the physicians is to understanding which patients are at risk of a disease evolution and to prescribe the right therapy to the right patients. Indeed, in addition to patients with a stable disease with no trend to evolution or even with a spontaneous recovery, patients with an active disease and patients with a rapidly evolving glomerulonephritis are described. Several histopathological, biological and clinical markers have been described and are currently used to a better understanding of patients at risk, to suggest the right therapy and to monitor the therapy effect and the IgAN evolution over time. The clinical markers are the most reliable and allow to divide the IgAN patients into three categories: The low risk patients, the intermediate risk patients and the high risk patients. Accordingly, the therapeutic measures range from no therapy with the only need of repeated controls, to supportive therapy eventually associated with low dose immunosuppression, to immunosuppressive treatment in the attempt to avoid the evolution to end stage renal disease. However the current evidence about the different therapies is still matter of discussion. New drugs are in the pipeline and are described. They are object of randomized controlled trials, but studies with a number of patients adequately powered and with a long follow up are needed to evaluate efficacy and safety of these new drugs.     

Laser treatment of rosacea

Rosacea is a common condition often resulting in persistent erythema and telangiectasia as well as rhinophyma in a number of patients. Over the last two decades lasers have been increasingly used in the treatment of these permanent changes. The literature is reviewed in terms of the different laser systems, side-effects and comparison with other surgical techniques. Laser studies on rosacea-associated telangiectasia and erythema are limited. Copper-bromide, krypton and KTP lasers have been used with good to excellent results. However, the most commonly applied system is the flash lamp-pumped pulsed dye laser. Rhinophyma can be treated with a variety of different surgical methods, including laser resurfacing. CO(2) lasers are the most widely used lasers, others are the Er:YAG and Nd:YAG lasers. Cosmetic end results are comparable to partial excision with a scalpel or electrosurgery. There does not appear to be an increased risk of infection or scarring, but the conventional surgical methods are quicker to perform and more cost effective.     

Autoantibody profiles in systemic sclerosis: Predictive value for clinical evaluation and prognosis

Systemic sclerosis (SSc) is thought to be an autoimmune disease, as autoantibodies against a variety of extractable nuclear antigens can be detected in patient sera. Subgrouping patients based on the type of autoantibodies present can be useful in diagnosis and management. Anti-centromere antibodies (ACA) and anti-topoisomerase I antibodies (anti-topo I) are the classic autoantibodies associated with SSc. ACA are associated with limited cutaneous involvement and isolated pulmonary hypertension, whereas anti-topo I are associated with diffuse skin involvement and pulmonary fibrosis. ACA are predictors for a favorable prognosis, while anti-topo I are correlated with a poor prognosis and SSc-related mortality. Additionally, anti-RNA polymerase antibodies (anti-RNAP) are associated with diffuse cutaneous disease and renal involvement. Anti-nucleolar antibodies define multiple subgroups of patients with SSc. Of these, anti-Th/To antibodies (anti-Th/To) and anti-PM-Scl antibodies (anti-PM-Scl) are associated with limited cutaneous SSc (lSSc), whereas anti-U3RNP antibodies (anti-U3RNP) are associated with diffuse cutaneous SSc (dSSc). In addition, anti-Th/To and anti-U3RNP can be predictors for a less favorable prognosis with a higher frequency of organ involvement, such as pulmonary fibrosis, pulmonary hypertension and renal crisis. Other autoantibodies are less frequently reported: anti-Ku antibodies, anti-U1RNP antibodies, anti-human upstream-binding factor, and anti-U11/U12 antibodies. These antibodies are generally less specific to SSc, but also define clinically distinct patient subsets. Thus, characterization of autoantibodies in SSc together with knowledge of disease characteristics intrinsic to distinct patient populations is helpful for assessing the clinical presentation and prognosis of this disease, and for monitoring patients with SSc.     

Treatments for chronic pruritus outside of the box

Patients with chronic pruritus are in desperate need of novel treatment options, as current therapeutic possibilities are often not effective, have a poor level of evidence and are mostly off‐label. In recent years, much effort has been put into the identification of potential targets for the treatment of chronic pruritus. More importantly, a number of promising new drugs that are aimed at treating pruritus in different conditions are currently in advanced stages of clinical trials. Here, current pharmacological developments leading to potential new drugs for the treatment of chronic pruritus within various conditions are summarized. Hopefully, these new approaches will result in effective and safe therapies for our patients with chronic pruritus associated with dermatological or non‐dermatological diseases in the near future.