The leukotriene B4 receptor BLT2 protects barrier function via actin polymerization with phosphorylation of myosin phosphatase target subunit 1 in human keratinocytes

Leukotriene B₄ (LTB₄) receptor type 2 (BLT2) is a novel G‐protein‐coupled receptor, which selectively binds to 12(S)‐hydroxyheptadeca‐5Z,8E,10E‐trienoic acid (12‐HHT) with stronger affinity than to LTB₄. Recently, 12‐HHT has been shown to have a protective effect on the epidermal barrier in human keratinocytes or transfectant cells overexpressing BLT2. Because the protective activity of BLT2 in high‐calcium conditions, which occurs in well‐differentiated cells, is exerted through increasing the integrity of tight junctions, we investigated the effects of 12‐HHT on the barrier function of human keratinocytes in low‐calcium conditions that mimic the basal layer; to our knowledge, this has not been reported previously. After stimulation with or without 12‐HHT, barrier function was measured using transepithelial electrical resistance (TER) and dextran permeability assay. Expression levels of adhesion molecules and actin polymerization were also evaluated. Treatment with 12‐HHT increased TER, along with decreased epidermal permeability of dextran in human keratinocytes. Furthermore, 12‐HHT induced actin polymerization with phosphorylation of myosin phosphatase target subunit 1. These results suggest that the ligation of BLT2 protects permeability barrier function by enhancing cell–cell contact, even under low‐calcium conditions, and indicate that a BLT2 agonist could be a novel therapeutic target for barrier‐disrupted skin diseases.     

Giant condyloma (Buschke-Löwenstein tumor). A case report

Buschke-L?wenstein tumor (BLT), or giant condyloma acuminatum, is a rare sexually transmitted disease. The virus responsible for condyloma is human papillomavirus, usually serotype 6 or 11. A BLT is always preceded by condyloma acuminatum and may occur at any age after puberty. It is characterized by invasive growth and recurrence after treatment, and malignant transformation is possible. We report the case of a 44-year-old male patient with a 2-year history of a penoscrotal Buschke-L?wenstein tumor.     

Involvement of leukotriene B4 in spontaneous itch-related behaviour in NC mice with atopic dermatitis-like skin lesions

To elucidate the mechanisms of severe itch in atopic dermatitis, we investigated the role of leukotriene B(4) , a potent itch mediator, in spontaneous itch-related behaviour in NC mice with atopic dermatitis-like skin lesions. Topical application of the BLT leukotriene B(4) receptor antagonist ONO-4057 inhibited spontaneous itch-related behaviour. The concentration of leukotriene B(4) was significantly increased in the lesional skin. The expression levels of 5-lipoxygenase were also elevated in the lesional skin, yet present throughout the epidermis of both healthy and lesional skin. These results suggest a role for leukotriene B(4) in chronic dermatitis-related itch. Sphingosylphosphorylcholine (SPC) was increased in the epidermis of the lesional skin. Moreover, intradermal injection of SPC elicited itch-related behaviours in healthy mice. Because SPC induces itch-related responses through the production of leukotriene B(4) in keratinocytes (J Invest Dermatol, 129, 2009, 2854), these results suggest that an increase in SPC induces leukotriene B(4) -mediated itching in chronic dermatitis. BLT1 receptor and 5-lipoxygenase in the skin may be effective pharmacological targets for the treatment of itch in atopic dermatitis.     

Giant condyloma acuminatum in pregnancy: A case report

The giant condyloma acuminatum (GCA), also known as Buschke–Löwenstein tumor (BLT), is a type of human papilloma virus‐associated sexually transmitted infection. Treatment options for condyloma acuminatum remain controversial, but surgery seems to be the best option. The management of GCA during pregnancy is more complicated since one has to evaluate the condition of both the mother and the fetus. In this report, we presented a GCA case in a pregnant woman with giant masses that covered the perineal and perianal region. Considering the gestational age and the fetal neurological risk from the anticipated lengthy procedure of mass removal surgery for tumor of this size, we decided to resect the tumor 2 weeks after the infant was delivered via C‐section.     

Detection of human papillomavirus type 11 in a case of Buschke-Löwenstein tumor

We here report a 31-year-old male affected by a papillary tumor in his pubic region. At 26 years of age, he consulted a nearby clinic and was prescribed a topical cream. Although the condition was not relieved, he left the disease untreated. The gradually growing tumor adversely affected his quality of life, and he consulted another clinic, where he was referred to our hospital for surgery. The tumor had infiltrated the tissue at the base of the penis, but not the glans. After careful examination, we performed local excision of the tumor and a split-thickness skin graft. On pathological examination, elongation of the epidermis and koilocytes in the uppermost portion of the spinous layer were observed. Moreover, PCR examination confirmed the presence of human papillomavirus (HPV) type 11 in the tumor tissue. These findings supported a diagnosis of Buschke-L?wenstein tumor (BLT).     

Trichotillomania ± trichobezoar: revisited

Trichotillomania is an intriguing psychosomatic entity in which there is an irresistible desire to pull out the hair from the scalp, eyelashes, eyebrows and other parts of the body. The process results in an instant release of tension, a sense of relief and security. However, non-scaring alopecia is its clinical presentation. The development of trichobezoar following ingestion of the pulled hair is its salient complication in a few cases. Subsequently, it may cause symptoms pertaining to the gastrointestinal tract culminating in intestinal obstruction, perforation, pancreatitis and obstructive jaundice. The Rapunzel syndrome (trichobezoar) may occur when gastrointestinal obstruction is produced by a rare manifestation of a trichobezoar with a long tail that extends to or beyond the ileocecal valve. In most cases in children, trichotillomania +/- trichobezoar is a habit disorder and thus has a better prognosis. However, in adults the psychopathology is usually deeper and thus entails a poor prognosis. The diagnosis is made after taking a thorough history, noting the clinical features and evaluating a hair-root examination, where telogen hair is (almost) completely lacking, which distinguish trichotillomania from other hair disorders. Treatment modalities vary in childhood and adult varieties. Apart from psychotherapy, the drug treatment involves several agents including selective serotonin reuptake inhibitors (SSRIs) and domipramine. Trichobezoar/Rapunzel syndrome requires surgical intervention.     

Diclofenac‐induced pseudoporphyria; an under‐recognized condition?

Pseudoporphyria is a photodistributed bullous disorder that is clinically and histologically similar to porphyria cutanea tarda (PCT), but without abnormal porphyrin biochemistry. Renal failure, dialysis, excessive ultraviolet A and medications, particularly nonsteroidal anti‐inflammatory drugs (NSAIDs), have been associated with pseudoporphyria. We report a case of diclofenac‐induced pseudoporphyria in a man with psoriatic arthritis. To our knowledge, this is only the second reported case of pseudoporphyria associated with diclofenac. Diclofenac has hitherto been considered by many dermatologists as a safe alternative in NSAID‐induced pseudoporphyria.     

Melanotropic peptides: more than just ‘Barbie drugs’ and ‘sun‐tan jabs’?

While ultraviolet radiation (UVR) is a major cause of skin ageing and carcinogenesis, public pursuit of a novel tanning strategy circumventing the need for UVR is increasingly reported in the media and scientific press. This involves the subcutaneous self‐administration of unregulated products labelled as melanotan I and/or II, synthetic analogues of α‐melanocyte stimulating hormone (α‐MSH), as obtained via the internet, tanning salons and gyms. The Medicines and Healthcare products Regulatory Authority has recently raised awareness of the public health risk of transmission of blood‐borne viruses from the needle sharing that may occur, and of the potential impurity of these products. Dermatologists should also be aware that these agents can complicate the clinical presentation of patients with pigmented lesions; their use may be suspected in unexpectedly tanned individuals with rapidly pigmenting naevi. Meanwhile, the regulated α‐MSH analogue afamelanotide (Clinuvel Pharmaceuticals Ltd, Melbourne, Australia) is showing promise for its photoprotective potential, and is undergoing phase II and III clinical trials in people with photosensitivity disorders and those prone to nonmelanoma skin cancer. The photoprotective and other biological effects of α‐MSH analogues await full determination.     

The “dysplastic” nevus

Dysplastic nevi have become an increasing focus clinically, with evidence that they are associated with a higher risk of developing melanoma. However, there still is contention regarding the significance of dysplastic nevi. This contribution provides an overview of the history, epidemiology, genetics, clinical and histologic features, and procedures for clinical management of dysplastic nevi. Since dysplastic nevi were described originally in 1978, a great deal of research has examined the epidemiology of these lesions and the genetic factors related to the development of dysplastic nevi. However, there is disagreement regarding the clinical management of dysplastic nevi and the histologic definition of dysplastic nevi. Current recommendations include preventative measures, such as sun protection and careful surveillance and biopsies of suspicious lesions as needed. The advent of new technologies, such as computer-vision systems, have the potential to significantly change treatment of dysplastic nevi in the future.     

Effect of vitamin D<Subscript>3</Subscript> on the increased expression of Bcl-x<Subscript>L</Subscript> in psoriasis

Psoriasis is a chronic skin disease characterized by epidermal hyperproliferation, which may be regulated by several mechanisms including apoptosis. In this study, we detected DNA fragmentation by the terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL) method and immunohistochemically examined the expression of Bcl-x and Bax in psoriasis. We determined the expression of bcl-xL mRNA by RT-PCR, and also determined the effect of vitamin D(3) (VD3) on bcl-xL mRNA expression in cultured normal human keratinocytes by RT-PCR, and the expression of Bcl-xL in psoriatic lesions before and after topical application of VD3. A large number of TUNEL-positive cells as well as Bcl-xL - and Bax-positive cells were observed throughout the epidermis in psoriatic lesions. Whereas, in nonlesional and normal skin, only a few TUNEL-positive cells were observed and only the lower epidermis showed positive staining for Bcl-x and Bax. We also observed higher expression of bcl-xL mRNA in psoriatic lesions than in nonlesional and normal skin. The expression of bcl-xL mRNA in cultured normal human keratinocytes stimulated or not with IFN-gamma and PMA was suppressed by VD3 in a dose-dependent manner, and the expression of Bcl-xL, but not Bax, in psoriatic lesional skin decreased after topical application of VD3 for 4 weeks. In conclusion, it is suggested that the apoptotic process in psoriatic lesions is in part regulated by Bcl-xL, and decreasing the expression of Bcl-xL by treatment with VD3 might ameliorate psoriatic lesions by contributing to the completion of the apoptotic process.     

“Retronychia – clinical and pathophysiological aspects”

Retronychia represents proximal ingrowth of the nail that occurs when the nail embeds backwards into the proximal nail fold. It is suspected when there is a persistent paronychia, particularly in the setting of trauma. Important clinical criteria for diagnosis are inflammation of the proximal nail fold, granulation tissue emerging from under the nail fold, thickening of the proximal portion of the nail plate and interruption of nail growth. The condition is rarely diagnosed and often misinterpreted, and is therefore unnecessarily treated with systemic antibiotics and antifungals. Avulsion of the nail confirms the diagnosis and it is the curative treatment. Conservative treatment with an adhesive technique is a valid option in early cases. We report 20 cases of retronychia diagnosed in our department between 2010 and 2013.     

Clouston syndrome associated with eccrine syringofibroadenoma

Eccrine syringofibroadenoma is a rare benign neoplasia derived from acrosyryngium cells of the eccrine sudoriferous glands. It affects the extremities of elderly individuals as solitary tumors, or may also present as multiple lesions. There are controversies about the pathogenesis and differentiation of the tumor. Eccrine syringofibroadenoma has been associated with subjacent conditions, such as for example, hypohidrotic ectodermic dysplasias. The authors describe a case report of a patient with Clouston Syndrome, who presented papules and nodules in extremities, clinically and histologically compatible with eccrine syringofibroadenoma. There are only three cases described in the literature, associated with Clouston Syndrome, and this is the fourth case.     

Screening for Sturge‐Weber syndrome: A state‐of‐the‐art review

Infants with a high‐risk distribution of port‐wine stains are commonly screened for Sturge‐Weber syndrome using brain magnetic resonance imaging. There is no consensus about which port‐wine stain phenotypes to screen, optimal timing, screening sensitivity, or whether presymptomatic diagnosis improves neurodevelopmental outcomes. This state‐of‐the‐art review examines the evidence in favor of screening for Sturge‐Weber syndrome, based on its effect on neurodevelopmental outcomes, against the risks and limitations of screening magnetic resonance imaging and electroencephalography. A literature search of PubMed/MEDLINE was conducted between January 2005 and May 2017 using key search terms. Relevant articles published in English were reviewed; 34 articles meeting the search criteria were analyzed according to the following outcome measures: neurodevelopmental outcome benefit of screening, diagnostic yield, financial costs, procedural risks, and limitations of screening magnetic resonance imaging and electroencephalography. There is no evidence that a presymptomatic Sturge‐Weber syndrome diagnosis with magnetic resonance imaging results in better neurodevelopmental outcomes. The utility of electroencephalographic screening is also unestablished. In Sturge‐Weber syndrome, neurodevelopmental outcomes depend on prompt recognition of neurologic red flags and early seizure control. Small numbers and a lack of prospective randomized controlled trials limit these findings. For infants with port‐wine stain involving skin derived from the frontonasal placode (forehead and hemifacial phenotypes), we recommend early referral to a pediatric neurologist for parental education, counselling, and monitoring for neurologic red flags and seizures and consideration of electroencephalography regardless of whether magnetic resonance imaging is performed or its findings.     

Neue und etablierte Indikationen der UV‐B‐311‐nm‐Phototherapie

Phototherapy with ultraviolet (UV) irradiation of wavelengths between 280 and 320 nm (UV‐B) is a safe and effective treatment for a variety of inflammatory skin diseases. In addition to standard broad band UVB, narrow band phototherapy with fluorescent bulbs emitting near monochromatic UV between 310 – 315 nm has become an important treatment for diseases such as psoriasis, atopic dermatitis or vitiligo. Other diseases respond favorably to narrow band UV‐B phototherapy, the number of potential indications for such phototherapy is continuously growing. The differential effects of narrow band UV‐B phototherapy in comparison to other UV phototherapies, as well as new and established indications for this treatment modality are reviewed.     

Gómez–López‐Hernández Syndrome: A Rare Cause of Bilateral Nonscarring Alopecia

Gómez–López‐Hernández syndrome is a rare neurocutaneous disorder characterized by the triad of rhombencephalosynapsis, parietal alopecia, and trigeminal anesthesia. We report a 16‐year‐old girl with bilateral parietotemporal alopecia in whom cranial magnetic resonance imaging revealed rhombencephalosynapsis, suggesting a diagnosis of Gómez–López‐Hernández syndrome. Neurologic examination and neuroimaging may be warranted in select patients with parietal alopecia to exclude this uncommon entity.     

Extracorporeal photopheresis in graft‐versus‐host disease

Graft‐versus‐host disease (GvHD) is a common and often serious complication of hematopoietic stem cell transplantation. There are two major forms of GvHD: an acute form which develops in the first 100days after HSCT, and a chronic form which develops later. Chronic GvHD is a multiorgan syndrome with many features of autoimmune diseases, such as sclerodermatous skin changes, cholestasis, pulmonary fibrosis, xerostomia, oral ulcerations, myositis and fasci‐itis. Unlike acute GvHD which is characterized by acute alloreactivity,the etiology of chronic GvHD is controversial and is believed to be either an extension of acute GvHD and/or a result of dysfunctional immune reconstitution with generation of autoantibodies and autoreactive T‐cell clones. GvHD is usually treated with corticosteroids and other immunosuppressants which do not always succeed in arresting its evolution. Extracorporeal photochemotherapy has been used in patients with both acute and chronic GvHD.     

Docetaxel‐induced photo‐recall phenomenon

Photo‐recall phenomenon is a phototoxic eruption occurring on areas of previous ultraviolet‐induced solar erythema following a systemic administration of a drug. It has been mostly described with methotrexate but remains rare with other antineoplastic drugs. We describe a case of docetaxel‐induced photo‐recall skin rash in a woman treated for a non‐small‐cell lung cancer. Although the patient has refused to receive a second infusion, chemotherapy can be carried on with photoprotection and the use of topical and/or systemic corticosteroids. In contrast, radiation recall is a well‐known reaction by oncologists, most of them may not be aware of a similar phenomenon called photo‐recall phenomenon. Recognizing this entity may avoid misdiagnosing a drug allergy and should avoid inappropriate decisions of drug discontinuation.     

Second‐degree burn within a tattoo after intense‐pulsed‐light epilation

The use of high energy light sources [laser, intense pulsed light (IPL)] is booming in aesthetic surgery. A trend, especially concerning usage of photoepilation in cosmetic institutes, is detectable. Photoepilation works through selective photothermolysis, by heating the chromophore melanin within the hair follicles. We present a case impressionably demonstrating that high‐energy light demands profound knowledge of its mechanism of action, and can cause severe harm in absence of basic knowledge. Photoepilation is a balancing act between maximal therapeutic effect and minimal side effect risk. Nevertheless, complications have to be clearly distinguished from professional errors. The latter are rising especially with IPL devices, mainly because its use depicts a legal grey area in most of the countries and is not bound to physicians' supervision. Due to its worse risk–benefit profile as compared with that of laser therapy, we advise against the use of IPL devices and claim for stricter regulation of its use, similar to laser devices.     

Acute Crohn’s colitis with lobular panniculitis – metastatic Crohn’s?

One of the common lesions in Crohn's colitis is erythema nodosum, a septal panniculitis that may appear before diagnosis or in conjunction with flare up. We report a case of Crohn's colitis where the presenting sign was neutrophilic lobular panniculitis with few granulomas. The possibility that this case represents a forme fruste of metastatic Crohn's is suggested. As skin biopsies are not usually performed by gastroenterologists in erythema nodosum-like skin lesions in Crohn's patients it may well be that the incidence of lobular panniculitis is higher than reported in the literature.