Scalp dysaesthesia and lichen simplex chronicus: diagnostic and therapeutic update with literature review.

Scalp dysaesthesia, considered a variant of the cutaneous dysaesthesia syndrome, is characterized by chronic sensory symptoms, including pruritus, pain, burning and stinging in a well-defined location, without objective findings. Its aetiology is not well elucidated and treatment options are limited, thus it can be challenging and frustrating for both patient and physician. It can be associated with lichen simplex chronicus. In this paper, we review the literature on the pathogenetic factors, diagnostic methods and therapeutic options in the management of scalp dysaesthesia. Dissociation, cervical spine disease and muscle tension seem to be the most important pathogenetic factors. Trichoscopy, reflectance confocal microscopy and biopsy are all helpful for the diagnosis of the disease. Therapies include high-potency topical or intralesional corticosteroids, capsaicin and topical anaesthetics, sedative antihistamines, tricyclic antidepressants, transcutaneous electric nerve stimulation, botulinum toxin and vitamin B12.

Clinical and trichoscopic features in various forms of scalp psoriasis.

BACKGROUND: Scalp psoriasis is often undiagnosed or inadequately treated. The patient himself underestimates the seriousness of this hair disease and consults too late to a dermatologist. OBJECTIVES: The aim of our study was to create a correlation between the clinical patterns and trichoscopy of scalp psoriasis such in a way to help the clinician to make the diagnosis and select the appropriate therapy. MATERIAL AND METHODS: We gathered all patients affected of scalp psoriasis afferent to Outpatient's hair consultation of the Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, from January 2012 to December 2018. All patients were evaluated through clinical, trichoscopic examination and a skin biopsy only in doubtful cases. We quantified the severity of the disease with several objective and subjective parameters every 4 months, up to 1 year. We recorded therapies, outcome data and quality of life. RESULTS: We collected 156 patients affected by scalp psoriasis, identifying seven clinical patterns with specific trichoscopical correlation. In the order of frequency, the clinical patterns were as follows: plaque psoriasis (with a prevalence of erythema, silver-white scales and twisted red loops vessels and red dots); thin scales (with silvery-white scales, simple red lines and signet red ring vessels); sebopsoriasis (with greasy scales, erythema with red dots, globules and twisted and bushy red loops at high magnification); psoriatic cap (with silver-white scales, erythema and polymorphic vascular pattern); pityriasis amiantacea (with yellowish adherent scales, erythema and simple red loops capillaries); cicatricial psoriatic alopecia (with erythema associated with yellowish, silver-white scales with twisted and bushy red loops capillaries) and pustular psoriasis (with 'flower shape' pustular lesions, erythema simple red loops capillaries). CONCLUSIONS: The description of different clinical patterns of scalp psoriasis and its trichoscopical correlations may help the clinician to make the diagnosis also in atypical presentations and to prescribe an adequate therapeutic regimen.

Common causes of hair loss - clinical manifestations, trichoscopy and therapy.

The field of hair disorders is constantly growing. The most important hair diseases are divided in non- cicatricial and cicatricial ones. Non-cicatricial alopecia are more frequent than cicatricial alopecia. The first step is to obtain a good history and physical examination. Laboratory testing is often unnecessary, while trichoscopy is fundamental for all hair diseases. Scalp biopsy is strongly suggested in cicatricial alopecia and in doubtful cases. Androgenetic alopecia, alopecia areata, telogen effluvium, trichotillomania are common causes of non- cicatricial alopecia. Frontal fibrosing alopecia, discoid lupus erythematosus, lichen planopilaris, follicullitis decalvans are some of the most common forms of cicatricial hair loss. Many treatments are available, and a prompt diagnosis is very important for the prognosis.

Trachyonychia: a retrospective study of 122 patients in a period of 30 years.

BACKGROUND: Trachyonychia is a nail disease characterized by longitudinal striations, ridges, fissures and/or pitting. This condition can be both idiopathic and associated with other dermatologic diseases. OBJECTIVE AND METHODS: The aim of this retrospective study was to analyse the clinical features, onychoscopy, therapy efficacy and outcome of 122 patients with trachyonychia visited at the Hair Disease Outpatient Consultations of the Dermatology Unit of the Department of Experimental, Diagnostic and Specialty Medicine of the University of Bologna, from 1988 to 2018. RESULTS: Opaque trachyonychia was the most observed type while shiny trachyonychia, less common, was present especially in milder cases. Pitting was the most frequently observed feature (80.3%), followed by koilonychia (45%) and hyperkeratosis (19.6%). Nail matrix longitudinal biopsy was performed for diagnosis confirmation in 29 cases, and spongiotic was the most common pattern. Topical therapy was prescribed in 109 patients while systemic treatments were reserved for severe cases (38 patients); 22 patients did not receive any treatment. A marked improvement in the appearance of the nails or even a total resolution was seen in 63 patients. CONCLUSIONS: Trachyonychia can occur at any age but is more frequent in children and often associated with alopecia areata. The pathological diagnosis of trachyonychia is not mandatory as the disease has generally a benign outcome. Considering the absence of pain and the high rate of spontaneous resolution, treatment is often prescribed only for cosmetic reasons or reserved for severe cases.

Frontal fibrosing alopecia: a case series of 65 patients seen in a single Italian centre.

BACKGROUND: Frontal fibrosing alopecia (FFA) is increasing in prevalence worldwide and several series from different countries have been published, in order to detect possible causes of the disease outbreak. OBJECTIVE: To analyze the epidemiological, clinical and trichoscopic features of FFA seen in an Italian Dermatology Unit. METHODS: Clinical, trichoscopy, histopathology and medical details of all patients were compared with literature and general population data. RESULTS: From 2005 to 2017, we diagnosed FFA in 65 Caucasian females, with the number of diagnoses per year progressively rising. Premenopausal onset was detected in 21%. Frontal hair line recession was associated with parietal involvement in 80% of cases, occipital in 12.3% and eyebrows alopecia in 86.1%. In six cases, eyebrow alopecia preceded hair loss. Non-inflammatory facial papules were detected in 1/3 of the patients. Itching was reported by 2/3 of the patients and was indicative of disease progression. Trichoscopy showed empty follicles/yellow dots, absence of follicular ostia, mild follicular hyperkeratosis, perifollicular erythema and 'lonely hair'. Scalp lichen plano-pilaris was seen in 15 patients, female pattern hair loss in 22. Therapy included short-term treatment with systemic or intralesional corticosteroids followed by therapy with 5α-reductase inhibitors of hydroxychloroquine and topical drugs. Arrest of FFA progression was seen in 75% of the patients, while 16 experienced worsening of the hairline despite therapy. CONCLUSIONS: Frontal fibrosing alopecia not rarely starts before menopause, loss of the eyebrows can be the first sign of the disease, about 50% of the patients have other autoimmune conditions, FFA severity is not related to its duration, itching, follicular hyperkeratosis and erythema at trichoscopy are signs of disease progression, 25% of the patients show progression of hairline recession despite therapy.

Nail apparatus melanoma: dermoscopic and histopathologic correlations on a series of 23 patients from a single centre.

BACKGROUND: Nail apparatus melanoma (NAM) is an uncommon tumour, and there are few studies focused on its dermoscopic features. OBJECTIVE: The aims of our study were to evaluate the diagnostic accuracy of dermoscopy in NAM. A diagnostic algorithm for adult patients with suspected NAM is proposed. METHODS: We collected NAM dermoscopic images of patients with a proven histopathology from 2008 until 2015. Clinical and dermoscopic images were blindly examined by two dermatologists, and correlations between histopathological aspects and dermoscopic features were investigated. RESULTS: We retrospectively collected NAM dermoscopic images associated with a proven histopathology of 23 Caucasian patients. Only cases with available both preoperative dermoscopic images and bioptic specimens were included. Seventeen women and six men were included. The mean age at diagnosis was 63 years (range 18-92). CONCLUSION: We created an algorithm to indicate the correct way to follow an adult patient with suspected NAM. This algorithm may ameliorate management in case of suspected NAM and possibly facilitate an early diagnosis.

Depletion of foxp3(+) T cells abrogates tolerance of skin and heart allografts in murine mixed chimeras without the loss of mixed chimerism.

The relative contribution of central and peripheral mechanisms to the generation and maintenance of allograft tolerance is of considerable interest. Here, we present new evidence that regulatory T cells (Foxp3(+) ) maintain skin and heart allograft tolerance in mixed hematopoietic chimeric mice. Transient depletion of both donor- and recipient-derived Foxp3(+) cells was necessary and sufficient to induce decisive rejection of long-accepted skin and heart allografts. In contrast, stable hematopoietic chimerism remained, and there was no detectable induction of donor-specific reactivity to hematopoietic cells. Foxp3(+) cell depletion did not result in the rejection of skin grafts of only MHC-disparate donors (B6.C-H2(d) /bByJ), indicating that MHC antigens were not the target in the graft. We conclude that two different mechanisms of tolerance are present in mixed chimeras. Hematopoietic chimerism, resistant to Foxp3(+) depletion, is probably due to deletional tolerance to MHC antigens, as supported by previous studies. In contrast, regulatory tolerance mechanisms involving Foxp3(+) cells are required to control reactivity against non-MHC antigens not present on hematopoietic lineages.

Androgenetic alopecia.

Androgenetic alopecia (AGA) is the most common form of alopecia, affecting up to 80% of men and 50% of women in the course of their life. AGA is caused by a progressive reduction in the diameter, length and pigmentation of the hair. Hair thinning results from the effects of the testosterone metabolite dehydrotestosterone (DHT) on androgen-sensitive hair follicles. In women, AGA produces diffuse thinning of the crown region with maintenance of the frontal hairline (Ludwig pattern AGA). In premenopausal women, AGA can be a sign of hyperandrogenism, together with hirsutism and acnes. Male pattern is characterized by bitemporal recession of the frontal hairline, followed by diffuse thinning at the vertex. Today, scalp dermoscopy is used routinely in patients with androgenetic alopecia, as it facilitates the diagnosis and differential diagnosis with other diseases, allows staging of severity, and allows you to monitor the progress of the disease in time and response to treatment. AGA is a progressive disease that tends to worsen with time. Medical treatment of AGA includes topical minoxidil, antiandrogen agents, 5-alpha reductase inhibitors.

Interdigital psoriasis of the feet (psoriasis alba): not a distinct form of psoriasis.

BACKGROUND: Interdigital psoriasis (IP) of the feet is often missed and is commonly mistaken for interdigital fungal infection. OBJECTIVE: To assess the characteristics and the clinical presentation of IP, in order to better understand if IP should be considered a distinct form of psoriasis or not. METHODS: We performed a 1-year observational study on 164 psoriatic patients, affected by moderate to severe cutaneous psoriasis and undergoing systemic therapy, examining each patient between the digits of both feet. In every suspected case of IP, differential diagnosis with interdigital fungal infection was excluded by direct microscopic examination of skin scrapings, by culture and by skin biopsy. RESULTS: We suspected IP in 7 of the 164 patients. IP was confirmed in 6 patients and in the other one a diagnosis of tinea pedis was made. CONCLUSION: IP proved to be not rare or atypical since IP localized between the toes usually presents as characteristic whitish and sodden plaques or patches. Such a diagnosis should be considered in all patients presenting characteristic lesions especially if these have a negative fungal culture, are resistant to antimycotic treatment and involve patients with a history of psoriasis.

Decreased mitogen activated protein kinase activities in congenital diaphragmatic hernia-associated pulmonary hypoplasia.

BACKGROUND/PURPOSE: The mechanisms that cause pulmonary hypoplasia associated with congenital diaphragmatic hernia (CDH) currently are unknown. The authors proposed that the reduced size and immaturity of these lungs may be associated with differences in the levels of mitogen activated protein (MAP) kinase phosphorylation (extracellular signal regulated protein kinases, ERK-1 and -2). METHODS: ERK-1 activities were measured using immune-complex kinase assays on fetal whole-lung lysates obtained from both nitrofen and olive oil-treated (control) pregnant rats. In addition, ERK-1 and ERK-2 functional activities were estimated by semiquantitative Western blot analysis, using an antibody specific for the diphosphorylated (dp-ERK, activated) forms of the enzymes. RESULTS: ERK-1 activities, measured using immune-complex kinase assays, were reduced in CDH lungs compared with olive oil-treated controls (P <.02). In addition, dp-ERK-1 and dp-ERK-2 levels were found to be reduced in CDH lungs compared with controls (dp-ERK-1, P =.003; dp-ERK-2, P =.04), whereas ERK-1 and ERK-2 protein levels were unchanged. CONCLUSIONS: The lower values of ERK-1 activity and reduced amounts of dp-ERK-1 and dp-ERK-2 in lung tissue from CDH animals, suggests that ERK-1 and ERK-2 activities are reduced in pulmonary hypoplasia associated with CDH. The observed reduction in ERK-1 and ERK-2 activities implicates attenuated cell signaling upstream of the ERK-1 and -2 enzymes.

Mitogen-activated protein kinase phosphorylates and targets inducible cAMP early repressor to ubiquitin-mediated destruction.

Inducible cAMP early repressor (ICER) is an important mediator of cAMP antiproliferative activity that acts as a putative tumor suppressor gene product. In this study, we examined the regulation of ICER protein by phosphorylation and ubiquitination in human choriocarcinoma JEG-3 and mouse pituitary AtT20 cells. We found that cAMP stabilized ICER protein by inhibiting the mitogen-activated protein kinase (MAPK) cascade. Activation of the MAPK pathway increased ICER phosphorylation. ICER phosphorylation was abrogated by inhibition of the MAPK pathway either by cAMP or directly by the MAPK inhibitor PD098059. The MAPKs extracellular signal-regulated kinases 1 and 2 physically interact with ICER and mediated the phosphorylation of ICER on a critical serine residue (Ser-41). A mutant form of ICER in which Ser-41 was substituted by alanine had a half-life 4-5 h longer than its wild-type counterpart. This alteration in stability was due to the inability of the Ser-41-mutant ICER to be efficiently ubiquitinated and degraded via the ubiquitin-proteasome pathway. These results present a novel cell signaling cross-talk mechanism at the cell nucleus between the MAPK and cAMP pathways, whereby MAPK targets a repressor of the cAMP-dependent gene expression for ubiquitination and proteasomal degradation.

Glycogen synthase kinase-3beta is a negative regulator of cardiomyocyte hypertrophy.

Hypertrophy is a basic cellular response to a variety of stressors and growth factors, and has been best characterized in myocytes. Pathologic hypertrophy of cardiac myocytes leads to heart failure, a major cause of death and disability in the developed world. Several cytosolic signaling pathways have been identified that transduce prohypertrophic signals, but to date, little work has focused on signaling pathways that might negatively regulate hypertrophy. Herein, we report that glycogen synthase kinase-3beta (GSK-3beta), a protein kinase previously implicated in processes as diverse as development and tumorigenesis, is inactivated by hypertrophic stimuli via a phosphoinositide 3-kinase-dependent protein kinase that phosphorylates GSK-3beta on ser 9. Using adenovirus-mediated gene transfer of GSK-3beta containing a ser 9 to alanine mutation, which prevents inactivation by hypertrophic stimuli, we demonstrate that inactivation of GSK-3beta is required for cardiomyocytes to undergo hypertrophy. Furthermore, our data suggest that GSK-3beta regulates the hypertrophic response, at least in part, by modulating the nuclear/cytoplasmic partitioning of a member of the nuclear factor of activated T cells family of transcription factors. The identification of GSK-3beta as a transducer of antihypertrophic signals suggests that novel therapeutic strategies to treat hypertrophic diseases of the heart could be designed that target components of the GSK-3 pathway.

Serine-threonine protein kinase Akt does not mediate ischemic tolerance after global ischemia in the gerbil.

The protein kinase Akt/PKB has been implicated in antiapoptosis and neuronal survival. The authors now show that Akt is phosphorylated in the hippocampus during the early reperfusion period after 3.5 minutes bilateral carotid artery occlusion (BCAO) in the gerbil. Repeated sublethal ischemia induces ischemic tolerance, which is known as ischemic preconditioning. Ischemic preconditioning does not affect the amount of Akt protein, but rather decreases the phosphorylation of Akt at Ser-473 after 10 minutes reperfusion after 3.5 minutes BCAO. These results suggest that although Akt may play a role in neuronal survival after ischemia, it may not play a role in ischemic tolerance by preconditioning.

Transfection of constitutively active mitogen-activated protein/extracellular signal-regulated kinase kinase confers tumorigenic and metastatic potentials to NIH3T3 cells.

Cellular growth and differentiation are controlled by multiple extracellular signals, many of which activate extracellular signal-regulated kinase (ERK)/mitogen-activated protein (MAP) kinases. Components of the MAP kinase pathways also cause oncogenic transformation in their constitutively active forms. Moreover, expression of activated ras can confer metastatic potential upon some cells. Activation of MAP kinases requires phosphorylation of both Thr and Tyr in the catalytic domain by a family of dual-specificity kinases, called MEKs (MAP kinase/ERK kinase). MEK1 is activated by phosphorylation at Ser218 and Ser222 by Raf. Mutation of these two sites to acidic residues, specifically [Asp218], [Asp218, Asp222], and [Glu218, Glu222], results in constitutively active MEK1. Using these mutant variants of MEK1, we showed previously that transfection of NIH/3T3 or Swiss 3T3 cells causes morphological transformation and increases growth on soft agar, independent of ERK activity. The transformed cell lines show increased expression of matrix metalloproteinases 2 and 9 and cathepsin L, proteinases that have been implicated in the metastatic process. We tested NIH3T3 cells transfected with the [Asp218] or [Asp218, Asp222] for metastatic potential after i.v. injection into athymic mice. Parental 3T3 cells formed no tumors grossly or histologically. However, all MEK1 mutant transformants formed macroscopic metastases. Thus, like activated Ras, MEK1 can confer both tumorigenic and metastatic potential upon NIH3T3 cells. These results refine the mechanism through which ras could confer tumorigenic and metastatic potential (ie., the critical determinants of tumorigenic and metastatic potential are downstream of MEK1).

[Use of the TUT (Tension-free Vaginal Tape) in the treatment of female urinary stress incontinence. Preliminary results]. / Utilizzazione del TVT (Tension-free Vaginal Tape) nel trattamento dell'incontinenza urinaria femminile da sforzo. Risultati preliminari.

BACKGROUND: The Tension-free Vaginal Tape (TVT) represents the most recent technique for the treatment of genuine stress urinary incontinence (GSUI). The various number of surgical procedures proposed for the treatment of GSI very often do not lead to a complete remission of this pathology. The data from the literature show how TVT is a effective procedure for the treatment of female urinary incontinence. METHODS: Twenty-nine women with diagnosis of urinary incontinence underwent application of polypropilene band (TVT: tension-free vaginal tape) underneath the uretra, in order to treat this disorder. The procedure has been carried out in peripheral anesthesia. RESULTS: A complete remission of the urinary incontinence was obtained in 24 patients. In the remaining cases there was an improvement of the symptoms in two patients, whereas in two patients remained a secondary detrusor instability. In one case the external iliac vein was perforated thus requiring a surgical repair. CONCLUSION: The short surgical time, the feasibility of the procedure and the following short hospitalization made this technique well accepted either by the surgeons ang the patients. Moreover the possibility to carry out the procedure in peripheral anesthesia allows to have the collaboration of the patient. However this technique is not free of risks, how the serious complication we had can demonstrate.

MEK1 activation rescues Jurkat T cells from Fas-induced apoptosis.

Although the protease cascade initiated by Fas (CD95, Apo-1) is well characterized, there remains little known about how kinase pathways may impact on Fas-mediated apoptosis. We recently observed that in T lymphocytes Fas strongly induced activation of JNK (c-Jun N-terminal kinase) but not of second messengers leading to activation of ERK (extracellular regulated kinase). Additionally, Fas-mediated apoptosis was significantly inhibited with PMA, a potent activator of the ERK signaling pathway. This suggested a model whereby activation of the ERK pathway might attenuate Fas-mediated apoptosis. This was confirmed in the current study by showing that activation of MEK1, the upstream regulator of ERK, reduces Fas-mediated apoptosis, whereas inhibition of MEK1 augments apoptosis by Fas. Furthermore, Fas-mediated apoptosis of Jurkat T cells is not affected by constitutively active or dominant negative variants that modulate the JNK pathway. These results demonstrate that Fas-induced JNK activation is not required for apoptosis by Jurkat T cells, but rather is more likely secondary to cell stress during the early phases of apoptosis. This is supported by the ability of the caspase blocker zVAD to inhibit both apoptosis and JNK activation by Fas.