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.

Microscopic structure of water in a water/oil emulsion.

We have determined the microscopic structure of water within a water/oil emulsion, by combining neutron diffraction data, exploiting the isotopic H/D substitution, and a fully atomistic Monte Carlo simulation of a portion of a water droplet, containing the water/oil interface. The dependence of the data on the simulation box size and the reliability of the water-water radial distribution functions are discussed. Although water in the emulsion forms shorter and stronger hydrogen bonds compared to pure bulk water, its overall microscopic structure looks more disordered.

Cranial osteolytic metastases as the only recurrence of gastric carcinoma.

The purpose of this case report is to increase the knowledge about bone metastatic pattern in gastric cancer. A 59-year-old man presented with headache three years after a total gastrectomy for signet-ring cell carcinoma. Head computed tomography and magnetic resonance imaging showed multiple osteolytic lesions of the cranial vault and base, consistent with metastatic or haematological disease. Bone scintigraphy confirmed areas of accumulation only in the skull. An extensive search didn't show any other tumor. Bone biopsy revealed metastatic signet-ring cell carcinoma. In gastric cancer, bone metastases are generally associated with metastases in lymph nodes, liver, and lung, and have a higher frequency in the thoracolumbar spine. However, cranial bone metastases presenting with headache may be the only manifestation of gastric cancer recurrence.

Laparoscopic treatment of bowel endometriosis in infertile women.

BACKGROUND: The purpose of the study was to determine the influence of bowel endometriosis on fertility, and to study whether its removal improves fecundity in women with endometriosis-associated infertility. METHODS: Three groups of infertile patients were included in the study. Group A (60 women) consisted of patients who underwent surgery for endometriosis with colorectal segmental resection. In group B, 40 patients with evidence of bowel endometriosis underwent endometriosis removal without bowel resection. Group C consisted of 55 women who underwent surgery for moderate or severe endometriosis with at least one endometrioma and deep infiltrating endometriosis but without bowel involvement. The women were clinically evaluated before laparoscopy and then at 1 month, at 6 months and at each year up to 4 years after surgery. Main outcome measures were surgical complications as well as post-operative pregnancy rate, time to conception and monthly fecundity rate. RESULTS: The monthly fecundity rates (MFR) in groups A, B and C were 2.3, 0.84 and 3.95%, respectively. The difference in the MFR between groups was significant (P < 0.05). CONCLUSIONS: The presence of bowel infiltration by endometriosis seems to negatively influence the reproductive outcome in women with endometriosis-associated infertility. The complete removal of endometriosis with bowel segmental resection seems to offer better results in terms of post-operative fertility.

Identification of bradykinin: related peptides from Phyllomedusa nordestina skin secretion using electrospray ionization tandem mass spectrometry after a single-step liquid chromatography

Amphibian skin secretions are a source of potential new drugs with medical and biotechnological applications. Rich in peptides produced by holocrine-type serous glands in the integument, these secretions play different roles, either in the regulation of physiological skin functions or in the defense against predators or microorganisms. The aim of the present work was to identify novel peptides with bradykinin-like structure and/or activity present in the skin of Phyllomedusa nordestina. In order to achieve this goal, the crude skin secretion of this frog was pre-fractionated by solid phase extraction and separated by reversed-phase chromatography. The fractions were screened for low-molecular-mass peptides and sequenced by mass spectrometry. It was possible to identify three novel bradykinin-related peptides, namely: KPLWRL-NH2 (Pnor 3), RPLSWLPK (Pnor 5) and VPPKGVSM (Pnor 7) presenting vascular activities as assessed by intravital microscopy. Pnor 3 and Pnor 7 were able to induce vasodilation. On the other hand, Pnor 5 was a potent vasoconstrictor. These effects were reproduced by their synthetic analogues.

A case of infliximab-induced psoriasis.

Anti-tumor necrosis factor (anti-TNF-alpha) are a group of new drugs able to inhibit the action of this cytokine. Although systemic side effects have been well described, cutaneous adverse reactions have not yet been clearly elucidated. The authors report a case of a 29-year-old man affected by Crohn disease and ankylosing spondylitis who developed psoriatic lesions after IV infusion of infliximab 5 mg/Kg. The patient underwent cyclosporine treatment after interruption of biological therapy, and had complete resolution of cutaneous lesions. The reason for this phenomenon is not clear, Obviously more studies are necessary to define more clearly this paradoxical reaction. In addition, dermatologists must be informed about this potential cutaneous adverse event.

Genetic influence in antithrombotic actions of atorvastatin in hypercholesterolaemia.

BACKGROUND: Recent data indicate that statins could offer coronary artery disease (CAD) benefit even by mechanisms beyond lipid lowering. Genetic influence has been shown for some antithrombotic actions of statins via oxidized-low-density lipoprotein cholesterol (ox-LDL) receptors and nitric oxide synthase (NOS) activity modulation. The present study was designed to evaluate the influence of ox-LDL lectin-like receptor-1 (LOX-1) and NOS polymorphisms in the incidence of cardiovascular events in pure hypercholesterolaemic subjects during statin treatment. MATERIALS AND METHODS: A prospective 4-year study involving 1039 event-free subjects (643 males, 396 females) treated with atorvastatin (10-40 mg day(-1)) to reach the appropriate Adult Treatment Panel-III LDL target of 3.36 mmol L(-1). Enrolled subjects were evaluated every 6 months or at a clinical event. LOX-1 3'UTR/T-C and NOS G894T polymorphisms were detected by allelic discrimination assays (polymerase chain reaction), lipid profile by enzymatic-colorimetric method, ox-LDL by enzyme linked immunosorbent assay, platelet activation by P-selectin (P-sel) expression (FACScan), NOS activity (by intracellular citrullin recovery) and homocysteine (high performance liquid chromatography), C-reactive protein (CRP) by sensitive nephelometric technique. RESULTS: LOX-1 3'UTR/T showed the strongest association with events in the whole cohort with respect to each other variable including LDL reduction and NOS G894T (OR 4.90, 95% CI 3.19-6.98, P < 0.00001). Smoking influenced events in LDL-targeted subjects (P < 0.0001). Ox-LDL and P-sel were better indicators than LDL or other variables according to 3'UTR/C genotype regardless of the magnitude of LDL reduction (OR 4.21, 95% CI 2.29-6.70 P < 0.0001). CONCLUSIONS: LOX-1 polymorphisms could influence statin effectiveness in CAD prevention by induction of sensitivity to antithrombotic mechanisms such as antiplatelet activity.

Effect of atorvastatin on different fibrinolyis mechanisms in hypercholesterolemic subjects.

BACKGROUND: Hydroxymethyl-glutaryl-CoA-reductase inhibitors (statins) reduce cardiovascular events by cholesterol lowering as well as non-lipid related actions. Among them, the modulation of fibrinolysis could play a relevant role in vascular protection. Atorvastatin is able of reducing platelet activity and thrombin generation before low-density lipoprotein cholesterol (LDL-C) decrease in hypercholesterolemic subjects in which coagulation and fibrinolysis are linked by the activation of thrombin activable fibrinolysis inhibitor (TAFI). The aim of our study was to evaluate whether atorvastatin could modulate fibrinolysis by interactions with endothelial mechanisms and thrombin generation. METHODS: Forty-four pure hypercholesterolemic subjects (26 M, 18 F, mean age 52.7+/-13.7, LDL-C 194.8+/-9.3t mg/dl) were evaluated for plasmin-antiplasmin complexes (PAP), tissue-plasminogen acivator (t-PA) and its inhibitor (PAI-1) (ELISA), TAFI activity (HPLC), platelet P-selectin (P-sel) (cytofluorymetric detection), platelet-dependent thrombin generation (PDTG, coagulative-chromogenic method) and lipid profile at baseline and after 7, 14, 28 and 90 days of atorvastatin (10 mg/die) treatment. RESULTS: PAP were significantly reduced at baseline in hypercholesterolemic versus control subjects (P<0.05) and were related to P-sel (P<0.01), PDTG (P<0.01) and its inhibitor (PAI-1) after venous occlusion (VO) (P<0.05). Atorvastatin induced a significant increase of PAP at T(2) related to modifications of P-sel (P<0.01) and PDTG (P<0.01) before significant LDL-C reduction (P=0.132). PAI-1 was significantly changed at T(3) with relation to LDL-C (P<0.01), Von Willebrand factor (VWF) (P<0.01) and sE-sel (P<0.05). CONCLUSIONS: The profibrinolytic activity of atorvastatin in hypercholesterolemic subjects is related, initially, to the positive effects exerted on platelet function and thrombin generation which can modulate fibrinolysis by TAFI activity.

T cell activation and enhanced apoptosis in non-ST elevation myocardial infarction.

Recent studies have shown that inflammation plays a major role in coronary plaque destabilization and in the induction of thrombosis in acute coronary syndromes. The aim of this study was to evaluate circulating lymphocyte activation and apoptosis in patients with non-ST elevation myocardial infarction (NSTEMI) in comparison with subjects with stable angina and with age-matched healthy controls. We considered T cell subpopulations, T cell surface HLA-DR and CD69 expression (evaluated by flow cytometry), lymphomonocyte spontaneous apoptosis (evaluated by ELISA), and IL2 production (evaluated by ELISA) in peripheral blood within 6 hours of onset of NSTEMI. We also investigated Fas expression on T cells (evaluated by flow cytometry) and FasL mRNA (evaluated by RT-PCR), as well as Fas functionality. In NSTEMI patients we found a significant increase of HLADR+ CD3+ and CD69+CD4+ cells. Spontaneous apoptosis was significantly increased in NSTEMI patients in comparison with the two control groups and was associated with an increased expression of Fas, an increased susceptibility to Fas agonist (CH11), and a normal production of IL2 in cell cultures. These data suggest that the enhanced apoptosis is due to a mechanism of "active" antigen-driven death, induced by the expression of death cytokines and not by the failure of cell growth factors. We conclude that peripheral lymphocytes are activated in NSTEMI and undergo an enhanced programmed cell death due to activation mechanisms. It is likely that lymphocyte activation occurs before the onset of acute ischemia and contributes to the plaque rupture and to the myocardial ischemic insult.

Cardiac papillary fibroelastoma: an unusual source of cerebral embolism solved with local fibrinolysis.

Fibroelastoma is an infrequent tumor affecting mainly cardiac valves. Before echocardiography, it was an occasional autoptic finding. With the development of ultrasonographic techniques, it is currently possible to carry out diagnosis in vivo. We report the case of a young woman with cerebral ischemia who was successfully treated by intra-arterial fibrinolysis with complete clinical resolution. Transesophageal echocardiography (TEE) identified a papillary fibroelastoma on the posterior leaflet of the mitral valve. Surgical excision of the tumor was performed. Sudden cerebral or peripheral embolization is frequently linked to thrombotic material which surrounds the neoplasm, and thus can be successfully treated with local fibrinolysis.

2-Arylpyrazolo[1,5-a]pyrimidin-3-yl acetamides. New potent and selective peripheral benzodiazepine receptor ligands.

A new class of N,N-diethyl-(2-arylpyrazolo[1,5-a]pyrimidin-3-yl)acetamides (3f-y), as azaisosters of Alpidem, was prepared following a novel synthetic method and their affinities for both the peripheral (PBR) and the central (CBR) benzodiazepine receptors were evaluated. Binding assays were carried out using both [3H]PK 11195 and [3H]Ro 5-4864 as radioligands for PBR, whereas [3H]Ro 15-1788 was used for CBR, in rat kidney and rat cortex, respectively. The tested compounds exhibited a broad range of binding affinities from as low as 0.76 nM to inactivity and most of them proved to be high selective ligands for PBR. The preliminary SAR studies suggested some of the structural features required for high affinity and selectivity; particularly the substituents on the pyrimidine moiety seemed to play an important role in PBR versus CBR selectivity. A subset of the highest affinity compounds was also tested for their ability to stimulate steroid biosynthesis in C6 glioma rat cells and some of these were found to increase pregnenolone formation with potency similar to Ro 5-4864 and PK 11195.

Different mechanisms of fibrinolysis impairment among dyslipidemic subjects.

To determine whether there is a correlation between fibrinolytic activity and dyslipidemia, we performed a study of 72 subjects (20 patients with hypercholesterolemia, 20 with hypertriglyceridemia, 12 with isolated low high-density lipoprotein (HDL)-cholesterol (mean age 47.7 +/- 6.3, body mass index 24.7 +/- 0.4) and 20 healthy controls. Plasminogen activator inhibitor-1 (PAI-1), tissue-plasminogen activator activity and plasmin-antiplasmin complexes (PAP) were detected at baseline and after venous occlusion test. We also measured at baseline lipidic pattern, soluble E and P selectins (sE-sel, sP-sel), prothrombin factor 1+2 (F1+2), lipoprotein(a), factor VII, plasma insulin, fibrinogen, homocysteine, and thrombin activable fibrinolysis inhibitor (TAFI) activity. Fibrinolysis was significantly reduced in hypertriglyceridemic patients compared with hypercholesterolemic patients and control subjects (PAP, p < 0.01 and p < 0.001) and was associated with increased PAI-1 (at baseline and after venous occlusion test, p < 0.001). sP-sel, F1 +2 and TAFI were not significantly different compared with controls, while hypercholesterolemic subjects showed a significant increase in these parameters (p < 0.001), which were related to decreased PAP only at the upper low-density lipoprotein (LDL)-cholesterol levels (>160 mg/dl) (p < 0.001, r = -0.76). Moreover, there was no significant difference in PAI-1 activity (at baseline and after venous occlusion test) compared with controls. In conclusion, endothelial dysfunction was the main mechanism of decreased fibrinolysis in subjects with hypertriglyceridemia and low HDL-cholesterol, while enhanced thrombin generation and TAFI activity were the main determinants in hypercholesterolemia.

POEMS syndrome with vascular lesions: a role for interleukin-1beta and interleukin-6 increase--a case report.

The authors describe the case of a 60-year-old man with POEMS syndrome associated with vascular lesions. The patient had osteosclerotic myeloma IgA (lambda), polyneuropathy, endocrinopathy, and skin changes. Subsequently, he developed gangrene of the lower limbs with no response to heparin therapy. The humoral study showed thrombocythemia, high levels of interleukin-1beta (IL-1beta) and IL-6 and of some coagulative/fibrinolytic and endothelial factors (von Willebrand factor, plasmin-antiplasmin complexes, plasminogen activator, and endothelial adhesion molecule ICAM-1). The authors suggest that these factors, induced by the increased levels of cytokines, could be responsible for microvascular damage, gangrene, and heparin resistance.

POEMS syndrome with vascular lesions and renal carcinoma - possible role of cytokines.

We describe here the case of a 60 years man with POEMS syndrome associated with renal tumor and vascular lesions. The patient had osteosclerotic myeloma IgA-lambda, polyneuropathy, endocrinopathy and skin changes. In addition, he developed renal clear cell carcinoma and gangrena of lower limbs. The humoral study showed thrombocytosis, high levels of IL-1beta and IL-6 and of some coagulative/fibrinolytic and endothelial factors (von Willebrand factor, plasmin-antiplasmine complexes, plasminogen activator). We suggest the hypothesis that these factors are capable of determining some manifestations of POEMS syndrome.