Pemphigus Vulgaris and Bullous Pemphigoid: Update on Diagnosis and Treatment.

Autoimmune bullous disorders are a heterogeneous spectrum of skin disorders characterized by the production of autoantibodies against adhesion molecules of the skin. The 2 major groups of diseases are "pemphigus diseases" and "autoimmune bullous diseases of the pemphigoid type." Pemphigus diseases are a group of autoimmune blistering diseases of the skin and mucous membranes characterized by intraepithelial cleft and acantholysis. The main subtypes of pemphigus include pemphigus vulgaris, pemphigus foliaceus, and paraneoplastic pemphigus. Diagnosis is based on clinical manifestations and confirmed with histological, immunofluorescence, and serological testing. Recently multivariant enzyme-linked immunosorbent assay systems have been developed as practical screening tools for patients with suspected autoimmune bullous dermatoses. The current first-line treatment of pemphigus is based on systemic corticosteroids that are often combined with immunosuppressive adjuvants, such as azathioprine, mycophenolate mofetil, and the anti-CD20 monoclonal antibody rituximab, usually at initiation of treatment. Rituximab efficacy is higher when it is administered early in the course of the disease. Therefore, it should be used as first-line treatment to improve efficacy and reduce cumulative doses of corticosteroids and their side effects. Treatment of bullous pemphigoid is based on disease extension. Localized and mild forms can be treated with superpotent topical corticosteroids or with nonimmunosuppressive agents. In patients with generalized disease or whose disease is resistant to the treatments described above, systemic corticosteroids are preferred and effective. Adjuvant immunosuppressants are often combined with steroids for their steroid-sparing effect.

Neonatal respiratory support strategies for the management of extremely low gestational age infants: an Italian survey.

BACKGROUND: We aimed to survey Delivery Room and Neonatal Intensive Care Unit (NICU) respiratory strategies dedicated to the extremely low gestational age newborn (ELGAN - GA < 28 wks) in Italy. METHODS: A questionnaire was sent to 113 Italian level III centres. A lead physician and a nurse with expertise in mechanical ventilation (MV) were identified in each unit to answer. Information about those aspects of ventilatory support considered by center's staff as needing improvement was also collected. RESULTS: A 100% response rate was obtained. In the Delivery Room, sustained lung inflation was performed in 74.8% of centres, and 89.2% used NCPAP. For ELGANs who need invasive MV, conventional MV was the most used strategy. Volume-targeted ventilation and High-frequency oscillatory ventilation (HFOV) were considered as primary mode in < 30% of centres. Among non-invasive strategies, NCPAP was the most utilized, followed by BiPAP, High-flow nasal cannula and nasal intermittent positive pressure ventilation. Nurses more commonly recorded in the nursing charts the ventilator's setting parameters rather than measured ones. HFOV and non-invasive ventilation were the most quoted aspects of neonatal ventilation felt as to be improved. CONCLUSION: The routine respiratory support practices in Italy showed marked variations among units. Focused interventions are largely required to improve clinical practice.

Extubation from high-frequency oscillatory ventilation in extremely low birth weight infants: a prospective observational study.

OBJECTIVE: To evaluate if weaning from high-frequency oscillatory ventilation (HFOV) directly to a non-invasive mode of respiratory support is feasible and results in successful extubation in extremely low birth weight (ELBW) infants. DESIGN: Prospective observational study. SETTING: Tertiary neonatal intensive care unit. PATIENTS: One hundred and eight ELBW infants of 26.2±1.4 weeks of gestational age (GA) directly extubated from HFOV. INTERVENTIONS: All infants were managed with elective HFOV and received surfactant after a recruitment HFOV manoeuvre. Extubation was attempted at mean airways pressure (MAP) ≤6 cm H2O with FiO2 ≤0.25. After extubation, all infants were supported by nasal continuous positive airway pressure (6-8 cm H2O). MAIN OUTCOME MEASURES: Extubation failure (clinical deterioration requiring reintubation) was defined as shorter than 7 days. RESULTS: Ninety patients (83%) were successfully extubated and 18 (17%) required reintubation. No significant differences were found between the two groups in terms of birth weight, day of life and weight at the time of extubation. Multivariable analysis showed that GA (OR 1.71; 95% CI 1.04, 2.08) and higher MAP prior to surfactant (OR 1.51; 95% CI 1.06, 2.15) were associated with successful extubation. CONCLUSIONS: In ELBW infants, direct extubation from HFOV at MAP ≤6 cm H2O with FiO2 ≤0.25 is feasible. Our extubation success rate (83%) is higher than conventional mechanical ventilation in this very vulnerable class of infants.

Nasal high-frequency oscillatory ventilation and CO2 removal: A randomized controlled crossover trial.

OBJECTIVE: To compare short-term application of nasal high-frequency oscillatory ventilation (nHFOV) with nasal continuous positive airway pressure (nCPAP). WORKING HYPOTHESIS: nHFOV improves CO2 removal with respect to nCPAP in preterm infants needing noninvasive respiratory support and persistent oxygen supply after the first 72 h of life. STUDY DESIGN: Multicenter non-blinded prospective randomized crossover study. PATIENT SELECTION: Thirty premature infants from eight tertiary neonatal intensive care units, of mean ± SD 26.4 ± 1.8 weeks of gestational age and 921 ± 177 g of birth weight. METHODOLOGY: Infants were randomly allocated in a 1:1 ratio to receive a starting treatment mode of either nCPAP or nHFOV delivered by the ventilator CNO (Medin, Germany), using short binasal prongs of appropriate size. A crossover design with four 1-h treatment periods was used, such that each infant received both treatments twice. The primary outcome was the mean transcutaneous partial pressure of CO2 (TcCO2 ) value during the 2-h cumulative period of nHFOV compared with the 2-h cumulative period of nCPAP. RESULTS: Significantly lower TcCO2 values were observed during nHFOV compared with nCPAP: 47.5 ± 7.6 versus 49.9 ± 7.2 mmHg, respectively, P = 0.0007. A different TcCO2 behavior was found according to the random sequence: in patients starting on nCPAP, TcCO2 significantly decreased from 50.0 ± 8.0 to 46.6 ± 7.5 mmHg during nHFOV (P = 0.001). In patients starting on nHFOV, TcCO2 slightly increased from 48.5 ± 7.8 to 49.9 ± 6.7 mmHg during nCPAP (P = 0.13). CONCLUSIONS: nHFOV delivered through nasal prongs is more effective than nCPAP in improving the elimination of CO2 .

Management of pneumothorax in hemodynamically stable preterm infants using high frequency oscillatory ventilation: report of five cases.

BACKGROUND: Despite an increased use of non-invasive ventilatory strategies and gentle ventilation, pneumothorax remains a common complication in preterm infants. The ventilator management of infants with air leaks remains challenging in terms of both prevention and treatment. Recently the safety and efficacy of expectant management avoiding chest tube drainage to treat large air leak in preterm infants hemodynamically stable has been reported. CASE PRESENTATION: In the present study, we report five cases of preterm infants with birth weight ≤ 1250 g affected by respiratory distress syndrome and treated with nasal continuous positive airway pressure as first intention. They were intubated for worsening of respiratory distress with increasing oxygen requirement and concomitant increase of respiratory rate and PCO2 values due to occurrence of pneumothorax, and they were successfully treated using high-frequency oscillatory ventilation without chest tube insertion. CONCLUSION: In our experience high-frequency oscillatory ventilation provided a conservative management of a significant pneumothorax in preterm newborns hemodynamically stable and requiring mechanical ventilation. This approach allowed us to avoid the increasing of air leak and the insertion of chest tube drainage and all the subsequent associated risks.

Fetal Doppler velocimetry and bronchopulmonary dysplasia risk among growth-restricted preterm infants: an observational study.

OBJECTIVE: To investigate whether fetal growth restriction (FGR) diagnosis, based on pathological prenatal fetal Doppler velocimetry, is associated with bronchopulmonary dysplasia (BPD) independently of being small for gestational age (SGA) per se at birth among very preterm infants. DESIGN: Prospective, observational study. FGR was defined as failing fetal growth in utero and fetal Doppler velocimetry abnormalities. SETTING: Policlinico Universitario Agostino Gemelli, Roma, Italy. PATIENTS: Preterm newborns with gestational age ≤30 weeks and birth weight (BW) ≤1250 g. MAIN OUTCOME MEASURES: Bronchopulmonary dysplasia. RESULTS: In the study period, 178 newborns were eligible for the study. Thirty-nine infants (22%) were considered fetal growth-restricted infants. Among the 154 survived babies at 36 weeks postmenstrual age, 12 out of 36 (33%) of the FGR group developed BPD versus 8 out of 118 (7%) of the NO-FGR group (p<0.001). BPD rate was sixfold higher among the SGA-FGR infants compared with the SGA-NO-FGR infants. In a multivariable model, FGR was significantly associated with BPD risk (OR 5.1, CI 1.4 to 18.8, p=0.01), independently from BW z-score that still remains a strong risk factor (OR 0.5, CI 0.3 to 0.9, p=0.01). CONCLUSION: Among SGA preterm infants, BPD risk dramatically increases when placenta dysfunction is the surrounding cause of low BW. Antenatal fetal Doppler surveillance could be a useful tool for studying placenta wellness and predicting BPD risk among preterm babies. Further research is needed to better understand how FGR affects lung development.

New Insights on Early Patterns of Respiratory Disease among Extremely Low Gestational Age Newborns.

BACKGROUND: The analysis of early patterns of lung disease among preterm infants may help to identify predictors of pulmonary deterioration. OBJECTIVES: To analyze FIO2 requirement in the first 14 days of life among preterm infants and to find predictors of bronchopulmonary dysplasia (BPD). METHODS: Retrospective cohort study. SETTING: 3 Italian level III NICUs. POPULATION: infants born between 240/7 and 276/7 weeks' gestational age (GA) who survived to 14 days. A consecutive sample of 588 infants was analyzed. Daily mode FIO2 in the first 2 weeks of life were analyzed according to the criteria defined by Laughon et al. [Pediatrics 2009;123:1124-1131], who found 3 early respiratory patterns: consistently low FIO2 (LowFIO2), pulmonary deterioration (PD), and early persistent pulmonary deterioration (EPPD). Factors associated with pulmonary deterioration were studied by univariate and multivariate analysis. RESULTS: Forty percent of infants had low FIO2, 18% had pulmonary deterioation, 21% had early persistent pulmonary deterioration, and 21% had a previously unreported pattern (pulmonary improvement, PI). The prevalence of BPD was 7% in the LowFIO2 group, 28% in the PI group, 44% in the PD group, and 62% in the EPPD group (p = 0.000). Infants with lung deterioration were more frequently males (OR = 2.019, CI: 1.319-3.090, p = 0.001), had lower GA (OR = 0.945, CI: 0.915-0.975, p = 0.000), higher incidence of severe respiratory distress syndrome (OR = 2.956, CI: 1.430-6.112, p = 0.003), and lack of postnatal caffeine (OR = 0.167, CI: 0.052-0.541, p = 0.003). CONCLUSIONS: We report 4 distinct patterns of early respiratory disease associated with significantly different prevalence of BPD and discuss risk factors for lung deterioration.

Glycaemic index, glycaemic load and risk of cutaneous melanoma in a population-based, case-control study.

Glycaemic index (GI) and glycaemic load (GL) are indicators of dietary carbohydrate quantity and quality and have been associated with increased risk of certain cancers and type 2 diabetes. Insulin resistance has been associated with increased melanoma risk. However, GI and GL have not been investigated for melanoma. We present the first study to examine the possible association of GI and GL with melanoma risk. We carried out a population-based, case-control study involving 380 incident cases of cutaneous melanoma and 719 age- and sex-matched controls in a northern Italian region. Dietary GI and GL were computed for each subject using data from a self-administered, semi-quantitative food frequency questionnaire. We computed the odds ratio (OR) for melanoma according to quintiles of distribution of GL and GL among controls. A direct association between melanoma risk and GL emerged in females (OR 2·38; 95 % CI 1·25, 4·52 for the highest v. the lowest quintile of GL score, P for trend 0·070) but not in males. The association in females persisted in the multivariable analysis after adjusting for several potential confounders. There was no evidence of an association between GI and melanoma risk. GL might be associated with melanoma risk in females.

Efficacy of a new technique - INtubate-RECruit-SURfactant-Extubate - "IN-REC-SUR-E" - in preterm neonates with respiratory distress syndrome: study protocol for a randomized controlled trial.

BACKGROUND: Although beneficial in clinical practice, the INtubate-SURfactant-Extubate (IN-SUR-E) method is not successful in all preterm neonates with respiratory distress syndrome, with a reported failure rate ranging from 19 to 69 %. One of the possible mechanisms responsible for the unsuccessful IN-SUR-E method, requiring subsequent re-intubation and mechanical ventilation, is the inability of the preterm lung to achieve and maintain an "optimal" functional residual capacity. The importance of lung recruitment before surfactant administration has been demonstrated in animal studies showing that recruitment leads to a more homogeneous surfactant distribution within the lungs. Therefore, the aim of this study is to compare the application of a recruitment maneuver using the high-frequency oscillatory ventilation (HFOV) modality just before the surfactant administration followed by rapid extubation (INtubate-RECruit-SURfactant-Extubate: IN-REC-SUR-E) with IN-SUR-E alone in spontaneously breathing preterm infants requiring nasal continuous positive airway pressure (nCPAP) as initial respiratory support and reaching pre-defined CPAP failure criteria. METHODS/DESIGN: In this study, 206 spontaneously breathing infants born at 24(+0)-27(+6) weeks' gestation and failing nCPAP during the first 24 h of life, will be randomized to receive an HFOV recruitment maneuver (IN-REC-SUR-E) or no recruitment maneuver (IN-SUR-E) just prior to surfactant administration followed by prompt extubation. The primary outcome is the need for mechanical ventilation within the first 3 days of life. Infants in both groups will be considered to have reached the primary outcome when they are not extubated within 30 min after surfactant administration or when they meet the nCPAP failure criteria after extubation. DISCUSSION: From all available data no definitive evidence exists about a positive effect of recruitment before surfactant instillation, but a rationale exists for testing the following hypothesis: a lung recruitment maneuver performed with a step-by-step Continuous Distending Pressure increase during High-Frequency Oscillatory Ventilation (and not with a sustained inflation) could have a positive effects in terms of improved surfactant distribution and consequent its major efficacy in preterm newborns with respiratory distress syndrome. This represents our challenge. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02482766 . Registered on 1 June 2015.

Diet Quality and Risk of Melanoma in an Italian Population.

BACKGROUND: Some results from laboratory and epidemiologic studies suggest that diet may influence the risk of melanoma, but convincing evidence for a role of single nutrients or food items is lacking. Diet quality, which considers the combined effect of multiple food items, may be superior for examining this relation. OBJECTIVE: We sought to assess whether diet quality, evaluated with the use of 4 different dietary indexes, is associated with melanoma risk. METHODS: In this population-based case-control study, we analyzed the relation between 4 diet quality indexes, the Healthy Eating Index 2010 (HEI-2010), Dietary Approaches to Stop Hypertension (DASH) index, Greek Mediterranean Index (GMI), and Italian Mediterranean Index (IMI), and melanoma risk in a northern Italian community, with the use of data from 380 cases and 719 matched controls who completed a semiquantitative food frequency questionnaire. RESULTS: In the overall sample, we found an inverse association between disease risk and the HEI-2010 and DASH index, but not the Mediterranean indexes, adjusting for potential confounders (skin phototype, body mass index, energy intake, sunburn history, skin sun reaction, and education). However, in sex stratified analyses, the association appeared only in women (P-trend: 0.10 and 0.04 for the HEI-2010 and DASH index, respectively). The inverse relations were stronger in women younger than age 50 y than in older women, for whom the GMI and IMI scores also showed an inverse association with disease risk (P-trend: 0.05 and 0.02, respectively). CONCLUSIONS: These results suggest that diet quality may play a role in cutaneous melanoma etiology among women.

Fluconazole-induced acute generalized exanthematous pustulosis.

Acute generalized exanthematous pustulosis (AGEP) is a severe cutaneous adverse reaction and is usually caused by drugs. It is characterized by fever and acute, extensive occurrence of disseminated sterile pustules, accompanied by fever, malaise and peripheral blood leucocytosis. There have been several reports to date of AGEP following exposure to antifungals. In particular, terbinafine is included in the list of the agents conferring the highest risk of AGEP. The authors report the case of a 70-year-old male patient who developed AGEP shortly after commencing treatment with fluconazole, which has been reported in association with AGEP in a single case report. To our knowledge, this is the first reported case of AGEP associated with positive fluconazole patch test.

Determination of Lung Volume and Hemodynamic Changes During High-Frequency Ventilation Recruitment in Preterm Neonates With Respiratory Distress Syndrome.

OBJECTIVES: To evaluate the changes in end-expiratory lung volume during an oxygenation-guided stepwise recruitment procedure in elective high-frequency ventilation. We hypothesized that high continuous distending pressure impedes pulmonary blood flow as evidenced by reduced lung volume measurements using respiratory inductive plethysmography. Changes in oxygenation, ventilation, and peripheral perfusion were evaluated as secondary outcomes. DESIGN: A prospective, single center, observational, nonrandomized study. SETTING: The study was conducted in a neonatal ICU in Italy. PATIENTS: High-frequency ventilated preterm infants with respiratory distress syndrome. INTERVENTIONS: During the recruitment procedure, end-expiratory lung volume measured by respiratory inductive plethysmography, oxygen saturation, perfusion index, regional cerebral and perirenal tissue oxygenation, heart rate, transcutaneous PCO2, and tidal volume were simultaneously recorded at each airway pressure step. MEASUREMENTS AND MAIN RESULTS: In 12 preterm newborns (gestational age, 27.4 ± 0.2 wk; birth weight, 979 ± 198 g), high-frequency ventilation was initiated at a continuous distending pressure of 10 cm H2O and incrementally increased by 1-2 cm H2O every 2-5 minutes until FIO2 was less than or equal to 0.25. End-expiratory lung volume progressively increased during the initial recruitment, but decreased at the maximum airway pressure in nine patients, indicative of a reduction in pulmonary perfusion. At the end of recruitment, tidal volume was significantly higher (p = 0.002) and oxygenation was significantly improved (p = 0.002); however, mean perfusion index, postductal saturation, and mean renal tissue oxygenation values were significantly reduced (p < 0.05) compared with baseline. Mean cerebral tissue oxygenation and mean transcutaneous PCO2 values were reduced but failed to reach significance. CONCLUSIONS: High distending lung pressures increased oxygenation but decreased peripheral perfusion with no adverse cerebral side effects. Coupled with the reduction in respiratory inductive plethysmography-derived lung volume, high continuous distending pressure had adverse cardiopulmonary effects. Incorporation of lung volume and hemodynamic and oxygenation variables may guide optimum lung volume determination during high-frequency ventilation recruitment procedure while preventing adverse effects on the pulmonary circulation.

When biopsy alone is not enough for the diagnosis: angiomatous florid proliferation hiding a merkel cell carcinoma.

Merkel cell carcinoma (MCC) is an aggressive tumor with an uncertain histogenesis typically arising on sun-damaged skin of the elderly. It has rarely been described in association with other tumors such as epithelial, melanocytic, and mesenchymal, but not vascular neoplasias. However, an exuberant vascular reaction is considered a common phenomenon in neuroendocrine neoplasms, where it can even obscure the proliferating cells and mimic a primary vascular neoplasia. A 47-year-old man was referred for the evaluation of a long-lasting reddish skin tumor located on the right buttock. After 2 punch biopsies, the patient underwent surgical excision of the lesion. Histological examination showed a dermal florid, benign vascular proliferation overlying some large deep coalescent nodules made up of monomorphous round cells with scant cytoplasm and a high mitotic activity. After the appropriate immunohistochemical stainings, a final diagnosis of hemangioma overlying a previously unrecognized MCC was rendered. Whether the angiomatous proliferation should be considered an exuberant reaction to the tumor, induced by an angiogenetic drive, or a true hemangioma is somewhat controversial. The main point is that such a neoplastiform angiomatous proliferation may represent a potential diagnostic pitfall, especially in limited specimens, and that an accurate clinicopathologic correlation is always needed. In our case, even if additional punch biopsies had been performed, the vascular proliferation would dominate the histological picture and an accurate diagnostic conclusion would probably not be reached due to the deep location of the MCC.

Clinical predictors of non-response to any tumor necrosis factor (TNF) blockers: a retrospective study.

BACKGROUND: Anti-tumor necrosis factor (TNF)-α therapies represent a significant innovation in therapy for psoriasis. However, a significant number of psoriasis patients do not respond well to TNF blockers or show an insufficient control of disease activity on a long-term basis. OBJECTIVE/AIM: The aim of this study was to recognize specific clinical factors that could be associated with a non-response to any available TNF blockers in patients with moderate-to-severe plaque psoriasis. MATERIALS AND METHODS: The authors reviewed the medical records of all patients who had started etanercept, infliximab, adalimumab and had achieved a minimum of 24 months follow-up. The authors identified subjects who were not responsive to all available anti-TNF agents, whatever the chronology of their use. RESULTS: A total of 110 patients were retrospectively examined. Thirteen patients were identified as "non-responders" to all available TNF-α blockers. Current smoking at the start of anti-TNF therapy was associated with non-response to TNF blockers. The group of "non-responders" presented a high mean body mass index and a high baseline PASI score with respect to the group of responders. CONCLUSIONS: The data showed that the majority of non-responder patients were smokers, overweight or obese and had a high baseline PASI score. Concomitant arthritis was not significantly associated with non-response.

Metastasizing basal cell carcinoma.

Basal cell carcinoma (BCC) is the most common malignancy worldwide and is characterized by invasive growth and local tissue destruction. Cure rates for BCC exceed 90% with most treatment modalities. Metastasizing BCC (MBCC) is a rare complication of BCC with high morbidity and mortality rates. We report the case of a 66-year-old man with a large ulcerative lesion on the left side of the flank that was histopathologically diagnosed as a BCC. Clinical and imaging evaluations revealed substantial local invasion with regional lymph node, lung, liver, bone marrow, and bone metastasis. The patient died 7 months after the diagnosis was made. Potentially metastasizing BCCs cannot be definitely identified; thus early intervention with adequate treatment of all BCCs is advised.

Problematic lesions in the elderly.

As the population continues to age, clinicians and dermatologists are increasingly faced with geriatric patients presenting with a range of dermatologic manifestations, including benign and malignant skin tumors. Knowledge of epidemiologic and morphologic features, including dermoscopy of common and benign melanocytic and nonmelanocytic skin tumors, provides the basis for a better understanding and management of problematic skin tumors in this age group. This article provides an overview of common and problematic skin lesions in elderly patients and addresses epidemiologic, clinical, and dermoscopic clues that aid the differential diagnosis and management of challenging skin lesions.

The light and the dark of dermatoscopy in the early diagnosis of melanoma: facts and controversies.

Early diagnosis remains the best method to reduce melanoma and non-melanoma skin cancer-related mortality and morbidity. Dermatoscopy was first introduced at the end of the last century, and besides the strict criticism that it initially received, the majority of the scientific community presently considers it revolutionary in the field of melanocytic lesion diagnostics. Cumulative evidence provides definite data that dermatoscopy improves the clinicians' diagnostic accuracy for melanoma compared with other clinical diagnostic approaches. There remain some barriers for its use such as lack of training, lack of time, and lack of reimbursement, as well as persisting skepticism about its true utility. In the current contribution, we focus on false beliefs and facts concerning dermatoscopy in the early diagnosis of melanoma and shed some light on some of the remaining "dark sides" of this issue.

Efficacy of exogenous surfactant during conventional and high-frequency oscillatory ventilation in preterm infants with RDS.

INTRODUCTION: The immediate effects of exogenous surfactant on lung volume and hemodynamics in preterm infants have been poorly studied. MATERIALS AND METHODS: Lung volume, SpO2, perfusion index, regional SO2, transcutaneous partial pressure of CO2 were simultaneously monitored and recorded ten minutes after surfactant tracheal instillation in elective HFOV ventilated preterm infants with RDS. OUTCOMES: Despite a reduction in gas exchange during the first 5 minutes post surfactant instillation, most likely dependent on airway obstruction, lung volume increases rapidly in HFOV preterm infants with RDS. After 5 minutes from administration of surfactant, lung volume, gas exchange and PI reach stable values and CDP can be safely reduced.