Cross-elicitation responses to 2-methoxymethyl-p-phenylenediamine in p-phenylenediamine highly allergic volunteers using allergy alert test: the Italian experience.

Summary: Background. Allergic contact dermatitis after exposure to p-phenylenediamine (PPD)-containing hair dye products is a common and important clinical problem. Because there is a high rate of cross-elicitation of allergic contact dermatitis to other important hair dye products (such as p-toluene diamine [PTD] and other aminophenol hair dyes) in PPD allergic patients, safer alternative dyes with excellent hair coloring options are needed. We studied 2-methoxy methyl-PPD (Me-PPD), a chemical derivative of PPD for tolerance versus cross-elicitation in a cohort of eight PPD-allergic volunteers. Objective. To study tolerance to Me-PPD in a PPD highly allergic Italian cohort. Methods. Eight volunteers with a history of contact dermatitis to hair dyes or other PPD-containing chemicals and positive patch tests to 1% PPD in petrolatum, were recruited to study their immediate and delayed skin reactivity to PPD, vehicle control and 2-methoxy-methyl-PPD (Me-PPD), using the allergy alert test (simulating hair dyeing conditions) on volar forearm skin. This is a short-contact open patch test. Results. All eight volunteers reacted to PPD allergy alert test (100%); none reacted to vehicle (0%), and seven of eight reacted to Me-PPD allergy alert test (88%). However, in those seven volunteers who exhibited cross-elicitation to Me-PPD, their aggregate skin test reactivity to Me-PPD was significantly less than that of PPD (figure 3, p minore 0.0062, highly significant, paired two-tailed, students t test). Conclusions. Me-PPD may offer a safer alternative for PPD-allergic patients with an absent or reduced elicitation response in the allergy alert test simulating hair dye use conditions. Even patients with strong patch test reactions, with appropriate selection by allergy alert test and counselling, may be able to tolerate hair dyeing with Me-PPD containing products.

A case of hypersensitivity to progesterone presenting as an eczematous eruption.

Hypersensitivity to progesterone is a rare condition, and it represents a hypersensitivity reaction to endogenous progesterone. Here we report a case of a woman who presented to our attention for evaluation of a rash for a few years on her posterior elbows, forearms, and right lateral lower extremity. We report this case because it describes a rare clinical entity, with an atypical clinical presentation pemphigoid-like, that is rarely described in literature.

Laparoscopic ventral rectopexy using biologic mesh for the treatment of obstructed defaecation syndrome and/or faecal incontinence in patients with internal rectal prolapse: a critical appraisal of the first 100 cases.

BACKGROUND: Laparoscopic ventral mesh rectopexy (LVR) is gaining wider acceptance as the preferred procedure to correct internal as well as external rectal prolapse associated with obstructed defaecation syndrome and/or faecal incontinence. Very few reports exist on the use of biologic mesh for LVR. The aim of our study was to report the complication and recurrence rate of our first 100 cases of LVR for symptomatic internal rectal prolapse and/or rectocele using a porcine dermal collagen mesh. METHODS: Prospectively collected data on LVR for internal rectal prolapse were analysed. Surgical complications and functional results in terms of faecal incontinence (measured with the Faecal Incontinence Severity Index = FISI) and constipation (measured with the Wexner Constipation Score = WCS) at 3, 6 and 12 months were analysed. It was considered an improvement if FISI or WCS scores were reduced by at least 25 % and a cure if the FISI score decreased to <10 and the WCS decreased to <5. RESULTS: Between April 2009 and April 2013, 100 consecutive female patients (mean age 63 years, range 24-88 years) underwent LVR. All patients had internal rectal prolapse (grade III [n = 25] and grade IV [n = 75] according to the Oxford classification) and rectocele. Mean operative time was 85 ± 40 min. Conversion rate to open technique was 1 %. There was no post-operative mortality. Overall 16 patients (16 %) experienced 18 complications, including rectal perforation (n = 1), small bowel obstruction (n = 2), urinary tract infection (n = 8), subcutaneous emphysema (n = 3), wound haematoma (n = 2), long lasting sacral pain (n = 1) and incisional hernia (1). Median post-operative length of stay was 2 days. Ninety-eight out of 100 patients completed follow-up. At the end of follow-up, the mean FISI score improved from 8.4 (±4.0 standard deviation (SD) p = 0.003) to 3.3 ± 2.3 SD (p = 0.04). Incontinence improved in 37 out of 43 patients (86 %), and 31 patients (72 %) were cured. Similarly, the mean WCS score improved from 18.4 ± 11.6 SD to 5.4 ± 4.1 SD (p = 0.04). Constipation improved in 82 out of 89 patients (92 %), and 70 patients (79 %) were cured. No worsening of continence status, constipation or sexual function was observed. Fourteen patients (14 %) experienced persistence or recurrence of prolapse. CONCLUSIONS: LVR using biologic mesh is a safe and effective procedure for improving symptoms of obstructed defaecation and faecal incontinence in patients with internal rectal prolapse associated with rectocele.

Modified laparoscopic ventral mesh rectopexy.

We present a modified laparoscopic ventral mesh rectopexy procedure using biological mesh and bilateral anterior mesh fixation. The rectopexy is anterior with a minimal posterior mobilization. The rectum is symmetrically suspended to the sacral promontory through a mesorectal window.

Defecatory disorders in anorexia nervosa: a clinical study.

BACKGROUND: Defecatory disorders in patients with eating disorders have been overlooked. We evaluated the prevalence and type of defecatory disorders in patients with anorexia nervosa. METHODS: The aim of our questionnaire-based study was to determine the prevalence of constipation and faecal incontinence (FI) in patients with anorexia nervosa attending our dedicated eating disorders outpatient clinics and whether length of illness and low body mass index (BMI) exacerbate both constipation and FI. The Wexner constipation score (WCS), Altomare's obstructed defecation score (OD score) and the faecal incontinence severity index (FISI) were used to evaluate constipation and incontinence. A WCS ≥5, OD score ≥10 and a FISI ≥10 were considered clinically relevant. RESULTS: Eighty-five patients (83 females; mean age 28 years ± 13) with anorexia nervosa (study group) and mean BMI of 16 ± 2 kg/m(2) (range 14-19 kg/m(2)) were studied. This group was compared to 57 healthy volunteers (control group) with mean BMI of 22 ± 3 kg/m(2) (range 20-27 kg/m(2)). In the study group, 79/85 (93%) patients suffered from defecatory disorders defined as at least one abnormal score, either WCS, OD score or FISI, compared to 7/57 (12%) controls (p < 0.001). Constipation (defined as WCS ≥5) was present in 70/85 (83%) patients with anorexia and in 7/57 (12%) controls (p = 0.001), while obstructed defecation syndrome (defined as OD score ≥10) was present in 71/85 (84%) patients with anorexia and 7/57 (12%) controls (p < 0.001). In patients with anorexia, the mean WCS score was 10 ± 5 standard deviation (SD) (3 ± 2 SD in controls; p < 0.001), and the mean OD score was 12 ± 4 SD (3 ± 4 SD in controls; p < 0.001). Overall, 62/85 (73%) patients with anorexia had FI defined as FISI score ≥10, and the mean FISI score in anorexia patients was 12 ± 9 SD. A combination of constipation and FI (either both WCS and FISI abnormal or both OD score and FISI abnormal) was present in 55/85 (64%) and 8/85 (9%) presented with FI alone. Moreover, all results are influenced by the severity of the disease measured by BMI and duration. The percentage of defecatory disorders rises from 75 to 100% when BMI is <18 kg/m(2) and from 60 to 75% when the duration of illness is ≥5 years (p < 0.001 and p = 0.021, respectively). CONCLUSIONS: Defecatory disorders are associated with anorexia nervosa and increased with the duration and severity of the illness.

Allergic contact dermatitis: epidemiology, molecular mechanisms, in vitro methods and regulatory aspects. Current knowledge assembled at an international workshop at BfR, Germany.

Contact allergies are complex diseases, and one of the important challenges for public health and immunology. The German 'Federal Institute for Risk Assessment' hosted an 'International Workshop on Contact Dermatitis'. The scope of the workshop was to discuss new discoveries and developments in the field of contact dermatitis. This included the epidemiology and molecular biology of contact allergy, as well as the development of new in vitro methods. Furthermore, it considered regulatory aspects aiming to reduce exposure to contact sensitisers. An estimated 15-20% of the general population suffers from contact allergy. Workplace exposure, age, sex, use of consumer products and genetic predispositions were identified as the most important risk factors. Research highlights included: advances in understanding of immune responses to contact sensitisers, the importance of autoxidation or enzyme-mediated oxidation for the activation of chemicals, the mechanisms through which hapten-protein conjugates are formed and the development of novel in vitro strategies for the identification of skin-sensitising chemicals. Dendritic cell cultures and structure-activity relationships are being developed to identify potential contact allergens. However, the local lymph node assay (LLNA) presently remains the validated method of choice for hazard identification and characterisation. At the workshop the use of the LLNA for regulatory purposes and for quantitative risk assessment was also discussed.

Autologous CD133+ cells augment the effect of portal embolization.

AIM: The standard to treat liver tumors is a resection. When the future liver remnant (FLRV) is below 30% (healthy livers) or 40% (cirrhotic livers or previous chemotherapy), surgery carries the risk of severe complications. Portal vein embolization (PVE) gained a worldwide diffusion as a tool to augment the FLRV. Cell therapies are recent players at the frontiers of medicine. This study presents a clinical experience to evaluate the synergistic effect of combined PVE and autologous CD133+ cells coadministration. METHODS: Sixteen patients have been enrolled in the study up today. Inclusion criteria were: primary or metastatic liver malignancy with a FLRV<30% or 40%. A baseline volumetric CT-scan was obtained. CD34+ were mobilized to the blood stream by G-CSF administration and collected by immunomagnetic separation. Simultaneously with PVE, cells were administered to the non occluded liver segments. Follow-up CT scans were taken at 30th post treatment day. RESULTS: The patients (N.=6) showed an increased volume gain (Mann-Whitney test P<0.001, two sided) compared to a set of cases whose treatment was PVE only (N.=10). DISCUSSION: The use of autologous stem cells as an augmenter of liver regeneration has a clinical potential to improve the resectability of liver tumors.

Dopaminergic receptors in the human skin.

Dopamine is a neurotransmitter which plays an important role in many human organs including the skin. In this study we will examine the presence and the distribution of D1 and D2 dopamine receptors in a particular zone of the human skin. Samples of the human plantar skin were harvested during autopsies after the consent of relatives of the dead donors. In this study the following experimental procedures were performed: 1) drawing of the human plantar skin; 2) cutting of tissues; 3) staining of tissues; 4) staining of the nerve fibres; 5) radio-binding methods for labelling D1 and D2 dopamine receptors; 6) light microscope autoradiography; 7) quantitative analysis of images and 8) statistical analysis of data. The dopamine receptors D1 are distributed particularly in the dermis layer of the human plantar skin. They are numerous in lower epidermal layers (with exclusion of the corneal layer) and few in subcutaneous tissue. On the contrary D2 dopamine receptors are prominent in the subcutaneous tissue near the vessels. Quantitative analysis of images and statistical analysis of the data confirm all our results. The specific distribution of D1 and D2 dopamine receptors in the human plantar skin is in close relation with the functions of a particular zone of the human skin that supports the weight of all the body. Moreover the character of dopamine receptors distribution is very important for further understanding the role of these receptors in the human skin.

Collagen matrix injection combined with flap repair for complex anal fistula.

Several biomaterials have been proposed to treat anal fistula alone or in combination with other surgical procedures aiming to reduce recurrence rates while minimizing continence impairment. More recently a porcine dermal matrix injection has been proposed as infill biomaterial to treat fistulae. We propose an approach consisting of non-cutting seton positioning followed several weeks later by flap repair associated with dermal matrix injection into the fistula tracts. We report our experience with this two-staged procedure on 24 consecutive patients with complex anal fistulae with a median follow up of > 12 months. In our experience this two-stage approach seems to be safe and effective.

Saving time stitching thick biological mesh during laparoscopic ventral rectopexy.

We present a trick to save time at stitching of thick biological mesh during laparoscopic ventral mesh rectopexy by the use of a belt hole puncher.

Contact allergic dermatitis to gold in a tattoo: a case report.

The art of tattooing has increasing in recent decades. Allergic sensitivity to one of the pigments is the most frequent cause of dermatological reactions at the site of the tattoo. Gold is a new pigment used in tattooing, because of its bright yellow color and luster. Allergy to this metal is uncommon. To our knowledge, this is the first reported case of allergic contact dermatitis to gold in a tattoo.

Longitudinal health surveillance in a cohort of Gulf War veterans 18 years after first exposure to depleted uranium.

As part of a longitudinal surveillance program, 35 members of a larger dynamic cohort of 79 Gulf War I veterans exposed to depleted uranium (DU) during combat underwent clinical evaluation at the Baltimore Veterans Administration Medical Center. Health outcomes and biomonitoring results were obtained to assess effects of DU exposure and determine the need for additional medical intervention. Clinical evaluation included medical and exposure histories, physical examination, and laboratory studies including biomarkers of uranium (U) exposure. Urine collections were obtained for U analysis and to measure renal function parameters. Other laboratory measures included basic hematology and chemistry parameters, blood and plasma U concentrations, and markers of bone metabolism. Urine U (uU) excretion remained above normal in participants with embedded DU fragments, with urine U concentrations ranging from 0.006 to 1.88 µg U/g creatinine. Biomarkers of renal effects showed no apparent evidence of renal functional changes or cellular toxicity related to U body burden. No marked differences in markers of bone formation or bone resorption were observed; however, a statistically significant decrease in levels of serum intact parathyroid hormone and significant increases in urinary calcium and sodium excretion were seen in the high versus the low uU groups. Eighteen years after first exposure, members of this cohort with DU fragments continue to excrete elevated concentrations of uU. No significant evidence of clinically important changes was observed in kidney or bone, the two principal target organs of U. Continued surveillance is prudent, however, due to the ongoing mobilization of uranium from fragment depots.

Ligation of the intersphincteric fistula tract (LIFT) to treat anal fistula: early results from a prospective observational study.

BACKGROUND: Ligation of the intersphincteric tract (LIFT), a novel sphincter-saving technique, has been recently described with promising results. Literature data are still scant. In this prospective observational study, we present our experience with this technique. METHODS: Between October 2010 and April 2011, 18 patients with 'complex' fistulas underwent LIFT. All patients were enrolled in the study after a physical examination including digital examination and proctoscopy. For the purpose of this pilot study, fistulas were classified as complex if any of the following conditions were present: tract crossing more than 30% of the external sphincter, anterior fistula in a woman, recurrent fistula or pre-existing incontinence. Endpoints were healing time, presence of recurrence, faecal incontinence and surgical complications. RESULTS: Ten patients were men and 8 were women; mean age was 39 years; minimum follow-up was 4 months. Three patients required drainage seton insertion and delayed LIFT. After LIFT, 1 patient experienced haemorrhoidal thrombosis. At the end of the follow-up, 15 patients (83%) healed with no recurrence. Three patients had persistent symptoms and required further surgical treatment. We did not observe postoperative worsening of continence. CONCLUSIONS: Results from our pilot study indicate that this novel sphincter-saving approach is effective and safe for treating complex anal fistula.

Nephrogenic systemic fibrosis with a spectrum of clinical and histopathological presentation: a disorder of aberrant dermal remodeling.

BACKGROUND: Nephrogenic fibrosing dermopathy (NFD) has emerged as a clinicopathologic entity since 1997 and recently renamed as nephrogenic systemic fibrosis (NSF). The etiology and pathogenesis remain uncertain. Characteristic clinical presentation is described as diffuse thickening and hardening of the skin occurring in patients with renal insufficiency. Typical histological features include proliferation of CD34 positive fibrocytes, increased thick collagen bundles and mucin deposition, without significant inflammatory infiltrate. Variations in clinical presentations have been reported, including papular and plaque-like skin lesions, focal lesion only, as well as systemic involvement. Histological changes can be subtle and non-specific, overlapping with other disease processes and harboring features including calcification and osteoclast-like giant cells with osseous metaplasia. METHODS: We reviewed patients with NSF that presented to our dermatology clinic by chart review, clinical examination and histological examination. Skin biopsy specimens were obtained from all cases. Histopathology evaluations were carried out by three dermatopathologists (AD, BS and GK) independently and the features were compared among all the cases. Special stains and immunohistochemistry study were also performed to highlight the histological features. RESULTS: Seven cases of NSF presented with a spectrum of clinical manifestations, from classic diffuse hardening of the skin to localized linear plaques. On histological examination, proliferation of CD34-positive fibrocytes ranged from sparse to dense, collagen bundles ranged from thin to thick, and the interstitial dermal mucin accumulation ranged from scant-patchy to abundant. In addition, the lesion displayed various degrees of vascular proliferation, inflammatory infiltrates and intensities of CD68 and Factor XIIIa staining. Two cases showed extensive dermal calcification and ossification. CONCLUSION: NSF may present with a spectrum of clinical abnormalities, and exhibit overlapping histopathological features resembling cicatrix and other dermal reparative/regenerative processes. NSF may in fact to be a disorder of aberrant extracellular matrix remodeling in patients with renal insufficiency.

Laparoscopic treatment of a gastric diverticulum.

Gastric diverticula are rare disorders which present usually with vague upper abdominal symptoms. The diagnosis is based on endoscopic and radiologic findings, but it may remain uncertain until the operation. Herein we report the case of a 46-year-old woman with a diverticulum of the posterior aspect of the upper part of the gastric fundus, referred to our attention for epigastric pain. The preoperative work out evidenced a pouch of the gastric fundus which was misinterpreted as a paraesophageal or a diaphragmatic hernia. The operation was performed by laparoscopy with a 4-port technique and the diverticulum was resected by an endoscopic stapler. The patient is well and symptom-free more than two months after the operation.

Langerhans cells in allergic contact dermatitis.

Allergic contact dermatitis (ACD) is a common skin disease that has significant socio-economic impact. ACD is mediated by a T-cell mediated inflammatory reaction. Langerhans cells (LCs) are an epidermal DCs subset specialized in antigen presentation. After hapten exposure, LCs play a major role as in induction adaptive immune response against allergens. LCs recognize, take up and process haptens and migrate to the local draining lymph nodes. However, LCs specific functions and the LCs migration to local draining lymph nodes are not yet clearly defined. Recent advance in the knowledge of LCs function has increased in the past decades including the evidence for a tolerogenic function of LCs. The present review will focus on the role for LCs response to contact allergens.

Th17/Tc17 infiltration and associated cytokine gene expression in elicitation phase of allergic contact dermatitis.

BACKGROUND: Allergic contact dermatitis (ACD) is a typical delayed-type hypersensitivity to sensitizing haptens mediated by T cells. Th1/Tc1 cells are currently considered to be the primary effectors in ACD. There is little information concerning the role played in ACD in humans by Th17/Tc17 cells, a recently defined subpopulation of effector T cells. OBJECTIVES: In the present report we attempted to characterize Th17/Tc17 cells in the infiltrates of the skin in the elicitation phase of ACD. METHODS: Th17 as well as Th1/Th2 cytokine gene expression was examined by semiquantitative real-time polymerase chain reaction in paired samples of positive patch test biopsies and normal skin from 11 patients allergic to nine different allergens. The in situ characterization of interleukin (IL)-17-producing cells was carried out using anti-RORC and anti-T-cell subset antibodies by double immunofluorescence. RESULTS: Compared with normal paired skin samples, gene expression of transcription factor for human Th17 cells, RORC, and Th17-related cytokines IL-17A, IL-17F and IL-23 was significantly increased in positive patch test biopsies. The mRNA for interferon-gamma and IL-4 was also increased. In the dermal infiltrates, about 20% of the infiltrating cells were IL-17-producing cells as they expressed RORC, and such RORC-expressing cells were detected in both CD4+ (approximately 30%) and CD8+ (approximately 20%) subsets. CONCLUSIONS: This is the first demonstration of Th17/Tc17 cells in the elicitation phase of human ACD, showing that they are a regular participant in the immunopathology of this common allergic reaction regardless of the nature of the triggering allergen.