Skin Erosion Research Articles

Mutation p.R156H of KRT10 responsible for severe phenotype of epidermolytic ichthyosis in a Chinese family.

Dear editor Epidermolytic ichthyosis is a rare genetic disorder characterized by diffuse erythroderma from the time of birth with subsequent appearance of thick, brown scales and occasional blister formation. Mutation has been found in keratin 1 (K1) and keratin 10 (K10) genes.1 Epidermolytic hyperkeratosis (EHK) is mostly inherited in a dominant mode. We report a Chinese family of EHK sufferers and their mutation findings. The pedigree of the EHK family showed an autosomal dominant inheritance pattern (Figure 1). The proband, a 41 year-old Chinese woman, had erythroderma on the head, trunk, and extremities. She exhibited skin blistering, erosions, erythrodermic, and hyperkeratosis on the skin since infancy and the blistering and erosion gradually diminished with age. Physical examination revealed hyperkeratosis of the entire body (Figure 2A) and desquamation of the palm (Figure 2B). Her son, a 13 year-old boy, has a similar history and clinical manifestation. He was born with typical extensive erythroderma and bullae, and his skin was covered with hyperkeratotic patches of scales. Hyperkeratotic plaques can be seen on the back of the hand (Figure 2C), this lesion healed quickly after retinoid acid treatment (Figure 2D). Pathological examination of the upper portion of his left arm showed granular degeneration in the suprabasal layers (Figure 2E). Figure 1 Pedigree figure. Figure 2 Clinical, histopathological, and gene sequencing of the patients. Direct sequencing of the whole coding regions of KRT1 and KRT10 was performed. A heterozygous KRT10 missense mutation c.467G>A(p.Arg156His) was identified in the proband and her son, while not in normal controls (Figure 2F and G). The mutation hotspots of EHK are located at the conserved sequences in helix initiative and helix terminal motifs of K1 and K10.2 The mutation of the reported family, c.467G>A, just occurred at the hotspots. A previous study has revealed that the relationship between the genotype and phenotype in these patients was complex, not only dependent on the position of the mutation but also on the actual amino acid substitution.3,4 The p.R156 of KRT10 can be substituted by many amino acids such as serine, glycine, cysteine, histidine, and leucine, of which histidine is the most similar to arginine. Theoretically, the p.Arg156His mutation should be accompanied by a mild clinical manifestation,3 but the reported patients experienced severe conditions. So we cannot conclude that the more similar between two amino acid substitution in the same codon, the milder consequence will be brought. The p.Arg156His mutation is rather common in previous reports,2,4 but the clinical manifestations vary greatly. Other genetic or epigenetic factors that were not identified may influence disease severity. In conclusion, we confirm the diagnosis of epidermolytic ichthyosis in the two patients according to the genetic testing and this is beneficial for their genetic counseling. The results reveal that the mutation p.R156H of KRT10 is responsible for severe clinical manifestations in a Chinese family with EHK, and also confirm the complexity of the genotype–phenotype correlation in EHK.

Role of Linseed oil in preventing peri-ileostomy skin excoriation

Introduction: Our gastrointestinal tract bears the entire burden to give us energy for living. Sometimes it gives way and causes lot of sufferings. Many surgeries have been devised to save the lives of patients suffering from these gastrointestinal diseases and stoma formation is one such surgery. Stoma though saves life but it itself causes lot of problems and the most dreaded one is peristomal skin excoriation. Peri-stomal excoriation can be broadly defined as any wound that is adjacent to a stoma, including erosion or ulceration of the peri-stomal skin. It is most dangerous in iliostomy patients. This study was carried out to study the effects of linseed oil in preventing peri-iliostomy skin excoriation. Materials and Methods: This study was carried out at Bundelkhand Medical College, Sagar from 2009 to 2012. 24 patients were included in this study in whom iliostomy was done due to perforation peritonitis. Linseed or flax seed oil was applied in all the patients to prevent peri-iliostomy skin excoriation. Results: In this study only 3 patients developed minor skin excoriation, rest all were having healthy peri-iliostomy skin with continued use of linseed oil till stoma closure was done. Conclusion: Linseed oil gives effective protection and helps in preventing peristomal skin excoriation rather than any other available modality. It is locally available, very economical and its indigenous use has the potential of minimizing the agony and complications associated with peri-ileostomy skin excoriation.

Anti-Angiotensin type 1 receptor antibodies in chronic graft-versus-host disease.

Activating anti-angiotensin type 1 receptor antibodies (AT1R-AA) have been described in patients with systemic scleroderma, an auto-immune disorder with clinical fibrotic features. Chronic graft-versus-host disease (cGvHD) after hematopoietic stem cell transplantation may have clinical fibrotic features, whose pathogenesis may be similar with systemic sclerosis. To evaluate the presence of AT1R-AA and their association with clinical and biological symptoms in cGvHD patients. Sera from 87 patients including 45 extensive cGvHD and 42 hematopoietic stem cell transplantation patients without cGvHD were retrospectively analyzed for the presence of AT1R-AA using an enzymatic immunoassay. The frequency of AT1R-AA was significantly increased (odds ratio [OR]=3.4, P=0.04) in the cGvHD group (24.4%) compared with the non-cGvHD group (7.1%). In the cGvHD group the positivity of AT1R-AA was significantly associated with: i/ the presence of antinuclear antibodies (OR=5.9, P=0.04) ii/ a more severe global and organ-specific cGvHD scoring (P<0.05), iii/ the presence of active skin or mucosal erosions (OR=19.2, P<0.01). There was no difference between the number and the types of organs involved by the cGvHD between the AT1R-AA-positive versus AT1R-AA-negative subgroups. This preliminary study suggests a potential role and prognostic value of AT1R-AA in cGvHD.

Evaluating and treating venous outflow stenoses is necessary for the successful open surgical treatment of arteriovenous fistula aneurysms

Arteriovenous fistula (AVF) aneurysms (AVFAs) can lead to skin erosion, bleeding, difficult access while on hemodialysis, and poor cosmetic appearance. We reviewed our experience in treating patients with aneurysmal dilatation of their AVF. We reviewed clinical data of 48 patients (37 men; overall mean age, 55 years; range, 28-85 years) with an AVFA who underwent treatment during a 30-month period. Relevant clinical variables and treatment outcomes were analyzed. All patients underwent a fistulogram, and 90% required percutaneous angioplasty to improve outflow. Fifty-six percent of patients had one stenotic outflow lesion, and 44% had at least two tandem outflow stenoses that required treatment. Open repair with aneurysmorrhaphy was performed in one stage in 64% of patients and in two stages in 36%. A tunneled hemodialysis catheter was required in 11 patients (23%) until the surgically repaired AVF was ready for use again, comprising 10 patients treated with single-stage surgery and only one patient in the staged group. All AVFAs were effectively treated, and patients were able to maintain functional use of their access when healed. There is a high association of venous outflow stenoses and AVFA. Comprehensive therapy should encompass treatment of any venous outflow stenoses before open AVFA repair. A two-stage repair may decrease tunneled hemodialysis catheter use in patients with multiple aneurysms.

Stevens–Johnson syndrome following cataract surgery

A case of Stevens–Johnson syndrome in a healthy 58-year-old woman who underwent cataract surgery under topical anesthesia is reported. General skin erosions developed 2 hours after surgery. The patient's family doctor diagnosed that she was allergic to seafood. One month later, she underwent phacoemulsification surgery in the other eye. After surgery, she developed Stevens–Johnson syndrome with general skin lesions, erythema nodosa, genital mucosa erosion, oral ulcers, gastritis, and conjunctiva edema. The symptoms subsided 2 weeks later after immunotherapy. Although nonpreserved anesthesia (2% lidocaine) has seldom been reported to cause allergic reactions via the intravenous or the intramuscular route, it is possible that an intracameral injection of 0.2% lidocaine during cataract surgery can induce Stevens–Johnson syndrome. Careful evaluation of the patient's history and proper treatment were recommended to prevent additional complications.

Blocking of Interleukin 6 Receptor By Nonviral Minicircle DNA Producing Antibody in Skin Allograft Rejection.

Blocking of proinflammatory cytokine, interleukin-6 (IL-6) is effective in decreasing resistance to allogenic tolerance. In this study, we investigated whether anti-IL-6 receptor producing nonviral minicircle (MC)-DNA, is competent to inhibit alloresponse-induced IL-6 in highly immunogenic murine skin allograft model. We designed MC-DNA producing IL-6R antibody and verified in vitro system. One day before skin allograft modeling, systemic MC-DNA exposed via hydrodynamic delivery of MC-DNA in vivo (50ug of DNA, tail vein, single injection). Using GFP tagging MC-DNA, we confirmed its organ distribution. At day 5, we measured the amount of IL-6 and IL-6R antibody in serum. As functional examinations, we evaluated survival rate, morphological changes of graft, immune cell infiltration, and population of T helper 17 cells (Th17, FACS marker: CD4+/RoRγt) and regulatory T cells (Treg, FACS marker: CD4+Foxp3+). We compared its alloimmunity and graft survival efficiency with the cyclosporine A (CsA)-treated group (50 mg/kg, daily administration via oral gavage). Hydrodynamic delivery of MC-DNA was mainly localized in hepatocytes. Serum IL-6 and IL-6R antibody detected in anti-IL-6R MC-DNA treated mice. At day 8.5, untreated mice completely rejected the graft confirming by daily observation of loss of skin graft and erosion. However, mice received either anti-IL-6R MC-DNA or CsA presented prolonged acceptance of graft until day 15 or 15.6, respectively. Results from morphological changes and immune cell infiltration in the graft were also consistent with survival rate. FACS results showed that anti-IL-6R MC-DNA treatment markedly suppressed Th17 population compared with the untreated mice. However, there was no effect on Treg population. On the other hand, administration of CsA showed the increased Th17 and decreased Treg population compared with untreated group. We found that single injection of nonviral minicircle DNA targeting IL-6R is effective in both acute allograft acceptance and allogenic tolerance. This suggests that simple and effective gene therapy method using antibody producing minicircle DNA may represent a powerful tool for the transplantation.

Percutaneous Cryoablation for Local Control of Metachronous Inguinal Lymph Node Metastases

Percutaneous Cryoablation for Local Control of Metachronous Inguinal Lymph Node Metastases

Chlorhexidine gluconate–impregnated central-line dressings and necrosis in complicated skin disorder patients

Although chlorhexidine gluconate (CHG) disks have been shown to help reduce the incidence of central line–associated blood stream infections, their use can result in local skin necrosis. The effects of CHG disks on patients with complex skin pathology have not been studied. We report 6 cases of dermal necrosis associated with Biopatch (Ethicon Inc, Somerville, NJ) CHG disks in adults with complex skin pathology including those with Stevens-Johnson syndrome, toxic epidermal necrolysis syndrome, graft-versus-host disease, burns, and anasarca. All patients had a CHG disk placed at a central venous catheter insertion site. Age range was from 21 to 84 years. Discovery of the reaction ranged from 4 to 14 days after disk placement. Resultant skin erosions required 2 to 10 weeks to reepithelialize. Complicated skin disorder patients represent a rare subset of the critically ill who appear prone to CHG disk necrosis. Continuous contact of CHG under occlusive dressings is speculated to predispose Stevens-Johnson syndrome, toxic epidermal necrolysis syndrome, graft-versus-host disease, and burn patients to local chemical injury secondary to loss of the epithelial tissue barrier, decreased cohesion of the epidermal-dermal junction, and increased tissue permeability. In these patients, the risk of placing the CHG disk may present more risk than using alternative antimicrobial dressings.

Effect of Blocking with Minicircle DNA of Interleukin-6 on Skin Allograft Rejection

Blocking of proinflammatory cytokine, interleukin-6 (IL-6) is effective in decreasing resistance to allogenic tolerance. In this study, we investigated whether anti-IL-6 receptor producing nonviral minicircle (MC)-DNA, is competent to inhibit alloresponse-induced IL-6 in highly immunogenic murine skin allograft model. We designed MC-DNA producing IL-6R antibody and verified in vitro system. One day before skin allograft modeling, systemic MC-DNA exposed via hydrodynamic delivery of MC-DNA in vivo (50 ug of DNA, tail vein, single injection). Using GFP tagging MC-DNA, we confirmed its organ distribution. At day 5, we measured the amount of IL-6 and IL-6R antibody in serum. As functional examinations, we evaluated survival rate, morphological changes of graft, immune cell infiltration, and population of T helper 17 cells (Th17, FACS marker: CD4+/RoRγt) and regulatory T cells (Treg, FACS marker: CD4+ Foxp3+). We compared its alloimmunity and graft survival efficiency with the cyclosporine A (CsA)-treated group (50 mg/kg, daily administration via oral gavage). Hydrodynamic delivery of MC-DNA was mainly localized in hepatocytes. Serum IL-6 and IL-6R antibody detected in anti-IL-6R MC-DNA treated mice. At day 8.5, untreated mice completely rejected the graft confirming by daily observation of loss of skin graft and erosion. However, mice received either anti-IL-6R MC-DNA or CsA presented prolonged acceptance of graft until day 15 or 15.6, respectively. Results from morphological changes and immune cell infiltration in the graft were also consistent with survival rate. FACS results showed that anti-IL-6R MC-DNA treatment markedly suppressed Th17 population compared with the untreated mice. However, there was no effect on Treg population. On the other hand, administration of CsA showed the increased Th17 and decreased Treg population compared with untreated group. We found that single injection of nonviral minicircle DNA targeting IL-6R is effective in both acute allograft acceptance and allogenic tolerance. This suggests that simple and effective gene therapy method using antibody producing minicircle DNA may represent a powerful tool for the transplantation.

The Genetics of Skin Fragility

Genetic skin fragility manifests with diminished resistance of the skin and mucous membranes to external mechanical forces and with skin blistering, erosions, and painful wounds as clinical features. Skin fragility disorders, collectively called epidermolysis bullosa, are caused by mutations in 18 distinct genes that encode proteins involved in epidermal integrity and dermal-epidermal adhesion. The genetic spectrum, along with environmental and genetic modifiers, creates a large number of clinical phenotypes, spanning from minor localized lesions to severe generalized blistering, secondary skin cancer, or early demise resulting from extensive loss of the epidermis. Laboratory investigations of skin fragility have greatly augmented our understanding of genotype-phenotype correlations in epidermolysis bullosa and have also advanced skin biology in general. Current translational research concentrates on the development of biologically valid treatments with therapeutic genes, cells, proteins, or small-molecule compounds in preclinical settings or human pilot trials.

Subcutaneous placement of lap band port without fascial fixation provides safe and durable access.

Laparoscopic adjustable gastric band access port has been routinely sutured to the anterior fascia of the abdominal wall using nonabsorbable sutures. We present our technique demonstrating that nonfascial fixation with using a mesh allows for a safe and durable placement of the port in the superficial subcutaneous tissue. Retrospective chart review included 102 consecutive patients who had Lap band surgery performed by single surgeon (EA) from June 2011 until April 2013. The port was sutured to a piece of polypropylene mesh and tunneled in the subcutaneous tissue away from the incision. Patients' demographics were analyzed as well as the following parameters: OR time for port placement, follow-up, port complications requiring revision, difficult access facilitated by fluoroscopy imaging, port infection, and skin erosion. The study included 102 consecutive patients (23 males and 79 females), mean age was 49 years old, mean weight was 284.7 lb, mean height was 66.2 in., and mean body mass index (BMI) was 46.3 kg/m(2). The average operative time for port placement was 4 min, mean follow-up was 12 months, port complications occurred in 2 % of the patients while fluoroscopy for difficult port access was required in 3 %. No cases of port infections or skin erosions occurred. Superficial subcutaneous placement of Lap Band Port using mesh fixation without anchoring the port to the fascia provides safe and durable access. Deep incisions to secure the port directly to the fascia might not be necessary.

A sine-wave-shaped skin incision for inserting deep-brain stimulators.

The sine-wave-shaped skin incision is a technique that minimizes skin-related complications near burr hole caps after electrode placement for deep-brain stimulation (DBS). Between 2011 and 2013, 54 DBS electrodes were implanted in 27 consecutive patients with Parkinson's disease (PD), essential tremor, or dystonia. The sine-wave incision was used in 26 patients and conventional bilateral linear scalp incisions were used in one patient. None of the patients whose operations involved sine-wave-shaped incisions developed hardware-linked complications such as skin infection or skin erosion. The one patient who underwent conventional bilateral linear scalp incisions developed a skin infection. By preserving the vascular anatomy of the scalp and reducing skin tension at the wound site, the sine-wave-shaped incision promotes wound healing.

Aneurysm formation and infection in AV prosthesis.

In contrast to autogenous arteriovenous (AV) fistulae where true aneurysms are the most frequent type, aneurysms in prosthetic AV grafts are mostly false aneurysms and less frequently anastomotic ones. Indications for repair comprise false aneurysms exceeding twofold the graft diameter, those with rapid enlargement or with skin thinning or erosion, the ruptured, those causing pain or severely limiting the cannulable area and the infected ones. They can be managed either with conventional surgery or with endovascular techniques; However, conventional surgery represents the current standard treatment consisting of either aneurysm resection and interposition graft in situ or resection/exclusion and bypass via a new route to avoid a potentially contaminated area.

Modeling AEC—New approaches to study rare genetic disorders

Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome is a rare monogenetic disorder that is characterized by severe abnormalities in ectoderm-derived tissues, such as skin and its appendages. A major cause of morbidity among affected infants is severe and chronic skin erosions. Currently, supportive care is the only available treatment option for AEC patients. Mutations in TP63, a gene that encodes key regulators of epidermal development, are the genetic cause of AEC. However, it is currently not clear how mutations in TP63 lead to the various defects seen in the patients' skin. In this review, we will discuss current knowledge of the AEC disease mechanism obtained by studying patient tissue and genetically engineered mouse models designed to mimic aspects of the disorder. We will then focus on new approaches to model AEC, including the use of patient cells and stem cell technology to replicate the disease in a human tissue culture model. The latter approach will advance our understanding of the disease and will allow for the development of new in vitro systems to identify drugs for the treatment of skin erosions in AEC patients. Further, the use of stem cell technology, in particular induced pluripotent stem cells (iPSC), will enable researchers to develop new therapeutic approaches to treat the disease using the patient's own cells (autologous keratinocyte transplantation) after correction of the disease-causing mutations.

The use of a simple anal sling in the management of anal incontinence

Background. Many patients presenting with anal incontinence (AI) are frail, with attendant comorbidities precluding the use of complicated, expensive reconstructive techniques. In these cases, revisiting a simple approach—designed to provide some sort of effective barrier to stool—is worthwhile where the options include a customized peri-anal sling or the use of an anal plug.Methods. Analysis of an unselected cohort of 33 patients (mean age 54 years; range 27–86 years) with AI is presented, these patients having undergone insertion of an elastic band peri-anal sling between December 2004 and December 2009. Pre- and post-operative assessment included the Jorge-Wexner score of incontinence, anorectal manometry and the Rockwood Fecal Incontinence Quality of Life (FIQoL) score.Results. The follow-up period ranged from 50 to 108 months with a mean of 65 months. Early post-operative complications included spontaneous disruption of the sling at the fourth and seventh post-operative day in two patients and local infection in a further two cases. Late complications included skin erosion in two patients, (one occurring 3 years post-operatively) and breakage of the sling in a further seven patients. Explantation was performed in 13 cases, and re-implantation in 10 patients. No differences were noted in resting or squeeze manometry, with significant improvement in the Jorge-Wexner scores in 32 cases and in all of the four Rockwood quality of life scales.Conclusions. An anal sling is an effective and simple surgical option for the management of selected cases presenting with anal incontinence. Longer-term data are awaited comparing this technique with other standard surgical alternatives.

A groove technique for securing an electrode connector on the cranial bone: case analysis of efficacy.

ObjectiveA groove technique for securing an electrode connector was described as an alternative surgical technique in deep brain stimulation (DBS) surgery to avoid electrode connector-related complications, such as skin erosion, infection, and migration.MethodsWe retrospectively reviewed 109 patients undergoing one of two techniques; the standard technique (52 patients using 104 electrodes) and the groove technique (57 patients using 109 electrodes) for securing the electrode connector in DBS surgery, regardless of patient disease. In the standard percutaneous tunneling technique, the connector was placed on the vertex of the cranial surface. The other technique, so called the groove technique, created a groove (about 4 cm long, 8 mm wide) in the cranial bone at the posterior parietal area. Wound erosion and migration related to the connectors were compared between the two techniques.ResultsThe mean follow-up period was 73 months for the standard method and 46 months for the groove technique. Connector-related complications were observed in three patients with the groove technique and in seven patients with the standard technique. Wound erosion at the connector sites per electrode was one (0.9%) with the groove technique and six (5.8%) with the standard technique. This difference was statistically significant. The electrode connector was migrated in two patients with the groove technique and in one patient with the standard technique.ConclusionsThe groove technique, which involves securing an electrode using a groove in the cranial bone at the posterior parietal area, offers an effective and safe method to avoid electrode connector-related complications during DBS surgery.

Burning sensation, oozing, and bleeding: A unique finding of septicemia with skin erosion

Septicemia is an inflammatory host response to infection, which rapidly progresses to multiorgan failure and may develop skin lesions. The skin lesions of septicemia often present as purpura, purpura fulminans, and bleeding from erosion. However, there is a paucity of literature describing the features of septicemia both on the intact and eroded skin. The diagnosis of septicemia by identifying its features on the skin is very important for a dermatologist. This case report describes the dermatological changes of septicemia on the eroded skin of pemphigus vulgaris under treatment.

Skin and vaginal erosion after adjustable miduretral sling operation

Skin and vaginal erosion after adjustable miduretral sling operation

A new mouse model of junctional epidermolysis bullosa: the LAMB3 628G&gt;A knockin mouse

Junctional epidermolysis bullosa (JEB) is a group of recessively inherited genodermatoses, characterized by tissue separation in the epidermal basement membrane due to defective anchoring proteins. The lethal Herlitz type of this disorder is caused by absence of laminin-332. Affected individuals suffer from widespread erosions of skin and mucous membranes and very often die within the first year of life. Mouse models lacking the α3- or γ2-chain of laminin-332 have been developed and a spontaneous s3-knockout mouse exists, but all die shortly after birth. We generated a new mouse model of JEB by knockin of the point mutation 628G>A (p.E210K) in the gene encoding the laminin-332 s3-chain, LAMB3. In compound heterozygous humans, this mutation has always been associated with lifelong skin blistering without reduced life expectancy. Fourteen homozygous LAMB3 628G>A knockin mice were analyzed. Most of them showed skin blistering with tissue separation in the basement membrane soon after birth. Laminin-332 was almost completely absent. None of the homozygous LAMB3 628G>A knockin mice survived longer than 72 hours. LAMB3 gene expression levels in heterozygous and homozygous LAMB3 628G>A knockin mice, however, were similar to wild-type mice. Analysis of the LAMB3 transcript revealed alternative splicing in homozygous LAMB3 628G>A knockin mice: a 64 base-pair deletion of exon 7 led to a frame-shift and a premature termination codon. Due to alternative splicing, the phenotype of this new mouse model resembles that of knockout mice. The LAMB3 628G>A knockin mouse may contribute to a better understanding of the molecular basis of JEB.

Seasonal occurrence of diseases in a recirculation system for salmonid fish in the Czech Republic

Aquaculture represents the fastest growing animal husbandry in many countries. However, higher intensity of fish farming can pose higher health hazards, too. We monitored the health status of fish from one fish farm in South Bohemia and discovered the main health problems in the breeding. For two years we examined a total of 224 specimens of brook trout (Salvelinus fontinalis), 126 specimens of hybrids (S. fontinalis×S. alpinus), 49 specimens of rainbow trout (Oncorhynchus mykiss) – all clinically healthy, and 100 clinically diseased or freshly dead fish. We registered skin erosions mainly in the caudal peduncle and tail fin. Two parasite species were identified (one protistIchthyophthirius multifiliisand one nematodeRaphidascaris acus) by parasitological examination. The epidemiological indicators ofI. multifiliiswere low. The prevalence of adultR. acuswas 0–86% with a maximum in June. From November, capsules with larval stages ofR. acusappeared in internal organs. Their highest intensity (200 pieces) and prevalence (100%) were detected in October. By microbiological examination of skin and gills, we identified changes in the density of bacterial population and its species composition dependent on water temperature and fish density. The most important problem on the monitored fish farm seems to be furunculosis of salmonid fish in all clinical forms, and the high intensity of larval stages ofR. acus. The originality of this study is based on the fact that the observed breeding employs the first Danish recirculation system in the Czech Republic and no recent information about health problems has been available.