A Rare Presentation of Polyarteritis Nodosa (PAN).

Polyarteritis nodosa (PAN) is a connective tissue disease that affects arteries, causing necrotizing inflammation that can weaken the arterial walls, dilatation into aneurysms, and rupture in some cases. We present a case of a male with acute abdomen from aneurysmal rupture. The 48-year-old patient with a history of polysubstance use including cocaine and methamphetamines was admitted for acute hypoxic respiratory failure secondary to coronavirus disease 2019 (COVID-19) pneumonia and treated with broad-spectrum antibiotics and steroids. He also reported generalized abdominal pain and discomfort, and examination revealed abdominal distension that was diffusely tender on palpation, bowel sounds intact. Laboratory workup showed a progressive drop in hemoglobin requiring blood transfusions, no coagulopathy, anion gap metabolic acidosis, and lactic acidosis. Abdominal CT showed a 2 cm lobulated saccular aneurysm involving either the left gastric artery or splenic artery, associated with an extensive moderate amount of hemoperitoneum with hematomas (largest measuring up to 8.6 cm) abutting the gastric fundus and greater curvature of the stomach, which was likely secondary to aneurysmal rupture. Additionally, several other mesenteric vessels displayed some degree of dilation. Interventional radiology (IR)-guided splenic artery embolization for splenic artery aneurysm was done, after which his hemoglobin remained stable. The patient was given vaccine recommendations since splenic artery embolization would lead to asplenia. The aneurysms were attributed to either cocaine-related aneurysms or polyarteritis nodosa with visceral artery aneurysms. He denied rashes, oral ulcers, joint pain, subcutaneous nodules, blood in the urine, history of hepatitis or syphilis. Tertiary syphilis was ruled out after the Venereal Disease Research Laboratory (VDRL) test and rapid plasma reagin (RPR) test were negative. Complement C3 and C4 levels were normal. He was treated with high-dose IV methylprednisone after infection was ruled out. Due to the severity of PAN, therapy with IV cyclophosphamide therapy 15 mg/kg once every two weeks for three doses was initiated, followed by 15 mg/kg once every three weeks for three to six months (in combination with glucocorticoids prednisone 1 mg/kg body weight with slow taper). Cyclophosphamide was given with IV hydration and mesna. The presentation of PAN can vary widely. Most commonly, individuals experience symptoms such as fatigue, weight loss, fever, and chills. However, in rare cases, patients may present with isolated abdominal pain, similar to our patient. It's crucial to note that the rupture of an aneurysm can manifest as an acute abdominal issue, potentially leading to life-threatening situations. Immediate interventions to control bleeding are imperative in such cases. The treatment of PAN has a high success rate when a combination of cyclophosphamide and steroids is administered.

Evaluation of tissue-engineered human acellular vessels as a Blalock-Taussig-Thomas shunt in a juvenile primate model.

Objectives: Palliative treatment of cyanotic congenital heart disease (CCHD) uses systemic-to-pulmonary conduits, often a modified Blalock-Taussig-Thomas shunt (mBTTs). Expanded polytetrafluoroethylene (ePTFE) mBTTs have associated risks for thrombosis and infection. The Human Acellular Vessel (HAV) (Humacyte, Inc) is a decellularized tissue-engineered blood vessel currently in clinical trials in adults for vascular trauma, peripheral artery disease, and end-stage renal disease requiring hemodialysis. In addition to restoring blood flow, the engineered HAV demonstrates the capacity for host cellular remodeling into native-like vasculature. Here we report preclinical evaluation of a small-diameter (3.5 mm) HAV as a mBTTs in a non-human primate model. Methods: We implanted 3.5 mm HAVs as right subclavian artery to pulmonary artery mBTTs in non-immunosuppressed juvenile rhesus macaques (n = 5). HAV patency, structure, and blood flow were assessed by postoperative imaging from 1 week to 6 months. Histology of HAVs and surrounding tissues was performed. Results: Surgical procedures were well tolerated, with satisfactory anastomoses, showing feasibility of using the 3.5 mm HAV as a mBTTs. All macaques had some immunological reactivity to the human extracellular matrix, as expected in this xenogeneic model. HAV mBTTs remained patent for up to 6 months in animals, exhibiting mild immunoreactivity. Two macaques displaying more severe immunoreactivity to the human HAV material developed midgraft dilatation without bleeding or rupture. HAV repopulation by host cells expressing smooth muscle and endothelial markers was observed in all animals. Conclusions: These findings may support use of 3.5 mm HAVs as mBTTs in CCHD and potentially other pediatric vascular indications.

New Insights in the Setting of Transplant Oncology.

Background and Objectives: Liver transplantation (LT) is the best strategy for curing several primary and secondary hepatic malignancies. In recent years, growing interest has been observed in the enlargement of the transplant oncology indications. This paper aims to review the most recent developments in the setting of LT oncology, with particular attention to LT for unresectable colorectal liver metastases (CRLM) and cholangiocellular carcinoma (CCA). Materials and Methods: A review of the recently published literature was conducted. Results: Growing evidence exists on the efficacy of LT in curing CRLM and peri-hilar and intrahepatic CCA in well-selected patients when integrating this strategy with (neo)-adjuvant chemotherapy, radiotherapy, or locoregional treatments. Conclusion: For unresectable CCA and CRLM management, several prospective protocols are forthcoming to elucidate LT's impact relative to alternative therapies. Advances in diagnosis, treatment protocols, and donor-to-recipient matching are needed to better define the oncological indications for transplantation. Prospective, multicenter trials studying these advances and their impact on outcomes are still required.

Tissue engineered vascular grafts transform into autologous neovessels capable of native function and growth.

Background: Tissue-engineered vascular grafts (TEVGs) have the potential to advance the surgical management of infants and children requiring congenital heart surgery by creating functional vascular conduits with growth capacity. Methods: Herein, we used an integrative computational-experimental approach to elucidate the natural history of neovessel formation in a large animal preclinical model; combining an in vitro accelerated degradation study with mechanical testing, large animal implantation studies with in vivo imaging and histology, and data-informed computational growth and remodeling models. Results: Our findings demonstrate that the structural integrity of the polymeric scaffold is lost over the first 26 weeks in vivo, while polymeric fragments persist for up to 52 weeks. Our models predict that early neotissue accumulation is driven primarily by inflammatory processes in response to the implanted polymeric scaffold, but that turnover becomes progressively mechano-mediated as the scaffold degrades. Using a lamb model, we confirm that early neotissue formation results primarily from the foreign body reaction induced by the scaffold, resulting in an early period of dynamic remodeling characterized by transient TEVG narrowing. As the scaffold degrades, mechano-mediated neotissue remodeling becomes dominant around 26 weeks. After the scaffold degrades completely, the resulting neovessel undergoes growth and remodeling that mimicks native vessel behavior, including biological growth capacity, further supported by fluid-structure interaction simulations providing detailed hemodynamic and wall stress information. Conclusions: These findings provide insights into TEVG remodeling, and have important implications for clinical use and future development of TEVGs for children with congenital heart disease.

Facilitating Success of the Early Stage Surgeon Scientist Trainee: Growing the Surgeon Scientist Pipeline.

OBJECTIVE: Surgeon scientists bring to bear highly specialized talent and innovative and impactful solutions for complicated clinical problems. Our objective is to inform and provide framework for early stage surgeon scientist training and support. SUMMARY OF BACKGROUND DATA: Undergraduate, medical student, and residency experiences impact the career trajectory of surgeon scientists. To combat the attrition of the surgeon scientist pipeline, interventions are needed to engage trainees and to increase the likelihood of success of future surgeon scientists. METHODS: A surgery resident writing group at an academic medical center, with guidance from faculty, prepared this guidance document for early stage surgeon scientist trainees with integration of the published literature to provide context. The publicly available National Institutes of Health RePORTER tool was queried to provide data salient to early stage surgeon scientist training. RESULTS: The educational path of surgeons and the potential research career entry points are outlined. Challenges and critical supportive elements needed to inspire and sustain progress along the surgeon scientist training path are detailed. Funding mechanisms available to support formal scientific training of early stage surgeon scientists are identified and obstacles specific to surgical careers are discussed. CONCLUSIONS: This guidance enhances awareness of essential education, communication, infrastructure, resources, and advocacy by surgery leaders and other stakeholders to promote quality research training in residency and to re-invigorate the surgeon scientist pipeline.

Diffuse Gastrointestinal Polyposis in Bannayan-Riley-Ruvalcaba Syndrome: A Rare Phenotype Among Phosphatase and Tensin Homolog Hamartoma Tumor Syndromes.

Bannayan-Riley-Ruvalcaba syndrome (BRRS) is a rare genetic disorder caused by germline mutations in the phosphatase and tensin homolog (PTEN) gene. Clinical manifestations arise early during childhood and include multiple lipomas, hamartomatous intestinal polyps, macrocephaly, developmental delay, and autism spectrum disorder among others. The case describes a 24-year-old female with a recent diagnosis of BRRS who presented for evaluation of burning epigastric pain for the previous six months. The esophagogastroduodenoscopy (EGD) and colonoscopy revealed an erosive gastric mucosa as well as numerous polyps throughout the gastrointestinal tract. Histopathologic examination confirmed gastric Helicobacter pylori infection and different histologic types of polyps.

Characterization of urgent versus nonurgent early readmissions (<30 days) following primary bariatric surgery: a single-institution experience.

BACKGROUND: Studies on early postoperative readmissions after bariatric surgery (BS) have examined readmissions as a single entity, regardless of urgency. Strategies to lower nonurgent readmissions would reduce unnecessary hospital utilization. OBJECTIVES: To identify predictors of urgent readmissions (UR) versus nonurgent readmissions (NUR) at 30 days post-BS. SETTING: Single academic institution. METHODS: Patients undergoing primary BS over 2 years (n = 589) were retrospectively reviewed. Baseline demographic, medical, and hospitalization data were compared between readmitted patients, stratified by urgency, and nonreadmitted patients. Multivariate regression models of UR and NUR were created using variables with a P value ≤ .2 on univariate analyses. A P value ≤ .05 was considered statistically significant. RESULTS: There were 39 documented instances of 30-day readmissions, of which 44% (n = 17) were NUR; NUR patients were more likely to be female (100% versus 78.2% male; P = .03) and trended toward being younger, experiencing ≥2 perioperative complications, and having a longer index hospital length of stay (LOS). Patients with URs had a higher baseline BMI (52.5 ± 11.4 kg/m2 versus 48.7 ± 8.3 kg/m2, respectively; P = .04), were more likely to have sleep apnea (77.3% versus 56.1%, respectively; P = .05), had a longer LOS (3 versus 2 d, respectively; P = .007), and were more likely to have ≥2 postoperative complications (46% versus 17.0%, respectively; P = .003) compared with those with an NUR. Independent predictors of NUR included public insurance (odds ratio [OR] = 3.7; 95% confidence interval [CI], 1.17-11.67; P = .03), younger age (OR = 1.05; 95% CI, 1-1.01; P = .04), and female sex, while URs were independently predicted by LOS (OR = 1.3; 95% CI, 1.04-1.5; P = .02). CONCLUSIONS: Public insurance appears to be associated with NURs, while LOS predicts URs after BS. This suggests an important dichotomy within readmissions based on urgency, which has important implications for targeted quality initiatives.

Continuous Glucose Monitoring for the Detection of Hypoglycemia in Patients With Diabetes of the Exocrine Pancreas.

BACKGROUND: Detailed evaluations of hypoglycemia and associated indices based on continuous glucose monitoring (CGM) are limited in patients with diabetes of the exocrine pancreas. Our study sought to evaluate the frequency and pattern of hypoglycemic events and to investigate hypoglycemia-specific indices in this population. METHODS: This was a cross-sectional study comprising 83 participants with diabetes of the exocrine pancreas. CGM and self-monitoring of blood glucose (SMBG) were performed on all participants for a minimum period of 72 hours. The frequency and pattern of hypoglycemic events, as well as hypoglycemia-related indices, were evaluated. RESULTS: Hypoglycemia was detected in 90.4% of patients using CGM and 38.5% of patients using SMBG. Nocturnal hypoglycemic events were more frequent (1.9 episodes/patient) and prolonged (142 minutes) compared with day-time events (1.1 episodes/patient; 82.8 minutes, P < 0.05). The mean low blood glucose index was 2.1, and glycemic risk assessment diabetes equation hypoglycemia was 9.1%. The mean time spent below (TSB) <70 mg/dL was 9.2%, and TSB <54 mg/dL was 3.7%. The mean area under curve (AUC) <70 mg/dL was 1.7 ± 2.5 mg/dL/hour and AUC <54 mg/dL was 0.6 ± 1.3 mg/dL/hour. All of the CGM-derived hypoglycemic indices were significantly more deranged at night compared with during the day (P < 0.05). CONCLUSION: Patients with diabetes of the exocrine pancreas have a high frequency of hypoglycemic episodes that are predominantly nocturnal. CGM is superior to SMBG in the detection of nocturnal and asymptomatic hypoglycemic episodes. CGM-derived hypoglycemic indices are beneficial in estimating the risk of hypoglycemia.

Intra-abdominal fat estimation by bio-electrical impedance analysis in patients with fibrocalculous pancreatic diabetes compared with BMI matched type 2 diabetic subjects and healthy controls.

BACKGROUND AND AIMS: Intra-abdominal adipose tissue (IAAT) is a major contributor to insulin resistance (IR) in type 2 diabetes mellitus (T2D). Prior studies have demonstrated evidence of IR in fibrocalculous pancreatic diabetes (FCPD). However, no data exists on IAAT estimation in FCPD. Hence, we compared IAAT area among FCPD patients and an equal number of body mass index (BMI) matched T2D patients and healthy controls. METHODS: We recruited 60 patients with FCPD between January 2019 and February 2020. Body composition analysis was performed via bio-electrical impedance analysis. RESULTS: The mean ages were 37.82 ± 10.07, 51.02 ± 9.9, and 30.7 ± 11.51 years for patients in the FCPD, T2D, and control groups, respectively. The mean BMI of patients in the three groups was 20.65 ± 2.01, 20.83 ± 1.49, and 20.91 ± 1.59 kg/m2, respectively (P = 0.684). The mean IAAT area of patients in the FCPD, T2D, and control groups was 67.93 ± 43.38, 117.78 ± 48.03, and 100.52 ± 42.31 cm2, respectively. IAAT was significantly lower in patients with FCPD compared with those in the other two groups (P < 0.0001). In the entire cohort, IAAT showed significant positive correlation with age (r = 0.20), abdominal circumference (r = 0.80), waist hip ratio (r = 0.75), and LDL level (r = 0.25) (P < 0.05). CONCLUSIONS: Patients with FCPD have significantly lower IAAT compared to BMI matched T2D subjects and healthy controls. IAAT does not appear to be a major contributor to insulin resistance observed in patients with FCPD.

Is BMI associated with post-operative complication risk among patients undergoing major abdominal surgery for cancer? A systematic review.

We systematically reviewed 118 studies comparing peri-operative outcomes among obese and non-obese patients. Obesity was associated with longer operative time in 60% of available studies. Just 35.8% of studies that evaluated overall morbidity identified high morbidity in obese patients. Lymph node yield or surgical margin status, was only affected by obesity in 19.6% of studies. In this review obesity was frequently found to have no effect on peri-operative and oncologic outcomes.

Discrimination of Dysplastic Nevi from Common Melanocytic Nevi by Cellular and Molecular Criteria.

Dysplastic nevi (DNs), also known as Clark's nevi or atypical moles, are distinguished from common melanocytic nevi by variegation in pigmentation and clinical appearance, as well as differences in tissue patterning. However, cellular and molecular differences between DNs and common melanocytic nevi are not completely understood. Using cDNA microarray, quantitative RT-PCR, and immunohistochemistry, we molecularly characterized DNs and analyzed the difference between DNs and common melanocytic nevi. A total of 111 probesets (91 annotated genes, fold change > 2.0 and false discovery rate < 0.25) were differentially expressed between the two lesions. An unexpected finding in DNs was altered differentiation and activation of epidermal keratinocytes with increased expression of hair follicle-related molecules (keratin 25, trichohyalin, ribonuclease, RNase A family, 7) and inflammation-related molecules (S100A7, S100A8) at both genomic and protein levels. The immune microenvironment of DNs was characterized by an increase of T helper type 1 (IFNγ) and T helper type 2 (IL13) cytokines as well as an upregulation of oncostatin M and CXCL1. DUSP3, which regulates cellular senescence, was identified as one of the disease discriminative genes between DNs and common melanocytic nevi by three independent statistical approaches and its altered expression was confirmed by immunohistochemistry. The molecular and cellular changes in which the epidermal-melanin unit undergoes follicular differentiation as well as upregulation of defined cytokines could drive complex immune, epidermal, and pigmentary alterations.

Acute kidney injury, hyperbilirubinemia, and ischemic skin necrosis due to massive sulindac overdose.

Sulindac is a long-acting nonsteroidal anti-inflammatory drug (NSAID) widely used for the management of osteoarthritis, rheumatoid arthritis, ankylosing sponydlitis, and acute gouty arthritis. Reports of sulindac toxicity in the literature are rare. We report the case of a 22-year old male with a history of bipolar disorder who was brought to the emergency department after ingesting approximately 15 g of sulindac in a suicide attempt. He was found to have acute kidney injury and hyperbilirubinemia. Despite aggressive fluid resuscitation, his renal function progressively worsened requiring the initiation of hemodialysis. Ten days following ingestion of sulindac, he began to develop ischemic skin changes with a gangrenous appearance in his hands and feet. He continued to receive supportive treatment, and his acute kidney injury, hyperbillirubinemia, and ischemic skin necrosis eventually resolved. Clinicians should be aware of this long-acting NSAID and its ability to cause prolonged multisystem organ dysfunction.

Hemodynamic Characterization of a Mouse Model for Investigating the Cellular and Molecular Mechanisms of Neotissue Formation in Tissue-Engineered Heart Valves.

Decellularized allograft heart valves have been used as tissue-engineered heart valve (TEHV) scaffolds with promising results; however, little is known about the cellular mechanisms underlying TEHV neotissue formation. To better understand this phenomenon, we developed a murine model of decellularized pulmonary heart valve transplantation using a hemodynamically unloaded heart transplant model. Furthermore, because the hemodynamics of blood flow through a heart valve may influence morphology and subsequent function, we describe a modified loaded heterotopic heart transplant model that led to an increase in blood flow through the pulmonary valve. We report host cell infiltration and endothelialization of implanted decellularized pulmonary valves (dPV) and provide an experimental approach for the study of TEHVs using mouse models.

Transplantation of pulmonary valve using a mouse model of heterotopic heart transplantation.

Tissue engineered heart valves, especially decellularized valves, are starting to gain momentum in clinical use of reconstructive surgery with mixed results. However, the cellular and molecular mechanisms of the neotissue development, valve thickening, and stenosis development are not researched extensively. To answer the above questions, we developed a murine heterotopic heart valve transplantation model. A heart valve was harvested from a valve donor mouse and transplanted to a heart donor mouse. The heart with a new valve was transplanted heterotopically to a recipient mouse. The transplanted heart showed its own heartbeat, independent of the recipient's heartbeat. The blood flow was quantified using a high frequency ultrasound system with a pulsed wave Doppler. The flow through the implanted pulmonary valve showed forward flow with minimal regurgitation and the peak flow was close to 100 mm/sec. This murine model of heart valve transplantation is highly versatile, so it can be modified and adapted to provide different hemodynamic environments and/or can be used with various transgenic mice to study neotissue development in a tissue engineered heart valve.

Gene expression profiling of the leading edge of cutaneous squamous cell carcinoma: IL-24-driven MMP-7.

The precise mechanisms governing invasion at the leading edge of squamous cell carcinoma (SCC) and its subsequent metastasis are not fully understood. We aimed to define the cancer-related molecular changes that distinguish noninvasive tumor from invasive SCC. To this end, we combined laser capture microdissection with complementary DNA (cDNA) microarray analysis. We defined invasion-associated genes as those differentially regulated only in invasive SCC nests, but not in actinic keratosis or in situ SCC, compared with normal epidermis. There were 383 upregulated and 354 downregulated genes in the "invasion set." SCC invasion was characterized by aberrant expression of various proteolytic molecules. We noted increased expression of MMP7 and IL-24 in invasive SCC. IL-24 induced the expression of matrix metallopeptidase 7 (MMP7) in SCC cells in culture. In addition, blocking of MMP7 by a specific antibody significantly delayed the migration of SCC cells in culture. These results suggest a possible contribution of IL-24 to SCC invasion via enhancing focal expression of MMP7, although IL-24 has been suggested to have antitumor growth effects in other cancer types. Identification of regional molecular changes that regulate cancer invasion may facilitate the development of new targeted treatments for aggressive cancer.

Identification of anaplastic lymphoma kinase as a potential therapeutic target in Basal Cell Carcinoma.

The pathogenesis of BCC is associated with sonic hedgehog (SHH) signaling. Vismodegib, a smoothened inhibitor that targets this pathway, is now in clinical use for advanced BCC patients, but its efficacy is limited. Therefore, new therapeutic options for this cancer are required. We studied gene expression profiling of BCC tumour tissues coupled with laser capture microdissection to identify tumour specific receptor tyrosine kinase expression that can be targeted by small molecule inhibitors. We found a >250 fold increase (FDR<10-4) of the oncogene, anaplastic lymphoma kinase (ALK) as well as its ligands, pleiotrophin and midkine in BCC compared to microdissected normal epidermis. qRT-PCR confirmed increased expression of ALK (p<0.05). Stronger expression of phosphorylated ALK in BCC tumour nests than normal skin was observed by immunohistochemistry. Crizotinib, an FDA-approved ALK inhibitor, reduced keratinocyte proliferation in culture, whereas a c-Met inhibitor did not. Crizotinib significantly reduced the expression of GLI1 and CCND2 (members of SHH-pathway) mRNA by approximately 60% and 20%, respectively (p<0.01). Our data suggest that ALK may increase GLI1 expression in parallel with the conventional SHH-pathway and promote keratinocyte proliferation. Hence, an ALK inhibitor alone or in combination with targeting SHH-pathway molecules may be a potential treatment for BCC patients.

CD200 upregulation in vascular endothelium surrounding cutaneous squamous cell carcinoma.

OBJECTIVE: To characterize the presence of CD200 and CD200 receptor (CD200R) in the human cutaneous squamous cell carcinoma (SCC) microenvironment and to define a possible role for the CD200 axis in immune evasion by SCC. DESIGN: Gene expression in SCC vs normal skin was studied. Laser capture microdissection was used to determine differential expression of CD200 in normal skin vs actinic keratosis vs SCC in situ vs invasive SCC. Immunofluorescence microscopy was used to define expression of CD200R on macrophages, myeloid dendritic cells, natural killer cells, and T cells in SCC vs normal skin. The effects of SCC supernatant on induction of CD200 in human blood endothelial cells was also examined. SETTING: Academic Medical Center with an established Section of Mohs and Dermatologic Surgery and an active Cutaneous Biology Research Program. PARTICIPANTS: Surgical discard tissue from deidentified patients and samples of normal skin from healthy volunteers were used in this study. MAIN OUTCOME MEASURES: Expression of CD200 on SCC-associated blood vessels; expression of CD200 receptor on SCC-associated macrophages and T cells; and induction of CD200 on endothelial cells by SCC supernatants. RESULTS: CD200 gene and message were upregulated in SCC stroma. Immunostaining revealed a higher number of CD200(+) cells in SCC stroma than in normal dermis (180.8 cells/mm(2) vs 24.6 cells/mm(2)) (P<.01). CD200 was further identified mainly on blood vessel endothelium in SCC. Tumor supernatant was able to induce CD200 expression on human dermal blood endothelial cells in culture. CD200R was identified on macrophages and dendritic cells in SCC microenvironment. CONCLUSIONS: CD200 expression on local blood vessels may promote tumor progression by suppressing CD200R myeloid cells during diapedesis. These data highlight a previously unrecognized mechanism of immune evasion by SCC and may provide guidance for the development of targeted therapy.

Cutaneous manifestations of gastrointestinal disease: part II.

The gastrointestinal (GI) and cutaneous organ systems are closely linked. In part I of this continuing medical education article, the intricacies of this relationship were explored as they pertained to hereditary polyposis disorders, hamartomatous disorders, and paraneoplastic disease. Part II focuses on the cutaneous system's links to inflammatory bowel disease and vascular disorders. An in-depth analysis of inflammatory bowel disease skin findings is provided to aid dermatologists in recognizing and facilitating early consultation and intervention by gastroenterologists. Cutaneous signs of inflammatory bowel disease include fissures and fistulae, erythema nodosum, pyoderma gangrenosum, pyostomatitis vegetans, oral aphthous ulcers, cutaneous polyarteritis nodosa, necrotizing vasculitis, and epidermolysis bullosa acquisita. Additional immune-mediated conditions, such as diverticulitis, bowel-associated dermatosis-arthritis syndrome, Henoch-Schönlein purpura, dermatitis herpetiformis, and Degos disease, in which the skin and GI system are mutually involved, will also be discussed. Genodermatoses common to both the GI tract and the skin include Hermansky-Pudlak syndrome, pseudoxanthoma elasticum, Ehlers-Danlos syndrome, hereditary hemorrhagic telangiectasia, and blue rubber bleb nevus syndrome. Kaposi sarcoma is a neoplastic disease with lesions involving both the skin and the gastrointestinal tract. Acrodermatitis enteropathica, a condition of zinc deficiency, likewise affects both the GI and dermatologic systems. These conditions are reviewed with updates on the genetic basis, diagnostic and screening modalities, and therapeutic options. Finally, GI complications associated with vascular disorders will also be discussed.

Cutaneous manifestations of gastrointestinal disease: part I.

Cutaneous findings are not uncommonly a concomitant finding in patients afflicted with gastrointestinal (GI) diseases. The dermatologic manifestations may precede clinically evident GI disease. Part I of this 2-part CME review focuses on dermatologic findings as they relate to hereditary and nonhereditary polyposis disorders and paraneoplastic disorders. A number of hereditary GI disorders have an increased risk of colorectal carcinomas. These disorders include familial adenomatous polyposis, Peutz-Jeghers syndrome, and juvenile polyposis syndrome. Each disease has its own cutaneous signature that aids dermatologists in the early diagnosis and detection of hereditary GI malignancy. These disease processes are associated with particular gene mutations that can be used in screening and to guide additional genetic counseling. In addition, there is a group of hamartomatous syndromes, some of which are associated with phosphatase and tensin homolog (PTEN) gene mutations, which present with concurrent skin findings. These include Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome, and Cronkhite-Canada syndrome. Finally, paraneoplastic disorders are another subcategory of GI diseases associated with cutaneous manifestations, including malignant acanthosis nigricans, Leser-Trélat sign, tylosis, Plummer-Vinson syndrome, necrolytic migratory erythema, perianal extramammary Paget disease, carcinoid syndrome, paraneoplastic dermatomyositis, and paraneoplastic pemphigus. Each of these disease processes have been shown to be associated with an increased risk of GI malignancy. This underscores the important role of dermatologists in the diagnosis, detection, monitoring, and treatment of these disorders while consulting and interacting with their GI colleagues.