Stromal cells control the epithelial residence of DCs and memory T cells by regulated activation of TGF-ß.

Cells of the immune system that reside in barrier epithelia provide a first line of defense against pathogens. Langerhans cells (LCs) and CD8(+) tissue-resident memory T cells (TRM cells) require active transforming growth factor-ß1 (TGF-ß) for epidermal residence. Here we found that integrins αvß6 and αvß8 were expressed in non-overlapping patterns by keratinocytes (KCs) and maintained the epidermal residence of LCs and TRM cells by activating latent TGF-ß. Similarly, the residence of dendritic cells and TRM cells in the small intestine epithelium also required αvß6. Treatment of the skin with ultraviolet irradiation decreased integrin expression on KCs and reduced the availability of active TGF-ß, which resulted in LC migration. Our data demonstrated that regulated activation of TGF-ß by stromal cells was able to directly control epithelial residence of cells of the immune system through a novel mechanism of intercellular communication.

Deep learning for dermatologists: Part II. Current applications.

Because of a convergence of the availability of large data sets, graphics-specific computer hardware, and important theoretical advancements, artificial intelligence has recently contributed to dramatic progress in medicine. One type of artificial intelligence known as deep learning has been particularly impactful for medical image analysis. Deep learning applications have shown promising results in dermatology and other specialties, including radiology, cardiology, and ophthalmology. The modern clinician will benefit from an understanding of the basic features of deep learning to effectively use new applications and to better gauge their utility and limitations. In this second article of a 2-part series, we review the existing and emerging clinical applications of deep learning in dermatology and discuss future opportunities and limitations. Part 1 of this series offered an introduction to the basic concepts of deep learning to facilitate effective communication between clinicians and technical experts.

Deep learning for dermatologists: Part I. Fundamental concepts.

Artificial intelligence is generating substantial interest in the field of medicine. One form of artificial intelligence, deep learning, has led to rapid advances in automated image analysis. In 2017, an algorithm demonstrated the ability to diagnose certain skin cancers from clinical photographs with the accuracy of an expert dermatologist. Subsequently, deep learning has been applied to a range of dermatology applications. Although experts will never be replaced by artificial intelligence, it will certainly affect the specialty of dermatology. In this first article of a 2-part series, the basic concepts of deep learning will be reviewed with the goal of laying the groundwork for effective communication between clinicians and technical colleagues. In part 2 of the series, the clinical applications of deep learning in dermatology will be reviewed and limitations and opportunities will be considered.

Chronic graft-versus-host disease in pancreas after kidney transplant recipients - An unrecognized entity.

Graft-versus-host disease (GVHD), a common complication after peripheral blood stem cell or bone marrow transplantation, rarely occurs in kidney and pancreas transplant recipients. The true incidence may be confounded by the rarity of the disorder, with a resultant lack of appreciation of the diagnosis as a potential cause of common clinical manifestations such as cytopenias and immune dysfunction. Reports of GVHD in kidney and pancreas transplant recipients almost uniformly describe patients in the early posttransplant period (days to months) with the typical manifestations of acute GVHD involving the skin, liver, and intestines. In contrast, reports of solid organ transplant recipients with clinical features more consistent with chronic GVHD (cGVHD) are lacking, raising concern of underrecognition of this severe complication. Occurrence later after transplant may be even more likely to result in lack of recognition. We report 2 cases of possible cGVHD occurring in recipients of pancreas after kidney transplantation, which were diagnosed at 5.5 and 42 months after pancreas transplant. Both patients presented with severe pancytopenia, multiple opportunistic infections, and features suggestive of cGVHD. Transplant professionals should be aware of the possibility of acute and cGVHD in pancreas after kidney transplant recipients and be able to recognize the clinical manifestations.

Use of teledermatology by dermatology hospitalists is effective in the diagnosis and management of inpatient disease.

BACKGROUND: Patient outcomes are improved when dermatologists provide inpatient consultations. Inpatient access to dermatologists is limited, illustrating an opportunity to use teledermatology. Little is known about the ability of dermatologists to accurately diagnose disease and manage inpatients with teledermatology, particularly when using nondermatologist-generated clinical data. METHODS: This prospective study assessed the ability of teledermatology to diagnose disease and manage 41 dermatology consultations from a large urban tertiary care center, using internal medicine referral documentation and photographs. Twenty-seven dermatology hospitalists were surveyed. Interrater agreement was assessed by the κ statistic. RESULTS: There was substantial agreement between in-person and teledermatology assessment of the diagnosis with differential diagnosis (median κ = 0.83), substantial agreement in laboratory evaluation decisions (median κ = 0.67), almost perfect agreement in imaging decisions (median κ = 1.0), and moderate agreement in biopsy decisions (median κ = 0.43). There was almost perfect agreement in treatment (median κ = 1.0), but no agreement in follow-up planning (median κ = 0.0). There was no association between raw photograph quality and the primary plus differential diagnosis or primary diagnosis alone. LIMITATIONS: Selection bias and single-center nature. CONCLUSIONS: Teledermatology may be effective in the inpatient setting, with concordant diagnosis, evaluation, and management decisions.

Viral panniculitis in a patient with disseminated opportunistic Enterovirus infection.

Infection-induced panniculitis has been described in association with a broad range of microorganisms. Among those, viral panniculitis represents a minor category, with only a few anecdotal reports in the literature documenting viral infection in the subcutaneous fat. Herein, we report a woman in her 30s with seropositive rheumatoid arthritis on rituximab and prednisone, who presented with a 6-month history of progressive multisystem manifestations, including unintentional weight loss, fever, fatigue, myopathy, pancreatitis, and sensorineural hearing loss. She had indurated plaques on her thighs characterized by predominantly lobular panniculitis with chronic lymphohistiocytic inflammation. Molecular studies performed at the Centers for Disease Control and Prevention identified evidence of Enterovirus group with the highest identity of Coxsackievirus A9. Enterovirus RNA was also detected in the cerebrospinal fluid and muscle. Based on the findings, a diagnosis of disseminated enteroviral infection in the setting of B-cell depletion was rendered. To the best of our knowledge, this represents the first reported case of viral panniculitis with documentation of Coxsackievirus A9 in the skin. Since rituximab may be used for the treatment of autoimmune dermatological diseases, familiarity of the potential occurrence of severe enteroviral infections in the setting of immunosuppressive treatment is important for dermatopathologists.

Kaposi sarcoma misdiagnosed as granuloma annulare: A case of mistaken identity.

The microscopic features of patch stage Kaposi sarcoma (KS) and interstitial granuloma annulare (GA) may be difficult to differentiate, because both may exhibit a subtle "busy" dermis due to infiltration of spindled cells between collagen bundles. The clinical distinction is particularly challenging in human immunodeficiency virus (HIV)-affected individuals, as the incidence of GA appears to be greater in the HIV-infected population. KS is the most common neoplasm in this population. Despite the significant decrease in the incidence of KS since the advent of highly active antiretroviral therapy (HAART), KS tends to occur with late onset and indolent progression in patients with preserved immune function and minimal viral load. We present a 47-year-old homosexual HIV-positive man, under virologic and immunologic control on long-term HAART therapy, with a 5-year history of progressive red-brown patches and plaques on the legs, feet, hands, and trunk. Prior skin biopsy specimens were interpreted as interstitial GA. Histopathology on new skin biopsy specimens along with review specimens supported the diagnosis of plaque and patch stages of KS, respectively, supported by immunohistochemical expression of human herpes virus-8 (HHV-8). This case underscores the importance of maintaining a high suspicion for KS in progressive, treatment-recalcitrant skin lesions, particularly in HIV-infected individuals.

Agminated segmental plaque-type blue nevus associated with hypertrichosis and soft tissue hypertrophy: Report of a case and review of the literature.

Blue nevi are common skin neoplasms that typically present as asymptomatic solitary papules, although they may rarely occur in an agminated configuration. We describe a case of agminated blue nevus in a segmental facial distribution associated with soft tissue hypertrophy and hypertrichosis in a 16-year-old boy and present a review of the literature. Although they are generally considered to be benign, concurrent soft tissue changes occurring within an agminated blue nevus should be investigated thoroughly to exclude alternate diagnoses.

Paraspinal neurofibromas and hypertrophic neuropathy in Noonan syndrome with multiple lentigines.

BACKGROUND: Noonan syndrome with multiple lentigines (NSML), formerly known as LEOPARD syndrome, is an autosomal-dominant disorder characterised by lentigines, EKG abnormalities, ocular hypertelorism, pulmonic stenosis, abnormal genitalia, growth retardation and deafness. There is significant clinical overlap between NSML and other disorders that result from dysregulated rat sarcoma/mitogen-activated protein kinase pathway (RASopathies). Except for neurofibromatosis type 1, other RASopathies are not known to be typically associated with neurogenic tumours. METHODS AND RESULTS: We evaluated patients from three families with pigmentary skin lesions, progressive neuropathy, enlarged nerves, massive burden of paraspinal tumours (neurofibroma was confirmed in one patient) and a clinical diagnosis of NSML. All patients had a mutation in the protein tyrosine phosphatase catalytic domain of the PTPN11 gene; two unrelated patients had the p.Thr468Met mutation, while the family consisting of two affected individuals harboured the p.Thr279Cys mutation. Molecular analysis performed on hypertrophic nerve tissue did not disclose a second somatic hit in NF1, PTPN11, NF2 or SMARCB1 genes. CONCLUSIONS: Neurogenic tumours and hypertrophic neuropathy are unusual complications of NSML and may be an under-recognised manifestation that would warrant surveillance. Our observation may also have implications for other disorders caused by RAS-pathway dysregulation.

Postoperative Pyoderma Gangrenosum Following Video-Assisted Thoracic Surgery.

Pyoderma gangrenosum (PG) is a neutrophilic, ulcerative dermatosis that can develop at sites of cutaneous trauma, including surgical incisions, a phenomenon known as pathergy. The characteristic lesion is a painful, rapidly expanding ulceration with a violaceous undermined border.1 A biopsy taken from the expanding violaceous border shows predominantly neutrophilic dermal inflammation with neutrophilic abscess formation.

The etiology of PG appears to be variable among patients, as about a half of the reported cases are associated with systemic disease such as inflammatory bowel disease, rheumatoid arthritis, or myeloproliferative disorders, while the other half seem to be idiopathic.2 PG is difficult to diagnose as other etiologies, including infectious, vasculitic, and other inflammatory dermatoses, must be excluded.1 Histopathologic and biochemical markers of PG, such as dermal neutrophilic infiltrate or overexpression of interleukin-8,3 respectively, are not pathognomonic. Given that several drugs, such as hydralazine, mesalamine, and sunitinib, are reportedly associated with PG, failure to recognize this association and stop these medications may delay diagnosis and therapy. We report a case of idiopathic postoperative PG following video-assisted thoracic surgery (VATS).

J Drugs Dermatol. 2017;16(7):711-713.

Pyostomatitis vegetans (PSV)-pyodermatitis vegetans (PDV): A clinicopathologic study of 7 cases at a tertiary referral center.

BACKGROUND: Pyostomatitis vegetans (PSV)-pyodermatitis vegetans (PDV) is a rare inflammatory mucocutaneous disease associated with inflammatory bowel disease. OBJECTIVE: We sought to evaluate the clinicopathologic findings of PSV-PDV in a series of 7 patients. METHODS: We conducted a retrospective review of all cases of PSV-PDV at the Mayo Clinic from 1995 to 2014. RESULTS: Seven patients with PSV-PDV were included, and all had inflammatory bowel disease. Three had Crohn's disease and 4 had ulcerative colitis. Three patients had peripheral blood eosinophilia. Two had concomitant pyoderma gangrenosum in which pyoderma gangrenosum lesions were recalcitrant to therapy. Primary sclerosing cholangitis was seen in 3 patients. Two patients had direct and 3 had indirect immunofluorescence findings. Tissue eosinophilia was seen in the majority of mucosal and cutaneous lesions. LIMITATIONS: Limited sample size and retrospective study design are limitations. CONCLUSIONS: PSV-PDV is associated with inflammatory bowel disease and primary sclerosing cholangitis and may precede gastrointestinal symptoms. Immunofluorescence findings in select PSV-PDV cases may indicate possible overlap with autoimmune bullous disease. Tissue eosinophilia may be helpful in distinguishing PSV-PDV from pyoderma gangrenosum. Strict control of bowel disease and close monitoring of patients with subclinical disease is warranted.

Clinical features, causes, treatments, and outcomes of peristomal pyoderma gangrenosum (PPG) in 44 patients: The Mayo Clinic experience, 1996 through 2013.

BACKGROUND: There are limited large case series of peristomal pyoderma gangrenosum (PPG), an uncommon cause of recalcitrant peristomal ulceration. OBJECTIVE: We sought to further characterize the clinical features, causes, treatments, and outcomes of PPG. METHODS: We conducted a retrospective chart review of patients with PPG seen at Mayo Clinic from January 1996 to July 2013. RESULTS: A total of 44 patients had PPG (mean age, 46 years; 32 women [73%]); 41 (93%) had inflammatory bowel disease. Mean time to PPG onset after stoma surgery was 5.2 months (excluding 1 outlier). Systemic therapies included corticosteroids (66%), immunosuppressants (41%), biologics (36%), and a combination of systemic treatments (36%). Mean time to reach a complete response was 10.7 weeks. Stoma closure had the greatest complete response (4 of 4 patients, no recurrences). Recurrence after any treatment was documented in 23 of 38 (61%) patients. Stoma relocation/revision recurred in 10 of 15 (67%) patients. Remission occurred in 29 of 31 (94%) patients. LIMITATIONS: Small sample size and retrospective study design are limitations. CONCLUSION: PPG is strongly associated with inflammatory bowel disease, is predominant in women, and has a prolonged time to onset and high recurrence rate. Systemic corticosteroid or combination therapies and surgical closure can be effective treatments. Timely recognition and management are paramount to achieving early remission.

Cutaneous microemboli from hydrophilic polymer after endovascular procedures.

BACKGROUND: Multiple devices and coatings assist with endovascular insertion of sheaths, catheters, and guide wires. Hydrophilic polymer coatings, a common component of endovascular surgical devices, reportedly cause microvascular obstruction and embolization, with various sequelae in organs and soft tissue. OBJECTIVE: We sought to describe clinical and histopathologic features of cutaneous manifestations of hydrophilic polymer gel emboli. METHODS: We evaluated the clinical and histopathologic characteristics of 8 patients with cutaneous complications of hydrophilic polymer gel emboli who presented in May 2013 through February 2015. RESULTS: Sudden onset of lower extremity livedo racemosa, purpuric patches, or both, occurred hours to days after endovascular procedures involving the aorta. Histopathologic evaluation showed basophilic lamellated material, consistent with hydrophilic polymer gel emboli, within small dermal vessels. LIMITATIONS: This was a retrospective study with small sample size and not controlled for all similar procedures in this population. CONCLUSION: Hydrophilic polymer gel coatings in endovascular devices can embolize to skin and cause microvascular occlusion, presenting as livedo racemosa, purpura, or both. Given the number of patients observed over a short period, this phenomenon may be underappreciated. Hydrophilic polymer gel emboli should be considered in differential diagnosis of livedo racemosa and purpura after endovascular procedure.

Postoperative pyoderma gangrenosum (PG): the Mayo Clinic experience of 20 years from 1994 through 2014.

BACKGROUND: Postoperative pyoderma gangrenosum (PG) is a neutrophilic dermatosis characterized by the development of PG-type lesions within surgical sites. OBJECTIVE: We sought to characterize postoperative PG as a distinct subtype of PG for earlier recognition and prevention of improper therapy. METHODS: We conducted a retrospective chart review of patients with nonperistomal postoperative PG at Mayo Clinic from 1994 to 2014.x RESULTS: Eighteen patients had postoperative PG with an average age of 58 years. Fifteen (83%) were female. Among patients with postoperative PG, 4 (22%) had an associated systemic disease traditionally associated with PG. Sites of postoperative PG included 7 breast (38%), 7 abdomen (38%), 1 back, 1 shoulder, 1 ankle, and 1 scrotum, witxxh breast reconstruction being the most common surgery. The average time to symptoms was 11 days. No patients had a fever. Eight (44%) had documented anemia and 5 (27%) had leukocytosis. Antibiotics and systemic corticosteroids were initiated in 10 (56%) and 14 (83%), respectively. Debridement was done in 11 (61%) patients. LIMITATIONS: Small sample size and retrospective study are limitations. CONCLUSION: Postoperative PG is a rare surgical complication with predilection for the breast and abdomen of females and has less association with systemic disease than idiopathic PG. Early recognition may prevent unnecessary debridements and morbidity.

Diffuse dermal angiomatosis of the breast: clinicopathologic study of 5 patients.

BACKGROUND: Diffuse dermal angiomatosis (DDA) is a rare skin condition considered to be a type of reactive angioendotheliomatosis. Histologic features are quite characteristic. It has been reported in association with vaso-occlusive disease, trauma, or underlying hypercoagulability. In the past, it was thought to be most common on the lower extremities. OBJECTIVE: The purpose of this study was to describe the clinical and histologic features of 5 patients with DDA. METHODS: The clinical and histologic features of 5 patients with DDA were evaluated. RESULTS: Five women (47-58 years old) had DDA of the breast. Histologic examination showed a diffuse proliferation of benign endothelial cells between the collagen bundles throughout the dermis. LIMITATIONS: The main limitation of our study is the limited number of patients. CONCLUSION: Involvement of the breast is much more common than previously reported. Smoking seems to be a strong risk factor for the disease. Revascularization, oral corticosteroids, and oral anticoagulation have all been reported to be somewhat successful in the treatment of DDA of the breast.

Reticulated acanthoma with sebaceous differentiation: another sebaceous neoplasm associated with Muir-Torre syndrome?

Reticulated acanthoma with sebaceous differentiation (RASD) represents a rare benign cutaneous epithelial neoplasm with sebaceous differentiation. There has been much speculation about the relationship between RASD and Muir-Torre syndrome (MTS). We report a 53 year-old man who presented with RASD in addition to a prior history of sebaceous adenomas. Immunohistochemically, the tumour cells in the RASD and sebaceous adenomas showed a significantly reduced MSH6 protein expression, whereas there was no loss of MLH1, MSH2 and PMS2. This benign neoplasm, which can be mistaken for various other cutaneous lesions with sebaceous differentiation, deserves wider recognition for its possible association with MTS.