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Junctional epidermolysis bullosa (JEB) is a rare genodermatosis characterized by a split in the lamina lucida usually because of mutations in LAMA3, LAMB3 and LAMC2 resulting in absence or reduction of laminin-332. Rare subtypes of JEB have mutations in COL17A1, ITGB4, ITGA6 and ITGA3 leading to reduction or dysfunction of collagen XVII, integrin α6β4 and integrin α3. The classic finding under light microscopy is a paucicellular, subepidermal split. We describe the unusual presence of an eosinophilic infiltrate in the bullae and subjacent dermis in a neonate with JEB, generalized intermediate (formerly known as non-Herlitz-type JEB), discuss the histologic differential diagnosis for a subepidermal blister in a neonate, review the literature regarding cases of epidermolysis bullosa (EB) presenting with inflammatory infiltrates, and discuss mechanisms to explain these findings. This case highlights that eosinophils can rarely be seen in EB and should not mislead the dermatopathologist into diagnosing an autoimmune blistering disorder., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Nevus anelasticus represents a rare entity that is most commonly classified as a connective tissue nevus. It typically presents before 20 years of age with asymmetrically distributed white-to-skin-toned or pink-to-red papules or plaques on the trunk and upper extremities. The lesion is defined histopathologically by the absence or degeneration of elastic fibers in the dermis. We report the case of a healthy 17-year-old female who presented with an asymptomatic slowly progressive plaque on the right inferior areola. Histopathologic examination showed the absence of elastic fibers in the papillary and upper reticular dermis and fragmented elastic tissue fibers in the deep reticular dermis. Although there is ongoing controversy regarding the nosology of this uncommon disorder, we propose that it is a distinct entity based on its histopathologic and clinical features., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Many current business trends in the field of dermatopathology deserve ethical scrutiny. An important point to consider in these analyses is that which is legal is not necessarily ethical. We examine the topics of client billing, contractual joint ventures, and health information technology donations, including both the legal implications as pertaining to the Stark Law and Anti-Kickback Statute, and the ethical ramifications of these practices., (© 2013 Elsevier Inc. All rights reserved.)

Summary: We report a case of a thermal burn that occurred during MR imaging likely caused by invisible silver-embedded microfibers in the fabric of an undershirt. As the prevalence of fabric containing nondetectable metallic microfiber increases in athletic and "tech" clothing, the importance of having patients change into safe facility-provided garments before MR imaging is emphasized.

Infantile hemangiomas are the most common tumors of infancy. The serendipitous discovery of the therapeutic efficacy of propranolol in the management of infantile hemangiomas has revolutionized the care and understanding of these lesions, and greatly improved the prognosis for a good cosmetic outcome. In addition, there has been an expansion of indications for treatment of hemangiomas, taking into account not only those hemangiomas that can cause airway compromise, amblyopia, and cardiac overload, but also those lesions that can lead to unsatisfactory cosmetic outcome or deformity after involution. Current concepts of pathogenesis of infantile hemangiomas, of segmental hemangiomas with systemic associations, of hepatic hemangiomas, and of the use of systemic and topical beta-blockers for the management of IH are all reviewed., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Late-onset focal dermal elastosis is a rare disorder that presents clinically with the development of small white-to-yellow papules simulating pseudoxanthoma elasticum (PXE) in otherwise healthy adults in the seventh through ninth decades. It is characterized histopathologically by foci of increased normal-appearing elastic tissue in the reticular dermis. The disorder lacks any of the systemic complications of PXE and clinically resembles several other elastic tissue disorders that mimic PXE. We report two cases of late-onset focal dermal elastosis. The first is of a 75-year-old female who presented with symmetrically distributed, 2-5 mm white-to-yellow, discrete and coalescing, non-follicular papules on the posterolateral neck, anterior chest and axillae. The second case involves a 39-year-old female who presented with asymptomatic flesh-colored lesions on the posterior neck, back, antecubital and popliteal fossae, thighs, forearms and wrists. Skin biopsies in each case revealed aggregates of elastic fibers in the reticular dermis without calcification. The differential diagnosis of clinical and histopathologic imitators of PXE is discussed., (Copyright © 2012 John Wiley & Sons A/S.)

Acrodynia, also known as pink disease, erythredema polyneuropathy, Feer syndrome, and raw-beef hands and feet, is thought to be a toxic reaction to elemental mercury and less commonly to organic and inorganic forms. Occurring commonly in the early 20th century, acrodynia is now a seemingly extinct disease in the modern world because of regulations to eliminate mercury from personal care products, household items, medications, and vaccinations. We present a case of a 3-year-old girl with acrodynia secondary to toxic exposure to elemental mercury in the home environment., (© 2012 Wiley Periodicals, Inc.)

Pseudoxanthoma elasticum (PXE), a prototypic heritable disorder with ectopic mineralization, manifests with characteristic skin findings, ocular involvement, and cardiovascular problems. The classic forms of PXE are due to loss-of-function mutations in the ABCC6 gene, which encodes ABCC6, a putative transmembrane efflux transporter expressed primarily in the liver. While considerable progress has recently been made in understanding the molecular genetics and pathomechanisms of PXE, no effective or specific treatment is currently available for this disorder. PXE International, the premiere patient advocacy organization, organized a workshop in November 2010 to assess the current state of diagnostics and research to develop an agenda towards treatment of PXE. This overview summarizes the progress in PXE research, with emphasis on molecular therapies for this, currently intractable, disorder., (Copyright © 2011 Wiley-Liss, Inc.)

Background: Pseudoxanthoma elasticum (PXE) is thought to be a metabolic disorder resulting from mutations in the gene encoding the cellular transporter, ABCC6, which is primarily expressed in liver and kidney. We encountered 3 patients who developed clinical and histopathological evidence of PXE after liver transplantation, suggesting that PXE could have been acquired from the transplanted organ., Objective: We sought to delineate the clinical features and screen each patient and samples of donor liver for mutations in the ABCC6 gene., Methods: Each patient underwent full clinical examination, skin biopsy, and ophthalmologic examination, and whole genome sequencing using standard techniques. Fixed samples of donor liver tissue were available for mutation analysis in two patients and of donor kidney tissue in one., Results: All 3 patients had unequivocal clinical and histopathologic evidence of PXE. No patient (or family member available for screening) had evidence of mutations in ABCC6. Neither liver specimen nor the single available kidney specimen showed evidence of mutations in ABCC6., Limitations: Liver tissue was not available from one patient and DNA was of poor quality in another, resulting in limited screening. Genetic testing does not detect ABCC6 mutations in 10% of patients with confirmed PXE., Conclusion: Although we were unable to demonstrate ABCC6 mutations in limited screening of fixed donor livers, the absence of any PXE mutations in the affected patients, the timing of onset of PXE, and the known acquisition of other metabolic disorders and coagulopathies from donor livers suggest that PXE was likely acquired via liver transplantation., (Copyright © 2010 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

As Internet access has become ubiquitous, electronic mail (e-mail) is becoming more widely used as a means of communication between patient and dermatologist. Dealing with the ethical, legal, and clinical consequences has lagged behind the technology. Privacy of e-mail cannot exist without security, and as a foundation for understanding e-mail security, the elements of e-mail technology are reviewed. One of the greatest risks of e-mail is compromise of privacy. Although self-documenting and convenient, e-mail lacks the emotional cues of face-to-face encounters, is asynchronous and not always read in timely fashion, and is not suitable for certain clinical concerns such as urgent matters and cancer diagnoses. Legal issues relating to federal privacy regulations, ethical issues such as autonomy and justice, and guidelines for the use of e-mail in clinical practice are reviewed. Case scenarios are used to present the pitfalls in clinical e-mail encounters, including establishment of the doctor-patient relationship, diagnosis and treatment over the Internet, and curbside consultations.

Teledermatology is the use of telecommunication for medical diagnosis and patient care in dermatology. The visual nature of diagnosis in dermatology makes it particularly well suited to the practice of telemedicine. The differences between the two basic types of teledermatology, real-time and store-and-forward, are reviewed. Case scenarios are used to examine some of the ethical and clinical issues that can occur, such as the nature of the doctor-patient relationship, follow-up of incidental diagnoses, limitations of telemedicine, privacy issues, and licensing. Guidelines for the use of telemedicine in dermatology are reviewed.

The Accreditation Council for Graduate Medical Education and the Royal College of Physicians and Surgeons of Canada both require the teaching and demonstration of general competencies, which include professionalism and ethics as a condition of training program accreditation and specialty certification, respectively. Residents in dermatology and other specialties perceive their training in ethics is inadequate in numerous areas. Residents and specialists in dermatology encounter numerous ethical and professional issues throughout their workday. A dermatoethics curriculum was developed at The Warren Alpert Medical School of Brown University in 2001 to address the need for training in bioethics and professionalism. The subject matter of the curriculum and didactic methods are reviewed. Guidelines for effective teaching of ethics and professionalism to dermatology residents are presented. It is important to make the teaching sessions relevant to the residents' day-to-day work experiences and personal needs. Honesty and openness on the part of faculty and trainees is important. Although informality fosters such exchanges, the sessions should be a learning experience. Resources outside the residency program should be used as necessary. Evaluation of ethics and professionalism in trainees is addressed.

Background: Pseudoxanthoma elasticum (PXE) is an autosomal recessive metabolic disorder with ectopic mineralization in the skin, eyes and cardiovascular system. PXE is caused by mutations in ABCC6., Objective: To examine 54 unrelated South African PXE patients for ABCC6 PXE causing mutations., Methods: Patients were screened for mutations in ABCC6 using two strategies. The first involved a comprehensive screening of all the ABCC6 exons and flanking regions by dHPLC or sequencing whereas the second involved screening patients only for the common PXE mutations. The ABCC6 gene was screened in ten white and ten black healthy unrelated South Africans in order to examine the level of common non-PXE associated variation., Results: The Afrikaner founder mutation, R1339C, was present in 0.41 of white ABCC6 PXE alleles, confirming the founder effect and its presence in both Afrikaans- (34/63 PXE alleles) and English-speakers (4/28). Eleven mutations were detected in the white patients (of European origin), including two nonsense mutations, 6 missense mutations, two frameshift mutations and a large deletion mutation. The five "Coloured" patients (of mixed Khoisan, Malay, European and African origin) included three compound heterozygotes with R1339C as one of the mutations. The three black patients (sub-Saharan African origin) were all apparent homozygotes for the R1314W mutation. Blacks showed a trend towards a higher degree of neurtral variation (18 variants) when compared to whites (12 variants)., Conclusion: Delineation of the ABCC6 mutation profile in South African PXE patients will be used as a guide for molecular genetic testing in a clinical setting and for genetic counselling.

Pseudoxanthoma elasticum (PXE) is an inherited disorder characterized by calcification of elastic fibres leading to dermatological and vascular alterations associated to premature aged features and to life threatening clinical manifestations. The severity of the disease is independent from the type of mutation in the ABCC6 gene, and it has been suggested that local and/or systemic factors may contribute to the occurrence of clinical phenotype. The redox balance in the circulation of 27 PXE patients and of 50 healthy subjects of comparable age was evaluated by measuring the advanced oxidation protein products (AOPP), the lipid peroxidation derivatives (LOOH), the circulating total antioxidant status (TAS), the thiol content and the extracellular superoxide dismutase activity (EC-SOD). Patients were diagnosed by clinical, ultrastructural and molecular findings. Compared to control subjects, PXE patients exhibited significantly lower antioxidant potential, namely circulating TAS and free thiol groups, and higher levels of parameters of oxidative damage, as LOOH and of AOPP, and of circulating EC-SOD activity. Interestingly, the ratio between oxidant and antioxidant parameters was significantly altered in PXE patients and related to various score indices. This study demonstrates, for the first time, that several parameters of oxidative stress are modified in the blood of PXE patients and that the redox balance is significantly altered compared to control subjects of comparable age. Therefore, in PXE patients the circulating impaired redox balance may contribute to the occurrence of several clinical manifestations in PXE patients, and/or to the severity of disease, thus opening new perspectives for their management.

Both American and Canadian residency accreditation bodies have formal requirements in core competencies that include training in ethics and professionalism without prescribing content. A structured seminar series in medical ethics and professionalism relating to dermatology practice was started at Brown Medical School's dermatology residency in 2001. Methods of instruction include discussion groups, review of medical and lay literature, book review, didactic teaching, case presentation, and informal e-mail exchange. Some of the topics that have been covered include basic medical ethics, research ethics, physician-industry relationships, truth telling, privacy and confidentiality, duty to treat, and ethical and legal issues in cosmetic dermatology, dermatologic surgery, dermatologic genetics, occupational dermatology, and pediatric dermatology. The main goals of the curriculum are to fulfill the core competency requirement in professionalism of the specialty certifying boards, introduce trainees to the cross-disciplinary literature of biomedical ethics and current ethical controversies, and encourage dialogue on ethics and professionalism among faculty, colleagues in other specialties, and dermatology trainees.

Although commonly used in the treatment of melanoma, sentinel lymph node biopsy has not yet been successfully used to detect lymphatic metastasis of basal cell carcinoma because of exceedingly low rates of metastasis. We describe the use of lymphatic mapping and sentinel lymph node biopsy in a patient after basal cell carcinoma was identified within a lymphatic vessel in the primary excisional specimen. As a result, the patient was found to have clusters of basal cell carcinoma in a sentinel lymph node resected from the right deltopectoral groove. Although metastatic basal cell carcinoma is exceedingly rare, we conclude that sentinel lymph node biopsy may be useful for certain high-risk lesions, such as lesions demonstrating histologic evidence of lymphatic invasion. Further experience is necessary to determine the clinical usefulness of sentinel node biopsy in these patients and its effect on patient survival.

Elastic fibers in the extracellular matrix are integral components of dermal connective tissue. The resilience and elasticity required for normal structure and function of the skin are attributable to the network of elastic tissue. Advances in our understanding of elastic tissue physiology provide a foundation for studying the pathogenesis of elastic tissue disorders. Many acquired disorders are nevertheless poorly understood owing to the paucity of reported cases. Several acquired disorders in which loss of dermal elastic tissue produces prominent clinical and histopathologic features have recently been described, including middermal elastolysis, papular elastorrhexis, and pseudoxanthoma-like papillary dermal elastolysis, which must be differentiated from more well-known disorders such as anetoderma, acquired cutis laxa, and acrokeratoelastoidosis. Learning objective At the conclusion of this learning activity, participants should have an understanding of the similarities and differences between acquired disorders of elastic tissue that are characterized by a loss of elastic tissue.

Elastic fibers in the extracellular matrix are an integral component of dermal connective tissue. The resilience and elasticity required for normal structure and function of the skin may be attributed to the network of elastic tissue. Advances in our understanding of elastic tissue physiology provide a foundation for studying the pathogenesis of elastic tissue disorders. Many acquired disorders are nevertheless poorly understood due to the paucity of reported cases. Several acquired disorders in which accumulation or elastotic degeneration of dermal elastic fibers produces prominent clinical and histopathologic features have recently been described. They include elastoderma, linear focal elastosis, and late-onset focal dermal elastosis and must be differentiated from better-known disorders, among them acquired pseudoxanthoma elasticum, elastosis perforans serpiginosa, and Favré-Racouchot syndrome. Learning objective At the conclusion of this learning activity, participants should understand the similarities and differences between acquired disorders of elastic tissue that are characterized by an increase in elastic tissue, as well as the spectrum of solar elastotic dermatoses.

Pseudoxanthoma elasticum (PXE) is caused by mutations in the ABCC6 gene, encoding for the membrane transporter MRP6, whose physiological role is still unknown. PXE is characterized by skin, eye, and cardiovascular alterations mainly due to mineralization of elastic fibers. The ultrastructural alterations of a large number of tissues obtained at autopsy from 2 PXE patients were analyzed and compared to clarify the involvement of the various organs in PXE and to identify cell types responsible for clinical manifestations. Ultrastructural alterations typical of PXE were present in all organs examined and consisted mostly of fragmentation and mineralization of a number of elastic fibers, abnormalities of collagen fibril shape and size, and, less frequently, deposition of aggregates of matrix constituents in the extracellular space. The severity of alterations was more pronounced in the organs affected by the clinical manifestations of PXE. Interestingly, veins and arteries were similarly damaged, the adventitia and the perivascular connective tissue being the most affected areas. Therefore, alterations in PXE are systemic and affect all soft connective tissues, even in the absence of specific clinical manifestations. The localization of alterations suggests that fibroblasts and/or smooth muscle cells are very likely involved in the pathogenesis of the disorder. These findings may help in the diagnosis of PXE when clinical manifestations affect internal organs.

We present a patient with an extensive cluster of exophytic nodules that developed on his chin. These nodules consisted of abscesses and fibrotic areas. Lesion morphology, histology, and microbiology support a follicular occlusion triad entity. However, the distribution is striking and does not fit the entities described in the triad. We present the case to show that follicular occlusion was the inciting factor in our patient's eruption and to broaden our concept of clinical manifestations that can arise from this pathologic process.

Pseudoxanthoma elasticum (PXE) is an inherited disease with many systemic complications. Its diagnosis can be easily overlooked. The purpose of this study was to assess a new clinical sign of PXE. A total of 47 consecutive patients with PXE were examined for mental creases and compared with 47 age-matched control patients. Photographs were evaluated by a blinded investigator. Mental creases were present in 43 of 47 patients with PXE, affected the majority of individuals in every age group, and were significantly more common than in control patients (P <.0001). Under the age of 30 years, two thirds of patients with PXE had mental creases whereas mental creases were not present in any age-matched control patients. Mental creases commonly occur in patients with PXE. In young patients they are a sensitive and highly specific physical finding of this disorder. The presence of exaggerated mental creases is, thus, a useful physical marker for PXE.

Background: There have been isolated case reports of arterial and skin calcification in mammograms of patients with pseudoxanthoma elasticum (PXE), and unpublished anecdotes of many women with PXE undergoing breast biopsy for evaluation of microcalcifications., Objective: Our aim was to systematically evaluate mammography and breast pathology in PXE., Methods: The mammograms of 51 women with confirmed PXE were compared with those of a control sample of 109 women without PXE, noting each of the following characteristics on each mammogram: breast density, skin thickening, skin microcalcifications, vascular calcification, breast microcalcifications and macrocalcifications, and masses. The characteristics of the 2 samples were compared using the 2-tailed t test with a pooled estimate of variance. The indications for mammography and data for each of the mammographic findings were analyzed using the chi(2) test. Available breast biopsy material was reviewed., Results: The PXE and control groups were similar in age and indications for mammography. There was a statistically significant increase in skin thickening, vascular calcification, and breast microcalcifications in the PXE group (P <.001 each). Breast density, masses, macrocalcifications, and skin calcification did not differ statistically in the 2 groups, but no control patient had axillary calcification, or both vascular calcification and microcalcifications (P <.001). Nearly 1 in 7 of the patients with PXE demonstrated at least 3 of the following: microcalcifications, skin calcifications, vascular calcification, and skin thickening; whereas none of the control group did. Histopathologic findings of breast tissue showed calcification of dermal elastic fibers, subcutaneous arteries, and elastic fibers of the deep fascia and interlobular septae of the fat adjacent to breast parenchyma., Conclusion: Breast microcalcification and arterial calcification are not rare in the normal population and are not of diagnostic value. The presence of both of these findings, especially with skin thickening or axillary skin calcification, should suggest a diagnosis of PXE. The majority of breast calcifications in PXE are benign.

Pseudoxanthoma elasticum (PXE) is a heritable elastic tissue disorder recently shown to be attributable to mutations in the ABCC6 ( MRP6) gene. Whereas PXE has been identified in all ethnic groups studied to date, the prevalence of this disease in various populations is uncertain, although often assumed to be similar. A notable exception however is the prevalence of PXE among South African Afrikaners. A previous report has suggested that a founder effect may explain the higher prevalence of PXE in Afrikaners, a European-derived population that first settled in South Africa in the 17th century. To investigate this hypothesis, we performed haplotype and mutational analysis of DNA from 24 South African families of Afrikaner, British and Indian descent. Among the 17 Afrikaner families studied, three common haplotypes and six different disease-causing variants were identified. Three of these mutant alleles were missense variants, two were nonsense mutations and one was a single base-pair insertion. The most common variant accounted for 53% of the PXE alleles, whereas other mutant alleles appeared at lower frequencies ranging from 3% to 12%. Haplotype analysis of the Afrikaner families showed that the three most frequent mutations were identical-by-descent, indicating a founder origin of PXE in this population.

The inheritance pattern of pseudoxanthoma elasticum (PXE) is controversial. Inheritance patterns are confounded by delayed diagnosis and mild or limited phenotypic expression among certain family members. Because testing for the genetic mutation(s) responsible for PXE is not routine, genetic counseling must be done with caution. We describe 4 families in which one or more children were diagnosed with PXE. Detailed examination of the parents was carried out, including skin biopsy and ophthalmologic examination. In 3 of the 4 families, one parent had limited phenotypic expression, such as ocular findings without skin lesions or very mild skin lesions with no ocular findings. In the other family, one parent had very mild skin and ocular disease. All 4 affected parents had diagnostic skin biopsy findings. In none of the 4 families was the inheritance pattern clear-cut. Although the inheritance pattern of PXE has been debated, clinically significant stigmata of PXE, which are not always readily apparent, can occur in successive generations. Therefore all first-degree relatives of affected patients should receive a full dermatologic examination as well as a funduscopic examination. If even mild typical skin or eye findings are present, then skin biopsy should be performed.

Pseudoxanthoma elasticum (PXE) is a heritable disorder characterized by calcification of elastic fibres in skin, arteries and retina that results in dermal lesions with associated laxity and loss of elasticity, arterial insufficiency and retinal haemorrhages leading to macular degeneration. PXE is usually found as a sporadic disorder, but examples of both autosomal recessive and autosomal dominant forms of PXE have been observed. Partial manifestations of the PXE phenotype have also been described in presumed carriers in PXE families. Linkage of both dominant and recessive forms of PXE to a 5-cM domain on chromosome 16p13.1 has been reported (refs 8,9). We have refined this locus to an 820-kb region containing 6 candidate genes. Here we report the exclusion of five of these genes and the identification of the first mutations responsible for the development of PXE in a gene encoding a protein associated with multidrug resistance (ABCC6).

We have performed linkage analysis on 21 families with pseudoxanthoma elasticum (PXE) using 10 polymorphic markers located on chromosome 16p13.1. The gene responsible for the PXE phenotype was localized to an 8-cM region of 16p13.1 between markers D16S500 and D16S3041 with a maximum lod score of 8.1 at a recombination fraction of 0.04 for marker D16S3017. The lack of any locus heterogeneity suggests that the major predisposing allele for the PXE phenotype is located in this region. Haplotype studies of a total of 36 PXE families identified several recombinations that further confined the PXE gene to a region (< 1 cM) between markers D16S3060 and D16S79. This PXE locus was identified within a single YAC clone and several overlapping BAC recombinants. From sequence analysis of these BAC recombinants, it is clear that the distance between markers D16S3060 and D16S79 is about 820 kb and contains a total of nine genes including three pseudogenes. We predict that mutations in one of the expressed genes in the locus will be responsible for the PXE phenotype in these families., (Copyright 1999 Academic Press.)

By using the Giemsa banding technique we identified three patients with chromosome deletion 4p-. All had anterior segment anomalies, exotropia, blepharoptosis, antimongoloid palpebral fissures, hypertelorism, and disk abnormalities. One patient (Case 1) had Rieger's anomaly. Some clinical features in patients with 4p- are similar to those in patients with chromosome deletion 5p-, cri-du-chat syndrome, although 4p- individuals do not have the distinctive cry. The ocular features which distinguish 4p- from other deletions include normal tearing, some degree of blepharoptosis, and the preponderance of anterior segment signs.