Treatment of Acute Graft-versus-Host Disease in Liver Transplant Recipients.

Acute graft-versus-host disease (aGvHD) is a rare complication of liver transplantation associated with high morbidity and mortality. Death typically occurs due to complications related to severe infection, shock, and multiorgan failure. The clinical presentation involves dysfunction of multiple organ systems with overlapping symptoms that often results in a diagnostic delay. As there are a limited number of cases reported in the literature, there are no clear guidelines for treatment. Many different therapeutic measures have been utilized that target various immune system pathways, but steroids remain the first line of therapy. We report on two patients who developed aGvHD after liver transplantation who were treated with ruxolitinib, a novel Janus kinase 1/2 (JAK) inhibitor that has been shown to improve outcomes in steroid refractory cases of aGvHD after allogenic hematopoietic stem cell transplantation. We reviewed the literature to discuss various therapeutic options currently available for aGvHD after liver transplantation.

Sweet Syndrome, Not so Sweet during an Ulcerative Colitis Flare Especially When You Cannot Eat.

Sweet syndrome is a rare skin condition characterized by painful papules, nodules, or plaques with dense neutrophilic infiltrate in the upper dermis. It has been observed as idiopathic (classical), malignancy-associated, and drug-induced. The pathogenesis is not completely understood, but it is thought to involve hypersensitivity reactions to specific triggers. In some cases the etiology is unclear or may be multifactorial. We present a case of Sweet syndrome secondary to ulcerative colitis flare versus adalimumab re-induction.

Proliferating pilomatricoma in a 9-year-old girl.

Proliferating pilomatricoma is a rare, benign tumor of hair matrix origin that rarely occurs in children. We report the case of a 9-year-old girl with a rapidly growing, proliferating pilomatricoma located on the glabella. The lesion was embolized and surgically excised, with histopathological examination of the tissue confirming the diagnosis of proliferating pilomatricoma.

Verruciform xanthoma in recessive dystrophic epidermolysis bullosa and keratitis-ichthyosis-deafness syndrome: Report of two cases and a review of the literature.

Verruciform xanthoma is a benign, wart-like lesion that can clinically mimic squamous cell carcinoma. We describe two teenage patients with severe genodermatoses, recessive dystrophic epidermolysis bullosa (RDEB), and keratitis-ichthyosis-deafness (KID) syndrome, respectively, each found to have plaques suspicious for malignancy, later demonstrated on histopathologic examination to be verruciform xanthoma. We discuss the connection between these severe genodermatoses and the suspected pathophysiology of verruciform xanthoma. In addition, we highlight the importance of recognizing verruciform xanthoma as a clinical mimicker of squamous cell carcinoma, for which patients with RDEB and KID syndrome are at increased risk.

Cutaneous refractile foreign body microemboli with intravascular injection of oral medication.

Injection drug abuse (IDA) is known to cause a spectrum of systemic and cutaneous complications. Despite the increasing incidence of IDA around the world, there is a paucity of literature discussing cutaneous complications from a dermatopathologic perspective. We present a case of a 35-year-old male with a complex medical history of Von Willebrand disease, Beçhet disease and diverticular disease. Following a sigmoidectomy/colostomy for diverticular perforation, he presented with fever and an indurated right arm displaying livedoid purpura. The right distal fingertips showed purpura with focal ulceration. A punch biopsy of the right wrist did not show evidence of inflammatory vasculitis or pyogenic infection, but instead showed a focus of polarizing, refractile material occluding a dilated arterial lumen within the mid-dermis. The patient admitted to injecting a suspension of crushed ondansetron (Zofran) tablets into the antecubital area to control post-operative nausea. It is known that direct intravascular injection of foreign material can cause distal ischemia and necrosis, either by local vasoconstriction, thrombosis, or formation of microemboli, as in this patient. Our objective is to bring awareness to this rarely reported phenomenon, and to raise clinical suspicion for IDA when confronted with such a unique vasculopathic pattern.

Molecular testing practices and perceptions among dermatopathologists.

BACKGROUND: We evaluated how dermatopathologists are employing molecular testing in the setting of neoplastic skin diseases, and assessed their opinions of the broader role and utility of molecular technologies in clinical practice. METHODS: A 15-question online survey was sent to Fellows of the American Society of Dermatopathology in April 2017. RESULTS: One hundred and thirty-six dermatopathologists completed the survey (response rate = 16%). A majority (94%) of respondents reported experience with one or more molecular testing strategies. Sixty-two percent of dermatopathologists order 12 or more molecular tests per year, while 5% of respondents order 2 or fewer assays per year. More frequent utilization of molecular testing is associated with relevant instruction during residency training (P = .009), primary board certification in pathology (P = .008), academic medical center affiliation (P = <.0001), higher volume clinical practice (P = .0004), presence of on-site clinical molecular pathology/cytogenetics laboratory (P = .007), and greater physician confidence incorporating test results into histopathological assessments (P = <.0001). CONCLUSIONS: Wider adoption of molecular testing in dermatopathology may be limited by factors such as physician training, test costs/insurance coverage, logistical issues and lack of evidence-based clinical practice guidelines. Dermatopathologists have concerns regarding clinical validity/utility and inappropriate/overuse of some molecular tests. The importance of longitudinal education in molecular technologies and their applications for trainee and practicing physicians is highlighted.

Syringoid Eccrine Carcinoma of the Foot: Report of a Rare Cutaneous Adnexal Neoplasm.

Syringoid eccrine carcinoma is a rare malignant adnexal tumor that typically presents in the head and neck region. Involvement of the extremities is uncommon, with only a few cases reported in the literature. Here, we report our experience with a rare case of syringoid eccrine carcinoma occurring on the plantar surface of the right foot in a 47-year-old African American woman. Histologically, incisional biopsy revealed a tumor consisting of tubulocystic structures lined by basaloid cells with an infiltrative growth pattern, extending from the reticular dermis to the deep biopsy margin. Some of the nests and cords of basaloid cells displayed syringoma-like, tadpole morphology. Immunohistochemical analysis showed diffuse immunoreactivity with monoclonal carcinoembryonic antigen, epithelial membrane antigen, cytokeratin 7, S100 protein, and CD117. These morphologic and immunophenotypic features were most consistent with syringoid eccrine carcinoma. Syringoid eccrine carcinoma has a broad differential diagnosis which must be carefully ruled out by morphology, immunohistochemistry, and thorough metastatic survey with imaging studies. Our case highlights the importance of recognizing this rare entity, which is locally destructive and has a propensity for recurrence. To the best of our knowledge, this is the first reported case of syringoid eccrine carcinoma presenting on the sole of the foot.

Development of a curriculum in molecular diagnostics, genomics and personalized medicine for dermatology trainees.

BACKGROUND: Results of molecular studies are redefining the diagnosis and management of a wide range of skin disorders. Dermatology training programs maintain a relative gap in relevant teaching. OBJECTIVE: To develop a curriculum in molecular diagnostics, genomics and personalized medicine for dermatology trainees at our institution. The aim is to provide trainees with a specialty-appropriate, working knowledge in clinical molecular dermatology. METHODS: The Departments of Dermatology and Pathology and Laboratory Medicine collaborated on the design and implementation of educational objectives and teaching modalities for the new curriculum. RESULTS: A multidisciplinary curriculum was developed. It comprises: (i) assigned reading from the medical literature and reference textbook; (ii) review of teaching sets; (iii) two 1 hour lectures; (iv) trainee presentations; (v) 1-week rotation in a clinical molecular pathology and cytogenetics laboratory; and (vi) assessments and feedback. Residents who participated in the curriculum to date have found the experience to be of value. CONCLUSIONS: Our curriculum provides a framework for other dermatology residency programs to develop their own specific approach to molecular diagnostics education. Such training will provide a foundation for lifelong learning as molecular testing evolves and becomes integral to the practice of dermatology.

Adult Onset Henoch-Schönlein Purpura: Case Report and Review of Literature.

Henoch-Schönlein purpura (HSP) is an IgA mediated small-vessel vasculitis, more common in children than adults. We present the case of a 37-year-old male who presented with complaints of nausea, vomiting, abdominal pain, purpuric rash over lower extremities, and migratory polyarthralgia five days after being treated with antibiotics for bronchitis. In addition to the abdominal pain, he developed diarrhea and colonic biopsy findings were suggestive of inflammatory bowel disease (IBD). Skin biopsy revealed leukocytoclastic vasculitis with direct immunofluorescence studies (DIF) staining of IgA deposition confirming the diagnosis of HSP. The clinical features of cutaneous eruption with abdominal complaints can be seen with either HSP or IBD; however the specific skin biopsy findings on DIF can distinguish between the two disease processes. Though HSP is primarily seen in the pediatric population, it is a disease process that must be considered in adults presenting with vasculitic skin rashes and abdominal complaints.

Molecular diagnostic strategies: a role in the practice of dermatology.

Molecular diagnostic strategies are gaining wider acceptance and use in dermatology and dermatopathology as more practitioners in this field develop an understanding of the principles and applications of genomic technologies. Molecular testing is facilitating more accurate diagnosis, staging, and prognostication, in addition to guiding the selection of appropriate treatment, monitoring of therapy, and identification of novel therapeutic targets, for a wide variety of skin diseases.

Ultrastructural and molecular confirmation of the trichodysplasia spinulosa-associated polyomavirus in biopsies of patients with trichodysplasia spinulosa.

Trichodysplasia spinulosa (TS) is a rare and only recently characterized cutaneous disease occurring in immunocompromised patients. The disease is characterized by spiny follicular papules on clinical examination and by the presence of viral inclusions at ultrastructural examination. In the last year, this virus has been identified as a new member of the polyomavirus family and designated as TS-associated polyomavirus (TSPyV). We report two organ transplant patients with this disease in which we were able to identify the TSPyV at ultrastructural and molecular level from formalin-fixed paraffin-embedded biopsies of lesional skin. Similar to prior described cases, the patients presented with follicular papules which were concentrated on the central face and associated with alopecia. Histopathology of both cases showed dilated follicular infundibula plugged with cornified eosinophilic cells containing large trichohyaline granules. Transmission electron microscopy on paraffin-embedded tissue in case 1 showed 28-nm intracellular viral particles morphologically consistent with polyoma virus. For both cases the presence of TSPyV was confirmed by polymerase chain reaction with virus-specific primers followed by identification by direct sequencing. These two cases show the presence of the newly described TSPyV in TS further establishing its association with this distinctive disease.

Molecular diagnostic testing in dermatology and dermatopathology

Molecular techniques are increasingly being employed in the field of dermatology, helping to facilitate the diagnosis and prognostication of a variety of skin diseases, in addition to guiding the selection of appropriate treatment, monitoring of therapy and identification of novel therapeutic targets. A basic knowledge of the principles of molecular diagnostics is now essential for physicians involved in the diagnosis and/or treatment of skin diseases, primarily dermatopathologists and dermatologists. Essentially, molecular diagnostic testing involves the analysis of nucleic acids (DNA and/or RNA) with a wide variety of laboratory methods. Nucleic acid amplification methods have traditionally dominated this field, with the most readily recognizable of these being polymerase chain reaction (PCR). Newer technologies are now being incorporated and can facilitate parallel gene analyses (i.e.,cDNA/oligonucleotide microarrays) and/or correlation of genomic changes with morphological features of disease [i.e., fluorescence in situ hybridization (FISH)]. This discussion provides an overview of the principles of molecular technologies most frequently used in dermatology and highlights their applications in particular disease categories.