Perforating lichen nitidus in the setting of atopic dermatitis.

Perforating lichen nitidus is a rare subtype of lichen nitidus, with approximately 11 cases reported worldwide. Lesions typically present in young male patients at sites prone to mechanical irritation, including the hands, feet, forearms, elbows, and knees. Classic histopathologic features of perforating lichen nitidus show a lymphohistiocytic infiltrate within the papillary dermis between hyperplastic rete ridges with transepidermal elimination of dermal contents. Very few cases are reported in the literature of lichen nitidus and its association with atopic dermatitis. This is the first case describing perforating lichen nitidus in a patient with a history of atopic dermatitis being treated with dupilumab injections. Lesions of perforating lichen nitidus worsened with successful treatment of atopic dermatitis. These findings suggest a unique pathophysiology of perforating lichen nitidus lesions.

Cutaneous Lymphoid Hyperplasia With T-Cell Clonality and Monotypic Plasma Cells Secondary to a Tick Bite: A Hidden Critter and the Power of Deeper Levels.

ABSTRACT: Cutaneous lymphoid hyperplasia (CLH) is a benign reactive process with T-cell or B-cell lymphocytic infiltration in the skin, which can simulate cutaneous lymphomas both clinically and histologically. Various antigenic stimuli have been implicated in the development of CLH, including tick bites. Finding histologic evidence of such triggering factors, however, is often difficult. Moreover, the presence of clonality in CLH can potentially be interpreted as a neoplastic process, posing a further diagnostic challenge to dermatopathologists, if one is not aware of such peculiar phenomena. Herein, we describe a case of CLH secondary to a tick bite, featuring both T-cell clonality and monotypic plasma cells with lambda light chain restriction; the diagnostic clue being tick parts, which became evident on assessment of deeper levels. To the best of our knowledge, this is the first reported case of a tick-associated clonal CLH with simultaneous detection of monoclonal T cells and monotypic lambda light chain restriction, mimicking primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder and Borrelia-associated primary cutaneous marginal zone B-cell lymphoma, respectively.

Acral verruca-like presentation of chronic graft-vs.-host disease.

BACKGROUND: Chronic graft-vs.-host disease (GVHD) is a severe and potentially fatal complication in patients after undergoing allogeneic stem cell transplant. This disease may be hard to diagnose as it has numerous cutaneous presentations. METHODS: We report four cases of patients seen at Stanford Hospital between January 2013 to December 2014 with hematologic malignancy who developed hyperkeratotic papules and plaques on the palms and soles after allogeneic hematopoietic stem cell transplant. RESULTS: In all four cases, standard treatments for verruca vulgaris failed. Histopathology uniformly showed basal vacuolar alteration at the dermal-epidermal junction and necrotic keratinocytes around the eccrine glands, consistent with GVHD. Interestingly, all four patients responded to topical immunosuppression. CONCLUSIONS: Acral verrucous lesions represent an underrecognized presentation of chronic GVHD. We describe four patients with verruca-like lesions on the palms and soles following allogeneic HSCT. Histopathology confirmed GVHD, and lesions improved with immunosuppression. It is important for dermatologists and dermatopathologists to recognize this rare presentation of cutaneous GVHD.

JAK2-positive cutaneous myelofibrosis presenting as sclerosing extramedullary hematopoietic tumors on the scalp: case presentation and review of the literature.

We report the second case of cutaneous myelofibrosis with a documented JAK2 activating mutation involving the scalp of a 67-year-old woman with primary myelofibrosis in her marrow. In contrast to the previous case, the biopsy revealed extensive lesional collagen deposition and closely mimicked a fibrohistiocytic proliferation. Similar rare lesions occurring in the setting of myeloproliferative neoplasms have been called sclerosing extramedullary hematopoietic tumors. These entities appear histomorphologically and etiologically distinct from extramedullary hematopoiesis, and their diagnosis should prompt the workup for a myeloproliferative neoplasm in the absence of an antecedent diagnosis. The presence of the JAK2 mutation in our case confirmed that the lesions represented skin involvement by a neoplastic myeloid proliferation and not compensatory extramedullary hematopoiesis. Our patient died of disease several months following the appearance of her lesions, which is in keeping with other reports that suggest that cutaneous myelofibrosis may serve as an independent poor prognostic sign in otherwise advanced primary myelofibrosis. A review of the literature further emphasizes the importance of distinguishing this entity from mesenchymal neoplasms and acute myeloid leukemia involving the skin.

Efficacy and safety of 12 weeks versus 18 weeks of treatment with grazoprevir (MK-5172) and elbasvir (MK-8742) with or without ribavirin for hepatitis C virus genotype 1 infection in previously untreated patients with cirrhosis and patients with previous null response with or without cirrhosis (C-WORTHY): a randomised, open-label phase 2 trial.

BACKGROUND: There is a high medical need for an interferon-free, all-oral, short-duration therapy for hepatitis C virus (HCV) that is highly effective across diverse patient populations, including patients with cirrhosis or previous null response to pegylated interferon (peginterferon) plus ribavirin (PR-null responders). We aimed to assess the efficacy, safety, and effective treatment duration of grazoprevir (an HCV NS3/4A protease inhibitor) combined with elbasvir (an HCV NS5A inhibitor) with or without ribavirin in patients with HCV genotype 1 infection with baseline characteristics of poor response. METHODS: The C-WORTHY trial is a randomised, open-label phase 2 trial of grazoprevir plus elbasvir with or without ribavirin; here we report findings for two cohorts of previously untreated patients with cirrhosis (cohort 1) and those with previous PR-null response with or without cirrhosis (cohort 2) enrolled in part B of the study. Eligible patients were adults aged 18 years or older with chronic HCV genotype 1 infection and HCV RNA concentrations of 10 000 IU/mL or higher in peripheral blood. We randomly assigned patients to receive grazoprevir (100 mg daily) and elbasvir (50 mg daily) with or without ribavirin for 12 or 18 weeks. Randomisation was done centrally with an interactive voice response system; patients and study investigators were masked to treatment duration up to week 12 but not to treatment allocation. The primary endpoint was the proportion of patients achieving HCV RNA less than 25 IU/mL at 12 weeks after end of treatment (SVR12), assessed by COBAS TaqMan version 2.0. This study is registered with ClinicalTrials.gov, number NCT01717326. FINDINGS: We describe findings for 253 patients enrolled in cohort 1 (n=123) or cohort 2 (n=130). In cohort 1, we randomly assigned 60 patients to the 12-week regimen (31 with ribavirin and 29 with no ribavirin) and 63 to the 18-week regimen (32 with ribavirin and 31 with no ribavirin); in cohort 2, we randomly assigned 65 patients to the 12-week regimen (32 with ribavirin and 33 with no ribavirin) and 65 to the 18-week regimen (33 with ribavirin and 32 with no ribavirin. High SVR12 rates were achieved irrespective of the use of ribavirin or extension of the treatment duration from 12 to 18 weeks; SVR12 rates ranged from 90% (95% CI 74-98; 28/31; cohort 1, 12 weeks, ribavirin-containing) to 100% (95% CI 89-100; 33/33; cohort 2, 18 weeks, ribavirin-containing). Among patients treated for 12 weeks with grazoprevir plus elbasvir without ribavirin, 97% (95% CI 82-100, 28/29) of patients in cohort 1 and 91% (76-98, 30/33) of patients in cohort 2 achieved SVR12. Adverse events reported in more than 10% of patients were fatigue (66 patients, 26% [95% CI 21-32]), headache (58 patients, 23% [95% CI 18-29]), and asthenia (35 patients, 14% [95% CI 10-19]). INTERPRETATION: Treatment with grazoprevir plus elbasvir, both with and without ribavirin and for both 12 and 18 weeks' treatment duration, showed high rates of efficacy in previously untreated patients with cirrhosis and previous PR-null responders with and without cirrhosis. These results support the phase 3 development of grazoprevir plus elbasvir. FUNDING: Merck & Co, Inc.

Systemic panniculitis-like T-cell lymphoma with involvement of mesenteric fat and subcutis.

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is an uncommon non-Hodgkins primary cutaneous lymphoma that typically presents as subcutaneous nodules on the extremities or trunk. Here, we report an unusual case of systemic panniculitic T-cell lymphoma with predominantly mesenteric extra-cutaneous involvement and an aggressive clinical course with histopathologic and immunophenotypic features that mimic SPTCL. This case serves to expand the body of literature regarding systemic SPTCL-like disorders with prominent extra-cutaneous involvement.

Influenza a outbreak in an ambulatory stem cell transplant center.

BACKGROUND: In the era of cost-consciousness regarding healthcare , provision of medical services in an outpatient setting has become increasingly attractive. We report an influenza outbreak in an ambulatory stem cell transplant center in 2013 that highlights unique identification and infection control challenges in this setting. METHODS: Nasopharyngeal swabs were performed on patients with suspected influenza-like illnesses (ILI), defined by subjective fever or measured temperature of ≥37.7°C (≥100°F) with cough or sore throat during July 25, 2013 through August 7, 2013. In addition, testing was triggered by an elevated C-reactive protein (CRP). Specimens were analyzed by using eSensor Respiratory Viral Panel. Clinical and epidemiologic information was collected in real time, and frequencies were calculated on demographics, baseline clinical parameters, treatment methods, comorbidities, and symptoms of affected persons. RESULTS: Thirty-one patients had influenza A (H3N2) infection during July 25, 2013 through August 7, 2013. Only 7 patients (23%) met the Centers for Disease Control and Prevention and Council of State and Territorial Epidemiologists ILI case definition. Twenty-five patients (81%) had received ≥1 transplant, with 13 (42%) having occurred within 1 year before the outbreak. Twenty-five patients (81%) had received B-cell active chemotherapy <60 days before influenza diagnosis, 6 (19%) were neutropenic, and 25 (81%) lymphopenic. Among clinical and laboratory markers analyzed, abnormal CRP was the most sensitive screening tool for influenza. Twelve (39%) patients were hospitalized (median stay, 10 days; range, 2-20). No deaths occurred. CONCLUSIONS: Immunocompromised hosts with influenza have atypical presentations. Existing surveillance case definitions might be insufficient to reliably identify influenza outbreaks in such patients.

Recognizing BRCA gene mutation risk subsequent to breast cancer diagnosis in southwestern Ontario.

OBJECTIVE: To describe the population of women in southwestern Ontario who were diagnosed with potentially preventable BRCA mutation-related breast cancer. DESIGN: Retrospective chart review. SETTING: The Cancer Genetics Clinic of the London Regional Cancer Program in London, Ont. PARTICIPANTS: Patients younger than 52 years of age who were referred to the London Regional Cancer Program Cancer Genetics Clinic between 1997 and 2007 for BRCA testing after being diagnosed with breast cancer (N = 1017). MAIN OUTCOME MEASURES: The proportion of women with BRCA1 or BRCA2 gene mutations and the proportion of women who would have qualified, based on family cancer history, for referral for genetic counseling and testing before their breast cancer diagnoses. RESULTS: Among the 1017 women referred for BRCA testing, 63 women younger than 52 years of age who had been diagnosed with breast cancer were found, subsequent to this diagnosis, to have BRCA1 or BRCA2 gene mutations. Of these, 41 (65%) had family cancer histories that would have qualified them for genetic counseling and testing, according to provincial criteria, before their own breast cancer diagnoses. Of the 63 women, most (81%) had been referred for BRCA gene mutation testing by their oncologists or surgeons. CONCLUSION: Our results suggest that the diagnosis of breast cancer could have been anticipated, and perhaps in some cases prevented, in up to two-thirds of high-risk women younger than 52 years of age in southwestern Ontario. If the high-risk status of these women had been recognized, they might have had the opportunity to choose genetic counseling, testing, more effective cancer surveillance, and potentially preventive options. The results of this study call for increased public and care provider awareness about hereditary breast cancer risk to promote women's ability to choose to access genetic counseling.

Dermatologic manifestations of colonic disorders.

PURPOSE OF REVIEW: The skin is often a mirror for matters of internal diseases including disorders of the gastrointestinal tract. Here we enumerate many cutaneous and gastrointestinal associations and focus closely on three of the lesser known cutaneous manifestations of colonic disorders. RECENT FINDINGS: Muir-Torre syndrome involves cutaneous sebaceous adenomas and internal malignancy; screening of cutaneous lesions for microsatellite instability, and absence of mismatch repair genes provides an opportunity for diagnosis of the syndrome. Degos' disease is a vasoocclusive disorder involving the cutaneous and gastrointestinal systems; this disease affects all ages with significant mortality, yet a benign variant only affecting the skin is described. Anecdotally reported treatments are listed. Metastatic Crohn's disease is the development of noncaseating granulomas at skin sites not contiguous with the gastrointestinal tract; cutaneous lesions may precede the onset of colonic disease or appear in the absence of active bowel disease, and extensive surgical debridement of perineal lesions is often necessary. SUMMARY: Knowledge of these cutaneous manifestations provides an insight into the state of colonic health. These clues alert the clinician to the potential for life-threatening consequences, which leads to vigilant screening and hopefully earlier diagnosis.

Severe cutaneous adverse drug reaction due to fluconazole.

Fluconazole is a rare cause of severe cutaneous adverse drug reactions. A case of a diffuse, exfoliative eruption due to fluconazole is presented. Convincing arguments for a diagnosis of both widespread bullous fixed drug eruption and toxic epidermal necrolysis are made. The clinical presentation, diagnosis, and differentiation of these 2 severe cutaneous acute drug reactions are discussed.

Liver transplant and hepatitis C in methadone maintenance therapy: a case report.

Methadone maintenance therapy for the treatment of opioid dependence continues to carry a social stigma. Until recently, patients on methadone were not considered for liver transplantation. We describe the first case of a patient on methadone who received a liver transplant for end stage liver disease and was successfully treated for recurrent hepatitis C. More than five years post transplant and three years post viral clearance, the patient continues to do well and is stable on low-dose methadone. This case emphasizes the need to reconsider the non-evidence based policy adopted by transplant centers that require methadone maintenance therapy patients to stop methadone prior to consideration for transplant evaluation.

Coping with sports injuries: an examination of the adolescent athlete.

Forty-eight injured adolescent athletes completed questionnaires over 3 months after injury to assess psychosocial outcomes. Depressive symptoms decreased over time, and the lack of positive stress and high athletic identity were associated with early depressive symptoms after accounting for injury severity. Increased social support was associated with lower initial depressive symptoms.