Hasan Khosravi

Ion-specific Effects on Prion Nucleation and Strain Formation

Background: Prion proteins may adopt multiple aggregate conformations, known as strains. Results: Kosmotropic and chaotropic anions exhibit opposite effects on aggregation kinetics and favor different strains. Conclusion: Both prion nucleation kinetics and prevailing strain patterns strongly depend on ionic composition of the aggregation mixture. Significance: Ionic composition is shown to be a critical determinant in the generation of prion strains. Ordered, fibrous, self-seeding aggregates of misfolded proteins known as amyloids are associated with important diseases in mammals and control phenotypic traits in fungi. A given protein may adopt multiple amyloid conformations, known as variants or strains, each of which leads to a distinct disease pattern or phenotype. Here, we study the effect of Hofmeister ions on amyloid nucleation and strain generation by the prion domain-containing fragment (Sup35NM) of a yeast protein Sup35p. Strongly hydrated anions (kosmotropes) initiate nucleation quickly and cause rapid fiber elongation, whereas poorly hydrated anions (chaotropes) delay nucleation and mildly affect the elongation rate. For the first time, we demonstrate that kosmotropes favor formation of amyloid strains that are characterized by lower thermostability and higher frangibility in vitro and stronger phenotypic and proliferation patterns effectively in vivo as compared with amyloids formed in chaotropes. These phenomena point to inherent differences in the biochemistry of Hofmeister ions. Our work shows that the ionic composition of a solution not only influences the kinetics of amyloid nucleation but also determines the amyloid strain that is preferentially formed.

Characteristics and outcomes of nonmelanoma skin cancer (NMSC) in children and young adults

BACKGROUND Pediatric and young adult nonmelanoma skin cancer (NMSC) is rare and traditionally associated with predisposing heritable or congenital conditions. Clinical characteristics, outcomes, and iatrogenic risk factors have not been well described. OBJECTIVES We sought to characterize clinical features, potential risk factors, and gaps in care associated with NMSC in children and young adults. METHODS This was a retrospective chart review of children and young adults with squamous and basal cell carcinoma. RESULTS We identified 28 patients with a total of 182 NMSC tumors. Of patients, 50% had predisposing conditions, and 46% had exposure to iatrogenic risk factors of prolonged immunosuppression, radiation therapy, chemotherapy, voriconazole use, or a combination of these. Of patients with iatrogenic risk factors, 62% developed subsequent cancerous or precancerous skin lesions. No patient was found to have chemotherapy or voriconazole exposure as a sole risk factor. Mean time to diagnosis of NMSC was 948 days with initial misdiagnosis in 36% of patients. The majority of patients underwent surgical excision. LIMITATIONS This was a retrospective single institution study with a small number of cases. CONCLUSIONS Physicians should be aware of risk factors associated with NMSC in children and young adults to provide appropriate counseling and early diagnosis and treatment.

Nail dystrophy, edema, and eosinophilia: harbingers of severe chronic GVHD of the skin in children

The prognostic value of adnexal findings in chronic GVHD (cGVHD) has not been investigated in children. Dermatologic examinations were performed in a severe cohort of 11 children with skin cGVHD seen over a 2-year period. Findings were compared with 25 additional patients with skin cGVHD and 97 control patients. In 36 patients with skin cGVHD, nail dystrophy was present in 45% of patients, and was significantly associated with sclerotic disease and lung cGVHD. Pterygium inversum unguis (PIU) was associated with severe lung disease, with significantly lower % predicted FVC and FEV1 in those with PIU than those without. Forty-four percent of GVHD patients had preceding peripheral edema and 56% had preceding peripheral eosinophilia. Peripheral edema and eosinophilia were significantly associated with sclerotic cGVHD and persisted until the diagnosis of cGVHD in all patients. Comparison of data with control patients showed that incidence of nail dystrophy, incidence of peripheral edema and mean peak peripheral eosinophil count of patients with skin cGVHD was significantly higher than those without cGVHD. This study suggests that nail dystrophy, persistent peripheral edema and persistent peripheral eosinophilia are harbingers of severe cGVHD of the skin in children. The presence of PIU may be a harbinger of severe lung involvement.

Metastatic melanoma with spontaneous complete regression of a thick primary lesion

Fig 1. Left side of the chest skin biopsy for primary malignant melanoma. Histopathologic examination found a thick primary melanoma characterized by atypical pigmented epithelioid cells with extensive ulceration. INTRODUCTION Spontaneous regression of malignant melanoma is defined by the disappearance of melanocytic neoplastic cells partially or completely. In contrast to the partial form, complete spontaneous regression of primary malignant melanoma is a rare-occurring phenomenon, with 76 cases reported in the literature since 1866. The criteria for the diagnosis of regression were established by Smith and Stehlin and modified later. Overall, the impact of partial or complete regression on prognosis is anecdotal and controversial; however, we report a case with complete regression of a histologically diagnosed thick primary malignant melanoma with rapid development of metastatic disease and death. (Hematoxylin-eosin stain; original magnification: 3100.)

Outcomes of Early Dermatology Consultation for Inpatients Diagnosed With Cellulitis

Importance Many inflammatory skin dermatoses mimic cellulitis (pseudocellulitis) and are treated with antibiotics and/or hospitalization, leading to unnecessary patient morbidity and substantial health care spending. Objective To evaluate the impact of early dermatology consultation on clinical and economic outcomes associated with misdiagnosed cellulitis. Design, Setting, and Participants This prospective cohort study enrolled patients with presumed diagnosis of cellulitis in the emergency department, in the emergency department observation unit, or within 24 hours of admission to an inpatient unit of a large urban teaching hospital between February and September 2017. Patients were provided with telephone and clinic follow-up during the 30-day postdischarge period. We screened 165 patients with the primary concern of cellulitis. Of these, we excluded 44 who required antibiotics for cutaneous, soft-tissue, and deeper-tissue and/or bone infections irrespective of cellulitis status, and 5 who were scheduled to be discharged by the emergency department. Interventions Early dermatology consultation for presumed cellulitis. Main Outcomes and Measures Primary outcomes were patient disposition and rates of antibiotic use. Results Of 116 patients (63 [54.3%] women; 91 [78.4%] non-Hispanic white; mean [SD] age, 58.4 [19.1] years), 39 (33.6%) were diagnosed with pseudocellulitis by dermatologists. Of these, 34 (87.2%) had started using antibiotics for presumed cellulitis as prescribed by the primary team at the time of enrollment. The dermatology team recommended antibiotic discontinuation in 28 of 34 patients (82.4%), and antibiotics were stopped in 26 of 28 cases (92.9%). The dermatologists also recommended discharge from planned observation or inpatient admission in 20 of 39 patients with pseudocellulitis (51.3%), and the primary team acted on this recommendation in 17 of 20 cases (85.0%). No patients diagnosed with pseudocellulitis experienced worsening condition after discharge based on phone and clinic follow-up (30 of 39 [76.9%] follow-up rate). Extrapolating the impact of dermatology consultation for presumed cellulitis nationally, we estimate 97 000 to 256 000 avoided hospitalization days, 34 000 to 91 000 patients avoiding unnecessary antibiotic exposure, and

Anagen hair loss, anti-desmoglein 1, and pemphigus disease area index: a significant relationship?: Correspondence

80 million to

Rituximab Induced Neutropenia in a Patient with Bullous Pemphigoid

210 million in net cost savings annually. Conclusions and Relevance Early consultation by dermatologists for patients with presumed cellulitis represents a cost-effective intervention to improve health-related outcomes through the reduction of inappropriate antibiotic use and hospitalization.

Changes in sex and racial diversity in academic dermatology faculty over 20 years

An autoimmune bullous disorder caused by antibodies against desmoglein (Dsg) 3 and/or Dsg1, pemphigus vulgaris (PV) is associated with symptoms such as mucosal erosions, fl accid blisters, and anagen hair loss (AHL) [ 1, 2 ] . In a previous study, AHL was observed in 61.5 % of PV patients and found to be an independent predictor of disease severity using the Harman score [ 3 ] . The objective of this study was to further evaluate PV-related AHL by assessing associations with anti-Dsg serum levels and the Pemphigus Disease Area Index (PDAI). The latter is a severity score used to compare different treatment protocols and shown to have high validity [ 4, 5 ] . Unlike the Harman score, which measures the number of oral and cutaneous lesions, the PDAI score takes into account defi ned anatomical regions along with the number and size of the lesions [ 4 ] . This cross-sectional study included 52 consecutive patients newly diagnosed with PV who attended Razi Hospital, Tehran, Iran in 2013. The diagnosis was based on clinical, histopathological, and direct immunofl uorescence fi ndings, as well as a positive Dsg3 ELISA [ 6 ] . Age, gender, pemphigus phenotype, PDAI scores, and Dsg1 and Dsg3 ELISA serum levels were recorded. Pull tests were performed by gently tugging at approximately 20 hairs in lesional and nonlesional skin on the temporal, occipital, and frontal scalp; this test was conducted by a single investigator (AG). The presence of anagen hairs, indicated by a broom-like hair bulb covered by an intact root sheath, was indicative of a positive anagen pull test. Fisher’s exact test and Mann-Whitney U test were used for categorical and continuous variables, respectively. Multivariate analysis was performed, and a pvalue < 0.05 was considered statistically signifi cant. Demographic and clinical features are summarized in Table 1 . Univariate analysis results of the association between a positive anagen pull test and anti-Dsg1, anti-Dsg3, and PDAI scores are depicted in Table 2 . In addition,

Ixazomib-induced cutaneous necrotizing vasculitis

Rituximab, a chimeric monoclonal antibody against the CD20 B-cell antigen, is used to treat B-cell malignancies, rheumatoid arthritis, and autoimmune blistering diseases. Adverse events seen with rituximab include infusion reactions, infections, and late or early-onset neutropenia. Specifically, neutropenia is classified as grade III, an absolute neutrophil count (ANC) of 0.5-1.5 x 109/L, or grade IV, an ANC less than 0.5 x 109/L. In this case, we present a bullous pemphigoid (BP) patient with grade IV rituximabinduced neutropenia and safe re-treatment after two years.

Comparison of ethylenediaminetetraacetic acid-treated desmoglein ELISA and conventional desmoglein ELISA in the evaluation of pemphigus vulgaris in remission

Disclosures: Drs Khemis, Lacour, and Passeron have been investigators from Amgen, AbbVie, Janssen, Pfizer, Novartis, MSD, UCB pharma, and Celgene. Dr Khemis has received honoraria and travel expenses from Amgen, AbbVie, Janssen, Pfizer, Novartis, MSD, UCB pharma, and Celgene. Dr Lacour has received honoraria and travel expenses from Amgen, AbbVie, Janssen, Pfizer, Novartis, MSD, UCB pharma, and Celgene. Dr Passeron has received honoraria and travel expenses from AbbVie, Janssen, Pfizer, and MSD.