Type I IFN receptor regulates neutrophil functions and innate immunity to Leishmania parasites.

Type I IFNs exert diverse effector and regulatory functions in host immunity to viral and nonviral infections; however, the role of endogenous type I IFNs in leishmaniasis is unclear. We found that type I IFNR-deficient (IFNAR-/-) mice developed attenuated lesions and reduced Ag-specific immune responses following infection with Leishmania amazonensis parasites. The marked reduction in tissue parasites, even at 3 d in IFNAR-/- mice, seemed to be indicative of an enhanced innate immunity. Further mechanistic analyses indicated distinct roles for neutrophils in parasite clearance; IFNAR-/- mice displayed a rapid and sustained infiltration of neutrophils, but a limited recruitment of CD11b+Ly-6C+ inflammatory monocytes, into inflamed tissues; interactions between IFNAR-/-, but not wild-type (WT) or STAT1-/-, neutrophils and macrophages greatly enhanced parasite killing in vitro; and infected IFNAR-/- neutrophils efficiently released granular enzymes and had elevated rates of cell apoptosis. Furthermore, although coinjection of parasites with WT neutrophils or adoptive transfer of WT neutrophils into IFNAR-/- recipients significantly enhanced infection, the coinjection of parasites with IFNAR-/- neutrophils greatly reduced parasite survival in WT recipients. Our findings reveal an important role for type I IFNs in regulating neutrophil/monocyte recruitment, neutrophil turnover, and Leishmania infection and provide new insight into innate immunity to protozoan parasites.

The dermatology acting internship.

Acting internships are an important component of modern day medical school curriculum. Several specialties outside of internal medicine now offer acting internship experiences to fourth year medical students. We have found that a dermatology acting internship is a valuable experience for fourth year medical students who are interested in pursuing a residency in dermatology. Our experience with the dermatology acting internship over the 2010-2011 academic year is described.

The imbalanced expression of matrix metalloproteinases in nephrogenic systemic fibrosis.

BACKGROUND: Nephrogenic systemic fibrosis (NSF) occurs in patients with renal dysfunction and gadolinium exposure. Although little is known about the pathogenesis of this disease, increased expression of transforming growth factor-beta has been recently demonstrated. Other fibrosing conditions have been shown to express an imbalance in matrix metalloproteinase (MMP) expression and their corresponding inhibitors. Myofibroblast differentiation, in which cells often express alpha-smooth muscle actin and achieve the ability to contract, is also a hallmark of fibrosis. OBJECTIVE: We theorized that NSF may overexpress tissue inhibitor of metalloproteinase-1 (TIMP-1), while simultaneously showing decreased expression of MMP-1. As a secondary aim, we sought to evaluate the presence of smooth muscle actin in our samples. METHODS: We applied immunohistochemistry to 16 skin biopsies from 10 patients with NSF using antibodies to TIMP-1, MMP-1, MMP-2, MMP-9, and alpha-smooth muscle actin. Samples from normal skin, scar, keloid and scleroderma were stained for comparison. RESULTS: TIMP-1 was strongly expressed in all NSF specimens compared to normal skin. MMP-1 expression was nearly absent in all tested samples. In all 16 NSF cases, the dermal spindle cells did not stain for alpha-smooth muscle actin. MMP-2 and MMP-9 expression was variable but was increased compared to normal skin. LIMITATIONS: The expression is semiquantitative and based on immunohistochemistry and unconfirmed by other techniques. CONCLUSIONS: In NSF, TIMP-1 is strongly expressed and MMP-1 is nearly absent, characteristic of the MMP imbalances seen in other fibrosing processes. Using smooth muscle actin immunohistochemistry, there was no evidence of myofibroblast differentiation.

Report of a case: primary mucinous carcinoma of the skin.

Primary mucinous carcinoma of the skin is an extremely rare adnexal tumor that is thought to originate from eccrine sweat glands. The neoplasm usually arises on the head and neck, with the most commonly involved area being the periorbital region. The tumor is typically a solitary, asymptomatic nodule, cyst, or ulcer that is slow growing with low metastatic potential. However, post-excisional local recurrence is common, affecting up to 36 percent of patients. Since primary mucinous carcinoma of the skin is such a rare neoplasm (fewer than 130 cases have been reported to date), a complete workup should be conducted to rule out other internal malignancies that may metastasize to the skin. We report a case of primary mucinous carcinoma of the skin, and discuss the clinical presentation, histology, treatment, course, and prognosis.

Drug-induced linear immunoglobulin A bullous dermatosis mimicking Stevens-Johnson syndrome: a case report.

Linear immunoglobulin A (IgA) bullous dermatosis (LABD) is a rare autoimmune disorder characterized by vesiculobullous mucocutaneous eruptions. LABD also has been reported as a drug-induced reaction. Idiopathic LABD and drug-induced LABD are clinically indistinguishable and can resemble bullous pemphigoid, dermatitis herpetiformis, or bullous erythema multiforme. LABD is diagnosed with direct immunofluorescence (DIF), and idiopathic LABD can be distinguished from drug-induced LABD with a careful medication history. We present the case of a 54-year-old man with drug-induced LABD after ingestion of rimantadine, zanamivir, and azithromycin for presumed influenza. The patient's bullous eruption resolved with discontinuation of the offending medications and treatment with prednisone and pentoxifylline.

Development of collagenomas during pregnancy.

Collagenomas are considered to be connective tissue nevi composed predominantly of collagen. Collagenomas have been classified into 4 different entities: familial cutaneous collagenoma, the Shagreen patch of tuberous sclerosis, eruptive collagenoma, and other isolated collagenomas. We describe a patient with multiple collagenomas that appeared and multiplied during gestation and discuss the reported cases of collagenomas that have been linked to pregnancy.

Incorporating resident research into the dermatology residency program.

Programmatic changes for the dermatology residency program at The University of Texas Medical Branch were first introduced in 2005, with the faculty goal incorporating formal dermatology research projects into the 3-year postgraduate training period. This curriculum initially developed as a recommendation for voluntary scholarly project activity by residents, but it evolved into a program requirement for all residents in 2009. Departmental support for this activity includes assignment of a faculty mentor with similar interest about the research topic, financial support from the department for needed supplies, materials, and statistical consultation with the Office of Biostatistics for study design and data analysis, a 2-week elective that provides protected time from clinical activities for the purpose of preparing research for publication and submission to a peer-reviewed medical journal, and a departmental award in recognition for the best resident scholarly project each year. Since the inception of this program, five classes have graduated a total of 16 residents. Ten residents submitted their research studies for peer review and published their scholarly projects in seven dermatology journals through the current academic year. These articles included three prospective investigations, three surveys, one article related to dermatology education, one retrospective chart review, one case series, and one article about dermatopathology. An additional article from a 2012 graduate about dermatology education has also been submitted to a journal. This new program for residents was adapted from our historically successful Dermatology Honors Research Program for medical students at The University of Texas Medical Branch. Our experience with this academic initiative to promote dermatology research by residents is outlined. It is recommended that additional residency programs should consider adopting similar research programs to enrich resident education.