Approach to Neuropathic Pain.

Neuropathic pain is a common chief complaint encountered by neurologists and primary care providers. It is caused by disorders involving the somatosensory nervous system. The clinical evaluation of neuropathic pain is challenging and requires a multifaceted systematic approach with an emphasis on a thorough history and physical examination to identify characteristic signs and symptoms. Ancillary laboratory investigations, targeted imaging, and electrodiagnostic studies further help identify underlying etiologies to guide specific treatments. Management of neuropathic pain encompasses treating the underlying pathology as well as symptomatic control with nonpharmacological, pharmacological, and interventional therapies. Here, we present an approach to help evaluate patients with neuropathic pain.

Successful treatment of bullous pemphigoid with dupilumab: a case and brief review of the literature.

Bullous pemphigoid is an autoimmune skin disease that results in formation of pruritic blisters. Most cases are treated with a combination of systemic and topical corticosteroids as well as other immunomodulatory drugs. Dupilumab is a fully human monoclonal antibody that acts as an antagonist against IL4Ra traditionally used in the treatment of atopic dermatitis. We present an 80-year-old man with moderate to severe bullous pemphigoid successfully treated with dupilumab.

Atypical Cellular Blue Nevus With Necrosis Mimicking Melanoma Ex-Blue Nevus.

ABSTRACT: Histologic distinction between melanoma ex-blue nevus and cellular blue nevus (CBN) can often be difficult, but features supporting melanoma include infiltrative growth pattern, frequent mitoses, cytologic atypia and pleomorphism, cell crowding, and tumor necrosis. Unfortunately, these features are not constantly dependable and frequently borderline lesions exist, so-called atypical CBN, which lack explicit malignant features. Furthermore, some CBN and atypical CBN show an assortment of features, which may lead to their misdiagnosis as melanoma, but to date necrosis is generally absent. We present an unusual case of an atypical cellular blue nevus with extensive necrosis mimicking melanoma ex-blue nevus.

Acquired Epidermodysplasia Verruciformis in the Setting of Renal Transplant.

ABSTRACT: Epidermodysplasia verruciformis (EV) is a rare dermatologic condition that is clinically characterized by flat, cutaneous, verrucous papules, pityriasis versicolor-like lesions, and similar lichenoid papules. There are 2 forms of EV: a classic inherited genodermatosis and a secondary acquired form. EV predisposes individuals to infections with certain types of human papillomavirus virus and subsequently increases the risk of cutaneous squamous cell carcinoma. The acquired form occurs in immunosuppressed patients, particularly in patients infected with HIV; however, it has also been described in patients who have undergone stem cell and solid organ transplantation. We report an additional case of renal transplantation and immunosuppressive therapy-associated acquired EV (AEV) in a 78-year-old man with multiple flesh-colored to violaceous, flat-topped papules distributed on the face and trunk clinically mimicking lichen planus. Biopsy was typical for that of EV, demonstrating enlarged keratinocytes with a blue-gray cytoplasm, a thickened granular layer, acanthosis, and hyperkeratosis. Herein, we discuss an unusual presentation of an AEV-mimicking lichen planus with review of the literature.

An Unusual Presentation of Pyemotes ventricosus Dermatitis Presenting With Umbilicated Papules Mimicking Poxvirus Infection.

Pyemotes ventricosus mites are an uncommon cause of pruritic dermatitis seen most commonly in occupational exposure, prominently found in professionals such as farmers, landscapers, and factory workers who work with grains, wheat, dried beans, or grasses. The clinical description of the rash has typically been described as papular, erythematous, with a central vesicular lesion. We describe a case of Pyemotes dermatitis with an atypical clinical presentation. A 30-year-old man presented with pruritic, umbilicated papules, which involved his right lateral trunk and upper thigh leading to the submitted clinical impression of molloscum contagiosum. A biopsy of the skin was taken, and fragments of arthropod consistent with P. ventricosus were identified within umbilicated indentations of skin. The patient subsequently admitted to the onset of the rash immediately after carrying bales of straw while supporting each bale with his right side. The possibility of Pyemotes dermatitis mimicking a poxvirus-like eruption should be considered when encountering an unusual umbilicated papular eruption in the appropriate patient with occupational exposure.

Current state of educational compensation in academic neurology: Results of a US national survey.

In the current medical climate, medical education is at risk of being de-emphasized, leading to less financial support and compensation for faculty. A rise in compensation plans that reward clinical or research productivity fails to incentivize and threatens to erode the educational missions of our academic institutions. Aligning compensation with the all-encompassing mission of academic centers can lead to increased faculty well-being, clinical productivity, and scholarship. An anonymous survey developed by members of the A.B. Baker Section on Neurologic Education was sent to the 133 chairs of neurology to assess the type of compensation faculty receive for teaching efforts. Seventy responses were received, with 59 being from chairs. Key results include the following: 36% of departments offered direct compensation; 36% did not; residency program directors received the most salary support at 36.5% full-time equivalent; and administrative roles had greatest weight in determining academic compensation. We believe a more effective, transparent system of recording and rewarding faculty for their educational efforts would encourage faculty to teach, streamline promotions for clinical educators, and strengthen undergraduate and graduate education in neurology.

Gender Differences in Skin Biopsy Findings in Small Fiber Neuropathy: A Retrospective Chart Review.

OBJECTIVES: To determine whether there are gender differences in the clinical presentation or skin biopsy measures of nerve fiber density in patients with small fiber neuropathy (SFN). METHODS: Retrospective chart review of subjects with suspected SFN. RESULTS: Of 218 cases (137 women and 81 men) with suspected SFN, 96 (44%), including 63% of the men and 33% of the women (P < 0.05), had low epidermal nerve fiber density (ENFD) or sweat gland nerve fiber density (SGNFD). There were no differences in the clinical presentation between men and women. In those with abnormal findings, low ENFD alone was more frequent in women than men (51.1% vs. 7.8%, P < 0.05), whereas abnormal SGNFD alone was more frequent in men than women (68.6% vs. 11.1%, P < 0.05). Both SGNFD and ENFD were low in 23.5% of men and 33.3% of women. Skin biopsy findings were independent of clinical presentation or etiology. CONCLUSIONS: The clinical presentation of SFN is similar in men and women. In skin biopsy studies, low ENFD is more common in women and low SGNFD in men.

The utility of using immunohistochemistry in the differentiation of metastatic, cutaneous clear cell renal cell carcinoma and clear cell hidradenoma.

BACKGROUND: Clear cell hidradenoma and cutaneous clear cell renal cell carcinoma (CCRCC) overlap morphologically. The distinction may be difficult in a patient with a history of CCRCC, presenting with a cutaneous nodule, potentially leading to an erroneous diagnosis. We investigated the usefulness of napsin A and paired box gene 8 (PAX-8) with previously studied markers epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA), vimentin and cluster of differentiation marker 10 (CD10) in differentiating CCRCC from hidradenoma. METHODS: We evaluated hidradenomas and cutaneous CCRCCs for immunohistochemical expression of napsin A, PAX-8, EMA, CEA, vimentin and CD10. RESULTS: PAX-8 was expressed in all CCRCCs (8/8) while negative in hidradenomas. Napsin A was negative in both hidradenomas (0/12) and CCRCCs (0/10). EMA showed membranous reactivity in 11 of 12 hidradenomas and 8 of 10 CCRCCs; and highlighted ductal epithelium in 1 of 12 hidradenomas and cystic areas in 4 of 10 CCRCCs. CD10 showed ductal expression in 3 of 12 hidradenomas and membranous staining in 8 of 9 CCRCCs. CEA highlighted ductal epithelium in 11 of 12 hidradenomas while absent in CCRCCs (0/10). Vimentin highlighted neoplastic cells in 8 of 8 CCRCCs and failed to stain the hidradenomas (0/12). CONCLUSION: A conservative immunohistochemical panel including PAX-8, vimentin and CEA allow for easy distinction of CCRCC from hidradenoma, whereas napsin A added no additional value.

Idiopathic livedo racemosa presenting with splenomegaly and diffuse lymphadenopathy.

Sneddon syndrome (SS) is a rare condition and the diagnosis is made only when other more common disease entities have been excluded. Common manifestations in SS patients include hypertension, coronary artery disease, venous thrombosis, miscarriages, psychiatric disturbances, and arterial and venous thrombotic events. Most patients present in their early 30s with classic neurovascular and dermatologic signs. Currently, the main criteria for the diagnosis of SS include livedo racemosa, focal neurological deficits or evidence of stroke on magnetic resonance imaging, or characteristic vascular alterations seen on biopsy. We present the case of a 37-year-old woman with extensive livedo racemosa, chronic migraine headaches, splenomegaly, and lymphadenopathy. Cutaneous biopsies demonstrated a superficial perivascular lymphocytic infiltrate without the subendothelial proliferative changes or fibrosis seen in some patients with SS. The patient's medical history suggested idiopathic livedo racemosa with possible full progression to SS. This case highlights the variability in the clinical presentation of SS and that the disease often can be diagnosed before neurovascular events. Earlier diagnosis can lead to prevention of chronic occlusive neurovascular manifestations and irreversible damage such as myocardial infarction and stroke. Familiarity with the highly variable early course of SS can aid in diagnosis and reduction of morbidity and mortality that is associated with this disease.

Fibroblastic connective tissue nevus.

Fibroblastic connective tissue nevus (FCTN) is a newly recognized, benign cutaneous mesenchymal lesion of fibroblasts/myofibroblastic lineage, which expands the classification of connective tissue nevi. We present three cases of FCTN and discuss significant clinical, morphologic and immunophenotypic overlap with dermatomyofibroma. Our cases were from young women, aged 32, 24 and 10, and presented as 1.2 and 1 cm nodules on the posterior neck and right upper flank, respectively while presenting as a linear plaque of the right posterior thigh in the latter case. The lesions showed a poorly circumscribed proliferation of hypercellular spindle cells arranged in short to longer intersecting fascicles entrapping adnexal structures. Superficial adipose tissue was also entrapped in one case. The spindle cells had fibroblastic features with pale eosinophilic cytoplasmic extensions and inconspicuous nucleoli. The spindle cells were positive for CD34 in two cases. One case was negative for CD34, smooth muscle actin (SMA), desmin and S100. The overall features were consistent with a diagnosis of FCTN. In two cases, we further elucidated the fibroblastic differentiation of the spindle cells in FCTN with electron microscopy, which has not been previously described.

Synthesis of monodisperse [Oct4N(+)][Au25(SR)18(-)] nanoparticles, with some mechanistic observations.

A single phase (THF) synthesis of monodisperse [Oct(4)N(+)][Au(25)(SR)(18)(-)] nanoparticles is described that yields insights into pathways by which it is formed from initially produced larger nanoparticles. Including the Oct(4)N(+)Br(-) salt in a reported single phase synthetic procedure enables production of reduced nanoparticles having a fully occupied HOMO molecular energy level (Au(25)(SR)(18)(-), as opposed to a partially oxidized state, Au(25)(SR)(18)(0)). The revised synthesis accommodates several (but not all) different thiolate ligands. The importance of acidity, bromide, and dioxygen on Au(25) formation was also assessed. The presence of excess acid in the reaction mixture steers the reaction toward making Au(25)(SR)(18); while bromide does not seem to affect Au(25) formation, but it may play a role in maintaining the -1 oxidation state. Conducting the nanoparticle synthesis and "aging" period in the absence of dioxygen (under Ar) does not produce small nanoparticles, providing insights into the pathway of reaction product "aging" in the synthesis solvent, THF. The "aging" process favors the Au(25)(-) moiety as an end point and possibly involves degradation of larger nanoparticles by hydroperoxides formed from THF and oxygen.

Can MDM2 analytical tests performed on core needle biopsy be relied upon to diagnose well-differentiated liposarcoma?

Well-differentiated liposarcoma/atypical lipomatous tumor can be difficult to differentiate from benign lipomatous tumors, especially on limited biopsy material. Adjunctive tests for MDM2 (murine double minute 2) have proven useful in whole-tissue sections; however, their utility has not been determined within the increasingly popular core needle biopsy. Herein, we compare the ability of MDM2 immunohistochemistry and MDM2 fluorescence in situ hybridization (FISH) to discriminate benign lipomatous tumors from well-differentiated liposarcoma on core needle biopsies. Well-differentiated liposarcoma (n=17) and an assortment of benign lipomatous tumors (n=37), which had concurrent or previous core needle biopsies, and resection specimens were subjected to both MDM2 immunohistochemistry and MDM2 FISH on both whole-tissue sections and corresponding core needle biopsy sections. Percentage tumor cells positive for MDM2 by immunohistochemistry and an MDM2:CEP12 FISH ratio was calculated in each biopsy and resection specimen pair and the results were compared. MDM2 FISH had a higher sensitivity (100%) and specificity (100%) compared with MDM2 immunohistochemistry (65 and 89%) in core needle biopsies, respectively. In addition, MDM2 immunohistochemistry had a false-positive rate of 11%, compared to 0% with FISH. The average MDM2:CEP12 ratio was similar in the biopsy material compared with the whole-tissue sections in both well-differentiated liposarcoma and the benign lipomatous tumor group of neoplasms. Detection of MDM2 amplification by FISH is a more sensitive and specific adjunctive test than MDM2 immunohistochemistry to differentiate well-differentiated liposarcoma from various benign lipomatous tumors, especially on limited tissue samples.