Carilyn N. Wieland

Anti–Bullous Pemphigoid 180 and 230 Antibodies in a Sample of Unaffected Subjects

OBJECTIVE To evaluate the prevalence of autoantibodies against 2 hemidesmosomal proteins typically found in patients with bullous pemphigoid (BP), BP antigen II (BP180) and BP antigen I (BP230), in persons without BP. DESIGN Cross-sectional study. SETTING Academic medical center. Patients An age- and sex-stratified, random, population-based sample of local county patients seen during 2007: 20 men and 20 women per decade of age (from age 20 to 89 years) and 57 patients (33 women and 24 men) aged 90 to 99 years. Intervention Stored serum samples were retrieved for analysis by enzyme-linked immunosorbent assay and indirect immunofluorescence. MAIN OUTCOME MEASURE Presence of circulating autoantibodies to BP180 and BP230. RESULTS Of the 337 study patients, 25 (7.4%) were positive for 1 or both autoantibodies; these 25 samples all tested negative with indirect immunofluorescence. Autoantibody levels did not vary by age or sex. CONCLUSIONS Bullous pemphigoid has a higher incidence in the elderly population, but the prevalence of antibodies to BP180 and BP230 did not increase significantly with age or vary by sex in this population-based sample. Other exogenous factors may affect the development of these autoantibodies in a population without clinically evident immunobullous disease, including limitations inherent to the test (false-positive rate).

A population-based study of the association between bullous pemphigoid and neurologic disorders

BACKGROUND Bullous pemphigoid (BP) has been associated with neurologic disorders. OBJECTIVE We sought to analyze the association between BP and neurologic disorders. METHODS We retrospectively identified residents of Olmsted County, Minnesota, with a first lifetime diagnosis of BP between January 1, 1960, and December 31, 2009. Three age- and sex-matched Olmsted County, Minnesota, residents without BP were selected as control subjects for each patient. We compared history of or development of neurologic disorders (dementia, Alzheimer disease, Parkinson disease, multiple sclerosis, cerebrovascular disease, and seizures) between groups using case-control and cohort designs. RESULTS In all, 87 patients with BP were identified and matched to 261 control subjects. The odds of a previous diagnosis of any neurologic disorder or a history of dementia were significantly increased among cases compared with controls (odds ratio 6.85; 95% confidence interval [CI] 3.00-15.64; P < .001; and odds ratio 6.75; 95% CI 2.08-21.92; P = .002, respectively). Both Parkinson disease (hazard ratio 8.56; 95% CI 1.55-47.25; P = .01) and any type of neurologic disorder (hazard ratio 2.02; 95% CI 1.17-3.49; P = .01) were significantly more likely to develop during follow-up in patients with than without BP. LIMITATIONS Small geographic area and retrospective study design are limitations. CONCLUSION Findings confirmed an association of BP with neurologic disorders, especially dementia and Parkinson disease.

The role of CD10 in distinguishing atypical fibroxanthoma from sarcomatoid (spindle cell) squamous cell carcinoma

Background: The role of CD10 needs clarification in a broader immunohistochemical battery for distinguishing atypical fibroxanthoma (AFX) from spindle cell squamous cell carcinoma (sSCC).

Molecular targeted therapies in metastatic melanoma

The advent of personalized medicine has ushered in a new era for cancer therapy with a significant impact on the management of advanced melanoma. Molecular targeted therapies have shown promise in the management of various malignancies, including melanoma, with lower toxicity profiles and better overall survival as compared with conventional therapy. The discovery of BRAF mutations in melanoma led to the development of BRAF inhibitors for the treatment of advanced melanoma. However, growing concerns over drug resistance to molecular targeted therapies including BRAF inhibitors, have spurred efforts to elucidate additional molecular targets for the treatment of advanced melanoma. In this review, we discuss the known molecular aberrations in melanoma, current and novel targeted approaches in its treatment, and drug resistance patterns.

Comparison of virtual microscopy and glass slide microscopy among dermatology residents during a simulated in-training examination

Virtual microscopy is increasingly being used in dermatopathology educational settings.

Tumor-induced osteomalacia resulting from primary cutaneous phosphaturic mesenchymal tumor: a case and review of the medical literature.

Tumor-induced osteomalacia, also known as oncogenic osteomalacia, is a rare paraneoplastic condition frequently associated with a distinct mesenchymal neoplasm, namely phosphaturic mesenchymal tumor, mixed connective tissue variant (hereafter, phosphaturic mesenchymal tumor). Although this neoplasm type has been reported in various anatomic locations, primary cutaneous involvement is exceptionally rare. Treatment involves complete surgical removal. Because of the locally infiltrative nature of the tumor, surgical margin control may be challenging. We describe a case of phosphaturic mesenchymal tumor that mimicked dermatofibrosarcoma protuberans and that was treated successfully with Mohs micrographic surgery. Furthermore, we review the clinicopathologic features of all cases of primary cutaneous phosphaturic mesenchymal tumor that have been described in the medical literature. A 40-year-old man presented with a 4-year history of progressive pain in his legs, lower back, and ribs. The patient denied any family history of the heritable forms of osteomalacia. Laboratory tests revealed an elevated total alkaline phosphatase level, low phosphorous level, and elevated fibroblast growth factor 23 level. Imaging studies showed multiple stress fractures involving the ribs and pelvis, and a bone density scan found a Z-score in the osteoporosis range. Findings were unremarkable on an F-18 fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) test. A clinical diagnosis of acquired hypophosphatemic osteomalacia was rendered by his endocrinologist, and the patient was referred to dermatology for a 2.0 × 1.7-cm subcutaneous nodule on the left shoulder. An excisional biopsy was performed and submitted with a clinical impression of an epidermal cyst. On scanning microscopy, the lesion demonstrated a predominantly dermal-based tumor invading the subcutis. The tumor was composed of a dense population of spindle-shaped cells with dark, but uniform, nuclei arranged in a honeycomb growth pattern within the subcutaneous tissue, reminiscent of that seen in dermatofibrosarcoma protuberans (Figure 1). Frequent small deposits of acellular, partially calcified basophilic matrix and scattered osteoclast-type multinucleated giant cells were also identified (Figure 2). The lesional

Scleroderma Induced by Pembrolizumab: A Case Series

Abstract Immune checkpoint inhibitors are approved for select cancer treatment and have shown survival benefit in patients with advanced melanoma. Adverse events, including immune‐related adverse events, are common and potentially life‐threatening. We describe cases of 2 patients with scleroderma (patient 1 had diffuse scleroderma, and patient 2 had limited scleroderma) that developed while they were receiving pembrolizumab therapy for metastatic melanoma. Prompt recognition and treatment of immune‐related adverse events may improve tolerance to immune checkpoint inhibitors and contribute to an understanding of the manifesting autoimmune disease.

The application of virtual microscopy in a dermatopathology educational setting: assessment of attitudes among dermatopathologists

Whole‐slide imaging with virtual microscopy is increasingly used as a tool in resident education and training, board certification and maintenance of certification examinations, and diagnostic evaluation. The objective of this study was to determine attitudes toward virtual microscopy compared with traditional glass slide microscopy during a continuing medical education dermatopathology workshop.

Adult‐onset systemic Langerhans cell histiocytosis mimicking inflammatory bowel disease: the value of skin biopsy and review of cases of Langerhans cell histiocytosis with cutaneous involvement seen at the Mayo Clinic

Langerhans cell histiocytosis (LCH) is frequently known to involve multiple organ systems. However, gastrointestinal involvement by LCH is rare.

Articular Involvement in Disseminated Histoplasmosis in a Kidney Transplant Patient Taking Azathioprine

To the Editor: Histoplasmosis can manifest itself in the joints of immunocompromised patients. It is a potentially fatal opportunistic infection and should be considered when these patients present with unexplained joint swelling, erythema nodosum, or sepsis. An 81-year-old farmer from Minnesota developed acute-onset painful swelling over the ulnar aspect of the right palm. He denied work-related injury or trauma. Hand radiographs did not show evidence of a foreign body. Cephalexin was started for presumed cellulitis, but 4 days later the hand lesion evolved into a localized area of purple discoloration, 3 × 2.5 cm, with central clearing. He developed generalized weakness, myalgias, large-joint arthralgias, worsening hand erythema, productive cough, fever (101.2°F), and hypotension (88/59 mm Hg), and was hospitalized for presumed sepsis. He was treated empirically with vancomycin and ceftriaxone. Physical examination showed a nontender, nonfluctuant, nonindurated ecchymotic lesion on the ulnar aspect of his right hand distal to the hypothenar eminence, with full active and passive range of motion of wrist and fingers and no tenderness along the digital tendon sheaths. There was no synovitis in the metacarpophalangeal, interphalangeal, or radiocarpal joints. His right knee and ankle were warm and swollen with limited range of motion but no erythema. He had a small palatal ulcer. His history was pertinent for hypertension, hyperlipidemia, ischemic cardiomyopathy, gout, and degenerative arthritis of the knees. He underwent a cadaveric kidney transplant in 1982 because of endstage renal disease from chronic interstitial nephritis and was maintained on azathioprine 100 mg and prednisone 5 mg daily with excellent allograft function. Surgical history was pertinent for splenectomy in … Address correspondence to Dr. A. Makol, Mayo Clinic, Division of Rheumatology, Department of Internal Medicine, 200 First St. SW, Rochester, MN 55905, USA. E-mail: makol.ashima{at}mayo.edu