Faculty Bibliography

Purpose: Coagulation is one of the first pathways to be elicited by vascular injury, and its activation is followed by proinflammatory phenomena, in part due to loss of the anti-inflammatory activity of both the Protein C pathway and membrane Endothelial Protein C receptor (mEPCR). It has been recently demonstrated that mEPCR is highly expressed in the cortical peritubular capillaries of kidneys from patients (pts) with active lupus nephritis compared to normal human kidney. Profound upregulation of mEPCR was observed even in areas absent tubulointerstitial damage. This study addressed the hypothesis that changes in the microvasculature extend beyond the clinically targeted organ and that dysregulation is a fundamental characteristic of SLE. Methods: The study included SLE pts in whom renal disease was considered active as assessed by proteinuria and urinary sediment. Renal biopsies were performed in all pts. Thirty skin biopsies from non-lesional nonsunexposed skin (buttocks) were obtained in 26 pts (23 females, 3 males) and five healthy controls (4 females, 1 male). The paraffin skin sections were individually stained with specific antibodies against mEPCR and adiponectin (protective markers), ICAM-1 (proinflammatory) and CD31 (pan endothelial marker). Immunohistochemistry (IHC) was scored by counting peroxidase-brown labeled blood vessels (10-20 microns in diameter) without knowledge of the clinical information associated with the biopsy. The number of blood vessels with an intensity of at least 1+ were quantitatively scored with ranges 1-12. To account for the number of blood vessels per slide, the CD31 count had to be 12 to be included in the analysis. Results: The 28 renal biopsies comprised the following ISN/RPS classifications: 4 Class III, 7 Class IV, 8 Class V, I Class VI, 3 Class III/V, 3 Class IV/V. Nineteen percent of the pts had a GFR <60 (mean GFR, 82 ml/min). Abnormal laboratory values for complement and anti-dsDNA antibodies were reported in 72% and 75% of pts, respectively. Nephrotic range proteinuria was present in 37%. For IHC skin assessments of the controls, the mean score for mEPCR was 1 (highest 2), ICAM-1 was 4 (highest 7) and adiponectin was 1 (highest 2). In 17/25 (68%) of the SLE non-lesional non-sun exposed skin sections, mEPCR was expressed above the highest control. In 16/30 (53%) ICAM-1 staining exceeded 7. In contrast, only 6/25 (19%) expressed adiponectin above 2. For each specific stain there were no apparent differences between biopsy class, degree of proteinuria, presence of anti dsDNA or low complement levels. However, pts with mEPCR staining above 2 had higher GFR measurements than those with staining < 2 (88 ml/min +/- 31 versus 53 +/- 32, p= 0.0168). In contrast, GFR was unrelated to ICAM-1 and adiponectin expression. Conclusion: These data are consistent with the notion that there is widespread activation of the microvasculature. The capacity of endothelial cells to utilize anticoagulation pathways is not restricted to the kidney and expression of mEPCR in the microcirculation likely represents an attempt to limit microvascular inflammation in kidney and skin

A 79-year-old woman presented with a four-year history of generalized, erythematous, indurated plaques on the malar areas, back, and extremities. The lesions had been recalcitrant in the past to topical glucocorticoid therapy. A skin biopsy specimen was diagnostic of discoid lupus erythematosus (DLE). A minority of patients with DLE progress to develop systemic lupus erythematosus although generalized DLE is more frequently associated with systemic involvement than is limited disease. Standard therapy of cutaneous lupus includes broad spectrum sunscreens, topical and intralesional glucocorticoids, and antimalarial agents

A 57-year-old woman presented with a 27-year history of vesicles and crusted erosions of the intertriginous folds. Prior treatments had included topical glucocorticoids, mupirocin, and minocycline, all of which provided minimal relief. A skin biopsy specimen was consistent with Hailey-Hailey disease. Hailey-Hailey disease is the result of mutations in the ATP2C1 gene and is characterized by recurrent vesicles and erosions in intertriginous areas. Whereas topical and/or systemic antibiotic/antifungal agents in combination with topical glucocorticoids is the mainstay of treatment, case reports have documented dramatic improvement with oral retinoids, calcitriol, and tacrolimus

A 49-year-old man presented with an eight-month history of intermittently painful, subcutaneous nodules that were increasing in size, number, and pain intensity. A biopsy specimen showed smooth muscle proliferation, which also stained positive for actin, and was consistent with piloleiomyoma. The patient was placed initially on gabapentin and then nifedipine with very limited success in pain control. The lesions continued to proliferate, and the patient was referred to surgery for excision

A 62-year-old woman with hypothyroidism presented with a seven-year history of paresthesias, itching, and edema of the skin. Physical examination showed indurated, edematous plaques on the lower extremities. A biopsy specimen showed increased mucin deposition that was consistent with myxedema, and monoclonal IgM was observed on immunofixation. The constellation of findings, which included paresthesias, endocrinopathy, monoclonal gammopathy, and skin changes was consistent with POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome, which is a rare multisystemic disease that is associated with an underlying plasma-cell dyscrasia

We describe a case of non-scarring, generalized, cutaneous and mucosal subepidermal bullous dermatosis that is characterized histopathologically by a neutrophilic infiltrate and strong linear staining with both IgA and IgG along the basement-membrane zone. Autoantibodies to collagen VII of both the IgA and IgG4 subtypes were detected by indirect immunofluorescence test, which led led to a diagnosis of epidermolysis bullosa aquisita (EBA). EBA is a subepidermal bullous disorder that is mediated by autoantibodies, which are directed against type VII collagen. The distinct clinical presentations of EBA are reviewed and discussed in the context of the unique autoantibody profile of this case

A 42-year-old man presented with asymptomatic, sharply-demarcated, round, scaly lesions on his forearms that had been present for several months. A skin biopsy specimen was consistent with pityriasis rotunda. Pityriasis rotunda is a disorder of keratinization, which is thought to be a form of acquired ichthyosis, a delayed presentation of congenital ichthyosis, or a cutaneous manifestation of systemic disease. Patients with pityriasis rotunda may be classified into one of two groups, which are based on ethnicity, number of lesions, family history, and association with systemic diseases. Treatment is challenging, but the use of lactic acid lotion and oral vitamin A has shown some promise

A 78-year-old man presented with an eight-month history of folliculocentric, pink, hyperkeratotic papules and plaques with thick white scale that involved the entire body, with confluence on the buttocks and genitalia. A biopsy specimen demonstrated superficial and focal, mild perivascular and perifollicular, band-like lymphocytic infiltrate and eosinophils. There were lymphocytes extending to the dermo-epidermal junction with vacuolar changes. A diagnosis of lichenoid drug eruption secondary to a proton-pump inhibitor was made. To the best of our knowledge, only one other case of lichenoid drug eruption secondary to a proton-pump inhibitor has been reported

Opaque exogenous material was frequently observed on the surface of keratoses during routine sign out by one of us (H.K.). To investigate this material further, 300 consecutive seborrheic keratoses were reviewed: 100 cases from the face of women, 100 cases from the face of men, and 100 cases from the trunk of men and women. All cases were evaluated by light microscopy for the presence and quantity of exogenous material, and 14 cases were studied by x-ray microanalysis to assess its composition. The material was present on 54% of facial keratoses from predominantly older women (mean age 67 years), 5% of facial keratoses from men, and 9% of truncal keratoses from men and women. The x-ray microanalysis showed the presence of a variety of elements, including titanium (13 cases), silicon (12 cases), iron (9 cases), aluminum (8 cases), magnesium (8 cases), zinc (4 cases), barium (2 cases), and bismuth (2 cases). We believe that the exogenous material represents cosmetic products such as colored facial cosmetics, sunscreens, and moisturizers. Further, because the exogenous material was found predominantly on facial keratoses of older women, the presence of this material in a specimen may serve as a clue to the patient's gender, age, and biopsy site

We present 17 penile traumatic neuromas. The mean patient age at presentation was 38 years (range 23-59 years). The most common site involved was the penile shaft. The lesions ranged from 1 to 7 mm in greatest dimension. The clinical diagnosis in all cases included condyloma acuminatum. In all cases, a history of trauma because of prior biopsy and/or circumcision was found. Histologically, all lesions showed similar features consisting of an increased number of dermal nerve bundles embedded within a fibrous stroma. Often, single or multiple Meissner corpuscle-like structures were noted in the papillary dermis. Our study suggests that circumcision or other forms of trauma to the skin of the penis likely plays an important role in the pathogenesis and clinical presentation of this peculiar neural neoplasm. We call attention to this entity because it is often clinically misdiagnosed as condyloma acuminatum