Squamous cell carcinoma arising in discoid lupus erythematosus lesions of the ears infected with human papillomavirus.

We describe a 51-year-old white man with discoid lupus erythematosus (DLE) of the head, neck, trunk, and upper extremities of more than 20 years' duration who developed rapidly progressive squamous cell carcinoma (SCC) of the bilateral ear helices. Human papillomavirus (HPV) was detected from excised specimens from the ears via tissue immunohistochemistry. Human papillomavirus infection of discoid lesions may be responsible for the rapid progression of SCC of this patient's bilateral ear helices.

Increased xanthine oxidase in the skin of preeclamptic women.

Xanthine oxioreductase is the holoenzyme responsible for terminal purine catabolism. Under conditions of metabolic stress or heightened proinflammatory cytokine production, this enzyme is preferentially in its oxidized form, xanthine oxidase, with catalytic action that generates uric acid and the free radical superoxide. As preeclampsia is characterized by heightened inflammation, oxidative stress, and hyperuricemia, it has been proposed that xanthine oxidase plays a pivotal role in this hypertensive disorder of pregnancy. We sought to determine whether xanthine oxidase protein content was higher in maternal tissue of preeclamptic mothers, compared to healthy pregnant controls, using immunohistochemical analysis of skin biopsies. We further compared xanthine oxidase immunoreactivity in skin biopsies from preeclamptic women and patients with several inflammatory conditions. In preeclamptic women, intense xanthine oxidase immunoreactivity was present within the epidermis. By contrast, only very faint xanthine oxidase staining was observed in skin biopsies from healthy pregnant controls. Further, a role for inflammation in the increase of xanthine oxidase was suggested by similar findings of heightened xanthine oxidase immunoreactivity in the skin biopsies from nonpregnant individuals diagnosed with conditions of systemic inflammation. The finding of increased xanthine oxidase in maternal tissue, most likely as the result of heightened maternal inflammation, suggests maternal xanthine oxidase as a source of free radical and uric acid generation in preeclampsia.

The predominance of IgG4 in prodromal bullous pemphigoid.

BACKGROUND: Prodromal bullous pemphigoid (PBP) and bullous pemphigoid (BP) demonstrate immunoglobulin G (IgG) and/or C3 deposition at the basement membrane zone (BMZ) on direct immunofluorescence. BP-180-specific IgG1, IgG4, and IgE antibodies have been detected in BP. However, the distribution of IgG subclasses is unknown in PBP. OBJECTIVES: We will describe the role of anti-BMZ IgG subclasses in PBP and we will correlate these findings to better understand the pathogenesis of PBP. METHODS: Skin biopsies and serum samples were obtained from 45 patients who had PBP. The skin tissue was processed for direct immunofluorescence studies. Sera were analyzed by indirect immunofluorescence for the presence of circulating anti-BMZ IgG antibodies (by standard IIF) and IgG subclasses antibodies (by sandwich double antibody immunofluorescence [SDAI]). Sera were also analyzed for antibodies against BP-180 and BP-230 antigens by enzyme-linked immunosorbent assay (ELISA). RESULTS: Thirty-two patients (71%) had IgG and C3 staining at the BMZ, while 13 patients (29%) had isolated C3 staining at the BMZ on direct immunofluorescence. All patients demonstrated staining on the epidermal side of the salt-split skin. Of the seven skin specimens that were available for C5-9 SDAI testing, all were found to be positive along BMZ area. Standard IIF studies demonstrated the presence of circulating BMZ antibodies in 11 of the 30 patients (36.6%). When SDAI for IgG subclass differentiation was utilized, 17 of 30 (56.6%) patients were found to have circulating anti-BMZ antibodies. All of these 17 patients had IgG4 subclass antibodies. Thirteen patients did not have detectable IgG subclass anti-BMZ antibody on SDAI. Sixteen of 30 patients had detectable anti-BP-180 or anti-BP-230 antibodies, while 12 (40%) did not have detectable antibody against BP antigens on ELISA. CONCLUSIONS: IgG4 is the initial and predominant anti-BMZ antibody subclass detected in PBP. Demonstration of linear C5-9 at the BMZ enhances the early diagnosis of PBP. Predominance of IgG4 and the initial presence of IgG4 on skin lesions as well as the presence of only IgG4 subclass anti-BMZ antibody suggest that IgG4 subclass antibody could be the initial immunologic event encountered in patients with PBP.

Prodromal bullous pemphigoid.

BACKGROUND: Prodromal bullous pemphigoid (PBP) can be difficult to diagnose. Early recognition in its early stages may decrease the morbidity and progression of the disease. Clinical presentations and current treatments available for PBP will be described. METHODS: A retrospective review was performed on 53 patients diagnosed with PBP. RESULTS: Overall, the average disease duration of PBP was 11.8 months. The average age of presentation of PBP was 70.8 years. The most common presentations were urticaria-like plaques (67.9%), eczema-like lesions (11.3%), and dermatitis herpetiformis-like lesions (9.4%). The majority of patients responded well to low doses of systemic corticosteroids, tetracycline, and/or high potency topical corticosteroids. CONCLUSIONS: Patients with PBP tend to be in their sixth or early seventh decade of life and, on average, the duration of disease is 1 year. The most common presentation of disease is urticaria-like plaques.

Matrikines and matricryptins: Implications for cutaneous cancers and skin repair.

Dermatologists are faced daily with the need to optimize skin repair and excise cutaneous cancers. The extracellular matrix plays a pivotal role in cellular migration, proliferation, and gene regulation during wound healing and progression of melanoma, basal cell carcinoma, and squamous cell carcinoma. Within the last few years, a new class of ligand, the matrikine or matricryptin, has been characterized as subdomains of various ECM proteins capable of signaling to the cell through receptors, such as growth factor receptors. Two classes exist: the "natural" matrikines, which signal directly from the extracellular milieu and "cryptic" matrikines (matricryptins) that require proteolytic processing to reveal the ligand or to release the ligand from its ECM protein. Unlike traditional soluble growth factors, most matrikines possess low binding affinity to their receptors and are often presented in multiple valency that likely increase avidity to receptors. The presentation of these ligands within the ECM can result in unique outcomes. The EGF-like repeats of tenascin-C and laminin-5 signal to EGFR preferentially to upregulate migration during skin repair and tumor progression. Other matrikines in collagen, elastin, decorin, and laminin-1 can promote chemotaxis, mitogenesis, and metastasis in cancers, such as melanoma. Finally, the unique properties of matrikines have been utilized in cancer therapeutics and tissue engineering. Within the next few years, the nature and function of this emerging class of matrikine ligands will have an impact on dermatology, as these proteins are altered in wound repair and skin diseases.

Immunofluorescence findings in granuloma faciale: report of two cases.

BACKGROUND: Immunofluorescence findings in granuloma faciale have been infrequently described. Reported findings include granular IgA, IgG, IgM, and C3 deposits in the dermoepidermal junction, in blood vessel walls, and on connective tissue fibers; IgG in the basement membrane zone, and IgG around blood vessels. OBSERVATIONS: We report two cases of granuloma faciale in which biopsy specimens were sent for routine pathology as well as immunofluorescence. Additional work-up included serologic testing for markers of lupus erythematosus (LE). Immunofluorescence in both cases revealed granular IgA, IgG, IgM, C3, and C5-9 deposits along the dermoepidermal junction only. Blood vessel walls and connective tissue fibers were spared. Serologic studies for markers of LE were negative. CONCLUSION: Immunofluorescence findings were essentially identical to those which would be expected in cutaneous LE; however, the combination of negative serologic studies for LE, histopathologic findings typical of granuloma faciale, and clinical findings most consistent with granuloma faciale allowed the diagnosis of granuloma faciale to be rendered with certainty. Interpretation of results of direct immunofluorescence of skin should be correlated with clinical presentation, histopathological findings and other laboratory results in order to render final diagnosis of a given patient.

A predominant IgG4 subclass may be responsible for false-negative direct immunofluorescence in bullous pemphigoid.

BACKGROUND: Bullous pemphigoid (BP) is an immune-mediated blistering disease, usually characterized immunopathologically by the linear deposition of IgG and C3 along the basement membrane zone (BMZ) of skin. However, positive deposition of C3 but negative staining for IgG on direct immunofluorescence (DIF) studies has been noted in some patients. METHODS: Twelve patients known to have BP but with absence of staining for IgG were included in this study. Frozen sections of skin specimens from the 12 patients were subjected to IgG DIF, as well as a sandwich double antibody method of staining for IgG, IgG subclasses, and light chains. Enzyme-linked immunosorbent assay (ELISA) using commercially available human IgG subclasses was used to analyze the subclass restriction of FITC-labeled antihuman IgG conjugates. RESULTS: Of the 12 skin specimens with positive C3 and negative IgG on DIF, nine were positive for IgG with the double antibody sandwich method. In addition, all 12 specimens had positive linear staining for the subclass IgG4 along the BMZ with this method. There was no IgG light chain restriction. Two commercially obtained antihuman IgG conjugates, both commonly used in our laboratory for DIF testing, were analyzed for separate IgG subclass specificity by ELISA. Both conjugates showed high reactivity to IgG1 and IgG3 with less reactivity to IgG2 and IgG4. CONCLUSION: These results suggest that the following factors contribute to false-negative staining for IgG on DIF in some BP patients: (i): subthreshold IgG in skin specimens; (ii) limited reactivity of commercial antihuman IgG conjugates to the IgG4 subclass; and (iii) decreased sensitivity of DIF compared with double antibody methods for the detection of IgG. The use of sandwich double antibody immunofluorescence methods to test for IgG and/or IgG subclasses may be helpful in definitively diagnosing BP in patients with negative IgG and positive C3 staining on DIF.