Mouth and genital ulcers with inflamed cartilage (MAGIC) syndrome complicated by aneurysmal aortitis.

"MAGIC syndrome" (Mouth And Genital ulcers with Inflamed Cartilage) has been proposed to describe patients with clinical features of both relapsing polychondritis and Behcet disease. A total of 18 cases have been reported with only 1 case associated with aneurysmal aortitis described in 1997. Herein, we describe a patient with MAGIC syndrome complicated by aneurysmal aortitis requiring cardiothoracic surgery and intensive immunosuppression. Monitoring for the possible development of inflammatory aortic aneurysms should thus be considered in patients with MAGIC syndrome who have persistently elevated serum inflammatory markers. If an aortic aneurysm is detected, cardiothoracic surgical referral is necessary, close monitoring for enlargement is mandatory, and intensification of immunosuppressive therapy should be considered.

Atypical fibroxanthoma with perineural or intraneural invasion: report of two cases.

We report two cases of atypical fibroxanthoma (AFX) that both had the previously unreported feature of neural invasion (one perineural and the other intraneural). AFXs recur in approximately 10% of cases but only rarely metastasize. Features associated with recurrence are inadequate excision and invasion into fat. Features associated with metastasis include recurrence, vascular invasion, deep tissue invasion, and tumor necrosis. Both of these tumors invaded deeply into subcutaneous fat and reached the deep fascia. Some authors would regard such cases as malignant fibrous histiocytoma (MFH) because of such deep extension; however, the concept of AFX as a superficial variant of MFH is outmoded--AFX is a distinct clinicopathologic entity with established clinical, histological, and immunohistochemical features.

An open-label, pilot study examining the efficacy of curettage followed by imiquimod 5% cream for the treatment of primary nodular basal cell carcinoma.

SUMMARY The short-term efficacy of imiquimod 5% cream for the treatment of primary superficial basal cell carcinoma has been established. This study investigated its efficacy following curettage (without electrodesiccation) for the treatment of primary nodular basal cell carcinoma on the trunk and limbs. Seventeen patients with a total of 34 lesions were enrolled. Curettage was used to de-bulk the lesion and confirm suitable histology. Lesions displaying more aggressive subtypes (such as micronodular or morpheoic components) were excluded. Lesions were treated daily for 6 to 10 weeks with imiquimod 5% cream. Three months post treatment all lesions were excised, and 32 of 34 treated lesions (94%) were histologically clear of basal cell carcinoma. Fourteen of 17 patients rated the cosmetic outcome of treatment as excellent or good. Curettage followed by imiquimod 5% cream is effective for the treatment of primary nodular basal cell carcinoma on the trunk and limbs, and most patients are pleased with the cosmetic outcome.

Generalized, pruritic, ulcerating maculopapular rash necessitating cessation of sirolimus in a liver transplantation patient.

The use of sirolimus as an alternative to calcineurin antagonists has enabled the continuation of immunosuppression in patients with renal impairment with preservation of kidney function. Sirolimus is generally well tolerated, with the main causes of cessation of therapy related to its effect on blood lipid profile as well as leukopenia and thrombocytopenia. We report a case of a debilitating ulcerating maculopapular rash necessitating cessation of the drug in a liver transplantation patient. A 56-year-old Caucasian liver transplantation patient presented with a diffuse, debilitating rash attributed to sirolimus use. This ultimately necessitated cessation of the immunosuppressant with subsequent resolution of her symptoms. From a review of the current literature, this is a highly unusual adverse reaction to sirolimus.

AP-2 transcription factor family member expression, activity, and regulation in human epidermal keratinocytes in vitro.

The AP-2 transcription factor family is presumed to play an important role in the regulation of the keratinocyte squamous differentiation program; however, limited functional data are available to support this. In the present study, the activity and regulation of AP-2 were examined in differentiating human epidermal keratinocytes. We report that (1) AP-2 transcriptional activity decreases in differentiated keratinocytes but remains unchanged in differentiation-insensitive squamous cell carcinoma cell lines, (2) diminished AP-2 transcriptional activity is associated with a loss of specific DNA-bound AP-2 complexes, and (3) there is an increase in the ability of cytoplasmic extracts, derived from differentiated keratinocytes, to phosphorylate AP-2 alpha and AP-2 beta when cells differentiate. In contrast, extracts from differentiation-insensitive squamous cell carcinoma cells are unable to phosphorylate AP-2 proteins. Finally, the phosphorylation of recombinant AP-2 alpha by cytosolic extracts from differentiated keratinocytes is associated with decreased AP-2 DNA-binding activity. Combined, these data indicate that AP-2 trans-activation and DNA-binding activity decrease as keratinocytes differentiate, and that this decreased activity is associated with an enhanced ability to phosphorylate AP-2 alpha and beta.

Use of biosynthetic dressings in paraneoplastic pemphigus.

A 77-year-old woman with paraneoplastic pemphigus and non-Hodgkin's lymphoma was treated with supportive therapy and oral prednisone. Biobrane, a biosynthetic dressing, was later applied to the extensive areas of erosion to assist in pain management and to provide a temporary barrier function. She reported an improvement in the pain associated with the areas of erosion. The use of biosynthetic dressings in blistering disorders has not been previously reported. Standard dressings such as silver sulfadiazine are messy and can cause discomfort with frequent changing. We feel that this is an area that warrants further evaluation as it may contribute to the overall treatment and comfort cares of these patients.

Psoriasis induced by topical imiquimod.

We report the provocation of localized psoriasis at the sites of application of topical imiquimod, possibly evolving into a generalized flare. A patient with pre-existing psoriasis that had been stable for 14 years was treated with imiquimod 5% cream daily for 6 weeks to three superficial basal cell carcinomas. During treatment one of the lesions developed severe local skin reactions necessitating rest periods, and received only 18 applications in 6 weeks. The other two lesions were treated for all 42 days. Psoriasiform changes developed at all three application sites. Nine-and-a-half weeks after completing treatment the patient developed disseminated small psoriatic lesions. Other recognized triggers of psoriasis were not identified. The psoriasis resolved slowly with conventional treatment.

Alterations in gene expression and activity during squamous cell carcinoma development.

This study focuses on characterizing the genetic and biological alterations associated with squamous cell carcinoma development. Normal human epidermal keratinocytes (HEKs), cells isolated from a preneoplastic lesion (IEC-1), and two neoplastic cell lines, SCC-25 and COLO-16, were grown as raft cultures, and their gene expression profiles were screened using cDNA arrays. Our data indicated that the expression levels of at least 37 genes were significantly (P

Isolation (from a basal cell carcinoma) of a functionally distinct fibroblast-like cell type that overexpresses Ptch.

In this study we report on the isolation and characterization of a nonepithelial, nontumorigenic cell type (BCC1) derived from a basal cell carcinoma from a patient. The BCC1 cells share many characteristics with dermal fibroblasts, such as the expression of vimentin, lack of expression of cytokeratins, and insensitivity to agents that cause growth inhibition and differentiation of epithelial cells; however, significant differences between BCC1 cells and fibroblasts also exist. For example, BCC1 cells are stimulated to undergo DNA synthesis in response to interferon-gamma, whereas dermal fibroblasts are not. More over, BCC1 cells overexpress the basal cell carcinoma-specific genes ptch and ptch2. These data indicate that basal cell carcinomas are associated with a functionally distinct population of fibroblast-like cells that overexpress known tumor-specific markers (ptch and ptch2).

Nuclear RelB+ cells are found in normal lymphoid organs and in peripheral tissue in the context of inflammation, but not under normal resting conditions.

Differentiated dendritic cells (DC) have been identified by the presence of nuclear RelB (nRelB) and HLA-DR, and the absence of CD20 or high levels of CD68, in lymph nodes and active rheumatoid arthritis synovial tissue. The current studies aimed to identify conditions in which nRelB is expressed in human tissues, by single and double immunohistochemistry of formalin-fixed peripheral and lymphoid tissue. Normal peripheral tissue did not contain nRelB+ cells. nRelB+ DC were located only in T- or B-cell areas of lymphoid tissue associated with normal organs or peripheral tissues, including tonsil, colon, spleen and thymus, or in association with T cells in inflamed peripheral tissue. Inflamed sites included skin delayed-type hypersensitivity reaction, and a wide range of tissues affected by autoimmune disease. Nuclear RelB+-HLA-DR- follicular DC were located in B-cell follicles in lymphoid organs and in lymphoid-like follicles of some tissues affected by autoimmune disease. Lymphoid tissue T-cell areas also contained nRelB(-)-HLA-DR+ cells,some of which expressed CD123 and/or CD68. Nuclear RelB+ cells are found in normal lymphoid organs and in peripheral tissue in the context of inflammation, but not under normal resting conditions.