Carlson Ja

Comparative immunophenotypic study of lichen sclerosus: epidermotropic CD57+ lymphocytes are numerous--implications for pathogenesis.

To characterize the immunophenotype of inflammatory cells in lichen sclerosus (LS), we performed a comparative case control study using one- and two-color immunohistochemistry and the nitro blue tetrazolium (NBT) reaction. Study material consisted of 100 biopsies from patients with LS or from 12 control groups consisting of inflammatory, scarring, and depigmenting cutaneous disorders. In addition, fresh tissue was sampled from four vulvectomy specimens for NBT testing. The typical inflammatory infiltrate of LS contained numerous epidermotropic CD3+, CD8+, CD57+ cells, increased intraepidermal HLA-DR+ cells, and a dermal infiltrate rich in CD8+, CD57+, HLA-DR+, and CD68+ inflammatory cells. Comparing LS to the 12 control groups, epidermotropic CD57+ lymphocytes independently predicted LS (P = 0.006, logistic regression, multivariate analysis). Among the 12 control groups, only specimens of the inflammatory stage of morphea exhibited numerous dermal CD57+ lymphocytes. Two-color immunohistochemistry confirmed the CD3+/CD8+CD57+ and CD3+/ CD8+/CD57+HLA-DR+ epidermotropic and dermal lymphocytic phenotypes and the dermal macrophage CD68+HLA-DR+ phenotype. In LS, the NBT reaction revealed evidence of superoxide production associated with CD68+HLA-DR+ cells. Expansion of CD8+CD57+lymphocytes is associated with viral infections, autoimmune disease, malignancies, and transplantation and is suspected to be the result of chronic excessive antigen challenge. In these pathologic states, CD8+CD57+ lymphocytes (as terminally differentiated, antigen-specific T cells) participate in the suppression of cytolytic activity to limit tissue damage. In LS, activated macrophages and lymphocytes indicate persistent antigen-driven inflammation. LSs numerous CD8+CD57+ lymphocytes may be either the mediators or the consequence of its hallmark sclerosis.

Possible mechanisms of hypopigmentation in lichen sclerosus.

Lichen sclerosus (LS) shares with vitiligo a milky-white appearance. By biopsy, pathognomonic dermal sclerosis readily distinguishes LS from vitiligo and other causes of leukoderma.To determine what the mechanism of hypopigmentation is in LS, we examined samples from LS cases for alterations in melanin content (Fontana-Masson stain) and melanocyte number (HMB-45 [PMEL-17/gp100], Mel-5 [TRP-1], Mart-1 [Melan A]) and compared these findings with those in controls of normal skin, acute scars, vitiligo, and lichen planus (LP; a common inflammatory cause of hyperpigmentation).The degree and extent of melanization found in LS overlapped with that in acute scars showing predominantly hypomelanized keratinocytes, with that in LP containing regions with numerous melanophages, and with that in vitiligo exhibiting focal regions of keratinocytes devoid of melanin pigment. By hematoxylin–eosin staining and immunocytochemistry for Mel-5 and Mart-1, LS had a lower mean count of melanocytes than acute scars, LP, and normal skin per 200 basal keratinocytes. In addition, a few LS cases had a significant loss of melanocytes comparable to that of vitiligo. Surprisingly, Mart-1 identified rare melanocytes in 67% of vitiligo cases and a significantly larger pool of melanocytes in LS and controls other than those labeled by Mel-5. Furthermore, LP and evolving lesions of LS contained the highest Mart-1 counts. HMB-45–immunoreactive melanocytes were found in the majority of acute scars and in LP and late-stage LS lesions at significantly lower levels than Mel-5– and Mart-1– labeled melanocytes, but they were not found in vitiligo or normal skin.We propose that several mechanisms may play a role in the production of leucoderma in LS: 1) decreased melanin production; 2) block in transfer of melanosomes to keratinocytes; and 3) melanocyte loss. The latter finding may be the pathogenic connection (lichenoid dermatitis of LS triggering an autoimmune reaction to melanocytes) that underlies the documented association of LS with vitiligo.

Silicon Granulomas and Dermatomyositis-like Changes Associated With Chronic Eyelid Edema After Silicone Breast Implant

Summary: Silicone medical products may be associated with various complications. Recent attention has focused particularly on health risks associated with silicone breast implants. The authors present the clinical and histopathological findings in a 71-year-old woman who had previously undergone breast reconstruction with a silicone gel—filled elastomer envelope—type breast implant and who developed severe chronic eyelid edema and inflammation. Extensive systemic evaluation and serologic studies were unrevealing, prompting biopsy of the eyelids. Histopathologic evaluation of the upper eyelids revealed scattered noncaseating granulomas throughout the dermis, an atrophying interface dermatitis with a sparse perivascular lymphocytic infiltrate, and focal perivascular and interstitial lymphocytic infiltrates of the muscles. Scanning electron microscopy demonstrated particles of material within the granulomas, which were revealed by electron probe x-ray microanalysis to contain silicon. The presence of silicon-containing material within areas of eyelid inflammation supports a role for silicon in the pathogenesis of this patients condition. In the absence of other predisposing conditions, migration of silicone breast implant material must be considered.

Sarcoidal foreign-body granulomatous dermatitis associated with ophthalmic drops.

Sarcoidal granulomas are found in sarcoidosis and in reactions to foreign materials. We report the case of an 81-year-old woman with glaucoma who presented with multiple brown-black asymptomatic papules over the chin and involving nasal mucosa and columella of 1-year duration. Biopsy of the nasal mucosa and cutaneous papules showed sarcoidal granulomas associated with brown-black intracellular pigment within multinucleated giant cells. Electron-probe x-ray microanalysis demonstrated high sulfur content. Clinical studies showed no evidence of systemic sarcoidosis. Two of three ophthalmologic drops contained sodium bisulfite; bisulfite is known to cause allergic reactions. Although the exact substance causing the granulomatous reaction is unknown, the distribution of the lesions--nasal mucosa and columella (via the nasal lacrimal duct) and the underlying chin--implicate the eyedrops in the production of the pigmented granulomatous nodules.