Stanislaw A. Buechner

Regression of basal cell carcinoma by intralesional interferon-alpha treatment is mediated by CD95 (Apo-1/Fas)-CD95 ligand-induced suicide.

Basal cell carcinoma (BCC) is the most common skin cancer in humans, and although metastasis rarely occurs, the tumor cells are nevertheless able to invade and destroy the surrounding tissue. Intralesional injection of IFN-alpha has been found to be highly effective in inducing BCC regression by an unknown mechanism. We show that in untreated patients, BCC cells express CD95 ligand, but not the receptor, which may allow tumor expansion by averting the attack of activated CD95 receptor-positive lymphoid effector cells. The CD95 ligand of BCC cells is functional as CD95-positive cells incubated on BCC cryosections become apoptotic and are lysed. In IFN-alpha-treated patients BCC cells express not only CD95 ligand but also CD95 receptor, whereas the peritumoral infiltrate that mainly consists of CD4+ T cells predominantly contains CD95 receptor and only few CD95 ligand-positive cells. Thus, in treated patients BCC most likely regresses by committing suicide through apoptosis induction via CD95 receptor-CD95 ligand interaction.

Rosacea: An Update

Rosacea is a common chronic cutaneous disorder of unknown etiology which occurs most commonly in middle-aged individuals. Cutaneous manifestations include transient or persistent facial erythema, telangiectasia, edema, papules and pustules that are usually confined to the central portion of the face. The National Rosacea Society’s Expert Committee on the Classification and Staging of Rosacea identified four subtypes of rosacea: erythematotelangiectatic, papulopustular, phymatous and ocular. Recently, a standard grading system for assessing gradations of the severity of rosacea has been reported. Little is known about the cause of rosacea. Genetic, environmental, vascular, inflammatory factors and microorganisms such as Demodex folliculorum and Helicobacter pylori have been considered. Topical metronidazole and azelaic acid have been demonstrated to be effective treatments for rosacea. Severer or persistent cases may be treated with oral metronidazole, tetracyclines or isotretinoin.

Changes of Epidermal Mu-Opiate Receptor Expression and Nerve Endings in Chronic Atopic Dermatitis

There is increasing evidence that neuropeptides such as a substance P, neurotrophins or β-endorphin, an endogenous agonist for µ-opioid receptor, are involved in the pathogenesis of atopic dermatitis in which mental stress and scratching deteriorate the disease. µ-Opioid receptor, a G-protein-coupled receptor, can be downregulated and internalized by agonists and other factors in vitro. In this study, we investigated the regulation of µ-opioid receptor and nerve endings in atopic dermatitis patients. Skin biopsies from atopic dermatitis patients revealed a significant downregulation of µ-opiate receptor expression in epidermis of atopic dermatitis. Permeabilization of the skin showed that the receptor in keratinocytes from atopic dermatitis is internalized. The mRNA expression pattern of the µ-opiate receptor is different in epidermis taken from patients with chronic atopic dermatitis compared to normal skin. In atopic dermatitis, the mRNA is concentrated in the subcorneal layers of the epidermis and in normal skin in the suprabasal layers. Staining of the nerve endings using protein gene product 9.5 shows a different pattern of epidermal nerve endings in normal skin compared to atopic dermatitis. In normal skin, the epidermal nerve endings are rather thick. However, in atopic dermatitis, the epidermal nerve endings are thin and run straight through the epidermis. Based on these observations and combining the ‘intensity’ and ‘pattern’ hypothesis, we propose a new theory especially for histamine-unrelated, peripheral induction of chronic pruritus. We suggest that ‘itch’ is elicited in the epidermal unmyelinated nerve C-fibers and ‘pain’ in the dermal unmyelinated nerve fibers. The downregulation of the opioid receptor in the epidermis contributes to the chronic itching. We call this new hypothesis the ‘layer hypothesis’.

Atrophoderma of Pasini and Pierini: Clinical and histopathologic findings and antibodies to Borrelia burgdorferi in thirty-four patients

BACKGROUND Idiopathic atrophoderma of Pasini and Pierini (IAPP) is a distinctive form of dermal atrophy, usually appearing as one or more sharply demarcated depressed areas. Little is known about the clinical variants of IAPP, and limited data are available on antibiotic therapy for this condition. OBJECTIVE Our purpose was to define the various types of IAPP clinically and histologically and to investigate a possible association with Borrelia burgdorferi infection. METHODS The records of 34 patients with IAPP were reviewed. Skin biopsy specimens for routine histologic examination were obtained from 17 patients. Serum from 26 patients was analyzed for antibodies against B. burgdorferi. RESULTS Of the 34 patients (21 female, 13 male, 7 to 66 years of age), 23 had well-circumscribed brown, depressed plaques. The back was most frequently involved (82%). Eleven patients had a superficial variant of IAPP, characterized by slightly atrophic brown macules forming large hyperpigmented patches with an irregular border. Secondary areas of induration developed in 7 of 34 patients. Ten of 26 patients (38%) had elevated serum antibodies to B. burgdorferi. Twenty of the 25 patients treated with oral antibiotics had clinical improvement with no evidence of new active lesions. CONCLUSION IAPP is an abortive, primarily atrophic variant of morphea. The clinical appearance of IAPP may be variable according to the stage of dermal atrophy and distribution of the lesions.

Intralesional interferon alfa-2b in the treatment of basal cell carcinoma: Immunohistochemical study on cellular immune reaction leading to tumor regression

Four patients with basal cell carcinomas were treated with intralesional injections of interferon alfa-2b (1.5 million IU per injection) three times a week for 2 weeks. Histopathologic examination of biopsy specimens of the lesions confirmed the absence of basal cell carcinoma in all cases 4 weeks after completion of therapy. A dense mononuclear cell infiltrate and numerous ectatic blood vessels were present in the dermis at the sites of previous basal cell carcinoma. Immunohistologic analysis of the dermal infiltrate revealed a marked increase of Leu-4+ T cells with a slight predominance of Leu-3+ helper/inducer T cells over Leu-2+ suppressor/cytotoxic T cells. Most of the dermal infiltrate expressed HLA-DR antigen. In addition, Leu-11+ natural killer cells were observed in the dermal infiltrate. Immunohistologic changes in the skin lesions at the sites of previous basal cell carcinoma suggest that intralesional interferon alfa-2b acts on tumor cells by enhancement of local T-cell-mediated immune responses.

Localized scleroderma associated with Borrelia burgdorferi infection: Clinical, histologic, and immunohistochemical observations

BACKGROUND Recent reports have implicated Borrelia burgdorferi infection as a possible cause of localized scleroderma (LS). OBJECTIVE Our purpose was to describe the clinical, histologic, and immunopathologic features of patients with LS who had serum antibodies to B. burgdorferi. METHODS Ten patients were examined clinically and by routine microscopy. Biopsy specimens from seven patients were studied immunohistochemically with monoclonal antibodies. The proliferative response of peripheral blood mononuclear cells to B. burgdorferi was investigated in seven patients by lymphocyte proliferation assay. RESULTS Seven patients had plaque-type morphea, and three patients had linear scleroderma. Two patients had a history of previous erythema migrans. One patient had coexistent acrodermatitis chronica atrophicans, and in two patients lichen sclerosus et atrophicus was observed. Histologically, a prominent inflammatory phase with sclerosis of the connective tissue was shown in all patients. Immunohistochemical studies revealed that the inflammatory infiltrates consisted of both B and T lymphocytes, predominantly of the CD4+ subset. All 10 patients had strongly elevated serum antibodies to B. burgdorferi. Patients with LS showed significantly elevated lymphoproliferative responses to B. burgdorferi when compared with healthy control subjects. CONCLUSION Our findings suggest that some cases of LS are linked to Borrelia infection.

Zosteriform metastases in melanoma

Zosteriform metastasis is a rare form of tumor spread to the skin that most often arises from an internal carcinoma or a hematologic malignancy. We describe a 29-year-old woman with malignant melanoma of the back in whom zosteriform metastases developed along the fifth thoracic dermatome.

Isolated lichen planus of the lip

Summary Oral lichen planus ((LP) is a relatively common disorder of unknown aetiology. Oral LP occurs most often on the buccal mucosa, but the gingivae, tongue, floor of the mouth, retromalar pads and lips may also be affected. Usually, patients have multiple sites of involvement. We report a 44‐year‐old patient with a 5‐year history of isolated swelling of the lower lip. erosions and crusting. Histology of a biopsy from the lip revealed features of LP. Oral treatment with acitretin and low‐dose steroid led to complete resolution of the lesions within 10 weeks. This is the first well‐documented case of isolated LP of the lip. Diagnostic difficulties and differential diagnosis are reviewed.

Cutaneous Myiasis due to Dermatobia hominis

Cutaneous myiasis caused by the human botfly Dermatobia hominis involves the infestation of tissue with dipterous fly larvae and is common in the neotropical region of the New World. We report a case of D. hominis imported in Switzerland from Costa Rica. In the past, various approaches to extract the botfly larva have been reported.

Segmental forms of autosomal dominant skin disorders: the puzzle of mosaicism.

Autosomal dominant inherited disorders of the skin sometimes present as a segmental phenotype. In recent years molecular studies have demonstrated that genetic mosaicism leads to such a clinical manifestation. In general the skin outside the segmental disorder is normal. This rather common variant of segmental manifestation has been termed type 1. Recently, Happle delineated a second type of segmental manifestation of autosomal dominant genodermatosis. This variant is characterized by a more diffuse clinical presentation of the disease, and a very marked linear pattern can be recognized. An explanation of this phenotype is a germline mutation of the gene manifests after a postzygotic mutation leading to double inactivation of the gene. The severe linear manifestation then reflects a doubling of the genetic burden. We present a number of clinical cases to demonstrate this phenomenon, and we present a case of the segmental Naegeli-Franceschetti-Jadassohn syndrome born to a mother with the diffuse manifestation of the disorder.