[Hereditary photodermatoses]. / Hereditäre Photodermatosen.

Hereditary photodermatoses are characterized by an increased photosensitivity caused by an inherited single gene defect. With few exceptions, they manifest in early childhood, reveal heterogeneous clinical symptoms, and are difficult to treat. Although these diseases are rare, it is very important to make an accurate diagnosis on the basis of clinical symptoms, specific diagnostic tests, and direct DNA analysis. We review the spectrum of inherited photodermatoses, including porphyria cutanea tarda, erythropoietic protoporphyria, actinic prurigo, Kindler syndrome, and disorders associated with a defect in DNA repair, including xeroderma pigmentosum, trichothiodystrophy, Cockayne syndrome, and Bloom syndrome. Early diagnosis may prevent complications associated with prolonged unprotected exposure to sunlight and makes it possible to offer genetic counseling and, when indicated, prenatal diagnosis to families at risk for these rare heritable disorders.

Induction of a chemoattractive proinflammatory cytokine response after stimulation of keratinocytes with Propionibacterium acnes and coproporphyrin III.

BACKGROUND: The inflammation in acne vulgaris is widely thought to be induced by an immunological reaction, but the role of Propionibacterium acnes is unclear. OBJECTIVES: To examine the local host response mechanism of a keratinocyte cell line 3 h and 6 h after stimulation with viable and heat-killed P. acnes. METHODS: The quantitative expression of cytokines was measured at the mRNA level by real-time reverse transcription-polymerase chain reaction. RESULTS: The coincubation of a keratinocyte cell line with viable, but not heat-killed, P. acnes modulated an adequate cytokine response for interleukin (IL)-1beta, granulocyte/macrophage colony-stimulating factor and IL-8. High-performance liquid chromatographic analysis of the in vivo porphyrin pattern secreted by P. acnes revealed a predominance of coproporphyrin III in acne lesions. This same porphyrin fraction also modestly induced IL-8 expression by keratinocytes. CONCLUSIONS: This cytokine pattern may favour a chemotactic response and implicates P. acnes and coproporphyrin III in the recruitment of inflammatory cells to the site of infection and in the development of acne lesions.

Macrolactam immunomodulators for topical treatment of inflammatory skin diseases.

The immunomodulatory macrolactams provide an alternative to glucocorticosteroids for the topical treatment of atopic dermatitis and other inflammatory dermatoses. Tacrolimus (FK506), as well as the newer ascomycin derivative ASM 981 (pimecrolimus), penetrate the inflamed epidermis and are suitable for topical therapy. Both substances inhibit the transcription of proinflammatory cytokine genes such as interleukin 2, which are dependent on the nuclear factor NF-AT. They block the catalytic function of calcineurin, which leads to the inhibition of the transport of the cytoplasmic component of NF-AT to the cell nucleus. Multicenter, randomized, double-blind clinical trials with topical formulations have shown the efficacy of both substances in moderate to severe atopic dermatitis. A review is presented of the biochemical and cell biologic properties, mode of action, pharmacokinetic data, side effects, results of the clinical trials, and further indications for tacrolimus and ASM 981, along with an overview of the related substances cyclosporine and sirolimus (rapamycin).

Cowden syndrome-diagnostic skin signs.

Cowden syndrome is a rare autosomal dominant familial cancer syndrome with a high risk of breast cancer. The most important clinical features include carcinomas of the breast and thyroid, and hamartomatous polyps of the gastrointestinal tract. There are characteristic mucocutaneous features which allow early recognition of the disease and are generally present before internal malignancies develop. We report on a woman in whom the diagnosis of Cowden syndrome was first made after she had been treated for both breast cancer and melanoma.

[Actinic prurigo. An assessment of current status]. / Aktinische Prurigo. Eine Standortbestimmung.

BACKGROUND AND OBJECTIVE: Actinic prurigo (AP) is a hereditary photodermatoses with typical symptoms and is quite common in North- and South-America. The key genetic factor appears to be a Native American background. In Europeans this type of AP is extremely rare; some dispute if this disease exists in Caucasians. Some newer publications postulate that these patients share HLA markers with the Native Americans. The most important differential diagnosis for AP is polymorphic light eruption which can be excluded relatively accurately by the clinical picture, typical histology and HLA pattern. PATIENTS/METHODS: The case of a female patient of Mayan ancestry living in Germany is presented. CONCLUSIONS: Since in literature sometimes cases from Europe are diagnosed as AP this is a problem of naming the disease. It would be helpful to integrate the terms hereditary or hereditaria into the name of the disease in indians.

Myxoid liposarcoma in a 12-year-old girl.

A 12-year-old girl developed a myxoid liposarcoma on the inner side of her right thigh. Liposarcomas are extremely rare at this age compared to benign lipoblastomas, which are the most frequent tumors of fatty tissue in childhood. The prognosis of myxoid liposarcoma is good, especially when, as in this patient, the tumor is located in the subcutis where a large and deep excision is possible and often curative.

Which direction do nevus cells move? Abtropfung reexamined.

In 1893, Unna published his theory of Abtropfung in which he suggested that melanocytic nevus cells originate in the epidermis and drop off into the dermis. We studied 3,534 nevi from patients of all ages to reassess this almost sacred concept. If Unna was correct, one would expect that in childhood most nevi would be junctional, while in late adult life almost all nevi would be intradermal. In our series, no child under age 10 had a purely junctional nevus, 52% had compound nevi, and 48% had dermal nevi. In patients older than age 60, 12% had junctional nevi, 23% had compound nevi, and 65% had dermal nevi. Our data fail to support the concept of Abtropfung; they fit better with the contradictory theory of upward migration of nevus cells.

Fetal and adult hair follicle. An immunohistochemical study of anticytokeratin antibodies in formalin-fixed and paraffin-embedded tissue.

The expression of cytokeratins (CK), involucrin, vimentin, CD34, and alpha-smooth-muscle actin was studied in fetal and adult hair follicles. The first stage of the developing hair follicle is characterized by palisaded, elongated epithelial cells budding from the epidermal basal layer. These cells express CK5/6, CK14, CK17, CK19, and vimentin. During the following weeks of gestation, different structures in the developing hair follicle can be identified and characterized. The matrical cells display only CK19. The keratinocytes of the outer root sheath express CK5/6, CK14, CK17, CK19, and involucrin; those of the inner root sheath, CK4, CK18, and involucrin; those of the isthmus, the same profile as the ORS. In the infundibulum, the basal-layer keratinocytes express CK5/6, CK14, CK17, and CK19, whereas in the suprabasal layers CK1, CK4, CK10, CK14, and CK17 are seen. The adult hair follicle in anagen fails to express CK19 in the matrical cells and isthmus and both CK17 and CK19 in the infundibulum. These profiles of intermediate filaments and other markers appear to be potentially useful in categorizing neoplasms with apparent follicular differentiation.

Trichoblastoma and basal cell carcinoma are neoplasms with follicular differentiation sharing the same profile of cytokeratin intermediate filaments.

Trichoblastoma and nodular basal cell carcinoma are generally held to be distinctive epithelial neoplasms with some overlapping features. We investigated 30 trichoblastomas in which the basaloid cells expressed cytokeratins (CK) CK5/6, CK14, CK17, CK19, and, in a few cells, vimentin. The cells of the periphery of small and large cysts showed the same profile. Cells lining the lumen of small cysts expressed CK14, CK17, and involucrin, and those in larger cysts showed a positivity for CK1, CK4, CK10, CK14, CK17, and involucrin. The remaining tested antibodies (CK7, CK8, CK13, CK18, CK20, alpha-smooth-muscle actin) were negative in all cases. The cells of the stroma expressed vimentin and in 22 cases, the CD34 antigen. Seventeen nodular basal cell carcinomas showed exactly the same staining pattern. Furthermore, there are striking immunohistochemical similarities between the neoplastic basaloid cells of both neoplasms and the cells of the hair germ. Therefore, trichoblastoma and nodular basal cell carcinoma cannot be distinguished by their pattern of cytokeratin expression in paraffin sections. The virtually identical cytokeratin pattern seen in trichoblastoma, basal cell carcinoma, and the developing fetal hair follicle is compelling evidence for common differentiation pathway.

Pathogenesis and treatment of acne in childhood.

Acne occurs more frequently in newborns and infants than one would gather from written accounts. Acne neonatorum tends to be overlooked because it is usually minor and transient. In contrast, acne infantum, which generally does not make its appearance until after 3 months of life, is more serious. Even acne conglobata may develop in infants. There are many other types of acne in childhood reflecting different pathogenetic mechanisms; included in this group are acne venenata infantum, steroid acne, hormonal disturbances, and toxic reactions.

The non-Langerhans' cell histiocytoses in childhood.

The cutaneous histiocytoses are best divided in the Langerhans' cell histiocytoses and non-Langerhans' cell histiocytoses. In the former group, the cells react with S100 and CD1a antibodies, while in the latter group they express a variety of macrophage markers. Xanthogranuloma is a frequent childhood tumor and the only common non-Langerhans' cell histiocytosis. Xanthogranulomas contain a mixture of several different types of histiocytes that also appear in more pure forms as both solitary tumors and disseminated processes. The varying histiocyte morphology provides a unifying concept for non-Langerhans' cell histiocytoses.

Melanocytic hyperplasia in scars. A histopathological investigation of 722 cases.

We studied 722 reexcision scars of benign and malignant lesions (except melanocytic lesions) excised over a 24-month period. The formalin-fixed, paraffin-embedded tissue sections were examined histologically and immunohistochemically. The histological features of melanocytic hyperplasia were present in 59 cases (8%), 56 from the sun-exposed skin of the face and neck and three from the trunk [p < 0.00001]. The most common sites were the nose and lower eyelids, but the forehead was also frequently involved. Of the 59 patients, 41 were women (p < 0.0001). Basal cell carcinoma was the most frequent original lesion in both sexes (80%). No melanocytic hyperplasia was found in 663 cases (298 on the trunk and extremities and 365 on the head and neck). We have seen this reaction pattern following reexcision of melanocytic lesions as well. Thus, interpreting reexcision margins when lentigo maligna or similar lesions are reexcised may be fraught with difficulty. It is important for pathologists and dermatopathologists to recognize this phenomenon because histologically the presence of increased numbers of large melanocytes could be misinterpreted as melanoma in situ.

Solitary and generalized variants of spindle cell xanthogranuloma (progressive nodular histiocytosis).

Twelve cases of solitary spindle cell xanthogranuloma, seven of which had originally been misdiagnosed as dermatofibroma/benign fibrous histiocytoma, were clinicopathologically compared with four cases of progressive nodular histiocytosis, a rare generalized non-X histiocytic disorder. Clinically, a single brown-yellowish papule or nodule is characteristic of solitary spindle cell xanthogranuloma, multiple generalized lesions of progressive nodular histiocytosis. Solitary spindle cell xanthogranuloma occurs with decreasing frequency on the head, neck, upper trunk, or occasionally the extremities of young adults (aged 20-40 years), progressive nodular histiocytosis mostly on the trunk of older patients (aged 40-60 years), both without sex predilection. Histologically, both entities are characterized by predominance (> 90%) of spindle-shaped histiocytes arranged in a storiform pattern. Other mononuclear (vacuolated, xanthomatized, scalloped, oncocytic) and multinucleate (Touton) histiocytes are also regularly seen. Immunohistochemically, both entities exhibit a macrophage/dendritic cell lineage positive for KP1/Ki-M1p (CD68), HAM 56 and factor XIIIa as well as for smooth muscle specific actin and HHF35. Ultrastructurally, dense, regularly laminated, myeloid or pleomorphic cytoplasmic inclusions may be found, but no Birbeck granules are present. This study documents that both solitary spindle cell xanthogranuloma and progressive nodular histiocytosis are distinct entities within the spectrum of a xanthogranulomatous reaction characterized by predominance of spindle-shaped histiocytes.