Constantin E. Orfanos

OBJECTIVE: To evaluate the efficacy and safety of systemic interferon alfa treatment in patients with Adamantiades-Behçet disease. DATA SOURCES: Reports and abstracts published in 1986 through 1997 in all languages were identified by the MEDLINE database, the Reference Index Related to Behcet's Disease, the Behçet disease conference proceedings, and abstract booklets. The indexing terms used Behçet and interferon. STUDY SELECTION: Twenty-two reports identified were included to estimate the efficacy of interferon alfa on mucocutaneous, ocular, and joint manifestations. Responses of individual mucocutaneous signs were evaluated in 8 reports. Adverse effects were sufficiently documented in 12 reports. All patients met the criteria of the Behçet Syndrome Research Committee of Japan or those of the International Study Group for Behçet's Disease. DATA EXTRACTION: Data were extracted and evaluated according to the following criteria: complete remission, disappearance of all manifestations during treatment; partial remission, greater than 50% decrease in the number, severity, duration and/or frequency of recurrence of the lesions; stable disease, less than 50% change in the manifestations; and progressive disease, greater than 50% deterioration of existing manifestations or/and the development of new ones. DATA SYNTHESIS: Systemic interferon alfa has been administered in 144 patients with Adamantiades-Behçet disease by subcutaneous or intramuscular injections of 3 to 18 x 10(6) units of interferon alfa-2a (70 patients) or 3 to 5 x 10(6) units of interferon alfa-2b (74 patients) daily or 3 times per week for 1 to 60 months. Seventy-four percent (92/124) of patients with mucocutaneous manifestations, 95% (37/39) of patients with uveitis, and 93% (51/55) of patients with arthropathy/arthritis exhibited a partial or complete response. Interferon alfa-2a regimens were more effective than interferon alfa-2b ones on mucocutaneous (47% vs 7% complete response) and ocular (67% vs 8% complete response; P < .001) manifestations. Mucocutaneous and ocular manifestations responded within 1 to 4 months after initiation of therapy. Thirty-eight percent (20/52) of patients with mucocutaneous lesions, 73% (8/11) of patients with uveitis, and 88% (21/24) of patients with arthropathy/arthritis experienced recurrences immediately or up to 7 months after discontinuation of treatment. Mild adverse effects were generally recorded; transient influenza-like symptoms (87% vs 63%; P < .05) and reversible leukopenia (24% vs 4%; P < .05) occurred more often under interferon alfa-2a regimens, while reversible mild alopecia was more common in patients receiving interferon alfa-2b (2% vs 28%; P < .01). CONCLUSIONS: Systemic interferon alfa treatment is reasonable for Adamantiades-Behçet disease. A 3-month high-dose regimen (9 x 10(6) units 3 times per week) followed by a low maintenance dose (3 x 10(6) units 3 times per week) is recommended.

Human sebocytes obtained as explants after in vitro culture of isolated sebaceous glands were recently shown to maintain in part a sebocytic differentiation. The aim of this study was to further identify markers of sebocytic differentiation in vitro. Therefore, the morphology of cultured human sebocytes, and their differentiation with lipid storing and expression of cellular proteins were investigated by microscopy, electron microscopy, study of cell kinetics, cytochemistry and immunocytochemistry, and were compared to cultured human keratinocytes obtained from the same skin specimens. At first, sebocytes in all stages of sebocytic differentiation were detected in vitro. Abundant cytoplasmic lipids and the absence of desmosomes were identified as their ultrastructural characteristics. Secondly, an increasing number of sebocytes storing lipids was detected during cell proliferation. Sebocytes contained up to 4 times more lipids than keratinocytes in vitro. Squalene and increased quantities of wax/sterol esters could be extracted from secondary sebocyte cultures. Thirdly, the monoclonal antibodies 6B10 (keratin 4), RPN1162 (keratin 7), and OM-1 labeled only sebocytes in vitro. Furthermore, sebocytes presented a marked expression of keratin 19 in comparison to keratinocytes, as detected with CK 4.62, and a lack of RPN1161 (keratins 1 and 2) expression, which was typically found to be expressed in cultured keratinocytes. The culture of human sebocytes possessing several characteristics of sebocytic differentiation in vivo offers unique possibilities in investigating direct effects on sebaceous cell growth, differentiation and their regulation.