alopecia
Association between alopecia and response to aggressive chemotherapy in patients with Hodgkin's disease.

Lishner M, Manor Y, Kitay-Cohen Y, Avishay AE.

Department of Medicine, Meir Hospital Kfar Saba and Sackler Faculty of Medicine, Tel Aviv University, Israel.

The clinical significance and implications of absence of alopecia and/or neutropenia in patients treated with chemotherapy for malignant disease is unknown. We hypothesized that there is a common mechanism of resistance to the effects and the adverse effects of anticancer treatment, which may have clinical implications. To evaluate this hypothesis, we conducted a retrospective analysis of the charts of 17 consecutive patients with Hodgkin's disease who received at least 4 courses of combination chemotherapy (ABVD or MOPP/ABV). Twelve patients underwent complete alopecia while 5 patients retained their hair or had only minimal hair loss. The two groups had similar pretreatment characteristics. Ten (83%) of the patients with alopecia achieved complete remission as compared with 2 (40%) of the patients who retained their hair (P = 0.11). Also, patients without alopecia had fewer episodes of neutropenia (0% vs 33%, P = 0.02), delays of scheduled treatments (0% vs 66%, P = 0.02) or number of courses with dose reductions (20% vs 41%, P = 0.39). These differences shows a clear trend which did not reach statistical significance due to the small number of patients. We suggest that, in intensively treated patients with Hodgkin's disease, the absence of alopecia may predict a poor response to treatment. Also, patients without alopecia probably have fewer episodes of leukopenia, deferral of treatment courses or number of courses with dose reductions. We hypothesize that there is a common mechanism of resistance to cytotoxic agents that may prevent apoptotic death in both normal and malignant cells.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10616048&dopt=Abstract alopecia, hair loss



alopecia
Role of cytotoxic T cells in chronic alopecia areata.

Bodemer C, Peuchmaur M, Fraitaig S, Chatenoud L, Brousse N, De Prost Y.

Department de Dermatologie, Paris, France.

Cytokines play a role in alopecia areata. We used immunohistochemical and in situ hybridization studies to demonstrate the persistence of pro-inflammatory as well as apoptotic mechanisms in skin biopsies from patients with chronic alopecia areata. In situ hybridization allows the visualization of the distribution of immunocompetent cells in vivo. We studied skin biopsies from 11 untreated alopecia areata patients and two normal controls. In situ hybridization was performed on frozen sections using 35S-radio-labeled riboprobes, specific for IL-1beta, IL-2, IL-6, INFgamma, and granzyme B mRNA. Immunohistochemistry was carried out using an anti-IL-1beta monoclonal antibody, and a monoclonal antibody directed against the human Fas protein. We demonstrated the presence of cells labeled with IL-1beta, IL-6, INFgamma, and granzyme B antisense probes. Similarly, cells labeled with anti-IL-1beta were found in 10 of 11 cases. The labeled cells were located in the mononuclear peri- and intrafollicular infiltrate. Cells expressing granzyme B were found in close contact with the follicle. Fas positivity was demonstrated in four of four cases at the level of the cytoplasmic membrane of the hair follicle keratinocytes. These results, based on visualizing the labeled cells, demonstrate that pro-inflammatory cytokines are produced by the mononuclear cell infiltrate in close contact with follicles in alopecia areata. Furthermore, they demonstrate for the first time that apoptotic mechanisms involving granzyme B and Fas-Fas ligand pathways may play a major role in the persistence of chronic alopecia areata.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10620125&dopt=Abstract alopecia, hair loss



alopecia
Diffuse reversible alopecia in patients with Lyme meningitis and tick-borne encephalitis.

Cimperman J, Maraspin V, Lotric-Furlan S, Ruzic-Sabljic E, Avsic-Zupanc T, Strle F.

University Medical Centre, Ljubljana, Slovenia.

Alopecia occurring after febrile bacterial and viral infection is a phenomenon well known since the beginning of the century. To evaluate the occurrence of alopecia in tick transmitted disease, 23 adult patients with Lyme meningitis and 71 patients with tick-borne encephalitis were included in a prospective study and were followed up for one year. Diffuse alopecia occurred within three months after the outbreak of disease in 3 out of 23 (13%) patients with Lyme meningitis and in 40 out of 71 (56.3%) patients with tick-borne encephalitis. The mean duration of alopecia was 2 to 3 months and alopecia was reversible in all patients.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10666812&dopt=Abstract alopecia, hair loss



alopecia
Alopecia areata is a T-lymphocyte mediated autoimmune disease: lesional human T-lymphocytes transfer alopecia areata to human skin grafts on SCID mice.

Gilhar A, Shalaginov R, Assy B, Serafimovich S, Kalish RS.

Skin Research Laboratory, The B. Rapaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.

Much evidence suggests that alopecia areata is a tissue restricted autoimmune disease. Alopecia areata responds to immunosuppressive agents, and is associated with other tissue restricted autoimmune diseases, including autoimmune thyroiditis and vitiligo. Furthermore, hair regrows when involved scalp is transplanted to nude mice. This study was undertaken to determine whether alopecia areata is mediated by T lymphocytes. Involved scalp from alopecia areata patients was grafted onto SCID mice. Additional biopsies from lesional scalp of the same patients were used to isolate T lymphocytes. These T lymphocytes were cultured with hair follicle homogenate, as well as autologous antigen presenting cells. The T lymphocytes were then injected into autologous scalp grafts on the SCID mice, which had regrown hair. Injection of scalp T lymphocytes resulted in hair loss. Hair loss was associated with the histologic and immunochemical changes of alopecia areata, including perifollicular infiltrates of T cells, along with HLA-DR and ICAM-1 expression by the follicular epithelium. Scalp T lymphocytes that had not been cultured with hair follicle homogenate did not have this effect. Preliminary data suggests hair loss requires a collaboration between CD8+ and CD4+T cells. These studies have demonstrated that alopecia areata can be induced by the transfer of T cells that recognize a hair follicle autoantigen.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10674367&dopt=Abstract alopecia, hair loss



alopecia
Alopecia areata and universalis in the Smyth chicken model for spontaneous autoimmune vitiligo.

Smyth JR Jr, McNeil M.

Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst 01003-7250, USA.

The Smyth line (SL) chicken model for spontaneous, postnatal expression of vitiligo may also show varying incidences and degrees of severity ranging from alopecia areata-like to universalis-like integumental changes. Although human vitiligo patients are known to have a four times greater chance of having alopecia areata than do people without vitiligo, in the SL model, feather loss is limited to birds that show some degree of amelanosis of feather and skin tissue. Both the vitiligo and the alopecia have an autoimmune component, as shown by histologic and immunologic studies, including the correctional influences of corticosterone and cyclosporine-A. The major histocompatibility haplotype (MHC) has a major effect on the incidence and expression of the vitiligo, as well as the alopecia that occurs within vitiliginous birds. Three different MHC haplotypes were identified in the original line that was selected for vitiligo, and from these, three sublines were developed, each homozygous for a different haplotype. Of the three sublines (SL101, SL102, and SL103) the vitiligo has a significantly earlier onset and severity in the SL101 than in the other two lines. The incidence of alopecia, however, is significantly lower in the SL101 subline than in the other two. Inheritance of the vitiligo is polygenic with an additional genetic component for the alopecia trait. It is hypothesized, but as yet unproven, that a feather development defect interacts with the SL melanization and immunologic defects to initiate the partial (areata) and complete (universalis) alopecias. The alopecia universalis is rarely seen until adulthood and is characterized by short (<0.5 cm), undeveloped feathers. If feather growth resumes in these birds, the feathers dry up, cease to grow, and often break off.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10674368&dopt=Abstract alopecia, hair loss



alopecia
The genetic basis of alopecia areata: HLA associations with patchy alopecia areata versus alopecia totalis and alopecia universalis.

Colombe BW, Lou CD, Price VH.

Thomas Jefferson University Department of Medicine and Hospital, Philadelphia, Pennsylvania 19107, USA. Beth.Colombe mail.tju.edu

Many diseases, notably those having a strong autoimmune component, have been shown to have an association with specific human leukocyte antigens (HLA). The molecular basis for this genetic association with disease is the fact that HLA bind and present peptides derived from self and foreign protein antigens to the immune system for recognition and activation of the immune response. Previous studies with heterogeneous groups of alopecia areata (AA) patients have suggested associations with some HLA class I and class II antigens. For this study we selected only patients with long-standing disease and stratified them into two groups by strict definitions of duration and extent of disease: those with patchy AA and those with either alopecia totalis (AT) or alopecia universalis (AU). The patients were tissue typed for HLA class II antigens by biomolecular methods that provided antigen discrimination at an allele level. More than 80% of all of the AA patients typed were positive for the antigen DQB1*03 (DQ3), suggesting that this antigen is a marker for general susceptibility to AA. In addition, two other antigens were found significantly increased in frequency only in the group of AT/AU patients, DRB1*0401 (DR4) and DQB1*0301(DQ7). This strongly suggests that the two clinical types of AA, namely patchy AA versus AT/AU, can be distinguished by a genetically based predisposition to extent of disease.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10674369&dopt=Abstract alopecia, hair loss