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Protection against chemotherapy-induced alopecia by cyclosporin A in the newborn rat animal model.

BACKGROUND: We have previously shown that several agents will protect against chemotherapy-induced alopecia in the newborn rat animal model. Such protective agents render the hair follicle keratinocytes resistant to chemotherapy possibly by the expression of P-glycoprotein (Pgp). Cyclosporin A (CSA) is a potent inhibitor of Pgp. METHODS AND RESULTS: Efficacy of CSA was tested in its effects on chemotherapy-induced alopecia in the newborn rat animal model. CSA, when applied topically, protected rats from local alopecia induced by various agents. CONCLUSION: The mechanism of protection by CSA and its relationship to Pgp remain uncertain. The potential clinical applicability of this observation remains to be determined.

Administration, Cutaneous↗

Changes in populations of HLA-DR+CD3+ cells and CD57-CD16+ cells in alopecia areata after corticosteroid therapy.

We investigated the populations of activated T (HLA-DR+CD3+) cells and natural killer (CD57-CD16+) cells in the peripheral blood of patients with various types of alopecia areata (AA) and noted any changes that occurred in the said populations after administration of local and systemic corticosteroid therapy. In type 2 (severe multiple AA and alopecia totalis) and type 3 (alopecia universalis), the mean percentages of HLA-DR+CD3+ cells and CD57-CD16+ cells were significantly higher when compared with those of the normal controls. The percentages of both subsets in type 1 (mild AA) and the normal controls were consistent. Twenty-four patients in types 2 and 3 had received corticosteroid treatment, and all patients experienced new hair growth. With the changes in disease activity, the populations of HLA-DR+CD3+ cells in these patients after corticosteroid therapy significantly decreased when compared with those recorded prior to treatment. Subsequent to treatment, the mean percentages of CD57-CD16+ cells decreased to levels that were not significant relative to that of the normal controls. These findings indicate that HLA-DR+CD3+ and CD57-CD16+ cells in the peripheral blood of patients with AA may be correlated with the disease activity of AA.

Adult↗

Alopecia areata and interleukin-2 receptor.

Interleukin-2 (IL-2) is a lymphokine produced by activated T cells and its receptor (IL-2R) is expressed on T cells; one of the IL-2R components can be measured as a soluble serum protein (sIL-2R). Levels of sIL-2R were measured as a sign of T cell activation in serum of 12 patients suffering from alopecia areata (totalis or universalis) and in a group of healthy control subjects. An enzyme-linked immunosorbent assay was used to determine the levels of sIL-2R in blood samples drawn during both the active and resting phase of the disease. In patients with alopecia areata in active phase the sIL-2R concentrations were significantly higher than in stable phase and in controls. The biologic role of sIL-2R is still unknown, but one could speculate that T lymphocyte activation with subsequent secretion of IL-2 and IL-2R expression may contribute to the immune inflammatory mechanism of alopecia areata.

Adolescent↗

Topical minoxidil in extensive alopecia areata, including 3-year follow-up.

Perhaps the most intriguing aspect of topical minoxidil is the fact that this drug can promote hair growth in two unrelated conditions: alopecia areata (AA) and androgenetic alopecia. The two conditions have quite different underlying mechanisms. In AA, hair follicles respond to some signal or cell injury by entering a state of aborted cyclical activity; this state can reverse itself spontaneously, or it can be temporarily circumvented with nonspecific immunomodulating agents. In androgenetic alopecia, genetically marked hair follicles undergo progressive, androgen-mediated miniaturization; antiandrogens have been conventionally sought to intercept this process. It is not known how minoxidil promotes hair growth except that living follicles capable of stimulation and hypertrophy are required. It may be that minoxidil influences some fundamental signal to the follicular apparatus, irrespective of the pathophysiology involved. We have used topical minoxidil solution in 90 patients, aged 7-63 years, with extensive AA affecting 25-100% of the scalp. One study was double-blind, and placebo-controlled for an entire year. Minoxidil-treated patients responded better than placebo-treated patients. Both 3 and 5% topical minoxidil solutions have been used, and treatment with the 3% solution has continued for up to 3 years. The results of these studies will be discussed. While topical minoxidil is not very effective for those with 100% scalp hair loss, it is an effective, easy and safe treatment for those with AA affecting 25-99% of the scalp.

Administration, Cutaneous↗

Increased number of OKT6-positive dendritic cells in the hair follicles of patients with alopecia areata.

In 6 patients with untreated alopecia areata in the progressive stage, 6 in the stationary stage, and 6 normal individuals as controls, an in situ analysis of OKT6-positive dendritic cells in hair follicles, and peribulbar and intrabulbar infiltrates was performed using the avidin-biotin-peroxidase method with monoclonal antibodies. In controls, OKT6-positive dendritic cells were distributed only in the upper portions of hair follicles and were not observed in the bulbar area, and the percentage of these cells among all epithelial cells of the hair follicles was 1.0 +/- 0.1% (mean +/- SE). In stationary-stage patients, the distribution and the percentage of positive cells were the same as those for the controls (1.1 +/- 0.1%). In the progressive stage, however, positive cells were distributed in both the upper portions of the hair follicles and the bulbar area, and the percentage of positive cells (4.9 +/- 0.3%) was significantly higher than that of controls. Staining for T, B lymphocytes and T cell subsets in the peribulbar infiltrates revealed a predominance of OKT4-positive cells (the OKT4/OKT8 ratio was from 3:1 to 4:1). This indicates that the number of OKT6-positive dendritic cells increases in the hair follicles of progressive alopecia areata and that these cells may play an important role in cooperation with T cells in the pathogenesis of alopecia areata.

Alopecia Areata↗

Alopecia areata: a clinical study.

100 cases of alopecia areata are examined and the possible relationship with the presumed etiological factors (atopy, autoimmunity and psychosomatics) are looked for. When atopy or autoantibodies are present alopecia areata always runs a serve course. It is, however, impossible to establish a definite etiological relation between atopy or autoimmunity and alopecia areata.

Adolescent↗

Autoimmune hair loss (alopecia areata) transferred by T lymphocytes to human scalp explants on SCID mice.

Alopecia areata is a tissue-restricted autoimmune disease of the hair follicle, which results in hair loss and baldness. It is often psychologically devastating. The role of T lymphocytes in this disorder was investigated with cell transfer experiments. Scalp explants from patients were transplanted to severe combined immunodeficiency (SCID) mice and injected with autologous T lymphocytes isolated from involved scalp. T lymphocytes which had been cultured with hair follicle homogenate along with antigen-presenting cells were capable of inducing the changes of alopecia areata, including hair loss and perifollicular infiltrates of T cells, along with HLA-DR and ICAM-1 expression of the follicular epithelium. Similar changes were not noted in grafts injected with scalp-derived T cells that had not been cultured with follicular homogenate. These data indicate that alopecia areata is mediated by T cells which recognize a follicular autoantigen.

Adult↗

A comparative study of a new food supplement, ViviScal, with fish extract for the treatment of hereditary androgenic alopecia in young males.

A controlled, randomized, double-blind, parallel-group study compared the effects of ViviScal (a new food supplement incorporating special marine extracts and a silica compound) with those of a fish extract in the treatment of young males with hereditary androgenic alopecia. The pretreatment histological diagnosis was alopecia with a mild to moderate perifollicular inflammation zone. The study consisted of 20 subjects who received two tablets of ViviScal once daily and 20 who received two tablets of fish extract once daily for 6 months. The mean patient age and mean duration and severity of baldness compared well between the two groups. Most patients had been treated with long-term topical 2% minoxidil for 1 year or more prior to the study. At baseline and after 6 months' treatment, a biopsy was taken for histological examination. A non-vellus hair count was performed at baseline and after 2, 4 and 6 months. In the fish extract treatment group three patients withdrew from the study before the fourth month due to lack of therapeutic effect. After 6 months' treatment, patients receiving ViviScal showed a mean increase in non-vellus hair of 38% compared with a 2% increase in the fish extract treatment group (P < 0.0001). In the ViviScal group, 19 (95%) subjects showed both clinical and histological cure, whereas none treated with fish extract showed any clinical or histological difference after 6 months' treatment (P < 0.0001). In both groups, a minimal decrease in the erythemal index was observed. In conclusion, ViviScal appears to be the first highly active treatment for androgenic alopecia in young males.

Administration, Oral↗

Congenital anemia, dyskeratosis, and progressive alopecia in Polled Hereford calves.

A new syndrome of anemia, alopecia, and dyskeratosis was identified in Polled Hereford calves in this study. Cutaneous changes included hyperkeratosis and hair loss around the muzzle and ear margins, which progressed to a generalized alopecia and hyperkeratotic dermatitis. Histologically, orthokeratotic hyperkeratosis with dyskeratosis of epidermal and follicular keratinocytes was present. Alopecia was correlated with dyskeratosis of Huxley's layer and an increasing proportion of follicles in the telogen phase of the hair cycle. Dermatitis was characterized by a mild dermal mononuclear cell infiltrate and mild lymphocytic perivascular dermatitis. The anemia present at birth was nonprogressive and was classified as normochromic and normocytic to macrocytic. Reticulocytosis was absent, but bone marrow was markedly hyperplastic. Nuclear cytoplasmic asynchrony of the rubricyte and metarubricyte stages occurred in the bone marrow. Abnormal rubricyte nuclei and maturation arrest at the late rubricyte stage were common. Cytologic features of the erythroid series are similar to those of type I congenital dyserythropoietic anemia of human beings. Genealogic features suggest that this is a primary hereditary defect. The mode of inheritance, however, remains to be determined.

Alopecia↗

Complete remission of alopecia universalis after allogeneic hematopoietic stem cell transplantation.

This case report is on a 40-year-old male patient with chronic myeloid leukemia (CML) receiving an allogeneic hematopoietic stem cell transplantation (HSCT) in first chronic phase from an HLA-identical sibling brother. He suffered from alopecia universalis occurring 11 years previously. The alopecia involved all body hair, including eyebrows and eyelashes. Between day 40 and day 55 after transplantation, hair started to grow on the chin, eyelashes, and on the top of his head. Immunosuppression was stopped at 6 months because of cytogenetic relapse and incomplete donor chimerism with some renewed hair loss. He returned to full donor chimerism with mild chronic graft-versus-host disease and continued hair growth. With 2 years of follow-up he has remained in continuous remission. Chimerism analyses of hair follicles did not show any donor alleles. Alopecia universalis is probably a chronic autoimmune disorder, curable with replacement of the immune system with an allogeneic HSCT.

Adult↗

Anti-alopecia effect of Gly-Leu-Phe, an immunostimulating peptide derived from alpha-lactalbumin.

Gly-Leu-Phe (GLF), an immunostimulating peptide derived from alpha-lactalbumin, prevented alopecia induced by an anticancer agent etoposide in a neonatal rat model after intraperitoneal injection at a dose of 100 mg/kg for 4 d or oral administration at a dose of 300 mg/kg for 6 d. By microscopic analysis of skin sections, GLF proved to inhibit etoposide-induced loss of hair, thickening of the epidermis, and thinning of the adipocyte layer. The anti-alopecia effect of GLF was inhibited by pyrilamine, a histamine H1 receptor antagonist, suggesting that the anti-alopecia effect is mediated by histamine release.

Adjuvants, Immunologic↗

Postpartum alopecia.

OBJECTIVE: To determine whether there are effective treatments for postpartum alopecia. DATA SOURCES: Clinical literature identified through MEDLINE (January 1966-May 2000), EMBASE (June 1980-March 2000), and International Pharmaceutical Abstracts (January 1970-March 2000). Key search terms included alopecia, puerperium, and postpartum. DATA SYNTHESIS: Postpartum alopecia is a diffuse shedding of scalp hair that can begin two to five months following parturition. Few articles examine the treatment of this condition. Treatments in the form of thyroid supplementation, topical progesterone and estradiol lotions, and an oral contraceptive have been studied. All available studies on this subject have significant limitations, such as small sample size, absence of a control group, or subjective measurement of treatment response. Nondrug therapy for a related type of hair loss has been recommended and includes education about hair cycles and reassurance to minimize anxiety. CONCLUSIONS: From the available studies, no specific treatment has been studied well enough with sufficient treatment justify recommendation or to be termed effective.

Adult↗

Investigational medications in the treatment of alopecia.

Androgenetic alopecia (hereditary thinning) is the most common cause of hair loss in both men and women. Chemotherapy-induced alopecia is another distressing cause of hair loss. With a better understanding of follicular biology and the signals responsible for hair growth and regression, targeted therapies for hair loss are being investigated. This review summarises investigational medications for androgenetic and chemotherapy-induced alopecia that are in preclinical stages or later.

Alopecia↗

The trichogram as a prognostic tool in alopecia areata.

The value of the trichogram as a prognostic tool in alopecia areata was investigated in 93 patients with not more than three lesions on the scalp. Evaluation of the clinical features was one year later. In each patient, two regions were investigated: the margin of one of the lesions and the control region. In 80% of the patients with a normal trichogram at the margin of the lesional hair at the first visit, hair growth was restored one year later, whereas in those with an abnormal trichogram, hair growth was restored in 62.5%. In 11.5% of the patients an alopecia totalis or universalis developed. At the margin of the lesion, no significant association was observed between the trichogram and the clinical features. In the control region, however, the prognosis was much better (p < 0.001) in patients with a normal trichogram than in those with an abnormal trichogram. Out of the 62 patients with a normal trichogram, hair growth was restored in 53 (85%), whereas out of the 31 patients with an abnormal trichogram hair growth was restored in only 6 (19%). These findings indicate that a normal trichogram in the control region is a valuable prognostic tool in alopecia areata.

Adolescent↗

E-selectin and interleukin-2 receptor alpha-chain expression in alopecia universalis.

A study of the histopathological abnormalities in a case of alopecia universalis was accompanied by immunohistochemical analysis of the expression of intercellular adhesion molecule-1 (ICAM-1) and E-selectin (formerly known as endothelial leukocyte adhesion molecule-1) within the skin. ICAM-1 expression on follicular epithelium co-localized with intraepithelial mononuclear cells (MNC) positive for the interleukin-2 receptor alpha-chain (IL-2R) or HLA-DR. Aberrant expression of E-selectin was observed on dermal endothelium. Although restricted to one case, these new observations concerning the expression of E-selectin and IL-2R in alopecia universalis are consistent with the view that extravascular trafficking of MNC into follicular epithelium may play a key role in the pathogenesis of alopecia universalis and that use of agents that interfere with this process may be an effective therapeutic strategy.

Adult↗

Growth factor mRNA levels in alopecia areata before and after treatment with the contact allergen diphenylcyclopropenone.

The early immune response in alopecia areata is characterized by a Th1 T helper cell cytokine pattern and an aberrant expression of ICAM-1 and HLA-DR molecules on lesional hair bulbs. A counteracting cytokine pattern induced by a therapeutic contact dermatitis is supposed to mediate the hair regrowth. In addition to cytokines, growth factors have been shown to influence immune responses, and we therefore investigated the expression levels for a panel of growth factors in untreated versus alopecia areata after treatment with the contact sensitizer diphenylcyclopropenone. Using semiquantitative reverse transcriptase polymerase chain reaction we detected a striking overexpression of transforming growth factor beta 1 mRNA in successfully treated patients. This cytokine has been shown to be a potent immune response modifier, which can suppress Th1 immune responses. The way in which topical immunotherapy induces hair regrowth in alopecia areata is unknown, but a lesional increased expression of transforming growth factor beta 1 may be a possible mechanism.

Administration, Topical↗

A case of alopecia universalis without the involvement of scalp hairs.

A case of alopecia universalis in a 45-year-old male was reported. The hair loss initiated on the eyebrows and progressed to the whole body, but the scalp hairs were well preserved. Histopathologic features of eyebrows were compatible findings with alopecia areata. This is a unique case of alopecia universalis without any involvement of scalp hairs.

Alopecia↗

The effects of clomipramine hydrochloride in cats with psychogenic alopecia: a prospective study.

A double-blind, placebo-controlled clinical trial was conducted to determine the efficacy of clomipramine hydrochloride in cats with psychogenic alopecia. Twenty-five cats were randomly assigned to receive clomipramine hydrochloride (0.5 mg/kg orally q 24 hours) or placebo for 56 days. Eleven cats in each group completed the trial. The results of this study showed that clomipramine hydrochloride failed to demonstrate significant changes in the number of grooming bouts, hair regrowth, and the area of alopecia in cats with psychogenic alopecia when compared to a placebo. It was uncertain whether these results reflected a lack of drug efficacy, insufficient treatment duration, or an insufficient number of cases enrolled.

Alopecia↗