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PubMed2000

Role of androgens in female-pattern androgenetic alopecia, either alone or associated with other symptoms of hyperandrogenism.

The roles of androgen hypersecretion, in situ enzyme activity, and androgen receptors in androgenetic alopecia in women are still a matter of debate. We studied 187 women with alopecia, which we graded I, II, or III, according to Ludwig's classification, and 21 healthy control women. All participants were subjected to full basal and 1 h post-beta-1-24 corticotropin stimulation endocrine profiles. Abnormal hormone profiles were observed in 67% of the patients with alopecia alone (group A, n = 110) and in 84% of the patients with alopecia plus other symptoms of hyperandrogenism including acne, hirsutism, and menstrual cycle disturbances (group B, n = 77). Mean serum 5alpha-androstane-3alpha,17beta-diol glucuronide (3alpha-AdiolG) levels in all three patient groups (6.50+/-4.10, 8.90+/-5.80, and 14.70+/-8.90 nmol/l, respectively) correlated with the grade of alopecia (I-III) and were significantly higher than in the control group (4.80+/-2.05 nmol/l, P < 0.005). Mean serum sex hormone-binding globulin (SHBG) levels were inversely correlated with the grade of alopecia (I-III) and were significantly lower in all three patient groups (50.55+/-23.50, 40.00+/-17.65, and 38.80+/-14.10 nmol/l, respectively) than in the control group (61.15+/-17.65 nmol/l, P < 0.05). Mean serum levels of delta4-androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and 3alpha-AdiolG were higher in group B than in group A, and higher in group A than in the control group. The significant correlations found between adrenal secretion - either positive (with 3alpha-AdiolG levels and the body mass index) or negative (with SHBG levels) - might reflect the important contribution of secretory and metabolic components in the development of alopecia, the severity of which has been shown to be very closely related to observed levels of two of these parameters (3alpha-AdiolG and SHBG).

Adolescent↗
PubMed2005

Primary cicatricial alopecia: histopathologic findings do not distinguish clinical variants.

BACKGROUND: Primary cicatricial alopecias encompass a group of disorders characterized by permanent destruction of the hair follicle. The varied clinical features and differences in terminology have led to difficulties in defining consistent clinicopathologic correlation. OBJECTIVE: We sought clinicopathologic correlation of 6 clinically distinct primary cicatricial alopecias: lichen planopilaris, frontal fibrosing alopecia, pseudopelade (Brocq), central centrifugal alopecia, folliculitis decalvans, and tufted folliculitis. METHODS: We conducted prospective and blinded histopathologic evaluation of clinically typical primary cicatricial alopecias. Biopsy specimens were taken from early affected scalp lesions and paired with samples from clinically unaffected areas in the same patient. RESULTS: The lymphocytic and neutrophilic groups were readily distinguished histologically. However, within the two groups clinically distinct primary cicatricial alopecias could not be distinguished with current histopathologic techniques. CONCLUSION: A descriptive, standardized histopathologic reporting of follicular architecture, type, location, and extent of the inflammatory infiltrate, and presence or absence of sebaceous glands, may be of greatest value in guiding the treatment of patients with primary cicatricial alopecias.

Adult↗
PubMed2006

[Hair darkening close to a patch of frontal fibrosing alopecia].

BACKGROUND: Fibrosing frontal alopecia is scarring form alopecia and is most often seen in menopausal women. It is currently considered as an anatomoclinical form of lichen planopilaris of selective topography. We report a case of hair repigmentation during the course of post-menopausal frontal fibrosing alopecia. CASE REPORT: A 78-year-old woman developed alopecia of the scalp and eyebrows in 1997. Her eyebrows had been white for some ten years. In 1999, she noted repigmentation of a strip of hair at the edge of her scalp, but the rest of her hair remained white. The patient had not been taking any long-term drugs or any hair treatment. Histological examination of the regions of alopecia revealed lesions of lichenoid appearance at the junction with erosion by lymphocytes and keratinocytic necroses of the lower layers of the epidermis. Direct cutaneous immunofluorescence testing was negative. A diagnosis of post-menopausal fibrosing frontal alopecia was made on the basis of the clinical and laboratory evidence. DISCUSSION: 96 cases of post-menopausal fibrosing frontal alopecia have so far been reported in the literature, but to our knowledge, this is the first case combined with or inducing hair repigmentation. The other cases of repigmentation were eliminated by history-taking, and clinical or laboratory examinations. The mechanism of hair repigmentation in our patient could have been the result of a post-inflammatory process.

Aged↗
PubMed2000

Elastic tissue in scars and alopecia.

A recent report suggests that elastic fibers appear in scars in a time-dependent fashion. This observation prompted our investigation, because we have found elastic tissue stains helpful in determining the pattern of scarring in cases of permanent alopecia. We carried out this investigation to determine if the Verhoeff-Van Gieson (VVG) elastic stain can reliably differentiate scarred from non-scarred dermis and to test our hypothesis that elastic stained sections are helpful in distinguishing lichen planopilaris (LPP) from lupus erythematosus (LE), central progressive alopecia in black females ("follicular degeneration syndrome" and "hot comb alopecia" are other terms used to describe this condition) and classic ivory white idiopathic pseudopelade. We studied histological sections from surgical scars of known duration, stained with the VVG elastic stain and VVG-stained sections of scalp biopsies from patients with established lesions of permanent alopecia. In most cases, both vertical and transverse sections were examined. In every case, the VVG stain clearly differentiated scar from the normal surrounding dermis. Distinct patterns of elastic tissue allowed for correct classification in most of the well-established cases of permanent alopecia studied. We determined that the Verhoeff-Van Gieson stain is an excellent stain to evaluate the pattern of scarring in cases of permanent alopecia and elastic tissue stains may be helpful in the histological evaluation of alopecia.

Alopecia↗
PubMed2001

A new strategy for modulating chemotherapy-induced alopecia, using PTH/PTHrP receptor agonist and antagonist.

Parathyroid hormone (PTH) related peptide (PTHrP) and the PTH/PTHrP receptor (PTH/PTHrP-R) show prominent cutaneous expression, where this signaling system may exert important paracrine and/or autocrine functions, such as in hair growth control. Chemotherapy-induced alopecia - one of the fundamental unsolved problems of clinical oncology - is driven in part by defined abnormalities in hair follicle cycling. We have therefore explored the therapeutic potential of a PTH/PTHrP-R agonist and two PTH/PTHrP-R antagonists in a mouse model of cyclophosphamide-induced alopecia. Intraperitoneal administration of the agonist PTH(1-34) or the antagonists PTH(7-34) and PTHrP(7-34) significantly altered the follicular response to cyclophosphamide in vivo. PTH(7-34) and PTHrP(7-34) shifted it towards a mild form of "dystrophic anagen", associated with a significant reduction in apoptotic (TUNEL+) hair bulb cells, thus mitigating the degree of follicle damage and retarding the onset of cyclophosphamide-induced alopecia. PTH(1-34), in contrast, forced hair follicles into "dystrophic catagen", associated with enhanced intrafollicular apoptosis. We had previously shown that an induced shift in the follicular damage-response towards "dystrophic catagen" mitigates cyclophosphamide-induced alopecia, whereas a shift towards "dystrophic catagen" initially enhanced the hair loss, yet subsequently promoted accelerated hair follicle recovery. Therefore, this study in an established animal model of chemotherapy-induced alopecia, which closely mimics human chemotherapy-induced alopecia, strongly encourages the exploration of PTH/PTHrP-R agonists and antagonists as novel therapeutic agents in chemotherapy-induced alopecia.

Alopecia↗
PubMed2002

Epidemiology and genetics of alopecia areata.

The frequency of alopecia areata and observed patterns of heritability are in keeping with a polygenic inheritance model but the genetics of alopecia areata is still poorly understood. The role of environmental factors in triggering disease initiation or exacerbation remains almost entirely speculative. Using the candidate gene approach, three susceptibility/severity factors have been identified. HLA alleles were the first to show a strong association with alopecia areata and some DQB and DR alleles have been demonstrated to confer a high risk for disease by both case-control and family-based studies. Interleukin (IL)-1 cluster genes, mainly the IL-1 receptor antagonist, show a strong association with disease severity in alopecia areata and a number of other autoimmune and inflammatory diseases. Finally, the association of alopecia areata with Down's syndrome, the high frequency of alopecia areata in autoimmune polyglandular syndrome type I due to mutations of the autoimmune regulator (AIRE) gene on chromosome 21q22.3 and the finding of association with MX1, another gene in the Down's syndrome region of chromosome 21 indicate this area of the genome as a promising target for future-family based investigations. The role of individual genes of the MHC, IL-1 cluster or chromosome 21q22.3 is difficult to establish and further genetic and functional investigations are needed to confirm their involvement in the pathogenesis of alopecia areata.

Alopecia Areata↗
PubMed2000

Treatment with an anti-CD44v10-specific antibody inhibits the onset of alopecia areata in C3H/HeJ mice.

A murine CD44v10-neutralizing antibody has been reported to impair delayed-type hypersensitivity reactions. Because alopecia areata is characterized by a delayed-type hypersensitivity-like T cell mediated immune response, we addressed the question whether an anti-CD44v10-antibody influences the onset of alopecia areata. Therefore, we used the C3H/HeJ mouse model with the induction of alopecia areata in unaffected mice by the grafting of lesional alopecia areata mouse skin. Six grafted mice were injected (intraperitoneally) with anti-CD44v10, six grafted mice with anti-CD44standard, and six with phosphate-buffered saline only. After 11 wk phosphate-buffered saline injected animals on average had developed alopecia areata on 36.8% of their body. The onset of hair loss was slightly delayed and its extent reduced to 17.2% of their body in anti-CD44standard-treated mice. By contrast, five of six anti-CD44v10-treated mice did not show any hair loss and one mouse developed alopecia areata on only 1% of the body. Immunohistochemical examination revealed a marked reduction of perifollicular CD8+ lymphocytes and, to a lesser degree, CD4+ cells as well as a decreased expression of major histocompatibility complex class I on hair follicle epithelium in anti-CD44v10-treated mice as compared with phosphate-buffered saline or anti-CD44 standard-treated mice. Our data show that anti-CD44v10 is able to inhibit the onset of alopecia areata in C3H/HeJ mice. This might be accomplished by an anti-CD44v10-triggered impairment of immune cell homing (e.g., CD8+ T cells), resulting in a decrease of their number in target tissues.

Alopecia Areata↗
PubMed2003

Major locus on mouse chromosome 17 and minor locus on chromosome 9 are linked with alopecia areata in C3H/HeJ mice.

Alopecia areata is an autoimmune disease that targets actively growing (anagen) hair follicles in humans, mice, rats, dogs, horses, and cattle. C3H/HeJ mice spontaneously develop alopecia areata from 5 mo of age and older in females and later in males. Frequency of disease approached 20% in a colony by 18 mo of age. C57BL/6J mice do not develop alopecia areata. A segregating F2 population of female mice (n=1096) was generated from crossing these two strains. Alopecia areata (n=138) and clinically normal (n=214) mice were genotyped at 12 mo of age using 211 microsatellite probes. The peak logarithm of odds ratio score on mouse chromosome 17 (10.9) was around marker D17Mit134 at 16.9 cM from the centromere. The mouse histocompatibility locus, H2, the mouse equivalent of human leukocyte antigen in humans, was a likely candidate. Twelve-month-old C3H.SW-H2b/SnJ mice (C3H/HeJ congenic mice in which the H2k purported susceptibility locus was replaced with the H2b purported resistance locus) did not develop alopecia areata, supporting this locus as being important in alopecia areata. A suggestive linkage was also found on mouse Chromosome 9 (logarithm of odds ratio score 2.0) around D9Mit206, 20 cM from the centromere. The interval on mouse Chromosome 17 contains several orthologous genes potentially associated with human alopecia areata.

Alopecia Areata↗
PubMed1993

Chemotherapy-induced alopecia: new developments.

Alopecia (hair loss) is one of the most physically and psychologically distressing side effects of cancer chemotherapeutic drugs. Since its first recognition as a common outcome to most chemotherapeutic agents, only a few trials have been reported, using either a method to temporarily reduce the scalp blood flow (scalp tourniquet or hypothermia) or vitamin E, with undocumented and variable efficacy. The lack of progress in the treatment and prevention of chemotherapy-induced alopecia is in part due to the lack of a reproducible animal model. In the past 2 years, we reported on the following observations: (1) treatment of 8-day-old rats with vidarabine (ara-C), doxorubicin, and cyclophosphamide consistently produced either total body alopecia (ara-C and cyclophosphamide) or alopecia confined to the head and proximal part of the back (doxorubicin); (2) Imuvert, a biologic response modifier derived from the bacterium Serratia marcescens, uniformly produced complete protection against alopecia induced by ara-C and doxorubicin but not that produced by cyclophosphamide; (3) the protective effect of Imuvert against chemotherapy-induced alopecia is mediated by a monocyte-mediated cytokine; and (4) this monocyte-derived cytokine is, possibly, interleukin-1. These observations constitute important progress in the understanding and prevention of chemotherapy-induced alopecia.

Alopecia↗
PubMed2005

Association between alopecia and response to chemotherapy in patients with Hodgkin lymphoma.

Alopecia and bone marrow suppression are prominent effects of doxorubicin-containing chemotherapy. The aim of the study was to validate our preliminary clinical observation that the lack of alopecia in Hodgkin lymphoma patients may predict poor response to chemotherapy and low rate of bone marrow suppression. Sixty-six patients with Hodgkin lymphoma were reviewed. They were treated between 1991 and 2001 with at least 4 courses of doxorubicin-containing chemotherapy (MOPP/ABV or ABVD) in 2 university-affiliated hematology departments. Thirty-four patients exhibited complete or near complete alopecia, and 32 retained their hair or had only minimal hair loss. The 2 groups were compared by response to treatment and episodes of bone marrow suppression. Alopecia was associated with a high rate of remission (OR 8.48, 95% CI 2.77-25.95), episodes of neutropenia (OR 3.55, 95% CI 1.28-9.84), leukopenia (OR 1.83, 95% CI 0.68-4.92), delays in scheduled treatments (OR 1.61, 95% CI 0.607-4.30), or number of courses with dose reduction (OR 1.63, 95% CI 0.56-4.74). Significantly more patients with alopecia had at least 1 of these parameters (88% versus 62%, P=0.015; OR 4.50, 95% CI 1.27-15.94). In conclusion, in patients with Hodgkin lymphoma treated with doxorubicin-containing chemotherapy, the absence of alopecia may predict poor response to treatment along with fewer episodes of bone marrow suppression. The absence of alopecia in such patients should alert clinicians to the possibility of treatment failure.

Adult↗
PubMed1994

Antibodies to hair follicles in alopecia areata.

Although alopecia areata is suspected to be an autoimmune disease, no direct evidence of an altered immune response to components of the hair follicle has been reported. We studied whether antibodies to normal human anagen scalp hair follicles are present in individuals with alopecia areata. Thirty-nine alopecia areata sera and 27 control sera were tested by Western immunoblotting for antibodies to 6 M urea-extractable proteins of normal anagen scalp hair follicles. At serum diluted 1:80, all alopecia areata subjects (100%), but only 44% of control individuals, had antibodies directed to one or more antigens of approximately 57, 52, 50, 47, or 44 kD. The incidence of antibodies to individual hair follicle antigens in alopecia areata was up to seven times more frequent than in control sera and their level up to 13 times greater and was statistically significant for all five antigens. Tissue specificity analysis indicated that these antigens were selectively expressed in hair follicles. These findings indicate that individuals with alopecia areata have abnormal antibodies directed to hair follicle antigens, and support the hypothesis that alopecia areata is an autoimmune disease.

Adolescent↗
PubMed1996

Clinical-epidemiologic study of alopecia areata.

BACKGROUND: Alopecia areata is a common disease and may be associated with autoimmune disease, atopy, Down syndrome, emotional stress, and foci of sepsis. METHODS: Seven cases of alopecia areata were diagnosed among workers in the Water and Effluent Treatment Sector (WETS) of a paper factory, representing a 0.6% incidence, when the value for the population at large is 0.1%. Three of these workers are assigned to the WETS on a permanent basis and four provide maintenance services. One of the latter patients had alopecia areata that fully regressed. Because biologic treatment of water and effluents involves saprophytic bacteria and fungi as well as chemical substances such as acrylamide, a clinical examination and laboratory tests were performed on all workers assigned permanently to the WETS (N = 9) and on 25% of the workers, selected at random providing services to the sector (N = 14). RESULTS: There was no association between alopecia areata and atopy, dermatophytosis, or bacteria isolated. Toxicologic evaluation revealed an acrylamide-like substance in 7 workers with alopecia areata, with a statistically significant correlation. Measures were taken at the workplace to decrease worker contact with the mists (probably containing acrylamide) in the pulp-pressing room; no other cases of alopecia areata had been detected 1 year after the study. CONCLUSIONS: A survey of the literature did not show reports of alopecia areata as an occupational dermatosis, but our conclusion is, that this dermatosis could be due to the professional activities of the workers at the paper factory studied.

Adult↗
PubMed2004

Medical and surgical therapies for alopecias in black women.

Hair loss is a common problem that challenges the patient and clinician with a host of cosmetic, psychological and medical issues. Alopecia occurs in both men and women, and in all racial and ethnic populations, but the etiology varies considerably from group to group. In black women, many forms of alopecia are associated with hair-care practices (e.g., traction alopecia, trichorrhexis nodosa, and central centrifugal cicatricial alopecia). The use of thermal or chemical hair straightening, and hair braiding or weaving are examples of styling techniques that place African American women at high risk for various "traumatic" alopecias. Although the exact cause of these alopecias is unknown, a multifactorial etiology including both genetic and environmental factors is suspected. A careful history and physical examination, together with an acute sensitivity to the patient's perceptions (e.g., self-esteem and social problems), are critical in determining the best therapy course. Therapeutic options for these patients range from alteration of current hair grooming practices or products, to use of specific medical treatments, to hair replacement surgery. Since early intervention is often a key to preventing irreversible alopecia, the purpose of the present article is to educate the dermatologist on all aspects of therapy for hair loss in black women--including not only a discussion of the main medical and surgical therapies but also an overview of ethnic hair cosmetics, specific suggestions for alterations of hair-care practices, and recommendations for patient education and compliance.

Adrenal Cortex Hormones↗
PubMed1988

Proliferation of eccrine sweat ducts associated with alopecia areata.

Proliferation of sweat ducts has been described as a reactive process in a variety of benign and malignant neoplasms and inflammatory conditions in the skin, including scarring alopecia. However, to our knowledge this phenomenon has not been observed in non-scarring alopecia. The following case documents such a proliferation arising in an alopecia consistent with alopecia areata. An 83-year-old female developed progressive, fairly well circumscribed patches of alopecia over a 2-3 year period. Unequivocal scarring was not present. Histopathological examination revealed non-scarring alopecia with miniaturized and telogen follicles and a proliferation of eccrine ductal structures in the reticular dermis. These ductal structures varied in size and degree of cystic dilatation and resembled a primary eccrine neoplasm, such as syringoma. Only minimal focal fibrosis was observed in association with the eccrine proliferation. In summary, this case indicates that eccrine sweat duct proliferation may occur in non-scarring alopecia and must be differentiated from a primary eccrine neoplasm.

Aged↗
PubMed1987

Human leukocyte antigen region involvement in the genetic predisposition to alopecia areata.

Human leukocyte antigens (HLA) of classes I and II were studied in 127 patients with alopecia areata (AA). The patients were subdivided into different groups depending on hair loss area, sex, pathogenesis, response to topical immune modulators (squaric acid dibutylester and diphencyprone) and age of onset of the disease. The frequencies of class I HLA markers (loci A, B, C) were not significantly different from the controls. However, among the class II antigens (loci DR, DQ), the frequency of DR5 was increased in both alopecia areata and alopecia universalis when compared with the control group. In particular, DR5 was strongly linked to the early-onset form. The highest DR5 frequency (62%) was found in the group of patients which presented both the early onset and the most severe form of the disease (p less than 0.01; RR = 3.14). A decrease of the HLA-B8 phenotype frequency was found in the alopecia areata group versus the alopecia universalis one. No significant deviation was found between the female patients and the control group. However, an increase of CW3 and a decrease of DR1 was seen in the males. In the group including 'combined', 'prehypertensive', 'atopic' alopecia of Ikeda's classification the frequency of HLA-A28 and DR5 was increased and that of DR1 was decreased in comparison with the 'common' type of alopecia and the controls. It was not possible to find any relationship between these genetic markers and the response to topical immune modulators.

Adolescent↗
PubMedDate not supplied

Alopecia areata. Pathogenesis, diagnosis, and therapy.

Alopecia areata is a common form of non-scarring alopecia that appears equally in males and females of any age, although children and adolescents are more commonly affected. The disorder is usually characterized by limited alopecic patches on the scalp, but more severe forms may affect the entire scalp (alopecia totalis) or body (alopecia universalis). Characteristic nail changes may also accompany hair loss. Alopecia areata has been linked with certain human leukocyte antigen (HLA) class II alleles, indicating a probable autoimmune etiology. Current research implicates T lymphocytes in the pathogenetic mechanism of disease. Other autoimmune diseases are also linked with alopecia areata. The diagnosis of alopecia areata is usually made clinically, although a biopsy is diagnostic for this condition. Treatment is challenging and aims at the regrowth of hair in affected individuals. Intralesional corticosteroid injections are widely used in mild disease. Topical anthralin and minoxidil may also be clinically efficacious. Topical sensitizers, such as squaric acid dibutlyester and diphenyl-cyclopropenone, are sometimes employed. Various therapies for the disease may have efficacy in different patients, making a universal treatment algorithm difficult to implement. Patients should be handled on an individual basis, with the final outcome based on the cosmetic regrowth of hair. Maintenance therapy is also important in patients that do achieve acceptable regrowth, necessitating a highly motivated patient and good rapport with the treating physician.

Alopecia Areata↗
PubMed1992

Treatment with ImuVert/N-acetylcysteine protects rats from cyclophosphamide/cytarabine-induced alopecia.

Chemotherapy-induced alopecia is a distressing problem to the cancer patient for which currently there is no effective preventive measure. Recently ImuVert, a biologic response modifier, has been shown to protect from cytarabine-induced alopecia in the young rat model, but not from alopecia induced by cyclophosphamide. In the present study, the rat model was used to examine the effect of N-acetylcysteine on the course of alopecia from cyclophosphamide and of ImuVert plus N-acetylcysteine on alopecia induced by cytarabine-cyclophosphamide combination. The following observations were made: (1) Cyclophosphamide-induced alopecia could be effectively prevented by N-acetylcysteine, administered parenterally or applied topically in liposomes. (2) Alopecia caused by the combination of cyclophosphamide and cytarabine could be prevented by the parenteral or topical administration of ImuVert plus N-acetylcysteine. The potential applicability of these observations to the clinical settings remains to be determined.

Acetylcysteine↗
PubMed1995

Alopecia associated with fluconazole therapy.

OBJECTIVE: To describe the association between fluconazole and reversible alopecia. DESIGN: A retrospective survey of 1) patients enrolled in NIAID Mycoses Study Group (MSG) protocols involving the long-term use of fluconazole for treatment of endemic mycoses and 2) patients treated with fluconazole outside of a protocol setting but by the MSG investigators who were MSG members. SETTING: 26 MSG sites in the United States. PATIENTS: 33 patients with various deep and superficial mycoses who developed alopecia while receiving fluconazole. RESULTS: 11 of 26 investigators reported a total of 33 patients with substantial alopecia related to fluconazole therapy. Underlying mycoses included blastomycosis, sporotrichosis, histoplasmosis, cryptococcosis, coccidioidomycosis, and mucosal candidiasis. In separate MSG studies, 17 of 136 (12.5%) and 8 of 40 (20%) patients had substantial reversible alopecia associated with fluconazole therapy. Eight patients who were not in the protocol had similar adverse effects. Twenty-nine of 33 patients (88%) received at least 400 mg of fluconazole daily for a mean of 7.1 months. Alopecia developed a median of 3 months after initiation of fluconazole therapy and involved the scalp in all patients. Other sites were involved in about one third of patients. Three patients required wigs because of extensive hair loss. Alopecia resolved within 6 months of discontinuation of fluconazole therapy or reduction of the daily dose by at least 50%. CONCLUSIONS: Alopecia appears to be a common adverse event associated with higher-dose (400 mg/d) fluconazole given for 2 months or longer. This effect may be severe but is reversed by discontinuing fluconazole therapy or substantially reducing the daily dose.

Adult↗