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PubMed2002

Targeted expression of human vitamin d receptor in the skin promotes the initiation of the postnatal hair follicle cycle and rescues the alopecia in vitamin D receptor null mice.

Alopecia is a predominant feature of vitamin D receptor inactivation in mice and humans. To determine the role of vitamin D receptor in the regulation of hair growth directly, we used the human keratin 14 promoter to target human vitamin D receptor expression to the skin of transgenic mice, and generated vitamin D receptor null mice that express the human vitamin D receptor transgene. Parallel studies were carried out in littermates of wild-type, vitamin D receptor null, transgenic, and human vitamin D receptor-expressing null mice in two transgenic lines. The transgenic mice were grossly normal. The vitamin D receptor null and vitamin D receptor null/human vitamin D receptor mice were growth retarded and developed hypocalcemia, secondary hyperparathyroidism, and rickets. In contrast to the vitamin D receptor null mice that developed alopecia, however, the vitamin D receptor null/human vitamin D receptor mice displayed a normal hair coat, and their hair shaft and skin histology were indistinguishable from those of the wild-type mice. Immunohistochemical analyses revealed that the human vitamin D receptor was highly expressed in the basal layer of the epidermis and outer root sheath of the hair follicle. During follicular morphogenesis, no major histologic differences were seen in the skin of wild-type, vitamin D receptor null, transgenic, and vitamin D receptor null/human vitamin D receptor littermates. When anagen was induced by hair depilation at day 20 after birth, the vitamin D receptor null mice failed to initiate the hair cycle, whereas the vitamin D receptor null/human vitamin D receptor mice displayed the same pattern of anagen follicle formation as the wild-type mice. Interestingly, the transgenic mice initiated the follicular cycle earlier than the wild-type and vitamin D receptor null/human vitamin D receptor mice in a gene concentration-dependent manner. Taken together, these data provide direct evidence that vitamin D receptor is required for the initiation of the postnatal hair follicular cycle in mice.

Alopecia↗
PubMed2003

Cytokines and signal transduction pathways mediated by anthralin in alopecia areata-affected Dundee experimental balding rats.

Although many therapeutic modalities have been tested on alopecia areata, patient outcomes have been disappointing. Use of animal models would help to develop more efficient therapies as well as understanding therapeutic mechanisms. We have demonstrated that 0.1% topical anthralin ointment is 100% effective in restoring follicular activity in Dundee experimental balding rats. This is the most promising topical treatment for Dundee experimental balding rats among the therapeutic agents tested on this model. Various cytokines have been shown to be associated with the pathogenesis of alopecia areata. To test whether any of these cytokines might be modulated by anthralin, an RNase protection assay and the real-time polymerase chain reaction were performed to compare their expression between anthralin-treated and control skins. These experiments showed that expression of tumor necrosis factor-alpha and interferon-gamma was inhibited by anthralin, whereas expression of interleukin-1alpha/beta and their receptor antagonist, interleukin-1Ra, and interleukin-10 was stimulated by anthralin. In addition, using an antibody-based multi-immunoblotting technique, we found that certain signaling regulatory proteins were modulated by anthralin. Their potential roles in reversing the autoimmune-arrested follicular activity in Dundee experimental balding rats are discussed.

Alopecia Areata↗
PubMed2003

Expression of cyclooxygenase isozymes during morphogenesis and cycling of pelage hair follicles in mouse skin: precocious onset of the first catagen phase and alopecia upon cyclooxygenase-2 overexpression.

Cyclooxygenase (COX)-1 and -2 catalyze the key reaction in prostaglandin biosynthesis. Whereas COX-1 is found in most tissues, COX-2, with a few exceptions, is not expressed in normal tissues but becomes transiently induced in the course of inflammatory reactions. In many neoplastic epithelia, COX-2 is constitutively overexpressed. Here we show that COX isozymes are spatiotemporally expressed during morphogenesis of dorsal skin epithelium of NMRI mice. COX-1 and COX-2 mRNA and protein were detected in embryonic and postnatal epidermal tissue by RT-PCR, northern blot, and immunoblot analysis indicating that both isoforms may contribute to prostaglandin production. Being barely detectable in interfollicular epidermis and resting hair follicles of adult mice, COX-2 protein appeared in embryonic skin first in epidermal precursor cells and later on in the basal cells and the peridermal layer of the stratified epidermis. In the course of pelage hair follicle morphogenesis, COX-2 remained expressed in the basal interfollicular compartment and, in addition, became apparent in elongated hair germs and hair pegs and later on in the outer root sheath cells of the distal and proximal hair follicles as well as in basal sebaceous gland cells. During the subsequent synchronous phases of hair cycling, COX-2 expression declined in catagen, was barely detectable in telogen, and was reinduced in the basal outer root sheath and basal sebaceous gland cells of anagen hair follicles. COX-1 immunosignals were detected predominantly in the interfollicular spinous and granular layers of the developing, neonatal, and adult epidermis but not in follicular epithelial cells of developing or cycling hair follicles. Dendritic cells in the interfollicular epidermis and distal hair follicles were also COX-1-positive. Transgenic overexpression of COX-2 under the control of a keratin 5 promoter in basal cells of the interfollicular and follicular epidermis induced a precocious entry into the first catagen stage of postnatal hair follicle cycling and a subsequent disturbance of hair follicle phasing. Furthermore, transgenic mice developed an alopecia. Inhibition of transgenic COX-2 activity by feeding the specific COX-2 inhibitor valdecoxib suppressed the development of alopecia, indicating that COX-2-mediated prostaglandin synthesis is involved in hair follicle biology.

Age Factors↗
PubMed2000

Multifactorial classification of male and female androgenetic alopecia.

BACKGROUND: Various classifications of male androgenetic alopecia have been described. In fact, all the classification schemes proposed so far are only topographic. A more objective, accurate, and detailed approach to classifying baldness is needed. OBJECTIVE: To propose a dynamic multifactorial classification of certain parameters that can be quantitated and computerized. METHODS: A multifactorial classification has been developed to study parameters such as fixed distances of the face, scalp mobility and thickness, and covering power of hair. This includes density, caliber, shape, length, growth rate, and hair color. RESULTS: Classification proved to be efficient during the fluctuations of different parameters in hormonal and minoxidil treatments. It also helps to determine surgical indications of hair transplant and the stage of maximal baldness. CONCLUSION: This approach will lead to a better evaluation of the evolution of androgenetic alopecia in both sexes, either spontaneously or under treatment.

Alopecia↗
PubMed2002

Fluridil, a rationally designed topical agent for androgenetic alopecia: first clinical experience.

BACKGROUND: Fluridil, a novel topical antiandrogen, suppresses the human androgen receptor. While highly hydrophobic and hydrolytically degradable, it is systemically nonresorbable. In animals, fluridil demonstrated high local and general tolerance. OBJECTIVE: To evaluate the safety and efficacy of a topical anti- androgen, fluridil, in male androgenetic alopecia. METHODS: In 20 men, for 21 days, occlusive forearm patches with 2, 4, and 6% fluridil, isopropanol, and/or vaseline were applied. In 43 men with androgenetic alopecia (AGA), Norwood grade II-Va, 2% fluridil was evaluated in a double-blind, placebo-controlled study after 3 months clinically by phototrichograms, hematology, and blood chemistry including analysis for fluridil, and at 9 months by phototrichograms. RESULTS: Neither fluridil nor isopropanol showed sensitization/irritation potential, unlike vaseline. In all AGA subjects, baseline anagen/telogen counts were equal. After 3 months, the average anagen percentage did not change in placebo subjects, but increased in fluridil subjects from 76% to 85%, and at 9 months to 87%. In former placebo subjects, fluridil increased the anagen percentage after 6 months from 76% to 85%. Sexual functions, libido, hematology, and blood chemistry values were normal throughout, except that at 3 months, in the spring, serum testosterone increased within the normal range equally in placebo and fluridil groups. No fluridil or its decomposition product, BP-34, was detectable in the serum at 0, 3, or 90 days. CONCLUSION: Topical fluridil is nonirritating, nonsensitizing, nonresorbable, devoid of systemic activity, and anagen promoting after daily use in most AGA males.

Administration, Topical↗
PubMed2002

A random study of Asian male androgenetic alopecia in Bangkok, Thailand.

BACKGROUND: Androgenetic alopecia remains the most common cause of male pattern baldness (MPB) in all races. The prevalence of MPB in Caucasians is well documented. The prevalence of MPB in Asians is believed to be very low, only one-fourth to one-third on average compared to Caucasians. However, according to my previous study, there is a clear trend indicating that it is approaching that of Caucasians. OBJECTIVE: To assess the prevalence of MPB in the Asian population in Bangkok, Thailand; to compare this prevalence to previous studies conducted on Asians; and to compare the results to previous studies conducted on Caucasian. METHODS: This study was conducted by two physicians and assisted by two registered nurses. The questionnaire included age, sex, Norwood classification, diet, family history of baldness, income, and education. The physicians examined the scalp of each interviewee upon completion of each questionnaire. The ethnic focus group in this study was Thai and Chinese who reside in Bangkok, Thailand. The interviews were conducted in hospitals, nursing homes, classroom, medical meetings, temples, parks, and villages. RESULTS: A total of 1124 men were randomized in this study. The prevalence of cosmetically significant MPB (Norwood III-VII) was 38.52% and steadily increasing with age, approaching that of Caucasians. Variant MPB was found to be 0.67% and other types of androgenetic alopecia was 0.6%. From an ethnic point of view, the majority of the groups were of mixed blood and mostly of Chinese origin, thus we were unable to distinguish between Chinese and Thai. CONCLUSION: This study shows that the prevalence of MPB in Asians is not as low as previously thought. The cause of this increasing prevalence is uncertain. There are no past studies in Thailand for comparison, however, it can be extrapolated that the socioeconomic environment and westernized diet may contribute to this prevalence.

Adolescent↗
PubMedDate not supplied

Temporal triangular alopecia: report of an African-American child with TTA misdiagnosed as refractory tinea capitis.

Temporal triangular alopecia is an underrecognized form of nonscarring alopecia that appears in children between the ages of 3 and 6 years and is often misdiagnosed. Increased awareness of this entity is needed to prevent ineffective and harmful treatments. We present a case misdiagnosed as tinea capitis in an African-American girl, review the literature, and elucidate the major differential diagnoses.

Alopecia↗
PubMed1999

Minoxidil and male-pattern alopecia: a potential role for a local regulator of sebum secretion with vasoconstrictive effects?

Regulation of the hair cycle takes place at the pilo-sebaceous unit with the sebaceous gland as a sex hormone-dependent part. Although minoxidil stimulates proliferation of follicular cells and activation of prostaglandin endoperoxide synthase-1, it was suggested that other mechanisms, such as an increase in the local blood flow, might mediate the drug effect on hair growth. If that is the case, it is possible that minoxidil counteracts some vasoconstrictive mediator of male-pattern alopecia. This hypothetical vasoconstrictive mediator X would have to meet some criteria: (I) vasoconstriction both in the general circulation and in the hair-growing skin; (II) local vasoconstrictive activity in the hair growing skin should be related to the circulating testosterone level; (III) only an increase in the local mediator X activity causes male-pattern alopecia, since hypertensive patients are not balder than expected. The sebaceous gland is a possible place of the mediator X secretion since it is a sex-hormone-dependent part of the pilo-sebaceous unit. ET-1 might be a suitable candidate for the mediator X, since male hormones raise ET-1 plasma levels and female hormones lower them. The speculation presented here is that ET-1, beside vasoconstriction in the general circulation, might also regulate the sebum secretion, by triggering contractions of the myoepithelial cells. This hypothetical mechanism would normally remain confined to the sebaceous gland. During puberty, sex hormones stimulate growth of sebaceous glands in both sexes. In women hypertrophied sebaceous glands under estrogen control would not increase its ET-1 content, while in men, testosterone would increase ET-1 secretion that might affect the neighboring arterioles. Induced vasoconstriction might reduce the hair growth and promote hair loss. If ET-1 plays the described role, then an ET-1 antagonist, i.e. bosentane, should also have some hair-growing properties.

Alopecia↗
PubMed1996

[Meralgia paresthetica. A rare differential diagnosis of circumscribed alopecia].

HISTORY AND CLINICAL FINDINGS: Two patients with circumscribed alopecia on the lateral aspect of the thigh underwent a neurological investigation after medical and dermatological examinations had failed to establish the cause. Patient 1 also had neuralgia of the genitofemoral nerve after osteotomy of the iliac crest; patient 2 had insulin-dependent diabetes mellitus. Within the affected part of the skin both patients had sensory dysfunctions over the area of distribution of the cutaneous lateral femoral nerve. Patient 2 additionally had sensory dysfunctions in other areas of innervation. INVESTIGATIONS: Neurogram and recordings of sensory evoked potentials revealed decreased amplitudes on the affected side, establishing the diagnosis of meralgia paresthetica. TREATMENT AND COURSE: The painful neuropathy was successfully treated in both patients with carbamazepine (patient 1: 1.600 mg daily; patient 2: 900 mg daily). CONCLUSION: Circumscribed alopecia can be caused by peripheral nerve lesions. It should be considered in the differential diagnosis, particularly as the cause can be easily established.

Adult↗
PubMed2002

Sulfasalazine for alopecia areata.

Sulfasalazine is used as a therapy for various autoimmune conditions, including psoriasis; its effectiveness is presumed to be the result of its immunomodulatory effects. We have treated patients with severe alopecia areata with sulfasalazine as part of our dermatology practice and have noticed cosmetically acceptable regrowth in 23% of patients in whom a response could be determined. In view of its good safety profile, sulfasalazine may be considered for systemic treatment of severe alopecia areata.

Adolescent↗
PubMed2002

Persistent depigmented regrowth after alopecia areata.

We report a case of persistent depigmented hair regrowth from the site of a patch of alopecia areata. It is well known that hair may regrow unpigmented from a site of alopecia areata; however, it was previously thought that this was temporary, lasting no longer than the first hair cycle.

Adolescent↗
PubMed2003

Clobetasol propionate 0.05% under occlusion in the treatment of alopecia totalis/universalis.

BACKGROUND: Efficacy of topical steroids in alopecia areata is still discussed. OBJECTIVE: The purpose of this study was to evaluate the efficacy of clobetasol propionate 0.05% ointment under occlusion in 28 patients with alopecia areata totalis (AT) or AT/alopecia universalis. METHODS: A total of 28 patients were instructed to apply 2.5 g of clobetasol propionate to the right side of the scalp every night under occlusion with a plastic film. Treatment was performed 6 days a week for 6 months. When regrowth of terminal hair occurred, treatment was extended over the entire scalp. All patients were followed up for another 6 months. RESULTS: Of the 28 patients included in the study, 8 were treated successfully (28.5%). Regrowth of terminal hair began on the treated side 6 to 14 weeks after the start of treatment. Of these 8 patients, 3 had a relapse and were not able to maintain hair regrowth. CONCLUSION: Our study shows that clobetasol propionate 0.05% under occlusion is effective in inducing hair regrowth in patients with AT or AT/alopecia universalis. Occurrence of hair regrowth only on the treated half of the scalp clearly shows that efficacy of treatment is a result of a local and not systemic effect of the drug. Although only 17.8% of patients had long-term benefit by treatment, our results were obtained in a population of patients with severe and refractory forms of the disease.

Administration, Topical↗
PubMed1997

Targeted ablation of the vitamin D receptor: an animal model of vitamin D-dependent rickets type II with alopecia.

Vitamin D, the major steroid hormone that controls mineral ion homeostasis, exerts its actions through the vitamin D receptor (VDR). The VDR is expressed in many tissues, including several tissues not thought to play a role in mineral metabolism. Studies in kindreds with VDR mutations (vitamin D-dependent rickets type II, VDDR II) have demonstrated hypocalcemia, hyperparathyroidism, rickets, and osteomalacia. Alopecia, which is not a feature of vitamin D deficiency, is seen in some kindreds. We have generated a mouse model of VDDR II by targeted ablation of the second zinc finger of the VDR DNA-binding domain. Despite known expression of the VDR in fetal life, homozygous mice are phenotypically normal at birth and demonstrate normal survival at least until 6 months. They become hypocalcemic at 21 days of age, at which time their parathyroid hormone (PTH) levels begin to rise. Hyperparathyroidism is accompanied by an increase in the size of the parathyroid gland as well as an increase in PTH mRNA levels. Rickets and osteomalacia are seen by day 35; however, as early as day 15, there is an expansion in the zone of hypertrophic chondrocytes in the growth plate. In contrast to animals made vitamin D deficient by dietary means, and like some patients with VDDR II, these mice develop progressive alopecia from the age of 4 weeks.

Alopecia↗
PubMed1999

Quantitative image analysis of hair follicles in alopecia areata.

We took biopsies from similar sites on the scalps of normal controls, normal looking and hair loss areas of patients with alopecia areata. The specimens were sectioned serially and horizontally. We measured morphological parameters, such as the diameter of the hair shaft, the thickness of the inner root sheath, the diameter of the outer root sheath, the irregularity of the outer root sheath and the ratio between the diameters of the hair shaft and the outer root sheath, using a computerized image analysis system. There were significant differences in 5 parameters between hair loss areas and normal controls. The proportions of vellus and telogen hair were significantly higher in the areata areas than in the controls. The 5 morphological parameters and most quantitative-measured parameters of normal-looking areas from patients with alopecia values intermediate between the other groups.

Adolescent↗
PubMed2005

Alopecia areata and multifocal bone involvement in a young adult with Hodgkin's disease.

A 17-year-old girl presented with a 3 month history of alopecia areata, a generalized scaling skin, enlargement of the inguinal lymph nodes and severe back pain. Staging procedures revealed multifocal bone disease and generalized lymphadenopathy. The diagnosis of nodular sclerosing Hodgkin's disease was established by biopsies of the os ileum and a left inguinal lymph node. Complete clinical remission was achieved after 2 OPPA (vincristine, prednisone, procarbazine, and doxorubicin) and 4 COPP (cyclophosphamide, vincristine, prednisone, and procarbazine) cycles and treatment completed with involved-field irradiation. After the completion of therapy, skeletal lesions had mostly resolved or become sclerotic and the patient had normal hair regrowth and skin appearance. Conclusively, this case illustrates that alopecia areata may occur as a paraneoplastic phenomenon or an autoimmune process related to the deranged cellular immune system in children and adolescents with Hodgkin's disease.

Adolescent↗
PubMedDate not supplied

Pseudo alopecia areata caused by skull-caps with metal pin fasteners used by Orthodox Jews in Israel.

BACKGROUND: Alopecia Areata (AA) is a disease characterized by hair loss that is widely believed to be autoimmune in origin. Thus treatment is generally aimed in this direction using immune inhibitors such as steroids and PUVA. OBJECTIVE: To describe a variant of AA, Pseudo Alopecia Areata, caused by a particular cupola pin holder (tic-tac) and to offer a non-pharmacological treatment option (NPT). METHODS: A prospective open label study in 37 Jewish religious patients (34 males, 3 females, mean 35 +/- 2 years), previously diagnosed and treated for scalp AA were randomly referred to one of the three NPT intervention methods: small cupola held by two pins, large cupola held by one pin and similar cupola held by a different pin. RESULTS: Three of the ten patients (33.3%) from the first group developed secondary AA from the additional pin. No changes were seen in the second group. Ten of the seventeen patients (58.8%) from the third group achieved immediate improvement subsequent to replacing the original pin with a new one on a larger cupola. CONCLUSIONS: Conservative pharmacological treatment failed to repair the lesions. The addition of a second pin caused an additional lesion. In contrast, replacing the cupola with a larger one and the original pin-fastener with a different type, successfully reduced the lesions.

Adult↗