Hair Loss

J Am Acad Dermatol. 2010 Feb;62(2):177-88

Alopecia areata update: part I. Clinical picture, histopathology, and pathogenesis.
Alkhalifah A, et al

Abstract
Alopecia areata (AA) is an autoimmune disease that presents as nonscarring hair loss, although the exact pathogenesis of the disease remains to be clarified. Disease prevalence rates from 0.1% to 0.2% have been estimated for the United States. AA can affect any hair-bearing area. It often presents as well demarcated patches of nonscarring alopecia on skin of overtly normal appearance. Recently, newer clinical variants have been described. The presence of AA is associated with a higher frequency of other autoimmune diseases. Controversially, there may also be increased psychiatric morbidity in patients with AA. Although some AA features are known poor prognostic signs, the course of the disease is unpredictable and the response to treatment can be variable. Part one of this two-part series on AA describes the clinical presentation and the associated histopathologic picture. It also proposes a hypothesis for AA development based on the most recent knowledge of disease pathogenesis. LEARNING OBJECTIVES: After completing this learning activity, participants should be familiar with the most recent advances in AA pathogenesis, recognize the rare and recently described variants of AA, and be able to distinguish between different histopathologic stages of AA.

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J Eur Acad Dermatol Venereol. 2010

Alopecia areata as another immune-mediated disease developed in patients treated with tumour necrosis factor-alpha blocker agents.
Ferran M, Calvet J, Almirall M, Pujol RM, Maymó J.

Department of Dermatology, Hospital del Mar, IMAS, Barcelona, Spain.

Abstract
Abstract Background Tumour necrosis factor antagonists (anti-TNF-alpha) have demonstrated the efficacy in different chronic immune inflammatory disorders. Within the spectrum of adverse events, autoimmune diseases have been observed, including cases of hair loss due to alopecia areata (AA). Objectives The objective of the study is to characterize AA developed during anti-TNF-alpha therapy. Methods We present five new cases and review all the cases reported in the literature (eleven). Results One third of the cases had a positive (personal or family) history of AA. Most of them presented with rapid extensive AA, usually involving the ophiasis area. Prognosis was usually poor, with slight response to treatments. In the cases where anti-TNF-alpha therapy was maintained, the course did not seem to change. Conclusions Although rare, AA developed during anti-TNF-alpha therapy might be more frequent than suggested by reports of isolated cases. Personal and family history of autoimmune disease might alert clinicians to their possible development or relapse once the anti-TNF-alpha therapy is started.

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J Clin Endocrinol Metab. 1987 Jul;65(1):188-93.

The effects of a 5 alpha-reductase inhibitor and antiandrogen, 4-MA, on the development of baldness in the stumptail macaque.
Rittmaster RS, et al

We used a model of male-pattern baldness to test the efficacy of a topically applied 5 alpha-reductase inhibitor and antiandrogen (4-MA) in the prevention of baldness. Six periadolescent stumptail macaques were given daily topical applications of either 4-MA in dimethylsulfoxide or dimethylsulfoxide alone for 27 months. The three control monkeys developed varying degrees of baldness, while the three 4-MA-treated monkeys retained their juvenile pattern of hair regrowth. snip… We conclude that topical 4-MA can prevent the development of baldness in the stumptail macaque, a primate model of androgen-dependent baldness.

Eur J Dermatol. 2001;11:195.

Influence of estrogens on the androgen metabolism in different subunits of human hair follicles.

Niiyama S,
The molecular pathways involved in estrogen-mediated induction of hair regrowth in male pattern hair loss are unknown. Some authors found that estradiol inhibited 5 alpha-activity and therefore we addressed the question whether 17alpha- or 17beta-E are able to modulate the activity of 5alpha-R, etc. in hair follicles. Scalp biopsies from volunteers were taken and from each biopsy root sheaths, connective tissue sheaths and dermal papillae were dissected and incubated in the presence of 3H-testosterone (T) and, in addition, either 17alpha-E, 17beta-E, progesterone or finasteride for up to 48 hrs. Then, analysis of culture supernatants was performed to detect T-metabolites. At the tested concentrations, finasteride was found to be a major inhibitor of dihydrotestosterone (DHT) formation. Even 1 nM finasteride inhibited DHT synthesis in DP by 86% and 1 nM progesterone by 75%. Estrogens were less able to inhibit the synthesis of DHT in DP (e.g. 100 nM 17alpha-E: 20%; 100 nM 17beta-E: 60%). snip…

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Hair biology and minoxidil:

Minoxidil stimulates hair regrowth. Vasodilatation and increased blood flow to the dermal papilla, or possible local irritation related to minoxidil or to one or more components of the vehicle used for topical application have been suggested ha mechanisms of action.. Direct drug effects include on the dermal papilla or hair matrix cells or possibly both. Biopsies in androgenetic alopecia (pattern hair loss) show miniaturization of terminal hair follicles along with Shortening and diminution of follicle, shortening of the hair regrowth cycle. The dermal papilla controls both regrowth and differentiation of hair matrix cells. The most probable site of minoxidil action in hair loss treatment is the dermal papilla.

Hair loss treatment at the Proctor clinic

Acta Derm Venereol. 1988;68(2):116-22
LPatche tests
Immunohistochemistry of lymphocytes and Langerhans’ cells in long-lasting allergic patch tests.

Kanerva L, et al

A long-lasting allergic patch test is a “normal” allergic patch test that remains positive for weeks or months. An immunohistochemical study of immunocompetent cells in the skin in this rare type of patch tests was performed. snip.. hair loss..An inflammatory reaction of hair follicles with moderate numbers of T6+ cells in the peribulbar infiltrate was observed indicating that hair follicles might act as shunt pathways for allergens. A defect in down regulation of the contact hypersensitivity reaction and/or a constant antigen stimulation could be responsible for the long-lasting allergic patch tests.

Low-sulfur hair syndrome associated with UVB photosensitivity and testicular failure.

Lucky PA, et al

A 16-year-old male patient had a syndrome that included growth retardation, mental retardation, hair shaft abnormalities, neurosensory hearing loss, contractures of the fifth fingers, ultraviolet B (UVB) photosensitivity, small testicular size, and elevated levels of follicle-stimulating hormone. Reduced hair sulfur content and a characteristic pattern of light and dark birefringent bands, seen when hairs were viewed with polarization microscopy, were typical of the low-sulfur hair syndrome. UVB photosensitivity and testicular failure have not previously been identified as components of this syndrome.

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Dermatology. 1997;195(1):96-8.

Congenital alopecia areata.

de Viragh PA, et al.

Alopecia areata has never been documented in a newborn. Thus, it is generally assumed that alopecia areata is acquired only postnatally, and it is believed that the presence of an alopecia at birth virtually excludes its diagnosis. In this report we document a case of alopecia areata in a premature newborn.

Lab Anim Sci. 1984 Dec;34(6):584-7.
Morphologic characteristics of the skin of bald mutant rats.

Inazu M, Sakaguchi T.

The skin of a new hairloss mutation in the rat termed “bald” was examined histologically and enzyme histochemically with animals from three weeks to 18 months of age. The loss of hair in homozygous (bald) rats proved to occur as follows: a club hair rising within the hair follicle in the first catagen phase was not anchored and fell out due to dilatation of the follicular lumen. In the skin of bald rats from two to three months of age on, two types of cyst developed, one from the infundibulum of the hair follicle and the other from a lower follicular portion left in the dermis. Each had histologic patterns different from each other. The wall of the former cyst contained various-sized keratohyaline granules in a large number, while the latter was keratinized without granules. In addition to cyst formation, foreign-body granulomas frequently appeared from three months of age on, originating from degenerated follicular portions in the dermis. In advanced cases after 12 months of age, the granulomatous lesions were sharply demarcated from the other tissue. Histochemically, acid phosphatase activity was observed in the skin of bald rats, in the wall of the dilated hair follicles and the cystic wall where progressive keratinization with age occurred. This enzymatic activity tended to heighten as keratinization proceeded.

Z Hautkr. 1990 Dec;65(12):1103-4, 1109-11.

Endocrinologic diagnosis in hirsutism and androgenetic alopecia in women

Pichl J, Schell H.

In women, hirsutism and male pattern baldness are due to an enhanced effect of androgens on the hair follicle, which in turn can be caused by an increased supply of bio-available androgens and/or an increased sensitivity of the target organ to androgens. There are no definite correlations between circulating androgens and the degree of their biological effects. Although in most cases the hyperandrogenemia is not severe, the patients should be treated with antiandrogens in order to avoid progression of the disturbance and its consequences on metabolism and fertility. Sometimes hirsutism or hai rloss can be observed as a clinical sign of a defect in the steroid biosynthesis or of Cushing’s syndrome. In severe hyperandrogenemia with a testosterone level of more than 2 ng/ml and a DHEA-S level of more than 8000 ng/ml, tumors of the ovaries or the adrenal glands have to be excluded.

Arch Dermatol. 1983 Dec;119(12):975-8.

PUVA treatment of alopecia areata.

Claudy AL, Gagnaire D.
Twenty-three patients with hair loss secondary to alopecia areata were treated with photochemotherapy combining oral or topical methoxsalen and UV-A irradiation of the scalp or of the whole body. Eleven of 17 patients with multiple plaques of alopecia areata, alopecia totalis, and alopecia universalis, who were treated with oral methoxsalen and total body irradiation, had complete or more than 90% hair regrowth. Three patients had a relapse. The mean energy required was 505 joules/sq cm. In six cases, topical applications of methoxsalen or oral methoxsalen combined with local irradiation of the scalp were treatment failures. In the patients responding to treatment, the result did not seem to depend on the age of onset or the extent or duration of disease. However, patients with long-lasting alopecia had a higher risk of recurrence notwithstanding a good initial regrowth of hair. Few side effects of psoralens and UV-A (PUVA) treatment were noted. The mean follow-up period was 18.6 months after the completion of treatment. We discuss the possible mechanisms of action of PUVA in the treatment of alopecia areata.

Am J Orthod. 1981 Apr;79(4):437-8.

Pressure-potential alopecia areata.

Zuehlke RL, Bishara S, Price V.

In order to create awareness of a potential adverse effect of extraoral orthodontic appliances, we report the development of hair loss secondary to alopecia areata in two patients. Both patients experienced the onset of alopecia areata directly under sites of pressure from thier “headgear.” In one patient the hair loss began 2 weeks after she began using her appliance. The other girl noticed patchy alopecia 2 to 3 weeks following an increase in the pressure and duration of use of an extraoral appliance. One of the patients also developed other areas of alopecia areata in sites unrelated to pressure. In both cases relief of the pressure was accompanied by hair regrowth in about 5 months. One of the patients received corticosteroid injections into the patches of alopecia areata; the other had no medical therapy. We conclude that alopecia areata can be made manifest by local pressure, such as that from orthodontic appliances.

Arch Dermatol. 1999 Mar;135(3):257-8.

Study of the Food and Drug Administration files on Propecia: dosages, side effects, and recommendations.
Frankel S.
University of Pennsylvania School of Arts and Sciences, Philadelphia, PA 19104-6396, USA.

PMID: 10086445

Cutis. 1989 Jan;43(1):94-8.

Topical minoxidil: review of efficacy and safety.
Katz HI.
Department of Dermatology, University of Minnesota, Minneapolis.

Topical minoxidil (Rogaine) has recently been approved by the Food and Drug Administration for treatment of androgenetic alopecia or male pattern hair loss. It has been approved for such use in many other countries. This paper is a review and summary of the reported efficacy and safety of topical minoxidil in hair loss treatment. The results of anecdotal and controlled clinical trials are included. Realistic appraisal of the restorative and/or preventative potentials of topical minoxidil in androgenetic alopecia is needed.

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Nippon Ronen Igakkai Zasshi. 2004 Nov;41(6):598-600.

Pathomechanism of androgenetic alopecia and new treatment
Itami S.

Hair Loss Blog

Hair follicles are composed primarily of epithelial and dermal components that develop from embryonic ectoderm and mesoderm respectively. The hair growth cycle is coordinated with complex processes that are dependent on the interactions of epithelial and dermal components. Beard and frontal scalp dermal papilla cells (DPCs) show the characteristics of androgen target cells. These DPCs expressed androgen receptor and type II 5alpha-reductase mRNA. To understand the mode of androgen action in human hair follicles, we developed an in vitro co-culture system using DPCs and follicular keratinocytes. Androgen significantly stimulated the proliferation of keratinocytes co-cultured with beard DPCs, suggesting that these DPCs produce androgen-dependent diffusible growth factors. Insulin-like growth factor-I (IGF-I) was identified as one of the androgen dependent paracrine growth factors from beard DPCs. On the other hand, we identified inhibitory roles of androgen on the growth of keratinocytes co-cultured with DPCs from human balding frontal scalp, when DPCs were transfected with the AR expression vector. This inhibitory effect was mediated by TGF-beta1 from the DPCs. Minoxidil and Finasteride were recently introduced for the treatment of androgenetic alopecia in Japan, and TGF-beta1 is the next target for innovative treatment.

Int J Clin Pract. 1999 Jan-Feb;53(1):50-3.

Androgenetic alopecia in men: the scale of the problem and prospects for treatment.
Rushton DH.

Hair Loss Blog

While the precise incidence of androgenetic alopecia is unknown, it is universally acknowledged to be the most common hair problem in men. Balding is generally associated with ageing; consequently, the desire to prolong a youthful appearance inevitably leads to demands for effective treatments. Further, changing attitudes in modern society have resulted in people becoming concerned about their appearance and less tolerant about conditions that might be alleviated by medical intervention. The importance of hair loss upon quality of life has been underestimated by the medical profession. Clinicians failing to accept hair loss as an important medical problem ignore the real distress suffered by a significant proportion of those affected. New options for treatment that selectively target the metabolic pathways involved in the balding process are showing promise. The first generation of such drugs, Propecia, is now available in some countries and other molecules are currently under development.

J Am Acad Dermatol. 1987 Mar;16(3 Pt 2):696-704.L

Use of topical minoxidil in the treatment of male pattern baldness.

Savin RC.
This 12-month, double-blind, randomized study evaluated the safety and efficacy of topical minoxidil in the treatment of male pattern baldness. Three formulations were compared: 2% minoxidil solution, 3% minoxidil solution, and placebo. After 4 months all placebo patients crossed over to treatment with the 3% solution. Of the 96 patients randomized into the study, 79 were evaluable at month 12; 25 of these were in the 2% minoxidil group, 24 were in the 3% minoxidil group, and 29 were in the placebo-to-3% solution switchover group. At monthly intervals a hair count was obtained within a 1-inch diameter area on the scalp vertex. In addition, a gross visual estimate of the degree of new hair growth over the entire balding area was made independently by the investigator and the patient. At the end of 4 months there was significant regrowth of nonvellus (terminal and indeterminate) hairs in the patients using the 2% and 3% solutions. The mean nonvellus hair count at month 4 was 162.8 in the 2% minoxidil group, 155.4 in the 3% minoxidil group, and 107.1 in the placebo group. The mean increase in the 2% and 3% treatment groups was 58.2 and 48.8, respectively, whereas the mean increase in the placebo group was 4.0. Total hair counts at month 4 demonstrated significantly more growth of hair in the 2% minoxidil group than in the placebo group (p = 0.013), with no significant difference between the 3% minoxidil group and the other two treatment groups

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Dermatol Clin. 1998 Apr;16(2):341-56. 

Hair regrowth. Therapeutic agents.

Shapiro J, Price VH.

Nippon Rinsho. 2008 May;66(5):892-6. 

Itami S.

Department of Regenerative Dermatology, Graduate School of Medicine, Osaka University.

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