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

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.

Adoptive Transfer↗

Postoperative pressure-induced alopecia: report of a case and discussion of the role of apoptosis in non-scarring alopecia.

We report a case of postoperative pressure induced alopecia in a 21-year-old black female after multiple intraoperative procedures. The histopathology is distinctive and demonstrated features in common with trichotillomania and alopecia areata, including the presence of pigment casts, catagen follicles, melanophages and apoptotic bodies. External hair manipulation is considered the primary event in the etiology of pigment casts, however, our present case demonstrated numerous pigment casts despite a complete lack of evidence of external hair manipulation. We performed pattern analysis and in situ end-labeling in 19 cases of non-scarring alopecia. Pigment casts were seen in postoperative alopecia (1 case), alopecia areata (1 case) and trichotillomania (5 cases). These forms of alopecia have in common the sudden termination of the anagen phase of the hair cycle. When the anagen portion of the hair cycle is prematurely disrupted hairs enter into catagen. Pigment casts may represent a non-specific reaction pattern of follicles that are suddenly transformed from anagen to catagen. We therefore propose that hair manipulation is not uniquely responsible for the formation of pigment casts. The primary pathophysiology resulting in the formation of pigment casts more correctly reflects the sudden termination of the anagen phase of the hair cycle.

Adult↗

Incidence of female androgenetic alopecia (female pattern alopecia).

BACKGROUND: Female pattern alopecia seems to be increasing. A recent article suggests that female androgenetic alopecia may not be androgen dependent and is a different entity than male androgenetic alopecia. OBJECTIVE: To determine the incidence at different ages of female androgenetic alopecia in 1000 Caucasian women 20 years of age and older. METHODS: A total of 1006 Caucasian women were examined for the presence of female androgenetic alopecia. CONCLUSION: Female androgenetic alopecia is quite common beginning in the late 20s and reaching its peak after 50 years of age.

Adult↗

Alopecia areata but not androgenetic alopecia is characterized by a restricted and oligoclonal T-cell receptor-repertoire among infiltrating lymphocytes.

Although the etiology of alopecia areata is still unknown, evidence has accumulated to support an autoimmune pathogenesis for this disease. To evaluate the role of T cells in alopecia areata the T-cell receptor VB-repertoire was investigated in lesional skin and blood of 5 patients by means of a semiquantitative technique based on the reverse transcriptase polymerase chain reaction. Three patients with androgenetic alopecia served as controls. Amplification products were screened for clonality by temperature gradient gel electrophoresis. Four of 5 patients with alopecia areata exhibited a lesional T-cell receptor-repertoire characterized by an almost exclusive utilization of variable regions beta 2, 4, and 13. Temperature gradient gel electrophoresis revealed the oligoclonal constitution of the infiltrate. The restricted nature of the lesional T-lymphocytic infiltrate in alopecia areata strongly suggests that an antigen-specific T-cell response plays an important role in the pathogenesis of this disease.

Adult↗

Melatonin increases anagen hair rate in women with androgenetic alopecia or diffuse alopecia: results of a pilot randomized controlled trial.

BACKGROUND: In addition to the well-known hormonal influences of testosterone and dihydrotestosterone on the hair cycle, melatonin has been reported to have a beneficial effect on hair growth in animals. The effect of melatonin on hair growth in humans has not been investigated so far. OBJECTIVES: To examine whether topically applied melatonin influences anagen and telogen hair rate in women with androgenetic or diffuse hair loss. METHODS: A double-blind, randomized, placebo-controlled study was conducted in 40 women suffering from diffuse alopecia or androgenetic alopecia. A 0.1% melatonin or a placebo solution was applied on the scalp once daily for 6 months and trichograms were performed to assess anagen and telogen hair rate. To monitor effects of treatment on physiological melatonin levels, blood samples were taken over the whole study period. RESULTS: Melatonin led to a significantly increased anagen hair rate in occipital hair in women with androgenetic hair loss compared with placebo (n=12; P=0.012). For frontal hair, melatonin gave a significant increase in the group with diffuse alopecia (n=28; P=0.046). The occipital hair samples of patients with diffuse alopecia and the frontal hair counts of those with androgenetic alopecia also showed an increase of anagen hair, but differences were not significant. Plasma melatonin levels increased under treatment with melatonin, but did not exceed the physiological night peak. CONCLUSIONS: To the authors' knowledge, this pilot study is the first to show that topically applied melatonin might influence hair growth in humans in vivo. The mode of action is not known, but the effect might result from an induction of anagen phase.

Administration, Topical↗

Clinical and immunologic response to Isoprinosine in alopecia areata and alopecia universalis: association with autoantibodies.

Twenty patients with alopecia universalis, alopecia semiuniversalis and alopecia areata were studied for their immune parameters. Fourteen of them received an oral treatment with Isoprinosine, a synthetic immunomodulator. Ten patients showed the presence of several autoantibodies. No significant abnormalities in various T cell rosette markers were found, but T4/T8 ratios tended to be elevated. Erythrocyte antibody complement (EAC) rosettes were usually decreased. Treatment with Isoprinosine produced a clinical response, as judged by total or partial hair growth, in nine of the fourteen patients treated. It was striking to observe that seven of the nine responders had autoantibodies prior to treatment. These autoantibodies disappeared or decreased with Isoprinosine therapy. In contrast, only one of five nonresponders had serum autoantibodies. After treatment, both groups showed an increase in blood-active T rosettes. These results suggest that alopecia is a heterogeneous disease subdivided by the presence or absence of autoantibodies since clinical response was mainly obtained in patients presenting autoantibodies.

Adolescent↗

Alopecia syphilitica, a simulator of alopecia areata: histopathology and differential diagnosis.

Alopecia syphilitica (AS) may be "moth-eaten" or diffuse, clinically, and be confused with alopecia areata (AA) or other alopecias. The English language literature contains scant information regarding the histopathology of AS, and the resemblance between AS and AA has not been given adequate recognition. We report the histopathological findings of AS from nine patients with secondary syphilis and acute hair loss. The alopecia was moth-eaten in four patients and diffuse, but slightly moth-eaten, in five. Microscopically, the dermoepidermal interface was not involved. The numbers of hair follicles were diminished, with increased numbers of catagens and telogens. Lymphocytic infiltration was present around the hair bulbs and fibrous tracts in eight cases. Plasma cells were present in four biopsies. Other less common findings included lymphocytes in the isthmus, parabulbal lymphoid aggregates, and granulomatous infiltrate in the upper dermis. The findings, save for the follicular changes, resembled those of macular/maculopapular syphilides outside the scalp. With the follicular changes, the overall patterns resembled AA closely. The modified Steiner stain did not reveal spirochetes in any of our cases and failed to differentiate between AS and AA. Comparing the AS cases to 13 cases of AA, we found only a few differentiating features. The presence of peribulbal eosinophils strongly suggests AA. Without peribulbal eosinophils, the presence of plasma cells, abundant lymphocytes in the isthmus, or parabulbal lymphoid aggregates suggests AS.

Adult↗

Case study: fibrosing alopecia in a pattern distribution localized on alopecia androgenetica areas and unaffected scalp.

A 54-year-old man with a 24-year history of androgenetic alopecia was referred to the Department of Dermatological Sciences with follicular inflammatory lesions leading to scleroatrophy in the vertex region (Figure 1) of 1-year duration. These lesions appeared a year ago. There was no previous history of this condition. On examination, the patient showed confluent infiltrative follicular lesions on the frontoparietal and occipital scalp (Figure 2). Some lesions evolved into erosions that developed in ivory white scleroatrophy within weeks. These lesions were localized both in and outside of are as affected by alopecia androgenetica and were associated with mild pruritus. Histopathologic examination, performed on an early lesion of the vertex, documented a mild thinning of follicular epithelium associated with an intense lymphohistiocytic perifollicular infiltrate. The damage of the basal cell layer was limited to the follicle, while epidermis was intact. In particular, follicular keratinocytes under the isthmus showed a very intense degeneration exactly where the infiltrate was the most prominent. The damage of the hair sheath was under the isthmus and involved the lower portions of the follicles (including the hair bulbs). The inflammatory infiltrate was exclusively represented by perifollicular lymphohistiocytes. Finally, a connective fibrotic shell with numerous fibroblasts formed a sheath around the atrophic follicle (Figure 3). Results of laboratory investigations (including complete blood cell counts, basal thyroid-stimulating hormone, C-reactive protein, serum ferritin levels, B and C hepatitis markers, antinuclear antibodies, and cultural examinations) were negative.We diagnosed the patient with fibrosing alopecia in a pattern distribution.

Alopecia↗

Cytokines in alopecia areata: contrasting cytokine profiles in localized form and extensive form (alopecia universalis).

Recent studies have suggested that cytokines play a critical role in the pathophysiology of alopecia areata; however, no information is available regarding the difference in cytokine profiles in these patients. Serum levels of cytokines, including interferon gamma (IFN-gamma), tumor necrosis factor alpha, interleukin 1 alpha (IL-1 alpha), IL-2, IL-4, and IL-6, were measured using radioimmunoassay or enzyme-linked immunosorbent assay techniques in patients with the localized form and the extensive form (alopecia universalis). The serum levels of IL-1 alpha and IL-4 were significantly elevated in patients with the localized form. In contrast, the serum levels of IFN-gamma and IL-2 were significantly elevated in patients with the extensive form. These results indicate that immune responses in the localized form and the extensive form of alopecia areata are regulated by Th2 cytokines and Th1 cytokines, respectively.

Adult↗

Long-term results of topical immunotherapy in children with alopecia totalis or alopecia universalis.

BACKGROUND: Topical immunotherapy has been used in the treatment of children with alopecia areata with encouraging results. OBJECTIVE: Our purpose was to determine the long-term results in 33 children with severe alopecia areata treated with topical immunotherapy. METHODS: From 1983 to 1989 we treated 33 children with topical immunotherapy with squaric acid dibutylester. RESULTS: Complete hair regrowth was observed in 10 children (30.3%). During the follow-up period (mean, 5.9 years; range, 4 to 12 years), 7 of these 10 patients had severe relapses that were not responsive to further treatment. Only three clinically benefited from topical immunotherapy. Two maintained complete hair regrowth after treatment was stopped. CONCLUSION: Our results indicate that only a small proportion of children with severe alopecia areata will obtain a persistent benefit from topical immunotherapy.

Administration, Cutaneous↗

Postoperative alopecia in five patients after treatment of aneurysm rupture with a Guglielmi detachable coil: pressure alopecia, radiation induced, or both?

Postoperative pressure alopecia is an uncommon complication of long anesthetic surgical procedures, typically affecting the occiput and resulting from pressure-induced tissue hypoxia. Generally, it develops after procedures of long duration, of more than four hours. Most alopecia is transient, but a few cases are permanent. Guglielmi detachable coil (GDC) coiling is a procedure guided by fluoroscopy that fills an intracranial aneurysm. Our cases were characterized by an unusual distribution of alopecia, short duration of procedure, and radiation exposure. The alopecic lesions of our patients were located on the temporal scalp as well as the occipital scalp. The total time of anesthesia was relatively short, two to three hours. During the procedure, these patients were exposed to ionizing radiation (over 2Gy). These cases are different from previous reports in that the duration of the procedure was short, the temporal scalp was affected in addition to the occipital scalp, and the pathology occurred after GDC coiling.

Adult↗

The emotional disturbance underlying alopecia areata, alopecia totalis and trichotillomania.

A psychological study on fifteen children with diverse etiologies of hair loss, viz., alopecia areata, alopecia totalis and trichotillomania was conducted in order to assess the degree of underlying psychodynamics in children with hair loss. The results confirm the relationship of the underlying emotional disturbance to the hair loss. Further, it appears that the more severe the psychopathology of the individual, the greater is the hair loss and/or the clinical manifestation of trichotillomania.

Affective Symptoms↗

Functional analysis of the stratum corneum of scalp skin: studies in patients with alopecia areata and androgenetic alopecia.

Because of the presence of thick long hairs on the scalp, little information is available concerning the functional characteristics of the stratum corneum (SC) of scalp skin. We therefore conducted a functional study of the SC of lesional scalp skin of patients with alopecia areata and of patients with androgenetic alopecia. We compared the scalp with the cheek and the flexor surface of the forearm (volar forearm). The water barrier function of the scalp SC of both patient groups, in terms of transepidermal water loss (TEWL), was almost comparable to that of the volar forearm, and was far better than that of facial skin. However, hydration of the scalp skin surface, as evaluated by measurement of high-frequency conductance, was markedly higher than that of facial skin, and showed significantly higher values than the volar forearm. These characteristics seem to be dependent, at least to some extent, on the amount of sebum-derived skin surface lipids because these were abundant on the scalp skin. Moreover, removal of skin surface lipids led to a significant decrease in skin surface hydration. The superficial corneocytes, the size of which reflects the proliferative activity of the epidermis, were substantially smaller on the scalp than on the volar forearm but significantly larger than on the cheek. These findings suggest that the rate of turnover of the scalp epidermis is intermediate between that of the facial and volar forearm epidermis. We conclude that the SC of the scalp skin in humans is functionally distinct from that of the face and extremities.

Adolescent↗

Alopecia neoplastica simulating alopecia areata and antedating the detection of primary breast carcinoma.

A woman with no previous history of breast carcinoma presented with focal hair loss, which was presumptively diagnosed as alopecia areata. After treatment failures, a scalp biopsy was performed, which subsequently led to the diagnosis of breast carcinoma. This case illustrates the subtle course which breast cancer can take and the insidious manner in which it may present. It alerts clinicians and pathologists to the possibility of secondary causes, including malignancy, in the differential diagnosis of alopecia refractory to usual treatments.

Adult↗

Hair growth in scalp grafts from patients with alopecia areata and alopecia universalis grafted onto nude mice.

A basic question in both mild and severe forms of alopecia areata (AA) relates to whether the disease is inherent to the affected tissue or secondary to circulating factors. This question has been addressed by grafting 2-mm grafts of scalp from affected areas of seven patients with AA or alopecia universalis (AU) onto congenitally athymic (nude) mice. Hair growth in these grafts has been compared with that of 2-mm grafts from hair-bearing skin remnants from two individuals undergoing elective plastic surgical procedures. Because cyclosporine seems to directly affect hair growth, a group of grafted mice was treated with this agent. By day 48, hair growth was present in many surviving grafts. Cyclosporine affected hair growth; this was most prominent by day 78 when the number of hairs per graft and the mean length of hair had increased significantly over untreated groups. Grafts from patients with AU had more hairs per graft and had greater hair length than did similar grafts from patients with AA. These experiments show that hair growth ability in situ is likely normal in AA and AU, and that the factors causative to this disease in situ are mediated humorally. Furthermore, cyclosporine seems to directly influence hair growth in this model system.

Alopecia↗

An auto-antibody profile in alopecia totalis and diffuse alopecia.

Thirty-one patients suffering from alopecia totalis and fourteen patients with idiopathic diffuse alopecia were examined for evidence of an endocrinopathy and their sera screened for organ-specific auto-antibodies. The results were compared with matched control groups of dermatological patients and a random group of dermatological patients. There was no statistically significant difference in the groups and the results were similar to those found in the general population.

Adolescent↗

Perinevoid alopecia. An unusual variety of alopecia areata.

We report three cases of alopecia areata occurring around central, pigmented nevi. The histologic appearance of the central nevus was that of the halo nevus. Removal of the nevus did not appear to alter the natural course of the alopecia. Histochemical studies showed a substantial increase of acid mucopolysaccharides in the dermis in each case.

Adult↗