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Update on primary cicatricial alopecias.

UNLABELLED: The cicatricial alopecias encompass a diverse group of disorders characterized by permanent destruction of the hair follicle and irreversible hair loss. Destruction of the hair follicle can result from primary, folliculocentric disease or as a secondary result. This article focuses on the former, or primary cicatricial alopecias. The cause and pathogenesis of many of these disorders are largely unknown. Although unique clinicopathologic features allow for accurate diagnosis in some cases, diagnostic certainty is often elusive and reflects the limits of present understanding. Classification of the primary cicatricial alopecias on the basis of pathology provides a diagnostic and investigational framework and, it is hoped, will facilitate future enlightenment. Details of classification, etiopathogenesis, clinicopathologic features, differential diagnosis, and practical management of the primary cicatricial alopecias will be discussed. LEARNING OBJECTIVES: Upon completion of this learning activity, participants should be familiar with the following aspects of the primary cicatricial alopecias: (1) the new, consensus-issued classification scheme, (2) current understanding about etiopathogenesis, (3) salient clinicopathologic features, (4) differential diagnosis, and (5) therapeutic management.

Alopecia↗

A comparison of vertical versus transverse sections in the evaluation of alopecia biopsy specimens.

BACKGROUND: Both vertical and transverse sections are used in the histologic interpretation of alopecia biopsy specimens. Although a combination of the two may be optimal, the pathologist is frequently only provided with a single specimen. Even though the trend in recent years has been toward transverse sections in this setting, we are not aware of any published data directly comparing the two methods. METHODS: One hundred two consecutive archived hair biopsy accessions that demonstrated comparable vertical and transverse sections were examined twice, each time in a random order. The pathologist's interpretation based only on the vertical sections and an interpretation based only on the transverse sections were compared with the original biopsy report, which had been based on the combination of vertical and transverse sections. RESULTS: In 76 cases, all 3 diagnoses were concordant (ie, the diagnosis made with vertical sections alone, the diagnosis made with transverse sections alone, and the original diagnosis were all in agreement). In 2 cases, neither the diagnosis made with vertical sections alone nor the diagnosis made with transverse sections alone were in full agreement with the original diagnosis. In 20 cases, only the diagnosis made with vertical sections was concordant with the original diagnosis. In 4 cases, only the diagnosis made with transverse sections alone was concordant with the original diagnosis. LIMITATIONS: Our practice is heavily weighted toward scarring alopecia, and the results of our study may not be applicable to practices weighted toward other forms of alopecia. Because the cases had been signed out over a period of several years, the nomenclature for some entities changed. For the purposes of our study, we counted the diagnoses of follicular degeneration syndrome and idiopathic pseudopelade to be subtypes of (and concordant with) a diagnosis of central centrifugal cicatricial alopecia. In some cases, a definitive diagnosis was not possible at the time of the original diagnosis, but rather the pathologist had provided a histologic description and a differential diagnosis. For purposes of this study, an interpretation was considered to be concordant with the original descriptive diagnosis if all of the important histologic features were identified that had been described in the original report. Sampling error could have contributed to discordant diagnoses, but would be expected to affect both vertical and transverse samples in a random manner. CONCLUSION: The combination of vertical and transverse sections is superior to either alone. Although transverse sections have revolutionized the evaluation of alopecia, in this study, the diagnosis made with vertical sections alone had a higher concordance rate with the combination than did transverse sections alone. As there are advantages and disadvantages inherent in either method, when only a single biopsy specimen is submitted, it may be sectioned either vertically or transversely, at the discretion of the pathologist. With either method, serial step sections should be obtained to reduce the risk of missing important histologic findings.

Alopecia↗

Psychotropic medication and drug-related alopecia.

The literature on alopecia as a side effect of psychotropic medications is reviewed. Drug-induced alopecia usually presents as a diffuse, nonscarring alopecia that is reversible upon withdrawal of the drug. Certain psychotropic drugs--such as the beta-blockers, lithium, and anticonvulsants--are most likely to induce a drug-related alopecia. The evaluation and management of psychiatric patients with drug-induced alopecia are discussed.

Alopecia↗

Eosinophils in fibrous tracts and near hair bulbs: a helpful diagnostic feature of alopecia areata.

BACKGROUND: When biopsy specimens lack a "swarm of bees" peribulbar lymphoid infiltrate, the diagnosis of alopecia areata depends on the recognition of other histologic features of the disease. OBJECTIVE: Our objective was to determine the frequency of the presence of eosinophils in biopsy specimens of alopecia area'a in relation to the other major histologic features of the disease. METHODS: Biopsy specimens from 71 patients with alopecia areata were studied. RESULTS: Eosinophils were present in 38 of the 71 cases. A peribulbar lymphoid infiltrate was absent in 27 of the 71 cases. Eosinophils were present in 13 of these cases. Multiple catagen hairs and pigment casts (features which may lead to confusion with trichotillomania) were present in 39 cases. The presence of eosinophils was found to be a helpful diagnostic feature in cases with potential for misdiagnoses as trichotillomania. CONCLUSION: Eosinophils are common in all stages of alopecia areata, both within the peribulbar infiltrate and within fibrous tracts. A "swarm of bees" peribulbar infiltrate may be absent. The presence of eosinophils is a helpful diagnostic feature of alopecia areata.

Alopecia Areata↗

The symptom experience of alopecia.

OBJECTIVES: To examine the physiology and pathophysiology of loss of hair, the impact of alopecia on the patient, nursing and self-care interventions, and available resources. DATA SOURCES: Published articles pertaining to alopecia and personal experiences of coping with alopecia. CONCLUSIONS: Hair loss often is the most traumatic side effect for cancer patients. It causes depression, loss of self-confidence, and humiliation in men and women of all ages. Too few studies exist to make a definitive recommendation for scalp hypothermia and the use of scalp tourniquets. The major controversy and issue to consider with these hair-preservation techniques is scalp metastases. Further studies are needed to identify the impact of alopecia on patient self-image and quality of life. IMPLICATIONS FOR NURSING PRACTICE: Nursing interventions should be directed toward helping the patient and family adapt to and cope with alopecia. Patient education, identification of available resources, and supportive listening are therapeutic interventions.

Adaptation, Psychological↗

Alopecia areata in childhood.

Aproximately 1% of the population will have had alopecia areata by the age of 50 and the peak incidence occurs in children and young adults. All body hair may be affected including lashes and brows. Alopecia areata is a systemic disease with frequent involvement of nails or eyes. Alopecia areata has been associated with atopic dermatitis, autoimmune disease, vitiligo, and endocrine disease. The pathogenesis is unclear. There is no excellent therapy for alopecia areata although many interventions are tried. Immunotherapy with diphenylcyprone is currently being optimistically evaluated. The harmful psychological effects of alopecia areata in children must be anticipated and prevented.

Adolescent↗

Diagnosis: alopecia areata or not?

Alopecia areata is a common cause of hair loss in children and adults. In most cases, the diagnosis is straight forward and is easily made based on the patient's history and clinical presentation. However, in two specific scenarios, the diagnosis can be difficult and may require a scalp biopsy. We present four cases that illustrate these two problematic differentials: alopecia areata versus trichotillomania in adolescent females; and diffuse alopecia areata versus telogen effluvium versus androgenetic alopecia in adult women. Tables compare and contrast the clinical and histopathologic features of these nonscarring localized and diffuse alopecias.

Adolescent↗

[Scarring alopecias].

The irreversibility and the possible important cosmetic consequences of scarring alopecia demand special diagnostic attention in order to promptly attain a precise diagnosis and specific treatment. Scarring alopecias are either due to permanent damage to essential parts of the hair follicle or destruction of the entire hair follicle. They are classified into the categories of primary scarring alopecias, where the hair follicle is the primary target of destruction, and secondary scarring alopecias, where the follicular damage results incidentally from events around impinging on the follicular unit. The differential diagnosis of the more common primary scarring alopecias, e.g. follicular lichen planus, chronic cutaneous lupus erythematosus and folliculitis decalvans, can be difficult when based only on anamnestic and clinical findings. The scalp biopsy is essential for appropriate nosologic classification and has prognostic relevance. The primary therapeutic goal is to halt progression of the irreversible process as early as possible by means of immunomodulatory, immunosuppressive or antiinfectious agents, respectively.

Alopecia↗

Topical estrogen accelerates hair regrowth in mice after chemotherapy-induced alopecia by favoring the dystrophic catagen response pathway to damage.

Estrogen receptor ligands are important modulators of skin physiology and are involved in the control of normal hair follicle cycling. Here, we have studied the effects of topically applied 17-beta-estradiol on pathologic hair follicle cycling as seen during chemotherapy-induced alopecia, one of the major unresolved problems of clinical oncology. For this study we employed a well-established murine model that mimics chemotherapy-induced alopecia in humans. For precisely quantifying the area of hair loss and hair regrowth in this model in vivo, we developed a simple planimetric assay (dotmatrix planimetry). We show that topical 17-beta-estradiol significantly alters the cycling response of murine follicles to cyclophosphamide, whereas the estrogen antagonist ICI 182.780 exerted no such effects. Initially, topical 17-beta-estradiol enhanced chemotherapy-induced alopecia significantly by forcing the follicles into the dystrophic catagen response pathway to hair follicle damage, whereas follicles treated by ICI 182.780 or vehicle shifted into the dystrophic anagen response pathway. Consequently, the regrowth of normally pigmented hair shafts after chemotherapy-induced alopecia was significantly accelerated in the 17-beta-estradiol treated group. Our data encourage one to explore topical estrogens as a potential stimulant for hair re-growth after chemotherapy-induced alopecia.

Administration, Topical↗

Effects of minoxidil 2% vs. cyproterone acetate treatment on female androgenetic alopecia: a controlled, 12-month randomized trial.

BACKGROUND: Hormone studies have demonstrated the androgen-dependent character of female androgenetic alopecia, but there have been few controlled studies of therapies for alopecia in women. OBJECTIVES: To compare topical minoxidil 2% and cyproterone acetate in the treatment of female alopecia. METHODS: Sixty-six women with female-pattern alopecia were randomly assigned for 12 cycles into two groups, 33 received two local applications (2 mL day-1) of topical minoxidil 2% plus combined oral contraceptive and 33 received cyproterone acetate 52 mg day-1 plus ethinyl oestradiol 35 microg for 20 of every 28 days. RESULTS: A mean reduction of 2.4 +/- 6.2 per 0.36 cm2 in hairs of diameter > 40 microm was observed in the cyproterone acetate group (P = 0.05) and a mean increase of 6.5 +/- 9 per 0.36 cm2 in the minoxidil group (P < 0.001). Comparison of the total number of hairs at 12 months and the body mass index (BMI) revealed a borderline positive correlation in the cyproterone acetate group (r = 0.39, P = 0.06) and a negative correlation in the minoxidil group (r = -0.42, P < 0.05). No significant difference was observed in the total number of hairs among cyproterone acetate patients according to the presence or absence of other symptoms of hyperandrogenism, whereas in the minoxidil group, the total number of new hairs was higher in patients with isolated alopecia (Delta = 8.1; P < 0.05). Variations in scalp seborrhoea were significant in both groups, but the result was better (for acne and hirsutism as well) in the cyproterone acetate group than in the minoxidil group (P < 0.001). CONCLUSIONS: Minoxidil treatment was more effective in the absence of other signs of hyperandrogenism, hyperseborrhoea, and menstrual cycle modifications when the BMI was low, and when nothing argued in favour of biochemical hyperandrogenism. Cyproterone acetate treatment was more effective when other signs were present and when the BMI was elevated, factors that favoured a diagnosis of biochemical hyperandrogenism.

Administration, Topical↗

Genetic analysis of the interleukin-1 receptor antagonist and its homologue IL-1L1 in alopecia areata: strong severity association and possible gene interaction.

Alopecia areata is an inflammatory hair loss disease with a major genetic component. The presence of focal inflammatory lesions with perifollicular T-cell infiltrates reflects the importance of local cytokine production in the pathogenesis. In addition to its fundamental pro-inflammatory role, the interleukin-1 (IL-1) system has major effects on hair growth regulation in vitro, with the inhibitory actions of IL-1alpha and IL-1beta being opposed by the receptor antagonist IL-1ra. The novel interleukin-1 like molecule 1 (IL-1L1) which has greatest gene sequence homology with IL1RN, the gene encoding IL-1ra, is another potential IL-1 antagonist. In view of previous studies suggesting a significant role for IL1RN polymorphisms in the pathogenesis of autoimmune/inflammatory disease, we have analysed polymorphisms of IL-1ra (IL1RN+2018) and its homologue IL-1L1 (IL1L1+4734) in a case-control association study on 165 patients and a large number of matched controls. Homozygosity for the rare allele of IL1RN (IL1RN*2) was significantly associated with alopecia areata [odds ratio (OR) = 1.89, 95% CI (1.09, 3.28); P = 0.02], confirming our previous findings of significant association with the IL1RN variable number tandem repeat (VNTR). The results also revealed a novel association involving a polymorphism of the interleukin-1 receptor antagonist homologue IL1L1 at position + 4734, IL1RN+2018, and alopecia areata. The effect of a genotype combining three copies of the rare alleles at the IL1RN and IL1L1 loci conferred a more than additive increase in the risk of disease compared to IL1RN+2018 or IL1L1+4734 alone [OR 3.37 (1.60, 7.06); P = 0.002], suggesting possible synergy between the IL1RN and IL1L1 genes. This effect was stronger in patients with severe disease (alopecia totalis/universalis) [OR 4.62 (1.87, 11.40), P = 0.0022], and in those with early age at onset (< 20 years) [OR = 6.38 (2.64, 15.42), P = 0.0002]. Our results suggest that these polymorphisms within IL1RN and IL1L1 themselves or a gene in linkage disequilibrium with IL1RN and IL1L1 predispose to the more severe forms of alopecia areata.

Adult↗

Nurse's cap alopecia.

BACKGROUND: Traction alopecia associated with the nurse's cap is a relatively common form of occupational hair loss. METHODS: We examined 199 healthy South Korean nurses to assess the clinical and pathologic characteristics of traction alopecia caused by prolonged traction exerted at the point of attachment of the nurse's cap. RESULTS: Seven nurses (3.5% of 199) had hair loss at the pin site used to secure the nurse's cap. The lesions were exclusively localized on the parieto-occipital scalp. Histopathologic findings revealed characteristic cicatricial changes which showed a marked decrease in the number of hair follicles without inflammation. CONCLUSIONS: Nurse's cap alopecia is not an uncommon occupational alopecia, and appears to be a distinct clinical entity which should be distinguished from other forms of patchy alopecia.

Adult↗

Psoriatic scarring alopecia: observations in four patients.

BACKGROUND AND DESIGN: Although acute or chronic hair loss in psoriasis of the scalp can be a symptom of the disease, until now there has been no agreement as to whether or not it is only restricted to erythrodermic, generalized pustular and scalp plaque psoriasis. The purpose of this study was to evaluate patients with chronic scalp psoriasis and alopecia and to determine if the alopecia was of the scarring type. RESULTS: We report four cases of psoriatic scarring alopecia and describe the clinical and histologic features of these patients. The diagnosis was made by scalp biopsies (vertical and transverse sections) and other causes of scarring alopecia were excluded. CONCLUSIONS: Psoriasis can cause scarring alopecia.

Adult↗

Time-specific occurrence of alopecia in neonatal C57BL mice treated with N-methyl-N-nitrosourea and the therapeutic efficacy of tacrolimus hydrate.

Alopecia was induced in male and female neonatal C57BL mice by a single intraperitoneal injection of 60 mg/kg N-methyl-N-nitrosourea (MNU). MNU administration was most effective in the 8-day-old mice and less effective in the 5-day-old mice (at active and early anagen stages of the first hair cycle, respectively). No alopecia was seen in the day 14 MNU-treated animals (at telogen stage of the first hair cycle). MNU effectively induced hair follicular cell apoptosis at the anagen stage by up-regulation of Bax protein without down-modulation of Bcl-2 protein. In day 8 MNU-treated mice, the immunosuppressive agent 0.01% tacrolimus hydrate (FK506), when topically applied for 5 days from 1 day after MNU treatment (before the occurrence of alopecia), decreased the severity of alopecia. However, it did not stimulate hair growth when applied for 5 days from 20 days of age (after occurrence of alopecia).

Alkylating Agents↗

Role of cytotoxic T cells in chronic alopecia areata.

Cytokines play a role in alopecia areata. We used immunohistochemical and in situ hybridization studies to demonstrate the persistence of pro-inflammatory as well as apoptotic mechanisms in skin biopsies from patients with chronic alopecia areata. In situ hybridization allows the visualization of the distribution of immunocompetent cells in vivo. We studied skin biopsies from 11 untreated alopecia areata patients and two normal controls. In situ hybridization was performed on frozen sections using 35S-radio-labeled riboprobes, specific for IL-1beta, IL-2, IL-6, INFgamma, and granzyme B mRNA. Immunohistochemistry was carried out using an anti-IL-1beta monoclonal antibody, and a monoclonal antibody directed against the human Fas protein. We demonstrated the presence of cells labeled with IL-1beta, IL-6, INFgamma, and granzyme B antisense probes. Similarly, cells labeled with anti-IL-1beta were found in 10 of 11 cases. The labeled cells were located in the mononuclear peri- and intrafollicular infiltrate. Cells expressing granzyme B were found in close contact with the follicle. Fas positivity was demonstrated in four of four cases at the level of the cytoplasmic membrane of the hair follicle keratinocytes. These results, based on visualizing the labeled cells, demonstrate that pro-inflammatory cytokines are produced by the mononuclear cell infiltrate in close contact with follicles in alopecia areata. Furthermore, they demonstrate for the first time that apoptotic mechanisms involving granzyme B and Fas-Fas ligand pathways may play a major role in the persistence of chronic alopecia areata.

Alopecia Areata↗

Psychological sequelae and alopecia among women with cancer.

PURPOSE: This article reviews the relevant literature on treatment-induced alopecia in women with cancer and describes the development of a computer-assisted intervention to reduce distress associated with this side effect. DESCRIPTION OF PROGRAM: Alopecia has been cited as the most disturbing anticipated side effect by up to 58% of women preparing for chemotherapy, with 8% being at risk for avoiding treatment. Women with cancer who experience alopecia as a side effect, compared with women with cancer and no alopecia, report lower self-esteem, poorer body image, and lower quality of life. Although physicians' recommendations are the most influential factor on cancer treatment choice, body image and effects on sexuality are the next most influential factors. A study of a computer-imaging intervention, based on concepts related to guided imagery and anticipatory grief, has been launched in an effort to aid women in coping with anticipated treatment-related alopecia. RESULTS: While we are still waiting for final data collection and analysis from the computer intervention study, the feedback thus far has been positive. CLINICAL IMPLICATIONS: The intervention described here may prove to be effective in desensitizing women with cancer to hair loss and facilitating an adjustment to self-acceptance. As such, a higher quality of life during the difficult time of coping may be maintained. The development of a computer-imaging intervention offers an opportunity to integrate a standard psychosocial intervention, personalized for each patient, into the routine patient care in the oncology setting.

Adaptation, Psychological↗

An evaluation system to enhance patient selection for alopecia-reducing surgery.

BACKGROUND: The author presents an evaluation system that helps optimize the chances of achieving good results with alopecia-reducing procedures. OBJECTIVE: To help hair restoration surgeons select patients properly for alopecia-reducing procedures. METHODS: Twenty criteria are scrutinized by the hair restoration surgeon during the initial consultation and given a score of one to five. The scores are added together and divided by 20. A patient with a score greater than four is considered a good candidate for alopecia reduction in most cases. RESULTS: This evaluation method has significantly decreased the number of patients undergoing alopecia-reducing procedures while helping the author achieve consistently good results. CONCLUSION: An evaluation system is presented that helps determine who is a good candidate for alopecia reduction and who is a poor candidate. This selection technique has helped the author achieve more consistently good results by eliminating poor and borderline candidates.

Age Factors↗

Profiling of alopecia areata autoantigens based on protein microarray technology.

Protein biochips have a great potential in future parallel processing of complex samples as a research tool and in diagnostics. For the generation of protein biochips, highly automated technologies have been developed for cDNA expression library production, high throughput protein expression, large scale analysis of proteins, and protein microarray generation. Using this technology, we present here a strategy to identify potential autoantigens involved in the pathogenesis of alopecia areata, an often chronic disease leading to the rapid loss of scalp hair. Only little is known about the putative autoantigen(s) involved in this process. By combining protein microarray technology with the use of large cDNA expression libraries, we profiled the autoantibody repertoire of sera from alopecia areata patients against a human protein array consisting of 37,200 redundant, recombinant human proteins. The data sets obtained from incubations with patient sera were compared with control sera from clinically healthy persons and to background incubations with anti-human IgG antibodies. From these results, a smaller protein subset was generated and subjected to qualitative and quantitative validation on highly sensitive protein microarrays to identify novel alopecia areata-associated autoantigens. Eight autoantigens were identified by protein chip technology and were successfully confirmed by Western blot analysis. These autoantigens were arrayed on protein microarrays to generate a disease-associated protein chip. To confirm the specificity of the results obtained, sera from patients with psoriasis or hand and foot eczema as well as skin allergy were additionally examined on the disease-associated protein chip. By using alopecia areata as a model for an autoimmune disease, our investigations show that the protein microarray technology has potential for the identification and evaluation of autoantigens as well as in diagnosis such as to differentiate alopecia areata from other skin diseases.

Adult↗