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Prognostic factors in the treatment of alopecia areata with diphenylcyclopropenone.

One hundred thirty-nine patients with alopecia areata were treated with diphenylcyclopropenone. Before treatment, 85 patients had subtotal or total hair loss (greater than 90% bald area) and in the remaining patients scalp involvement was between 40% and 90%. The following three factors were found to be of prognostic significance: type of alopecia areata as documented before treatment, duration of the disease before therapy, and presence of nail changes. Other factors such as age at onset, sex, presence of atopic features, the extent of variation in the range of diphenylcyclopropenone concentrations during treatment, and sleep disturbances caused by pruritus did not influence the prognosis significantly.

Adolescent↗

The effect of dietary change on in vitro erythrocyte haemolysis, skin lesions and alopecia in common marmosets (Callithrix jacchus).

1. The effect of dietary change on common marmosets (Callithrix jacchus) exhibiting high in vitro erythrocyte haemolysis, skin lesions and alopecia was investigated. 2. The experimental diet was low in lipid, high in vitamin E and was devoid of n-3 long chain polyunsaturated fatty acids. 3. There were significant increases in the concentrations of plasma alpha-tocopherol (vitamin E) (P less than 0.05), all-trans retinol (vitamin A) (P less than 0.001) and total lipid (P less than 0.025), and a reduction in fibrinogen (P less than 0.02) concentration and neutrophil count (P less than 0.02). 4. Moreover, the mean in vitro erythrocyte haemolysis declined from an initial value of 64% to less than 2%, and there was a regression of skin lesions and alopecia with complete fur regrowth. 5. The amelioration of the conditions appear to be due to high circulating vitamin E which provided protection against oxidative stress, and the correction of membrane n-6:n-3 balance.

Alopecia↗

Alopecia of the unburned scalp.

Alopecia of the unburned scalp, the temporary or permanent loss of hair, is a preventable complication. Patients at highest risk of developing alopecia are those with burn encephalopathy and in a prolonged shock state. The occipital scalp is the most common site and localized pressure-induced ischaemia is the likely cause. Frequent head repositioning and use of devices to decrease the pressure effect may decrease the incidence of this complication.

Adult↗

Topical application of nitroxide protects radiation-induced alopecia in guinea pigs.

We have recently found that treatment of Chinese hamster V79 cells with the stable nitroxide radical TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl) afforded significant protection against superoxide, hydrogen peroxide, and X-ray mediated cytotoxicity. Radiation-induced alopecia is a common radiotherapeutic problem. Topical application of TEMPOL was evaluated for possible protective effects against radiation-induced alopecia using guinea pig skin as a model. For single acute X-ray doses up to 30 Gy, TEMPOL, when topically applied 15 min prior to irradiation provided a marked increase in the rate and extent of new hair recovery when compared to untreated skin. TEMPOL was detected in treated skin specimens with electron paramagnetic resonance (EPR) spectroscopy. Similar measurements of blood samples failed to show any signal resulting from topical application, nor could TEMPOL be detected in brain tissue after application on the scalp. TEMPOL represents a new class of compounds with potential for selective cutaneous radioprotection without systemic absorption.

Administration, Topical↗

Animal models of alopecia.

A genetic model of androchronogenic alopecia has yet to be described in the rat or mouse, two of the better characterized species. It may be relevant that the best current animal model of androchronogenic alopecia, the stumptailed macaque, is a primate. The age of onset and the pattern of hair loss closely resemble human male-pattern baldness and morphologically, as well as mechanistically, may be analogous to the corresponding process in humans. Since genetically controlled regional hairlessness is a phenomenon relatively unique to Homo sapiens, it may be too much to expect to find an analogous process among rodents.

Alopecia↗

The aetiology and pathogenesis of alopecia areata.

In common with a number of inflammatory autoimmune diseases, genetic factors including HLA class II associations have been identified in alopecia areata. No consensus has been reached on the identity of a specific disease target within the hair follicle in alopecia areata. Suggested candidate cell types include the dermal papilla cells, the keratinocytes of the matrix and presumptive cortex and the hair bulb melanocytes, but these need not be mutually exclusive. The pathogenesis is known to involve disturbance of immune function but there is no proof that an autoimmune mechanism is fundamental. We propose a pathogenetic model incorporating polygenic determination of disease susceptibility and severity with additional, possibly environmental, factors as triggers for disease expression.

Alopecia Areata↗

Apoptosis resistance in peripheral blood lymphocytes of alopecia areata patients.

Alopecia areata (AA) is a putative, cell-mediated autoimmune disease of anagen stage hair follicles. Inter- and intra-follicular lymphocytic infiltrates are associated with alopecia that may progress from an initially patchy presentation to extensive, even universal, hair loss. We previously noted in a mouse model of AA that regulatory T cells (Treg) are absent from draining lymph nodes and that expression of CD44v7 is transiently upregulated. Both features might explain autoreactive T cell persistence. Here we explored whether similar changes are seen in AA patients' peripheral blood mononuclear cells (PBMC). There was no clear evidence for a reduction in Treg as a possible means to support sustained T cell activation. However, progressive AA patients' PBMC displayed increased resistance towards apoptosis, which was accompanied by a decrease in CD95L+ and an increase in CD44v7+ cells. Notably, an expanded population of CD4+CD25+CD154+ T cells in progressive AA patients' PBMC was apoptosis resistant and expressed CD44v7. Thus, survival of activated T cells in progressive AA patients' PBMC is apparently sustained by downregulation of CD95L and upregulation of CD44v7 which is known to be associated with anti-apoptotic gene expression.

Adolescent↗

Temporary alopecia after subarachnoid haemorrhage.

Primary endovascular intervention is increasingly the first choice of treatment for cerebral aneurysms, particularly for those with complex anatomy in the posterior circulation. However, their clinical management and follow-up continue to be predominantly in the hands of neurosurgeons. In this report, the development of alopecia following the coiling of posterior circulation aneurysms is described. The alopecia was transient and lasted for approximately 6 months, and occurred in the occipital and suboccipital regions of the scalp. This report aims to highlight this condition, which has not been previously reported in the neurosurgical literature. The potential hazards of irradiation should be borne in mind while carrying out complex endovascular procedures. The patient should be counselled and all necessary steps undertaken to limit radiation exposure.

Adult↗

Clinical approach to the patient with alopecia.

Hair loss, or alopecia, is a common patient complaint and a source of significant psychological and physical distress. The majority of common hair loss disorders can be accurately diagnosed in the outpatient setting with a systematic evaluation of the patient. This review will present a clinical approach to the patient with alopecia by describing the history, clinical findings, and diagnosis of various hair loss disorders.

Alopecia↗

The dominant alopecia phenotypes Bareskin, Rex-denuded, and Reduced Coat 2 are caused by mutations in gasdermin 3.

Reduced Coat 2 (Rco2) is an ENU-induced mutation affecting hair follicle morphogenesis by an abnormal and protracted catagen. We describe chromosomal mapping and molecular identification of the autosomal dominant Rco2 mutation. The Rco2 critical region on mouse chromosome 11 encompasses the alopecia loci, Bareskin (Bsk), Rex-denuded (Re(den)), Recombination induced mutation 3 (Rim3), and Defolliculated (Dfl). Recently, the gasdermin (Gsdm) gene was described as predominantly expressed in skin and gastric tissues. We provide evidence for a murine-specific gene cluster consisting of Gsdm and two closely related genes which we designate as Gsdm2 and Gsdm3. We show that Gsdm3 reflects a mutation hotspot and that Gsdm3 mutations cause alopecia in Rco2, Re(den), and Bsk mice. We infer a role of Gsdm3 during the catagen to telogen transition at the end of hair follicle morphogenesis and the formation of hair follicle-associated sebaceous glands.

Alleles↗

Asebia-2J (Scd1(ab2J)): a new allele and a model for scarring alopecia.

A spontaneous, autosomal, recessive mouse mutation exhibiting mild scaly skin, progressive scarring alopecia, slightly runted growth, and photophobia arose at The Jackson Laboratory in 1993 in the inbred mouse strain DBA/1LacJ. Because this mutant mouse showed genetic, anatomical, and laboratory similarities to the asebia mutation, crosses were done between the new mutant and mice carrying the asebia-J allele. Because the F1 offspring were affected, indicating the two mutants were allelic, the new mutation was named asebia-2J. Careful histological analysis of skin development of mice homozygous and heterozygous for either asebia-J or asebia-2J revealed that both types of mutant mice are very similar regardless of their background. Notable histopathological features of mice homozygous for either allele included extreme sebaceous gland hypoplasia, abnormally long anagen follicles, retained inner root sheath, hair fiber perforation of the anagen follicle base, and progressive follicular replacement by scarring. In this article we present a new pathogenetic hypothesis based on the importance of the sebaceous gland in hair fiber sheath dissociation: in the absence of a functional sebaceous gland the hair follicle is destroyed. The cutaneous pathology of this mutant mouse underscores the importance of the sebaceous gland to follicular biology and presents an animal model for studying the human scarring alopecias, which characteristically begin with sebaceous gland ablation.

Alleles↗

Inhibitory effect of M50054, a novel inhibitor of apoptosis, on anti-Fas-antibody-induced hepatitis and chemotherapy-induced alopecia.

M50054, 2,2'-methylenebis (1,3-cyclohexanedione), was identified as a novel inhibitor of apoptosis (programmed cell death) using an in vitro cell death assay system induced in human Fas-expressing WC8 cells by soluble human Fas ligand. Furthermore, M50054 inhibited the apoptotic cell death of U937, a human monocytic leukemic cell line, induced by anticancer agents such as etoposide; it was also confirmed that M50054 inhibited apoptotic features such as DNA fragmentation and phosphatidylserine exposure in these cells. These anti-apoptotic effects were attributable to inhibition of caspase-3 activation. Additionally, M50054 significantly inhibited anti-Fas-antibody-induced elevation of plasma alanine aminotransferase and aspartate aminotransferase. Alopecia (hair loss) symptoms were also significantly improved with topical treatment with M50054. In conclusion, M50054 inhibits apoptosis induced by a variety of stimuli via inhibition of caspase-3 activation, and may thus be effective for hepatitis and chemotherapy-induced alopecia.

Alopecia↗

Reversible alopecia after single-dose methotrexate treatment in a patient with ectopic pregnancy.

OBJECTIVE: To report a case of a women who received a single 50 mg/m2 dose of methotrexate (MTX) on two occasions for two separate ectopic pregnancies. After both treatments the patient experienced reversible alopecia. DESIGN: Case report. SETTING: Single human patient in a university-run clinic. PATIENTS: A patient with an ectopic pregnancy presenting for treatment on two separate occasions. INTERVENTIONS: A single dose of 50 mg/m2 MTX given to the patient on both occasions. MAIN OUTCOME MEASURE: Loss of scalp hair. RESULTS: On two separate occasions the patient lost a significant portion (33% to 50%) of her scalp hair. CONCLUSION: Even single-dose MTX as used for the treatment of ectopic pregnancy may induce alopecia in a susceptible patient.

Adult↗

[Premature androgenetic alopecia in adult male with nonclassic 21-OH deficiency. A novel nonsense CYP21A2 mutation (Y336X) in 2 affected siblings].

BACKGROUND AND OBJECTIVE: Nonclassical congenital adrenal hyperplasia due to 21-hydroxylase deficiency mainly manifests with symptoms and signs of hyperandrogenism, which are usually obvious in women and sometimes obvious in children or adolescents, but are rarely observed in adult men especially with increasing age. Male pattern alopecia is considered an androgenetic and age-related symptom. However, its early appearance should raise the suspicion of an underlying endocrinological disease, and biochemical screening should be done. PATIENTS AND METHOD: Here we present the case of 2 siblings (female and male) where the man complains about premature alopecia. RESULTS: Molecular study of CYP21A2 revealed that both siblings were compound heterozygotes for the mild mutation (V281L) and for a novel nonsense mutation (Y336X). CONCLUSIONS: Given the high prevalence of carriers with severe mutations, we discuss the risk for such patients of conceiving a child with a classical disease and the need for a reliable molecular diagnosis in order to provide accurate genetic counselling.

Adrenal Hyperplasia, Congenital↗

Whorled scarring alopecia: a rare phenomenon in incontinentia pigmenti?

Incontinentia pigmenti is a rare X-linked dominant disease that affects the ectodermal tissues and is usually lethal in males. Two girls, 1 Malay and 1 Chinese, with incontinentia pigmenti of the Bloch-Sulzberger type had a whorled pattern of scarring alopecia. This phenomenon, hitherto unreported in association with this disorder, corresponded to the lines of Blaschko. The mother and maternal grandmother of the Malay girl also had whorled scarring alopecia. This phenomenon is permanent and can be used as a marker to ascertain affected adult women who may no longer have cutaneous manifestations. X chromosome inactivation in females during early embryogenesis results in a mosaic population of cells, which explains the linear and patchy cutaneous manifestations of incontinentia pigmenti.

Alopecia Areata↗

An open-label trial of immunomodulation therapy with inosiplex (Isoprinosine) in patients with alopecia totalis and cell-mediated immunodeficiency.

Nine patients with alopecia totalis and associated defects in T lymphocyte function were admitted to an open-label trial of inosiplex therapy. All nine developed enhanced T cell function and seven had clinically significant hair regrowth. The immunologic response to inosiplex was dose-dependent in five patients. These data provide new information on the in vivo effects of inosiplex on the human immune system and support the hypothesis that disturbances of immunologic mechanisms may play a pathogenetic role in alopecia totalis in certain patients.

Adjuvants, Immunologic↗

Alopecia areata: pathogenesis and treatment.

Although its etiology remains unknown, evidence has accumulated to support an autoimmune pathogenesis for alopecia areata. Our review summarizes the immunologic data and also examines the role of genetics, atopy, and psychologic stress in this disorder. Until etiology is better understood, treatments for alopecia areata are likely to remain palliative. Nevertheless, newer therapies such as photochemotherapy, topical immunotherapy, and perhaps systemic immunotherapy (e.g., inosiplex) offer new hope for patients with extensive disease.

Adrenal Cortex Hormones↗