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Alopecia areata, stress and psychiatric disorders: a review.

Although the results of some studies have proven negative, the influence of psychological factors in the development, evolution and therapeutic management of alopecia areata is, in general, well documented. Life events and intrapsychically generated stress can play an important role in triggering of some episodes. The comorbidity of psychiatric disorders, mainly generalized anxiety disorder, depression, and phobic states, is high. The role of treatment of concomitant psychopathological disorders is a vital one. Indeed this treatment can positively affect how the patient adapts to his/her alopecia and social setting and perhaps can even lead to a better dermatological evolution of the alopecia. Therefore, controlled studies analyzing the possible links between psychiatric symptoms, treatment with antidepressants or benzodiacepines, evolution of alopecia, medium term prognosis, and immune function are necessary. Basic psychotherapeutic support may prove to be of use in many cases and can be carried out by the dermatologist, although a subgroup of patients may need psychopharmacological or psychotherapeutic specialized treatments. Studies using operative diagnostic criteria and structured interviews are still scarce. Therefore, it seems necessary to design studies using modern psychiatric methodology. Controlled clinical trials to test the efficiency of psychoactive drugs and psychotherapy in the disease are also needed. By studying in depth these and other related aspects, we may improve the clinical management of our patients.

Alopecia Areata↗

Association between alopecia areata and HLA Class I and II in Turkey.

HLA class I and II alleles have been described in patients with alopecia areata (AA). As in other immune mediated diseases, the HLA alleles associated with AA may influence the patient's ability to respond to immune challenges from both self and non-self antigens and can offer clues to the cause, prognosis, and potential therapy for the disease. The aim of this study was to determine which HLA class I and II alleles are associated with Turkish alopecia areata patients. Sixty-three patients with AA, alopecia totalis, or alopecia universalis were included in this study and compared with seventy-six healthy transplant donors. HLA DNA typing was performed by the PCR/SSP method. The frequency of HLA-B62 was significantly higher in patients than in controls. HLA-A2, HLA-A24, HLA-B35, HLA-DRB1*11, and HLA-DRB1*15 were significantly less common in patients than in the control group.

Alleles↗

Male pattern alopecia and coronary artery disease in men.

The prevalence of male pattern alopecia, coronary artery disease, hypertension and smoking habits were studied in 478 male Caucasian hospital in-patients, over the age of 20 years. No association was shown between coronary artery disease and either male pattern alopecia, premature male pattern alopecia or male pattern alopecia with a positive family history.

Adult↗

Alopecia areata and auto-immunity.

The prevalence of auto-antibodies against thyroid constituents, gastric parietal cells, smooth muscle cells, mitochondria, reticulin, nuclear constituents and rheumatoid factor in 108 patients with alopecia areata was compared with that found in a previous survey of the local population. Female patients had a significantly increased prevalence of anti-thyroid antibodies which were present in 30% overall and in 44% of the youngest age group (11-17 years). Smooth muscle antibodies were more frequent in female patients but the increase was not significant. Male patients had a significant increased prevalence of thyroid and gastric parietal cell antibodies (11.4% each). In females, antithyroid antibodies were associated with extensive hair loss: they were found in 42% of female patients with total alopecia and only 20% of males with total hair loss. A family history of alopecia areata was obtained from 24% of patients; 10% had relatives with thyroid disease and 10% had diabetic relatives. These findings confirm the association between alopecia areata and the other auto-immune diseases.

Adolescent↗

The DEBR rat: an animal model of human alopecia areata.

The Dundee experimental bald rat (DEBR) is reported as a model for human alopecia areata. Parallels with human alopecia areata were observed in relation to the gradual and patchy loss of hair and the penetration of both pelage and vibrissa follicles by mononuclear cells. In particular, the apparent disruption of the follicles within the precortical region of the epidermal component and consequent alterations of normal geometrical relationships between dermal and epidermal components relate directly to similar studies on human alopecia areata. In comparison with other previously described hypotrichotic rodent mutants, the DEBR rat exhibits a unique mechanism of hair loss which may provide important information regarding the pathomechanism of human alopecia areata.

Alopecia Areata↗

Decreased sweat-gland number and function in patients with alopecia areata.

In this study the number and function of sweat glands on the dorsum of the hand and foot were evaluated using a silastic imprint method. Twenty patients, 11 females and nine males with either alopecia areata, alopecia totalis, or alopecia universalis were included in the study. Patients showed a significant decrease in activated sweat-gland number and function compared to matched controls (P less than 0.001). There was no significant relationship between the degree of sweat-gland dysfunction and extent of hair loss, concurrent illnesses, or treatment. These findings suggest that eccrine sweat-gland function is compromised in patients with alopecia areata.

Adolescent↗

Psychological characteristics of women with androgenetic alopecia: a controlled study.

The psychological characteristics and the hair problems of 58 females with androgenetic alopecia were compared with a group of women with non-apparent dermatological diseases, and with a group of men with androgenetic alopecia. The women with androgenetic alopecia had higher scores for self-sufficiency and social inadequacy compared to women with non-visible dermatological complaints, and they scored higher for inadequacy, rigidity and general psychological maladjustment than the men and had lower scores for injuredness self-evaluation and self-esteem. The women with androgenetic alopecia had more psychosocial problems, which they attributed to the hair loss, than the other groups.

Adolescent↗

Normal sweat secretion rate in patients with alopecia areata.

We have examined sweat secretion rates in 22 patients with alopecia areata, and 22 age- and sex-matched controls. Mean sweat rate on the forearm in patients with alopecia areata was 20 mg/cm2 per h (95% confidence limits 15-25 mg/cm2 per h), and in controls was 24.1 mg/cm2 per h (95% confidence limits 19.1-29.1 mg/cm2 per h). Sweat secretion was higher in males than females in both the disease and control groups (27.8 mg/cm2 per h [95% confidence limits 21.3-34.3 mg/cm2 per h], compared with 18.08 mg/cm2 per h [95% confidence limits 14.63-21.6 mg/cm2]; P > 0.01). Our results confirm the previously reported sex difference in sweat secretion rate, and demonstrate that there is no statistically significant difference between patients with alopecia areata and controls. We discuss our results in the light of a previous report claiming that patients with alopecia areata have reduced rates of cholinergic-induced sweating.

Adult↗

A natural canine homologue of alopecia areata in humans.

BACKGROUND: Alopecia areata (AA) is suspected to be an autoimmune disease directed preferentially against hair follicles (HF) affecting both humans and various mammalian species. Recently, two rodent models of AA were described, namely the ageing C3H/HeJ mouse and the DEBR rat. Despite several case reports of canine AA in the literature, there has been no systematic assessment of the disease in these companion animals, and it is also not known whether dogs with AA could be useful as an outbred homologue of this disease in humans. OBJECTIVES: To evaluate the clinical, histopathological and immunopathological features of 25 dogs with AA and compare these data with those found in the human disease. PATIENTS/METHODS: Twenty-five client-owned dogs exhibiting macroscopic alopecia with peri- or intrabulbar lymphocytic infiltrates were selected for study. Biopsies and sera were obtained and assessed by histopathology, direct immunofluorescence of immunoreactant deposition, immunohistochemistry for lymphocyte markers, indirect immunofluorescence and immunoblotting analysis of circulating serum IgG, selective immunoprecipitation of HF proteins by serum IgG, and passive transfer of purified canine IgG into naïve C57BL/10 mice. RESULTS: Clinical signs including alopecia, skin hyperpigmentation and leucotrichia usually developed during adulthood and were first seen on the face, followed by the forehead, ears and legs. Spontaneous remission of alopecia occurred in 60% of dogs and regrowing hair shafts were often non-pigmented. Histological examination of skin biopsy specimens revealed peri- and intrabulbar mononuclear cell infiltrates affecting almost exclusively anagen HF. Direct immunofluorescence analysis detected HF-specific IgG in 73% of dogs, while indirect immunofluorescence revealed circulating IgG autoantibodies to the HF inner and outer root sheaths, matrix and precortex. Immunoblotting analysis revealed IgG reactivity to proteins in the 45-60 kDa molecular weight range and with a 200-220 kDa doublet. The latter was identified as trichohyalin by selective immunoprecipitation. Purified HF-reactive IgG, pooled from AA-affected dogs, was injected intradermally to the anagen skin of naïve mice where it was associated with the local retention of HFs in an extended telogen phase in AA-treated skin compared with that seen in controls. CONCLUSIONS: These findings are very similar to those reported for human AA patients; therefore, they support the consideration of dogs with AA as a useful homologue for the study of the pathogenesis of this common autoimmune disease of humans.

Alopecia Areata↗

Permanent alopecia after busulfan chemotherapy.

Systemic chemotherapy is a well known cause of reversible hair loss. Busulfan chemotherapy, however, is responsible for a permanent alopecia that usually occurs in bone marrow transplant patients. We report two patients with permanent alopecia due to busulfan chemotherapy. Both patients had a diffuse alopecia characterized by greatly reduced hair density with short, thin hair. The pathology showed reduced follicular density in the absence of fibrosis, suggesting that alopecia may result either from hair follicle stem cell destruction or from acute damage to the keratinocytes of the lower portion of some follicles.

Adult↗

Treatment of alopecia totalis with a combination of inosine pranobex and diphencyprone compared to each treatment alone.

Recent developments in alopecia areata have included the use of oral inosine pranobex and the introduction of diphencyprone as a contact sensitizer. Good results have been claimed for these treatments even in severe forms of the disease. We performed a study to investigate the efficacy of a combination of these treatments in the most severe form of alopecia areata. Thirty-three patients suffering from alopecia totalis were enrolled. Subjects were divided into three groups matched for age and sex. One group received treatment with inosine pranobex (50 mg/kg/day) for 6 months. The second was sensitized to diphencyprone and treated for 6 months by maintenance of contact allergic dermatitis on the scalp. The third received both treatments. There was no evidence of response to inosine pranobex in any of the 22 subjects who received this treatment. Only two of 22 patients responded to diphencyprone. Patients with long-standing alopecia totalis contemplating diphencyprone therapy should be advised that the chances of success are only around 10%. Inosine pranobex does not appear to improve the response rate.

Adolescent↗

Increased HLA-DR+ T-lymphocyte population in peripheral blood of alopecia areata.

The populations of activated T-cell subsets [HLA-DR(+)-Leu 4+ cells, interleukin 2 receptor positive (IL-2R+)-Leu 4+ cells] in the peripheral blood of patients with alopecia areata (AA) were investigated using double direct immunofluorescence staining. Fifty-eight patients with AA were classified into one of three types: those with inactive single AA (type 1) lesions, active multiple alopecia areata (MAA) lesions and active alopecia totalis (AT) (type 2) and chronic alopecia universalis (AU) (type 3). Compared to normal controls, high percentages of HLA-DR(+)-Leu4+ cells were detected in types 2 and 3 AA patients, but not in type 1 AA patients. These findings suggest that T cells are activated in the peripheral blood of active MAA, AT and chronic AU.

Adult↗

Alopecia areata with lymphocytic mural folliculitis affecting the isthmus in a thoroughbred mare.

A 13-year-old, thoroughbred mare was presented with an 8-year history of multifocal, generalized, noninflammatory alopecia and a 3-month history of alopecia, erythema and scaling of the white star on the forehead and muzzle. Histopathological examination of biopsy samples from multiple sites on the body (mane, neck, shoulder, flank and gluteal region) showed a subtle lymphocytic inflammatory infiltrate affecting and surrounding the anagen hair bulbs, consistent with a diagnosis of alopecia areata. The biopsy sample from the star on the forehead showed atrophic hair follicles with perifollicular and mural mononuclear folliculitis affecting the isthmus. Immunohistochemical staining with a CD3 marker confirmed the T-lymphocytic origin of the inflammatory infiltrate in all the samples. The concurrent presence of lymphocytic infiltration at the bulbar and isthmic level of the hair follicles in the same horse is unusual. This finding may represent a variation of the histological appearance of alopecia areata.

Alopecia Areata↗

Use of topical minoxidil therapy for androgenetic alopecia in women.

BACKGROUND: Androgenetic alopecia is the most common cause of hair loss in men and women. Androgenetic alopecia in women begins as a diffuse and progressive thinning of the frontoparietal area of the scalp. In women, hair loss at any age is socially unacceptable and may be the basis of psychiatric illness. METHODS: A 32-week, double-blind, placebo-controlled trial was conducted in 10 European centers to assess the efficacy and safety of 2% topical minoxidil solution for the treatment of androgenetic alopecia in women. Two hundred ninety-four of the 346 women enrolled (85%) completed the 32-week trial. Photographic and computer imaging techniques were used at each visit to determine objectively the number of nonvellus hairs present in a 1-cm2 area selected as the target evaluation site. RESULTS: In the 2% minoxidil group, the mean increase in nonvellus hair count was 33 hairs, which was significantly greater than that of 19 hairs in the placebo group (P = 0.0001). The investigators observed that 44% of the patients in the 2% minoxidil group achieved new hair growth compared with 29% in the placebo group. When asked to evaluate their own hair growth, 55% of the women in the 2% minoxidil group compared to 41% of the women in the placebo group believed that they had achieved new hair growth. No clinically significant changes in vital signs were observed during the study and no serious or unexpected medical events were reported. CONCLUSION: Topical minoxidil solution was significantly more effective than placebo in the treatment of androgenetic alopecia in women.

Administration, Cutaneous↗

Pseudopelade: an inherited alopecia.

BACKGROUND: Pseudopelade is a rare idiopathic progressive alopecia that has no initial inflammatory phase. Even so, pseudopelade has been classified as scarring alopecia with postinflammatory alopecias. Atrophy rather than true scarring is the cardinal feature of pseudopelade. MATERIALS AND METHODS: A review of reported cases of pseudopelade, especially those with a family history, was undertaken. The discovery of a young man and his mother, who had pseudopelade, plus two other familial cases prompted this study. RESULTS: Examination of the clinical and pathologic material shows pseudopelade to be a disease separate from other alopecias. The striking familial association in these cases demonstrates a plausible etiology. CONCLUSIONS: Pseudopelade is an autosomal dominant disorder of the scalp marked by atrophic loss of hair follicles.

Adult↗

Isolated eyebrow and eyelash trichotillomania mimicking alopecia areata.

BACKGROUND: Isolated Trichotillomania (TM) of the eyebrows and eyelashes is occasionally seen and may be mistaken for alopecia areata (AA). OBJECTIVE: The clinical study of the patients with isolated eyebrows and eyelashes alopecia suggesting of TM. PATIENTS AND METHOD: Seven children and young adult patients who referred with recalcitrant eyebrows and eyelashes alopecia were diagnosed as TM based on the clinical criteria for TM. The hair specifications for TM were include: hairs are broken at different levels, they may be tufted, tortuous and some hair fibers may be abnormally longer than others. The hair follicles may be prominent. The patients and their parents studied for psychopathology using a semistructured interview based on the Diagnostic Statistical manual of Psychiatric disorders (DSM-1V) and maudsley inventory. RESULTS: Our clinical study, interview with the patients and their parents and the clinical criteria used to differentiate TM from AA all support the clinical diagnosis of TM. The patients and their parents mainly suffered from obsessive-compulsive disorders (OCD) and obsessive-compulsive spectrum disorders (OCSDs). CONCLUSION: TM as a hair pulling habit in patients with underlying psychopathology can be considered in cases with isolated eyebrows and eyelashes alopecia when the hair are broken at different levels. And they may be malaligned, nonuniform, tortuous, and tufted.

Adolescent↗

Quantification of hair follicle parameters using computer image analysis: a comparison of androgenetic alopecia with normal scalp biopsies.

Computer image analysis enables large numbers of hairs to be measured in an automated fashion. In this study, we examined horizontal scalp biopsies from 10 patients with a histological diagnosis of androgenetic alopecia and 10 normal control subjects. The density of hair follicles and the ratio of terminal to vellus hairs were determined. Hair shaft, hair canal and hair follicle diameter, inner root sheath width and outer root sheath area were measured using the Chromatic Colour Image Analysis program. This study showed a statistically significant progressive decrease in size of hair canal diameters from normal terminal hairs (85.93 +/- 10.07 microns) through to androgenetic alopecia terminal (68.83 +/- 13.60 microns) and vellus hairs (28.67 +/- 5.60 microns). This pattern is also seen with hair follicle diameters; normal terminal (268.41 +/- 24.88 microns), androgenetic alopecia terminal (236.34 +/- 17.23 microns), and vellus hairs (130.88 +/- 19.96 microns). Outer root sheath areas, hair shaft diameters and ratio of terminal to vellus hairs were significantly larger in normal (18,500 +/- 4222 microns 2; 82.71 +/- 13.79 microns; 36:1; respectively) compared with androgenetic alopecia scalp biopsies (8403 +/- 3322 microns 2; 61.11 +/- 14.42 microns; 3:1; respectively), whereas inner root sheath width and density did not vary significantly. Computer image analysis can be adapted for use in clinical trials where large numbers and objectivity are critical in determining the efficacy of hair growth promoters.

Adult↗

Efficacy and safety of a new clobetasol propionate 0.05% foam in alopecia areata: a randomized, double-blind placebo-controlled trial.

BACKGROUND: Clinical efficacy of topical corticosteroids in alopecia areata (AA) is still controversial. Positive clinical results have been obtained using ointments with occlusive dressing but this approach has a low patient compliance. Recently, a new topical formulation (thermophobic foam: Versafoam) of clobetasol propionate 0.05% has been introduced on the market (Olux, Mipharm, Milan, Italy) (CF). This formulation is easy to apply. After application to the skin the foam quickly evaporates without residues and it has a good patient compliance. In vitro studies have also shown that this formulation enhances the delivery of the active compound through the skin. AIM: To evaluate the efficacy, safety and tolerability of CF in the treatment of moderate to severe AA. SUBJECTS AND METHODS: Thirty-four patients with moderate to severe AA (eight men, mean age 40+/-13 years) were enrolled in a randomized, double-blind, right-to-left, placebo-controlled, 24-week trial. Alopecia grading score (AGS) was calculated at baseline and after 12 and 24 weeks of treatment using a 0-5 score (0=no alopecia; 5=alopecia totalis). Clobetasol foam and the corresponding placebo foam (PF) were applied twice a day for 5 days/week for 12 weeks (phase 1) using an intrapatient design (right vs. left). From weeks 13 to 24 each enrolled patient continued only with the treatment (both on the right and left site) that was judged to have a greater efficacy than that on the contralateral side (phase 2). The primary outcome of the trial, evaluated on an intention-to-treat basis, was the hair regrowth rate, which was evaluated using a semiquantitative score (RGS) (from 0: no regrowth, to 4: regrowth of 75%). RESULTS: At baseline the AGS was 4.1 (range: 2-5). Nine (26%) patients prematurely concluded the trial. At the end of phase 1, a greater hair regrowth was observed in 89% of the head sites treated with CF vs. 11% in the sites treated with PF. The RGS was 1.2+/-1.6 in the CF-treated sites and 0.4+/-0.8 in the PF-treated sites (P=0.001). A RGS of 2 (hair regrowth of more than 25%) was observed in 42% CF-treated sites and in 13% of PF-treated sites (P=0.027). In seven subjects (20%) a RGS of 3 to 4 (hair regrowth of 50%) was observed in CF-treated sites. In three subjects (9%) a RGS of 4 (hair regrowth of 75%) was observed in CF-treated sites. In one patient only, in a PF-treated region, a RGS of 3 was observed. The AS was reduced to 3.8 by CF treatment at the end of phase 1 and to 3.3 at the end of phase 2 (P=0.01). From weeks 12 to 24 the treatment with CF induced a further increase in the RGS (from 1.2 to 1.5+/-1.4). Forty-seven per cent of CF-treated patients had a RGS of 2 at the end of the trial. A total of eight patients (25%) at the end of the treatment with CF showed a RGS of 3. Folliculitis occurred in two patients. No significant modifications in cortisol and ACTH blood levels were observed during the trial. CONCLUSION: This new formulation of clobetasol propionate foam is an effective, safe and well-tolerated topical treatment for AA. This formulation has a good cosmetic acceptance and patient compliance profile.

Administration, Topical↗